Pantoprazole BEXIMCO 20 mg Gastro-Resistant Tablet: Each tablet contains Pantoprazole Sodium Sesquihydrate Ph Eur equivalent to Pantoprazole 20 mg.
Length: 9.0mm ± 2mm; Width: 4.8mm ± 2mm.
Pantoprazole BEXIMCO 40 mg Gastro-Resistant Tablet: Each tablet contains Pantoprazole Sodium Sesquihydrate Ph Eur equivalent to Pantoprazole 40 mg.
Length: 11.9mm ± 2mm; Width: 6.0mm ± 2mm.
Pharmacology: Pharmacodynamics: 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 (simple to adenomatoid hyperplasia). However, so far, the formation of carcinoid precursors (atypical hyperplasia) or gastric carcinoids 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.
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: Pantoprazole is rapidly absorbed and the maximal plasma concentration is achieved even after one single 20 mg oral dose. On average at about 2.0 h - 2.5 h p.a. the maximum serum concentrations of about 1-1.5 μg/ml are achieved, and these values remain constant after multiple administration. Volume of distribution is about 0.15 l/kg and clearance is about 0.1 l/h/kg. Terminal half-life is about 1 h. There were a few cases of subjects with delayed elimination. Because of the specific binding of Pantoprazole to the proton pumps of the parietal cell the elimination half-life does not correlate with the much longer duration of action (inhibition of acid secretion).
Pharmacokinetics do not vary after single or repeated administration. In the dose range of 10 to 80 mg, the plasma kinetics of Pantoprazole are linear after both oral and intravenous administration.
Pantoprazole's serum protein binding is about 98%. The substance is almost exclusively metabolized in the liver. Renal elimination represents the major route of excretion (about 80%) for the metabolites of Pantoprazole, the rest is excreted with the faeces. The main metabolite in both the serum and urine is desmethylpantoprazole which is conjugated with sulphate. The half-life of the main metabolite (about 1.5 h) is not much longer than that of Pantoprazole.
20 mg Tablet: Treatment of mild reflux disease and associated symptoms (eg, heartburn, acid regurgitation, pain on swallowing); long-term management and prevention of relapse in reflux esophagitis; prevention of gastroduodenal ulcers induced by nonselective, nonsteroidal anti-inflammatory drugs (NSAIDs), in patients at risk with a need for a continuous NSAID treatment.
40 mg Tablet: In combination with 2 appropriate antibiotics for the eradication of Helicobacter pylori in patients with peptic ulcers to reduce recurrence of duodenal and gastric ulcers caused by the microorganism; duodenal and gastric ulcers; moderate and severe cases of inflammation of the esophagus (reflux esophagitis); Zollinger-Ellison syndrome and other pathological hypersecretory conditions.
20 mg Tablet: Adults and Adolescents ≥12 years: Mild Reflux Disease and Associated Symptoms (eg. heartburn, acid regurgitation, pain on swallowing): Recommended Oral Dose: One 20 mg tablet per day.
Type and Duration of Treatment: Symptom relief is generally accomplished within 2-4 weeks, and a 4-week treatment period is usually required for healing of associated esophagitis. If this is not sufficient, healing is usually achieved within a further 4 weeks. When symptom relief has been achieved, reoccurring symptoms can be controlled using an on-demand regimen of 20 mg once daily, when required. A switch to continuous therapy may be considered in case satisfactory symptom control cannot be maintained with on-demand treatment.
Long-Term Management and Prevention of Relapse in Reflux Oesophagitis: Long-term Management: Maintenance dose: One 20-mg tablet per day is recommended. Increase to 40 mg Pantoprazole per day if a relapse occurs. For this case, 40 mg Pantoprazole tablet is available. After healing of the relapse, the dosage can be reduced back to 20 mg Pantoprazole.
Type and Duration of Treatment: Long-Term Treatment: A treatment period of 1 year should be exceeded only after careful consideration of the benefit/risk ratio, as drug safety over several years is not sufficiently established.
Adults: Prevention of Gastroduodenal Ulcers Induced by NSAIDs in Patients at Risk with a Need for Continuous NSAID Treatment: Recommended Dose: One 20-mg tablet per day.
Children below 12 years of age: Not recommended for use in children below 12 years of age due to limited data in this age group.
A daily dose of 20-mg Pantoprazole should not be exceeded in patients with severe liver impairment. No dose adjustment is necessary in elderly patients or in those with impaired renal function.
