Pantoprazole Sodium
HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use pantoprazole sodium safely and effectively. See full prescribing information for pantoprazole sodium delayed-release tablets. Pantoprazole Sodium Delayed-Release Tablets, USPInitial U.S. approval: 2000 RECENT MAJOR CHANGES5.8INDICATIONS AND USAGE 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) DOSAGE AND 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 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 DOSAGE FORMS AND STRENGTHS Delayed-Release Tablets, 20 mg and 40 mg (3) CONTRAINDICATIONS4WARNINGS AND PRECAUTIONS Symptomatic response does not preclude presence of gastric malignancy (5.1) Atrophic gastritis has been noted with long-term therapy (5.2) 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) Hypomagnesemia has been reported rarely with prolonged treatment with PPIs (5.5) Side Effects For adult use (>2%) are headache, diarrhea, nausea, abdominal pain, vomiting, flatulence, dizziness, and arthralgia. (6) To report SUSPECTED ADVERSE REACTIONS, contact CARACO Pharmaceutical Laboratories Ltd. at 1-800-818-4555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. DRUG INTERACTIONS Do not coadminister 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 (7.4) May produce false-positive urine screen for THC (7.5) Methotrexate: Pantoprazole may increase serum level of methotrexate (7.6)
FULL PRESCRIBING INFORMATION: CONTENTS*
- 1 PANTOPRAZOLE SODIUM INDICATIONS AND USAGE
- 2 PANTOPRAZOLE SODIUM DOSAGE AND ADMINISTRATION
- 3 DOSAGE FORMS AND STRENGTHS
- 4 PANTOPRAZOLE SODIUM CONTRAINDICATIONS
- 5 WARNINGS AND PRECAUTIONS
- 6 PANTOPRAZOLE SODIUM ADVERSE REACTIONS
- 7 DRUG INTERACTIONS
- 8 USE IN SPECIFIC POPULATIONS
- 10 OVERDOSAGE
- 11 PANTOPRAZOLE SODIUM DESCRIPTION
- 12 CLINICAL PHARMACOLOGY
- 13 NONCLINICAL TOXICOLOGY
- 14 CLINICAL STUDIES
- 16 HOW SUPPLIED/STORAGE AND HANDLING
- 17 PATIENT COUNSELING INFORMATION
- FDA-approved Patient Information
- PRINCIPAL DISPLAY PANEL - 20 mg
- PRINCIPAL DISPLAY PANEL - 40 mg
FULL PRESCRIBING INFORMATION
1 INDICATIONS AND USAGE
1.1 Short-Term Treatment of Erosive Esophagitis Associated With Gastroesophageal Reflux Disease (GERD)
1.2 Maintenance of Healing of Erosive Esophagitis
1.3 Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosing Schedule
| Indication | Dose | Frequency |
|---|---|---|
|
Short-Term Treatment of Erosive Esophagitis Associated With GERD
|
||
| Adults |
40 mg |
Once daily for up to 8 weeks |
|
Maintenance of Healing of Erosive Esophagitis
|
||
| Adults |
40 mg |
Once daily |
|
Pathological Hypersecretory Conditions Including Zollinger-Ellison Syndrome
|
||
| Adults |
40 mg |
Twice daily |
2.2 Administration Instructions
| Formulation | Route | Instructions |
|---|---|---|
|
Delayed-Release Tablets
|
Oral |
Swallowed whole, with or without food |
3 DOSAGE FORMS AND STRENGTHS
- 40 mg, yellow round biconvex tablets imprinted with ‘124’ (black ink) on one side
- 20 mg, yellow round biconvex tablets imprinted with ‘144’ (black ink) on one side
4 CONTRAINDICATIONS
see Description (11)
5 WARNINGS AND PRECAUTIONS
5.1 Concurrent Gastric Malignancy
5.2 Atrophic Gastritis
H. pylori
5.3 Cyanocobalamin (Vitamin B-12) Deficiency
5.4 Bone Fracture
see Dosage and Administration (2) and Adverse Reactions (6.2)
5.5 Hypomagnesemia
Hypomagnesemia
ForSee Adverse Reactions (6.2)
5.6 Tumorigenicity
see Nonclinical Toxicology (13.1)
5.7 Interference with Urine Screen for THC
Drug Interactions (7.5).
