These Highlights Do Not Include All The Information Needed To Use Telmisartan And Amlodipine Tablets Safely And Effectively. See Full Prescribing Information For Telmisartan And Amlodipine Tablets.

SPL v9

SPL

SPL Set ID ca60a4d5-ace7-4889-94ee-e2265fd63811

Route

ORAL

Published

Effective Date 2018-11-14

Document Type 34391-3 HUMAN PRESCRIPTION DRUG LABEL

Drug Facts

Composition & Product

Active Ingredients

Telmisartan (40 mg) Amlodipine (5 mg)

Inactive Ingredients

Silicon Dioxide Starch, Corn Fd&c Blue No. 1 Magnesium Stearate Mannitol Meglumine Microcrystalline Cellulose Povidone, Unspecified Sodium Hydroxide

Identifiers & Packaging

Pill Appearance

Imprint: TA4M Shape: oval Color: blue Color: white Size: 16 mm Size: 18 mm Score: 1

Marketing Status

ANDA Active Since 2014-09-19

Description

• When pregnancy is detected, discontinue telmisartan and amlodipine tablets as soon as possible [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ]. • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ].

Indications and Usage

Telmisartan and amlodipine tablets are indicated for the treatment of hypertension, alone or with other antihypertensive agents to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including angiotensin II receptor blockers and dihydropyridine calcium channel blockers. There are no controlled trials demonstrating risk reduction with telmisartan and amlodipine tablets. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Telmisartan and amlodipine tablets may also be used as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals. Base the choice of telmisartan and amlodipine tablets as initial therapy for hypertension on an assessment of potential benefits and risks including whether the patient is likely to tolerate the starting dose of telmisartan and amlodipine tablets. Patients with moderate or severe hypertension are at relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. Consider the patient's baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared with monotherapy when deciding whether to use telmisartan and amlodipine tablets as initial therapy. Individual blood pressure goals may vary based upon the patient’s risk. Data from an 8-week, placebo-controlled, multidose, factorial trial provide estimates of the probability of reaching a blood pressure goal with telmisartan and amlodipine tablets compared to telmisartan or amlodipine monotherapy and placebo [ see Clinical Studies (14.1) ]. The figures below provide estimates of the likelihood of achieving systolic and diastolic blood pressure control with telmisartan and amlodipine 80/10 mg tablets, based upon baseline systolic or diastolic blood pressure. The curve of each treatment group was estimated by logistic regression modeling. The estimated likelihood at the right tail of each curve is less reliable due to small numbers of subjects with high baseline blood pressures. Figure 1a: Probability of Achieving Systolic Blood Pressure < 140 mmHg at Week 8 Figure 1b: Probability of Achieving Systolic Blood Pressure < 130 mmHg at Week 8 Figure 2a: Probability of Achieving Diastolic Blood Pressure < 90 mmHg at Week 8 Figure 2b: Probability of Achieving Diastolic Blood Pressure < 80 mmHg at Week 8 The figures above provide an approximation of the likelihood of reaching a targeted blood pressure goal at 8 weeks. For example, a patient with a baseline blood pressure of 160/110 mmHg has about a 16% likelihood of achieving a goal of < 140 mmHg (systolic) and 16% likelihood of achieving < 90 mmHg (diastolic) on placebo. The likelihood of achieving these same goals on telmisartan is about 46% (systolic) and 26% (diastolic). The likelihood of achieving these same goals on amlodipine is about 69% (systolic) and 22% (diastolic). These likelihoods rise to 79% for systolic and 55% for diastolic with telmisartan and amlodipine tablets.

Dosage and Administration

• Substitute telmisartan and amlodipine tablets for its individually titrated components for patients on amlodipine and telmisartan. Telmisartan and amlodipine tablets may also be given with increased amounts of amlodipine, telmisartan, or both, as needed. ( 2.2 , 2.3 ) • Use telmisartan and amlodipine tablets to provide additional blood pressure lowering for patients not adequately controlled with amlodipine (or another dihydropyridine calcium channel blocker) alone or with telmisartan (or another angiotensin receptor blocker) alone. ( 2.3 ) • Dosage may be increased after at least 2 weeks to a maximum dose of 80/ 10 mg once daily, usually by increasing one component at a time but both components can be raised to achieve more rapid control. ( 2.1 , 2.2 ) • Majority of antihypertensive effect is attained within 2 weeks. ( 2.1 ) • Initiate with 40/5 mg or 80/5 mg once daily. ( 2.4 ) • Switch patients who experience dose-limiting adverse reactions on amlodipine to telmisartan and amlodipine tablets containing a lower dose of that component. ( 2.3 )

Warnings and Precautions

• Avoid fetal or neonatal exposure. ( 5.1 ) • Hypotension: Correct any volume or salt depletion before initiating therapy. Observe for signs and symptoms of hypotension. Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. ( 5.2 ) • Titrate slowly in patients with hepatic ( 5.4 ) or severe renal impairment. ( 5.5 ) • Heart failure: Monitor for worsening. ( 5.8 ) • Avoid concomitant use with an ACE inhibitor. ( 5.6 ) • Myocardial infarction: Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of telmisartan and amlodipine tablets, particularly in patients with severe obstructive coronary artery disease. ( 5.7 )

Contraindications

Telmisartan and amlodipine tablets are contraindicated in patients with known hypersensitivity (e.g., anaphylaxis or angioedema) to telmisartan, amlodipine, or any other component of this product [see Adverse Reactions (6.2) ] . Do not co-administer aliskiren with telmisartan and amlodipine tablets in patients with diabetes [see Drug Interactions (7.2) ] .

Adverse Reactions

• In the placebo-controlled factorial design study, the most common reasons for discontinuation of therapy with telmisartan and amlodipine tablets were peripheral edema, dizziness, and hypotension, each leading to discontinuation of ≤ 0.5% of telmisartan and amlodipine tablet-treated patients. Adverse reactions that occurred at a ≥ 2% higher incidence on telmisartan and amlodipine tablets than placebo were peripheral edema (4.8% vs 0%), dizziness (3.0% vs 2.2%), and back pain (2.2% vs 0%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

Drug Interactions

• NSAIDs: Increased risk of renal impairment and loss of antihypertensive effect. ( 7 ) • If simvastatin is co-administered with amlodipine, do not exceed doses greater than 20 mg daily of simvastatin. ( 7 ) • Do not co-administer aliskiren with telmisartan and amlodipine tablets in patients with diabetes. ( 7.2 )

Storage and Handling

Telmisartan and Amlodipine Tablets, USP are available containing 40 mg or 80 mg of telmisartan, USP and 5 mg or 10 mg of amlodipine (present as 6.935 mg or 13.87 mg amlodipine besylate, USP respectively), providing for the following combinations: 40 mg/5 mg, 40 mg/10 mg, 80 mg/5 mg or 80 mg/10 mg. The 40 mg/5 mg tablets are bi-layered, mottled light blue and white to off-white, capsule shaped, unscored tablets with TA1M debossed on the white to off-white side of the tablet and blank on the mottled light blue side. The white to off-white layer may have a blue tinge or blue specks. They are available as follows: NDC 0378-1075-93 bottles of 30 tablets The 40 mg/10 mg tablets are bi-layered, mottled blue and white to off-white, capsule shaped, unscored tablets with TA2M debossed on the white to off-white side of the tablet and blank on the mottled blue side. The white to off-white layer may have a blue tinge or blue specks. They are available as follows: NDC 0378-1076-93 bottles of 30 tablets The 80 mg/5 mg tablets are bi-layered, mottled light blue and white to off-white, capsule shaped, unscored tablets with TA3M debossed on the white to off-white side of the tablet and blank on the mottled light blue side. The white to off-white layer may have a blue tinge or blue specks. They are available as follows: NDC 0378-1077-93 bottles of 30 tablets The 80 mg/10 mg tablets are bi-layered, mottled blue and white to off-white, capsule shaped, unscored tablets with TA4M debossed on the white to off-white side of the tablet and blank on the mottled blue side. The white to off-white layer may have a blue tinge or blue specks. They are available as follows: NDC 0378-1078-93 bottles of 30 tablets Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from moisture and light. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

How Supplied

Patient Information

Telmisartan and Amlodipine Tablets, USP (tel″ mi sar′ tan am loe′ di peen) Read this Patient Information before you start taking telmisartan and amlodipine tablets and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment. What is the most important information I should know about telmisartan and amlodipine tablets? Telmisartan and amlodipine tablets can cause harm or death to an unborn baby. Talk to your doctor about other ways to lower your blood pressure if you plan to become pregnant. If you get pregnant while taking telmisartan and amlodipine tablets, tell your doctor right away. What are telmisartan and amlodipine tablets? Telmisartan and amlodipine tablets are a prescription medicine that contains telmisartan and amlodipine. Telmisartan and amlodipine tablets may be used to treat high blood pressure (hypertension): • when one of these medicines (or a similar one) is not enough to lower your high blood pressure • as the first medicine to lower your high blood pressure if your doctor decides you are likely to need more than one medicine It is not known if telmisartan and amlodipine tablets are safe and effective in children. Who should not take telmisartan and amlodipine tablets? You should not take telmisartan and amlodipine tablets if you are allergic (hypersensitive) to the active ingredients (telmisartan or amlodipine) or any of the other ingredients listed at the end of this leaflet. For patients with diabetes, if you are taking telmisartan and amlodipine tablets you should not take aliskiren. What should I tell my doctor before taking telmisartan and amlodipine tablets? Before you take telmisartan and amlodipine tablets, tell your doctor if you: • are pregnant or are planning to become pregnant. See “ What is the most important information I should know about telmisartan and amlodipine tablets? ” • are breast-feeding or plan to breast-feed. Telmisartan and amlodipine can pass into your breast milk and may harm your baby. You and your doctor should decide if you will take telmisartan and amlodipine tablets or breast-feed. You should not do both. Talk with your doctor about the best way to feed your baby if you take telmisartan and amlodipine tablets. • have liver problems • have kidney problems • have heart problems • have any other medical conditions Tell your doctor about all the medicines you take , including prescription and nonprescription medicines, vitamins and herbal supplements. For patients with diabetes, if you are taking telmisartan and amlodipine tablets you should not take aliskiren. Telmisartan and amlodipine tablets may affect the way other medicines work, and other medicines may affect how telmisartan and amlodipine tablets work. Especially tell your doctor if you take: • aliskiren • digoxin (Lanoxin ® ) • lithium (Lithobid ® , lithium carbonate, lithium citrate) • aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) • other medicines that may be used to treat high blood pressure or a heart problem • simvastatin (Zocor ® , Vytorin ® ) • water pills (diuretics) Know the medicines you take. Keep a list of them and show it to your doctor or pharmacist when you get a new medicine. How should I take telmisartan and amlodipine tablets? • Take telmisartan and amlodipine tablets exactly as your doctor tells you to take them. • Your doctor will tell you how many telmisartan and amlodipine tablets to take and when to take them. Your doctor may change your dose if needed. • Take telmisartan and amlodipine tablets one time each day at the same time. • Take telmisartan and amlodipine tablets with or without food. • If you miss a dose, take it as soon as you remember. If it is close to your next dose, do not take the missed dose. Take the next dose at your regular time. • If you take too many telmisartan and amlodipine tablets, call your doctor or go to the nearest hospital emergency room right away. What are possible side effects of telmisartan and amlodipine tablets? Telmisartan and amlodipine tablets may cause serious side effects, including: • Injury or death to your unborn baby. See “What is the most important information I should know about telmisartan and amlodipine tablets?” • Low blood pressure (hypotension) is most likely to happen if you also: • take water pills (diuretics) • are on a low-salt diet • get dialysis treatments • have heart problems • get sick with vomiting or diarrhea If you feel faint or dizzy, lie down and call your doctor right away. • Kidney problems . Kidney problems may get worse if you already have kidney disease. You may have changes in your kidney test results, and you may need a lower dose of telmisartan and amlodipine tablets. Call your doctor if you get: • swelling in your feet, ankles, or hands • unexplained weight gain Call your doctor right away if you get any of the symptoms listed above. • Heart problems or heart attack. Heart problems may get worse in people that already have heart disease. This may happen when you start telmisartan and amlodipine tablets or when there is an increase in your dose of telmisartan and amlodipine tablets. Get emergency help if you get worse chest pain or chest pain that does not go away. • High potassium in the blood (hyperkalemia). Your doctor may check your potassium levels as needed. • Muscle rigidity, tremor and/or abnormal muscle movement. Rare, serious allergic reactions may happen. Tell your doctor right away if you get any of these symptoms: • swelling of face, tongue, throat • difficulty breathing • skin rash The most common side effects of telmisartan and amlodipine tablets include: • swelling in your hands, ankles, or feet • feeling like your heart is pounding or racing • flushing or sudden redness of the face and neck • dizziness • back pain • feeling tired or sleepy • abdominal pain, nausea, or diarrhea • low blood pressure or a sudden drop in blood pressure with fainting These are not all the possible side effects of telmisartan and amlodipine tablets. Tell your doctor if you have any side effect that bothers you or that does not go away. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store telmisartan and amlodipine tablets? • Store telmisartan and amlodipine tablets at room temperature 20 ° to 25 ° C (68 ° to 77 ° F). • Do not remove telmisartan and amlodipine tablets from bottles until right before you take them. • Keep telmisartan and amlodipine tablets out of the light and away from moisture. Keep telmisartan and amlodipine tablets and all medicines out of the reach of children. General information about telmisartan and amlodipine tablets Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use telmisartan and amlodipine tablets for a condition for which they were not prescribed. Do not give telmisartan and amlodipine tablets to other people, even if they have the same symptoms that you have. They may harm them. This Patient Information leaflet summarizes the most important information about telmisartan and amlodipine tablets. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about telmisartan and amlodipine tablets that is written for health professionals. For more information, call Mylan at 1-877-446-3679 (1-877-4-INFO-RX). What are the ingredients in telmisartan and amlodipine tablets? Active Ingredients: telmisartan and amlodipine besylate Inactive Ingredients: colloidal silicon dioxide, corn starch, FD&C Blue No. 1 Aluminum Lake, magnesium stearate, mannitol, meglumine, microcrystalline cellulose, povidone, pregelatinized starch (corn) and sodium hydroxide. What is high blood pressure (hypertension)? Blood pressure is the force in your blood vessels when your heart beats and when your heart rests. You have high blood pressure when the force is too much. Telmisartan and amlodipine tablets can help your blood vessels relax so your blood pressure is lower. Medicines that lower your blood pressure lower your chance of having a stroke or heart attack. High blood pressure makes the heart work harder to pump blood throughout the body and causes damage to the blood vessels. If high blood pressure is not treated, it can lead to stroke, heart attack, heart failure, kidney failure, and vision problems. This Patient Information has been approved by the U.S. Food and Drug Administration The brands listed are trademarks of their respective owners. Manufactured for: Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A. Manufactured by: Mylan Laboratories Limited Hyderabad — 500 096, India 75066865 Revised: 11/2018 MX:TLMSAM:R7

Medication Information

Warnings and Precautions

Indications and Usage

Dosage and Administration

Contraindications

Adverse Reactions

Drug Interactions

Storage and Handling

How Supplied

Patient Information

Telmisartan and Amlodipine Tablets, USP

(tel″ mi sar′ tan am loe′ di peen)

Read this Patient Information before you start taking telmisartan and amlodipine tablets and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

What is the most important information I should know about telmisartan and amlodipine tablets?

Telmisartan and amlodipine tablets can cause harm or death to an unborn baby. Talk to your doctor about other ways to lower your blood pressure if you plan to become pregnant. If you get pregnant while taking telmisartan and amlodipine tablets, tell your doctor right away.

What are telmisartan and amlodipine tablets?

