Omeprazole Delayed-release Capsules, Usp. These Highlights Do Not Include All The Information Needed To Use Omeprazole Delayed-release Capsules, Usp, Safely And Effectively. See Full Prescribing Information For Omeprazole Delayed-release Capsules, Usp.

Triple Therapy

Omeprazole delayed-release capsules in combination with clarithromycin and amoxicillin, is indicated for treatment of patients with H. pylori infection and duodenal ulcer disease (active or up to 1-year history) to eradicate H. pylori in adults.

Storage

Store Omeprazole delayed-release capsules in a tight container protected from light and moisture. Store between 15°C and 30°C (59°F and 86°F).

Reports have been received of overdosage with omeprazole in humans. Doses ranged up to 2400 mg (120 times the usual recommended clinical dose). Manifestations were variable, but included confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, dry mouth, and other adverse reactions similar to those seen in normal clinical experience [see Adverse Reactions (6)]. Symptoms were transient, and no serious clinical outcome has been reported when omeprazole was taken alone. No specific antidote for omeprazole overdosage is known. Omeprazole is extensively protein bound and is, therefore, not readily dialyzable. In the event of overdosage, treatment should be symptomatic and supportive.

If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Tenth Edition. CLSI Document M07-A10, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania, 19087, USA 2015.

The active ingredient in Omeprazole delayed-release capsules, USP, is a substituted benzimidazole, 5-methoxy-2-[[(4-methoxy-3, 5-dimethyl-2-pyridinyl) methyl] sulfinyl]-1 H-benzimidazole, a compound that inhibits gastric acid secretion. Its empirical formula is C ₁₇H ₁₉N ₃O ₃S, with a molecular weight of 345.42. The structural formula is:

Omeprazole is a white to off-white crystalline powder that melts with decomposition at about 155°C. It is a weak base, freely soluble in ethanol and methanol, and slightly soluble in acetone and isopropanol and very slightly soluble in water. The stability of omeprazole is a function of pH; it is rapidly degraded in acid media, but has acceptable stability under alkaline conditions.

Omeprazole is supplied as delayed-release capsules for oral administration. Each delayed-release capsule contains either 10 mg, 20 mg or 40 mg of omeprazole in the form of enteric-coated granules with the following inactive ingredients: ammonium hydroxide, colloidal anhydrous silica, dibutyl sebacate, ethylcellulose 20 cP, hypromellose, maize starch, methacrylic acid-ethyl acrylate copolymer, oleic acid, polysorbate 80, sodium lauryl sulfate, sucrose, talc, titanium dioxide, and triethyl citrate. The capsule shells have the following inactive ingredients: ammonium hydroxide, black iron oxide, ethyl alcohol, gelatin, isopropyl alcohol, n-butyl alcohol, potassium hydroxide, propylene glycol, shellac, and titanium dioxide.

Omeprazole delayed-release capsules meet USP Dissolution Test 2.

Read this Medication Guide before you start taking Omeprazole delayed-release capsules and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.

What is the most important information I should know about Omeprazole delayed-release capsules?

You should take omeprazole delayed-release capsules exactly as prescribed, at the lowest dose possible and for the shortest time needed.

Omeprazole delayed-release capsules may help your acid-related symptoms, but you could still have serious stomach problems. Talk with your doctor.

Omeprazole delayed-release capsules can cause serious side effects, including:

• A type of kidney problem (acute tubulointerstitial nephritis). Some people who take proton pump inhibitor (PPI) medicines, including omeprazole delayed-release capsules, may develop a kidney problem called acute tubulointerstitial nephritis that can happen at any time during treatment with omeprazole delayed-release capsules. Call your doctor right away if you have a decrease in the amount that you urinate or if you have blood in your urine.
• Diarrhea. Omeprazole delayed-release capsules may increase your risk of getting severe diarrhea. This diarrhea may be caused by an infection ( Clostridium difficile) in your intestines. Call your doctor right away if you have watery stool, stomach pain, and fever that does not go away.
• Bone fractures. People who take multiple daily doses of PPI medicines for a long period of time (a year or longer) may have an increased risk of fractures of the hip, wrist, or spine. You should take Omeprazole delayed-release capsules exactly as prescribed, at the lowest dose possible for your treatment and for the shortest time needed. Talk to your doctor about your risk of bone fracture if you take Omeprazole delayed-release capsules.
• Certain types of lupus erythematosus. Lupus erythematosus is an autoimmune disorder (the body's immune cells attack other cells or organs in the body). Some people who take proton PPI medicines, including Omeprazole delayed-release capsules, may develop certain types of lupus erythematosus or have worsening of the lupus they already have. Call your doctor right away if you have new or worsening joint pain or a rash on your cheeks or arms that gets worse in the sun.

Omeprazole delayed-release capsules can have other serious side effects. See " What are the possible side effects of Omeprazole delayed-release capsules?"

What are Omeprazole delayed-release capsules?

Omeprazole delayed-release capsules are a prescription medicine called a proton pump inhibitor (PPI). Omeprazole delayed-release capsules reduces the amount of acid in your stomach.

Omeprazole delayed-release capsules are used in adults:

• for up to 8 weeks for the healing of duodenal ulcers. The duodenal area is the area where food passes when it leaves the stomach.
• with certain antibiotics for 10 to 14 days to treat an infection caused by bacteria called H. pylori. If needed, your doctor may decide to prescribe another 14 to 18 days of Omeprazole delayed-release capsules by itself after the antibiotics. Sometimes H. pylori bacteria can cause duodenal ulcers. The infection needs to be treated to prevent the ulcers from coming back.
• for up to 8 weeks for healing stomach ulcers.
• for up to 4 weeks to treat heartburn and other symptoms that happen with gastroesophageal reflux disease (GERD). GERD happens when acid in your stomach backs up into the tube (esophagus) that connects your mouth to your stomach. This may cause a burning feeling in your chest or throat, sour taste, or burping.
• for up to 8 weeks to heal acid-related damage to the lining of the esophagus (called erosive esophagitis or EE). If needed, your doctor may decide to prescribe another 4 weeks of Omeprazole delayed-release capsules.
• to maintain healing of the esophagus. It is not known if Omeprazole delayed-release capsules are safe and effective when used for longer than 12 months (1 year) for this purpose.
• for the long-term treatment of conditions where your stomach makes too much acid. This includes a rare condition called Zollinger-Ellison Syndrome.

For children 2 to 16 years of age, Omeprazole Delayed-Release Capsules are used:

• for up to 4 weeks to treat heartburn and other symptoms that happen with gastroesophageal reflux disease (GERD).
• for up to 8 weeks to treat gastroesophageal reflux disease (GERD) with acid-related damage to the lining of the esophagus [called erosive esophagitis (or EE) due to acid-mediated GERD].
• to maintain healing of the esophagus. It is not known if Omeprazole delayed-release capsules are safe and effective when used longer than 12 months (1 year) for this purpose. It is not known if Omeprazole Delayed-Release Capsules is safe and effective in children less than 1 month of age.

Who should not take Omeprazole delayed-release capsules?

Do not take Omeprazole delayed-release capsules if you:

• are allergic to omeprazole or any of the ingredients in Omeprazole delayed-release capsules. See the end of this Medication Guide for a complete list of ingredients in Omeprazole delayed-release capsules.
• are allergic to any other proton pump inhibitor (PPI) medicine.
• are taking a medicine that contains rilpivirine (EDURANT, COMPLERA) used to treat HIV-1 (Human Immunodeficiency Virus).

What should I tell my doctor before taking Omeprazole delayed-release capsules?

Before taking Omeprazole delayed-release capsules, tell your doctor about all of your medical conditions, including if you:

• have low magnesium levels, low calcium levels and low potassium levels in your blood.
• have liver problems.
• have any other medical conditions.
• are pregnant or plan to become pregnant. It is not known if Omeprazole delayed-release capsules will harm your unborn baby.
• are breastfeeding or plan to breastfeed. Omeprazole passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take Omeprazole delayed-release capsules.
• Tell your doctor about all of the medicines you take including prescription and over-the-counter medicines, vitamins and herbal supplements. Omeprazole delayed-release capsules may affect how other medicines work, and other medicines may affect how Omeprazole delayed-release capsules work. Especially tell your doctor if you take an antibiotic that contains clarithromycin or amoxicillin, or if you take clopidogrel (Plavix), methotrexate (Otrxup, Rasuvo, Trexall), St. John's Wort ( Hypericum perforatum) , or rifampin (Rimactane, Rifater, Rifamate).

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

How should I take Omeprazole delayed-release capsules?

• Take Omeprazole delayed-release capsules exactly as prescribed by your doctor.
• Do not change your dose or stop Omeprazole delayed-release capsules without talking to your doctor.
• Omeprazole delayed-release capsules are usually taken 1 time each day. Your doctor will tell you the time of day to take Omeprazole delayed-release capsules, based on your medical condition.
• Take Omeprazole delayed-release capsules before a meal.
• Antacids may be taken with Omeprazole delayed-release capsules.
• Swallow Omeprazole delayed-release capsules whole. Do not chew or crush Omeprazole delayed-release capsules.
• If you have trouble swallowing a whole capsule, you can open the capsule and take the contents in applesauce. See the " Instructions for Use" at the end of this Medication Guide for instructions on how to take Omeprazole delayed-release capsules with applesauce.

If you miss a dose of Omeprazole delayed-release capsules, take it as soon as you remember. If it is almost time for your next dose, do not take the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time to make up for the missed dose.

If you take too much Omeprazole delayed-release capsules, call your doctor or your poison control center at 1-800-222-1222 right away or go to the nearest emergency room.

What are the possible side effects of Omeprazole delayed-release capsules?

