Omeprazole

Warnings and Precautions, Interactions with Diagnostic Investigations for Neuroendocrine Tumors ( 5.10 ) 03/2014 Indications and Usage, Treatment of Gastroesophageal Reflux Disease (GERD) (adults and pediatric patients) ( 1.3 ) 12/2014 Dosage and Administration, Maintenance of Healing of Erosive Esophagitis ( 2.5 ) 12/2014 Warnings and Precautions, Acute Interstitial Nephritis ( 5.3 ) 12/2014 Warnings and Precautions, Cyanocobalamin (vitamin B-12) Deficiency ( 5.4 ) 12/2014

1 INDICATIONS AND USAGE Omeprazole Delayed-Release Capsules is 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 1 year of age and older (1.4) Treatment of erosive esophagitis (EE) due to acid-mediated GERD in patients 1 year of age and older (1.5) Maintenance of healing of EE due to acid-mediated GERD in patients 1 year of age and older (1.6) Pathologic hypersecretory conditions in adults (1.7) The safety and effectiveness of Omeprazole Delayed-Release Capsules in pediatric patients < 1 year of age have not been established ( 8.4 ). 1.1 Treatment of Active Duodenal Ulcer Omeprazole Delayed-Release Capsules is 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. 1.2 Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence. 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. Dual Therapy Omeprazole Delayed-Release Capsules in combination with clarithromycin is indicated for treatment of patients with H. pylori infection and duodenal ulcer disease to eradicate H . pylori in adults. Among patients who fail therapy, Omeprazole Delayed-Release Capsules with clarithromycin is more likely to be associated with the development of clarithromycin resistance as compared with triple therapy. In patients who fail therapy, susceptibility testing should be done. If resistance to clarithromycin is demonstrated or susceptibility testing is not possible, alternative antimicrobial therapy should be instituted [see C l i nical Pharmacology (12.4) and the clarithromycin prescribing information, Microbiology section ]. 1.3 Treatment of Active Benign Gastric Ulcer Omeprazole Delayed-Release Capsules is indicated for short-term treatment (4 to 8 weeks) of active benign gastric ulcer in adults. 1.4 Treatment of Symptomatic Gastroesophageal Reflux Disease (GERD) Omeprazole Delayed-Release Capsules is indicated for the treatment of heartburn and other symptoms associated with GERD for up to 4 weeks in patients 1 year of age and older. 1.5 Treatment of Erosive Esophagitis (EE) Due to Acid-Mediated GERD Pediatric Patients 1 Year of Age to Adults Omeprazole Delayed-Release Capsules is indicated for the short-term treatment (4 to 8 weeks) of EE due to acid-mediated GERD that has been diagnosed by endoscopy in patients 1 year of age and older. The efficacy of Omeprazole Delayed-Release Capsules used for longer than 8 weeks in patients with EE has not been established. If a patient does not respond to 8 weeks of treatment, an additional 4 weeks of treatment may be given. If there is recurrence of EE or GERD symptoms (e.g., heartburn), additional 4 to 8 week courses of Omeprazole Delayed-Release Capsules may be considered. The safety and effectiveness of Omeprazole Delayed-Release Capsules in pediatric patients < 1 year of age have not been established ( 8.4 ). 1.6 Maintenance of Healing of EE Due to Acid-Mediated GERD Omeprazole Delayed-Release Capsules is indicated for the maintenance healing of EE due to acid-mediated GERD in patients 1 year of age and older. Controlled studies do not extend beyond 12 months. 1.7 Pathological Hypersecretory Conditions Omeprazole Delayed-Release Capsules is indicated for the long-term treatment of pathological hypersecretory conditions (e.g., Zollinger-Ellison syndrome, multiple endocrine adenomas and systemic mastocy …

