For patients who have a nasogastric tube or gastrostomy tube in place, PROTONIX For Delayed-Release Oral Suspension can be given as follows:
- Remove the plunger from the barrel of a 2 ounce (60 mL) catheter-tip syringe. Discard the plunger.
- Connect the catheter tip of the syringe to a 16 French (or larger) tube.
- Hold the syringe attached to the tubing as high as possible while giving PROTONIX For Delayed-Release Oral Suspension to prevent any bending of the tubing.
- Empty the contents of the packet into the barrel of the syringe.
- Add 10 mL (2 teaspoonfuls) of apple juice and gently tap and/or shake the barrel of the syringe to help rinse the syringe and tube. Repeat at least twice more using the same amount of apple juice (10 mL or 2 teaspoonfuls) each time. No granules should remain in the syringe.
Safety in nine randomized comparative US clinical trials in patients with GERD included 1,473 patients on oral PROTONIX (20 mg or 40 mg), 299 patients on an H2-receptor antagonist, 46 patients on another PPI, 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 PROTONIX 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
Nervous: depression, vertigo
Skin and Appendages: urticaria, rash, pruritus
Special Senses: blurred vision
Safety of PROTONIX in the treatment of 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 PROTONIX are 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 PROTONIX 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 (ZE) Syndrome
In clinical studies of ZE Syndrome, adverse reactions reported in 35 patients taking PROTONIX 80 mg/day to 240 mg/day for up to 2 years were similar to those reported in adult patients with GERD.
Pregnancy Category C
Reproduction studies have been performed in rats at oral pantoprazole doses up to 450 mg/kg/day (about 88 times the recommended human dose based on body surface area) and in rabbits at oral doses up to 40 mg/kg/day (about 16 times the recommended human dose based on body surface area) with administration of pantoprazole sodium during organogenesis in pregnant animals. The studies have revealed no evidence of impaired fertility or harm to the fetus due to pantoprazole.
A pre- and postnatal development toxicity study in rats with additional endpoints to evaluate the effect on bone development was performed with pantoprazole sodium. Oral pantoprazole doses of 5, 15, and 30 mg/kg/day (approximately 1, 3, and 6 times the human dose of 40 mg/day on a body surface area basis) were administered to pregnant females from gestation day (GD) 6 through lactation day (LD) 21. On postnatal day (PND 4) through PND 21, the pups were administered oral doses at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (AUC) in humans at a dose of 40 mg). There were no drug-related findings in maternal animals. During the preweaning dosing phase (PND 4 to 21) of the pups, there were increased mortality and/or moribundity and decreased body weight and body weight gain at 5 mg/kg/day (approximately equal exposures (AUC) in humans receiving the 40 mg dose) and higher doses. On PND 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (AUC) in humans at the 40 mg dose) and higher doses. The femur findings included lower total area, bone mineral content and density, periosteal and endosteal circumference, and cross-sectional moment of inertia. There were no microscopic changes in the distal femur, proximal tibia, or stifle joints. Changes in bone parameters were partially reversible following a recovery period, with findings on PND 70 limited to lower femur metaphysis cortical/subcortical bone mineral density in female pups at 5 mg/kg/day (approximately equal exposures (AUC) in humans at the 40 mg dose) and higher doses.
There are no adequate and well-controlled studies in pregnant women. Advise pregnant women of the potential risk of fetal harm. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
1 year through 16 years of age
Use of PROTONIX in pediatric patients 1 year through 16 years of age for short-term treatment (up to eight weeks) of EE associated with GERD is supported by: a) extrapolation of results from adequate and well-controlled studies that supported the approval of PROTONIX for treatment of EE associated with GERD in adults, and b) safety, effectiveness, and pharmacokinetic studies performed in pediatric patients [see Clinical Studies (14.1), Clinical Pharmacology (12.3)].