Omeprazole delayed-release capsules can cause serious side effects, including:

• See " What is the most important information I should know about Omeprazole delayed-release capsules?"
• Vitamin B-12 deficiency. Omeprazole delayed-release capsules reduces the amount of acid in your stomach. Stomach acid is needed to absorb vitamin B-12 properly. Talk with your doctor about the possibility of vitamin B-12 deficiency if you have been on Omeprazole delayed-release capsules for a long time (more than 3 years).
• Low magnesium levels in your body. This problem can be serious. Low magnesium can happen in some people who take a PPI medicine for at least 3 months. If low magnesium levels happen, it is usually after a year of treatment.

You may or may not have symptoms of low magnesium. Tell your doctor right away if you develop any of these symptoms:

Your doctor may check the level of magnesium in your body before you start taking Omeprazole delayed-release capsules or during treatment if you will be taking Omeprazole delayed-release capsules for a long period of time.

• Stomach growths (fundic gland polyps). People who take PPI medicines for a long time have an increased risk of developing a certain type of stomach growths called fundic gland polyps, especially after taking PPI medicines for more than 1 year.
• Severe skin reactions. Omeprazole delayed-release capsules can cause rare but severe skin reactions that may affect any part of your body. These serious skin reactions may need to be treated in a hospital and may be life threatening:
  • Skin rash which may have blistering, peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands or feet).
  • You may also have fever, chills, body aches, shortness of breath, or enlarged lymph nodes.
    
    Stop taking Omeprazole delayed-release capsules and call your doctor right away. These symptoms may be the first sign of a severe skin reaction.

The most common side effects with Omeprazole delayed-release capsules in adults and children include:

In addition to the side effects listed above, the most common side effects in children 1 to 16 years of age include:

Other side effects:

Serious allergic reactions. Tell your doctor if you get any of the following symptoms with Omeprazole delayed-release capsules:

Your doctor may stop Omeprazole delayed-release capsules if these symptoms happen. Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects with Omeprazole delayed-release capsules. For more information, ask your doctor or pharmacist. 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 Omeprazole delayed-release capsules?

• Store Omeprazole delayed-release capsules at room temperature between 59°F to 86°F (15°C to 30°C).
• Keep the container of Omeprazole delayed-release capsules closed tightly.
• Keep the container of Omeprazole delayed-release capsules dry and away from light.

Keep Omeprazole delayed-release capsules and all medicines out of the reach of children.

General information about the safe and effective use of Omeprazole delayed-release capsules.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Omeprazole delayed-release capsules for a condition for which it was not prescribed. Do not give Omeprazole delayed-release capsules to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about Omeprazole delayed-release capsules. For more information, ask your doctor. You can ask your doctor or pharmacist for information that is written for healthcare professionals. For more information, go to www.bpirx.com or call toll free 1-800-367-3395.

What are the ingredients in Omeprazole delayed-release capsules?

Active ingredient in Omeprazole delayed-release capsules: omeprazole

Inactive ingredients in Omeprazole delayed-release capsules (including the capsule shells): ammonium hydroxide, black iron oxide, colloidal anhydrous silica, dibutyl sebacate, ethyl alcohol, ethylcellulose 20 cP, gelatin, hypromellose, isopropyl alcohol, maize starch, methacrylic acid-ethyl acrylate copolymer, n-butyl alcohol, oleic acid, polysorbate 80, potassium hydroxide, propylene glycol, shellac, sodium lauryl sulfate, sucrose, talc, titanium dioxide, triethyl citrate.

Trademarks are the property of their respective owners.

This Medication Guide and Instructions for Use has been approved by the U.S. Food and Drug Administration.

Omeprazole and clarithromycin dual therapy and omeprazole, clarithromycin and amoxicillin triple therapy have been shown to be active against most strains of Helicobacter pylori in vitro and in clinical infections [see Indications and Usage (1.2), Clinical Studies (14.2)].

Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration (2.1), Adverse Reactions (6.3)].

The safety and effectiveness of omeprazole delayed-release capsules have been established in pediatric patients 2 to 16 years for the treatment of symptomatic GERD, treatment of EE due to acid-mediated GERD, and maintenance of healing of EE due to acid-mediated GERD. Use of Omeprazole delayed-release capsules in this age group is supported by adequate and well-controlled studies in adults and uncontrolled safety, efficacy and pharmacokinetic studies performed in pediatric and adolescent patients [see Clinical Pharmacology (12.3), Clinical Studies (14.8)] .

In the pediatric population, adverse reactions of the respiratory system were frequently reported in the entire (2 to 16 years) age group. Accidental injuries were frequently reported in the 2 to 16 year age group [see Adverse Reactions (6.1)].

The safety and effectiveness of Omeprazole delayed-release capsules have not been established in:

• patients less than 1 year of age for:
  • Treatment of symptomatic GERD
  • Maintenance of healing of EE due to acid-mediated GERD

• pediatric patients for:
  • Treatment of active duodenal ulcer
  • H. pylori eradication to reduce the risk of duodenal ulcer recurrence
  • Treatment of active benign gastric ulcer
  • Pathological hypersecretory conditions
• patients less than 1 month of age for any indication.

Omeprazole was administered to over 2000 elderly individuals (≥ 65 years of age) in clinical trials in the U.S. and Europe. There were no differences in safety and effectiveness between the elderly and younger subjects. Other reported clinical experience has not identified differences in response between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

Pharmacokinetic studies have shown the elimination rate was somewhat decreased in the elderly and bioavailability was increased. The plasma clearance of omeprazole was 250 mL/min (about half that of young volunteers) and its plasma half-life averaged one hour, about twice that of young healthy volunteers. However, no dosage adjustment is necessary in the elderly [see Clinical Pharmacology (12.3)].

• Omeprazole delayed-release capsules are contraindicated in patients with known hypersensitivity reactions including anaphylaxis to the formulation or any substituted benzimidazole. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see Warnings and Precautions (5.2), Adverse Reactions (6)].
• Proton pump inhibitors (PPIs), including Omeprazole delayed-release capsules, are contraindicated in patients receiving rilpivirine-containing products [see Drug Interactions (7)] .
• For information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with omeprazole, refer to the CONTRAINDICATIONS section of their package inserts.

The following serious adverse reactions are described below and elsewhere in labeling:

• Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.2)]
• Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.3)]
• Bone Fracture [see Warnings and Precautions (5.4)]
• Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.6)]
• Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.8)]
• Hypomagnesemia [see Warnings and Precautions (5.9)]
• Fundic Gland Polyps [see Warnings and Precautions (5.13)]

Tables 3 and 4 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with Omeprazole delayed-release capsules and instructions for preventing or managing them.

Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs.

In studies of healthy subjects, Asians had approximately a four-fold higher exposure than Caucasians. Dosage reduction of Omeprazole delayed-release capsules to 10 mg once daily is recommended for Asian patients for maintenance of healing of EE [see Dosage and Administration (2.1), Clinical Pharmacology (12.5)].

Omeprazole delayed-release capsules

Taking Omeprazole delayed-release capsules with applesauce:

• Place 1 tablespoon of applesauce into a clean container.
• Carefully open the capsule and sprinkle the pellets onto the applesauce. Mix the pellets with the applesauce.
• Swallow the applesauce and pellet mixture right away. Do not chew or crush the pellets. Do not store the applesauce and pellet mixture for later use.

Manufactured for: Breckenridge Pharmaceutical, Inc., Berlin, CT 06037



Manufactured by: Towa Pharmaceutical Europe, S.L., Barcelona, Spain

Revised: 02/2022

Marketed by:

GSMS, Inc.

Camarillo, CA 93012 USA

Omeprazole is a time-dependent inhibitor of CYP2C19, resulting in autoinhibition and nonlinear pharmacokinetics. The systemic exposure increases in a more than dose proportional manner after multiple oral doses of omeprazole. Compared to the first dose, the systemic exposure (C _max and AUC _0-24h) at steady state following once a day dosing increased by 61% and 62%, respectively, compared to after the first dose for the 20 mg dose of Omeprazole delayed-release capsules and increased by 118% and 175%, respectively, for the 40 mg dose of Omeprazole delayed-release capsules.

CYP2C19, a polymorphic enzyme, is involved in the metabolism of omeprazole. The CYP2C19*1 allele is fully functional while the CYP2C19*2 and *3 alleles are nonfunctional. There are other alleles associated with no or reduced enzymatic function. Patients carrying two fully functional alleles are extensive metabolizers and those carrying two loss-of-function alleles are poor metabolizers. In extensive metabolizers, omeprazole is primarily metabolized by CYP2C19. The systemic exposure to omeprazole varies with a patient's metabolism status: poor metabolizers > intermediate metabolizers > extensive metabolizers. Approximately 3% of Caucasians and 15 to 20% of Asians are CYP2C19 poor metabolizers.

In a pharmacokinetic study of single 20 mg omeprazole dose, the AUC of omeprazole in Asian subjects was approximately four-fold of that in Caucasians [see Dosage and Administration (2.1), Use in Specific Populations (8.7)].

A placebo-controlled study was conducted in Scandinavia to compare the efficacy of omeprazole 20 mg or 10 mg once daily for up to 4 weeks in the treatment of heartburn and other symptoms in GERD patients without EE. Results are shown below.

In patients with hepatic impairment (Child-Pugh Class A, B, or C) exposure to omeprazole substantially increased compared to healthy subjects. Dosage reduction of Omeprazole delayed-release capsules to 10 mg once daily is recommended for patients with hepatic impairment for maintenance of healing of EE [see Dosage and Administration (2.1), Clinical Pharmacology (12.3)].

Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.

