SDAMLO

Sdamlo contains the besylate salt of amlodipine, a long-acting calcium channel blocker. Amlodipine besylate is chemically described as 3-Ethyl-5-methyl (±)-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5 pyridinedicarboxylate, monobenzenesulphonate. Its empirical formula is C 20 H 25 CIN 2 O 5 •C 6 H 6 O 3 S, and its structural formula is: Amlodipine besylate is a white crystalline powder with a molecular weight of 567.1. It is slightly soluble in water and sparingly soluble in ethanol. Sdamlo is supplied as a white to off-white powder or powder cake packaged in a unit-dose, single-use container. Each vial of Sdamlo contains 2.5, 5, and 10 mg of amlodipine, provided as 3.47, 6.94, and 13.88 mg of amlodipine besylate, respectively, and the following inactive ingredients: mannitol and neotame. Sdamlo is for oral administration after reconstitution with water [see Dosage and Administration (2.3) ] . Chemical Structure

Sdamlo is a calcium channel blocker and may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of: Hypertension ( 1.1 ) Sdamlo is indicated for the treatment of hypertension, to lower blood pressure in adults and pediatric patients 6 years of age and older. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. Coronary Artery Disease in adults ( 1.2 ) Chronic Stable Angina Vasospastic Angina (Prinzmetal's or Variant Angina) Angiographically Documented Coronary Artery Disease in patients without heart failure or an ejection fraction <40% 1.1 Hypertension Sdamlo is indicated for the treatment of hypertension, to lower blood pressure in adults and pediatric patients 6 years of age and older. 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 amlodipine. 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. Sdamlo may be used alone or in combination with other antihypertensive agents. 1.2 Coronary Artery Disease (CAD) Chronic Stable Angina Sdamlo is indicated for the symptomatic treatment of chronic stable angina in adults. Sdamlo may be used alone or in combination with other antianginal agents. Vasospastic-Angina (Prinzmetal's or Variant Angina) Sdamlo is indicated for the treatment of confirmed or suspected vasospastic angina in adults. Sdamlo may be used as monotherapy or in combination with other antianginal agents. Angiographically Documented CAD In adult patients with recently documented CAD by angiography and without heart failure or an ejection fraction <40%, Sdamlo is indicated to reduce the risk of hospitalization for angina and to reduce the risk of a coronary revascularization procedure.

Adult recommended starting dose: 5 mg orally once daily with maximum dose 10 mg orally once daily. ( 2.1 ) Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg orally once daily. ( 2.1 ) Pediatric starting dose: 2.5 mg to 5 mg orally once daily. ( 2.2 ) Important Limitation: Doses in excess of 5 mg daily have not been studied in pediatric patients. ( 2.2 ) 2.1 Recommended Dosage in Adults Hypertension The usual initial antihypertensive oral dose of Sdamlo is 5 mg orally once daily, and the maximum dose is 10 mg orally once daily. Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg orally once daily and this dose may be used when adding Sdamlo to other antihypertensive therapy. Adjust dosage according to blood pressure goals. In general, wait 7 to 14 days between titration steps. Titrate more rapidly, however, if clinically warranted, provided the patient is assessed frequently. Angina The recommended dose for chronic stable or vasospastic angina is 5 mg to 10 mg orally once daily, with the lower dose suggested in the elderly and in patients with hepatic insufficiency. Most patients will require 10 mg orally once daily for adequate effect. Coronary Artery Disease The recommended dose range for patients with coronary artery disease is 5 mg to 10 mg once daily. In clinical studies, the majority of patients required 10 mg orally once daily [see Clinical Studies (14.4) ] . 2.2 Recommended Dosage in Pediatric Patients for Hypertension The recommended antihypertensive dose in pediatric patients ages 6 to 17 years is 2.5 mg to 5 mg orally once daily. Doses in excess of 5 mg orally once daily have not been studied in pediatric patients [see Clinical Pharmacology (12.4), Clinical Studies (14.1) ] . 2.3 Preparation and Administration of Sdamlo for Oral Solution • Remove the cap and peel off the seal. • Use one tablespoon to measure 15 mL of room temperature water. Add the 15 ml water to the container. • Wait for 60 seconds to allow the content to fully dissolve. Shaking the container is not required. • Consume the entire content of the container immediately or within 60 minutes. • Rinse the container with similar amount of water 1 to 2 times and consume the rinses.