Safety of PROTONIX in the treatment of EE associated with GERD in pediatric patients 1 through 16 years of age was evaluated in three multicenter, randomized, double-blind, parallel-treatment studies, involving 249 pediatric patients, including 8 with EE (4 patients ages 1 year to 5 years and 4 patients 5 years to 11 years). The children ages 1 year to 5 years with endoscopically diagnosed EE (defined as an endoscopic Hetzel-Dent score ≥2) were treated once daily for 8 weeks with one of two dose levels of PROTONIX (approximating 0.6 mg/kg or 1.2 mg/kg). All 4 of these patients with EE were healed (Hetzel-Dent score of 0 or 1) at 8 weeks. Because EE is uncommon in the pediatric population, predominantly pediatric patients with endoscopically-proven or symptomatic GERD were also included in these studies. Patients were treated with a range of doses of PROTONIX once daily for 8 weeks. For safety findings see Adverse Reactions (6.1). Because these pediatric trials had no placebo, active comparator, or evidence of a dose response, the trials were inconclusive regarding the clinical benefit of PROTONIX for symptomatic GERD in the pediatric population. The effectiveness of PROTONIX for treating symptomatic GERD in pediatric patients has not been established.
Although the data from the clinical trials support use of PROTONIX for the short-term treatment of EE associated with GERD in pediatric patients 1 year through 5 years, there is no commercially available dosage formulation appropriate for patients less than 5 years of age [see Dosage and Administration (2)].
In a population pharmacokinetic analysis, clearance values in the children 1 to 5 years old with endoscopically proven GERD had a median value of 2.4 L/h. Following a 1.2 mg/kg equivalent dose (15 mg for ≤12.5 kg and 20 mg for >12.5 to <25 kg), the plasma concentrations of pantoprazole were highly variable and the median time to peak plasma concentration was 3 to 6 hours. The estimated AUC for patients 1 to 5 years old was 37% higher than for adults receiving a single 40 mg tablet, with a geometric mean AUC value of 6.8 µg∙hr/mL.
Neonates to less than one year of age
PROTONIX was not found to be effective in a multicenter, randomized, double-blind, placebo-controlled, treatment-withdrawal study of 129 pediatric patients 1 through 11 months of age. Patients were enrolled if they had symptomatic GERD based on medical history and had not responded to non-pharmacologic interventions for GERD for two weeks. Patients received PROTONIX daily for four weeks in an open-label phase, then patients were randomized in equal proportion to receive PROTONIX treatment or placebo for the subsequent four weeks in a double-blind manner. Efficacy was assessed by observing the time from randomization to study discontinuation due to symptom worsening during the four-week treatment-withdrawal phase. There was no statistically significant difference between PROTONIX and placebo in the rate of discontinuation.
In this trial, the adverse reactions that were reported more commonly (difference of ≥4%) in the treated population compared to the placebo population were elevated CK, otitis media, rhinitis, and laryngitis.
In a population pharmacokinetic analysis, the systemic exposure was higher in patients less than 1 year of age with GERD compared to adults who received a single 40 mg dose (geometric mean AUC was 103% higher in preterm infants and neonates receiving single dose of 2.5 mg of PROTONIX, and 23% higher in infants 1 through 11 months of age receiving a single dose of approximately 1.2 mg/kg). In these patients, the apparent clearance (CL/F) increased with age (median clearance: 0.6 L/hr, range: 0.03 to 3.2 L/hr).
These doses resulted in pharmacodynamic effects on gastric but not esophageal pH. Following once daily dosing of 2.5 mg of PROTONIX in preterm infants and neonates, there was an increase in the mean gastric pH (from 4.3 at baseline to 5.2 at steady-state) and in the mean % time that gastric pH was > 4 (from 60% at baseline to 80% at steady-state). Following once daily dosing of approximately 1.2 mg/kg of PROTONIX in infants 1 through 11 months of age, there was an increase in the mean gastric pH (from 3.1 at baseline to 4.2 at steady-state) and in the mean % time that gastric pH was > 4 (from 32% at baseline to 60% at steady-state). However, no significant changes were observed in mean intraesophageal pH or % time that esophageal pH was <4 in either age group.