Purpose Acid reducer

2 DOSAGE AND ADMINISTRATION Indications Recommended Adult ( Error! Hyperlink reference not valid.) and Pediatric Dosage ( Error! Hyperlink reference not valid.) Treatment of Active Duodenal Ulcer 20 mg once daily for 4 weeks; some patients may require an additional 4 weeks ( Error! Hyperlink reference not valid. ) H. pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Triple Therapy: Omeprazole Delayed-Release Capsules 20 mg Each drug twice daily for 10 days ( Error! Hyperlink reference not valid. )* Amoxicillin 1000 mg Clarithromycin 500 mg Dual Therapy: Omeprazole Delayed-Release Capsules 40 mg once daily for 14 days** Clarithromycin 500 mg three times daily for 14 days ( Error! Hyperlink reference not valid. ) Active Benign Gastric Ulcer 40 mg once daily for 4 to 8 weeks ( Error! Hyperlink reference not valid. ) Symptomatic GERD 20 mg once daily for up to 4 weeks ( Error! Hyperlink reference not valid. ) See full prescribing information for weight based dosing in pediatric patients 1 year of age and older ( Error! Hyperlink reference not valid. ) EE due to Acid-Mediated GERD 20 mg once daily for 4 to 8 weeks ( Error! Hyperlink reference not valid. )*** See full prescribing information for weight based dosing in pediatric patients 1 year of age and older ( Error! Hyperlink reference not valid. ) Maintenance of Healing of EE due to Acid-Mediated GERD 20 mg once daily ( Error! Hyperlink reference not valid. )**** See full prescribing information for weight based dosing in pediatric patients 1 year of age and older ( Error! Hyperlink reference not valid. ) Pathological Hypersecretory Conditions Starting dose is 60 mg once daily (varies with individual patient, see full prescribing information) as long as clinically indicated ( Error! Hyperlink reference not valid. ) * if ulcer present, continue Omeprazole Delayed-Release Capsules 20 mg once daily for an additional 18 days. ** if ulcer present, continue Omeprazole Delayed-Release Capsules 20 mg once daily for an additional 14 days. *** an additional 4 weeks of treatment may be given if no response; if recurrence additional 4 to 8 week courses may be considered. **** studied for 12 months. Reduce the dosage to 10 mg once daily for patients with hepatic impairment (Child Pugh Class A, B, or C) and Asian patients ( Error! Hyperlink reference not valid. ) 2.1 Recommended Adult Dosage Regimen by Indication Table 1 shows the recommended dosage of Omeprazole Delayed-Release Capsules in adult patients by indication. Table 1: Recommended Dosage Regimen of Omeprazole Delayed-Release Capsules in Adults by Indication Indication Dosage of Omeprazole Delayed-Release Capsules Treatment Duration Treatment of Active Duodenal Ulcer 20 mg once daily 4 weeks 1 Helicobacter pylori Eradication to Reduce the Risk of Duodenal Ulcer Recurrence Triple Therapy Omeprazole Delayed-Release Capsules 20 mg Amoxicillin 1000 mg Clarithromycin 500 mg Take all three drugs twice daily 10 days In patients with an ulcer present at the time of initiation of therapy, continue Omeprazole Delayed-Release Capsules 20 mg once daily for an additional 18 days for ulcer healing and symptom relief. Dual Therapy Omeprazole Delayed-Release Capsules 40 mg once daily Clarithromycin 500 mg three times daily 14 days In patients with an ulcer present at the time of initiation of therapy, an additional 14 days of Omeprazole Delayed-Release Capsules 20 mg once daily is recommended for ulcer healing and symptom relief. Active Benign Gastric Ulcer 40 mg once daily 4 to 8 weeks Treatment of Symptomatic GERD 20 mg once daily Up to 4 weeks Maintenance of Healing of EE due to Acid-Mediated GERD 20 mg once daily 4 to 8 weeks 2 Pathological Hypersecretory Conditions 20 mg once daily 3 Controlled studies do not extend beyond 12 months. 1. Most patients heal within 4 weeks; some patients may require an additional 4 weeks of therapy to achieve healing. 2. The efficacy of Omeprazole Delayed-Release Capsules used for longer than 8 we …

