RiteMED Pantoprazole

Each vial contains: Pantoprazole (as sodium sesquihydrate) 40 mg.
The powder dissolves completely, leaving no visible residue as undissolved matter.
The solvent is a clear colorless solution.

Pharmacology: Pharmacodynamics: Pantoprazole is a benzimidazole derivative that accumulates in the acidic environment of the parietal cells after absorption. It is then converted into the active form, a cyclic sulfenamide, which covalently binds to the (H+, K+)-ATPase enzyme system (proton pump) at the secretory surface of the gastric parietal cell. By acting specifically on the proton pump, pantoprazole blocks the final step in acid production, thus reducing gastric acidity. This effect is dose-dependent and leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus.
Pharmacokinetics: The onset of action of pantoprazole occurs within 15 to 30 minutes after a single dose of 20 to 120 mg IV and the duration of action is 24 hours.
Pantoprazole's apparent volume of distribution is 11 to 23.6 L. It is 98% bound to plasma proteins. Pantoprazole is extensively metabolized in the liver by the CYP450 enzyme system. The main metabolic pathway is demethylation by CYP2C19 with subsequent sulfation; other metabolic pathways include oxidation by CYP3A4.
The total plasma clearance of pantoprazole is approximately 7.6 to 14 L/h after a single dose. The plasma elimination half-life is approximately 1 hour. Almost 71% of the metabolites are excreted in the urine while the remaining 18% are excreted in the feces via biliary excretion.
Special Populations: Poor Metabolizers: Approximately 3% of the Caucasian population lack a functional CYP2C19 isoenzyme and are called poor metabolizers. In such individuals, the metabolism of pantoprazole is probably mainly catalyzed by CYP3A4. After a single dose of 40 mg pantoprazole, the mean area under the plasma concentration-time curve (AUC) was approximately 6 times higher in poor metabolizers than in patients having a functional CYP2C19 enzyme (extensive metabolizers). The mean C_max values were also increased by 60%.
Elderly: There is a slight increase in AUC (43%) and C_max (26%) in elderly patients (64-76 years of age). The half-life of pantoprazole in the elderly is approximately 1.25 hours.
Hepatic Impairment: The half-life of pantoprazole is prolonged between 7 to 9 hours. The AUC is 5 to 7 times higher in patients with liver cirrhosis compared with healthy patients while the C_max is 1.5 times higher.

Gastric ulcer.
Duodenal ulcer.
Moderate and severe reflux esophagitis.
Zollinger-Ellison Syndrome and other pathological hypersecretory conditions.
Treatment of bleeding peptic ulcer and prevention of re-bleeding.
Prophylaxis of acute bleeding stress ulcer.

Alternative to oral therapy: IV Pantoprazole is not indicated for mild gastrointestinal complaints such as nervous dyspepsia.
Pantoprazole should be administered IV over 2 to 15 minutes.
Pantoprazole should not be administered concomitantly with any other medications through the same IV line.
The IV line should always be flushed with either 0.9% sodium chloride solution or 5% dextrose solution before and after administration.
As soon as oral treatment is possible, IV administration of pantoprazole should be discontinued and the treatment should be continued orally.
Gastric and duodenal ulcer, moderate and severe reflux esophagitis: Recommended Dose: 40 mg per day.
For the management of reflux esophagitis, pantoprazole can be administered either by slow IV injection over 2 to 5 minutes, or by IV infusion over 15 minutes.
Zollinger-Ellison Syndrome and other pathological hypersecretory conditions: Recommended Initial Dose: 80 mg IV injection per day.
The dose and duration of treatment should be adjusted according to patient's response.
Daily doses above 80 mg should be administered in two divided doses.
Doses above 160 mg may be used temporarily but should not be administered longer than required for adequate acid control.
In case a rapid acid control is needed, a starting dose of 160 mg is sufficient to manage a decrease of acid output into the target range (<10 mEq/h) within one hour in the majority of patients.
Treatment of bleeding peptic ulcer and prevention of re-bleeding: Recommended Dose: 80 mg IV bolus followed by infusion of 8 mg/h for 3 days.
Prophylaxis of acute bleeding stress ulcer: Recommended Dose: 40 to 80 mg once or twice a day.
The solution may be given as a bolus for at least 2 minutes, or as an infusion for 15 minutes.
Dosage in Elderly: The daily dose should not exceed 40 mg.
Dosage in Patients with Hepatic Impairment: The daily dose should not exceed 20 mg in patients with severe hepatic impairment.
Dosage in Patients with Renal Impairment: The daily dose should not exceed 40 mg.