Because PROTONIX was not shown to be effective in the randomized, placebo-controlled study in this age group, the use of PROTONIX for treatment of symptomatic GERD in infants less than 1 year of age is not indicated.
Animal Toxicity Data
In a pre- and post-natal development study in rats, the pups were administered oral doses of pantoprazole at 5, 15, and 30 mg/kg/day (approximately 1, 2.3, and 3.2 times the exposure (AUC) in children aged 6 to 11 years at a dose of 40 mg) on postnatal day (PND 4) through PND 21, in addition to lactational exposure through milk. On PND 21, decreased mean femur length and weight and changes in femur bone mass and geometry were observed in the offspring at 5 mg/kg/day (approximately equal exposures (AUC) in children aged 6 to 11 years at the 40 mg dose) and higher doses. Changes in bone parameters were partially reversible following a recovery period.
In neonatal/juvenile animals (rats and dogs) toxicities were similar to those observed in adult animals, including gastric alterations, decreases in red cell mass, increases in lipids, enzyme induction and hepatocellular hypertrophy. An 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, was observed in the fundic mucosa of stomachs in repeated-dose studies. Full to partial recovery of these effects were noted in animals of both age groups following a recovery period.
Under maximal acid stimulatory conditions using pentagastrin, a dose-dependent decrease in gastric acid output occurs after a single dose of oral (20–80 mg) or a single dose of intravenous (20–120 mg) pantoprazole in healthy subjects. 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 5.
Table 5: Effect of Single Daily Doses of Oral Pantoprazole on Intragastric pH
|Median pH on day 7|
|Time||Placebo||20 mg||40 mg||80 mg|
|8 a.m. – 8 a.m. (24 hours)||1.3||2.9|
Significantly different from placebo
Significantly different from 20 mg
|8 a.m. – 10 p.m. (Daytime)||1.6||3.2||4.4||4.8|
|10 p.m. – 8 a.m. (Nighttime)||1.2||2.1||3.0||2.6|
Serum Gastrin Effects
Fasting serum gastrin levels were assessed in two double-blind studies of the acute healing of EE in which 682 patients with gastroesophageal reflux disease (GERD) received 10, 20, or 40 mg of PROTONIX 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 PROTONIX 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 PROTONIX, 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 PPIs. 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 [see Nonclinical Toxicology (13.1)].
In a clinical pharmacology study, PROTONIX 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.
In a 1-year study of GERD patients treated with PROTONIX 40 mg or 20 mg, there were no changes from baseline in overall levels of T3, T4, and TSH.
After administration of a single or multiple oral 40 mg doses of PROTONIX Delayed-Release Tablets, the peak plasma concentration of pantoprazole was achieved in approximately 2.5 hours, and Cmax was 2.5 μg/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 PROTONIX 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, PROTONIX Delayed-Release Tablets may be taken without regard to timing of meals.
Administration of pantoprazole granules, 40 mg, with a high-fat meal delayed median time to peak plasma concentration by 2 hours. With a concomitant high-fat meal, the Cmax and AUC of pantoprazole granules, 40 mg, sprinkled on applesauce decreased by 51% and 29%, respectively. Thus, PROTONIX For Delayed-Release Oral Suspension should be taken approximately 30 minutes before a meal.
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.
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.
After a single oral or intravenous dose of 14C-labeled pantoprazole to healthy, normal metabolizer subjects, 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.
Only slight to moderate increases in the AUC (43%) and Cmax (26%) of pantoprazole were found in elderly subjects (64 to 76 years of age) after repeated oral administration, compared with younger subjects [see Use in Specific Populations (8.5)].
The pharmacokinetics of pantoprazole were studied in children less than 16 years of age in four randomized, open-label clinical trials in pediatric patients with presumed/proven GERD. A pediatric granule formulation was studied in children through 5 years of age, and PROTONIX Delayed-Release Tablets were studied in children older than 5 years.
In a population PK analysis, total clearance increased with increasing bodyweight in a non-linear fashion. The total clearance also increased with increasing age only in children under 3 years of age.
