Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Pantoprazole Sodium Delayed-Release Tablets, USP are supplied as 40 mg yellow to pale yellow, oval, biconvex, delayed-release tablets imprinted “H126” on one side with black ink and plain on the other side. They are supplied as follows: Bottles of 30 tablets NDC 63187-654-30 Bottles of 90 tablets NDC 63187-654-90 Storage Store pantoprazole sodium delayed-release tablets, USP at 20 to 25°C (68 to 77°F) [see USP Controlled Room Temperature].; PACKAGE LABEL.PRINCIPAL DISPLAY PANEL 63187-654-30
- 16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Pantoprazole Sodium Delayed-Release Tablets, USP are supplied as 40 mg yellow to pale yellow, oval, biconvex, delayed-release tablets imprinted “H126” on one side with black ink and plain on the other side. They are supplied as follows: Bottles of 30 tablets NDC 63187-654-30 Bottles of 90 tablets NDC 63187-654-90 Storage Store pantoprazole sodium delayed-release tablets, USP at 20 to 25°C (68 to 77°F) [see USP Controlled Room Temperature].
- PACKAGE LABEL.PRINCIPAL DISPLAY PANEL 63187-654-30
Overview
The active ingredient in Pantoprazole Sodium Delayed-Release Tablets, USP is a substituted benzimidazole, 5-(Difluoromethoxy) -2- [[(3,4 dimethoxy-2- pyridyl)methyl] sulfinyl]benzimidazole, sodium salt, sesquihydrate, a compound that inhibits gastric acid secretion. Its empirical formula is C 16 H 14 F 2 N 3 NaO 4 S . 1.5 H 2 O, with a molecular weight of 432.4. The structural formula is: Pantoprazole sodium sesquihydrate, USP is a white to off-white powder. Pantoprazole sodium sesquihydrate, USP is freely soluble in water, in methanol, in dehydrated alcohol, practically insoluble in hexane and dichloromethane. 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, available in two strengths (20 mg and 40 mg). Each Pantoprazole Sodium Delayed-Release Tablet, USP contains 45.11 mg or 22.55 mg of pantoprazole sodium sesquihydrate, USP (equivalent to 40 mg or 20 mg pantoprazole, respectively) with the following inactive ingredients: calcium stearate, ferric oxide yellow, hydroxy propyl cellulose, hypromellose, lactose monohydrate, methacrylic acid copolymer, polysorbate 80, propylene glycol, sodium carbonate anhydrous, sodium lauryl sulfate, titanium dioxide and triethyl citrate. The tablets are imprinted with opacode black containing ammonium hydroxide, iron oxide black, propylene glycol and shellac. Pantoprazole Sodium Delayed-Release Tablets, (40 mg and 20 mg) complies with USP dissolution test 2. structure.jpg
Indications & Usage
INDICATIONS & USAGE Pantoprazole Sodium Delayed-Release Tablets, USP are indicated for: Pantoprazole sodium delayed-release tablet, USP is a proton pump inhibitor indicated for the following: • Short-Term Treatment of Erosive Esophagitis Associated with Gastroesophageal Reflux Disease (GERD) ( 1.1 ) • Maintenance of Healing of Erosive Esophagitis ( 1.2 ) • Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome ( 1.3 ) 1.1 Short-Term Treatment of Erosive Esophagitis Associated With Gastroesophageal Reflux Disease (GERD) Pantoprazole Sodium Delayed-Release Tablet, USP is indicated in adults and pediatric patients five years of age and older for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis. For those adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole sodium may be considered. Safety of treatment beyond 8 weeks in pediatric patients has not been established. 1.2 Maintenance of Healing of Erosive Esophagitis Pantoprazole Sodium Delayed-Release Tablets, USP are indicated for maintenance of healing of erosive esophagitis and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with GERD. Controlled studies did not extend beyond 12 months. 1.3 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome Pantoprazole Sodium Delayed-Release Tablets USP are indicated for the long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.