Sdamlo is contraindicated in patients with known sensitivity to amlodipine. Known sensitivity to amlodipine ( 4 )

Most common adverse reaction to amlodipine is edema which occurred in a dose related manner. Other adverse experiences not dose related but reported with an incidence >1.0% are fatigue, nausea, abdominal pain, and somnolence. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Pangea Pharmaceuticals at 1-855-892-8224 or FDA at 1-800-332-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Amlodipine has been evaluated for safety in more than 11,000 patients in U.S. and foreign clinical trials. In general, treatment with amlodipine was well-tolerated at doses up to 10 mg daily. Most adverse reactions reported during therapy with amlodipine were of mild or moderate severity. In controlled clinical trials directly comparing amlodipine (N=1730) at doses up to 10 mg to placebo (N=1250), discontinuation of amlodipine because of adverse reactions was required in only about 1.5% of patients and was not significantly different from placebo (about 1%). The most commonly reported side effects more frequent than placebo are reflected in the table below. The incidence (%) of side effects that occurred in a dose related manner are as follows: Amlodipine Placebo 2.5 mg N=275 5 mg N=296 10 mg N=268 N=520 Edema 1.8 3.0 10.8 0.6 Dizziness 1.1 3.4 3.4 1.5 Flushing 0.7 1.4 2.6 0.0 Palpitation 0.7 1.4 4.5 0.6 Other adverse reactions that were not clearly dose related but were reported with an incidence greater than 1.0% in placebo-controlled clinical trials include the following: Amlodipine (%) (N=1730) Placebo (%) (N=1250) Fatigue 4.5 2.8 Nausea 2.9 1.9 Abdominal Pain 1.6 0.3 Somnolence 1.4 0.6 For several adverse reactions, there was a greater incidence in women than men associated with amlodipine treatment as show in the following table: Amlodipine Placebo Male=% (N=1218) Female=% (N=512) Male=% (N=914) Female=% (N=336) Edema 5.6 14.6 1.4 5.1 Flushing 1.5 4.5 0.3 0.9 Palpitations 1.4 3.3 0.9 0.9 Somnolence 1.3 1.6 0.8 0.3 The safety of amlodipine at doses of 2.5 mg and 5 mg once daily was evaluated in a randomized placebo-controlled trial in 268 pediatric patients aged 6 to 17 years with hypertension [see Clinical Studies (14.1)]. Adverse reactions were similar to those in adults. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of amlodipine. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. General: gynecomastia Hepatic: jaundice and hepatic enzyme elevations, some require hospitalization. Neurologic: extrapyramidal disorder.

Do not exceed doses greater than 20 mg daily of simvastatin. ( 7.2 ) 7.1 Impact of Other Drugs on Amlodipine CYP3A Inhibitors Co-administration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is co-administered with CYP3A inhibitors to determine the need for dose adjustment [see Clinical Pharmacology (12.3) ] . CYP3A Inducers No information is available on the quantitative effects of CYP3A inducers on amlodipine. Blood pressure should be closely monitored when amlodipine is co-administered with CYP3A inducers. Sildenafil Monitor for hypotension when sildenafil is co-administered with amlodipine [see Clinical Pharmacology (12.2) ]. 7.2 Impact of Amlodipine on Other Drugs Simvastatin Co-administration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily [see Clinical Pharmacology (12.3) ] . Immunosuppressants Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. Frequent monitoring of trough blood levels of cyclosporine and tacrolimus is recommended and adjust the dose when appropriate [see Clinical Pharmacology (12.3) ] .