Telmisartan and amlodipine tablets are a prescription medicine that contains telmisartan and amlodipine.

Telmisartan and amlodipine tablets may be used to treat high blood pressure (hypertension):

•
when one of these medicines (or a similar one) is not enough to lower your high blood pressure
•
as the first medicine to lower your high blood pressure if your doctor decides you are likely to need more than one medicine

It is not known if telmisartan and amlodipine tablets are safe and effective in children.

Who should not take telmisartan and amlodipine tablets?

You should not take telmisartan and amlodipine tablets if you are allergic (hypersensitive) to the active ingredients (telmisartan or amlodipine) or any of the other ingredients listed at the end of this leaflet.

For patients with diabetes, if you are taking telmisartan and amlodipine tablets you should not take aliskiren.

What should I tell my doctor before taking telmisartan and amlodipine tablets?

Before you take telmisartan and amlodipine tablets, tell your doctor if you:

•
are pregnant or are planning to become pregnant. See “What is the most important information I should know about telmisartan and amlodipine tablets?”
•
are breast-feeding or plan to breast-feed. Telmisartan and amlodipine can pass into your breast milk and may harm your baby. You and your doctor should decide if you will take telmisartan and amlodipine tablets or breast-feed. You should not do both. Talk with your doctor about the best way to feed your baby if you take telmisartan and amlodipine tablets.
•
have liver problems
•
have kidney problems
•
have heart problems
•
have any other medical conditions

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements.

For patients with diabetes, if you are taking telmisartan and amlodipine tablets you should not take aliskiren.

Telmisartan and amlodipine tablets may affect the way other medicines work, and other medicines may affect how telmisartan and amlodipine tablets work. Especially tell your doctor if you take:

•
aliskiren
•
digoxin (Lanoxin^®)
•
lithium (Lithobid^®, lithium carbonate, lithium citrate)
•
aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs)
•
other medicines that may be used to treat high blood pressure or a heart problem
•
simvastatin (Zocor^®, Vytorin^®)
•
water pills (diuretics)

Know the medicines you take. Keep a list of them and show it to your doctor or pharmacist when you get a new medicine.

How should I take telmisartan and amlodipine tablets?

•
Take telmisartan and amlodipine tablets exactly as your doctor tells you to take them.
•
Your doctor will tell you how many telmisartan and amlodipine tablets to take and when to take them. Your doctor may change your dose if needed.
•
Take telmisartan and amlodipine tablets one time each day at the same time.
•
Take telmisartan and amlodipine tablets with or without food.
•
If you miss a dose, take it as soon as you remember. If it is close to your next dose, do not take the missed dose. Take the next dose at your regular time.
•
If you take too many telmisartan and amlodipine tablets, call your doctor or go to the nearest hospital emergency room right away.

What are possible side effects of telmisartan and amlodipine tablets?

Telmisartan and amlodipine tablets may cause serious side effects, including:

•
Injury or death to your unborn baby. See “What is the most important information I should know about telmisartan and amlodipine tablets?”
•
Low blood pressure (hypotension) is most likely to happen if you also:
- •
  take water pills (diuretics)
- •
  are on a low-salt diet
- •
  get dialysis treatments
- •
  have heart problems
- •
  get sick with vomiting or diarrhea
If you feel faint or dizzy, lie down and call your doctor right away.
•
Kidney problems. Kidney problems may get worse if you already have kidney disease. You may have changes in your kidney test results, and you may need a lower dose of telmisartan and amlodipine tablets. Call your doctor if you get:
- •
  swelling in your feet, ankles, or hands
- •
  unexplained weight gain
Call your doctor right away if you get any of the symptoms listed above.
•
Heart problems or heart attack. Heart problems may get worse in people that already have heart disease. This may happen when you start telmisartan and amlodipine tablets or when there is an increase in your dose of telmisartan and amlodipine tablets. Get emergency help if you get worse chest pain or chest pain that does not go away.
•
High potassium in the blood (hyperkalemia). Your doctor may check your potassium levels as needed.
•
Muscle rigidity, tremor and/or abnormal muscle movement.

Rare, serious allergic reactions may happen. Tell your doctor right away if you get any of these symptoms:

•
swelling of face, tongue, throat
•
difficulty breathing
•
skin rash

The most common side effects of telmisartan and amlodipine tablets include:

•
swelling in your hands, ankles, or feet
•
feeling like your heart is pounding or racing
•
flushing or sudden redness of the face and neck
•
dizziness
•
back pain
•
feeling tired or sleepy
•
abdominal pain, nausea, or diarrhea
•
low blood pressure or a sudden drop in blood pressure with fainting

These are not all the possible side effects of telmisartan and amlodipine tablets. Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store telmisartan and amlodipine tablets?

•
Store telmisartan and amlodipine tablets at room temperature 20° to 25°C (68° to 77°F).
•
Do not remove telmisartan and amlodipine tablets from bottles until right before you take them.
•
Keep telmisartan and amlodipine tablets out of the light and away from moisture.

Keep telmisartan and amlodipine tablets and all medicines out of the reach of children.

General information about telmisartan and amlodipine tablets

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use telmisartan and amlodipine tablets for a condition for which they were not prescribed. Do not give telmisartan and amlodipine tablets to other people, even if they have the same symptoms that you have. They may harm them.

This Patient Information leaflet summarizes the most important information about telmisartan and amlodipine tablets. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about telmisartan and amlodipine tablets that is written for health professionals. For more information, call Mylan at 1-877-446-3679 (1-877-4-INFO-RX).

What are the ingredients in telmisartan and amlodipine tablets?

Active Ingredients: telmisartan and amlodipine besylate

Inactive Ingredients: colloidal silicon dioxide, corn starch, FD&C Blue No. 1 Aluminum Lake, magnesium stearate, mannitol, meglumine, microcrystalline cellulose, povidone, pregelatinized starch (corn) and sodium hydroxide.

What is high blood pressure (hypertension)?

Blood pressure is the force in your blood vessels when your heart beats and when your heart rests. You have high blood pressure when the force is too much. Telmisartan and amlodipine tablets can help your blood vessels relax so your blood pressure is lower. Medicines that lower your blood pressure lower your chance of having a stroke or heart attack.

High blood pressure makes the heart work harder to pump blood throughout the body and causes damage to the blood vessels. If high blood pressure is not treated, it can lead to stroke, heart attack, heart failure, kidney failure, and vision problems.

This Patient Information has been approved by the U.S. Food and Drug Administration

The brands listed are trademarks of their respective owners.

Manufactured for:

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Manufactured by:

Mylan Laboratories Limited

Hyderabad — 500 096, India

75066865

Revised: 11/2018

MX:TLMSAM:R7

Description

Data

Telmisartan was present in the milk of lactating rats at concentrations of 1.5 to 2 times those found in plasma from 4 to 8 hours after administration.

Gender

Plasma concentrations of telmisartan are generally 2 to 3 times higher in females than in males. In clinical trials, however, no significant increases in blood pressure response or in the incidence of orthostatic hypotension were found in women. No dosage adjustment is necessary.

Digoxin

When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed. Therefore, monitor digoxin levels when initiating, adjusting, and discontinuing telmisartan for the purpose of keeping the digoxin level within the therapeutic range.

Lithium

Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists including telmisartan. Therefore, monitor serum lithium levels during concomitant use.

8.7 Race

The magnitude of blood pressure lowering in black patients approached that observed in non-black patients but the number of black patients was limited (237 of 1461 patients).

Aliskiren

Do not co-administer aliskiren with telmisartan and amlodipine tablets in patients with diabetes. Avoid use of aliskiren with telmisartan and amlodipine tablets in patients with renal impairment (GFR < 60 mL/min).

Amlodipine

Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. Because of the gradual onset of action, acute hypotension is unlikely.

Creatinine

A 0.5 mg/dL rise or greater in creatinine was observed in 0.4% telmisartan patients compared with 0.3% placebo patients. One telmisartan-treated patient discontinued therapy due to increases in creatinine and blood urea nitrogen.

Hemoglobin

A greater than 2 g/dL decrease in hemoglobin was observed in 0.8% telmisartan patients compared with 0.3% placebo patients. No patients discontinued therapy due to anemia.

Animal Data

No reproductive toxicity studies have been conducted with the combination of telmisartan and amlodipine besylate. However, these studies have been conducted for telmisartan and amlodipine besylate alone.

Other Drugs

Co-administration of telmisartan did not result in a clinically significant interaction with acetaminophen, amlodipine, glyburide, simvastatin, hydrochlorothiazide, warfarin, or ibuprofen. Telmisartan is not metabolized by the cytochrome P450 system and had no effects in vitro on cytochrome P450 enzymes, except for some inhibition of CYP2C19. Telmisartan is not expected to interact with drugs that inhibit cytochrome P450 enzymes; it is also not expected to interact with drugs metabolized by cytochrome P450 enzymes, except for possible inhibition of the metabolism of drugs metabolized by CYP2C19.

Simvastatin

Co-administration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.

Telmisartan

In patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of therapy with telmisartan and amlodipine tablets. Either correct this condition prior to administration of telmisartan and amlodipine tablets, or start treatment under close medical supervision with a reduced dose.

If hypotension does occur, place the patient in the supine position and, if necessary, give an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.

Risk Summary

Telmisartan and amlodipine tablets can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death (see Clinical Considerations). Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Studies in rats and rabbits with telmisartan showed fetotoxicity only at maternally toxic doses (see Data). In animal reproduction studies, there was no evidence of adverse developmental effects when pregnant rats and rabbits were treated orally with amlodipine maleate during organogenesis at doses approximately 10 and 20-times the maximum recommended human dose (MRHD), respectively. However for rats, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold). Amlodipine has been shown to prolong both the gestation period and the duration of labor in rats at this dose (see Data). When pregnancy is detected, discontinue telmisartan and amlodipine tablets as soon as possible.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major malformations and miscarriage in clinically recognized pregnancies is 2% to 4%, and 15% to 20%, respectively.

10 Overdosage

Telmisartan

Limited data are available with regard to overdosage in humans. The most likely manifestations of overdosage with telmisartan tablets would be hypotension, dizziness, and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Telmisartan is not removed by hemodialysis.

Amlodipine

Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional overdosage of amlodipine is limited.

Single oral doses of amlodipine maleate equivalent to 40 mg amlodipine/kg and 100 mg amlodipine/kg in mice and rats, respectively, caused deaths. Single oral amlodipine maleate doses equivalent to 4 or more mg amlodipine/kg or higher in dogs (11 or more times the maximum recommended human dose on a mg/m² basis) caused a marked peripheral vasodilation and hypotension.

If massive overdose should occur, initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential. Should hypotension occur, provide cardiovascular support including elevation of the extremities and the judicious administration of fluids. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors (such as phenylephrine) with attention to circulating volume and urine output. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.

Liver Enzymes

Occasional elevations of liver chemistries occurred in patients treated with telmisartan; all marked elevations occurred at a higher frequency with placebo. No telmisartan-treated patients discontinued therapy due to abnormal hepatic function.

Telmisartan

The most frequently spontaneously reported events include: headache, dizziness, asthenia, coughing, nausea, fatigue, weakness, edema, face edema, lower limb edema, angioneurotic edema, urticaria, hypersensitivity, sweating increased, erythema, chest pain, atrial fibrillation, congestive heart failure, myocardial infarction, blood pressure increased, hypertension aggravated, hypotension (including postural hypotension), hyperkalemia, syncope, dyspepsia, diarrhea, pain, urinary tract infection, erectile dysfunction, back pain, abdominal pain, muscle cramps (including leg cramps), myalgia, bradycardia, eosinophilia, thrombocytopenia, uric acid increased, abnormal hepatic function/liver disorder, renal impairment including acute renal failure, anemia, and increased CPK, anaphylactic reaction, tendon pain (including tendonitis, tenosynovitis), drug eruption (e.g., toxic skin eruption mostly reported as toxicoderma, rash, and urticaria), hypoglycemia (in diabetic patients), and angioedema (with fatal outcome).

Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers, including telmisartan.

11 Description

Telmisartan and amlodipine tablets, USP are a fixed dose combination of telmisartan and amlodipine.

Telmisartan and amlodipine tablets contain telmisartan, a non-peptide angiotensin II receptor (type AT₁) antagonist. Telmisartan, USP is a white or slightly yellowish crystalline powder. It is practically insoluble in water and in the pH range of 3 to 9, sparingly soluble in strong acid (except insoluble in hydrochloric acid), and soluble in strong base. Telmisartan is chemically described as 4′-[[4-Methyl-6-(1-methyl-1H-benzimidazol-2yl)-2-propyl-1H-benzimidazol-1yl]methyl]biphenyl-2-carboxylic acid. Its molecular formula is C₃₃H₃₀N₄O₂ and its structural formula is:

Telmisartan and amlodipine tablets contain the besylate salt of amlodipine, a dihydropyridine calcium-channel blocker (CCB). Amlodipine besylate, USP is a white or almost white powder, slightly soluble in water and sparingly soluble in ethanol. Amlodipine besylate’s chemical name is 3-ethyl 5-methyl (4RS)-2-[(2-aminoethoxy) methyl]-4-(2-chlorophenyl)-6-methyl-1,4 dihydropyridine-3,5-dicarboxylate benzenesulfonate. Its molecular formula is C₂₀H₂₅ClN₂O₅•C₆H₆O₃S and its structural formula is:

Telmisartan and amlodipine tablets are formulated in four strengths for oral administration with a combination of amlodipine besylate, equivalent to 5 mg or 10 mg of amlodipine free-base, with 40 mg or 80 mg of telmisartan provided in the following four combinations: 40/5 mg, 40/10 mg, 80/5 mg and 80/10 mg.

Telmisartan and amlodipine tablets also contain the following inactive ingredients: colloidal silicon dioxide, corn starch, FD&C Blue No. 1 Aluminum Lake, magnesium stearate, mannitol, meglumine, microcrystalline cellulose, povidone, pregelatinized starch (corn) and sodium hydroxide.

Telmisartan and amlodipine tablets are hygroscopic and require protection from moisture.

Telmisartan and amlodipine tablets require protection from light.

Meets USP Dissolution Test 2

14.3 Amlodipine

The antihypertensive efficacy of amlodipine has been demonstrated in a total of 15 double-blind, placebo-controlled, randomized studies involving 800 patients on amlodipine and 538 on placebo. Once daily administration produced statistically significant placebo-corrected reductions in supine and standing blood pressures at 24 hours post-dose, averaging about 12/6 mmHg in the standing position and 13/7 mmHg in the supine position in patients with mild to moderate hypertension. Maintenance of the blood pressure effect over the 24-hour dosing interval was observed, with little difference in peak and trough effect.

Cyp3a4 Inducers

No information is available on the quantitative effects of CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone, rifampicin, St. John’s Wort) on amlodipine. Patients should be monitored for adequate clinical effect when amlodipine is co-administered with CYP3A4 inducers.

Telmisartan

Telmisartan is highly bound to plasma proteins (> 99.5%), mainly albumin and α₁-acid glycoprotein. Plasma protein binding is constant over the concentration range achieved with recommended doses. The volume of distribution for telmisartan is approximately 500 liters indicating additional tissue binding.

14.2 Telmisartan

The antihypertensive effects of telmisartan have been demonstrated in six principal placebo-controlled clinical trials, studying a range of 20 to 160 mg; one of these examined the antihypertensive effects of telmisartan and hydrochlorothiazide in combination. The studies involved a total of 1773 patients with mild to moderate hypertension (diastolic blood pressure of 95 to 114 mmHg), 1031 of whom were treated with telmisartan. Following once daily administration of telmisartan, the magnitude of blood pressure reduction from baseline after placebo subtraction was approximately (SBP/DBP) 6-8/6 mmHg for 20 mg, 9-13/6-8 mmHg for 40 mg, and 12-13/7-8 mmHg for 80 mg. Larger doses (up to 160 mg) did not appear to cause a further decrease in blood pressure.