3 DOSAGE FORMS AND STRENGTHS Omeprazole delayed-release capsules USP, 10 mg are off-white to pale yellow, spherical, enteric coated pellets filled in size '4' hard gelatin capsule shells with opaque purple colored cap and opaque yellow colored body imprinted, 'OMERPAZOLE' over 10 mg on cap and 'R643' on body with black ink. Omeprazole delayed-release capsules USP, 20 mg are off-white to pale yellow, spherical, enteric coated pellets filled in size '2' hard gelatin capsule shells with opaque purple colored cap and opaque grey colored body, imprinted 'OMEPRAZOLE' over 20 mg on cap and 'R644' on body with black ink. Omeprazole delayed-release capsules USP, 40 mg are off-white to pale yellow, spherical, enteric coated pellets filled in size '1' hard gelatin capsule shells with opaque yellow colored cap and opaque purple colored body, imprinted 'OMEPRAZOLE' 40 mg on cap and 'R645' on body with black ink. Omeprazole delayed-release capsules: 10 mg, 20 mg and 40 mg (3)

4 CONTRAINDICATIONS Omeprazole Delayed-Release Capsules is contraindicated in patients with known hypersensitivity to substituted benzimidazoles or to any component of the formulation. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, interstitial 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 Delayed-Release Capsules, refer to the CONTRAINDICATIONS section of their package inserts. Patients with known hypersensitivity to substituted benzimidazoles or any component of the formulation. ( Error! Hyperlink reference not valid. ) Patients receiving rilpivirine-containing products. ( Error! Hyperlink reference not valid. , Error! Hyperlink reference not valid. ) Refer to the Contraindications section of the prescribing information for clarithromycin and amoxicillin, when administered in combination with Omeprazole Delayed-Release Capsules. ( Error! Hyperlink reference not valid. )

Do not use if you have: • trouble or pain swallowing food, vomiting with blood, or bloody or black stools • heartburn with lightheadedness, sweating or dizziness • chest pain or shoulder pain with shortness of breath; sweating; pain spreading to arms, neck or shoulders; or lightheadedness • frequent chest pain These may be signs of a serious condition. See your doctor.

Ask a doctor before use if you have: • had heartburn over 3 months. This may be a sign of a more serious condition. • frequent wheezing, particularly with heartburn • unexplained weight loss • nausea or vomiting • stomach pain

Stop use and ask a doctor if: • your heartburn continues or worsens • you need to take this product for more than 14 days • you need to take more than 1 course of treatment every 4 months • you get diarrhea • you develop a rash or joint pain

6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in labeling: Acute Tubulointerstitial Nephritis [see W arnings and Precautions ( 5.2 )] Clostridium difficile -Associated Diarrhea [see W arnings and Precautions ( 5.3 )] Bone Fracture [see W arnings and Precautions ( 5.4 )] Cutaneous and Systemic Lupus Erythematosus [see W arnings and Precautions ( 5.6 )] Cyanocobalamin (Vitamin B-12) Deficiency [see W arnings and Precautions ( 5.8 )] Hypomagnesemia [see W arnings and Precautions ( 5.9 )] Fundic Gland Polyps [see Warnings and Precautions ( 5.13 )] Adults: Most common adverse reactions in adults (incidence ≥2%) are Headache, abdominal pain, nausea, diarrhea, vomiting, and flatulence. ( 6 ) Pediatric patients (1 to 16 years of age): Safety profile similar to that in adults, except that respiratory system events and fever were the most frequently reported reactions in pediatric studies. ( 8.4 ) To report SUSPECTED ADVERSE REACTIONS, contact Lannett Company, Inc. at 1-844-834-0530 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience with Omeprazole Delayed-Release Capsules Monotherapy Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data described below reflects exposure to Omeprazole Delayed-Release Capsules in 3096 patients from worldwide clinical trials (465 patients from US studies and 2,631 patients from international studies). Indications clinically studied in US trials included duodenal ulcer, resistant ulcer, and Zollinger-Ellison syndrome. The international clinical trials were double blind and open-label in design. The most common adverse reactions reported (i.e., with an incidence rate ≥ 2%) from Omeprazole Delayed-Release Capsules-treated patients enrolled in these studies included headache (7%), abdominal pain (5%), nausea (4%), diarrhea (4%), vomiting (3%), and flatulence (3%). Additional adverse reactions that were reported with an incidence ≥ 1% included acid regurgitation (2%), upper respiratory infection (2%), constipation (2%), dizziness (2%), rash (2%), asthenia (1%), back pain (1%), and cough (1%). The clinical trial safety profile in patients greater than 65 years of age was similar to that in patients 65 years of age or less. The clinical trial safety profile in pediatric patients who received Omeprazole Delayed-Release Capsules was similar to that in adult patients. Unique to the pediatric population, however, adverse reactions of the respiratory system were frequently reported in the 1 to <2 year age group and the 2 to 16 year age group (75% and 19% respectively). In addition, fever was frequently reported in the 1 <2 year age group (33%), and accidental injuries were reported frequently in the 2 to 16 year age group (4%) [see Use in Specific Populations ( 8.4 )] . 6.2 Clinical Trials Experience with Omeprazole Delayed-Release Capsules in Combination Therapy for H. pylori Eradication In clinical trials using either dual therapy with Omeprazole Delayed-Release Capsules and clarithromycin, or triple therapy with Omeprazole Delayed-Release Capsules, 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. Dual Therapy (Omeprazole Delayed-Release Capsules/clarithromycin) Adverse reactions observed in controlled clinical trials using combination therapy with Omeprazole Delayed-Release Capsules and clarithromycin (n = 346) that differed from those previously described for Omeprazole Delayed-Release Capsules alone were taste perversion (15%), tongue discoloration (2%), rhinitis (2%), pharyngitis (1%) and flu-syndrome (1%). (For more information on clari …

