PANTOPRAZOLE SODIUM

2.2 Administration Instructions

3 DOSAGE FORMS AND STRENGTHS

• 40 mg yellow colored, biconvex oval shaped tablets plain on one side and imprinted with “W434” (brown ink) on other side.
• 20 mg yellow colored, biconvex oval shaped tablets plain on one side and imprinted with “W433” (brown ink) on other side.

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Concurrent Gastric Malignancy

5.2 Atrophic Gastritis

5.3 Cyanocobalamin (Vitamin B-12) Deficiency

5.4 Bone Fracture

5.5 Tumorigenicity

5.6 Interference with Urine Screen for THC

6 ADVERSE REACTIONS

6.1 Clinical Trial Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Interference with Antiretroviral Therapy

Concomitant use of atazanavir or nelfinavir with proton pump inhibitors is not recommended. Coadministration of atazanavir or nelfinavir with proton pump inhibitors is expected to substantially decrease atazanavir or nelfinavir plasma concentrations and may result in a loss of therapeutic effect and development of drug resistance.

7.2 Coumarin Anticoagulants

There have been postmarketing reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including pantoprazole sodium delayed-release tablets, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly should be monitored for increases in INR and prothrombin time.

7.3 Drugs for Which Gastric pH Can Affect Bioavailability

Pantoprazole causes long-lasting inhibition of gastric acid secretion. Therefore, pantoprazole may interfere with absorption of drugs where gastric pH is an important determinant of their bioavailability (e.g., ketoconazole, ampicillin esters, and iron salts).

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

Pantoprazole and its metabolites are excreted in the milk of rats. Pantoprazole excretion in human milk has been detected in a study of a single nursing mother after a single 40 mg oral dose. The clinical relevance of this finding is not known. Many drugs which are excreted in human milk have a potential for serious adverse reactions in nursing infants. Based on the potential for tumorigenicity shown for pantoprazole in rodent carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the benefit of the drug to the mother.

8.4 Pediatric Use

The effectiveness of pantoprazole sodium delayed-release tablets for treating symptomatic GERD in pediatric patients has not been established. Information describing use in pediatric patients with erosive esophagitis associated with GERD is approved for Wyeth Pharmaceuticals Inc.'s pantoprazole sodium delayed-release tablets.  However, due to Wyeth Pharmaceuticals Inc.'s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

8.5 Geriatric Use

In short-term U.S. clinical trials, erosive esophagitis healing rates in the 107 elderly patients (≥ 65 years old) treated with pantoprazole sodium delayed-release tablets were similar to those found in patients under the age of 65. The incidence rates of adverse reactions and laboratory abnormalities in patients aged 65 years and older were similar to those associated with patients younger than 65 years of age.

8.6 Gender

Erosive esophagitis healing rates in the 221 women treated with pantoprazole sodium delayed-release tablets in U.S. clinical trials were similar to those found in men. In the 122 women treated long-term with pantoprazole sodium delayed-release tablets 40 mg or 20 mg, healing was maintained at a rate similar to that in men. The incidence rates of adverse reactions were also similar for men and women.

8.7 Patients with Hepatic Impairment

Doses higher than 40 mg/day have not been studied in patients with hepatic impairment [ ]. see Clinical Pharmacology (12.3)

10 OVERDOSAGE

11 DESCRIPTION

The active ingredient in pantoprazole sodium delayed-release tablets, USP is a substituted benzimidazole, sodium 5-(difluoromethoxy)-2-[[(3,4-dimethoxy-2-pyridinyl)methyl] sulfinyl]1 -benzimidazole sesquihydrate, a compound that inhibits gastric acid secretion. Its empirical formula is C H F N NaO S x 1.5 H O, with a molecular weight of 432.4. The structural formula is: Pantoprazole sodium sesquihydrate, USP is a white to off-white powder and is racemic. Pantoprazole has weakly basic and acidic properties. Pantoprazole sodium sesquihydrate, USP is freely soluble in water and practically insoluble in hexane. The stability of the compound in aqueous solution is pH-dependent. The rate of degradation increases with decreasing pH. At ambient temperature, the degradation half-life is approximately 2.8 hours at pH 5 and approximately 220 hours at pH 7.8. Pantoprazole sodium is supplied as a delayed-release tablet for oral administration, available in 2 strengths (40 mg and 20 mg). Each delayed-release tablet contains 45.1 mg or 22.56 mg of pantoprazole sodium sesquihydrate USP (equivalent to 40 mg or 20 mg pantoprazole, respectively) with the following inactive ingredients: aerosil 200, calcium stearate, colloidal silicon dioxide, mannitol, pregelatinized starch, shellac glaze, sodium carbonate anhydrous, sodium starch glycolate and talc. Each delayed-release tablet contains ammonium hydroxide, eudragit L 100-55, FD and C Blue #2, hypromellose, iron oxide black, iron oxide red, iron oxide yellow, polyethylene glycol 400, polyethylene glycol 4000, polyethylene glycol 6000, propylene glycol, sodium hydroxide, titanium dioxide and triethyl citrate as the coating ingredients. Pantoprazole sodium delayed-release tablets USP, 20 mg and 40 mg, meet USP Dissolution Test 3. H _{16 14 2 3 4 2}