Upon initiation of antihypertensive treatment with telmisartan, blood pressure was reduced after the first dose, with a maximal reduction by about 4 weeks. With cessation of treatment with telmisartan tablets, blood pressure gradually returned to baseline values over a period of several days to 1 week. During long-term studies (without placebo control) the effect of telmisartan appeared to be maintained for up to at least 1 year. The antihypertensive effect of telmisartan is not influenced by patient age, gender, weight, or body mass index. Blood pressure response in black patients (usually a low-renin population) is noticeably less than that in Caucasian patients. This has been true for most, but not all, angiotensin II antagonists and ACE inhibitors.

In a controlled study, the addition of telmisartan to hydrochlorothiazide produced an additional dose-related reduction in blood pressure that was similar in magnitude to the reduction achieved with telmisartan monotherapy. Hydrochlorothiazide also had an added blood pressure effect when added to telmisartan.

The onset of antihypertensive activity occurs within 3 hours after administration of a single oral dose. At doses of 20, 40, and 80 mg, the antihypertensive effect of once daily administration of telmisartan is maintained for the full 24-hour dose interval. With automated ambulatory blood pressure monitoring and conventional blood pressure measurements, the 24-hour trough-to-peak ratio for 40 to 80 mg doses of telmisartan was 70% to 100% for both systolic and diastolic blood pressure. The incidence of symptomatic orthostasis after the first dose in all controlled trials was low (0.04%).

There were no changes in the heart rate of patients treated with telmisartan in controlled trials.

Renal Impairment

No initial dosage adjustment is required for patients with mild or moderate renal impairment. Titrate slowly in patients with severe renal impairment.

8.4 Pediatric Use

Safety and effectiveness of telmisartan and amlodipine tablets in pediatric patients have not been established.

Cyp3a4 Inhibitors

Co-administration of a 180 mg daily dose of diltiazem with 5 mg amlodipine in elderly hypertensive patients resulted in a 60% increase in amlodipine systemic exposure. Erythromycin co-administration in healthy volunteers did not significantly change amlodipine systemic exposure. However, strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, ritonavir) may increase the plasma concentrations of amlodipine to a greater extent. Monitor for symptoms of hypotension and edema when amlodipine is co-administered with CYP3A4 inhibitors.

5.1 Fetal Toxicity

Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue telmisartan and amlodipine tablets as soon as possible [see Use in Specific Populations (8.1) ].

Hepatic Impairment

In most patients, initiate amlodipine therapy at 2.5 mg. Titrate slowly in patients with hepatic impairment.

Immunosuppressants

Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. Frequent monitoring of trough blood levels of cyclosporine and tacrolimus and dose adjustment when appropriate is recommended.

The following have no clinically relevant effects on the pharmacokinetics of amlodipine: cimetidine, grapefruit juice, magnesium and aluminum hydroxide antacid, sildenafil.

Amlodipine has no clinically relevant effects on the pharmacokinetics or pharmacodynamics of the following: atorvastatin, digoxin, warfarin.

2.4 Initial Therapy

A patient may be initiated on telmisartan and amlodipine tablets if it is unlikely that control of blood pressure would be achieved with a single agent. The usual starting dose of telmisartan and amlodipine tablets is 40/5 mg once daily. Patients requiring larger blood pressure reductions may be started on telmisartan and amlodipine tablets 80/5 mg once daily.

Initial therapy with telmisartan and amlodipine tablets is not recommended in patients ≥ 75 years old or with hepatic impairment [see Dosage and Administration (2.5), Warnings and Precautions (5.4), and Use in Specific Populations (8.5, 8.6) ].

Correct imbalances of intravascular volume- or salt-depletion, before initiating therapy with telmisartan and amlodipine tablets [see Warnings and Precautions (5.2) ].

4 Contraindications

Do not co-administer aliskiren with telmisartan and amlodipine tablets in patients with diabetes [see Drug Interactions (7.2)].

6 Adverse Reactions

•
In the placebo-controlled factorial design study, the most common reasons for discontinuation of therapy with telmisartan and amlodipine tablets were peripheral edema, dizziness, and hypotension, each leading to discontinuation of ≤ 0.5% of telmisartan and amlodipine tablet-treated patients. Adverse reactions that occurred at a ≥ 2% higher incidence on telmisartan and amlodipine tablets than placebo were peripheral edema (4.8% vs 0%), dizziness (3.0% vs 2.2%), and back pain (2.2% vs 0%). (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 Drug Interactions

•
NSAIDs: Increased risk of renal impairment and loss of antihypertensive effect. (7)
•
If simvastatin is co-administered with amlodipine, do not exceed doses greater than 20 mg daily of simvastatin. (7)
•
Do not co-administer aliskiren with telmisartan and amlodipine tablets in patients with diabetes. (7.2)

1 Indications and Usage

Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC).

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly.

Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal.

Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy.

Telmisartan and amlodipine tablets may also be used as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals.

Base the choice of telmisartan and amlodipine tablets as initial therapy for hypertension on an assessment of potential benefits and risks including whether the patient is likely to tolerate the starting dose of telmisartan and amlodipine tablets.

Patients with moderate or severe hypertension are at relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. Consider the patient's baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared with monotherapy when deciding whether to use telmisartan and amlodipine tablets as initial therapy. Individual blood pressure goals may vary based upon the patient’s risk.

Data from an 8-week, placebo-controlled, multidose, factorial trial provide estimates of the probability of reaching a blood pressure goal with telmisartan and amlodipine tablets compared to telmisartan or amlodipine monotherapy and placebo [see Clinical Studies (14.1) ].

The figures below provide estimates of the likelihood of achieving systolic and diastolic blood pressure control with telmisartan and amlodipine 80/10 mg tablets, based upon baseline systolic or diastolic blood pressure. The curve of each treatment group was estimated by logistic regression modeling. The estimated likelihood at the right tail of each curve is less reliable due to small numbers of subjects with high baseline blood pressures.

Figure 1a: Probability of Achieving Systolic Blood Pressure < 140 mmHg at Week 8

Figure 1b: Probability of Achieving Systolic Blood Pressure < 130 mmHg at Week 8

Figure 2a: Probability of Achieving Diastolic Blood Pressure < 90 mmHg at Week 8

Figure 2b: Probability of Achieving Diastolic Blood Pressure < 80 mmHg at Week 8

The figures above provide an approximation of the likelihood of reaching a targeted blood pressure goal at 8 weeks. For example, a patient with a baseline blood pressure of 160/110 mmHg has about a 16% likelihood of achieving a goal of < 140 mmHg (systolic) and 16% likelihood of achieving < 90 mmHg (diastolic) on placebo. The likelihood of achieving these same goals on telmisartan is about 46% (systolic) and 26% (diastolic). The likelihood of achieving these same goals on amlodipine is about 69% (systolic) and 22% (diastolic). These likelihoods rise to 79% for systolic and 55% for diastolic with telmisartan and amlodipine tablets.

2.2 Replacement Therapy

Patients receiving amlodipine and telmisartan from separate tablets may instead receive telmisartan and amlodipine tablets containing the same component doses once daily. When substituting for individual components, increase the dose of telmisartan and amlodipine tablets if blood pressure control has not been satisfactory.

Warning: Fetal Toxicity

•
When pregnancy is detected, discontinue telmisartan and amlodipine tablets as soon as possible [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].
•
Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].

8.6 Hepatic Insufficiency

Monitor carefully and uptitrate slowly in patients with biliary obstructive disorders or hepatic insufficiency [see Dosage and Administration (2) and Warnings and Precautions (5.4) ]. Since patients with hepatic impairment have decreased clearance of amlodipine, start amlodipine or add amlodipine 2.5 mg to telmisartan. The lowest dose of telmisartan and amlodipine tablets is 40/5 mg; therefore, initial therapy with telmisartan and amlodipine tablets is not recommended in hepatically impaired patients [see Dosage and Administration (2.4) ].

2.1 General Considerations

Telmisartan is an effective treatment of hypertension in once daily doses of 20 to 80 mg while amlodipine is effective in doses of 2.5 to 10 mg.

Dosage must be individualized and may be increased after at least 2 weeks. Most of the antihypertensive effect is apparent within 2 weeks and maximal reduction is generally attained after 4 weeks. The maximum recommended dose of telmisartan and amlodipine tablets is 80/10 mg once daily.

The adverse reactions of telmisartan are uncommon and independent of dose; those of amlodipine are a mixture of dose-dependent phenomena (primarily peripheral edema) and dose-independent phenomena, the former much more common than the latter [see Adverse Reactions (6.1) ].

Telmisartan and amlodipine tablets may be taken with or without food.

5 Warnings and Precautions

•
Avoid fetal or neonatal exposure. (5.1)
•
Hypotension: Correct any volume or salt depletion before initiating therapy. Observe for signs and symptoms of hypotension. Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. (5.2)
•
Titrate slowly in patients with hepatic (5.4) or severe renal impairment. (5.5)
•
Heart failure: Monitor for worsening. (5.8)
•
Avoid concomitant use with an ACE inhibitor. (5.6)
•
Myocardial infarction: Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of telmisartan and amlodipine tablets, particularly in patients with severe obstructive coronary artery disease. (5.7)

2 Dosage and Administration

•
Substitute telmisartan and amlodipine tablets for its individually titrated components for patients on amlodipine and telmisartan. Telmisartan and amlodipine tablets may also be given with increased amounts of amlodipine, telmisartan, or both, as needed. (2.2, 2.3)
•
Use telmisartan and amlodipine tablets to provide additional blood pressure lowering for patients not adequately controlled with amlodipine (or another dihydropyridine calcium channel blocker) alone or with telmisartan (or another angiotensin receptor blocker) alone. (2.3)
•
Dosage may be increased after at least 2 weeks to a maximum dose of 80/ 10 mg once daily, usually by increasing one component at a time but both components can be raised to achieve more rapid control. (2.1, 2.2)
•
Majority of antihypertensive effect is attained within 2 weeks. (2.1)
•
Initiate with 40/5 mg or 80/5 mg once daily. (2.4)
•
Switch patients who experience dose-limiting adverse reactions on amlodipine to telmisartan and amlodipine tablets containing a lower dose of that component. (2.3)

3 Dosage Forms and Strengths

•
The 40 mg/5 mg tablets are bi-layered, mottled light blue and white to off-white, capsule shaped, unscored tablets with TA1M debossed on the white to off-white side of the tablet and blank on the mottled light blue side. The white to off-white layer may have a blue tinge or blue specks.
•
The 40 mg/10 mg tablets are bi-layered, mottled blue and white to off-white, capsule shaped, unscored tablets with TA2M debossed on the white to off-white side of the tablet and blank on the mottled blue side. The white to off-white layer may have a blue tinge or blue specks.
•
The 80 mg/5 mg tablets are bi-layered, mottled light blue and white to off-white, capsule shaped, unscored tablets with TA3M debossed on the white to off-white side of the tablet and blank on the mottled light blue side. The white to off-white layer may have a blue tinge or blue specks.
•
The 80 mg/10 mg tablets are bi-layered, mottled blue and white to off-white, capsule shaped, unscored tablets with TA4M debossed on the white to off-white side of the tablet and blank on the mottled blue side. The white to off-white layer may have a blue tinge or blue specks.

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of telmisartan or amlodipine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to telmisartan or amlodipine.

Clinical Laboratory Findings

In placebo-controlled clinical trials, clinically relevant changes in standard laboratory test parameters were rarely associated with administration of telmisartan tablets.

8 Use in Specific Populations

•
Patients ≥ 75 years of age or hepatically impaired patients: Start with amlodipine or add amlodipine 2.5 mg to telmisartan. (2.5, 8.5, 8.6)
•
Lactation: Do not breastfeed during treatment with telmisartan and amlodipine tablets. (8.2)

6.1 Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reactions rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Fetal/neonatal Adverse Reactions

Use of drugs that act on the RAS in the second and third trimesters of pregnancy can result in the following: oligohydramnios, reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus.

In patients taking telmisartan and amlodipine tablets during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. If oligohydramnios is observed, discontinue telmisartan and amlodipine tablets, unless it is considered lifesaving for the mother. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury.

Closely observe infants with histories of in utero exposure to telmisartan and amlodipine tablets for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function [see Use in Specific Populations (8.4)].

17 Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Pregnancy: Advise female patients of childbearing age about the consequences of exposure to telmisartan and amlodipine tablets during pregnancy. Discuss treatment options with women planning to become pregnant. Tell patients to report pregnancies to their physicians as soon as possible [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].

Lactation: Advise nursing women not to breastfeed during treatment with telmisartan and amlodipine tablets [see Use in Specific Populations (8.2)].

Symptomatic Hypotension: Advise patients that lightheadedness can occur, especially during the first days of therapy, and to report it to their healthcare provider. Inform patients the inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of lightheadedness and possible syncope. Advise patients to contact their healthcare provider if syncope occurs [see Warnings and Precautions (5.2)].

Patients 75 Years of Age and Older

In most patients, initiate amlodipine therapy at 2.5 mg. Titrate slowly in patients 75 years of age and older.

Telmisartan and Amlodipine Tablets

The concomitant use of telmisartan and amlodipine has been evaluated for safety in more than 3700 patients with hypertension; approximately 1900 of these patients were exposed for at least 6 months and over 160 of these patients were exposed for at least 1 year. Adverse reactions have generally been mild and transient in nature and have only infrequently required discontinuation of therapy.

In the placebo-controlled factorial design study, the population treated with a telmisartan and amlodipine combination had a mean age of 53 years and included approximately 50% males, 79% were Caucasian, 17% Blacks, and 4% Asians. Patients received doses ranging from 20/2.5 mg to 80/10 mg orally, once daily.

The frequency of adverse reactions was not related to gender, age, or race.

The adverse reactions that occurred in the placebo-controlled factorial design trial in ≥ 2% of patients treated with telmisartan and amlodipine tablets and at a higher incidence in telmisartan and amlodipine tablet-treated patients (n = 789) than placebo-treated patients (n = 46) were peripheral edema (4.8% vs 0%), dizziness (3.0% vs 2.2%), and back pain (2.2% vs 0%). Edema (other than peripheral edema), hypotension, and syncope were reported in < 2% of patients treated with telmisartan and amlodipine tablets.

In the placebo-controlled factorial design trial, discontinuation due to adverse events occurred in 2.2% of all treatment cells of patients in the telmisartan/amlodipine-treated patients and in 4.3% in the placebo-treated group. The most common reasons for discontinuation of therapy with telmisartan and amlodipine tablets were peripheral edema, dizziness, and hypotension (each ≤ 0.5%).

Peripheral edema is a known, dose-dependent adverse reaction of amlodipine, but not of telmisartan. In the factorial design study, the incidence of peripheral edema during the 8-week, randomized, double-blind treatment period was highest with amlodipine 10 mg monotherapy. The incidence was notably lower when telmisartan was used in combination with amlodipine 10 mg.