There is limited information on pantoprazole overdose. Daily doses of up to 272 mg I.V. and single doses of up to 240 mg I.V. administered over 2 minutes were well tolerated.
Pantoprazole is highly protein bound. Therefore, it is not readily dialyzable. If overdose occurs, symptomatic and supportive treatment should be given.

Patients who are hypersensitive to pantoprazole, other proton pump inhibitors (PPIs) or to any component of the product.
In combination treatment for eradication of H. pylori in patients with moderate to severe renal and hepatic impairment.
Patients who are receiving atazanavir.

Gastric Malignancy: Symptomatic response to therapy with pantoprazole does not preclude the presence of gastric malignancy or any alarm symptom (e.g., significant weight loss, recurrent vomiting, dysphagia, hematemesis, anemia, or melena). When gastric ulcer is suspected or present, malignancy should be excluded.
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. Pantoprazole should be discontinued if acute interstitial nephritis develops.
Clostridium difficile-Associated Diarrhea: Decreased gastric acidity due to any means, including PPIs, increases gastric counts of bacteria normally present in the gastrointestinal tract. Treatment with PPIs can lead to an increased risk of gastrointestinal infections such as Salmonella, Campylobacter, and Clostridium difficile.
PPI therapy, such as pantoprazole, may be associated with an increased risk of Clostridium difficile-associated diarrhea (CDAD), especially in hospitalized patients, the use of antibiotics, old age, and the presence of co-morbidities. This diagnosis should be considered for diarrhea that does not improve. Patients should use the lowest dose and the shortest duration of PPI therapy appropriate to the condition being treated.
Bone Fracture: 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: Symptomatic and asymptomatic hypomagnesemia 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), physicians may consider monitoring magnesium levels prior to initiation of PPI treatment and periodically.
Cyanocobalamin (Vitamin B₁₂) Deficiency: The prolonged use of PPIs (e.g., longer than 3 years) may lead to malabsorption of cyanocobalamin (Vitamin B12) caused by hypo- or achlorhydria and may contribute to the development of cyanocobalamin deficiency. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported.
Atrophic Gastritis: Atrophic gastritis has been noted occasionally in gastric corpus biopsies from patients treated long-term with pantoprazole, particularly in patients with H. pylori.
Respiratory Effects: Administration of PPIs has been associated with an increased risk of developing certain infections such as community-acquired pneumonia.
Subacute Cutaneous Lupus Erythematosus (SCLE): PPIs, such as pantoprazole, are associated with very infrequent cases of SCLE. If lesions occur, especially in sun-exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical help immediately. Discontinuation of pantoprazole treatment should be considered.
Hypersensitivity and Severe Skin Reactions: Anaphylaxis and other serious reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis (TEN) have been reported with the use of IV pantoprazole. An emergency medical treatment may be required.
Effects on Ability to Drive and Use Machine: Pantoprazole causes headache, dizziness, and visual disturbances. Patients should be cautioned against engaging in activities requiring alertness such as operating machinery or driving a car.
Hepatic Impairment: The liver enzymes of patients with severe hepatic impairment should be monitored during pantoprazole treatment, particularly on long-term use. If the liver enzymes increased, the treatment should be discontinued.
Dose reduction should be considered in patients with severe hepatic impairment. Daily doses higher than 40 mg/day have not been studied.
Renal Impairment: The recommended dose should not be exceeded in patients with renal impairment.
Use in Children: The safety and efficacy of pantoprazole in pediatric patients 1 to 16 years of age have been established for short-term treatment of erosive esophagitis associated with GERD. However, the efficacy of pantoprazole in pediatric patients less than 1 year of age has not been established.
Use in the Elderly: No significant differences in safety and efficacy were observed between the elderly and younger individuals.
Benefits of pantoprazole treatment should be weighed against the increased risk of fractures as patients in this group may already be at high risk for osteoporosis-related fractures. If pantoprazole treatment is required, patients should be carefully managed according to established treatment guidelines.