Neonate through 5 Years of Age
[see Use in Specific Populations (8.4)]
Children and Adolescents 6 through 16 Years of Age
The pharmacokinetics of PROTONIX Delayed-Release Tablets were evaluated in children ages 6 through 16 years with a clinical diagnosis of GERD. The PK parameters following a single oral dose of 20 mg or 40 mg of PROTONIX tablets in children ages 6 through 16 years were highly variable (%CV ranges 40 to 80%). The geometric mean AUC estimated from population PK analysis after a 40 mg PROTONIX tablet in pediatric patients was about 39% and 10% higher respectively in 6 to 11 and 12 to 16 year-old children, compared to that of adults (Table 7).
Table 7: PK Parameters in Children and Adolescents 6 through 16 years with GERD receiving 40 mg PROTONIX Tablets
|6–11 years (n=12)||12–16 years (n=11)|
Geometric mean values
Male and Female Patients
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.
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.
Patients with Renal Impairment
In patients with severe renal impairment, pharmacokinetic parameters for pantoprazole were similar to those of healthy subjects.
Patients with 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 7–9 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. Doses higher than 40 mg/day have not been studied in hepatically impaired patients.
Drug Interaction Studies
Effect of Other Drugs on Pantoprazole
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.
Effect of Pantoprazole on Other Drugs
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.
Mycophenolate Mofetil (MMF)
Administration of pantoprazole 40 mg twice daily for 4 days and a single 1000 mg dose of MMF approximately one hour after the last dose of pantoprazole to 12 healthy subjects in a cross-over study resulted in a 57% reduction in the Cmax and 27% reduction in the AUC of MPA. Transplant patients receiving approximately 2000 mg per day of MMF (n=12) were compared to transplant patients receiving approximately the same dose of MMF and pantoprazole 40 mg per day (n=21). There was a 78% reduction in the Cmax and a 45% reduction in the AUC of MPA in patients receiving both pantoprazole and MMF [see Drug Interactions (7)].
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, metoprolol, nifedipine, carbamazepine, midazolam, clarithromycin, diclofenac, naproxen, piroxicam, and oral contraceptives [levonorgestrel/ethinyl estradiol]). In other in vivo studies, digoxin, ethanol, glyburide, antipyrine, caffeine, metronidazole, and amoxicillin had no clinically relevant interactions with pantoprazole.
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.
There was also no interaction with concomitantly administered antacids.
A US multicenter, double-blind, placebo-controlled study of PROTONIX 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 8.
Table 8: Erosive Esophagitis Healing Rates (Per Protocol)
|Week||10 mg daily|
(n = 153)
|20 mg daily|
(n = 158)
|40 mg daily |
(n = 162)
|(n = 68)|
(p < 0.001) PROTONIX versus placebo
(p < 0.05) versus 10 mg PROTONIX
(p < 0.05) versus 10 mg or 20 mg PROTONIX
In this study, all PROTONIX 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 PROTONIX treatment groups. The 40 mg dose of PROTONIX 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 PROTONIX 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 PROTONIX consumed significantly fewer antacid tablets per day than those taking placebo.
PROTONIX 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 9.
Table 9: Erosive Esophagitis Healing Rates (Per Protocol)
|Week||20 mg daily|
(n = 72)
|40 mg daily|
(n = 70)
|150 mg twice daily|
(n = 70)
(p < 0.001) PROTONIX versus nizatidine
Once-daily treatment with PROTONIX 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 PROTONIX 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 PROTONIX consumed significantly fewer antacid tablets per day than those taking nizatidine.
Pediatric Patients Ages 5 Years through 16 Years
The efficacy of PROTONIX in the treatment of EE associated with GERD in pediatric patients ages 5 years through 16 years is extrapolated from adequate and well-conducted trials in adults, as the pathophysiology is thought to be the same. Four pediatric patients with endoscopically diagnosed EE were studied in multicenter, randomized, double-blind, parallel-treatment trials. Children with endoscopically diagnosed EE (defined as an endoscopic Hetzel-Dent score ≥2) were treated once daily for 8 weeks with one of two dose levels of PROTONIX (20 mg or 40 mg). All 4 patients with EE were healed (Hetzel-Dent score of 0 or 1) at 8 weeks.
