Pantovaz

Each Enteric-Coated Tablet contains Pantoprazole (as sodium sesquihydrate), USP 40 mg.
The active ingredient in Pantoprazole sodium sesquihydrate for delayed-release tablet is substituted benzimidazole, sodium 5-(difluromethoxy)-2[[3,5-dimethoxy-2 pyridinyl) methyl]methyl] sulfinyl] 1H-benzimidazole sesquihydrate, a compound that inhibits gastric acid secretion. Its empirical formula is C₁₆H₁₄F₂N₃NaO₄S x 1.5 H₂O, with a molecular weight of 432.4. Pantoprazole sodium sesquihydrate is a white to off-white crystalline powder and is racemic. Pantoprazole has weekly basic and acidic properties. Pantoprazole sodium as sesquihydrate is freely soluble in water, very slightly soluble in phosphate buffer at pH 7.4, and practically insoluble in n-hexane.
Pantoprazole sodium sesquihydrate is proton pump inhibitor. It inhibits secretion of gastric acid by irreversibly blocking the enzyme system of hydrogen/potassium adenosine triphosphate (H+/K+-ATPase), the "proton pump" of the gastric parietal cell. It is used in conditions where inhibition of the gastric acid secretion may be beneficial, including aspiration syndromes, dyspepsia, gastro-esophageal reflux disease, peptic ulcer disease and the Zollinger-Ellison syndrome.

Pharmacology: Pharmacodynamics: Mechanism of Action: Pantoprazole sodium sesquihydrate is a specific inhibitor of the gastric H+, K+-ATPase enzyme (the proton pump) that is responsible for gastric acid secretion by the parietal cells of the stomach. Pantoprazole is a substituted benzimidazole that accumulates in the acidic environment of the parietal cells after absorption. Pantoprazole is then converted into the active form, a cyclic sulphenamide, which binds selectively to the proton translocating region of the H+, K+-ATPase, thus inhibiting both the basal and stimulated gastric acid secretion. Pantoprazole exerts its effect in an acidic environment (pH < 3), and it is mostly inactive at higher pH. Its pharmacological and therapeutic effect is achieved in the acid-secretory parietal cells. As pantoprazole action is distal to the receptor levels, it can inhibit gastric acid secretion irrespective of the nature of the stimulus (acetylcholine, histamine, and gastrin).
In clinical studies investigating intravenous (i.v.) and oral administration, pantoprazole sodium inhibited pentagastrin stimulated gastric acid secretion. With a daily oral dose of 40 mg, inhibition was 51% on Day 1 and 85% on Day 7. Basal 24-hour acidity was reduced by 37% and 98% on Days 1 and 7, respectively.
Pharmacokinetics: Pantoprazole sodium sesquihydrate is rapidly variably absorbed following oral administration. Absorption is not affected by food. Pantoprazole is acid-labile and pharmacokinetics may vary between the various formulations developed to improve oral bioavailability. The absorption pantoprazole sodium as sesquihydrate also appears to be dose-dependent: increasing the dosage above 40 mg has been reported to increase the plasma concentrations in a non-linear fashion because of saturable first-pass hepatic metabolism. In addition, absorption is higher after a long-term administration. Bioavailability of Pantoprazole sodium sesquihydrate may be increased in elderly patients, in some ethnic groups such as Chinese, and in patients with impaired hepatic function, but is not markedly affected in patients with renal impairment.
Following absorption Pantoprazole sodium sesquihydrate is almost completely metabolized in the liver, primarily by the cytochrome P450 isoenzyme CYP2C19, to des-methylpantoprazole; small amounts are also metabolized by CY3A4, CYP2D6, and CYP2C9. Metabolites are excreted mainly (about 80%) in the urine, with the remainder being excreted in bile. The terminal elimination half-life is about 1 hour, and is prolonged in hepatic impairment: the half-life in patients with cirrhosis was 3 to 6 hours.

Pantoprazole sodium sesquihydrate is used in conditions where inhibition of gastric acid secretion may be beneficial, including syndromes, dyspepsia, gastro-esophageal reflux disease, peptic ulcer disease, and the Zollinger-Ellison syndrome.

