Pantor-20/Pantor-40/Pantor IV

Pantoprazole (tab: sodium sesquihydrate; inj: sodium).

Pantor-20/Pantor-40: Each enteric-coated tablet contains: Pantoprazole (as sodium sesquihydrate) 20 mg or 40 mg.
Pantor IV: Each vial contains: Pantoprazole Sodium Eq. to Pantoprazole 40 mg.

Pharmacology: Pharmacodynamics: Pantor-20/Pantor-40: Mechanism of Action: Pantoprazole is a proton pump inhibitor (PPI) that suppresses the final step in gastric acid production by covalently binding to the (H+, K+)-ATPase enzyme system at the secretory surface of the gastric parietal cell. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. The binding to the (H+, K+)-ATPase results in a duration of antisecretory effect that persists longer than 24 hours for all doses tested (20 mg to 120 mg).
Pharmacokinetics: Pantor-20/Pantor-40: 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 (C_max) 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 (C_max) is 2.5 mcg/mL; the time to reach the peak concentration (t_max) 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 14.0 L/h, and its apparent volume of distribution is 11.0 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 C_max 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 C_max 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 11.0 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.
Special Populations and Conditions: Geriatric: Only slight to moderate increases in pantoprazole AUC (43%) and C_max (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. The daily dose in elderly patients, as a rule, should not exceed the recommended dosage regimens.
Pediatric: The safety and effectiveness of pantoprazole for short-term treatment (up to eight weeks) of erosive esophagitis (EE) associated with GERD have been established in pediatric patients 1 year through 16 years of age. Effectiveness for EE has not been demonstrated in patients less than 1 year of age. In addition, for patients less than 5 years of age, there is no appropriate dosage strength in an age appropriate formulation available. Therefore, pantoprazole is indicated for the short-term treatment of EE associated with GERD for patients 5 years and older. The safety and effectiveness of pantoprazole for pediatric uses other than EE have not been established.
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.
Pantor IV: Absorption and Distribution: Following intravenous administration of Pantoprazole, serum/plasma concentrations decline biexponentially. The terminal half-life is about 1 hour. The total serum clearance is approximately 0.1/11/h/kg and the volume of distribution is about 0.15 L/kg.
The plasma kinetics for Pantoprazole after both oral and intravenous is linear over the dose range 10 to 80 mg.
Metabolism: Pantoprazole is almost exclusively metabolised in the liver. The main metabolite is desmethylpantoprazole, which is conjugated with sulfate.
Elimination: Renal elimination represents the most important route of excretion (approximately 80%) for the metabolite of Pantoprazole. The balance is excreted with faeces. The half-life of the main metabolite is approximately 1 and half hours which is slightly longer than that of Pantoprazole.

Pantor-20/Pantor-40: Pantoprazole sodium is used for the treatment of conditions where reduction of gastric acid secretion is required, such as the following: Short-Term Treatment of Erosive Esophagitis Associated with Gastroesophageal Reflux Disease (GERD).
Maintenance of healing of erosive esophagitis and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with gastro-esophageal reflux disease (GERD).
Long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome.
Prophylaxis for non-steroidal anti-inflammatory drugs (NSAIDs)-associated ulceration in patients with a need for continuous NSAID treatment, who have increased risk to develop NSAID-associated upper gastrointestinal lesions.
Eradication of Helicobacter pylori.
Treatment of peptic ulcer disease.
Pantor IV: It used in conditions where inhibition of gastric acid secretion may be beneficial, including aspiration syndromes, dyspepsia, gastroesophageal reflux disease, peptic ulcer disease, and the Zollinger-Ellison syndrome.