PROTONIX (pantoprazole sodium) Delayed-Release Tablets are supplied as yellow, oval biconvex delayed-release tablets imprinted with PROTONIX (brown ink) on one side containing 40 mg pantoprazole and are available as follows:
- NDC 0008-0841-81, bottles of 90
PROTONIX (pantoprazole sodium) Delayed-Release Tablets are supplied as yellow oval biconvex delayed-release tablets imprinted with P20 (brown ink) on one side containing 20 mg pantoprazole and are available as follows:
- NDC 0008-0843-81, bottles of 90
PROTONIX (pantoprazole sodium) For Delayed-Release Oral Suspension is supplied as pale yellowish to dark brownish, enteric-coated granules containing 40 mg pantoprazole in a unit-dose packet and are available as follows:
- NDC 0008-0844-02, unit-dose carton of 30
Advise patients to return to their healthcare provider if they have a suboptimal response or an early symptomatic relapse [see Warnings and Precautions (5.1)].
Acute Interstitial Nephritis
Advise patients to call their healthcare provider immediately if they experience signs and/or symptoms associated with acute interstitial nephritis [see Warnings and Precautions (5.2)].
Clostridium difficile-Associated Diarrhea
Advise patients to immediately call their healthcare provider if they experience diarrhea that does not improve [see Warnings and Precautions (5.3)].
Advise patients to report any fractures, especially of the hip, wrist or spine, to their healthcare provider [see Warnings and Precautions (5.4)].
Cutaneous and Systemic Lupus Erythematosus
Advise patients to immediately call their healthcare provider for any new or worsening of symptoms associated with cutaneous or systemic lupus erythematosus [see Warnings and Precautions (5.5)].
Cyanocobalamin (Vitamin B-12) Deficiency
Advise patients to report any clinical symptoms that may be associated with cyancobalamin deficiency to their healthcare provider if they have been receiving PROTONIX for longer than 3 years [see Warnings and Precautions (5.6)].
Advise patients to report any clinical symptoms that may be associated with hypomagnesemia to their healthcare provider, if they have been receiving PROTONIX for at least 3 months [see Warnings and Precautions (5.7)].
Instruct patients to inform their healthcare provider of any other medications they are currently taking, including rilpivirine-containing products [see Contraindications (4)] digoxin [see Warnings and Precautions (5.7)] and high dose methotrexate [see Warnings and Precautions (5.11)].
Inform female patients of reproductive potential that PROTONIX may cause fetal harm and to inform their prescriber of a known or suspected pregnancy [see Use in Specific Populations (8.1)].
- Do not split, crush, or chew PROTONIX For Delayed-Release Oral Suspension and PROTONIX Delayed-Release Tablets.
- PROTONIX oral suspension packet is a fixed dose and cannot be divided to make a smaller dose.
- Swallow PROTONIX Delayed-Release Tablets whole, with or without food in the stomach.
- Concomitant administration of antacids does not affect the absorption of PROTONIX Delayed-Release Tablets.
- Take PROTONIX For Delayed-Release Oral Suspension approximately 30 minutes before a meal.
- Administer PROTONIX For Delayed-Release Oral Suspension in apple juice or applesauce, as described in the Instructions for Use. Do not administer in water, other liquids, or foods.
- For patients with a nasogastric (NG) or gastrostomy tube, PROTONIX For Delayed-Release Oral Suspension can be administered with apple juice, as described in the Instructions for Use.
- Take a missed dose as soon as possible. If it is almost time for the next dose, skip the missed dose and take the next dose at the regular scheduled time. Do not take 2 doses at the same time.
This product's label may have been updated. For current full prescribing information, please visit www.pfizer.com.
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