40 mg Tablet: Adults and Adolescents ≥ 12 years: Treatment of Moderate and Severe Reflux Esophagitis: One 40 mg tablet per day. In individual cases, the dose may be doubled (increased to two 40 mg tablet daily) especially when there has been no response to other medicines.
Adults: Eradication of H. pylori in Combination with 2 Appropriate Antibiotics: In cases of duodenal or gastric ulcer in which infection with Helicobacter pylori has been confirmed, the microorganism should be eradicated by combination treatment.
Depending upon the resistance pattern, the following combinations can be recommended: One 40 mg tablet twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily; one 40 mg tablet twice daily + metronidazole 500 mg twice daily + clarithromycin 500 mg twice daily; one 40 mg tablet twice daily + amoxicillin 1000 mg twice daily + metronidazole 500 mg twice daily.
Duodenal and Gastric Ulcers: One 40 mg tablet daily. In individual cases, the dose may be doubled (increased to two 40 mg tablet daily) especially when there has been no response to other medicines.
Long-Term Management of Zollinger-Ellison Syndrome and Other Pathological Hypersecretory Conditions: The recommended daily dose at the beginning of treatment is 80 mg (two 40 mg tablet). Thereafter, the dosage can be titrated up or down as needed using measurements of gastric acid secretion to guide. Doses >80 mg daily should be divided and given twice daily. A temporary increase in dosage to >160 mg Pantoprazole is possible but should not be applied longer than required for adequate acid control. Treatment duration in Zollinger-Ellison-Syndrome and other pathological hypersecretory conditions is not limited and should be adapted according to clinical needs.
Type and Duration of Treatment: Combination therapy for eradication of Helicobacter pylori infection usually lasts 7 days and can be extended to a maximum of 2 weeks. If after this time, further treatment with Pantoprazole 40 mg is indicated to ensure complete healing of ulcers, dose recommendations for gastric and duodenal ulcers must be observed. In majority of cases, duodenal ulcer heals completely within 2 weeks. If a 2-week treatment period is not sufficient, healing will be achieved in almost all cases within a further 2 weeks. Gastric ulcers and reflux oesophagitis usually require a 4-week course of treatment. If this should be inadequate, healing will be achieved within a further 4 weeks in most cases.
Treatment should not exceed 8 weeks as experience with long-term use is limited.
Treatment duration in Zollinger-Ellison Syndrome and other pathological hypersecretory conditions is not limited and should be adapted according to clinical needs.
Administration: Oral. Should be taken on an empty stomach. Take 1 hr before meals. Swallow whole, do not chew/crush.
There are no known symptoms of overdosage in man. Doses up to 240 mg i.v. were administered over 2 minutes and were well tolerated. As Pantoprazole is extensively protein bound, it is not readily dialysable.
Cases of overdosage or poisoning should be treated according to the standard treatment practice of toxic conditions.
Pantoprazole must not be used in combination treatment for eradication of Helicobacter pylori in patients with moderate to severe hepatic or renal dysfunction since currently no data are available on the efficacy and safety of Pantoprazole in combination treatment of these patients. It should not be used in patients with known hypersensitivity to Pantoprazole or of the combination partners. Pantoprazole, like other PPIs, should not be co-administered with atazanavir.
Pantoprazole is not indicated for mild gastrointestinal complaints eg, nervous stomach. In the case of combination therapy, the prescribing information for the respective drugs should be observed. In the presence of any alarm symptom (eg 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. In patients with Zollinger-Ellison-Syndrome and other pathological hypersecretory conditions requiring long-term treatment, Pantoprazole, as all acid-blocking medicines, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered if respective clinical symptoms are observed.
Interference with laboratory tests: Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours. If the patient(s) are due to have a test on Chromogranin A level, Pantoprazole BEXIMCO treatment should be stopped for at least 5 days before CgA measurements to avoid this interference (see Pharmacology: Pharmacodynamics under Actions). 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.
Regular Surveillance: Patients on proton pump inhibitor treatment (particularly those treated for long term) should be kept under regular surveillance.
Subacute Cutaneous Lupus Erythematosus (SCLE): Proton pump inhibitors are associated with very infrequent cases of subacute cutaneous lupus erythematosus (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 BEXIMCO. SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with other proton pump inhibitors.