Table 1: Incidence of Peripheral Edema During the 8-Week Treatment Period

	Telmisartan
	Placebo	40 mg	80 mg
Amlodipine	Placebo	0%	0.8%	0.7%
5 mg	0.7%	1.4%	2.1%
10 mg	17.8%	6.2%	11.3%

16 How Supplied/storage and Handling

The 40 mg/5 mg tablets are bi-layered, mottled light blue and white to off-white, capsule shaped, unscored tablets with TA1M debossed on the white to off-white side of the tablet and blank on the mottled light blue side. The white to off-white layer may have a blue tinge or blue specks. They are available as follows:

NDC 0378-1075-93

bottles of 30 tablets

The 40 mg/10 mg tablets are bi-layered, mottled blue and white to off-white, capsule shaped, unscored tablets with TA2M debossed on the white to off-white side of the tablet and blank on the mottled blue side. The white to off-white layer may have a blue tinge or blue specks. They are available as follows:

NDC 0378-1076-93

bottles of 30 tablets

The 80 mg/5 mg tablets are bi-layered, mottled light blue and white to off-white, capsule shaped, unscored tablets with TA3M debossed on the white to off-white side of the tablet and blank on the mottled light blue side. The white to off-white layer may have a blue tinge or blue specks. They are available as follows:

NDC 0378-1077-93

bottles of 30 tablets

The 80 mg/10 mg tablets are bi-layered, mottled blue and white to off-white, capsule shaped, unscored tablets with TA4M debossed on the white to off-white side of the tablet and blank on the mottled blue side. The white to off-white layer may have a blue tinge or blue specks. They are available as follows:

NDC 0378-1078-93

bottles of 30 tablets

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Protect from moisture and light.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Telmisartan and Amlodipine Tablets

Of the total number of 3282 hypertensive patients receiving a telmisartan/amlodipine combination in clinical studies, 605 (18%) patients were 65 years of age or older and of these, 88 (3%) patients were 75 years and older. No overall differences in efficacy or safety of telmisartan and amlodipine tablets were observed in this patient population.

7.3 Drug Interactions With Amlodipine

In clinical trials, amlodipine has been safely administered with thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, non-steroidal anti-inflammatory drugs, antibiotics, and oral hypoglycemic drugs.

14.1 Telmisartan and Amlodipine Tablets

The efficacy of telmisartan and amlodipine tablets for treatment of hypertension was studied in one placebo-controlled and two active-controlled trials.

An 8-week multicenter, randomized, double-blind, placebo-controlled, parallel group factorial study in patients with mild to severe hypertension was conducted to determine if treatment with telmisartan and amlodipine tablets was more effective in reducing blood pressure compared to the respective monotherapies. The study randomized 1461 patients with baseline systolic blood pressure between 117 and 179 mmHg (mean 153 mmHg) and a baseline diastolic blood pressure between 90 and 119 (mean 102 mmHg) to one of the 16 treatment arms. Patients assigned to receive amlodipine 10 mg started on amlodipine 5 mg or combinations thereof for the first 2 weeks. The four key treatment combinations (including combinations of telmisartan 40 or 80 mg and amlodipine 5 or 10 mg) had statistically significant reduction in in-clinic seated trough cuff systolic and diastolic blood pressure compared to the respective individual monotherapies (Table 5).

Table 5: Placebo-Subtracted Mean Change from Baseline in Seated Systolic/Diastolic Blood Pressure (mmHg): Combination Therapy vs Monotherapy Components

Amlodipine, mg	Telmisartan, mg
0	40	80
0	---	-12.1/-7.2	-11.8/-7.8
5	-12.9/-7.2	-19.3/-10.3	-19.6/-12.0
10	-18.2/-10.9	-22.2/-14.0	-23.9/-13.9

The majority of the antihypertensive effect of the telmisartan/amlodipine combination was attained within 2 weeks after initiation of therapy. In patients receiving a telmisartan/amlodipine combination, significantly larger reductions in seated diastolic and systolic blood pressure compared to patients treated with the respective monotherapies were observed at every assessment (Week 2, 4, 6, and 8).

The antihypertensive effect of telmisartan and amlodipine tablets was similar in patients ≥ 65 years than below 65 years of age, in male and female patients, and in patients with and without diabetes.

The magnitude of blood pressure lowering in black patients approached that observed in non-black patients but the number of black patients was limited (237 of 1461 patients).

Automated ambulatory blood pressure monitoring (ABPM) performed in a subset of 562 patients confirmed the results seen with in-clinic systolic and diastolic blood pressure reductions over the entire 24-hour dosing period.

In a double-blind, active-controlled study, a total of 1097 patients with mild to severe hypertension (mean baseline systolic/diastolic BP 149.5/96.6 mmHg) who were not adequately controlled on amlodipine 5 mg received telmisartan and amlodipine tablets (40/5 mg or 80/5 mg) or amlodipine alone (5 mg or 10 mg). After 8 weeks administration, each of the combination treatments was statistically significantly superior to both amlodipine monotherapy doses in reducing diastolic and systolic blood pressures. Edema related events (peripheral edema, generalized edema, and edema) in patients who received telmisartan and amlodipine tablets (40/5 mg or 80/5 mg) were significantly lower as compared to patients who received amlodipine 10 mg (4.3% vs 27.2%, respectively).

Table 6: Effect on Seated Systolic/Diastolic Blood Pressure: Combination Therapy vs Monotherapy

Treatment Group	Mean Change Mean change from baseline at Week 8 in seated systolic/diastolic blood pressure	Difference from Amlodipine 5 mg	Difference from Amlodipine 10 mg
Telmisartan and Amlodipine 40/5 mg; n = 270	-13.6/-9.4	-7.4 p < 0.05 /-3.6	-2.4 /-1.4
Telmisartan and Amlodipine 80/5 mg; n = 271	-15.0/-10.6	-8.8 /-4.9	-3.9 /-2.7
Amlodipine 5 mg; n = 255	-6.2/-5.7	---	---
Amlodipine 10 mg; n = 261	-11.1/-8.0	---	---

In a second double-blind, active-controlled study, a total of 947 patients with mild to severe hypertension (mean baseline systolic/diastolic BP 147.5/95.6 mmHg) who were not adequately controlled on amlodipine 10 mg received telmisartan and amlodipine tablets (40/10 mg or 80/10 mg) or amlodipine alone (10 mg). After 8 weeks, each of the combination treatments was statistically significantly superior to amlodipine monotherapy in reducing diastolic and systolic blood pressures.

Table 7: Effect on Seated Systolic/Diastolic Blood Pressure: Combination Therapy vs Monotherapy

Treatment Group	Mean Change Mean change from baseline at Week 8 in seated systolic/diastolic blood pressure	Difference from Amlodipine 10 mg
Telmisartan and Amlodipine 40/10 mg; n = 306	-11.1/-9.2	-3.7 p < 0.05 /-2.8
Telmisartan and Amlodipine 80/10 mg; n = 310	-11.3/-9.3	-3.9 /-2.8
Amlodipine 10 mg; n = 305	-7.4/-6.5	---

There are no trials of telmisartan and amlodipine tablets demonstrating reductions in cardiovascular risk in patients with hypertension, but at least one pharmacologically similar drug has demonstrated such benefits.

Principal Display Panel – 80 Mg/5 Mg

NDC 0378-1077-93

Telmisartan and

Amlodipine

Tablets, USP

80 mg/5 mg

Important: Do not remove from bottle until

immediately before administration.

Rx only 30 Tablets

Each tablet contains 80 mg of telmisartan,

USP and 6.935 mg of amlodipine besylate,

USP equivalent to 5 mg of amlodipine.

Usual Dosage: See accompanying

prescribing information.

Keep this and all medication out of the

reach of children.

Store at 20° to 25°C (68° to 77°F). [See

USP Controlled Room Temperature.]

Protect from moisture and light.

Manufactured for:

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Made in India

Mylan.com

RMX1077H6

Dispense in a tight, light-resistant

container as defined in the USP

using a child-resistant closure.

Keep container tightly closed.

Code No.: MH/DRUGS/25/NKD/89

Principal Display Panel – 80 Mg/10 Mg

NDC 0378-1078-93

Telmisartan and

Amlodipine

Tablets, USP

80 mg/10 mg

Important: Do not remove from bottle until

immediately before administration.

Rx only 30 Tablets

Each tablet contains 80 mg of telmisartan,

USP and 13.87 mg of amlodipine besylate,

USP equivalent to 10 mg of amlodipine.

Usual Dosage: See accompanying

prescribing information.

Keep this and all medication out of the

reach of children.

Store at 20° to 25°C (68° to 77°F). [See

USP Controlled Room Temperature.]

Protect from moisture and light.

Manufactured for:

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Made in India

Mylan.com

RMX1078H6

Dispense in a tight, light-resistant

container as defined in the USP

using a child-resistant closure.

Keep container tightly closed.

Code No.: MH/DRUGS/25/NKD/89

Principal Display Panel – 40 Mg/5 Mg

NDC 0378-1075-93

Telmisartan and

Amlodipine

Tablets, USP

40 mg/5 mg

Important: Do not remove from bottle until

immediately before administration.

Rx only 30 Tablets

Each tablet contains 40 mg of telmisartan,

USP and 6.935 mg of amlodipine besylate,

USP equivalent to 5 mg of amlodipine.

Usual Dosage: See accompanying

prescribing information.

Keep this and all medication out of the

reach of children.

Store at 20° to 25°C (68° to 77°F). [See

USP Controlled Room Temperature.]

Protect from moisture and light.

Manufactured for:

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Made in India

Mylan.com

RMX1075H6

Dispense in a tight, light-resistant

container as defined in the USP

using a child-resistant closure.

Keep container tightly closed.

Code No.: MH/DRUGS/25/NKD/89

Principal Display Panel – 40 Mg/10 Mg

NDC 0378-1076-93

Telmisartan and

Amlodipine

Tablets, USP

40 mg/10 mg

Important: Do not remove from bottle until

immediately before administration.

Rx only 30 Tablets

Each tablet contains 40 mg of telmisartan,

USP and 13.87 mg of amlodipine besylate,

USP equivalent to 10 mg of amlodipine.

Usual Dosage: See accompanying

prescribing information.

Keep this and all medication out of the

reach of children.

Store at 20° to 25°C (68° to 77°F). [See

USP Controlled Room Temperature.]

Protect from moisture and light.

Manufactured for:

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Made in India

Mylan.com

RMX1076H6

Dispense in a tight, light-resistant

container as defined in the USP

using a child-resistant closure.

Keep container tightly closed.

Code No.: MH/DRUGS/25/NKD/89

Disease Associated Maternal And/or Embryo/fetal Risk

Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly.

7.1 Drug Interactions With Telmisartan and Amlodipine Tablets

The pharmacokinetics of amlodipine and telmisartan are not altered when the drugs are co-administered.

No drug interaction studies have been conducted with telmisartan and amlodipine tablets and other drugs, although studies have been conducted with the individual amlodipine and telmisartan components of telmisartan and amlodipine tablets, as described below:

Neonates With A History of in Utero Exposure to Telmisartan and Amlodipine

If oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.

Non Steroidal Anti Inflammatory Agents Including Selective Cyclooxygenase 2 Inhibitors (cox 2 Inhibitors)

In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including telmisartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving telmisartan and NSAID therapy.

The antihypertensive effect of angiotensin II receptor antagonists, including telmisartan may be attenuated by NSAIDs including selective COX-2 inhibitors.

2.3 Add On Therapy for Patients With Hypertension Not Adequately Controlled On Antihypertensive Monotherapy

Telmisartan and amlodipine tablets may be used to provide additional blood pressure lowering for patients not adequately controlled with amlodipine (or another dihydropyridine calcium channel blocker) alone or with telmisartan (or another angiotensin receptor blocker) alone.

Patients treated with 10 mg amlodipine who experience any dose-limiting adverse reactions such as edema, may be switched to telmisartan and amlodipine 40/5 mg tablets once daily, reducing the dose of amlodipine without reducing the overall expected antihypertensive response [see Adverse Reactions (6.1) ].

Structured Label Content

Data

Telmisartan was present in the milk of lactating rats at concentrations of 1.5 to 2 times those found in plasma from 4 to 8 hours after administration.

Gender

Digoxin

Lithium

8.7 Race

The magnitude of blood pressure lowering in black patients approached that observed in non-black patients but the number of black patients was limited (237 of 1461 patients).

Aliskiren

Amlodipine

Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. Because of the gradual onset of action, acute hypotension is unlikely.

Creatinine

Hemoglobin

A greater than 2 g/dL decrease in hemoglobin was observed in 0.8% telmisartan patients compared with 0.3% placebo patients. No patients discontinued therapy due to anemia.

Animal Data

Other Drugs

Simvastatin

Telmisartan

Risk Summary

10 Overdosage (10 OVERDOSAGE)

Liver Enzymes

Telmisartan

Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers, including telmisartan.

11 Description (11 DESCRIPTION)

Telmisartan and amlodipine tablets, USP are a fixed dose combination of telmisartan and amlodipine.

Telmisartan and amlodipine tablets are hygroscopic and require protection from moisture.

Telmisartan and amlodipine tablets require protection from light.

Meets USP Dissolution Test 2

14.3 Amlodipine

Cyp3a4 Inducers (CYP3A4 Inducers)

Telmisartan

14.2 Telmisartan

There were no changes in the heart rate of patients treated with telmisartan in controlled trials.

Renal Impairment

No initial dosage adjustment is required for patients with mild or moderate renal impairment. Titrate slowly in patients with severe renal impairment.

8.4 Pediatric Use

Safety and effectiveness of telmisartan and amlodipine tablets in pediatric patients have not been established.

Cyp3a4 Inhibitors (CYP3A4 Inhibitors)

5.1 Fetal Toxicity

Hepatic Impairment

In most patients, initiate amlodipine therapy at 2.5 mg. Titrate slowly in patients with hepatic impairment.

Immunosuppressants

The following have no clinically relevant effects on the pharmacokinetics of amlodipine: cimetidine, grapefruit juice, magnesium and aluminum hydroxide antacid, sildenafil.

Amlodipine has no clinically relevant effects on the pharmacokinetics or pharmacodynamics of the following: atorvastatin, digoxin, warfarin.

2.4 Initial Therapy

Correct imbalances of intravascular volume- or salt-depletion, before initiating therapy with telmisartan and amlodipine tablets [see Warnings and Precautions (5.2) ].

4 Contraindications (4 CONTRAINDICATIONS)

Do not co-administer aliskiren with telmisartan and amlodipine tablets in patients with diabetes [see Drug Interactions (7.2)].

6 Adverse Reactions (6 ADVERSE REACTIONS)

•
In the placebo-controlled factorial design study, the most common reasons for discontinuation of therapy with telmisartan and amlodipine tablets were peripheral edema, dizziness, and hypotension, each leading to discontinuation of ≤ 0.5% of telmisartan and amlodipine tablet-treated patients. Adverse reactions that occurred at a ≥ 2% higher incidence on telmisartan and amlodipine tablets than placebo were peripheral edema (4.8% vs 0%), dizziness (3.0% vs 2.2%), and back pain (2.2% vs 0%). (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 Drug Interactions (7 DRUG INTERACTIONS)

•
NSAIDs: Increased risk of renal impairment and loss of antihypertensive effect. (7)
•
If simvastatin is co-administered with amlodipine, do not exceed doses greater than 20 mg daily of simvastatin. (7)
•
Do not co-administer aliskiren with telmisartan and amlodipine tablets in patients with diabetes. (7.2)

Patient Information

Telmisartan and Amlodipine Tablets, USP

(tel″ mi sar′ tan am loe′ di peen)

What is the most important information I should know about telmisartan and amlodipine tablets?

What are telmisartan and amlodipine tablets?

Telmisartan and amlodipine tablets are a prescription medicine that contains telmisartan and amlodipine.

Telmisartan and amlodipine tablets may be used to treat high blood pressure (hypertension):

•
when one of these medicines (or a similar one) is not enough to lower your high blood pressure
•
as the first medicine to lower your high blood pressure if your doctor decides you are likely to need more than one medicine

It is not known if telmisartan and amlodipine tablets are safe and effective in children.

Who should not take telmisartan and amlodipine tablets?

For patients with diabetes, if you are taking telmisartan and amlodipine tablets you should not take aliskiren.

What should I tell my doctor before taking telmisartan and amlodipine tablets?