Omeprazole delayed-release capsules, USP, are a proton pump inhibitor (PPI) indicated for the:

• Treatment of active duodenal ulcer in adults ( 1.1)
• Eradication of Helicobacter pylori to reduce the risk of duodenal ulcer recurrence in adults ( 1.2)
• Treatment of active benign gastric ulcer in adults ( 1.3)
• Treatment of symptomatic gastroesophageal reflux disease (GERD) in patients 2 years of age and older ( 1.4)
• Treatment of erosive esophagitis (EE) due to acid-mediated GERD in patients 2 years of age and older ( 1.5)
• Maintenance of healing of EE due to acid-mediated GERD in patients 2 years of age and older ( 1.6)
• Pathologic hypersecretory conditions in adults ( 1.7)

Omeprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that suppress gastric acid secretion by specific inhibition of the H ⁺/K ⁺ ATPase enzyme system at the secretory surface of the gastric parietal cell. Because this enzyme system is regarded as the acid (proton) pump within the gastric mucosa, omeprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.

PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated.

Published observational studies suggest that PPI therapy like Omeprazole delayed-release capsules may be associated with an increased risk of Clostridium difficile-associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions (6.2)]. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with Omeprazole delayed-release capsules, refer to Warnings and Precautions sections of the corresponding prescribing information.

In a multicenter, double-blind, placebo-controlled study of 147 patients with endoscopically documented duodenal ulcer, the percentage of patients healed (per protocol) at 2 and 4 weeks was significantly higher with omeprazole 20 mg once daily than with placebo (p ≤ 0.01).

Complete daytime and nighttime pain relief occurred significantly faster (p ≤ 0.01) in patients treated with omeprazole 20 mg than in patients treated with placebo. At the end of the study, significantly more patients who had received omeprazole had complete relief of daytime pain (p ≤ 0.05) and nighttime pain (p ≤ 0.01).

In a multicenter, double-blind study of 293 patients with endoscopically documented duodenal ulcer, the percentage of patients healed (per protocol) at 4 weeks was significantly higher with omeprazole 20 mg once daily than with ranitidine 150 mg b.i.d. (p < 0.01).

Healing occurred significantly faster in patients treated with omeprazole than in those treated with ranitidine 150 mg b.i.d. (p < 0.01).

In a foreign multinational randomized, double-blind study of 105 patients with endoscopically documented duodenal ulcer, 20 mg and 40 mg of omeprazole were compared with 150 mg b.i.d. of ranitidine at 2, 4 and 8 weeks. At 2 and 4 weeks both doses of omeprazole were statistically superior (per protocol) to ranitidine, but 40 mg was not superior to 20 mg of omeprazole, and at 8 weeks there was no significant difference between any of the active drugs.

• Gastric Malignancy: In adults, symptomatic response does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing. ( 5.1)
• Acute Tubulointerstitial Nephritis: discontinue treatment and evaluate patients. ( 5.2)
• Clostridium difficile-Associated Diarrhea: PPI therapy may be associated with increased risk. ( 5.3)
• Bone Fracture: Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. ( 5.4)
• Severe Cutaneous Adverse Reactions: Discontinue at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation ( 5.5)
• Cutaneous and Systemic Lupus Erythematosus: Mostly cutaneous; new onset or exacerbation of existing disease; discontinue Omeprazole delayed-release capsules and refer to specialist for evaluation. ( 5.6)
• Interaction with Clopidogrel: Avoid concomitant use of Omeprazole delayed-release capsules. ( 5.7, 7)
• Cyanocobalamin (Vitamin B-12) Deficiency: Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin. ( 5.8)
• Hypomagnesemia and Mineral Metabolism: Reported rarely with prolonged treatment with PPIs. ( 5.9)
• Interaction with St. John's Wort or Rifampin: Avoid concomitant use of Omeprazole delayed-release capsules. ( 5.10, 7)
• Interactions with Diagnostic Investigations for Neuroendocrine Tumors: Increased Chromogranin A (CgA) levels may interfere with diagnostic investigations for neuroendocrine tumors; temporarily stop Omeprazole delayed-release capsules at least 14 days before assessing CgA levels. ( 5.11, 7)
• Interaction with Methotrexate: Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. With high dose methotrexate administration, consider a temporary withdrawal of Omeprazole delayed-release capsules. ( 5.12, 7)
• Fundic Gland Polyps: Risk increases with long-term use, especially beyond one year. Use the shortest duration of therapy. ( 5.13)

The following adverse reactions have been identified during post-approval use of Omeprazole delayed-release capsules. Because these reactions are voluntarily reported from a population of uncertain size, it is not always possible to reliably estimate their actual frequency or establish a causal relationship to drug exposure.

Body As a Whole: Hypersensitivity reactions including anaphylaxis, anaphylactic shock, angioedema, bronchospasm, interstitial nephritis, urticaria, (see also Skin below); fever; pain; fatigue; malaise; systemic lupus erythematosus

Cardiovascular: Chest pain or angina, tachycardia, bradycardia, palpitations, elevated blood pressure, peripheral edema

Endocrine: Gynecomastia

Gastrointestinal: Pancreatitis (some fatal), anorexia, irritable colon, fecal discoloration, esophageal candidiasis, mucosal atrophy of the tongue, stomatitis, abdominal swelling, dry mouth, microscopic colitis, fundic gland polyps.

Gastroduodenal carcinoids have been reported in patients with ZE syndrome on long-term treatment with omeprazole. This finding is believed to be a manifestation of the underlying condition, which is known to be associated with such tumors.

Hepatic: Liver disease including hepatic failure (some fatal), liver necrosis (some fatal), hepatic encephalopathy hepatocellular disease, cholestatic disease, mixed hepatitis, jaundice, and elevations of liver function tests [ALT, AST, GGT, alkaline phosphatase, and bilirubin]

Infections and Infestations: Clostridium difficile-associated diarrhea

Metabolism and Nutritional disorders: Hypoglycemia, hypomagnesemia, with or without hypocalcemia and/or hypokalemia, hyponatremia, weight gain [See Warnings and Precautions (5.9)]

Musculoskeletal: Muscle weakness, myalgia, muscle cramps, joint pain, leg pain, bone fracture

Nervous System/Psychiatric: Psychiatric and sleep disturbances including depression, agitation, aggression, hallucinations, confusion, insomnia, nervousness, apathy, somnolence, anxiety, and dream abnormalities; tremors, paresthesia; vertigo

Respiratory: Epistaxis, pharyngeal pain

Skin: Severe generalized skin reactions including toxic epidermal necrolysis (some fatal), Stevens-Johnson syndrome, cutaneous lupus erythematosus and erythema multiforme; photosensitivity; urticaria; rash; skin inflammation; pruritus; petechiae; purpura; alopecia; dry skin; hyperhidrosis

Special Senses: Tinnitus, taste perversion

Ocular: Optic atrophy, anterior ischemic optic neuropathy, optic neuritis, dry eye syndrome, ocular irritation, blurred vision, double vision

Urogenital: Interstitial nephritis, hematuria, proteinuria, elevated serum creatinine, microscopic pyuria, urinary tract infection, glycosuria, urinary frequency, testicular pain

Hematologic: Agranulocytosis (some fatal), hemolytic anemia, pancytopenia, neutropenia, anemia, thrombocytopenia, leukopenia, leukocytosis

Omeprazole delayed-release capsules, USP, 10 mg, are opaque, hard gelatin, white-colored capsules, coded in black ink "OM" on the cap and "10" on the body.

Omeprazole delayed-release capsules, USP, 20 mg, are opaque, hard gelatin, white-colored capsules, coded in black ink "OM" on the cap and "20" on the body.

Omeprazole delayed-release capsules, USP, 40 mg, are opaque, hard gelatin, white-colored capsules, coded in black ink "OM" on the cap and "40" on the body.

• Take Omeprazole delayed-release capsules before meals.
• Antacids may be used concomitantly with Omeprazole delayed-release capsules.
• Missed doses: If a dose is missed, administer as soon as possible. However, if the next scheduled dose is due, do not take the missed dose, and take the next dose on time. Do not take two doses at one time to make up for a missed dose.

In a U.S. multicenter, double-blind, study of omeprazole 40 mg once daily, 20 mg once daily, and placebo in 520 patients with endoscopically diagnosed gastric ulcer, the following results were obtained.

For the stratified groups of patients with ulcer size less than or equal to 1 cm, no difference in healing rates between 40 mg and 20 mg was detected at either 4 or 8 weeks. For patients with ulcer size greater than 1 cm, 40 mg was significantly more effective than 20 mg at 8 weeks.

In a foreign, multinational, double-blind study of 602 patients with endoscopically diagnosed gastric ulcer, omeprazole 40 mg once daily, 20 mg once daily, and ranitidine 150 mg twice a day were evaluated.

Avoid concomitant use of Omeprazole delayed-release capsules with clopidogrel. Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by use with concomitant medications, such as omeprazole, that inhibit CYP2C19 activity. Concomitant use of clopidogrel with 80 mg omeprazole reduces the pharmacological activity of clopidogrel, even when administered 12 hours apart. When using Omeprazole delayed-release capsules, consider alternative anti-platelet therapy [see Drug Interactions (7) and Clinical Pharmacology (12.3)].

In a U.S. multicenter double-blind placebo controlled study of 20 mg or 40 mg of Omeprazole delayed-release capsules in patients with symptoms of GERD and endoscopically diagnosed EE of grade 2 or above, the percentage healing rates (per protocol) were as follows:

In this study, the 40 mg dose was not superior to the 20 mg dose of omeprazole in the percentage healing rate. Other controlled clinical trials have also shown that omeprazole is effective in severe GERD. In comparisons with histamine H ₂-receptor antagonists in patients with EE, grade 2 or above, omeprazole in a dose of 20 mg was significantly more effective than the active controls. Complete daytime and nighttime heartburn relief occurred significantly faster (p < 0.01) in patients treated with omeprazole than in those taking placebo or histamine H ₂-receptor antagonists.