7 DRUG INTERACTIONS 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. Table 3: Clinically Relevant Interactions Affecting Drugs Co-Administered with Omeprazole Delayed-Release Capsules and Interaction with Diagnostics Antiretrovirals Clinical Impact: The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known. Decreased exposure of some antiretroviral drugs (e.g., rilpivirine, atazanavir and nelfinavir) when used concomitantly with omeprazole may reduce antiviral effect and promote the development of drug resistance [see C li n i cal P harmacology ( 12.3 )] . Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with omeprazole may increase toxicity [see C l i n i cal P harmacology ( 12.3 )] . There are other antiretroviral drugs which do not result in clinically relevant interactions with omeprazole. Intervention: R il p i v i rine-containing products : Concomitant use with Omeprazole Delayed-Release Capsules is contraindicated [see C o ntraindications ( 4 )] . A t azanavir : Avoid concomitant use with Omeprazole Delayed-Release Capsules. See prescribing information for atazanavir for dosing information. Nelfinavir : Avoid concomitant use with Omeprazole Delayed-Release Capsules. See prescribing information for nelfinavir. S aquinavir : See the prescribing information for saquinavir for monitoring of potential saquinavir-related toxicities. Other antiretrovirals : See prescribing information for specific antiretroviral drugs. Warfarin Clinical Impact: Increased INR and prothrombin time in patients receiving PPIs, including omeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Intervention: Monitor INR and prothrombin time and adjust the dose of warfarin, if needed, to maintain target INR range. Methotrexate Clinical Impact: Concomitant use of omeprazole with methotrexate (primarily at high dose) may elevate and prolong serum concentrations of methotrexate and/or its metabolite hydroxymethotrexate, possibly leading to methotrexate toxicities. No formal drug interaction studies of high-dose methotrexate with PPIs have been conducted [see W arnings and Precautions ( 5.12 )] . Intervention: A temporary withdrawal of Omeprazole Delayed-Release Capsules may be considered in some patients receiving high-dose methotrexate. CYP2C19 Substrates (e.g., clopidogrel, citalopram, cilostazol, phenytoin, diazepam) Clopidogrel Clinical Impact: Concomitant use of omeprazole 80 mg results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition [see C li n i cal P harmacology ( 12.3 )] . There are no adequate combination studies of a lower dose of omeprazole or a higher dose of clopidogrel in comparison with the approved dose of clopidogrel. Intervention: Avoid concomitant use with Omeprazole Delayed-Release Capsules. Consider use of alternative anti-platelet therapy [see W arnings and Precautions ( 5.7 )] . Citalopram Clinical Impact: Increased exposure of citalopram leading to an increased risk of QT prolongation [ see C li n i cal Pharmacology ( 12.3 )] . Intervention: Limit the dose of citalopram to a maximum of 20 mg per day. See prescribing information for citalopram. Cilostazol Clinical Impact: Increased exposure of one of the active metabolites of cilostazol (3,4-dihydro-cilostazol) [see C l i nical Pharmacology ( 12.3 )] . Intervention: Reduce the dose of cilostazol to 50 mg twice daily. See prescribing information for cilostazol. Phenytoin Clinical Impact: Potential for increased exposure of phenytoin. Interv …

