Pantokem/Pantokem IV

Pantokem: Pantoprazole sodium sesquihydrate.
Pantokem IV: Pantoprazole sodium.

Pantokem: Each enteric-coated tablet contains: Pantoprazole (as Sodium sesquihydrate) USP equivalent to Pantoprazole 40 mg.
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 molecular formula is C16H14F2N3NaO4S x 1.5 H2O, with a molecular weight of 432.4.
Pantoprazole sodium sesquihydrate, USP is a white to off-white crystalline powder and is racemic. Pantoprazole has weakly basic and acidic properties. Pantoprazole sodium is supplied as a delayed-release tablet available in 40 mg strength.
Pantokem IV: Each vial contains: Pantoprazole Sodium Eq. to Pantoprazole 40 mg.

Pharmacotherapeutic Group: Proton Pump Inhibitors. ATC Code: A02BC02.
Pharmacology: Pharmacodynamics: Mechanism of Action: Pantokem: Pantoprazole is a proton-pump inhibitor (PPI) that suppresses the final step in gastric acid production by forming a covalent bond to 2 sites of the (H+, K+)-ATPase enzyme system at the secretory surface of the gastric parietal cell. This effect is dose-related and 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 hrs.
Pantokem IV: Pantoprazole is a substituted benzimidazole which inhibits the secretion of hydrochloric acid in the stomach by specific blockade of the proton pumps of the parietal cells.
Pantoprazole is converted to its active form in the acidic environment in the parietal cells where it inhibits the H+/K+-ATPase enzyme i.e. the final stage in the production of hydrochloric acid in the stomach. The inhibition is dose-dependent and affects both basal and stimulated acid secretion. In most patients, freedom from symptoms is achieved within 2 weeks. As with other proton pump inhibitors and H2 receptor inhibitors, treatment with pantoprazole reduces acidity in the stomach and thereby increases gastrin in proportion to the reduction in acidity. The increase in gastrin is reversible.
Since pantoprazole binds to the enzyme distal to the cell receptor level, it can inhibit hydrochloric acid secretion independently of stimulation by other substances (acetylcholine, histamine, gastrin). The effect is the same whether the product is given orally or intravenously.
The fasting gastrin values increase under pantoprazole. On short-term use, in most cases they do not exceed the upper limit of normal. During long term treatment, gastrin levels double in most cases. An excessive increase, however, occurs only in isolated cases. As a result, a mild to moderate increase in the number of specific endocrine (ECL) cells in the stomach is observed in a minority of cases during long-term treatment (similar to adenomatoid hyperplasia). However, according to the studies conducted so far, the formation of carcinoid precursors (atypical hyperplasia) or gastric carcinoids as were found in animal experiments have not been observed in humans.
An influence of a long term treatment with pantoprazole exceeding one year cannot be completely ruled out on endocrine parameters of the thyroid according to results in animal studies.
During treatment with antisecretory medicinal products, serum gastrin increases in response to the decreased acid secretion. Also CgA increases due to decreased gastric acidity. The increased CgA level may interfere with investigations for neuroendocrine tumours.
Available published evidence suggests that proton pump inhibitors should be discontinued between 5 days and 2 weeks prior to CgA measurements.
This is to allow CgA levels that might be spuriously elevated following PPI treatment to return to reference range.
Pharmacokinetics: Pantokem: Pantoprazole is rapidly absorbed and peak plasma pantoprazole concentrations are achieved about 2 to 2.5 hours after an oral dose. The oral bioavailability is about 77% with the enteric-coated tablet formulation, and does not vary after single or multiple doses. Pantoprazole is about 98% bound to plasma proteins. It is extensively metabolised in the liver, primarily by the cytochrome P450 isoenzyme CYP2C19, to desmethylpantoprazole; small amounts are also metabolised by CYP3A4, CYP2D6, and CYP2C9. Metabolites are excreted mainly (about 80%) in the urine, with the remainder being excreted in faeces via the 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. Although the elimination half-life has been reported to be 3.5 to 10 hours in slow metabolisers, minimal accumulation occurs with once-daily dosing.
Pantokem 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.