Before you take telmisartan and amlodipine tablets, tell your doctor if you:

•
are pregnant or are planning to become pregnant. See “What is the most important information I should know about telmisartan and amlodipine tablets?”
•
are breast-feeding or plan to breast-feed. Telmisartan and amlodipine can pass into your breast milk and may harm your baby. You and your doctor should decide if you will take telmisartan and amlodipine tablets or breast-feed. You should not do both. Talk with your doctor about the best way to feed your baby if you take telmisartan and amlodipine tablets.
•
have liver problems
•
have kidney problems
•
have heart problems
•
have any other medical conditions

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements.

For patients with diabetes, if you are taking telmisartan and amlodipine tablets you should not take aliskiren.

Telmisartan and amlodipine tablets may affect the way other medicines work, and other medicines may affect how telmisartan and amlodipine tablets work. Especially tell your doctor if you take:

•
aliskiren
•
digoxin (Lanoxin^®)
•
lithium (Lithobid^®, lithium carbonate, lithium citrate)
•
aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs)
•
other medicines that may be used to treat high blood pressure or a heart problem
•
simvastatin (Zocor^®, Vytorin^®)
•
water pills (diuretics)

Know the medicines you take. Keep a list of them and show it to your doctor or pharmacist when you get a new medicine.

How should I take telmisartan and amlodipine tablets?

•
Take telmisartan and amlodipine tablets exactly as your doctor tells you to take them.
•
Your doctor will tell you how many telmisartan and amlodipine tablets to take and when to take them. Your doctor may change your dose if needed.
•
Take telmisartan and amlodipine tablets one time each day at the same time.
•
Take telmisartan and amlodipine tablets with or without food.
•
If you miss a dose, take it as soon as you remember. If it is close to your next dose, do not take the missed dose. Take the next dose at your regular time.
•
If you take too many telmisartan and amlodipine tablets, call your doctor or go to the nearest hospital emergency room right away.

What are possible side effects of telmisartan and amlodipine tablets?

Telmisartan and amlodipine tablets may cause serious side effects, including:

•
Injury or death to your unborn baby. See “What is the most important information I should know about telmisartan and amlodipine tablets?”
•
Low blood pressure (hypotension) is most likely to happen if you also:
- •
  take water pills (diuretics)
- •
  are on a low-salt diet
- •
  get dialysis treatments
- •
  have heart problems
- •
  get sick with vomiting or diarrhea
If you feel faint or dizzy, lie down and call your doctor right away.
•
Kidney problems. Kidney problems may get worse if you already have kidney disease. You may have changes in your kidney test results, and you may need a lower dose of telmisartan and amlodipine tablets. Call your doctor if you get:
- •
  swelling in your feet, ankles, or hands
- •
  unexplained weight gain
Call your doctor right away if you get any of the symptoms listed above.
•
Heart problems or heart attack. Heart problems may get worse in people that already have heart disease. This may happen when you start telmisartan and amlodipine tablets or when there is an increase in your dose of telmisartan and amlodipine tablets. Get emergency help if you get worse chest pain or chest pain that does not go away.
•
High potassium in the blood (hyperkalemia). Your doctor may check your potassium levels as needed.
•
Muscle rigidity, tremor and/or abnormal muscle movement.

Rare, serious allergic reactions may happen. Tell your doctor right away if you get any of these symptoms:

•
swelling of face, tongue, throat
•
difficulty breathing
•
skin rash

The most common side effects of telmisartan and amlodipine tablets include:

•
swelling in your hands, ankles, or feet
•
feeling like your heart is pounding or racing
•
flushing or sudden redness of the face and neck
•
dizziness
•
back pain
•
feeling tired or sleepy
•
abdominal pain, nausea, or diarrhea
•
low blood pressure or a sudden drop in blood pressure with fainting

These are not all the possible side effects of telmisartan and amlodipine tablets. Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store telmisartan and amlodipine tablets?

•
Store telmisartan and amlodipine tablets at room temperature 20° to 25°C (68° to 77°F).
•
Do not remove telmisartan and amlodipine tablets from bottles until right before you take them.
•
Keep telmisartan and amlodipine tablets out of the light and away from moisture.

Keep telmisartan and amlodipine tablets and all medicines out of the reach of children.

General information about telmisartan and amlodipine tablets

What are the ingredients in telmisartan and amlodipine tablets?

Active Ingredients: telmisartan and amlodipine besylate

What is high blood pressure (hypertension)?

This Patient Information has been approved by the U.S. Food and Drug Administration

The brands listed are trademarks of their respective owners.

Manufactured for:

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Manufactured by:

Mylan Laboratories Limited

Hyderabad — 500 096, India

75066865

Revised: 11/2018

MX:TLMSAM:R7

1 Indications and Usage (1 INDICATIONS AND USAGE)

Telmisartan and amlodipine tablets may also be used as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals.

Figure 1a: Probability of Achieving Systolic Blood Pressure < 140 mmHg at Week 8

Figure 1b: Probability of Achieving Systolic Blood Pressure < 130 mmHg at Week 8

Figure 2a: Probability of Achieving Diastolic Blood Pressure < 90 mmHg at Week 8

Figure 2b: Probability of Achieving Diastolic Blood Pressure < 80 mmHg at Week 8

2.2 Replacement Therapy

Warning: Fetal Toxicity (WARNING: FETAL TOXICITY)

•
When pregnancy is detected, discontinue telmisartan and amlodipine tablets as soon as possible [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].
•
Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].

8.6 Hepatic Insufficiency

2.1 General Considerations

Telmisartan is an effective treatment of hypertension in once daily doses of 20 to 80 mg while amlodipine is effective in doses of 2.5 to 10 mg.

Telmisartan and amlodipine tablets may be taken with or without food.

5 Warnings and Precautions (5 WARNINGS AND PRECAUTIONS)

•
Avoid fetal or neonatal exposure. (5.1)
•
Hypotension: Correct any volume or salt depletion before initiating therapy. Observe for signs and symptoms of hypotension. Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. (5.2)
•
Titrate slowly in patients with hepatic (5.4) or severe renal impairment. (5.5)
•
Heart failure: Monitor for worsening. (5.8)
•
Avoid concomitant use with an ACE inhibitor. (5.6)
•
Myocardial infarction: Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of telmisartan and amlodipine tablets, particularly in patients with severe obstructive coronary artery disease. (5.7)

2 Dosage and Administration (2 DOSAGE AND ADMINISTRATION)

•
Substitute telmisartan and amlodipine tablets for its individually titrated components for patients on amlodipine and telmisartan. Telmisartan and amlodipine tablets may also be given with increased amounts of amlodipine, telmisartan, or both, as needed. (2.2, 2.3)
•
Use telmisartan and amlodipine tablets to provide additional blood pressure lowering for patients not adequately controlled with amlodipine (or another dihydropyridine calcium channel blocker) alone or with telmisartan (or another angiotensin receptor blocker) alone. (2.3)
•
Dosage may be increased after at least 2 weeks to a maximum dose of 80/ 10 mg once daily, usually by increasing one component at a time but both components can be raised to achieve more rapid control. (2.1, 2.2)
•
Majority of antihypertensive effect is attained within 2 weeks. (2.1)
•
Initiate with 40/5 mg or 80/5 mg once daily. (2.4)
•
Switch patients who experience dose-limiting adverse reactions on amlodipine to telmisartan and amlodipine tablets containing a lower dose of that component. (2.3)

3 Dosage Forms and Strengths (3 DOSAGE FORMS AND STRENGTHS)

•
The 40 mg/5 mg tablets are bi-layered, mottled light blue and white to off-white, capsule shaped, unscored tablets with TA1M debossed on the white to off-white side of the tablet and blank on the mottled light blue side. The white to off-white layer may have a blue tinge or blue specks.
•
The 40 mg/10 mg tablets are bi-layered, mottled blue and white to off-white, capsule shaped, unscored tablets with TA2M debossed on the white to off-white side of the tablet and blank on the mottled blue side. The white to off-white layer may have a blue tinge or blue specks.
•
The 80 mg/5 mg tablets are bi-layered, mottled light blue and white to off-white, capsule shaped, unscored tablets with TA3M debossed on the white to off-white side of the tablet and blank on the mottled light blue side. The white to off-white layer may have a blue tinge or blue specks.
•
The 80 mg/10 mg tablets are bi-layered, mottled blue and white to off-white, capsule shaped, unscored tablets with TA4M debossed on the white to off-white side of the tablet and blank on the mottled blue side. The white to off-white layer may have a blue tinge or blue specks.

6.2 Postmarketing Experience

Clinical Laboratory Findings

In placebo-controlled clinical trials, clinically relevant changes in standard laboratory test parameters were rarely associated with administration of telmisartan tablets.

8 Use in Specific Populations (8 USE IN SPECIFIC POPULATIONS)

•
Patients ≥ 75 years of age or hepatically impaired patients: Start with amlodipine or add amlodipine 2.5 mg to telmisartan. (2.5, 8.5, 8.6)
•
Lactation: Do not breastfeed during treatment with telmisartan and amlodipine tablets. (8.2)

6.1 Clinical Trials Experience

Fetal/neonatal Adverse Reactions (Fetal/Neonatal Adverse Reactions)

17 Patient Counseling Information (17 PATIENT COUNSELING INFORMATION)

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Lactation: Advise nursing women not to breastfeed during treatment with telmisartan and amlodipine tablets [see Use in Specific Populations (8.2)].

Patients 75 Years of Age and Older

In most patients, initiate amlodipine therapy at 2.5 mg. Titrate slowly in patients 75 years of age and older.

Telmisartan and Amlodipine Tablets

The frequency of adverse reactions was not related to gender, age, or race.

Table 1: Incidence of Peripheral Edema During the 8-Week Treatment Period

	Telmisartan
	Placebo	40 mg	80 mg
Amlodipine	Placebo	0%	0.8%	0.7%
5 mg	0.7%	1.4%	2.1%
10 mg	17.8%	6.2%	11.3%

16 How Supplied/storage and Handling (16 HOW SUPPLIED/STORAGE AND HANDLING)

NDC 0378-1075-93

bottles of 30 tablets

NDC 0378-1076-93

bottles of 30 tablets

NDC 0378-1077-93

bottles of 30 tablets

NDC 0378-1078-93

bottles of 30 tablets

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Protect from moisture and light.

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Telmisartan and Amlodipine Tablets

7.3 Drug Interactions With Amlodipine (7.3 Drug Interactions with Amlodipine)

14.1 Telmisartan and Amlodipine Tablets

The efficacy of telmisartan and amlodipine tablets for treatment of hypertension was studied in one placebo-controlled and two active-controlled trials.

Table 5: Placebo-Subtracted Mean Change from Baseline in Seated Systolic/Diastolic Blood Pressure (mmHg): Combination Therapy vs Monotherapy Components

Amlodipine, mg	Telmisartan, mg
0	40	80
0	---	-12.1/-7.2	-11.8/-7.8
5	-12.9/-7.2	-19.3/-10.3	-19.6/-12.0
10	-18.2/-10.9	-22.2/-14.0	-23.9/-13.9

The magnitude of blood pressure lowering in black patients approached that observed in non-black patients but the number of black patients was limited (237 of 1461 patients).

Table 6: Effect on Seated Systolic/Diastolic Blood Pressure: Combination Therapy vs Monotherapy

Treatment Group	Mean Change Mean change from baseline at Week 8 in seated systolic/diastolic blood pressure	Difference from Amlodipine 5 mg	Difference from Amlodipine 10 mg
Telmisartan and Amlodipine 40/5 mg; n = 270	-13.6/-9.4	-7.4 p < 0.05 /-3.6	-2.4 /-1.4
Telmisartan and Amlodipine 80/5 mg; n = 271	-15.0/-10.6	-8.8 /-4.9	-3.9 /-2.7
Amlodipine 5 mg; n = 255	-6.2/-5.7	---	---
Amlodipine 10 mg; n = 261	-11.1/-8.0	---	---

Table 7: Effect on Seated Systolic/Diastolic Blood Pressure: Combination Therapy vs Monotherapy

Treatment Group	Mean Change Mean change from baseline at Week 8 in seated systolic/diastolic blood pressure	Difference from Amlodipine 10 mg
Telmisartan and Amlodipine 40/10 mg; n = 306	-11.1/-9.2	-3.7 p < 0.05 /-2.8
Telmisartan and Amlodipine 80/10 mg; n = 310	-11.3/-9.3	-3.9 /-2.8
Amlodipine 10 mg; n = 305	-7.4/-6.5	---

Principal Display Panel – 80 Mg/5 Mg (PRINCIPAL DISPLAY PANEL – 80 mg/5 mg )

NDC 0378-1077-93

Telmisartan and

Amlodipine

Tablets, USP

80 mg/5 mg

Important: Do not remove from bottle until

immediately before administration.

Rx only 30 Tablets

Each tablet contains 80 mg of telmisartan,

USP and 6.935 mg of amlodipine besylate,

USP equivalent to 5 mg of amlodipine.

Usual Dosage: See accompanying

prescribing information.

Keep this and all medication out of the

reach of children.

Store at 20° to 25°C (68° to 77°F). [See

USP Controlled Room Temperature.]

Protect from moisture and light.

Manufactured for:

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Made in India

Mylan.com

RMX1077H6

Dispense in a tight, light-resistant

container as defined in the USP

using a child-resistant closure.

Keep container tightly closed.

Code No.: MH/DRUGS/25/NKD/89

Principal Display Panel – 80 Mg/10 Mg (PRINCIPAL DISPLAY PANEL – 80 mg/10 mg )

NDC 0378-1078-93

Telmisartan and

Amlodipine

Tablets, USP

80 mg/10 mg

Important: Do not remove from bottle until

immediately before administration.

Rx only 30 Tablets

Each tablet contains 80 mg of telmisartan,

USP and 13.87 mg of amlodipine besylate,

USP equivalent to 10 mg of amlodipine.

Usual Dosage: See accompanying

prescribing information.

Keep this and all medication out of the

reach of children.

Store at 20° to 25°C (68° to 77°F). [See

USP Controlled Room Temperature.]

Protect from moisture and light.

Manufactured for:

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Made in India

Mylan.com

RMX1078H6

Dispense in a tight, light-resistant

container as defined in the USP

using a child-resistant closure.

Keep container tightly closed.

Code No.: MH/DRUGS/25/NKD/89

Principal Display Panel – 40 Mg/5 Mg (PRINCIPAL DISPLAY PANEL – 40 mg/5 mg )

NDC 0378-1075-93

Telmisartan and

Amlodipine

Tablets, USP

40 mg/5 mg

Important: Do not remove from bottle until

immediately before administration.

Rx only 30 Tablets

Each tablet contains 40 mg of telmisartan,

USP and 6.935 mg of amlodipine besylate,

USP equivalent to 5 mg of amlodipine.

Usual Dosage: See accompanying

prescribing information.

Keep this and all medication out of the

reach of children.

Store at 20° to 25°C (68° to 77°F). [See

USP Controlled Room Temperature.]

Protect from moisture and light.

Manufactured for:

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Made in India

Mylan.com

RMX1075H6

Dispense in a tight, light-resistant

container as defined in the USP

using a child-resistant closure.

Keep container tightly closed.

Code No.: MH/DRUGS/25/NKD/89

Principal Display Panel – 40 Mg/10 Mg (PRINCIPAL DISPLAY PANEL – 40 mg/10 mg )

NDC 0378-1076-93

Telmisartan and

Amlodipine

Tablets, USP

40 mg/10 mg

Important: Do not remove from bottle until

immediately before administration.

Rx only 30 Tablets

Each tablet contains 40 mg of telmisartan,

USP and 13.87 mg of amlodipine besylate,

USP equivalent to 10 mg of amlodipine.