Dosage & Administration
DOSAGE & ADMINISTRATION Indication Dose Frequency Short-Term Treatment of Erosive Esophagitis Associated With GERD ( 2.1 ) Adults 40 mg Once Daily for up to 8 wks Children (5 years and older) ≥ 15 kg to < 40 kg 20 mg Once Daily for up to 8 wks ≥ 40 kg 40 mg Maintenance of Healing of Erosive Esophagitis ( 2.1 ) Adults 40 mg Once Daily Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome ( 2.1 ) Adults 40 mg Twice Daily *Controlled studies did not extend beyond 12 months See full prescribing information for administration instructions 2.1 Recommended Dosing Schedule Pantoprazole Sodium is supplied as Delayed-Release Tablets. The recommended dosages are outlined in Table 1. Table 1: Recommended Dosing Schedule for Pantoprazole SodiumDelayed-Release Tablets Indication Dose Frequency Short-Term Treatment of Erosive Esophagitis Associated With GERD Adults 40 mg Once daily for up to 8 weeks* Children (5 years and older) ≥ 15 kg to < 40 kg 20 mg Once daily for up to 8 weeks ≥ 40 kg 40 mg Maintenanceof Healing of Erosive Esophagitis Adults 40 mg Once daily PathologicalHypersecretory Conditions Including Zollinger-Ellison Syndrome Adults 40 mg Twice daily ** * For adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole sodium delayed-release tablets may be considered. ** Dosage regimens should be adjusted to individual patient needs and should continue for as long as clinically indicated. Doses up to 240 mg daily have been administered. *** Controlled studies did not extend beyond 12 months 2.2 Administration Instructions Directions for method of administration for each dosage form are presented in Table 2. Table 2: Administration Instructions Formulation Route Instructions* Delayed-Release Tablets Oral Swallowed whole, with or without food * Patients should be cautioned that pantoprazole sodium delayed-release tablets should not be split, chewed, or crushed. Pantoprazole Sodium Delayed-Release Tablets should be swallowed whole, with or without food in the stomach. If patients are unable to swallow a 40 mg tablet, two 20 mg tablets may be taken. Concomitant administration of antacids does not affect the absorption of Pantoprazole Sodium Delayed-Release Tablets.
Warnings & Precautions
• Symptomatic response does not preclude presence of gastric malignancy ( 5.1 ) • Atrophic gastritis has been noted with long-term therapy ( 5.2 ) • Acute gastritis has been observed in patients taking PPIs. ( 5.3 ) • Cyanocobalamin (vitamin B-12) Deficiency: Daily long-term use (e.g., longer than 3 years) may lead to malabsorption or a deficiency of cyanocobalamin.( 5.4 ) • PPI therapy may be associated with increased risk of Clostridium difficile associated diarrhea. ( 5.5 ) • 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. ( 5.6 ) • Hypomagnesemia has been reported rarely with prolonged treatment with PPIs ( 5.7 ) 5.1 Concurrent Gastric Malignancy Symptomatic response to therapy with pantoprazole sodium does not preclude the presence of gastric malignancy. 5.2 Atrophic Gastritis Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-term with pantoprazole sodium, particularly in patients who were H. pylori positive. 5.3 Acute Interstitial Nephritis Acute interstitial nephritis has been observed in patients taking PPIs including pantoprazole sodium delayed-release tablets. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue pantoprazole sodium delayed-release tablets if acute interstitial nephritis develops [see Contraindications ( 4 )] . 5.4 Cyanocobalamin (Vitamin B-12) Deficiency Generally, 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. 5.5 Clostridium difficile associated diarrhea Published observational studies suggest that PPI therapy like pantoprazole sodium 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. 5.6 Bone Fracture 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 ) and Adverse Reactions ( 6.2 )] . 5.7 Hypomagnesemia 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. 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 )]. 5.8 Tumorigenicity Due to the chronic nature of GERD, there may be a potential for prolonged administration of pantoprazole sodium. In long-term rodent studies, pantoprazole was carcinogenic and caused rare types of gastrointestinal tumors. The relevance of these findings to tumor development in humans is unknown [see Nonclinical Toxicology ( 13.1 )]. 5.9 Interference with Urine Screen for THC See Drug Interactions ( 7.5 ) 5.10 Concomitant use of Pantoprazole Sodium with Methotrexate Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see methotrexate prescribing information) 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 ( 7.6 )].