5.8 Concomitant use of Pantoprazole with Methotrexate
see Drug Interactions (7.6)
6 ADVERSE REACTIONS
6.1 Clinical Trial Experience
Adults
2
| Pantoprazole (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 |
4.3 |
3.5 |
2.4 |
| Flatulence |
3.9 |
2.9 |
3.7 |
| Dizziness |
3 |
2.9 |
1.2 |
| Arthralgia |
2.8 |
1.4 |
1.2 |
Additional adverse reactions that were reported for pantoprazole 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:
Pediatric Patients
Zollinger-Ellison Syndrome
6.2 Postmarketing Experience
The following adverse reactions have been identified during postapproval use of pantoprazole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
General Disorders and Administration Conditions: asthenia, fatigue, malaise
Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure
Immune System Disorders: anaphylaxis (including anaphylactic shock)
Investigations: weight changes
Metabolism and Nutritional Disorders: hyponatremia, hypomagnesemia
Musculoskeletal Disorders: rhabdomyolysis, bone fracture
Psychiatric Disorders: hallucination, confusion, insomnia, somnolence
Renal and Urinary Disorders: interstitial nephritis
Skin and Subcutaneous Tissue Disorders:7 DRUG INTERACTIONS
7.1 Interference with Antiretroviral Therapy
7.2 Coumarin Anticoagulants
7.3 Clopidogrel
Clinical Pharmacology (12.3).
7.4 Drugs for Which Gastric pH Can Affect Bioavailability
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
Casesee Warnings and Precautions (5.8)
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Teratogenic Effects
Pregnancy Category B
see Nonclinical Toxicology (13.2)8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Gender
8.7 Patients with Hepatic Impairment
see Clinical Pharmacology (12.3)
10 OVERDOSAGE
Experience in patients taking very high doses of pantoprazole (> 240 mg) is limited. Spontaneous postmarketing reports of overdose are generally within the known safety profile of pantoprazole.
Pantoprazole is not removed by hemodialysis. In case of overdosage, treatment should be symptomatic and supportive.
11 DESCRIPTION
H16142342
Pantoprazole sodium sesquihydrate is a white to off-white crystalline powder and is racemic. Pantoprazole has weakly basic and acidic properties. Pantoprazole sodium sesquihydrate is freely soluble in water, very slightly soluble in phosphate buffer at pH 7.4, and practically insoluble in n-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, USP is supplied as a delayed-release tablet, available in two strengths (20 mg and 40 mg).
Each pantoprazole sodium delayed-release tablet, USP contains 45.1 mg or 22.56 mg of pantoprazole sodium sesquihydrate (equivalent to 40 mg or 20 mg pantoprazole, respectively) with the following inactive ingredients: mannitol, sodium carbonate anhydrous, anhydrous lactose, crospovidone, povidone, calcium stearate, hypromellose, polyethylene glycol, talc, methacrylic acid copolymer type C, triethyl citrate, titanium dioxide and ferric oxide yellow.
Imprinting ink contains shellac glaze, isopropyl alcohol, N-butyl alcohol, propylene glycol, ammonium hydroxide, and iron oxide black.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
++++
12.2 Pharmacodynamics
Antisecretory Activity
| Time | -----------------Median pH on day 7---------------- | |||
|---|---|---|---|---|
| Placebo | 20 mg | 40 mg | 80 mg | |
| 8 a.m. to 8 a.m. (24 hours) |
1.3 |
2.9 |
3.8 |
3.9 |
| 8 a.m. to 10 p.m. (Daytime) |
1.6 |
3.2 |
4.4 |
4.8 |
| 10 p.m. to 8 a.m. (Nighttime) |
1.2 |
2.1 |
3 |
2.6 |
Serum Gastrin Effects
In long-term international studies involving over 800 patients, a 2- to 3-fold mean increase from the pretreatment fasting serum gastrin level was observed in the initial months of treatment with pantoprazole at doses of 40 mg per day during GERD maintenance studies and 40 mg or higher per day in patients with refractory GERD. Fasting serum gastrin levels generally remained at approximately 2 to 3 times baseline for up to 4 years of periodic follow-up in clinical trials.