In this and five other controlled GERD studies, significantly more patients taking 20 mg omeprazole (84%) reported complete relief of GERD symptoms than patients receiving placebo (12%).

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

In adults, symptomatic response to therapy with Omeprazole delayed-release capsules does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. In older patients, also consider an endoscopy.

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration a temporary withdrawal of the PPI may be considered in some patients [see Drug Interactions (7)].

Omeprazole delayed-release capsules, USP, 40 mg, are opaque, hard gelatin, white-colored capsules, coded in black ink "OM" on the cap and "40" on the body. They are supplied as follows:

NDC 51407-664-01 bottles of 100

NDC 51407-664-05 bottles of 500

NDC 51407-814-30 bottles of 30

NDC 51407-814-90 bottles of 90

NDC 51407-814-01 bottles of 100

NDC 51407-814-05 bottles of 500

Omeprazole delayed-release capsules, USP, are indicated for short-term treatment of active duodenal ulcer in adults. Most patients heal within four weeks. Some patients may require an additional four weeks of therapy.

Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions, to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue Omeprazole delayed-release capsules and evaluate patients with suspected acute TIN [see Contraindications (4)].

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs [see Adverse Reactions (6.2)] . Discontinue Omeprazole delayed-release capsules at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.

For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2)].

Consider monitoring magnesium and calcium levels prior to initiation of Omeprazole delayed-release capsules and periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism). Supplement with magnesium and/or calcium, as necessary. If hypocalcemia is refractory to treatment, consider discontinuing the PPI.

Omeprazole is indicated for the long-term treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome, multiple endocrine adenomas and systemic mastocytosis) in adults.

In open studies of 136 patients with pathological hypersecretory conditions, such as Zollinger-Ellison (ZE) syndrome with or without multiple endocrine adenomas, Omeprazole delayed-release capsules significantly inhibited gastric acid secretion and controlled associated symptoms of diarrhea, anorexia, and pain. Doses ranging from 20 mg every other day to 360 mg per day maintained basal acid secretion below 10 mEq/hr in patients without prior gastric surgery, and below 5 mEq/hr in patients with prior gastric surgery.

Initial doses were titrated to the individual patient need, and adjustments were necessary with time in some patients [see Dosage and Administration (2)]. Omeprazole was well tolerated at these high dose levels for prolonged periods (> 5 years in some patients). In most ZE patients, serum gastrin levels were not modified by omeprazole. However, in some patients serum gastrin increased to levels greater than those present prior to initiation of omeprazole therapy. At least 11 patients with ZE syndrome on long-term treatment with omeprazole developed gastric carcinoids. These findings are believed to be a manifestation of the underlying condition, which is known to be associated with such tumors, rather than the result of the administration of omeprazole [see Adverse Reactions (6)].

Omeprazole delayed-release capsules are indicated for short-term treatment (4 to 8 weeks) of active benign gastric ulcer in adults.

Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B-12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed in patients treated with Omeprazole delayed-release capsules.

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including omeprazole. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematosus cases were CLE. The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement.

Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported.

Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving Omeprazole delayed-release capsules, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g., ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations.

Drugs which induce CYP2C19 or CYP3A4 (such as St. John's Wort or rifampin) can substantially decrease omeprazole concentrations [see Drug Interactions (7)] . Avoid concomitant use of Omeprazole delayed-release capsules with St. John's Wort or rifampin.

Table 1 shows the recommended dosage of Omeprazole delayed-release capsules in adult patients by indication.

NDC 51407-664-05

Omeprazole



Delayed-Release Capsules, USP

40 mg

PHARMACIST: Dispense the Patient Information to each patient.

Rx Only



500 Capsules

NDC 51407-814-05

Omeprazole



Delayed-Release Capsules, USP

40 mg

PHARMACIST: Dispense the Medication Guide to each patient.

Rx Only



500 Capsules

Table 2 shows the recommended dosage of Omeprazole delayed-release capsules in pediatric patients by indication.

In two 24-month carcinogenicity studies in rats, omeprazole at daily doses of 1.7, 3.4, 13.8, 44.0 and 140.8 mg/kg/day (about 0.4 to 34 times a human dose of 40 mg/day, as expressed on a body surface area basis) produced gastric ECL cell carcinoids in a dose-related manner in both male and female rats; the incidence of this effect was markedly higher in female rats, which had higher blood levels of omeprazole. Gastric carcinoids seldom occur in the untreated rat. In addition, ECL cell hyperplasia was present in all treated groups of both sexes. In one of these studies, female rats were treated with 13.8 mg omeprazole/kg/day (about 3.4 times a human dose of 40 mg/day, based on body surface area) for one year, and then followed for an additional year without the drug. No carcinoids were seen in these rats. An increased incidence of treatment-related ECL cell hyperplasia was observed at the end of one year (94% treated vs. 10% controls). By the second year the difference between treated and control rats was much smaller (46% vs. 26%) but still showed more hyperplasia in the treated group. Gastric adenocarcinoma was seen in one rat (2%). No similar tumor was seen in male or female rats treated for two years. For this strain of rat no similar tumor has been noted historically, but a finding involving only one tumor is difficult to interpret. In a 52-week toxicity study in Sprague-Dawley rats, brain astrocytomas were found in a small number of males that received omeprazole at dose levels of 0.4, 2, and 16 mg/kg/day (about 0.1 to 3.9 times the human dose of 40 mg/day, based on a body surface area basis). No astrocytomas were observed in female rats in this study. In a 2-year carcinogenicity study in Sprague-Dawley rats, no astrocytomas were found in males or females at the high dose of 140.8 mg/kg/day (about 34 times the human dose of 40 mg/day on a body surface area basis). A 78-week mouse carcinogenicity study of omeprazole did not show increased tumor occurrence, but the study was not conclusive. A 26-week p53 (+/-) transgenic mouse carcinogenicity study was not positive. Omeprazole was positive for clastogenic effects in an in vitro human lymphocyte chromosomal aberration assay, in one of two in vivo mouse micronucleus tests, and in an in vivo bone marrow cell chromosomal aberration assay. Omeprazole was negative in the in vitro Ames test, an in vitro mouse lymphoma cell forward mutation assay, and an in vivo rat liver DNA damage assay.

Omeprazole at oral doses up to 138 mg/kg/day in rats (about 34 times an oral human dose of 40 mg on a body surface area basis) was found to have no effect on fertility and reproductive performance.

In 24-month carcinogenicity studies in rats, a dose-related significant increase in gastric carcinoid tumors and ECL cell hyperplasia was observed in both male and female animals [see Warnings and Precautions (5)] . Carcinoid tumors have also been observed in rats subjected to fundectomy or long-term treatment with other proton pump inhibitors or high doses of H ₂-receptor antagonists.

Omeprazole is indicated for the maintenance healing of EE due to acid-mediated GERD in patients 2 years of age and older. Controlled studies do not extend beyond 12 months.

In a U.S. double-blind, randomized, multicenter, placebo controlled study, two dose regimens of omeprazole were studied in patients with endoscopically confirmed healed esophagitis. Results to determine maintenance of healing of EE are shown below.

In an international multicenter double-blind study, omeprazole 20 mg daily and 10 mg daily were compared with ranitidine 150 mg twice daily in patients with endoscopically confirmed healed esophagitis. The table below provides the results of this study for maintenance of healing of EE.

In patients who initially had grades 3 or 4 erosive esophagitis, for maintenance after healing 20 mg daily of omeprazole was effective, while 10 mg did not demonstrate effectiveness.

Omeprazole is indicated for the treatment of heartburn and other symptoms associated with GERD for up to 4 weeks in patients 2 years of age and older.

Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Healthcare providers should temporarily stop omeprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary [see Drug Interactions (7)] .

In clinical trials using either dual therapy with omeprazole and clarithromycin, or triple therapy with omeprazole, clarithromycin, and amoxicillin, no adverse reactions unique to these drug combinations were observed. Adverse reactions observed were limited to those previously reported with omeprazole, clarithromycin, or amoxicillin alone.

Triple Therapy

Omeprazole delayed-release capsules in combination with clarithromycin and amoxicillin, is indicated for treatment of patients with H. pylori infection and duodenal ulcer disease (active or up to 1-year history) to eradicate H. pylori in adults.

Storage

Store Omeprazole delayed-release capsules in a tight container protected from light and moisture. Store between 15°C and 30°C (59°F and 86°F).

Reports have been received of overdosage with omeprazole in humans. Doses ranged up to 2400 mg (120 times the usual recommended clinical dose). Manifestations were variable, but included confusion, drowsiness, blurred vision, tachycardia, nausea, vomiting, diaphoresis, flushing, headache, dry mouth, and other adverse reactions similar to those seen in normal clinical experience [see Adverse Reactions (6)]. Symptoms were transient, and no serious clinical outcome has been reported when omeprazole was taken alone. No specific antidote for omeprazole overdosage is known. Omeprazole is extensively protein bound and is, therefore, not readily dialyzable. In the event of overdosage, treatment should be symptomatic and supportive.

If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Tenth Edition. CLSI Document M07-A10, Clinical and Laboratory Standards Institute, 950 West Valley Road, Suite 2500, Wayne, Pennsylvania, 19087, USA 2015.

The active ingredient in Omeprazole delayed-release capsules, USP, is a substituted benzimidazole, 5-methoxy-2-[[(4-methoxy-3, 5-dimethyl-2-pyridinyl) methyl] sulfinyl]-1 H-benzimidazole, a compound that inhibits gastric acid secretion. Its empirical formula is C ₁₇H ₁₉N ₃O ₃S, with a molecular weight of 345.42. The structural formula is:

Omeprazole is a white to off-white crystalline powder that melts with decomposition at about 155°C. It is a weak base, freely soluble in ethanol and methanol, and slightly soluble in acetone and isopropanol and very slightly soluble in water. The stability of omeprazole is a function of pH; it is rapidly degraded in acid media, but has acceptable stability under alkaline conditions.

