Pantoprazole Information
Pantoprazole () Indications And Usage
Pantoprazole () sodium delayed-release tablets USP are indicated for:
Pantoprazole () sodium delayed-release tablets USP are indicated in adults 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 delayed-release tablets USP may be considered. Safety of treatment beyond 8 weeks in pediatric patients has not been established.
Pediatric indication and usage information in pediatric patients ages five years and older 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
Pantoprazole () Dosage And Administration
See Full Prescribing Information for administration instructions
Pantoprazole () sodium is supplied as delayed-release tablets. The recommended dosages are outlined in Table 1.
* For adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of Pantoprazole () sodium delayed-release tablets USP 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.
Pediatric dosing information in pediatric patients ages five years and older 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.
Directions for method of administration for each dosage form are presented in Table 2.
Table 2: Administration Instructions
* Patients should be cautioned that Pantoprazole () sodium delayed-release tablets USP should not be split, chewed, or crushed.
Pantoprazole () Sodium Delayed-Release Tablets USP
Pantoprazole () sodium delayed-release tablets USP 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 USP.
Pantoprazole () Dosage Forms And Strengths
Pantoprazole () Contraindications
Pantoprazole () sodium delayed-release tablets USP are contraindicated in patients with known hypersensitivity to any component of the formulation [] or any substituted benzimidazole.
Pantoprazole () Warnings And Precautions
Pantoprazole () Adverse Reactions
The adverse reaction profiles for Pantoprazole () sodium delayed-release oral suspension and Pantoprazole () sodium delayed-release tablets are similar.
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-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%
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
Adverse reaction information 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.
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.
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:
Immune System Disorders: anaphylaxis (including anaphylactic shock)
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)
Musculoskeletal and Connective Tissue Disorders: rhabdomyolysis, bone fracture
Renal and Urinary Disorders: interstitial nephritis
Hepatobiliary Disorders: hepatocellular damage leading to jaundice and hepatic failure
Psychiatric Disorders: hallucination, confusion
Pantoprazole () Drug Interactions
Pantoprazole () Use In Specific Populations
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Teratogenic Effects
Pregnancy Category B
Reproduction studies have been performed in rats at oral doses up to 88 times the recommended human dose and in rabbits at oral doses up to 16 times the recommended human dose and have revealed no evidence of impaired fertility or harm to the fetus due to Pantoprazole () . There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed [].
The effectiveness of Pantoprazole () sodium 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
Pantoprazole () Overdosage
Experience in patients taking very high doses of Pantoprazole () sodium (> 240 mg) is limited. Spontaneous post-marketing reports of overdose are generally within the known safety profile of Pantoprazole () sodium.
Pantoprazole () is not removed by hemodialysis. In case of overdosage, treatment should be symptomatic and supportive.
Single oral doses of Pantoprazole () at 709 mg/kg, 798 mg/kg, and 887 mg/kg were lethal to mice, rats, and dogs, respectively. The symptoms of acute toxicity were hypoactivity, ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex, and tremor.
Pantoprazole () 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]1H- benzimidazole sesquihydrate, a compound that inhibits gastric acid secretion. Its empirical formula is CHFNNaOS x 1.5 HO, with a molecular weight of 432.4. The structural formula is:
Pantoprazole () sodium sesquihydrate is a white to cream color powder and is racemic. Pantoprazole () has weakly basic and acidic properties. Pantoprazole () sodium sesquihydrate is freely soluble in water and ethanol.
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 for oral administration, available in 2 strengths. Each delayed-release tablet contains 45.1 mg or 22.6 mg of Pantoprazole () sodium sesquihydrate (equivalent to 40 mg or 20 mg Pantoprazole () , respectively) with the following inactive ingredients: calcium stearate, crospovidone, hydroxypropyl cellulose, hypromellose, iron oxide black, isopropyl alcohol, mannitol, methacrylic acid copolymer, methylated spirit, N-butyl alcohol, polyethylene glycol, propylene glycol, shellac, sodium carbonate anhydrous, synthetic yellow iron oxide, talc, titanium dioxide, triethyl citrate, zein.
USP dissolution test is pending.
Pantoprazole () Clinical Pharmacology
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Antisecretory Activity
Under maximal acid stimulatory conditions using pentagastrin, a dose-dependent decrease in gastric acid output occurs after a single dose of oral (20 to 80 mg) or a single dose of intravenous (20 to 120 mg) Pantoprazole () in healthy volunteers. Pantoprazole () given once daily results in increasing inhibition of gastric acid secretion. Following the initial oral dose of 40 mg Pantoprazole () , a 51% mean inhibition was achieved by 2.5 hours. With once-a-day dosing for 7 days, the mean inhibition was increased to 85%. Pantoprazole () suppressed acid secretion in excess of 95% in half of the subjects. Acid secretion had returned to normal within a week after the last dose of Pantoprazole () ; there was no evidence of rebound hypersecretion.