Following short-term treatment with pantoprazole, elevated gastrin levels return to normal by at least 3 months.
Enterochromaffin-Like (ECL) Cell Effects
In 39 patients treated with oral pantoprazole 40 mg to 240 mg daily (majority receiving 40 mg to 80 mg) for up to 5 years, there was a moderate increase in ECL-cell density, starting after the first year of use, which appeared to plateau after 4 years.
see Nonclinical Toxicology (13.1)12.3 Pharmacokinetics
Pantoprazole sodium delayed-release tablets are prepared as enteric-coated tablets so that absorption of pantoprazole begins only after the tablet leaves the stomach. Peak serum concentration (Cmax) and area under the serum concentration time curve (AUC) increase in a manner proportional to oral and intravenous doses from 10 mg to 80 mg. Pantoprazole does not accumulate, and its pharmacokinetics are unaltered with multiple daily dosing. Following oral or intravenous administration, the serum concentration of pantoprazole declines biexponentially, with a terminal elimination half-life of approximately one hour.
In extensive metabolizers with normal liver function receiving an oral dose of the enteric-coated 40 mg pantoprazole tablet, the peak concentration (Cmax) is 2.5 mcg/mL; the time to reach the peak concentration (tmax) is 2.5 h, and the mean total area under the plasma concentration versus time curve (AUC) is 4.8 mcg•h/mL (range 1.4 to 13.3 mcg•h/mL). Following intravenous administration of pantoprazole to extensive metabolizers, its total clearance is 7.6 to 14 L/h, and its apparent volume of distribution is 11 to 23.6 L.
Absorption
After administration of a single or multiple oral 40 mg doses of pantoprazole sodium delayed-release tablets, the peak plasma concentration of pantoprazole was achieved in approximately 2.5 hours, and Cmax was 2.5 mcg/mL. Pantoprazole undergoes little first-pass metabolism, resulting in an absolute bioavailability of approximately 77%. Pantoprazole absorption is not affected by concomitant administration of antacids.
Administration of pantoprazole sodium delayed-release tablets with food may delay its absorption up to 2 hours or longer; however, the Cmax and the extent of pantoprazole absorption (AUC) are not altered. Thus, pantoprazole sodium delayed-release tablets may be taken without regard to timing of meals.
Distribution
The apparent volume of distribution of pantoprazole is approximately 11 to 23.6 L, distributing mainly in extracellular fluid. The serum protein binding of pantoprazole is about 98%, primarily to albumin.
Metabolism
Pantoprazole is extensively metabolized in the liver through the cytochrome P450 (CYP) system. Pantoprazole metabolism is independent of the route of administration (intravenous or oral). The main metabolic pathway is demethylation, by CYP2C19, with subsequent sulfation; other metabolic pathways include oxidation by CYP3A4. There is no evidence that any of the pantoprazole metabolites have significant pharmacologic activity.
Elimination
After a single oral or intravenous dose of 14C-labeled pantoprazole to healthy, normal metabolizer volunteers, approximately 71% of the dose was excreted in the urine, with 18% excreted in the feces through biliary excretion. There was no renal excretion of unchanged pantoprazole.
Geriatric
Only slight to moderate increases in pantoprazole AUC (43%) and Cmax (26%) were found in elderly volunteers (64 to 76 years of age) after repeated oral administration, compared with younger subjects. No dosage adjustment is recommended based on age.
Pediatric
Pharmacokinetic information in pediatric patients 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.
Gender
There is a modest increase in pantoprazole AUC and Cmax in women compared to men. However, weight-normalized clearance values are similar in women and men. No dosage adjustment is recommended based on gender. In pediatric patients ages 1 through 16 years there were no clinically relevant effects of gender on clearance of pantoprazole, as shown by population pharmacokinetic analysis.