Omeprazole is supplied as delayed-release capsules for oral administration. Each delayed-release capsule contains either 10 mg, 20 mg or 40 mg of omeprazole in the form of enteric-coated granules with the following inactive ingredients: ammonium hydroxide, colloidal anhydrous silica, dibutyl sebacate, ethylcellulose 20 cP, hypromellose, maize starch, methacrylic acid-ethyl acrylate copolymer, oleic acid, polysorbate 80, sodium lauryl sulfate, sucrose, talc, titanium dioxide, and triethyl citrate. The capsule shells have the following inactive ingredients: ammonium hydroxide, black iron oxide, ethyl alcohol, gelatin, isopropyl alcohol, n-butyl alcohol, potassium hydroxide, propylene glycol, shellac, and titanium dioxide.

Omeprazole delayed-release capsules meet USP Dissolution Test 2.

Read this Medication Guide before you start taking Omeprazole delayed-release capsules and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.

What is the most important information I should know about Omeprazole delayed-release capsules?

You should take omeprazole delayed-release capsules exactly as prescribed, at the lowest dose possible and for the shortest time needed.

Omeprazole delayed-release capsules may help your acid-related symptoms, but you could still have serious stomach problems. Talk with your doctor.

Omeprazole delayed-release capsules can cause serious side effects, including:

• A type of kidney problem (acute tubulointerstitial nephritis). Some people who take proton pump inhibitor (PPI) medicines, including omeprazole delayed-release capsules, may develop a kidney problem called acute tubulointerstitial nephritis that can happen at any time during treatment with omeprazole delayed-release capsules. Call your doctor right away if you have a decrease in the amount that you urinate or if you have blood in your urine.
• Diarrhea. Omeprazole delayed-release capsules may increase your risk of getting severe diarrhea. This diarrhea may be caused by an infection ( Clostridium difficile) in your intestines. Call your doctor right away if you have watery stool, stomach pain, and fever that does not go away.
• Bone fractures. People who take multiple daily doses of PPI medicines for a long period of time (a year or longer) may have an increased risk of fractures of the hip, wrist, or spine. You should take Omeprazole delayed-release capsules exactly as prescribed, at the lowest dose possible for your treatment and for the shortest time needed. Talk to your doctor about your risk of bone fracture if you take Omeprazole delayed-release capsules.
• Certain types of lupus erythematosus. Lupus erythematosus is an autoimmune disorder (the body's immune cells attack other cells or organs in the body). Some people who take proton PPI medicines, including Omeprazole delayed-release capsules, may develop certain types of lupus erythematosus or have worsening of the lupus they already have. Call your doctor right away if you have new or worsening joint pain or a rash on your cheeks or arms that gets worse in the sun.

Omeprazole delayed-release capsules can have other serious side effects. See " What are the possible side effects of Omeprazole delayed-release capsules?"

What are Omeprazole delayed-release capsules?

Omeprazole delayed-release capsules are a prescription medicine called a proton pump inhibitor (PPI). Omeprazole delayed-release capsules reduces the amount of acid in your stomach.

Omeprazole delayed-release capsules are used in adults:

• for up to 8 weeks for the healing of duodenal ulcers. The duodenal area is the area where food passes when it leaves the stomach.
• with certain antibiotics for 10 to 14 days to treat an infection caused by bacteria called H. pylori. If needed, your doctor may decide to prescribe another 14 to 18 days of Omeprazole delayed-release capsules by itself after the antibiotics. Sometimes H. pylori bacteria can cause duodenal ulcers. The infection needs to be treated to prevent the ulcers from coming back.
• for up to 8 weeks for healing stomach ulcers.
• for up to 4 weeks to treat heartburn and other symptoms that happen with gastroesophageal reflux disease (GERD). GERD happens when acid in your stomach backs up into the tube (esophagus) that connects your mouth to your stomach. This may cause a burning feeling in your chest or throat, sour taste, or burping.
• for up to 8 weeks to heal acid-related damage to the lining of the esophagus (called erosive esophagitis or EE). If needed, your doctor may decide to prescribe another 4 weeks of Omeprazole delayed-release capsules.
• to maintain healing of the esophagus. It is not known if Omeprazole delayed-release capsules are safe and effective when used for longer than 12 months (1 year) for this purpose.
• for the long-term treatment of conditions where your stomach makes too much acid. This includes a rare condition called Zollinger-Ellison Syndrome.

For children 2 to 16 years of age, Omeprazole Delayed-Release Capsules are used:

• for up to 4 weeks to treat heartburn and other symptoms that happen with gastroesophageal reflux disease (GERD).
• for up to 8 weeks to treat gastroesophageal reflux disease (GERD) with acid-related damage to the lining of the esophagus [called erosive esophagitis (or EE) due to acid-mediated GERD].
• to maintain healing of the esophagus. It is not known if Omeprazole delayed-release capsules are safe and effective when used longer than 12 months (1 year) for this purpose. It is not known if Omeprazole Delayed-Release Capsules is safe and effective in children less than 1 month of age.

Who should not take Omeprazole delayed-release capsules?

Do not take Omeprazole delayed-release capsules if you:

• are allergic to omeprazole or any of the ingredients in Omeprazole delayed-release capsules. See the end of this Medication Guide for a complete list of ingredients in Omeprazole delayed-release capsules.
• are allergic to any other proton pump inhibitor (PPI) medicine.
• are taking a medicine that contains rilpivirine (EDURANT, COMPLERA) used to treat HIV-1 (Human Immunodeficiency Virus).

What should I tell my doctor before taking Omeprazole delayed-release capsules?

Before taking Omeprazole delayed-release capsules, tell your doctor about all of your medical conditions, including if you:

• have low magnesium levels, low calcium levels and low potassium levels in your blood.
• have liver problems.
• have any other medical conditions.
• are pregnant or plan to become pregnant. It is not known if Omeprazole delayed-release capsules will harm your unborn baby.
• are breastfeeding or plan to breastfeed. Omeprazole passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take Omeprazole delayed-release capsules.
• Tell your doctor about all of the medicines you take including prescription and over-the-counter medicines, vitamins and herbal supplements. Omeprazole delayed-release capsules may affect how other medicines work, and other medicines may affect how Omeprazole delayed-release capsules work. Especially tell your doctor if you take an antibiotic that contains clarithromycin or amoxicillin, or if you take clopidogrel (Plavix), methotrexate (Otrxup, Rasuvo, Trexall), St. John's Wort ( Hypericum perforatum) , or rifampin (Rimactane, Rifater, Rifamate).

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

How should I take Omeprazole delayed-release capsules?

• Take Omeprazole delayed-release capsules exactly as prescribed by your doctor.
• Do not change your dose or stop Omeprazole delayed-release capsules without talking to your doctor.
• Omeprazole delayed-release capsules are usually taken 1 time each day. Your doctor will tell you the time of day to take Omeprazole delayed-release capsules, based on your medical condition.
• Take Omeprazole delayed-release capsules before a meal.
• Antacids may be taken with Omeprazole delayed-release capsules.
• Swallow Omeprazole delayed-release capsules whole. Do not chew or crush Omeprazole delayed-release capsules.
• If you have trouble swallowing a whole capsule, you can open the capsule and take the contents in applesauce. See the " Instructions for Use" at the end of this Medication Guide for instructions on how to take Omeprazole delayed-release capsules with applesauce.

If you miss a dose of Omeprazole delayed-release capsules, take it as soon as you remember. If it is almost time for your next dose, do not take the missed dose. Take the next dose at your regular time. Do not take 2 doses at the same time to make up for the missed dose.

If you take too much Omeprazole delayed-release capsules, call your doctor or your poison control center at 1-800-222-1222 right away or go to the nearest emergency room.

What are the possible side effects of Omeprazole delayed-release capsules?

Omeprazole delayed-release capsules can cause serious side effects, including:

• See " What is the most important information I should know about Omeprazole delayed-release capsules?"
• Vitamin B-12 deficiency. Omeprazole delayed-release capsules reduces the amount of acid in your stomach. Stomach acid is needed to absorb vitamin B-12 properly. Talk with your doctor about the possibility of vitamin B-12 deficiency if you have been on Omeprazole delayed-release capsules for a long time (more than 3 years).
• Low magnesium levels in your body. This problem can be serious. Low magnesium can happen in some people who take a PPI medicine for at least 3 months. If low magnesium levels happen, it is usually after a year of treatment.

You may or may not have symptoms of low magnesium. Tell your doctor right away if you develop any of these symptoms:

Your doctor may check the level of magnesium in your body before you start taking Omeprazole delayed-release capsules or during treatment if you will be taking Omeprazole delayed-release capsules for a long period of time.

• Stomach growths (fundic gland polyps). People who take PPI medicines for a long time have an increased risk of developing a certain type of stomach growths called fundic gland polyps, especially after taking PPI medicines for more than 1 year.
• Severe skin reactions. Omeprazole delayed-release capsules can cause rare but severe skin reactions that may affect any part of your body. These serious skin reactions may need to be treated in a hospital and may be life threatening:
  • Skin rash which may have blistering, peeling or bleeding on any part of your skin (including your lips, eyes, mouth, nose, genitals, hands or feet).
  • You may also have fever, chills, body aches, shortness of breath, or enlarged lymph nodes.
    
    Stop taking Omeprazole delayed-release capsules and call your doctor right away. These symptoms may be the first sign of a severe skin reaction.