Pantor-20/Pantor-40: Pantoprazole (Pantor-20/Pantor-40) Enteric-Coated tablets should be swallowed whole, with or without food in the stomach. If patients are unable to swallow a 40 mg tablet, two 20 mg tablets may be taken. Concomitant administration of antacids does not affect the absorption of Pantoprazole sodium enteric-coated tablets.
Short-Term Treatment of Erosive Esophagitis Associated with Gastroesophageal Reflux Disease (GERD): Adults: 40 mg once daily up to 8 weeks*.
Children (5 years and older): >15 kg to <40 kg: 20 mg once daily for up to 8 weeks.
>40 kg: 40 mg.
* For adult patients who have not healed after 8 weeks of treatment, an additional 8-week course may be considered.
Maintenance of healing of erosive esophagitis and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with gastro-esophageal reflux disease (GERD): Adults: 40 mg once daily**.
**Controlled studies did not extend beyond 12 months.
Long-term treatment of pathological hypersecretory conditions, including Zollinger-Ellison syndrome: Adults: 40 mg twice daily***.
***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.
Prophylaxis for NSAID-associated ulceration: The recommended adult oral dose of pantoprazole is 20 mg once daily.
Eradication of Helicobacter pylori: Pantoprazole may be combined with two antibacterials in a 1-week triple therapy regimen.
Effective regimens include pantoprazole 40 mg twice daily combined with clarithromycin 500 mg twice daily and either amoxicillin 1 g twice daily or metronidazole 400 mg twice daily.
Peptic Ulcer Disease: 40 mg once daily. Treatment is usually given for 2 to 4 weeks for duodenal ulceration, or 4 to 8 weeks for benign gastric ulceration.
Administration in Hepatic Impairment: Dosage may need to be reduced in severe hepatic impairment, or doses given only on alternate days. A maximum dose of 20 mg daily, or 40 mg on alternate days.
Administration in Renal Impairment: Maximum dose of 40 mg should be observed.
Pantor IV: The recommended dosage is one vial per day administered over 2 to 15 minutes.
Pantoprazole should be reconstituted with 10 mL of physiological sodium chloride solution into the vial containing the dry substance. The solution may be administered directly.
DIRECTION FOR USE: Dissolve the contents of the vial with given sterile Sodium Chloride Injection USP and use immediately. Use the ampoule only once and discard the ampoule.

Pantor-20/Pantor-40: Experience in patients taking very high doses of pantoprazole (>240 mg) is limited. Spontaneous post marketing 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.
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 hypo activity, ataxia, hunched sitting, limb-splay, lateral position, segregation, absence of ear reflex, and tremor.

Pantor-20/Pantor-40: Pantoprazole sodium is contraindicated in patients with known hypersensitivity to any component of the formulation or any substituted benzimidazole. Hypersensitivity reactions may include anaphylaxis, anaphylactic shock, angioedema, bronchospasm, acute interstitial nephritis, and urticaria.
Pantor IV: Pantoprazole should generally not be used in cases of known hypersensitivity to Pantoprazole.

Concurrent Gastric Malignancy: Symptomatic response to therapy with pantoprazole does not preclude the presence of gastric malignancy.
Before giving Pantoprazole or other proton pump inhibitors to patients with gastric ulcers the possibility of malignancy should be considered since these drugs may mask symptoms and delay diagnosis.
Hepatic impairment: Pantoprazole and other proton pump inhibitors should be used with caution in hepatic impairment.
Pantor-20/Pantor-40: Atrophic Gastritis: Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long term with pantoprazole, particularly in patients who were H. pylori positive.
Acute Interstitial Nephritis: Acute interstitial nephritis has been observed in patients taking PPIs including pantoprazole. Acute interstitial nephritis may occur at any point during PPI therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue pantoprazole if acute interstitial nephritis develops.
Cyanocobalamin (Vitamin B-12) Deficiency: Generally, daily treatment with any acid-suppressing medications over a long period of time (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (Vitamin B-12) caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed.
Clostridium difficile associated diarrhea: Published observational studies suggest that PPI therapy like pantoprazole may be associated with an increased risk of Clostridium difficile associated diarrhea, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated.
Bone Fracture: Several published observational studies suggest that proton pump inhibitor (PPI) therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high-dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to established treatment guidelines.
Hypomagnesemia: Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least three months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI.
For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically.
Tumorigenicity: Due to the chronic nature of GERD, there may be a potential for prolonged administration of pantoprazole. In long-term rodent studies, pantoprazole was carcinogenic and caused rare types of gastrointestinal tumors. The relevance of these findings to tumor development in humans is unknown.
Concomitant Use of Pantoprazole with Methotrexate: Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients.