Renal Impairment
In patients with severe renal impairment, pharmacokinetic parameters for pantoprazole were similar to those of healthy subjects. No dosage adjustment is necessary in patients with renal impairment or in patients undergoing hemodialysis.
Hepatic Impairment
In patients with mild to severe hepatic impairment (Child-Pugh A to C cirrhosis), maximum pantoprazole concentrations increased only slightly (1.5-fold) relative to healthy subjects. Although serum half-life values increased to 7 to 9 hours and AUC values increased by 5- to 7-fold in hepatic-impaired patients, these increases were no greater than those observed in CYP2C19 poor metabolizers, where no dosage adjustment is warranted. These pharmacokinetic changes in hepatic-impaired patients result in minimal drug accumulation following once-daily, multiple-dose administration. No dosage adjustment is needed in patients with mild to severe hepatic impairment. Doses higher than 40 mg/day have not been studied in hepatically impaired patients.
Drug-Drug Interactions
Pantoprazole is metabolized mainly by CYP2C19 and to minor extents by CYPs 3A4, 2D6, and 2C9. In in vivo drug-drug interaction studies with CYP2C19 substrates (diazepam [also a CYP3A4 substrate] and phenytoin [also a CYP3A4 inducer] and clopidogrel), nifedipine, midazolam, and clarithromycin (CYP3A4 substrates), metoprolol (a CYP2D6 substrate), diclofenac, naproxen and piroxicam (CYP2C9 substrates), and theophylline (a CYP1A2 substrate) in healthy subjects, the pharmacokinetics of pantoprazole were not significantly altered.
Clopidogrel is metabolized to its active metabolite in part by CYP2C19. In a crossover clinical study, 66 healthy subjects were administered clopidogrel (300 mg loading dose followed by 75 mg per day) alone and with pantoprazole (80 mg at the same time as clopidogrel) for 5 days. On Day 5, the mean AUC of the active metabolite of clopidogrel was reduced by approximately 14% (geometric mean ratio was 86%, with 90% CI of 79 to 93%) when pantoprazole was coadministered with clopidogrel as compared to clopidogrel administered alone. Pharmacodynamic parameters were also measured and demonstrated that the change in inhibition of platelet aggregation (induced by 5 µM ADP) was correlated with the change in the exposure to clopidogrel active metabolite. The clinical significance of this finding is not clear.
In vivo studies also suggest that pantoprazole does not significantly affect the kinetics of the following drugs (cisapride, theophylline, diazepam [and its active metabolite, desmethyldiazepam], phenytoin, warfarin, metoprolol, nifedipine, carbamazepine, midazolam, clarithromycin, naproxen, piroxicam, and oral contraceptives [levonorgestrel/ethinyl estradiol]). Dosage adjustment of these drugs is not necessary when they are coadministered with pantoprazole. In other in vivo studies, digoxin, ethanol, glyburide, antipyrine, caffeine, metronidazole, and amoxicillin had no clinically relevant interactions with pantoprazole.
Based on studies evaluating possible interactions of pantoprazole with other drugs, no dosage adjustment is needed with concomitant use of the following: theophylline, cisapride, antipyrine, caffeine, carbamazepine, diazepam (and its active metabolite, desmethyldiazepam), diclofenac, naproxen, piroxicam, digoxin, ethanol, glyburide, an oral contraceptive (levonorgestrel/ethinyl estradiol), metoprolol, nifedipine, phenytoin, warfarin, midazolam, clarithromycin, metronidazole, or amoxicillin.
There was also no interaction with concomitantly administered antacids.
There have been postmarketing reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including pantoprazole, and warfarin concomitantly [see Drug Interactions (7.2)].
Although no significant drug-drug interactions have been observed in clinical studies, the potential for significant drug-drug interactions with more than once-daily dosing with high doses of pantoprazole has not been studied in poor metabolizers or individuals who are hepatically impaired.
Other Effects
In a clinical pharmacology study, pantoprazole 40 mg given once daily for 2 weeks had no effect on the levels of the following hormones: cortisol, testosterone, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), thyronine-binding protein, parathyroid hormone, insulin, glucagon, renin, aldosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, and growth hormone.