The most common side effects with Omeprazole delayed-release capsules in adults and children include:

In addition to the side effects listed above, the most common side effects in children 1 to 16 years of age include:

Other side effects:

Serious allergic reactions. Tell your doctor if you get any of the following symptoms with Omeprazole delayed-release capsules:

Your doctor may stop Omeprazole delayed-release capsules if these symptoms happen. Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all the possible side effects with Omeprazole delayed-release capsules. For more information, ask your doctor or pharmacist. 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 Omeprazole delayed-release capsules?

• Store Omeprazole delayed-release capsules at room temperature between 59°F to 86°F (15°C to 30°C).
• Keep the container of Omeprazole delayed-release capsules closed tightly.
• Keep the container of Omeprazole delayed-release capsules dry and away from light.

Keep Omeprazole delayed-release capsules and all medicines out of the reach of children.

General information about the safe and effective use of Omeprazole delayed-release capsules.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Omeprazole delayed-release capsules for a condition for which it was not prescribed. Do not give Omeprazole delayed-release capsules to other people, even if they have the same symptoms you have. It may harm them.

This Medication Guide summarizes the most important information about Omeprazole delayed-release capsules. For more information, ask your doctor. You can ask your doctor or pharmacist for information that is written for healthcare professionals. For more information, go to www.bpirx.com or call toll free 1-800-367-3395.

What are the ingredients in Omeprazole delayed-release capsules?

Active ingredient in Omeprazole delayed-release capsules: omeprazole

Inactive ingredients in Omeprazole delayed-release capsules (including the capsule shells): ammonium hydroxide, black iron oxide, colloidal anhydrous silica, dibutyl sebacate, ethyl alcohol, ethylcellulose 20 cP, gelatin, hypromellose, isopropyl alcohol, maize starch, methacrylic acid-ethyl acrylate copolymer, n-butyl alcohol, oleic acid, polysorbate 80, potassium hydroxide, propylene glycol, shellac, sodium lauryl sulfate, sucrose, talc, titanium dioxide, triethyl citrate.

Trademarks are the property of their respective owners.

This Medication Guide and Instructions for Use has been approved by the U.S. Food and Drug Administration.

Omeprazole and clarithromycin dual therapy and omeprazole, clarithromycin and amoxicillin triple therapy have been shown to be active against most strains of Helicobacter pylori in vitro and in clinical infections [see Indications and Usage (1.2), Clinical Studies (14.2)].

Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines [see Dosage and Administration (2.1), Adverse Reactions (6.3)].

The safety and effectiveness of omeprazole delayed-release capsules have been established in pediatric patients 2 to 16 years for the treatment of symptomatic GERD, treatment of EE due to acid-mediated GERD, and maintenance of healing of EE due to acid-mediated GERD. Use of Omeprazole delayed-release capsules in this age group is supported by adequate and well-controlled studies in adults and uncontrolled safety, efficacy and pharmacokinetic studies performed in pediatric and adolescent patients [see Clinical Pharmacology (12.3), Clinical Studies (14.8)] .

In the pediatric population, adverse reactions of the respiratory system were frequently reported in the entire (2 to 16 years) age group. Accidental injuries were frequently reported in the 2 to 16 year age group [see Adverse Reactions (6.1)].

The safety and effectiveness of Omeprazole delayed-release capsules have not been established in:

• patients less than 1 year of age for:
  • Treatment of symptomatic GERD
  • Maintenance of healing of EE due to acid-mediated GERD

• pediatric patients for:
  • Treatment of active duodenal ulcer
  • H. pylori eradication to reduce the risk of duodenal ulcer recurrence
  • Treatment of active benign gastric ulcer
  • Pathological hypersecretory conditions
• patients less than 1 month of age for any indication.

Omeprazole was administered to over 2000 elderly individuals (≥ 65 years of age) in clinical trials in the U.S. and Europe. There were no differences in safety and effectiveness between the elderly and younger subjects. Other reported clinical experience has not identified differences in response between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.

Pharmacokinetic studies have shown the elimination rate was somewhat decreased in the elderly and bioavailability was increased. The plasma clearance of omeprazole was 250 mL/min (about half that of young volunteers) and its plasma half-life averaged one hour, about twice that of young healthy volunteers. However, no dosage adjustment is necessary in the elderly [see Clinical Pharmacology (12.3)].

• Omeprazole delayed-release capsules are contraindicated in patients with known hypersensitivity reactions including anaphylaxis to the formulation or any substituted benzimidazole. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute tubulointerstitial nephritis, and urticaria [see Warnings and Precautions (5.2), Adverse Reactions (6)].
• Proton pump inhibitors (PPIs), including Omeprazole delayed-release capsules, are contraindicated in patients receiving rilpivirine-containing products [see Drug Interactions (7)] .
• For information about contraindications of antibacterial agents (clarithromycin and amoxicillin) indicated in combination with omeprazole, refer to the CONTRAINDICATIONS section of their package inserts.

The following serious adverse reactions are described below and elsewhere in labeling:

• Acute Tubulointerstitial Nephritis [see Warnings and Precautions (5.2)]
• Clostridium difficile-Associated Diarrhea [see Warnings and Precautions (5.3)]
• Bone Fracture [see Warnings and Precautions (5.4)]
• Cutaneous and Systemic Lupus Erythematosus [see Warnings and Precautions (5.6)]
• Cyanocobalamin (Vitamin B-12) Deficiency [see Warnings and Precautions (5.8)]
• Hypomagnesemia [see Warnings and Precautions (5.9)]
• Fundic Gland Polyps [see Warnings and Precautions (5.13)]

Tables 3 and 4 include drugs with clinically important drug interactions and interaction with diagnostics when administered concomitantly with Omeprazole delayed-release capsules and instructions for preventing or managing them.

Consult the labeling of concomitantly used drugs to obtain further information about interactions with PPIs.

In studies of healthy subjects, Asians had approximately a four-fold higher exposure than Caucasians. Dosage reduction of Omeprazole delayed-release capsules to 10 mg once daily is recommended for Asian patients for maintenance of healing of EE [see Dosage and Administration (2.1), Clinical Pharmacology (12.5)].

Omeprazole delayed-release capsules

Taking Omeprazole delayed-release capsules with applesauce:

• Place 1 tablespoon of applesauce into a clean container.
• Carefully open the capsule and sprinkle the pellets onto the applesauce. Mix the pellets with the applesauce.
• Swallow the applesauce and pellet mixture right away. Do not chew or crush the pellets. Do not store the applesauce and pellet mixture for later use.

Manufactured for: Breckenridge Pharmaceutical, Inc., Berlin, CT 06037



Manufactured by: Towa Pharmaceutical Europe, S.L., Barcelona, Spain

Revised: 02/2022

Marketed by:

GSMS, Inc.

Camarillo, CA 93012 USA

Omeprazole is a time-dependent inhibitor of CYP2C19, resulting in autoinhibition and nonlinear pharmacokinetics. The systemic exposure increases in a more than dose proportional manner after multiple oral doses of omeprazole. Compared to the first dose, the systemic exposure (C _max and AUC _0-24h) at steady state following once a day dosing increased by 61% and 62%, respectively, compared to after the first dose for the 20 mg dose of Omeprazole delayed-release capsules and increased by 118% and 175%, respectively, for the 40 mg dose of Omeprazole delayed-release capsules.

CYP2C19, a polymorphic enzyme, is involved in the metabolism of omeprazole. The CYP2C19*1 allele is fully functional while the CYP2C19*2 and *3 alleles are nonfunctional. There are other alleles associated with no or reduced enzymatic function. Patients carrying two fully functional alleles are extensive metabolizers and those carrying two loss-of-function alleles are poor metabolizers. In extensive metabolizers, omeprazole is primarily metabolized by CYP2C19. The systemic exposure to omeprazole varies with a patient's metabolism status: poor metabolizers > intermediate metabolizers > extensive metabolizers. Approximately 3% of Caucasians and 15 to 20% of Asians are CYP2C19 poor metabolizers.

In a pharmacokinetic study of single 20 mg omeprazole dose, the AUC of omeprazole in Asian subjects was approximately four-fold of that in Caucasians [see Dosage and Administration (2.1), Use in Specific Populations (8.7)].

A placebo-controlled study was conducted in Scandinavia to compare the efficacy of omeprazole 20 mg or 10 mg once daily for up to 4 weeks in the treatment of heartburn and other symptoms in GERD patients without EE. Results are shown below.

In patients with hepatic impairment (Child-Pugh Class A, B, or C) exposure to omeprazole substantially increased compared to healthy subjects. Dosage reduction of Omeprazole delayed-release capsules to 10 mg once daily is recommended for patients with hepatic impairment for maintenance of healing of EE [see Dosage and Administration (2.1), Clinical Pharmacology (12.3)].

Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.

Omeprazole delayed-release capsules, USP, are a proton pump inhibitor (PPI) indicated for the:

• Treatment of active duodenal ulcer in adults ( 1.1)
• Eradication of Helicobacter pylori to reduce the risk of duodenal ulcer recurrence in adults ( 1.2)
• Treatment of active benign gastric ulcer in adults ( 1.3)
• Treatment of symptomatic gastroesophageal reflux disease (GERD) in patients 2 years of age and older ( 1.4)
• Treatment of erosive esophagitis (EE) due to acid-mediated GERD in patients 2 years of age and older ( 1.5)
• Maintenance of healing of EE due to acid-mediated GERD in patients 2 years of age and older ( 1.6)
• Pathologic hypersecretory conditions in adults ( 1.7)

Omeprazole belongs to a class of antisecretory compounds, the substituted benzimidazoles, that suppress gastric acid secretion by specific inhibition of the H ⁺/K ⁺ ATPase enzyme system at the secretory surface of the gastric parietal cell. Because this enzyme system is regarded as the acid (proton) pump within the gastric mucosa, omeprazole has been characterized as a gastric acid-pump inhibitor, in that it blocks the final step of acid production. This effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespective of the stimulus.