In a series of dose-response studies, Pantoprazole () , at oral doses ranging from 20 to 120 mg, caused dose-related increases in median basal gastric pH and in the percent of time gastric pH was > 3 and > 4. Treatment with 40 mg of Pantoprazole () produced significantly greater increases in gastric pH than the 20 mg dose. Doses higher than 40 mg (60, 80, 120 mg) did not result in further significant increases in median gastric pH. The effects of Pantoprazole () on median pH from one double-blind crossover study are shown in Table 4.
Table 4: Effect of Single Daily Doses of Oral Pantoprazole () on Intragastric pH
* Significantly different from placebo
# Significantly different from 20 mg
Serum Gastrin Effects
Fasting serum gastrin levels were assessed in two double-blind studies of the acute healing of erosive esophagitis (EE) in which 682 patients with gastroesophageal reflux disease (GERD) received 10, 20, or 40 mg of Pantoprazole () sodium for up to 8 weeks. At 4 weeks of treatment there was an increase in mean gastrin levels of 7%, 35%, and 72% over pretreatment values in the 10, 20, and 40 mg treatment groups, respectively. A similar increase in serum gastrin levels was noted at the 8-week visit with mean increases of 3%, 26%, and 84% for the three Pantoprazole () dose groups. Median serum gastrin levels remained within normal limits during maintenance therapy with Pantoprazole () sodium delayed-release tablets.
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 () sodium, 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.
In a nonclinical study in Sprague-Dawley rats, lifetime exposure (24 months) to Pantoprazole () at doses of 0.5 to 200 mg/kg/day resulted in dose-related increases in gastric ECL cell proliferation and gastric neuroendocrine (NE)-cell tumors. Gastric NE-cell tumors in rats may result from chronic elevation of serum gastrin concentrations. The high density of ECL cells in the rat stomach makes this species highly susceptible to the proliferative effects of elevated gastrin concentrations produced by proton pump inhibitors. However, there were no observed elevations in serum gastrin following the administration of Pantoprazole () at a dose of 0.5 mg/kg/day. In a separate study, a gastric NE-cell tumor without concomitant ECL-cell proliferative changes was observed in 1 female rat following 12 months of dosing with Pantoprazole () at 5 mg/kg/day and a 9 month off-dose recovery [.
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 (t) 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 to14 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 C-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]), 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.
In vivo
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 () sodium, 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 () sodium has not been studied in poor metabolizers or individuals who are hepatically impaired.
Other Effects
In a clinical pharmacology study, Pantoprazole () sodium 40 mg given once daily for 2 weeks had no effect on the levels of the following hormones: cortisol, testosterone, triiodothyronine (T), thyroxine (T), thyroid-stimulating hormone (TSH), thyronine-binding protein, parathyroid hormone, insulin, glucagon, renin, aldosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, and growth hormone.
In a 1-year study of GERD patients treated with Pantoprazole () sodium 40 mg or 20 mg, there were no changes from baseline in overall levels of T, T, and TSH.
CYP2C19 displays a known genetic polymorphism due to its deficiency in some subpopulations (e.g., approximately 3% of Caucasians and African-Americans and 17% to 23% of Asians are poor metabolizers). Although these subpopulations of Pantoprazole () poor metabolizers have elimination half-life values of 3.5 to 10 hours in adults, they still have minimal accumulation (≤ 23%) with once-daily dosing. For adult patients who are CYP2C19 poor metabolizers, no dosage adjustment is needed.
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.
For known pediatric poor metabolizers, a dose reduction should be considered.
Pantoprazole () Nonclinical Toxicology
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In a 24-month carcinogenicity study, Sprague-Dawley rats were treated orally with doses of 0.5 to 200 mg/kg/day, about 0.1 to 40 times the exposure on a body surface area basis of a 50 kg person dosed at 40 mg/day. In the gastric fundus, treatment at 0.5 to 200 mg/kg/day produced enterochromaffin-like (ECL) cell hyperplasia and benign and malignant neuroendocrine cell tumors in a dose-related manner. In the forestomach, treatment at 50 and 200 mg/kg/day (about 10 and 40 times the recommended human dose on a body surface area basis) produced benign squamous cell papillomas and malignant squamous cell carcinomas. Rare gastrointestinal tumors associated with Pantoprazole () treatment included an adenocarcinoma of the duodenum at 50 mg/kg/day and benign polyps and adenocarcinomas of the gastric fundus at 200 mg/kg/day. In the liver, treatment at 0.5 to 200 mg/kg/day produced dose-related increases in the incidences of hepatocellular adenomas and carcinomas. In the thyroid gland, treatment at 200 mg/kg/day produced increased incidences of follicular cell adenomas and carcinomas for both male and female rats.
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).
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
Reproduction studies have been performed in rats at oral doses up to 450 mg/kg/day (88 times the recommended human dose based on body surface area) and rabbits at oral doses up to 40 mg/kg/day (16 times the recommended human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to Pantoprazole () .