3412.4 Pharmacogenomics
Similar to adults, pediatric patients who have the poor metabolizer genotype of CYP2C19 (CYP2C19 *2/*2) exhibited greater than a 6-fold increase in AUC compared to pediatric extensive (CYP2C19 *1/*1) and intermediate (CYP2C19 *1/*x) metabolizers. Poor metabolizers exhibited approximately 10-fold lower apparent oral clearance compared to extensive metabolizers.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
In a 24-month carcinogenicity study, Fischer 344 rats were treated orally with doses of 5 to 50 mg/kg/day, approximately 1 to 10 times the recommended human dose based on body surface area. In the gastric fundus, treatment at 5 to 50 mg/kg/day produced enterochromaffin-like (ECL) cell hyperplasia and benign and malignant neuroendocrine cell tumors. Dose selection for this study may not have been adequate to comprehensively evaluate the carcinogenic potential of pantoprazole.
In a 24-month carcinogenicity study, B6C3F1 mice were treated orally with doses of 5 to 150 mg/kg/day, 0.5 to 15 times the recommended human dose based on body surface area. In the liver, treatment at 150 mg/kg/day produced increased incidences of hepatocellular adenomas and carcinomas in female mice. Treatment at 5 to 150 mg/kg/day also produced gastric-fundic ECL cell hyperplasia.
A 26-week p53 +/- transgenic mouse carcinogenicity study was not positive.
Pantoprazole was positive in the in vitro human lymphocyte chromosomal aberration assays, in one of two mouse micronucleus tests for clastogenic effects, and in the in vitro Chinese hamster ovarian cell/HGPRT forward mutation assay for mutagenic effects. Equivocal results were observed in the in vivo rat liver DNA covalent binding assay. Pantoprazole was negative in the in vitro Ames mutation assay, the in vitro unscheduled DNA synthesis (UDS) assay with rat hepatocytes, the in vitro AS52/GPT mammalian cell-forward gene mutation assay, the in vitro thymidine kinase mutation test with mouse lymphoma L5178Y cells, and the in vivo rat bone marrow cell chromosomal aberration assay.
There were no effects on fertility or reproductive performance when pantoprazole was given at oral doses up to 500 mg/kg/day in male rats (98 times the recommended human dose based on body surface area) and 450 mg/kg/day in female rats (88 times the recommended human dose based on body surface area).
13.2 Animal Toxicology and/or Pharmacology
Studies in neonatal/juvenile and adult rats and dogs were performed. The data from these studies revealed that animals in both age groups respond to pantoprazole in a similar manner. Gastric alterations, including increased stomach weights, increased incidence of eosinophilic chief cells in adult and neonatal/juvenile rats, and atrophy of chief cells in adult rats and in neonatal/juvenile dogs, were observed in the fundic mucosa of stomachs in repeated-dose studies. Decreases in red cell mass parameters, increases in cholesterol and triglycerides, increased liver weight, enzyme induction, and hepatocellular hypertrophy were also seen in repeated-dose studies in rats and/or dogs. Full to partial recovery of these effects were noted in animals of both age groups following a recovery period.
Reproductive Toxicology Studies
14 CLINICAL STUDIES
14.1 Erosive Esophagitis (EE) Associated with Gastroesophageal Reflux Disease (GERD)
Adult Patients
| Week | ––––Pantoprazole Sodium Delayed-Release Tablets –––– | Placebo (n = 68) |
||
|---|---|---|---|---|
| 10 mg daily (n = 153) |
20 mg daily (n = 158) |
40 mg daily (n = 162) |
||
| 4 |
45.6% |
58.4% |
75% |
14.3% |
| 8 |
66% |
83.5 % |
92.6% |
39.7% |
In this study, all pantoprazole sodium delayed-release tablets treatment groups had significantly greater healing rates than the placebo group. This was true regardless of H. pylori status for the 40 mg and 20 mg pantoprazole sodium delayed-release tablets treatment groups. The 40 mg dose of pantoprazole sodium delayed-release tablets resulted in healing rates significantly greater than those found with either the 20 mg or 10 mg dose.