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

Pantokem: Erosive Esophagitis: Adults: Recommended Dose: 40 mg once daily for up to 8 weeks. For those patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole may be considered.
Peptic Ulcer Disease: 40 mg once daily. Treatment is usually given for 2-4 weeks for duodenal ulcer, or 4-8 weeks for benign gastric ulcer.
Helicobacter pylori Eradication: Pantoprazole may be combined with 2 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.
Pantokem 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. The recommended solution must be used within 24 hours of preparation. Or as directed by the physician.

Pantokem: Experience in patients taking very high doses of pantoprazole sodium delayed-release (>240 mg) is limited.
Spontaneous post-marketing reports of overdose are generally within the known safety profile of pantoprazole sodium delayed-release tablets. Pantoprazole is not removed by hemodialysis. In case of overdosage, treatment should be symptomatic and supportive.
Pantokem IV: There are no known symptoms of over dosage in man.
Systemic exposure with up to 240 mg administered intravenously over 2 minutes were well tolerated. As pantoprazole is extensively protein bound, it is not readily dialysable.
In the case of overdose with clinical signs of intoxication, apart from symptomatic and supportive treatment, no specific therapeutic recommendations can be made.

Pantokem: Known hypersensitivity to any component of Pantoprazole tablets.
Pantokem IV: Pantoprazole should generally not be used in cases of known hypersensitivity of pantoprazole.

Pantokem: Symptomatic response does not preclude gastric malignancy; not indicated for maintenance therapy. Safety and efficacy for use beyond 16 weeks have not been established.
Use in Pregnancy: See Use in Pregnancy & Lactation section for further information.
Use in Children: Pantoprazole is not recommended for use in children <12 years. Safety and efficacy in pediatric patients have not been established.
Pantokem IV: In presence of alarm symptoms: In the presence of any alarm symptom (e. g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis, anaemia or melaena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with pantoprazole may alleviate symptoms and delay diagnosis.
Further investigation is to be considered if symptoms persist despite adequate treatment.
Hepatic impairment: In patients with severe liver impairment, the liver enzymes should be monitored during therapy. In the case of a rise in the liver enzymes, the treatment should be discontinued.
Co-administration with atazanavir: Co-administration of atazanavir with proton pump inhibitors is not recommended. If the combination of atazanavir with a proton pump inhibitor is judged unavoidable, close clinical monitoring (e.g. virus load) is recommended in combination with an increase in the dose of atazanavir to 400 mg with 100 mg of ritonavir.
A pantoprazole dose of 20 mg per day should not be exceeded.
Gastrointestinal infections caused by bacteria: Pantoprazole, like all proton pump inhibitors (PPIs), might be expected to increase the counts of bacteria normally present in the upper gastrointestinal tract. Treatment with pantoprazole may lead to a slightly increased risk of gastrointestinal infections caused by bacteria (e.g. Salmonella and Campylobacter and C. difficile).
Subacute cutaneous lupus erythematosus (SCLE): Proton pump inhibitors 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 promptly and the health care professional should consider stopping Pantoprazole.
SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.
Interference with laboratory tests: Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. To avoid this interference, treatment should best topped for at least 5 days before CgA measurements. If CgA and gastrin levels have not returned to reference range after initial measurement, measurements should be repeated 14 days after cessation of proton pump inhibitor treatment.
Sodium: This medicinal product contains less than 1 mmol (23 mg) sodium per dose, i.e. essentially "sodium-free".
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. Pantoprazole and other proton pump inhibitors should be used with caution in hepatic impairment.

Pregnancy: Pantokem: Either animal-reproduction studies have not demonstrated a foetal risk but there are no controlled studies in pregnant women or animal-reproduction studies have shown an adverse effect (other than a decrease in fertility) that was not confirmed in controlled studies in women in the 1st trimester (and there is no evidence of a risk in later trimesters).
Pantokem IV: There are no adequate data from the use of pantoprazole in pregnant women. Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown. Pantoprazole 40 mg should not be used during pregnancy unless clearly necessary.
Breast-feeding: Pantokem IV: Animal studies have shown excretion of pantoprazole in breast milk. Excretion into human milk has been reported. Therefore, a decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Pantoprazole 40 mg should be made taking into account the benefit of breastfeeding to the child and the benefit of Pantoprazole 40 mg therapy to women.