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary There are no adequate and well-controlled studies with omeprazole in pregnant women. Available epidemiologic data fail to demonstrate an increased risk of major congenital malformations or other adverse pregnancy outcomes with first trimester omeprazole use. Reproduction studies in rats and rabbits resulted in dose-dependent embryo-lethality at omeprazole doses that were approximately 3.4 to 34 times an oral human dose of 40 mg (based on a body surface area for a 60 kg person). Teratogenicity was not observed in animal reproduction studies with administration of oral esomeprazole (an enantiomer of omeprazole) magnesium in rats and rabbits during organogenesis with doses about 68 times and 42 times, respectively, an oral human dose of 40 mg esomeprazole or 40 mg omeprazole (based on body surface area for a 60 kg person). Changes in bone morphology were observed in offspring of rats dosed through most of pregnancy and lactation at doses equal to or greater than approximately 34 times an oral human dose of 40 mg esomeprazole or 40 mg omeprazole. When maternal administration was confined to gestation only, there were no effects on bone physeal morphology in the offspring at any age [see Data]. The estimated background risks of major birth defects and miscarriage for the indicated population are unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Human Data Four published epidemiological studies compared the frequency of congenital abnormalities among infants born to women who used omeprazole during pregnancy with the frequency of abnormalities among infants of women exposed to H 2 -receptor antagonists or other controls. A population-based retrospective cohort epidemiological study from the Swedish Medical Birth Registry, covering approximately 99% of pregnancies, from 1995 to 99, reported on 955 infants (824 exposed during the first trimester with 39 of these exposed beyond first trimester, and 131 exposed after the first trimester) whose mothers used omeprazole during pregnancy. The number of infants exposed in utero to omeprazole that had any malformation, low birth weight, low Apgar score, or hospitalization was similar to the number observed in this population. The number of infants born with ventricular septal defects and the number of stillborn infants was slightly higher in the omeprazole-exposed infants than the expected number in this population. A population-based retrospective cohort study covering all live births in Denmark from 1996 to 2009, reported on 1,800 live births whose mothers used omeprazole during the first trimester of pregnancy and 837,317 live births whose mothers did not use any proton pump inhibitor. The overall rate of birth defects in infants born to mothers with first trimester exposure to omeprazole was 2.9% and 2.6% in infants born to mothers not exposed to any proton pump inhibitor during the first trimester. A retrospective cohort study reported on 689 pregnant women exposed to either H 2 -blockers or omeprazole in the first trimester (134 exposed to omeprazole) and 1,572 pregnant women unexposed to either during the first trimester. The overall malformation rate in offspring born to mothers with first trimester exposure to omeprazole, an H 2 -blocker, or were unexposed was 3.6%, 5.5%, and 4.1% respectively. A small prospective observational cohort study followed 113 women exposed to omeprazole during pregnancy (89% with first trimester exposures). The reported rate of major congenital malformations was 4% in the omeprazole group, 2% in controls exposed to non-teratogens, and 2.8% in disease-paired controls. Rates of spontaneous and elective abortions, preterm deliveries, gestational age at delivery, and mean birt …

12.1 Mechanism of Action 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. Animal studies indicate that after rapid disappearance from plasma, omeprazole can be found within the gastric mucosa for a day or more.