A significantly greater proportion of patients taking pantoprazole sodium delayed-release tablets 40 mg experienced complete relief of daytime and nighttime heartburn and the absence of regurgitation, starting from the first day of treatment, compared with placebo. Patients taking pantoprazole sodium delayed-release tablets consumed significantly fewer antacid tablets per day than those taking placebo.
| Week | - Pantoprazole Sodium Delayed-Release Tablets - | Nizatidine | |
|---|---|---|---|
| 20 mg daily (n = 72) |
40 mg daily (n = 70) |
150 mg twice daily (n = 70) |
|
| 4 |
61.4% |
64% |
22.2% |
| 8 |
79.2% |
82.9% |
41.4% |
Once-daily treatment with pantoprazole sodium delayed-release tablets 40 mg or 20 mg resulted in significantly superior rates of healing at both 4 and 8 weeks compared with twice-daily treatment with 150 mg of nizatidine. For the 40 mg treatment group, significantly greater healing rates compared to nizatidine were achieved regardless of the H. pylori status.
A significantly greater proportion of the patients in the pantoprazole sodium delayed-release tablets treatment groups experienced complete relief of nighttime heartburn and regurgitation, starting on the first day and of daytime heartburn on the second day, compared with those taking nizatidine 150 mg twice daily. Patients taking pantoprazole sodium delayed-release tablets consumed significantly fewer antacid tablets per day than those taking nizatidine.
14.2 Long-Term Maintenance of Healing of Erosive Esophagitis
| Pantoprazole Sodium Delayed-Release Tablets 20 mg daily | Pantoprazole Sodium Delayed-Release Tablets 40 mg daily | Ranitidine 150 mg twice daily |
|
|---|---|---|---|
| Note: Pantoprazole sodium delayed-release tablets 10 mg was superior (p < 0.05) to ranitidine in Study 2, but not Study 1. |
|||
|
Study 1
|
n = 75 |
n = 74 |
n = 75 |
| Month 1 |
91 |
99 |
68 |
| Month 3 |
82 |
93 |
54 |
| Month 6 |
76 |
90 |
44 |
| Month 12 |
70 |
86 |
35 |
|
Study 2
|
n = 74 |
n = 88 |
n = 84 |
| Month 1 |
89 |
92 |
62 |
| Month 3 |
78 |
91 |
47 |
| Month 6 |
72 |
88 |
39 |
| Month 12 |
72 |
83 |
37 |
| Pantoprazole Sodium Delayed-Release Tablets 40 mg daily |
Ranitidine 150 mg twice daily |
||
|---|---|---|---|
| Month 1 |
Daytime |
5.1 ± 1.6 |
18.3 ± 1.6 |
| Nighttime |
3.9 ± 1.1 |
11.9 ± 1.1 |
|
| Month 12 |
Daytime |
2.9 ± 1.5 |
17.5 ± 1.5 |
| Nighttime |
2.5 ± 1.2 |
13.8 ± 1.3 |
|
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.
see Dosage and Administration (216 HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
Pantoprazole sodium delayed-release tablets, USP are supplied as 40 mg yellow, round, biconvex, delayed-release tablets imprinted with ‘124’ (black ink) on one side and are available as follows:
Pantoprazole sodium delayed-release tablets, USP are supplied as 20 mg yellow, round, biconvex, delayed-release tablets imprinted with ‘144’ (black ink) on one side and are available as follows:
Storage
17 PATIENT COUNSELING INFORMATION
FDA-Approved Patient Labeling
- Caution patients that pantoprazole sodium delayed-release tablets should not be split, crushed, or chewed.
- Tell patients that pantoprazole sodium delayed-release tablets 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.
- Advise patients to immediately report and seek care for any cardiovascular or neurological symptoms including palpitation, dizziness, seizures, and tetany as these may be signs of hypomagnesemia. [See Warnings and Precautions (5.5)]
FDA-approved Patient Information
PATIENT INFORMATION
Pantoprazole Sodium Delayed-Release Tablets, USP
What are pantoprazole sodium delayed-release tablets?