PPI use is associated with an increased risk of fundic gland polyps that increases with long-term use, especially beyond one year. Most PPI users who developed fundic gland polyps were asymptomatic and fundic gland polyps were identified incidentally on endoscopy. Use the shortest duration of PPI therapy appropriate to the condition being treated.

Published observational studies suggest that PPI therapy like Omeprazole delayed-release capsules may be associated with an increased risk of Clostridium difficile-associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve [see Adverse Reactions (6.2)]. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.

Clostridium difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents. For more information specific to antibacterial agents (clarithromycin and amoxicillin) indicated for use in combination with Omeprazole delayed-release capsules, refer to Warnings and Precautions sections of the corresponding prescribing information.

In a multicenter, double-blind, placebo-controlled study of 147 patients with endoscopically documented duodenal ulcer, the percentage of patients healed (per protocol) at 2 and 4 weeks was significantly higher with omeprazole 20 mg once daily than with placebo (p ≤ 0.01).

Complete daytime and nighttime pain relief occurred significantly faster (p ≤ 0.01) in patients treated with omeprazole 20 mg than in patients treated with placebo. At the end of the study, significantly more patients who had received omeprazole had complete relief of daytime pain (p ≤ 0.05) and nighttime pain (p ≤ 0.01).

In a multicenter, double-blind study of 293 patients with endoscopically documented duodenal ulcer, the percentage of patients healed (per protocol) at 4 weeks was significantly higher with omeprazole 20 mg once daily than with ranitidine 150 mg b.i.d. (p < 0.01).

Healing occurred significantly faster in patients treated with omeprazole than in those treated with ranitidine 150 mg b.i.d. (p < 0.01).

In a foreign multinational randomized, double-blind study of 105 patients with endoscopically documented duodenal ulcer, 20 mg and 40 mg of omeprazole were compared with 150 mg b.i.d. of ranitidine at 2, 4 and 8 weeks. At 2 and 4 weeks both doses of omeprazole were statistically superior (per protocol) to ranitidine, but 40 mg was not superior to 20 mg of omeprazole, and at 8 weeks there was no significant difference between any of the active drugs.

• Gastric Malignancy: In adults, symptomatic response does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing. ( 5.1)
• Acute Tubulointerstitial Nephritis: discontinue treatment and evaluate patients. ( 5.2)
• Clostridium difficile-Associated Diarrhea: PPI therapy may be associated with increased risk. ( 5.3)
• Bone Fracture: Long-term and multiple daily dose PPI therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. ( 5.4)
• Severe Cutaneous Adverse Reactions: Discontinue at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation ( 5.5)
• Cutaneous and Systemic Lupus Erythematosus: Mostly cutaneous; new onset or exacerbation of existing disease; discontinue Omeprazole delayed-release capsules and refer to specialist for evaluation. ( 5.6)
• Interaction with Clopidogrel: Avoid concomitant use of Omeprazole delayed-release capsules. ( 5.7, 7)
• Cyanocobalamin (Vitamin B-12) Deficiency: Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin. ( 5.8)
• Hypomagnesemia and Mineral Metabolism: Reported rarely with prolonged treatment with PPIs. ( 5.9)
• Interaction with St. John's Wort or Rifampin: Avoid concomitant use of Omeprazole delayed-release capsules. ( 5.10, 7)
• Interactions with Diagnostic Investigations for Neuroendocrine Tumors: Increased Chromogranin A (CgA) levels may interfere with diagnostic investigations for neuroendocrine tumors; temporarily stop Omeprazole delayed-release capsules at least 14 days before assessing CgA levels. ( 5.11, 7)
• Interaction with Methotrexate: Concomitant use with PPIs may elevate and/or prolong serum concentrations of methotrexate and/or its metabolite, possibly leading to toxicity. With high dose methotrexate administration, consider a temporary withdrawal of Omeprazole delayed-release capsules. ( 5.12, 7)
• Fundic Gland Polyps: Risk increases with long-term use, especially beyond one year. Use the shortest duration of therapy. ( 5.13)

The following adverse reactions have been identified during post-approval use of Omeprazole delayed-release capsules. Because these reactions are voluntarily reported from a population of uncertain size, it is not always possible to reliably estimate their actual frequency or establish a causal relationship to drug exposure.

Body As a Whole: Hypersensitivity reactions including anaphylaxis, anaphylactic shock, angioedema, bronchospasm, interstitial nephritis, urticaria, (see also Skin below); fever; pain; fatigue; malaise; systemic lupus erythematosus

Cardiovascular: Chest pain or angina, tachycardia, bradycardia, palpitations, elevated blood pressure, peripheral edema

Endocrine: Gynecomastia

Gastrointestinal: Pancreatitis (some fatal), anorexia, irritable colon, fecal discoloration, esophageal candidiasis, mucosal atrophy of the tongue, stomatitis, abdominal swelling, dry mouth, microscopic colitis, fundic gland polyps.

Gastroduodenal carcinoids have been reported in patients with ZE syndrome on long-term treatment with omeprazole. This finding is believed to be a manifestation of the underlying condition, which is known to be associated with such tumors.

Hepatic: Liver disease including hepatic failure (some fatal), liver necrosis (some fatal), hepatic encephalopathy hepatocellular disease, cholestatic disease, mixed hepatitis, jaundice, and elevations of liver function tests [ALT, AST, GGT, alkaline phosphatase, and bilirubin]

Infections and Infestations: Clostridium difficile-associated diarrhea

Metabolism and Nutritional disorders: Hypoglycemia, hypomagnesemia, with or without hypocalcemia and/or hypokalemia, hyponatremia, weight gain [See Warnings and Precautions (5.9)]

Musculoskeletal: Muscle weakness, myalgia, muscle cramps, joint pain, leg pain, bone fracture

Nervous System/Psychiatric: Psychiatric and sleep disturbances including depression, agitation, aggression, hallucinations, confusion, insomnia, nervousness, apathy, somnolence, anxiety, and dream abnormalities; tremors, paresthesia; vertigo

Respiratory: Epistaxis, pharyngeal pain

Skin: Severe generalized skin reactions including toxic epidermal necrolysis (some fatal), Stevens-Johnson syndrome, cutaneous lupus erythematosus and erythema multiforme; photosensitivity; urticaria; rash; skin inflammation; pruritus; petechiae; purpura; alopecia; dry skin; hyperhidrosis

Special Senses: Tinnitus, taste perversion

Ocular: Optic atrophy, anterior ischemic optic neuropathy, optic neuritis, dry eye syndrome, ocular irritation, blurred vision, double vision

Urogenital: Interstitial nephritis, hematuria, proteinuria, elevated serum creatinine, microscopic pyuria, urinary tract infection, glycosuria, urinary frequency, testicular pain

Hematologic: Agranulocytosis (some fatal), hemolytic anemia, pancytopenia, neutropenia, anemia, thrombocytopenia, leukopenia, leukocytosis

Omeprazole delayed-release capsules, USP, 10 mg, are opaque, hard gelatin, white-colored capsules, coded in black ink "OM" on the cap and "10" on the body.

Omeprazole delayed-release capsules, USP, 20 mg, are opaque, hard gelatin, white-colored capsules, coded in black ink "OM" on the cap and "20" on the body.

Omeprazole delayed-release capsules, USP, 40 mg, are opaque, hard gelatin, white-colored capsules, coded in black ink "OM" on the cap and "40" on the body.

• Take Omeprazole delayed-release capsules before meals.
• Antacids may be used concomitantly with Omeprazole delayed-release capsules.
• Missed doses: If a dose is missed, administer as soon as possible. However, if the next scheduled dose is due, do not take the missed dose, and take the next dose on time. Do not take two doses at one time to make up for a missed dose.

In a U.S. multicenter, double-blind, study of omeprazole 40 mg once daily, 20 mg once daily, and placebo in 520 patients with endoscopically diagnosed gastric ulcer, the following results were obtained.

For the stratified groups of patients with ulcer size less than or equal to 1 cm, no difference in healing rates between 40 mg and 20 mg was detected at either 4 or 8 weeks. For patients with ulcer size greater than 1 cm, 40 mg was significantly more effective than 20 mg at 8 weeks.

In a foreign, multinational, double-blind study of 602 patients with endoscopically diagnosed gastric ulcer, omeprazole 40 mg once daily, 20 mg once daily, and ranitidine 150 mg twice a day were evaluated.

Avoid concomitant use of Omeprazole delayed-release capsules with clopidogrel. Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by use with concomitant medications, such as omeprazole, that inhibit CYP2C19 activity. Concomitant use of clopidogrel with 80 mg omeprazole reduces the pharmacological activity of clopidogrel, even when administered 12 hours apart. When using Omeprazole delayed-release capsules, consider alternative anti-platelet therapy [see Drug Interactions (7) and Clinical Pharmacology (12.3)].

In a U.S. multicenter double-blind placebo controlled study of 20 mg or 40 mg of Omeprazole delayed-release capsules in patients with symptoms of GERD and endoscopically diagnosed EE of grade 2 or above, the percentage healing rates (per protocol) were as follows:

In this study, the 40 mg dose was not superior to the 20 mg dose of omeprazole in the percentage healing rate. Other controlled clinical trials have also shown that omeprazole is effective in severe GERD. In comparisons with histamine H ₂-receptor antagonists in patients with EE, grade 2 or above, omeprazole in a dose of 20 mg was significantly more effective than the active controls. Complete daytime and nighttime heartburn relief occurred significantly faster (p < 0.01) in patients treated with omeprazole than in those taking placebo or histamine H ₂-receptor antagonists.