Effects on the CNS include occasional insomnia, somnolence, and vertigo; reversible confusional states, agitation, depression, and hallucinations have occurred in severely ill patients. Raised liver enzymes, and isolated cases of hepatitis, jaundice, hepatic failure, and hepatic encephalopathy, have been reported. Other adverse effects reported rarely include paraesthesia, blurred vision, alopecia, stomatitis, increased sweating, taste disturbances, peripheral oedema, malaise, hyponatraemia, blood disorders (including agranulocytosis, leucopenia, and thrombocytopenia), gynaecomastia (for Pantokem only), impotence (for Pantokem only) and interstitial nephritis. Proton pump inhibitors may increase the risk of gastrointestinal infections because of their acid suppressive effects.
Pantokem: Proton pump inhibitors are generally well tolerated, and adverse effects are relatively infrequent. The adverse effects reported most often with omeprazole and other proton pump inhibitors have been headache, diarrhoea, and skin rashes; they have sometimes been severe enough to require stopping treatment. 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, Stevens-Johnson syndrome, and toxic epidermal necrolysis have occurred. Hypersensitivity reactions, including fever, bronchospasm, angioedema, and anaphylaxis have been reported
Pantokem 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.

Pantokem: Phenazone (antipyrine), diazepam, digoxin, theophylline, carbamazepine, diclofenac, phenprocoumon, phenytoin, warfarin, nifedipine, caffeine, metoprolol or ethanol: No clinically relevant interaction at therapeutic doses.
Oral Contraceptives: Pantoprazole does not appear to compromise hormonal contraceptive efficacy as no interaction with low dose combined oral contraceptive has been seen.
Pantokem IV: Effect of pantoprazole on the absorption of other medicinal products: Because of profound and long lasting inhibition of gastric acid secretion, pantoprazole may reduce the absorption of drugs with a gastric pH dependent bioavailability, e.g. some azole antifungals as ketoconazole, itraconazole, posaconazole and other medicine as erlotinib.
HIV protease inhibitors (atazanavir): Co-administration of atazanavir and other HIV medications whose absorption is pH-dependent with proton-pump inhibitors might result in a substantial reduction in the bioavailability of these HIV medications and might impact the efficacy of these medicines. Therefore, the coadministration of proton pump inhibitors with atazanavir is not recommended.
Coumarin anticoagulants (phenprocoumon or warfarin): Although no interaction during concomitant administration of phenprocoumon or warfarin has been observed in clinical pharmacokinetic studies, a few isolated cases of changes in International Normalised Ratio (INR) have been reported during concomitant treatment in the post-marketing period. Therefore, in patients treated with coumarin anticoagulants (e.g. phenprocoumon or warfarin), monitoring of prothrombin time / INR is recommended after initiation, termination or during irregular use of pantoprazole.
Methotrexate: Concomitant use of high dose methotrexate (e.g. 300 mg) and proton-pump inhibitors has been reported to increase methotrexate levels in some patients. Therefore, in settings where high-dose methotrexate is used, for example cancer and psoriasis, a temporary withdrawal of pantoprazole may need to be considered.
Other interactions studies: Pantoprazole is extensively metabolized in the liver via the cytochrome P450 enzyme system. The main metabolic pathway is demethylation by CYP2C19 and other metabolic pathways include oxidation by CYP3A4.
Interaction studies with drugs also metabolized with these pathways, like carbamazepine, diazepam, glibenclamide, nifedipine, and an oral contraceptive containing levonorgestrel and ethinyl oestradiol did not reveal clinically significant interactions.
Results from a range of interaction studies demonstrate that pantoprazole does not effect the metabolism of active substances metabolised by CYP1A2 (such as caffeine, theophylline), CYP2C9 (such as piroxicam, diclofenac, naproxen), CYP2D6 (such as metoprolol), CYP2E1 (such as ethanol) or does not interfere with p-glycoprotein related absorption of digoxin.
There were no interactions with concomitantly administered antacids.
Interaction studies have also been performed administering pantoprazole concomitantly with the respective antibiotics (clarithromycin, metronidazole, amoxicillin). No clinically relevant interactions were found.

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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