Pantor-20/Pantor-40: 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.
Pantoprazole and its metabolites are excreted in the milk of rats. Pantoprazole excretion in human milk has been detected in a study of a single nursing mother after a single 40 mg oral dose. The clinical relevance of this finding is not known. Many drugs which are excreted in human milk have a potential for serious adverse reactions in nursing infants. Based on the potential for tumorigenicity shown for pantoprazole in rodent carcinogenicity studies, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the benefit of the drug to the mother.

Pantor-20/Pantor-40: The most frequently occurring adverse reactions for adults are headache, diarrhea, nausea, abdominal pain, vomiting, flatulence, dizziness and arthralgia.
Adverse reactions that were reported for pantoprazole in adults with a frequency of ≤2% are listed as follows 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.
All adult adverse reactions to pantoprazole 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.
Additional adverse reactions that were reported for pantoprazole in pediatric patients with a frequency of ≤4% are listed as follows 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 were not reported in pediatric patients, but are considered relevant to pediatric patients: photosensitivity reaction, dry mouth, hepatitis, thrombocytopenia, generalized edema, depression, pruritus, leukopenia, and blurred vision.
Pantor IV: Headache, diarrhea, and skin rashes: Other effects include pruritus, dizziness, fatigue, constipation, nausea and vomiting, flatulence, abdominal pain, arthralgia and myalgia, urticaria, and dry mouth. Isolated cases of photosensitivity, bullous eruption, erythema multiforme, angioedema, and anaphylaxis have been reported.
Effects on the CNS include occasional insomnia, somnolence, and vertigo; reversible confusional states, agitation, depression, and hallucination have occurred in severely ill patients raised liver enzymes, and isolated cases of hepatitis, jaundice, and hepatic encephalopathy, have been reported. Other adverse effects reported rarely or in isolated cases include paraesthesia, blurred vision, alopecia, stomatitis, sweating, taste disturbances, peripheral oedema, malaise, hyponatraemia, blood disorder (including agranulocytosis, leucopenia, and thrombocytopenia), and interstitial nephritis.
Proton pump inhibitors may increase the risk of gastrointestinal infections because of their acid suppressive effects.

Pantor-20/Pantor-40: Interference with Antiretroviral Therapy: Concomitant use of atazanavir or nelfinavir with proton pump inhibitors is not recommended. Coadministration of atazanavir or nelfinavir with proton pump inhibitors is expected to substantially decrease atazanavir or nelfinavir plasma concentrations and may result in a loss of therapeutic effect and development of drug resistance.
Coumarin Anticoagulants: There have been postmarketing reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including pantoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Patients treated with proton pump inhibitors and warfarin concomitantly should be monitored for increases in INR and prothrombin time.
Clopidogrel: Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition. No dose adjustment of clopidogrel is necessary when administered with an approved dose of pantoprazole.
Drugs for Which Gastric pH Can Affect Bioavailability: Due to its effects on gastric acid secretion, pantoprazole can reduce the absorption of drugs where gastric pH is an important determinant of their bioavailability. Like with other drugs that decrease the intragastric acidity, the absorption of drugs such as ketoconazole, ampicillin esters, atazanavir, iron salts, erlotinib, and mycophenolate mofetil (MMF) can decrease.
Co-administration of pantoprazole in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving pantoprazole and MMF. Use pantoprazole with caution in transplant patients receiving MMF.
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.
Methotrexate: Concomitant administration of PPIs and methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of Methotrexate with PPIs have been conducted.

Store at temperatures not exceeding 30°C.

Antacids, Antireflux Agents & Antiulcerants

A02BC02 - pantoprazole ; Belongs to the class of proton pump inhibitors. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).

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