Pantoprazole () Clinical Studies
Pantoprazole () sodium delayed-release tablets were used in the following clinical trials.
Adult Patients
A US multicenter, double-blind, placebo-controlled study of Pantoprazole () sodium 10 mg, 20 mg, or 40 mg once daily was conducted in 603 patients with reflux symptoms and endoscopically diagnosed EE of grade 2 or above (Hetzel-Dent scale). In this study, approximately 25% of enrolled patients had severe EE of grade 3, and 10% had grade 4. The percentages of patients healed (per protocol, n = 541) in this study are shown in Table 5.
Table 5: Erosive Esophagitis Healing Rates (Per Protocol)
+ (
* (p
#
In this study, all Pantoprazole () sodium 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 treatment groups. The 40 mg dose of Pantoprazole () sodium 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 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 consumed significantly fewer antacid tablets per day than those taking placebo.
Pantoprazole () sodium 40 mg and 20 mg once daily were also compared with nizatidine 150 mg twice daily in a US multicenter, double-blind study of 243 patients with reflux symptoms and endoscopically diagnosed EE of grade 2 or above. The percentages of patients healed (per protocol, n = 212) are shown in Table 6.
+
Once-daily treatment with Pantoprazole () sodium 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 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 consumed significantly fewer antacid tablets per day than those taking nizatidine.
Clinical study information in pediatric patients ages five years through 16 years 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.
Two independent, multicenter, randomized, double-blind, comparator-controlled trials of identical design were conducted in adult GERD patients with endoscopically confirmed healed erosive esophagitis to demonstrate efficacy of Pantoprazole () sodium in long-term maintenance of healing. The two US studies enrolled 386 and 404 patients, respectively, to receive either 10 mg, 20 mg, or 40 mg of Pantoprazole () sodium delayed-release tablets once daily or 150 mg of ranitidine twice daily. As demonstrated in Table 7, Pantoprazole () sodium 40 mg and 20 mg were significantly superior to ranitidine at every timepoint with respect to the maintenance of healing. In addition, Pantoprazole () sodium 40 mg was superior to all other treatments studied.
* (p
#
Note: Pantoprazole () sodium 10 mg was superior (p
Pantoprazole () sodium 40 mg was superior to ranitidine in reducing the number of daytime and nighttime heartburn episodes from the first through the twelfth month of treatment. Pantoprazole () sodium 20 mg, administered once daily, was also effective in reducing episodes of daytime and nighttime heartburn in one trial, as presented in Table 8.
* (p
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 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 was well tolerated at these dose levels for prolonged periods (greater than 2 years in some patients).
Pantoprazole () How Supplied/storage And Handling
Pantoprazole () sodium delayed-release tablets USP 20 mg are yellow, round, biconvex coated tablets printed with “R332” on one side with black ink and plain on the other side.
Pantoprazole () sodium delayed-release tablets USP 40 mg are yellow, round, biconvex coated tablets printed with “R333” on one side with black ink and plain on the other side. They are supplied in unit dose box of 100 (10 x 10).
Unit dose package of 100 (10 x 10) NDC 0904-6235-61
Store Pantoprazole () sodium delayed-release tablets at 20°–25°C (68°–77°F); excursions permitted to 15°-30°C (59°-86°F). [See USP Controlled Room Temperature].
Pantoprazole () Patient Counseling Information
See FDA-Approved Patient Labeling ().
PATIENT INFORMATION
Pantoprazole () Sodium Delayed-Release Tablets USP
Read the Patient Information that comes with Pantoprazole () sodium delayed-release tablets before you start taking it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or your treatment.
Pantoprazole () sodium delayed-release tablet is a prescription medicine called a proton pump inhibitor (PPI).
Pantoprazole () sodium delayed-release tablet is used in adults for:
Information describing use in pediatric patients ages five years through 16 years old 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. Pantoprazole () sodium delayed-release tablets is not for children under 5 years old.
Do not take Pantoprazole () sodium delayed-release tablets if you are:
Tell your doctor about all of the medicines you take, including prescription and non-prescription drugs, vitamins and herbal supplements. Pantoprazole () sodium delayed-release tablets may affect how other medicines work, and other medicines may affect how Pantoprazole () sodium delayed-release tablet works. Especially tell your doctor if you take:
o how to take Pantoprazole () sodium delayed-release tablets
Pantoprazole () sodium delayed-release tablets can cause serious side effects including
The most common side effects with Pantoprazole () sodium delayed-release tablets in adults include:
The most common side effects with Pantoprazole () sodium delayed-release tablets in children include:
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.
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 1-888-375-3784.
Active ingredient
Inactive ingredients in Pantoprazole () sodium delayed-release tablets
Patient Instructions for Use
Pantoprazole () Sodium Delayed-Release Tablets
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Distributed by: Major Pharmaceuticals
Livonia, MI 48150
Manufactured by:
Bachepalli – 502 325 INDIA
Issued: 1110
Pantoprazole ()