Contraindications
Pantoprazole Sodium Delayed-Release Tablets are contraindicated in patients with known hypersensitivity to any component of the formulation or any substituted benzimidazole . Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticarial [see Adverse Reactions ( 6 )] . Known hypersensitivity to any component of the formulation or to substituted benzimidazoles ( 4 )
Adverse Reactions
The most frequently occurring adverse reactions are as follows: • For adult use (>2%) are headache, diarrhea, nausea, abdominal pain, vomiting, flatulence, dizziness, and arthralgia. ( 6 ) • For pediatric use (>4%) are URI, headache, fever, diarrhea, vomiting, rash, and abdominal pain. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Hetero Labs Limited at 866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Adults Safety in nine randomized comparative US clinical trials in patients with GERD included 1,473 patients on oral pantoprazole sodium (20 mg or 40 mg), 299 patients on an H 2 -receptor antagonist, 46 patients on another proton pump inhibitor, and 82 patients on placebo. The most frequently occurring adverse reactions are listed in Table 3. Table 3: Adverse Reactions Reported in Clinical Trials of Adult Patients with GERD at a Frequency of > 2% Pantoprazole sodium (n=1473) % Comparators (n=345) % Placebo (n=82) % Headache 12.2 12.8 8.5 Diarrhea 8.8 9.6 4.9 Nausea 7 5.2 9.8 Abdominal pain 6.2 4.1 6.1 Vomiting Flatulence 4.3 3.9 3.5 2.9 2.4 3.7 Dizziness 3 2.9 1.2 Arthralgia 2.8 1.4 1.2 Additional adverse reactions that were reported for pantoprazole sodium in clinical trials with a frequency of ≤ 2% are listed below by body system: Body as a Whole : allergic reaction, pyrexia, photosensitivity reaction, facial edema Gastrointestinal : constipation, dry mouth, hepatitis Hematologic : leukopenia, thrombocytopenia Metabolic/Nutritional : elevated CK (creatine kinase), generalized edema, elevated triglycerides, liver enzymes elevated Musculoskeletal : myalgia Nervous : depression, vertigo Skin and Appendages : urticaria, rash, pruritus Special Senses : blurred vision Pediatric Patients Safety of pantoprazole sodium in the treatment of Erosive Esophagitis (EE) associated with GERD was evaluated in pediatric patients ages 1 year through 16 years in three clinical trials. Safety trials involved pediatric patients with EE; however, as EE is uncommon in the pediatric population, 249 pediatric patients with endoscopically-proven or symptomatic GERD were also evaluated. All adult adverse reactions to pantoprazole sodium is considered relevant to pediatric patients. In patients ages 1 year through 16 years, the most commonly reported (> 4%) adverse reactions include: URI, headache, fever, diarrhea, vomiting, rash, and abdominal pain. For safety information in patients less than 1 year of age see Use in Specific Populations ( 8.4 ) . Additional adverse reactions that were reported for pantoprazole sodium in pediatric patients in clinical trials with a frequency of ≤ 4% are listed below by body system: Body as a Whole : allergic reaction, facial edema Gastrointestinal : constipation, flatulence, nausea Metabolic/Nutritional : elevated triglycerides, elevated liver enzymes, elevated CK (creatine kinase) Musculoskeletal : arthralgia, myalgia Nervous : dizziness, vertigo Skin and Appendages : urticaria The following adverse reactions seen in adults in clinical trials were not reported in pediatric patients in clinical trials, but are considered relevant to pediatric patients: photosensitivity reaction, dry mouth, hepatitis, thrombocytopenia, generalized edema, depression, pruritus, leukopenia, and blurred vision. Zollinger-Ellison Syndrome In clinical studies of Zollinger-Ellison Syndrome, adverse reactions reported in 35 patients taking pantoprazole sodium 80 mg/day to 240 mg/day for up to 2 years were similar to those reported in adult patients with GERD. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of pantoprazole sodium. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These adverse reactions are listed below by body system: General Disorders and Administration Conditions : asthenia, fatigue, malaise Hematologic : pancytopenia, agranulocytosis Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure Immune System Disorders : anaphylaxis (including anaphylactic shock) Infections and Infestations : Clostridium difficile associated diarrhea Investigations : weight changes Metabolism and Nutritional Disorders : hyponatremia, hypomagnesemia Musculoskeletal Disorders : rhabdomyolysis, bone fracture Nervous : ageusia, dysgeusia Psychiatric Disorders : hallucination, confusion, insomnia, somnolence Renal and Urinary Disorders : interstitial nephritis Skin and Subcutaneous Tissue Disorders : severe dermatologic reactions (some fatal), including erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN, some fatal), and angioedema (Quincke’s edema)
Drug Interactions
• Do not co-administer with atazanavir or nelfinavir ( 7.1 ) • Concomitant warfarin use may require monitoring ( 7.2 ) • May interfere with the absorption of drugs where gastric pH is important for bioavailability (e.g. ketoconazole, ampicillin esters, atazanavir, iron salts, erlotinib and mycophenolate mofetil) ( 7.4 ) • May produce false-positive urine screen for THC ( 7.5 ) • Methotrexate: Pantoprazole sodium may increase serum level of methotrexate ( 7.6 ) 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, 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 Clopidogrel Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition [see Clinical Pharmacology ( 12.3 )]. No dose adjustment of clopidogrel is necessary when administered with an approved dose of pantoprazole sodium. 7.4 Drugs for Which Gastric pH Can Affect Bioavailability Due to its effects on gastric acid secretion, pantoprazole can reduce the absorption of drugs where gastric pH is an important determinant of their bioavailability. Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ketoconazole, ampicillin esters, atazanavir, iron salts, erlotinib, and mycophenolate mofetil (MMF) can decrease. Co-administration of pantoprazole in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving pantoprazole sodium delayed-release tablets and MMF. Use pantoprazole sodium delayed-release tablets with caution in transplant patients receiving MMF [see Clinical Pharmacology ( 12.3 )] . 7.5 False Positive Urine Tests for THC There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving proton pump inhibitors. An alternative confirmatory method should be considered to verify positive results. 7.6 Methotrexate Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPIs and methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of methotrexate with PPIs have been conducted [see Warnings and Precautions (5 .10 )].
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