Pregnancy: Pregnancy Category B. There are no adequate and well-controlled studies in pregnant women. Pantoprazole should only be used in pregnant women or women suspected of being pregnant if the potential benefits outweigh the potential risks of treatment.
Lactation: Pantoprazole is distributed in human milk. A decision should be made whether to discontinue breastfeeding or to discontinue pantoprazole, taking into account the importance of the drug to the woman.

The most frequently reported adverse effects with pantoprazole include headache, diarrhea, flatulence, abdominal pain, nausea, constipation, dyspepsia, insomnia, vomiting, and dizziness.
Infections and infestations: Clostridium difficile-associated diarrhea, sepsis, viral infection.
Neoplasms benign, malignant and unspecified (including cysts and polyps): Neoplasm.
Blood and lymphatic system disorders: Agranulocytosis, eosinophilia, leukopenia, pancytopenia, thrombocytopenia.
Immune system disorders: Anaphylactic reaction/shock, angioedema.
Metabolism and nutrition disorders: Decreased appetite, facial edema, generalized edema, hyperglycemia, hyperkalemia, hyperlipidemia, hypernatremia, hypertriglyceridemia, hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia, peripheral edema.
Psychiatric disorders: Confusion, depression, disorientation, hallucinations, nervousness, sleep disorders.
Nervous system disorders: Dysgeusia, hypokinesia, migraine, paresthesia, somnolence, speech disorder, taste loss, tremor.
Eye disorders: Anterior ischemic optic neuropathy, blurred vision.
Ear and labyrinth disorders: Tinnitus, vertigo.
Cardiac disorders: Chest pain, myocardial infarction, tachycardia.
Vascular disorders: Hemorrhoids, hypertension, thrombophlebitis (IV only).
Respiratory, thoracic and mediastinal disorders: Bronchitis, cough, dyspnea, nasal congestion, nasopharyngitis, pharyngitis, pneumonia, rhinitis, sinusitis, tonsillitis, upper respiratory tract infection.
Gastrointestinal disorders: Abdominal discomfort, abdominal distension, abdominal tenderness, dry mouth, eructation, esophagitis, gastric polyps, gastroenteritis, gastroesophageal reflux, increased salivation, pancreatitis, rectal hemorrhage, stomatitis, toothache.
Hepatobiliary disorders: Cholelithiasis, hepatitis, hepatocellular failure, hepatocellular injury, increased bilirubin, increased liver enzymes, jaundice.
Skin and subcutaneous tissue disorders: Acne, alopecia, eczema, erythema multiforme, exfoliative dermatitis, photosensitivity, pruritus, rash, Stevens-Johnson syndrome, subacute cutaneous lupus erythematosus, toxic epidermal necrolysis (Lyell syndrome), urticaria.
Musculoskeletal and connective tissue disorders: Arthralgia, arthritis, back pain, bone fracture, fracture of the hip, wrist, or spine, muscle spasms, myalgia, muscle twitching, neck pain, osteoarthritis, osteoporosis, pain in limb, rhabdomyolysis, tendonitis.
Renal and urinary disorders: Cystitis, hematuria, interstitial nephritis, urinary tract infection.
Reproductive system and breast disorders: Decreased libido, gynecomastia, impotence.
General disorders and administration site conditions: Asthenia, fatigue, fever, flu-like disorder, increased body temperature, increased sweating, inflammation, malaise, pain.
Investigations: Abnormal ECG, abnormal liver function tests, increased alanine aminotransferase, increased aspartate aminotransferase, increased blood triglycerides, increased body temperature, increased creatinine kinase, increased transaminases, weight gain/loss.
Injury, poisoning and procedural complications: Contusion.