Pantovaz is formulated as an enteric-coated tablet. A whole tablet should not be chewed or crushed, and should be swallowed with fluid in the morning either before, during, or after breakfast.
Gastro-esophageal reflux disease: 20 mg to 40 mg once daily for 4 weeks or as prescribed by the physician.
Dyspepsia: 10 mg to 20 mg for 2 to 4 weeks or as prescribed by the physician.
Peptic Ulcer Disease: 20 mg daily as single dose, or 40 mg in severe cases or as prescribed by the physician.
NSAID-associated ulceration: 20 mg daily or as prescribed by the physician.
Zollinger-Ellison syndrome: 40 mg once daily or as prescribed by the physician.
Acid aspiration prophylaxis during general anesthesia: 40 mg in the evening before surgery and a further 40 mg two to six hours before the procedure or as prescribed by the physician.

Some reports of overdosage with pantoprazole have been received. No consistent symptom profile was observed after ingestion of high doses of pantoprazole. Daily doses of up to 272 mg pantoprazole i.v., and single doses of up to 240 mg i.v. administered over 2 minutes, have been administered and were well tolerated. As pantoprazole is extensively protein bound, it is not readily dialyzable. In the case of overdosage with clinical signs of intoxication, apart from symptomatic and supportive treatment, no specific therapeutic recommendations can be made.

Patients who are hypersensitive to pantoprazole, substituted benzimidazoles, or to any ingredient in the formulation. Co-administration with rilpivirine is contraindicated.

Before giving Pantoprazole sodium sesquihydrate to patients with gastric ulcers the possibility of malignancy should be considered since these drugs may mask symptoms and delay diagnosis. It should also be used with caution in hepatic impairment.
Antibiotic Combination Therapy: Pseudomembranous colitis has been reported with nearly all antibacterial agents, including clarithromycin and amoxicillin, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.
Clostridium Difficile-Associated Diarrhea: Decreased gastric acidity due to any means, including proton pump inhibitors (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. An increased risk for Clostridium difficile infection (CDI) and Clostridium difficile associated diarrhea (CDAD) has been observed in association with PPI use in several observational studies. CDI/CDAD should be considered in the differential diagnosis for diarrhea that does not improve.
Concomitant Use 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. A temporary withdrawal of the PPI may be considered in some patients receiving treatments with high dose methotrexate.
Bone Fracture: Several published observational studies suggest that 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.
Carcinogenesis and Mutagenesis: Effects of long-term treatment include hypergastrinemia, possible enterochromaffin-like (ECL) cell hyperplasia and carcinoid formation in the stomach, adenomas and carcinomas in the liver and neoplastic changes in the thyroid.

Clinical experience in pregnant women is limited. In animal reproduction studies. Signs of slight fetotoxicity were observed at doses above 5mg/kg. There is no information on the excretion of Pantoprazole into human breast milk. Pantoprazole tablets should only be used when the benefit to the mother is considered greater than the potential risk to the fetus/baby.

Adverse effects reported most frequently with Pantoprazole sodium sesquihydrate have been headache, diarrhea and skin rashes: they have sometimes been severe enough to require discontinuation of treatment. Other effects include pruritus, fatigue, constipation, nausea and vomiting, flatulence, abdominal pain, arthralgia and myalgia, urticaria and dry mouth. Pantoprazole sodium sesquihydrate may also increase the risk of gastrointestinal infections because of their acid suppressive effects.

Pantoprazole sodium does not interact with carbamazepine, caffeine, diclofenac, naproxen, piroxicam, ethanol, glibenclamide, metoprolol, antipyrine, diazepam, phenytoin, nifedipine, theophylline, digoxin, oral contraceptives containing (levonorgestrel and ethinyl oestradiol), or cyclosporine. Concomitant use of antacids does not affect the pharmacokinetics of pantoprazole sodium.
In a preclinical study, pantoprazole sodium in combination therapy with various antibiotics (including tetracycline, clarithromycin, and amoxicillin) was shown to have a potentiating effect on the elimination rate of Helicobacter pylori infection.
Although no interaction during concomitant administration of warfarin has been observed in clinical pharmacokinetic studies, a few isolated cases of changes in INR have been reported during concomitant treatment in the post-marketing period. Therefore, in patients being treated with coumarin anticoagulants, monitoring of prothrombin time/INR is recommended after initiation, termination or during irregular use of pantoprazole.
Co-administration of pantoprazole is not recommended with HIV protease inhibitors for which absorption is dependent on acidic intragastric pH such as atazanavir due to significant reduction in their bioavailability.

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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