Hypomagnesaemia: Severe hypomagnesaemia has been reported in patients treated with PPI like Pantoprazole BEXIMCO for at least three months, and in most cases for a year. Serious manifestations of hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmia can occur but they may begin insidiously and be overlooked. In most affected patients, hypomagnesaemia improved after magnesium replacement and discontinuation of the PPI.
For patients expected to be on prolonged treatment or who take PPI with digoxin or drugs that may cause hypomagnesaemia (e.g., diuretics), health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment.
Fracture: Proton pump inhibitors, especially if used in high doses and over long durations (>1 year), may modestly increase the risk of hip, wrist and spine fracture, predominantly in the elderly or in presence of other recognised risk factors. Observational studies suggest that proton pump inhibitors may increase the overall risk of fracture by 10-40%. Some of this increase may be due to other risk factors. Patients at risk of osteoporosis should receive care according to current clinical guidelines and they should have an adequate intake of vitamin D and calcium.
Clostridium difficile Diarrhea: Published observational studies suggest that PPI therapy 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.
Vitamin B12 Deficiency: 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 B12) 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.
There are no adequate or well-controlled studies in pregnant women. Pantoprazole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
It is not known whether Pantoprazole is excreted in human breast milk. Pantoprazole should be used during lactation only if the potential benefit justifies the potential risk.
Inform the physician regardless if the side effects experienced are listed as follows or not: Blood and lymphatic system:
Very rare: Leukopenia, thrombocytopenia.
Common: Upper abdominal pain, diarrhea, constipation, flatulence, fundic gland polyps (Benign). Uncommon: Nausea/vomiting. Rare: Dry mouth.
Very rare: Severe hepatocellular damage leading to jaundice with or without hepatic failure.
Immune System Disorders:
Very rare: Anaphylactic reactions including anaphylactic shock.
Infections & infestations: Clostridium difficile
Very rare: Increased liver enzymes (transaminases, γ-GT), elevated triglycerides, increased body temperature.
Metabolism and nutritional disorders:
Vitamin B12 deficiency. Not known: hypomagnesaemia.
Musculoskeletal, connective tissue disorder:
Uncommon: Fracture of the hip, wrist or spine. Rare: Arthralgia. Very rare: Myalgia.
Nervous system disorders:
Common: Headache. Uncommon: Dizziness, disturbances in vision (blurred vision).
Rare: Depression, hallucination, disorientation, confusion (especially in predisposed patients, as well as aggravation of these symptoms in case of preexistence).
Renal and Urinary disorders:
Skin and subcutaneous tissue disorders:
Uncommon: Allergic reactions (eg. Pruritus and skin rash). Very rare: Urticaria, angioedema, severe skin reactions (eg. Stevens-Johnson syndrome), erythema multiforme, photosensitivity, Lyell-syndrome. Not known: Subacute cutaneous lupus erythematosus.
Changes in absorption should be observed when drugs whose absorption is pH-dependent eg, ketoconazole, are taken concomitantly.
It has been shown that co-administration of atazanavir 300mg/ritonavir 100mg with omeprazole (40mg once daily) or atazanavir 400mg with lansoprazole (60mg single dose) to healthy volunteers resulted in a substantial reduction in the bioavailability of atazanavir. The absorption of atazanavir is pH dependent. Therefore PPIs, including Pantoprazole, should not be co-administered with atazanavir.
Please note that this information also applies to drugs which patient might have used recently.
Pantoprazole sodium is metabolized in the liver via the cytochrome P-450 enzyme system. An interaction of Pantoprazole with other drugs or compounds which are metabolized using the same enzyme system cannot be excluded. However, no clinically significant interactions were observed in targeted studies with drugs or compounds such as carbamazepine, caffeine, diazepam, diclofenac, digoxin, ethanol, glibenclamide, metoprolol, naproxen, nifedipine, piroxicam, theophylline, phenytoin and an oral contraceptive.
Although no interaction during concomitant administration of phenprocoumon or warfarin has been observed, a few isolated cases of changes in INR have been reported. Therefore, in patients being treated with coumarin anticoagulants, monitoring of prothrombin time/INR is recommended after initiation, termination or during irregular use of pantoprazole.
There were also no interactions with concomitantly administered antacids.
Store below 30°C. Keep in a dry place, protected from light.
A02BC02 - pantoprazole ; Belongs to the class of proton pump inhibitors. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).
Gastro-resistant tab (yellow colored, oval, biconvex, enteric coated tablets plain on both sides) 20 mg x 3 x 10's. 40 mg x 3 x 10's.