In this and five other controlled GERD studies, significantly more patients taking 20 mg omeprazole (84%) reported complete relief of GERD symptoms than patients receiving placebo (12%).

Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).

In adults, symptomatic response to therapy with Omeprazole delayed-release capsules does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a PPI. In older patients, also consider an endoscopy.

Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration a temporary withdrawal of the PPI may be considered in some patients [see Drug Interactions (7)].

Omeprazole delayed-release capsules, USP, 40 mg, are opaque, hard gelatin, white-colored capsules, coded in black ink "OM" on the cap and "40" on the body. They are supplied as follows:

NDC 51407-664-01 bottles of 100

NDC 51407-664-05 bottles of 500

NDC 51407-814-30 bottles of 30

NDC 51407-814-90 bottles of 90

NDC 51407-814-01 bottles of 100

NDC 51407-814-05 bottles of 500

Omeprazole delayed-release capsules, USP, are indicated for short-term treatment of active duodenal ulcer in adults. Most patients heal within four weeks. Some patients may require an additional four weeks of therapy.

Acute tubulointerstitial nephritis (TIN) has been observed in patients taking PPIs and may occur at any point during PPI therapy. Patients may present with varying signs and symptoms from symptomatic hypersensitivity reactions, to non-specific symptoms of decreased renal function (e.g., malaise, nausea, anorexia). In reported case series, some patients were diagnosed on biopsy and in the absence of extra-renal manifestations (e.g., fever, rash or arthralgia). Discontinue Omeprazole delayed-release capsules and evaluate patients with suspected acute TIN [see Contraindications (4)].

Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use of PPIs [see Adverse Reactions (6.2)] . Discontinue Omeprazole delayed-release capsules at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation.

Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. Hypomagnesemia may lead to hypocalcemia and/or hypokalemia and may exacerbate underlying hypocalcemia in at-risk patients. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.

For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically [see Adverse Reactions (6.2)].

Consider monitoring magnesium and calcium levels prior to initiation of Omeprazole delayed-release capsules and periodically while on treatment in patients with a preexisting risk of hypocalcemia (e.g., hypoparathyroidism). Supplement with magnesium and/or calcium, as necessary. If hypocalcemia is refractory to treatment, consider discontinuing the PPI.

Omeprazole is indicated for the long-term treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome, multiple endocrine adenomas and systemic mastocytosis) in adults.

In open studies of 136 patients with pathological hypersecretory conditions, such as Zollinger-Ellison (ZE) syndrome with or without multiple endocrine adenomas, Omeprazole delayed-release capsules significantly inhibited gastric acid secretion and controlled associated symptoms of diarrhea, anorexia, and pain. Doses ranging from 20 mg every other day to 360 mg per day maintained basal acid secretion below 10 mEq/hr in patients without prior gastric surgery, and below 5 mEq/hr in patients with prior gastric surgery.

Initial doses were titrated to the individual patient need, and adjustments were necessary with time in some patients [see Dosage and Administration (2)]. Omeprazole was well tolerated at these high dose levels for prolonged periods (> 5 years in some patients). In most ZE patients, serum gastrin levels were not modified by omeprazole. However, in some patients serum gastrin increased to levels greater than those present prior to initiation of omeprazole therapy. At least 11 patients with ZE syndrome on long-term treatment with omeprazole developed gastric carcinoids. These findings are believed to be a manifestation of the underlying condition, which is known to be associated with such tumors, rather than the result of the administration of omeprazole [see Adverse Reactions (6)].

Omeprazole delayed-release capsules are indicated for short-term treatment (4 to 8 weeks) of active benign gastric ulcer in adults.

Daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (vitamin B-12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed in patients treated with Omeprazole delayed-release capsules.

Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including omeprazole. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The majority of PPI-induced lupus erythematosus cases were CLE. The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. Generally, histological findings were observed without organ involvement.

Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. PPI associated SLE is usually milder than non-drug induced SLE. Onset of SLE typically occurred within days to years after initiating treatment primarily in patients ranging from young adults to the elderly. The majority of patients presented with rash; however, arthralgia and cytopenia were also reported.

Avoid administration of PPIs for longer than medically indicated. If signs or symptoms consistent with CLE or SLE are noted in patients receiving Omeprazole delayed-release capsules, discontinue the drug and refer the patient to the appropriate specialist for evaluation. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks. Serological testing (e.g., ANA) may be positive and elevated serological test results may take longer to resolve than clinical manifestations.

Drugs which induce CYP2C19 or CYP3A4 (such as St. John's Wort or rifampin) can substantially decrease omeprazole concentrations [see Drug Interactions (7)] . Avoid concomitant use of Omeprazole delayed-release capsules with St. John's Wort or rifampin.

Table 1 shows the recommended dosage of Omeprazole delayed-release capsules in adult patients by indication.

NDC 51407-664-05

Omeprazole



Delayed-Release Capsules, USP

40 mg

PHARMACIST: Dispense the Patient Information to each patient.

Rx Only



500 Capsules

NDC 51407-814-05

Omeprazole



Delayed-Release Capsules, USP

40 mg

PHARMACIST: Dispense the Medication Guide to each patient.

Rx Only



500 Capsules

Table 2 shows the recommended dosage of Omeprazole delayed-release capsules in pediatric patients by indication.

In two 24-month carcinogenicity studies in rats, omeprazole at daily doses of 1.7, 3.4, 13.8, 44.0 and 140.8 mg/kg/day (about 0.4 to 34 times a human dose of 40 mg/day, as expressed on a body surface area basis) produced gastric ECL cell carcinoids in a dose-related manner in both male and female rats; the incidence of this effect was markedly higher in female rats, which had higher blood levels of omeprazole. Gastric carcinoids seldom occur in the untreated rat. In addition, ECL cell hyperplasia was present in all treated groups of both sexes. In one of these studies, female rats were treated with 13.8 mg omeprazole/kg/day (about 3.4 times a human dose of 40 mg/day, based on body surface area) for one year, and then followed for an additional year without the drug. No carcinoids were seen in these rats. An increased incidence of treatment-related ECL cell hyperplasia was observed at the end of one year (94% treated vs. 10% controls). By the second year the difference between treated and control rats was much smaller (46% vs. 26%) but still showed more hyperplasia in the treated group. Gastric adenocarcinoma was seen in one rat (2%). No similar tumor was seen in male or female rats treated for two years. For this strain of rat no similar tumor has been noted historically, but a finding involving only one tumor is difficult to interpret. In a 52-week toxicity study in Sprague-Dawley rats, brain astrocytomas were found in a small number of males that received omeprazole at dose levels of 0.4, 2, and 16 mg/kg/day (about 0.1 to 3.9 times the human dose of 40 mg/day, based on a body surface area basis). No astrocytomas were observed in female rats in this study. In a 2-year carcinogenicity study in Sprague-Dawley rats, no astrocytomas were found in males or females at the high dose of 140.8 mg/kg/day (about 34 times the human dose of 40 mg/day on a body surface area basis). A 78-week mouse carcinogenicity study of omeprazole did not show increased tumor occurrence, but the study was not conclusive. A 26-week p53 (+/-) transgenic mouse carcinogenicity study was not positive. Omeprazole was positive for clastogenic effects in an in vitro human lymphocyte chromosomal aberration assay, in one of two in vivo mouse micronucleus tests, and in an in vivo bone marrow cell chromosomal aberration assay. Omeprazole was negative in the in vitro Ames test, an in vitro mouse lymphoma cell forward mutation assay, and an in vivo rat liver DNA damage assay.

Omeprazole at oral doses up to 138 mg/kg/day in rats (about 34 times an oral human dose of 40 mg on a body surface area basis) was found to have no effect on fertility and reproductive performance.

In 24-month carcinogenicity studies in rats, a dose-related significant increase in gastric carcinoid tumors and ECL cell hyperplasia was observed in both male and female animals [see Warnings and Precautions (5)] . Carcinoid tumors have also been observed in rats subjected to fundectomy or long-term treatment with other proton pump inhibitors or high doses of H ₂-receptor antagonists.

Omeprazole is indicated for the maintenance healing of EE due to acid-mediated GERD in patients 2 years of age and older. Controlled studies do not extend beyond 12 months.

In a U.S. double-blind, randomized, multicenter, placebo controlled study, two dose regimens of omeprazole were studied in patients with endoscopically confirmed healed esophagitis. Results to determine maintenance of healing of EE are shown below.

In an international multicenter double-blind study, omeprazole 20 mg daily and 10 mg daily were compared with ranitidine 150 mg twice daily in patients with endoscopically confirmed healed esophagitis. The table below provides the results of this study for maintenance of healing of EE.

In patients who initially had grades 3 or 4 erosive esophagitis, for maintenance after healing 20 mg daily of omeprazole was effective, while 10 mg did not demonstrate effectiveness.

Omeprazole is indicated for the treatment of heartburn and other symptoms associated with GERD for up to 4 weeks in patients 2 years of age and older.

Serum chromogranin A (CgA) levels increase secondary to drug-induced decreases in gastric acidity. The increased CgA level may cause false positive results in diagnostic investigations for neuroendocrine tumors. Healthcare providers should temporarily stop omeprazole treatment at least 14 days before assessing CgA levels and consider repeating the test if initial CgA levels are high. If serial tests are performed (e.g., for monitoring), the same commercial laboratory should be used for testing, as reference ranges between tests may vary [see Drug Interactions (7)] .

In clinical trials using either dual therapy with omeprazole and clarithromycin, or triple therapy with omeprazole, clarithromycin, and amoxicillin, no adverse reactions unique to these drug combinations were observed. Adverse reactions observed were limited to those previously reported with omeprazole, clarithromycin, or amoxicillin alone.