Antiretroviral Drugs: Concomitant use of atazanavir, nelfinavir, rilpivirine, saquinavir or raltegravir with PPIs is not recommended. Pantoprazole is expected to substantially decrease atazanavir, nelfinavir or rilpivirine plasma concentrations and may result in a loss of therapeutic effect and the development of drug resistance. In contrast, coadministration of saquinavir or raltegravir with PPIs is expected to increase saquinavir or raltegravir concentrations, which may increase toxicity and require dose reduction.
pH-dependent Drugs: Pantoprazole can reduce the absorption of drugs where gastric pH is an important determinant of their bioavailability. As with other drugs that decrease intragastric acidity, the absorption of drugs such as ketoconazole, ampicillin esters, atazanavir, iron salts, erlotinib, and mycophenolate mofetil (MMF) may decrease.
Mycophenolate mofetil (MMF): Coadministration of pantoprazole in healthy patients 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 in organ rejection has not been established in transplant patients receiving pantoprazole and MMF.
Drugs Affecting/Metabolized by Hepatic Microsomal Enzymes: Pantoprazole is metabolized in the liver through CYP2C19 and CYP3A4. Drugs known to inhibit CYP2C19 such as fluvoxamine may increase the plasma concentrations of pantoprazole by decreasing the rate of its metabolism. In contrast, drugs known to induce CYP2C19 or CYP3A4 or both (e.g., rifampicin and St. John's Wort) may decrease the plasma concentrations of pantoprazole by increasing the rate of its metabolism.
Warfarin: Increased international normalized ratio (INR) and prothrombin time have been reported in patients receiving PPIs and warfarin concomitantly. Since such increases may lead to abnormal bleeding and even death, patients treated with PPIs and warfarin should be monitored for increases in INR and prothrombin time.
Clopidogrel: Concomitant use of pantoprazole with clopidogrel may reduce exposure to the active metabolite of clopidogrel and decrease platelet inhibitory effects.
Drugs that Cause Hypomagnesemia: Possible increased risk of hypomagnesemia; 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., loop or thiazide diuretics), physicians may consider monitoring the magnesium levels prior to initiation of PPI treatment and periodically thereafter.
Methotrexate: Concomitant administration of PPIs and methotrexate, primarily at high doses, may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate which may lead to methotrexate toxicity. In high-dose methotrexate administration, a temporary withdrawal of the PPI may be considered in some patients.
Sucralfate: Concomitant administration of pantoprazole with sucralfate resulted in delayed absorption and decreased bioavailability of pantoprazole. It should be administered at least 30 minutes before sucralfate.
Laboratory Interactions: There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs such as pantoprazole. An alternative confirmatory method should be considered to verify positive results.

Preparation of the Dosage Form: For IV Injection: A ready-to-use solution is prepared by injecting 10 mL of 0.9% sodium chloride solution into the vial containing the powder.
For IV Infusion: Pantoprazole should be reconstituted with 10 mL of 0.9% sodium chloride solution and further diluted with 100 mL of 5% dextrose solution or 100 mL of 0.9% sodium chloride solution.
Pantoprazole should not be prepared or mixed with solvents other than those stated.
Stability: The reconstituted solution should be used immediately. If not, it can be stored for up to a maximum of 3 hours at temperatures not exceeding 25°C.

Store at temperatures not exceeding 30°C.
Store in a cool dry place.
Protect from light.
In case that reconstituted pantoprazole is not used immediately, it can be stored for up to a maximum of 3 hours at temperatures not exceeding 25°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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