- 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
Pantoprazole sodium delayed-release tablets are not for children under 5 years old.
Who should not take pantoprazole sodium delayed-release tablets ?
- 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.
Before taking pantoprazole sodium delayed-release tablets, tell your doctor if you:
- have been told that you have low magnesium levels in your blood
- are 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.
- are breastfeeding or planning to breastfeed. Pantoprazole 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
- Methotrexate
How should I take pantoprazole sodium delayed-release tablets?
- 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 many 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
-
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
- Stomach lining weakening with long-term use
- Vitamin B-12 deficiency
- Low magnesium levels in your body.This problem can be serious. Low magnesium can happen in some people who take a proton pump inhibitor 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.
- seizures
- dizziness
- abnormal or fast heartbeat
- jitteriness
- jerking movements or shaking (tremors)
- muscle weakness
- spasms of the hands and feet
- cramps or muscle aches
- spasm of the voice box
- Headache
- Vomiting
- Diarrhea
- Gas
- Nausea
- Dizziness
- Stomach pain
- Pain in your joints
- Upper respiratory infection
- Vomiting
- Headache
- Rash
- Fever
- Stomach pain
- Diarrhea
People who are taking multiple daily doses of proton pump inhibitor medicines for a long period of time may have an increased risk of fractures of the hip, wrist or spine.
Tell your doctor about any side effects that bother you or that do not go away.
These are not all the possible side effects with pantoprazole sodium delayed-release tablets. Talk with your doctor or pharmacist if you have any questions about side effects.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
How should I store pantoprazole sodium delayed-release tablets?
- Store pantoprazole sodium delayed-release tablets at room temperature 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F).
- Keep pantoprazole sodium delayed-release tablets and all medicines out of the reach of children.
- Store pantoprazole sodium delayed-release tablets in the original container.
General Information
Medicines are sometimes prescribed for purposes other than those listed in the Patient Information leaflet. Do not use pantoprazole sodium delayed-release tablets for a condition for which it was not prescribed. Do not give pantoprazole sodium delayed-release tablets to other people, even if they have the same symptoms you have. It may harm them.
This Patient Information leaflet provides a summary of the most important information about pantoprazole sodium delayed-release tablets. For more information, ask your doctor. You can ask your doctor or pharmacist for information that is written for healthcare professionals.
For more information, call toll-free 1-800-818-4555.
What are the ingredients in pantoprazole sodium delayed-release tablets?
Active ingredient: pantoprazole sodium sesquihydrate
Inactive ingredients: mannitol, sodium carbonate anhydrous, anhydrous lactose, crospovidone, povidone, calcium stearate, hypromellose, polyethylene glycol, talc, methacrylic acid copolymer type C, triethyl citrate, titanium dioxide and ferric oxide yellow.
Imprinting ink contains shellac glaze, isopropyl alcohol, N-butyl alcohol, propylene glycol, ammonium hydroxide, and iron oxide black.
Patient Instructions for Use
- 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 40 mg tablet, you can take two 20 mg tablets instead.
- Do not split, chew, or crush pantoprazole sodium delayed-release tablets.
Caraco Pharmaceutical Laboratories, Ltd.
Sun Pharmaceutical Ind. Ltd.
PRINCIPAL DISPLAY PANEL - 20 mg
NDC 47335-144-81
Pantoprazole Sodium Delayed-Release Tablets, USP
20 mg
Rx only
90 TABLETS
SUN PHARMACEUTICAL INDUSTRIES LTD.
PHARMACIST: Dispense with Patient Information Leaflet
PRINCIPAL DISPLAY PANEL - 40 mg
NDC 47335-580-81
Pantoprazole Sodium Delayed-Release Tablets, USP
40 mg
Rx only
90 TABLETS
SUN PHARMACEUTICAL INDUSTRIES LTD.
PHARMACIST: Dispense with Patient Information Leaflet
Pantoprazole SodiumPantoprazole Sodium TABLET, DELAYED RELEASE
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Pantoprazole SodiumPantoprazole Sodium TABLET, DELAYED RELEASE
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