11 DESCRIPTION The active ingredient in omeprazole delayed-release capsule, 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 molecular formula is C 17 H 19 N 3 O 3 S, 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. The Dissolution test to be performed according to USP Test 2. 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. The 10 mg and 20 mg capsules contain the following inactive ingredients: anhydrous lactose, low-substituted hydroxypropyl cellulose, magnesium oxide, magnesium stearate, microcrystalline cellulose, methacrylic acid copolymer dispersion type C, polysorbate 80, povidone and talc, triethyl citrate. The capsule shells for the 10 mg have the following inactive ingredients: black iron oxide, gelatin, red iron oxide, titanium dioxide and yellow iron oxide. The capsule shells for the 20 mg have the following inactive ingredients: gelatin and titanium dioxide. The ink used for printing contains: black iron oxide, propylene glycol and shellac. The 40 mg capsule contains the following inactive ingredients: acetone, anhydrous lactose, croscarmellose sodium, dehydrated alcohol, dibutyl sebacate, hypromellose phthalate, low-substituted hydroxypropyl cellulose, microcrystalline cellulose, polysorbate 80, povidone and talc. The capsule shells for the 40 mg have the following inactive ingredients: hypromellose, red iron oxide, titanium dioxide, and yellow iron oxide. In addition, the capsule shells may also contain black iron oxide, carrageenan, and potassium chloride. The ink used for printing contains black iron oxide. structure

Active ingredient (in each capsule) Omeprazole delayed-release capsules, USP 20 mg (equivalent to 20.6 mg omeprazole magnesium USP)

10 OVERDOSAGE 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 Delayed-Release Capsules 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. As with the management of any overdose, the possibility of multiple drug ingestion should be considered. For current information on treatment of any drug overdose, contact a Poison Control Center at 1-800-222-1222. Single oral doses of omeprazole at 1350, 1339, and 1200 mg/kg were lethal to mice, rats, and dogs, respectively. Animals given these doses showed sedation, ptosis, tremors, convulsions, and decreased activity, body temperature, and respiratory rate and increased depth of respiration.

16 HOW SUPPLIED/STORAGE AND HANDLING Omeprazole Delayed-Release Capsules, USP 10 mg are size ‘3’ two piece hard gelatin capsules with a light blue to blue body with “G” imprinted in black ink and an orange cap with “G230” imprinted in black ink. The capsules are filled with white to off-white pellets. They are supplied as follows: NDC 76420-878-03 bottles of 30 (relabeled from NDC 68462-395-30) NDC 76420-878-06 bottles of 60 (repackaged from NDC 68462-395-XX) NDC 76420-878-09 bottles of 90 (relabeled from NDC 68462-395-90) NDC 76420-878-01 bottles of 100 (relabeled from NDC 68462-395-01) NDC 76420-878-12 bottles of 120 (repackaged from NDC 68462-395-XX) NDC 76420-878-00 bottles of 1000 (relabeled from NDC 68462-395-10) Omeprazole Delayed-Release Capsules, USP 20 mg are size ‘2’ two piece hard gelatin capsules with a light blue to blue body with “G” imprinted in black ink and a light blue to blue cap with “G231” imprinted in black ink. The capsules are filled with white to off-white pellets. They are supplied as follows: NDC 76420-055-03 bottles of 30 (relabeled/repackage from NDC 68462-396-30/68462-396-XX) NDC 76420-055-06 bottles of 60 (repackaged from NDC 68462-396-XX) NDC 76420-055-09 bottles of 90 (relabeled from NDC 68462-396-90) NDC 76420-055-10 bottles of 100 (relabeled from NDC 68462-396-01) NDC 76420-055-12 bottles of 120 (repackaged from NDC 68462-396-XX) NDC 76420-055-00 bottles of 1000 (relabeled from NDC 68462-396-10) Omeprazole Delayed-Release Capsules, USP 40 mg are size ‘1’ two piece hard gelatin capsules with an orange body with ‘G’ imprinted in black ink and light blue to blue cap with ‘G232’ imprinted in black ink. The capsules are filled with white to off-white pellets. They are supplied as follows: NDC 76420-879-03 bottles of 30 (relabeled/repackage from NDC 68462-397-30/68462-397-XX) NDC 76420-879-06 bottles of 60 (repackaged from NDC 68462-397-XX) NDC 76420-879-09 bottles of 90 (relabeled from NDC 68462-397-90) NDC 76420-879-01 bottles of 100 (relabeled from NDC 68462-397-01) NDC 76420-879-12 bottles of 120 (repackaged from NDC 68462-397-XX) NDC 76420-879-00 bottles of 1000 (relabeled from NDC 68462-397-10) Storage Store Omeprazole Delayed-Release Capsules in a tight container protected from light and moisture. Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].