Usual Dosage: See accompanying

prescribing information.

Keep this and all medication out of the

reach of children.

Store at 20° to 25°C (68° to 77°F). [See

USP Controlled Room Temperature.]

Protect from moisture and light.

Manufactured for:

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Made in India

Mylan.com

RMX1076H6

Dispense in a tight, light-resistant

container as defined in the USP

using a child-resistant closure.

Keep container tightly closed.

Code No.: MH/DRUGS/25/NKD/89

Disease Associated Maternal And/or Embryo/fetal Risk (Disease-associated Maternal and/or Embryo/Fetal Risk)

7.1 Drug Interactions With Telmisartan and Amlodipine Tablets (7.1 Drug Interactions with Telmisartan and Amlodipine Tablets)

The pharmacokinetics of amlodipine and telmisartan are not altered when the drugs are co-administered.

Neonates With A History of in Utero Exposure to Telmisartan and Amlodipine (Neonates with a History of in Utero Exposure to Telmisartan and Amlodipine)

Non Steroidal Anti Inflammatory Agents Including Selective Cyclooxygenase 2 Inhibitors (cox 2 Inhibitors) (Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors))

The antihypertensive effect of angiotensin II receptor antagonists, including telmisartan may be attenuated by NSAIDs including selective COX-2 inhibitors.

2.3 Add On Therapy for Patients With Hypertension Not Adequately Controlled On Antihypertensive Monotherapy (2.3 Add-on Therapy for Patients with Hypertension Not Adequately Controlled on Antihypertensive Monotherapy)

Advanced Ingredient Data

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Raw Label Data

All Sections (JSON)