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

12.4 Pharmacogenomics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

14 CLINICAL STUDIES

14.1 Erosive Esophagitis (EE) Associated with Gastroesophageal Reflux Disease (GERD)

14.2 Long-Term Maintenance of Healing of Erosive Esophagitis

14.3 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome

In a multicenter, open-label trial of 35 patients with pathological hypersecretory conditions, such as Zollinger-Ellison syndrome, with or without multiple endocrine neoplasia-type I, pantoprazole sodium delayed-release tablets successfully controlled gastric acid secretion. Doses ranging from 80 mg daily to 240 mg daily maintained gastric acid output below 10 mEq/h in patients without prior acid-reducing surgery and below 5 mEq/h in patients with prior acid-reducing surgery. Doses were initially titrated to the individual patient needs, and adjusted in some patients based on the clinical response with time [ ]. Pantoprazole sodium delayed-release tablet was well tolerated at these dose levels for prolonged periods (greater than 2 years in some patients).

see Dosage and Administration (2)

17 PATIENT COUNSELING INFORMATION

• Caution patients that pantoprazole sodium delayed-release tablets, should not be split, crushed, or chewed.
• Tell patients that pantoprazole sodium delayed-release tablets, USP should be swallowed whole, with or without food in the stomach.
• Let patients know that concomitant administration of antacids does not affect the absorption of pantoprazole sodium delayed-release tablets, USP.

• Up to 8 weeks for short-term treatment of acid-related damage to the lining of the esophagus (erosive esophagitis) caused by gastroesophageal reflux disease (GERD). If needed, your doctor may prescribe an additional 8 weeks of pantoprazole sodium delayed-release tablets.
• Maintain healing of acid-related damage to the lining of the esophagus and helps prevent return of heartburn symptoms caused by GERD. Pantoprazole sodium delayed-release tablets have not been studied for treatment lasting longer than 1 year
• Treating a rare condition called Zollinger-Ellison Syndrome, where the stomach makes more than the normal amount of acid

• allergic to any of the ingredients in pantoprazole sodium delayed-release tablets. See the end of this leaflet for a complete list of ingredients in pantoprazole sodium delayed-release tablets.
• allergic to any proton pump inhibitor (PPI). If you do not know if your medicines are PPIs, please ask your doctor.

• pregnant, think you may be pregnant, or are planning to become pregnant. It is not known if pantoprazole sodium delayed-release tablets will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.
• breastfeeding or planning to breastfeed. Pantoprazole sodium delayed-release tablets may pass into your milk. Talk with your doctor about the best way to feed your baby if you take pantoprazole sodium delayed-release tablets.  

• Warfarin (Coumadin , Athrombin -K , Jantoven , Panwarfin ) ^{† † † †}
• Ketoconazole (Nizoral ) ^†
• Atazanavir (Reyataz ), Nelfinavir (Viracept ) ^{† †}
• Iron supplements
• Ampicillin antibiotics

• Take pantoprazole sodium delayed-release tablets exactly as prescribed by your doctor.
• Do not change your dose or stop pantoprazole sodium delayed-release tablets without talking to your doctor.
• If you forget to take a dose of pantoprazole sodium delayed-release tablets, 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 two doses to try to make up for a missed dose.
• If you take too much pantoprazole sodium delayed-release tablets, call your doctor right away.
• See the Patient Instructions for Use at the end of this leaflet for detailed instructions about:
  • how to take pantoprazole sodium delayed-release tablets .

• Stomach lining weakening with long-term use
• Vitamin B-12 deficiency
• Serious allergic reactions. Tell your doctor if you get any of the following symptoms with pantoprazole sodium delayed-release tablets
  • rash
  • face swelling
  • throat tightness
  • difficult breathing

• Store pantoprazole sodium delayed-release tablets at 20°-25°C (68°-77°F); [See USP Controlled Room Temperature].
• Keep pantoprazole sodium delayed-release tablets and all medicines out of the reach of children.  

• You can take pantoprazole sodium delayed-release tablets with food or on an empty stomach.  
• Swallow pantoprazole sodium delayed-release tablets whole.
• If you have trouble swallowing a pantoprazole sodium delayed-release tablet 40 mg tablet, you can take two 20 mg tablets instead.
• Do not split, chew or crush pantoprazole sodium delayed-release tablets.

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PANTOPRAZOLE SODIUM DR

PANTOPRAZOLE SODIUM PANTOPRAZOLE SODIUM TABLET, DELAYED RELEASE Product Information Product Type Human prescription drug label Item Code (Source) NDC:50436-8102(NDC:64679-433) Route of Administration ORAL DEA Schedule Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength PANTOPRAZOLE SODIUM PANTOPRAZOLE 20 mg Inactive Ingredients Ingredient Name Strength mannitol STARCH, CORN SILICON DIOXIDE SODIUM CARBONATE CALCIUM STEARATE talc SODIUM STARCH GLYCOLATE TYPE A POTATO titanium dioxide POLYETHYLENE GLYCOL 4000 FERRIC OXIDE YELLOW FD&C BLUE NO. 2 METHACRYLIC ACID - ETHYL ACRYLATE COPOLYMER (1:1) TYPE A SODIUM HYDROXIDE TRIETHYL CITRATE polyethylene glycol 400 polyethylene glycol 6000 SHELLAC FERROSOFERRIC OXIDE ferric oxide red propylene glycol HYPROMELLOSES Product Characteristics Color Size Imprint Code Shape yellow (yellow) 9 mm W433 OVAL Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:50436-8102-2 60 in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA091231 2011-01-19