{"Data": "Telmisartan was present in the milk of lactating rats at concentrations of 1.5 to 2 times those found in plasma from 4 to 8 hours after administration.", "Gender": "Plasma concentrations of telmisartan are generally 2 to 3 times higher in females than in males. In clinical trials, however, no significant increases in blood pressure response or in the incidence of orthostatic hypotension were found in women. No dosage adjustment is necessary.", "Digoxin": "When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed. Therefore, monitor digoxin levels when initiating, adjusting, and discontinuing telmisartan for the purpose of keeping the digoxin level within the therapeutic range.", "Lithium": "Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin II receptor antagonists including telmisartan. Therefore, monitor serum lithium levels during concomitant use.", "8.7 Race": "The magnitude of blood pressure lowering in black patients approached that observed in non-black patients but the number of black patients was limited (237 of 1461 patients).", "Aliskiren": "Do not co-administer aliskiren with telmisartan and amlodipine tablets in patients with diabetes. Avoid use of aliskiren with telmisartan and amlodipine tablets in patients with renal impairment (GFR < 60 mL/min).", "Amlodipine": "Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. Because of the gradual onset of action, acute hypotension is unlikely.", "Creatinine": "A 0.5 mg/dL rise or greater in creatinine was observed in 0.4% telmisartan patients compared with 0.3% placebo patients. One telmisartan-treated patient discontinued therapy due to increases in creatinine and blood urea nitrogen.", "Hemoglobin": "A greater than 2 g/dL decrease in hemoglobin was observed in 0.8% telmisartan patients compared with 0.3% placebo patients. No patients discontinued therapy due to anemia.", "Animal Data": "No reproductive toxicity studies have been conducted with the combination of telmisartan and amlodipine besylate. However, these studies have been conducted for telmisartan and amlodipine besylate alone.", "Other Drugs": "Co-administration of telmisartan did not result in a clinically significant interaction with acetaminophen, amlodipine, glyburide, simvastatin, hydrochlorothiazide, warfarin, or ibuprofen. Telmisartan is not metabolized by the cytochrome P450 system and had no effects in vitro on cytochrome P450 enzymes, except for some inhibition of CYP2C19. Telmisartan is not expected to interact with drugs that inhibit cytochrome P450 enzymes; it is also not expected to interact with drugs metabolized by cytochrome P450 enzymes, except for possible inhibition of the metabolism of drugs metabolized by CYP2C19.", "Simvastatin": "Co-administration of multiple doses of 10 mg of amlodipine with 80 mg simvastatin resulted in a 77% increase in exposure to simvastatin compared to simvastatin alone. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.", "Telmisartan": "In patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of therapy with telmisartan and amlodipine tablets. Either correct this condition prior to administration of telmisartan and amlodipine tablets, or start treatment under close medical supervision with a reduced dose. If hypotension does occur, place the patient in the supine position and, if necessary, give an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment, which usually can be continued without difficulty once the blood pressure has stabilized.", "Risk Summary": "Telmisartan and amlodipine tablets can cause fetal harm when administered to a pregnant woman. Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death (see Clinical Considerations ). Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Studies in rats and rabbits with telmisartan showed fetotoxicity only at maternally toxic doses (see Data ) . In animal reproduction studies, there was no evidence of adverse developmental effects when pregnant rats and rabbits were treated orally with amlodipine maleate during organogenesis at doses approximately 10 and 20-times the maximum recommended human dose (MRHD), respectively. However for rats, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold). Amlodipine has been shown to prolong both the gestation period and the duration of labor in rats at this dose (see Data ). When pregnancy is detected, discontinue telmisartan and amlodipine tablets as soon as possible. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major malformations and miscarriage in clinically recognized pregnancies is 2% to 4%, and 15% to 20%, respectively.", "10 OVERDOSAGE": "Telmisartan Limited data are available with regard to overdosage in humans. The most likely manifestations of overdosage with telmisartan tablets would be hypotension, dizziness, and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Telmisartan is not removed by hemodialysis. Amlodipine Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia. In humans, experience with intentional overdosage of amlodipine is limited. Single oral doses of amlodipine maleate equivalent to 40 mg amlodipine/kg and 100 mg amlodipine/kg in mice and rats, respectively, caused deaths. Single oral amlodipine maleate doses equivalent to 4 or more mg amlodipine/kg or higher in dogs (11 or more times the maximum recommended human dose on a mg/m 2 basis) caused a marked peripheral vasodilation and hypotension. If massive overdose should occur, initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential. Should hypotension occur, provide cardiovascular support including elevation of the extremities and the judicious administration of fluids. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors (such as phenylephrine) with attention to circulating volume and urine output. As amlodipine is highly protein bound, hemodialysis is not likely to be of benefit.", "Liver Enzymes": "Occasional elevations of liver chemistries occurred in patients treated with telmisartan; all marked elevations occurred at a higher frequency with placebo. No telmisartan-treated patients discontinued therapy due to abnormal hepatic function.", "Telmisartan ": "The most frequently spontaneously reported events include: headache, dizziness, asthenia, coughing, nausea, fatigue, weakness, edema, face edema, lower limb edema, angioneurotic edema, urticaria, hypersensitivity, sweating increased, erythema, chest pain, atrial fibrillation, congestive heart failure, myocardial infarction, blood pressure increased, hypertension aggravated, hypotension (including postural hypotension), hyperkalemia, syncope, dyspepsia, diarrhea, pain, urinary tract infection, erectile dysfunction, back pain, abdominal pain, muscle cramps (including leg cramps), myalgia, bradycardia, eosinophilia, thrombocytopenia, uric acid increased, abnormal hepatic function/liver disorder, renal impairment including acute renal failure, anemia, and increased CPK, anaphylactic reaction, tendon pain (including tendonitis, tenosynovitis), drug eruption (e.g., toxic skin eruption mostly reported as toxicoderma, rash, and urticaria), hypoglycemia (in diabetic patients), and angioedema (with fatal outcome). Rare cases of rhabdomyolysis have been reported in patients receiving angiotensin II receptor blockers, including telmisartan.", "11 DESCRIPTION": "Telmisartan and amlodipine tablets, USP are a fixed dose combination of telmisartan and amlodipine. Telmisartan and amlodipine tablets contain telmisartan, a non-peptide angiotensin II receptor (type AT 1 ) antagonist. Telmisartan, USP is a white or slightly yellowish crystalline powder. It is practically insoluble in water and in the pH range of 3 to 9, sparingly soluble in strong acid (except insoluble in hydrochloric acid), and soluble in strong base. Telmisartan is chemically described as 4′-[[4-Methyl-6-(1-methyl-1 H -benzimidazol-2yl)-2-propyl-1 H -benzimidazol-1yl]methyl]biphenyl-2-carboxylic acid. Its molecular formula is C 33 H 30 N 4 O 2 and its structural formula is: Telmisartan and amlodipine tablets contain the besylate salt of amlodipine, a dihydropyridine calcium-channel blocker (CCB). Amlodipine besylate, USP is a white or almost white powder, slightly soluble in water and sparingly soluble in ethanol. Amlodipine besylate’s chemical name is 3-ethyl 5-methyl (4 RS )-2-[(2-aminoethoxy) methyl]-4-(2-chlorophenyl)-6-methyl-1,4 dihydropyridine-3,5-dicarboxylate benzenesulfonate. Its molecular formula is C 20 H 25 ClN 2 O 5 •C 6 H 6 O 3 S and its structural formula is: Telmisartan and amlodipine tablets are formulated in four strengths for oral administration with a combination of amlodipine besylate, equivalent to 5 mg or 10 mg of amlodipine free-base, with 40 mg or 80 mg of telmisartan provided in the following four combinations: 40/5 mg, 40/10 mg, 80/5 mg and 80/10 mg. Telmisartan and amlodipine tablets also contain the following inactive ingredients: colloidal silicon dioxide, corn starch, FD&C Blue No. 1 Aluminum Lake, magnesium stearate, mannitol, meglumine, microcrystalline cellulose, povidone, pregelatinized starch (corn) and sodium hydroxide. Telmisartan and amlodipine tablets are hygroscopic and require protection from moisture. Telmisartan and amlodipine tablets require protection from light. Meets USP Dissolution Test 2", "14.3 Amlodipine": "The antihypertensive efficacy of amlodipine has been demonstrated in a total of 15 double-blind, placebo-controlled, randomized studies involving 800 patients on amlodipine and 538 on placebo. Once daily administration produced statistically significant placebo-corrected reductions in supine and standing blood pressures at 24 hours post-dose, averaging about 12/6 mmHg in the standing position and 13/7 mmHg in the supine position in patients with mild to moderate hypertension. Maintenance of the blood pressure effect over the 24-hour dosing interval was observed, with little difference in peak and trough effect.", "CYP3A4 Inducers": "No information is available on the quantitative effects of CYP3A4 inducers ( e.g., carbamazepine, phenobarbital, phenytoin, fosphenytoin, primidone, rifampicin, St. John’s Wort ) on amlodipine. Patients should be monitored for adequate clinical effect when amlodipine is co-administered with CYP3A4 inducers.", "Telmisartan ": "Telmisartan is highly bound to plasma proteins (> 99.5%), mainly albumin and α 1 -acid glycoprotein. Plasma protein binding is constant over the concentration range achieved with recommended doses. The volume of distribution for telmisartan is approximately 500 liters indicating additional tissue binding.", "14.2 Telmisartan": "The antihypertensive effects of telmisartan have been demonstrated in six principal placebo-controlled clinical trials, studying a range of 20 to 160 mg; one of these examined the antihypertensive effects of telmisartan and hydrochlorothiazide in combination. The studies involved a total of 1773 patients with mild to moderate hypertension (diastolic blood pressure of 95 to 114 mmHg), 1031 of whom were treated with telmisartan. Following once daily administration of telmisartan, the magnitude of blood pressure reduction from baseline after placebo subtraction was approximately (SBP/DBP) 6-8/6 mmHg for 20 mg, 9-13/6-8 mmHg for 40 mg, and 12-13/7-8 mmHg for 80 mg. Larger doses (up to 160 mg) did not appear to cause a further decrease in blood pressure. Upon initiation of antihypertensive treatment with telmisartan, blood pressure was reduced after the first dose, with a maximal reduction by about 4 weeks. With cessation of treatment with telmisartan tablets, blood pressure gradually returned to baseline values over a period of several days to 1 week. During long-term studies (without placebo control) the effect of telmisartan appeared to be maintained for up to at least 1 year. The antihypertensive effect of telmisartan is not influenced by patient age, gender, weight, or body mass index. Blood pressure response in black patients (usually a low-renin population) is noticeably less than that in Caucasian patients. This has been true for most, but not all, angiotensin II antagonists and ACE inhibitors. In a controlled study, the addition of telmisartan to hydrochlorothiazide produced an additional dose-related reduction in blood pressure that was similar in magnitude to the reduction achieved with telmisartan monotherapy. Hydrochlorothiazide also had an added blood pressure effect when added to telmisartan. The onset of antihypertensive activity occurs within 3 hours after administration of a single oral dose. At doses of 20, 40, and 80 mg, the antihypertensive effect of once daily administration of telmisartan is maintained for the full 24-hour dose interval. With automated ambulatory blood pressure monitoring and conventional blood pressure measurements, the 24-hour trough-to-peak ratio for 40 to 80 mg doses of telmisartan was 70% to 100% for both systolic and diastolic blood pressure. The incidence of symptomatic orthostasis after the first dose in all controlled trials was low (0.04%). There were no changes in the heart rate of patients treated with telmisartan in controlled trials.", "Renal Impairment": "No initial dosage adjustment is required for patients with mild or moderate renal impairment. Titrate slowly in patients with severe renal impairment.", "8.4 Pediatric Use": "Safety and effectiveness of telmisartan and amlodipine tablets in pediatric patients have not been established.", "CYP3A4 Inhibitors": "Co-administration of a 180 mg daily dose of diltiazem with 5 mg amlodipine in elderly hypertensive patients resulted in a 60% increase in amlodipine systemic exposure. Erythromycin co-administration in healthy volunteers did not significantly change amlodipine systemic exposure. However, strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, ritonavir) may increase the plasma concentrations of amlodipine to a greater extent. Monitor for symptoms of hypotension and edema when amlodipine is co-administered with CYP3A4 inhibitors.", "5.1 Fetal Toxicity": "Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue telmisartan and amlodipine tablets as soon as possible [see Use in Specific Populations (8.1) ].", "Hepatic Impairment": "In most patients, initiate amlodipine therapy at 2.5 mg. Titrate slowly in patients with hepatic impairment.", "Immunosuppressants": "Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. Frequent monitoring of trough blood levels of cyclosporine and tacrolimus and dose adjustment when appropriate is recommended. The following have no clinically relevant effects on the pharmacokinetics of amlodipine: cimetidine, grapefruit juice, magnesium and aluminum hydroxide antacid, sildenafil. Amlodipine has no clinically relevant effects on the pharmacokinetics or pharmacodynamics of the following: atorvastatin, digoxin, warfarin.", "2.4 Initial Therapy": "A patient may be initiated on telmisartan and amlodipine tablets if it is unlikely that control of blood pressure would be achieved with a single agent. The usual starting dose of telmisartan and amlodipine tablets is 40/5 mg once daily. Patients requiring larger blood pressure reductions may be started on telmisartan and amlodipine tablets 80/5 mg once daily. Initial therapy with telmisartan and amlodipine tablets is not recommended in patients ≥ 75 years old or with hepatic impairment [ see Dosage and Administration (2.5) , Warnings and Precautions (5.4) , and Use in Specific Populations (8.5 , 8.6) ]. Correct imbalances of intravascular volume- or salt-depletion, before initiating therapy with telmisartan and amlodipine tablets [ see Warnings and Precautions (5.2) ].", "4 CONTRAINDICATIONS": "Telmisartan and amlodipine tablets are contraindicated in patients with known hypersensitivity (e.g., anaphylaxis or angioedema) to telmisartan, amlodipine, or any other component of this product [see Adverse Reactions (6.2) ] . Do not co-administer aliskiren with telmisartan and amlodipine tablets in patients with diabetes [see Drug Interactions (7.2) ] .", "6 ADVERSE REACTIONS": "• In the placebo-controlled factorial design study, the most common reasons for discontinuation of therapy with telmisartan and amlodipine tablets were peripheral edema, dizziness, and hypotension, each leading to discontinuation of ≤ 0.5% of telmisartan and amlodipine tablet-treated patients. Adverse reactions that occurred at a ≥ 2% higher incidence on telmisartan and amlodipine tablets than placebo were peripheral edema (4.8% vs 0%), dizziness (3.0% vs 2.2%), and back pain (2.2% vs 0%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .", "7 DRUG INTERACTIONS": "• NSAIDs: Increased risk of renal impairment and loss of antihypertensive effect. ( 7 ) • If simvastatin is co-administered with amlodipine, do not exceed doses greater than 20 mg daily of simvastatin. ( 7 ) • Do not co-administer aliskiren with telmisartan and amlodipine tablets in patients with diabetes. ( 7.2 )", "Patient Information": "Telmisartan and Amlodipine Tablets, USP (tel″ mi sar′ tan am loe′ di peen) Read this Patient Information before you start taking telmisartan and amlodipine tablets and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment. What is the most important information I should know about telmisartan and amlodipine tablets? Telmisartan and amlodipine tablets can cause harm or death to an unborn baby. Talk to your doctor about other ways to lower your blood pressure if you plan to become pregnant. If you get pregnant while taking telmisartan and amlodipine tablets, tell your doctor right away. What are telmisartan and amlodipine tablets? Telmisartan and amlodipine tablets are a prescription medicine that contains telmisartan and amlodipine. Telmisartan and amlodipine tablets may be used to treat high blood pressure (hypertension): • when one of these medicines (or a similar one) is not enough to lower your high blood pressure • as the first medicine to lower your high blood pressure if your doctor decides you are likely to need more than one medicine It is not known if telmisartan and amlodipine tablets are safe and effective in children. Who should not take telmisartan and amlodipine tablets? You should not take telmisartan and amlodipine tablets if you are allergic (hypersensitive) to the active ingredients (telmisartan or amlodipine) or any of the other ingredients listed at the end of this leaflet. For patients with diabetes, if you are taking telmisartan and amlodipine tablets you should not take aliskiren. What should I tell my doctor before taking telmisartan and amlodipine tablets? Before you take telmisartan and amlodipine tablets, tell your doctor if you: • are pregnant or are planning to become pregnant. See “ What is the most important information I should know about telmisartan and amlodipine tablets? ” • are breast-feeding or plan to breast-feed. Telmisartan and amlodipine can pass into your breast milk and may harm your baby. You and your doctor should decide if you will take telmisartan and amlodipine tablets or breast-feed. You should not do both. Talk with your doctor about the best way to feed your baby if you take telmisartan and amlodipine tablets. • have liver problems • have kidney problems • have heart problems • have any other medical conditions Tell your doctor about all the medicines you take , including prescription and nonprescription medicines, vitamins and herbal supplements. For patients with diabetes, if you are taking telmisartan and amlodipine tablets you should not take aliskiren. Telmisartan and amlodipine tablets may affect the way other medicines work, and other medicines may affect how telmisartan and amlodipine tablets work. Especially tell your doctor if you take: • aliskiren • digoxin (Lanoxin ® ) • lithium (Lithobid ® , lithium carbonate, lithium citrate) • aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) • other medicines that may be used to treat high blood pressure or a heart problem • simvastatin (Zocor ® , Vytorin ® ) • water pills (diuretics) Know the medicines you take. Keep a list of them and show it to your doctor or pharmacist when you get a new medicine. How should I take telmisartan and amlodipine tablets? • Take telmisartan and amlodipine tablets exactly as your doctor tells you to take them. • Your doctor will tell you how many telmisartan and amlodipine tablets to take and when to take them. Your doctor may change your dose if needed. • Take telmisartan and amlodipine tablets one time each day at the same time. • Take telmisartan and amlodipine tablets with or without food. • If you miss a dose, take it as soon as you remember. If it is close to your next dose, do not take the missed dose. Take the next dose at your regular time. • If you take too many telmisartan and amlodipine tablets, call your doctor or go to the nearest hospital emergency room right away. What are possible side effects of telmisartan and amlodipine tablets? Telmisartan and amlodipine tablets may cause serious side effects, including: • Injury or death to your unborn baby. See “What is the most important information I should know about telmisartan and amlodipine tablets?” • Low blood pressure (hypotension) is most likely to happen if you also: • take water pills (diuretics) • are on a low-salt diet • get dialysis treatments • have heart problems • get sick with vomiting or diarrhea If you feel faint or dizzy, lie down and call your doctor right away. • Kidney problems . Kidney problems may get worse if you already have kidney disease. You may have changes in your kidney test results, and you may need a lower dose of telmisartan and amlodipine tablets. Call your doctor if you get: • swelling in your feet, ankles, or hands • unexplained weight gain Call your doctor right away if you get any of the symptoms listed above. • Heart problems or heart attack. Heart problems may get worse in people that already have heart disease. This may happen when you start telmisartan and amlodipine tablets or when there is an increase in your dose of telmisartan and amlodipine tablets. Get emergency help if you get worse chest pain or chest pain that does not go away. • High potassium in the blood (hyperkalemia). Your doctor may check your potassium levels as needed. • Muscle rigidity, tremor and/or abnormal muscle movement. Rare, serious allergic reactions may happen. Tell your doctor right away if you get any of these symptoms: • swelling of face, tongue, throat • difficulty breathing • skin rash The most common side effects of telmisartan and amlodipine tablets include: • swelling in your hands, ankles, or feet • feeling like your heart is pounding or racing • flushing or sudden redness of the face and neck • dizziness • back pain • feeling tired or sleepy • abdominal pain, nausea, or diarrhea • low blood pressure or a sudden drop in blood pressure with fainting These are not all the possible side effects of telmisartan and amlodipine tablets. Tell your doctor if you have any side effect that bothers you or that does not go away. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store telmisartan and amlodipine tablets? • Store telmisartan and amlodipine tablets at room temperature 20 ° to 25 ° C (68 ° to 77 ° F). • Do not remove telmisartan and amlodipine tablets from bottles until right before you take them. • Keep telmisartan and amlodipine tablets out of the light and away from moisture. Keep telmisartan and amlodipine tablets and all medicines out of the reach of children. General information about telmisartan and amlodipine tablets Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use telmisartan and amlodipine tablets for a condition for which they were not prescribed. Do not give telmisartan and amlodipine tablets to other people, even if they have the same symptoms that you have. They may harm them. This Patient Information leaflet summarizes the most important information about telmisartan and amlodipine tablets. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about telmisartan and amlodipine tablets that is written for health professionals. For more information, call Mylan at 1-877-446-3679 (1-877-4-INFO-RX). What are the ingredients in telmisartan and amlodipine tablets? Active Ingredients: telmisartan and amlodipine besylate Inactive Ingredients: colloidal silicon dioxide, corn starch, FD&C Blue No. 1 Aluminum Lake, magnesium stearate, mannitol, meglumine, microcrystalline cellulose, povidone, pregelatinized starch (corn) and sodium hydroxide. What is high blood pressure (hypertension)? Blood pressure is the force in your blood vessels when your heart beats and when your heart rests. You have high blood pressure when the force is too much. Telmisartan and amlodipine tablets can help your blood vessels relax so your blood pressure is lower. Medicines that lower your blood pressure lower your chance of having a stroke or heart attack. High blood pressure makes the heart work harder to pump blood throughout the body and causes damage to the blood vessels. If high blood pressure is not treated, it can lead to stroke, heart attack, heart failure, kidney failure, and vision problems. This Patient Information has been approved by the U.S. Food and Drug Administration The brands listed are trademarks of their respective owners. Manufactured for: Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A. Manufactured by: Mylan Laboratories Limited Hyderabad — 500 096, India 75066865 Revised: 11/2018 MX:TLMSAM:R7", "1 INDICATIONS AND USAGE": "Telmisartan and amlodipine tablets are indicated for the treatment of hypertension, alone or with other antihypertensive agents to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including angiotensin II receptor blockers and dihydropyridine calcium channel blockers. There are no controlled trials demonstrating risk reduction with telmisartan and amlodipine tablets. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than one drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education Program’s Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Telmisartan and amlodipine tablets may also be used as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals. Base the choice of telmisartan and amlodipine tablets as initial therapy for hypertension on an assessment of potential benefits and risks including whether the patient is likely to tolerate the starting dose of telmisartan and amlodipine tablets. Patients with moderate or severe hypertension are at relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. Consider the patient's baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared with monotherapy when deciding whether to use telmisartan and amlodipine tablets as initial therapy. Individual blood pressure goals may vary based upon the patient’s risk. Data from an 8-week, placebo-controlled, multidose, factorial trial provide estimates of the probability of reaching a blood pressure goal with telmisartan and amlodipine tablets compared to telmisartan or amlodipine monotherapy and placebo [ see Clinical Studies (14.1) ]. The figures below provide estimates of the likelihood of achieving systolic and diastolic blood pressure control with telmisartan and amlodipine 80/10 mg tablets, based upon baseline systolic or diastolic blood pressure. The curve of each treatment group was estimated by logistic regression modeling. The estimated likelihood at the right tail of each curve is less reliable due to small numbers of subjects with high baseline blood pressures. Figure 1a: Probability of Achieving Systolic Blood Pressure < 140 mmHg at Week 8 Figure 1b: Probability of Achieving Systolic Blood Pressure < 130 mmHg at Week 8 Figure 2a: Probability of Achieving Diastolic Blood Pressure < 90 mmHg at Week 8 Figure 2b: Probability of Achieving Diastolic Blood Pressure < 80 mmHg at Week 8 The figures above provide an approximation of the likelihood of reaching a targeted blood pressure goal at 8 weeks. For example, a patient with a baseline blood pressure of 160/110 mmHg has about a 16% likelihood of achieving a goal of < 140 mmHg (systolic) and 16% likelihood of achieving < 90 mmHg (diastolic) on placebo. The likelihood of achieving these same goals on telmisartan is about 46% (systolic) and 26% (diastolic). The likelihood of achieving these same goals on amlodipine is about 69% (systolic) and 22% (diastolic). These likelihoods rise to 79% for systolic and 55% for diastolic with telmisartan and amlodipine tablets.", "2.2 Replacement Therapy": "Patients receiving amlodipine and telmisartan from separate tablets may instead receive telmisartan and amlodipine tablets containing the same component doses once daily. When substituting for individual components, increase the dose of telmisartan and amlodipine tablets if blood pressure control has not been satisfactory.", "WARNING: FETAL TOXICITY": "• When pregnancy is detected, discontinue telmisartan and amlodipine tablets as soon as possible [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ]. • Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ].", "8.6 Hepatic Insufficiency": "Monitor carefully and uptitrate slowly in patients with biliary obstructive disorders or hepatic insufficiency [ see Dosage and Administration (2) and Warnings and Precautions (5.4) ]. Since patients with hepatic impairment have decreased clearance of amlodipine, start amlodipine or add amlodipine 2.5 mg to telmisartan. The lowest dose of telmisartan and amlodipine tablets is 40/5 mg; therefore, initial therapy with telmisartan and amlodipine tablets is not recommended in hepatically impaired patients [ see Dosage and Administration (2.4) ].", "2.1 General Considerations": "Telmisartan is an effective treatment of hypertension in once daily doses of 20 to 80 mg while amlodipine is effective in doses of 2.5 to 10 mg. Dosage must be individualized and may be increased after at least 2 weeks. Most of the antihypertensive effect is apparent within 2 weeks and maximal reduction is generally attained after 4 weeks. The maximum recommended dose of telmisartan and amlodipine tablets is 80/10 mg once daily. The adverse reactions of telmisartan are uncommon and independent of dose; those of amlodipine are a mixture of dose-dependent phenomena (primarily peripheral edema) and dose-independent phenomena, the former much more common than the latter [ see Adverse Reactions (6.1) ]. Telmisartan and amlodipine tablets may be taken with or without food.", "5 WARNINGS AND PRECAUTIONS": "• Avoid fetal or neonatal exposure. ( 5.1 ) • Hypotension: Correct any volume or salt depletion before initiating therapy. Observe for signs and symptoms of hypotension. Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. ( 5.2 ) • Titrate slowly in patients with hepatic ( 5.4 ) or severe renal impairment. ( 5.5 ) • Heart failure: Monitor for worsening. ( 5.8 ) • Avoid concomitant use with an ACE inhibitor. ( 5.6 ) • Myocardial infarction: Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of telmisartan and amlodipine tablets, particularly in patients with severe obstructive coronary artery disease. ( 5.7 )", "2 DOSAGE AND ADMINISTRATION": "• Substitute telmisartan and amlodipine tablets for its individually titrated components for patients on amlodipine and telmisartan. Telmisartan and amlodipine tablets may also be given with increased amounts of amlodipine, telmisartan, or both, as needed. ( 2.2 , 2.3 ) • Use telmisartan and amlodipine tablets to provide additional blood pressure lowering for patients not adequately controlled with amlodipine (or another dihydropyridine calcium channel blocker) alone or with telmisartan (or another angiotensin receptor blocker) alone. ( 2.3 ) • Dosage may be increased after at least 2 weeks to a maximum dose of 80/ 10 mg once daily, usually by increasing one component at a time but both components can be raised to achieve more rapid control. ( 2.1 , 2.2 ) • Majority of antihypertensive effect is attained within 2 weeks. ( 2.1 ) • Initiate with 40/5 mg or 80/5 mg once daily. ( 2.4 ) • Switch patients who experience dose-limiting adverse reactions on amlodipine to telmisartan and amlodipine tablets containing a lower dose of that component. ( 2.3 ) ", "3 DOSAGE FORMS AND STRENGTHS": "Telmisartan and Amlodipine Tablets, USP are available containing 40 mg or 80 mg of telmisartan, USP and 5 mg or 10 mg of amlodipine (present as 6.935 mg or 13.87 mg amlodipine besylate, USP respectively), providing for the following combinations: 40 mg/5 mg, 40 mg/10 mg, 80 mg/5 mg or 80 mg/10 mg. • The 40 mg/5 mg tablets are bi-layered, mottled light blue and white to off-white, capsule shaped, unscored tablets with TA1M debossed on the white to off-white side of the tablet and blank on the mottled light blue side. The white to off-white layer may have a blue tinge or blue specks. • The 40 mg/10 mg tablets are bi-layered, mottled blue and white to off-white, capsule shaped, unscored tablets with TA2M debossed on the white to off-white side of the tablet and blank on the mottled blue side. The white to off-white layer may have a blue tinge or blue specks. • The 80 mg/5 mg tablets are bi-layered, mottled light blue and white to off-white, capsule shaped, unscored tablets with TA3M debossed on the white to off-white side of the tablet and blank on the mottled light blue side. The white to off-white layer may have a blue tinge or blue specks. • The 80 mg/10 mg tablets are bi-layered, mottled blue and white to off-white, capsule shaped, unscored tablets with TA4M debossed on the white to off-white side of the tablet and blank on the mottled blue side. The white to off-white layer may have a blue tinge or blue specks.", "6.2 Postmarketing Experience": "The following adverse reactions have been identified during post-approval use of telmisartan or amlodipine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to telmisartan or amlodipine.", "Clinical Laboratory Findings": "In placebo-controlled clinical trials, clinically relevant changes in standard laboratory test parameters were rarely associated with administration of telmisartan tablets.", "8 USE IN SPECIFIC POPULATIONS": "• Patients ≥ 75 years of age or hepatically impaired patients: Start with amlodipine or add amlodipine 2.5 mg to telmisartan. ( 2.5 , 8.5 , 8.6 ) • Lactation: Do not breastfeed during treatment with telmisartan and amlodipine tablets. ( 8.2 )", "6.1 Clinical Trials Experience": "Because clinical studies are conducted under widely varying conditions, adverse reactions rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.", "Fetal/Neonatal Adverse Reactions": "Use of drugs that act on the RAS in the second and third trimesters of pregnancy can result in the following: oligohydramnios, reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. In patients taking telmisartan and amlodipine tablets during pregnancy, perform serial ultrasound examinations to assess the intra-amniotic environment. Fetal testing may be appropriate, based on the week of gestation. If oligohydramnios is observed, discontinue telmisartan and amlodipine tablets, unless it is considered lifesaving for the mother. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to telmisartan and amlodipine tablets for hypotension, oliguria, and hyperkalemia. If oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function [see Use in Specific Populations (8.4) ] .", "17 PATIENT COUNSELING INFORMATION": "Advise the patient to read the FDA-approved patient labeling (Patient Information). Pregnancy: Advise female patients of childbearing age about the consequences of exposure to telmisartan and amlodipine tablets during pregnancy. Discuss treatment options with women planning to become pregnant. Tell patients to report pregnancies to their physicians as soon as possible [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] . Lactation: Advise nursing women not to breastfeed during treatment with telmisartan and amlodipine tablets [see Use in Specific Populations (8.2) ] . Symptomatic Hypotension: Advise patients that lightheadedness can occur, especially during the first days of therapy, and to report it to their healthcare provider. Inform patients the inadequate fluid intake, excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure, with the same consequences of lightheadedness and possible syncope. Advise patients to contact their healthcare provider if syncope occurs [see Warnings and Precautions (5.2) ] .", "Patients 75 Years of Age and Older": "In most patients, initiate amlodipine therapy at 2.5 mg. Titrate slowly in patients 75 years of age and older.", "Telmisartan and Amlodipine Tablets": "The concomitant use of telmisartan and amlodipine has been evaluated for safety in more than 3700 patients with hypertension; approximately 1900 of these patients were exposed for at least 6 months and over 160 of these patients were exposed for at least 1 year. Adverse reactions have generally been mild and transient in nature and have only infrequently required discontinuation of therapy. In the placebo-controlled factorial design study, the population treated with a telmisartan and amlodipine combination had a mean age of 53 years and included approximately 50% males, 79% were Caucasian, 17% Blacks, and 4% Asians. Patients received doses ranging from 20/2.5 mg to 80/10 mg orally, once daily. The frequency of adverse reactions was not related to gender, age, or race. The adverse reactions that occurred in the placebo-controlled factorial design trial in ≥ 2% of patients treated with telmisartan and amlodipine tablets and at a higher incidence in telmisartan and amlodipine tablet-treated patients (n = 789) than placebo-treated patients (n = 46) were peripheral edema (4.8% vs 0%), dizziness (3.0% vs 2.2%), and back pain (2.2% vs 0%). Edema (other than peripheral edema), hypotension, and syncope were reported in < 2% of patients treated with telmisartan and amlodipine tablets. In the placebo-controlled factorial design trial, discontinuation due to adverse events occurred in 2.2% of all treatment cells of patients in the telmisartan/amlodipine-treated patients and in 4.3% in the placebo-treated group. The most common reasons for discontinuation of therapy with telmisartan and amlodipine tablets were peripheral edema, dizziness, and hypotension (each ≤ 0.5%). Peripheral edema is a known, dose-dependent adverse reaction of amlodipine, but not of telmisartan. In the factorial design study, the incidence of peripheral edema during the 8-week, randomized, double-blind treatment period was highest with amlodipine 10 mg monotherapy. The incidence was notably lower when telmisartan was used in combination with amlodipine 10 mg. Table 1: Incidence of Peripheral Edema During the 8-Week Treatment Period Telmisartan Placebo 40 mg 80 mg Amlodipine Placebo 0% 0.8% 0.7% 5 mg 0.7% 1.4% 2.1% 10 mg 17.8% 6.2% 11.3%", "16 HOW SUPPLIED/STORAGE AND HANDLING": "Telmisartan and Amlodipine Tablets, USP are available containing 40 mg or 80 mg of telmisartan, USP and 5 mg or 10 mg of amlodipine (present as 6.935 mg or 13.87 mg amlodipine besylate, USP respectively), providing for the following combinations: 40 mg/5 mg, 40 mg/10 mg, 80 mg/5 mg or 80 mg/10 mg. The 40 mg/5 mg tablets are bi-layered, mottled light blue and white to off-white, capsule shaped, unscored tablets with TA1M debossed on the white to off-white side of the tablet and blank on the mottled light blue side. The white to off-white layer may have a blue tinge or blue specks. They are available as follows: NDC 0378-1075-93 bottles of 30 tablets The 40 mg/10 mg tablets are bi-layered, mottled blue and white to off-white, capsule shaped, unscored tablets with TA2M debossed on the white to off-white side of the tablet and blank on the mottled blue side. The white to off-white layer may have a blue tinge or blue specks. They are available as follows: NDC 0378-1076-93 bottles of 30 tablets The 80 mg/5 mg tablets are bi-layered, mottled light blue and white to off-white, capsule shaped, unscored tablets with TA3M debossed on the white to off-white side of the tablet and blank on the mottled light blue side. The white to off-white layer may have a blue tinge or blue specks. They are available as follows: NDC 0378-1077-93 bottles of 30 tablets The 80 mg/10 mg tablets are bi-layered, mottled blue and white to off-white, capsule shaped, unscored tablets with TA4M debossed on the white to off-white side of the tablet and blank on the mottled blue side. The white to off-white layer may have a blue tinge or blue specks. They are available as follows: NDC 0378-1078-93 bottles of 30 tablets Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from moisture and light. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.", "Telmisartan and Amlodipine Tablets ": "Of the total number of 3282 hypertensive patients receiving a telmisartan/amlodipine combination in clinical studies, 605 (18%) patients were 65 years of age or older and of these, 88 (3%) patients were 75 years and older. No overall differences in efficacy or safety of telmisartan and amlodipine tablets were observed in this patient population.", "7.3 Drug Interactions with Amlodipine": "In clinical trials, amlodipine has been safely administered with thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, non-steroidal anti-inflammatory drugs, antibiotics, and oral hypoglycemic drugs.", "14.1 Telmisartan and Amlodipine Tablets": "The efficacy of telmisartan and amlodipine tablets for treatment of hypertension was studied in one placebo-controlled and two active-controlled trials. An 8-week multicenter, randomized, double-blind, placebo-controlled, parallel group factorial study in patients with mild to severe hypertension was conducted to determine if treatment with telmisartan and amlodipine tablets was more effective in reducing blood pressure compared to the respective monotherapies. The study randomized 1461 patients with baseline systolic blood pressure between 117 and 179 mmHg (mean 153 mmHg) and a baseline diastolic blood pressure between 90 and 119 (mean 102 mmHg) to one of the 16 treatment arms. Patients assigned to receive amlodipine 10 mg started on amlodipine 5 mg or combinations thereof for the first 2 weeks. The four key treatment combinations (including combinations of telmisartan 40 or 80 mg and amlodipine 5 or 10 mg) had statistically significant reduction in in-clinic seated trough cuff systolic and diastolic blood pressure compared to the respective individual monotherapies (Table 5). Table 5: Placebo-Subtracted Mean Change from Baseline in Seated Systolic/Diastolic Blood Pressure (mmHg): Combination Therapy vs Monotherapy Components Amlodipine, mg Telmisartan, mg 0 40 80 0 --- -12.1/-7.2 -11.8/-7.8 5 -12.9/-7.2 -19.3/-10.3 -19.6/-12.0 10 -18.2/-10.9 -22.2/-14.0 -23.9/-13.9 The majority of the antihypertensive effect of the telmisartan/amlodipine combination was attained within 2 weeks after initiation of therapy. In patients receiving a telmisartan/amlodipine combination, significantly larger reductions in seated diastolic and systolic blood pressure compared to patients treated with the respective monotherapies were observed at every assessment (Week 2, 4, 6, and 8). The antihypertensive effect of telmisartan and amlodipine tablets was similar in patients ≥ 65 years than below 65 years of age, in male and female patients, and in patients with and without diabetes. The magnitude of blood pressure lowering in black patients approached that observed in non-black patients but the number of black patients was limited (237 of 1461 patients). Automated ambulatory blood pressure monitoring (ABPM) performed in a subset of 562 patients confirmed the results seen with in-clinic systolic and diastolic blood pressure reductions over the entire 24-hour dosing period. In a double-blind, active-controlled study, a total of 1097 patients with mild to severe hypertension (mean baseline systolic/diastolic BP 149.5/96.6 mmHg) who were not adequately controlled on amlodipine 5 mg received telmisartan and amlodipine tablets (40/5 mg or 80/5 mg) or amlodipine alone (5 mg or 10 mg). After 8 weeks administration, each of the combination treatments was statistically significantly superior to both amlodipine monotherapy doses in reducing diastolic and systolic blood pressures. Edema related events (peripheral edema, generalized edema, and edema) in patients who received telmisartan and amlodipine tablets (40/5 mg or 80/5 mg) were significantly lower as compared to patients who received amlodipine 10 mg (4.3% vs 27.2%, respectively). Table 6: Effect on Seated Systolic/Diastolic Blood Pressure: Combination Therapy vs Monotherapy Treatment Group Mean Change Mean change from baseline at Week 8 in seated systolic/diastolic blood pressure Difference from Amlodipine 5 mg Difference from Amlodipine 10 mg Telmisartan and Amlodipine 40/5 mg; n = 270 -13.6/-9.4 -7.4 p < 0.05 /-3.6 -2.4 /-1.4 Telmisartan and Amlodipine 80/5 mg; n = 271 -15.0/-10.6 -8.8 /-4.9 -3.9 /-2.7 Amlodipine 5 mg; n = 255 -6.2/-5.7 --- --- Amlodipine 10 mg; n = 261 -11.1/-8.0 --- --- In a second double-blind, active-controlled study, a total of 947 patients with mild to severe hypertension (mean baseline systolic/diastolic BP 147.5/95.6 mmHg) who were not adequately controlled on amlodipine 10 mg received telmisartan and amlodipine tablets (40/10 mg or 80/10 mg) or amlodipine alone (10 mg). After 8 weeks, each of the combination treatments was statistically significantly superior to amlodipine monotherapy in reducing diastolic and systolic blood pressures. Table 7: Effect on Seated Systolic/Diastolic Blood Pressure: Combination Therapy vs Monotherapy Treatment Group Mean Change Mean change from baseline at Week 8 in seated systolic/diastolic blood pressure Difference from Amlodipine 10 mg Telmisartan and Amlodipine 40/10 mg; n = 306 -11.1/-9.2 -3.7 p < 0.05 /-2.8 Telmisartan and Amlodipine 80/10 mg; n = 310 -11.3/-9.3 -3.9 /-2.8 Amlodipine 10 mg; n = 305 -7.4/-6.5 --- There are no trials of telmisartan and amlodipine tablets demonstrating reductions in cardiovascular risk in patients with hypertension, but at least one pharmacologically similar drug has demonstrated such benefits.", "PRINCIPAL DISPLAY PANEL – 80 mg/5 mg ": "NDC 0378-1077-93 Telmisartan and Amlodipine Tablets, USP 80 mg/5 mg Important: Do not remove from bottle until immediately before administration. Rx only 30 Tablets Each tablet contains 80 mg of telmisartan, USP and 6.935 mg of amlodipine besylate, USP equivalent to 5 mg of amlodipine. Usual Dosage: See accompanying prescribing information. Keep this and all medication out of the reach of children. Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from moisture and light. Manufactured for: Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A. Made in India Mylan.com RMX1077H6 Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Keep container tightly closed. Code No.: MH/DRUGS/25/NKD/89", "PRINCIPAL DISPLAY PANEL – 80 mg/10 mg ": "NDC 0378-1078-93 Telmisartan and Amlodipine Tablets, USP 80 mg/10 mg Important: Do not remove from bottle until immediately before administration. Rx only 30 Tablets Each tablet contains 80 mg of telmisartan, USP and 13.87 mg of amlodipine besylate, USP equivalent to 10 mg of amlodipine. Usual Dosage: See accompanying prescribing information. Keep this and all medication out of the reach of children. Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from moisture and light. Manufactured for: Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A. Made in India Mylan.com RMX1078H6 Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Keep container tightly closed. Code No.: MH/DRUGS/25/NKD/89", "PRINCIPAL DISPLAY PANEL – 40 mg/5 mg ": "NDC 0378-1075-93 Telmisartan and Amlodipine Tablets, USP 40 mg/5 mg Important: Do not remove from bottle until immediately before administration. Rx only 30 Tablets Each tablet contains 40 mg of telmisartan, USP and 6.935 mg of amlodipine besylate, USP equivalent to 5 mg of amlodipine. Usual Dosage: See accompanying prescribing information. Keep this and all medication out of the reach of children. Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from moisture and light. Manufactured for: Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A. Made in India Mylan.com RMX1075H6 Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Keep container tightly closed. Code No.: MH/DRUGS/25/NKD/89", "PRINCIPAL DISPLAY PANEL – 40 mg/10 mg ": "NDC 0378-1076-93 Telmisartan and Amlodipine Tablets, USP 40 mg/10 mg Important: Do not remove from bottle until immediately before administration. Rx only 30 Tablets Each tablet contains 40 mg of telmisartan, USP and 13.87 mg of amlodipine besylate, USP equivalent to 10 mg of amlodipine. Usual Dosage: See accompanying prescribing information. Keep this and all medication out of the reach of children. Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from moisture and light. Manufactured for: Mylan Pharmaceuticals Inc. Morgantown, WV 26505 U.S.A. Made in India Mylan.com RMX1076H6 Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Keep container tightly closed. Code No.: MH/DRUGS/25/NKD/89", "Disease-associated Maternal and/or Embryo/Fetal Risk": "Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section, and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly.", "7.1 Drug Interactions with Telmisartan and Amlodipine Tablets": "The pharmacokinetics of amlodipine and telmisartan are not altered when the drugs are co-administered. No drug interaction studies have been conducted with telmisartan and amlodipine tablets and other drugs, although studies have been conducted with the individual amlodipine and telmisartan components of telmisartan and amlodipine tablets, as described below:", "Neonates with a History of in Utero Exposure to Telmisartan and Amlodipine": "If oliguria or hypotension occurs, support blood pressure and renal perfusion. Exchange transfusions or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.", "Non-Steroidal Anti-Inflammatory Agents Including Selective Cyclooxygenase-2 Inhibitors (COX-2 Inhibitors)": "In patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of NSAIDs, including selective COX-2 inhibitors, with angiotensin II receptor antagonists, including telmisartan, may result in deterioration of renal function, including possible acute renal failure. These effects are usually reversible. Monitor renal function periodically in patients receiving telmisartan and NSAID therapy. The antihypertensive effect of angiotensin II receptor antagonists, including telmisartan may be attenuated by NSAIDs including selective COX-2 inhibitors.", "2.3 Add-on Therapy for Patients with Hypertension Not Adequately Controlled on Antihypertensive Monotherapy": "Telmisartan and amlodipine tablets may be used to provide additional blood pressure lowering for patients not adequately controlled with amlodipine (or another dihydropyridine calcium channel blocker) alone or with telmisartan (or another angiotensin receptor blocker) alone. Patients treated with 10 mg amlodipine who experience any dose-limiting adverse reactions such as edema, may be switched to telmisartan and amlodipine 40/5 mg tablets once daily, reducing the dose of amlodipine without reducing the overall expected antihypertensive response [ see Adverse Reactions (6.1) ]."}

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Source: dailymed · Ingested: 2026-02-15T11:41:48.623973 · Updated: 2026-03-14T22:06:52.986948