GENERIC NAME OF THE MEDICINAL PRODUCT:

Pantoprazole Gastro-resistant Tablets 20mg (Pantotaj)
Pantoprazole Gastro-resistant Tablets 40mg (Pantotaj)

QUALITATIVE AND QUANTITATIVE COMPOSITION:

a) Each film-coated tablet contains; Pantoprazole Sodium IP Eqquivalent to Pantoprazole 20mg b) Each film-coated tablet contains; Pantoprazole Sodium IP Eqquivalent to Pantoprazole 40mg

THERAPEUTIC INDICATIONS:

Pantoprazole is indicated for short-term treatment (7-10 days) of patients having gastroesophageal reflux disease (GERD) with a history of erosive esophagitis, as an alternative to oral medication in patients who are unable to continue taking pantoprazole delayed-release tablets. Safety and efficacy of pantoprazole as the initial treatment of patients having GERD with a history of erosive esophagitis have not been demonstrated at this time. Pantoprazole is indicated for the treatment of pathological hypersecretory conditions associated with Zollinger-Ellison Syndrome or other neoplastic conditions. Indicated in adults and pediatric patients five years of age and above for the short-term treatment (up to 8 weeks) in the healing and symptomatic relief of erosive esophagitis. For adult patients who have not healed after 8 weeks of treatment, an additional 8-week course of pantoprazole may be considered. Safety of treatment beyond 8 weeks in pediatric patients has not been determined. Indicated for maintenance of healing of erosive esophagitis and reduction in relapse rates of daytime and nighttime heartburn symptoms in adult patients with GERD.

DIRECTION OF USE:

Do not swallow whole or chew.
Take this medicine on an empty stomach.

CAUTION & SCHEDULE:

CAUTION: KEEP OUT OF REACH AND SIGHT OF CHILDREN.
SCHEDULE: SCHEDULE ‘H’ DRUG – To be sold by retail on the prescription of a Registered Medical Practitioner only.

STORAGE & DOSAGE:

STORAGE: Preserve in tight container.
Keep in cool & dry place.
Protect from light & moisture.
DOSAGE: As directed by Physician.

Pantoprazole Gastro-resistant Tablets IP 40mg (Pantotaj) Taj Pharma

Overview

INTRODUCTION OF PANTOTAJ TABLET

Pantoprazole Gastro-resistant Tablets 40mg, Pantoprazole Gastro-resistant Tablets 40mg manufacturer in India, Generic Manufacturers exporters India, Pantoprazole Gastro-resistant Tablets 40mg Information from Drugs, indian Pantoprazole Gastro-resistant Tablets 40mg

Pantotaj 40 mg Tablet is a medicine that reduces the amount of acid produced in your stomach. It is used to treat heartburn, acid reflux and problems in your esophagus (which connects your throat to your stomach. It is also used to prevent and treat stomach ulcers.

You should take Pantotaj 40 mg Tablet as your doctor advises. The dose will depend on what you are being treated for, but it should be the lowest dose for the shortest amount of time needed to treat your condition. Normally it should be swallowed whole about an hour before a meal and at the same time each day. It may take up to a few weeks to work properly but your doctor will tell you how long you need to be taking it for. You should keep on taking it as prescribed even if your symptoms disappear quickly. If you are taking this medicine for a long time, your doctor may carry out regular tests to check your levels of magnesium which can fall with this medicine.

Common side effects include headache, constipation or diarrhea, stomach pain, and feeling or being sick. These tend to be mild but talk to your pharmacist or doctor if they bother you or do not go away. The risk of side effects may increase the longer you take this medicine. Serious side effects are rare, but some need immediate medical attention. Ask your doctor what these are. You may be more likely to have a broken bone if you take it for a long time. It is best to avoid foods that seem to make your symptoms worse, such as rich, spicy and fatty foods. It also helps to cut down on caffeinated drinks, such as tea, coffee, and cola, as well as alcohol.

Pantotaj 40 mg Tablet is not suitable for some people. Before taking this medicine, you need to tell your doctor if you have severe liver problems, are taking medicines for HIV, have had an allergic reaction to similar medicines in the past or have osteoporosis. Alcohol does not interfere with the way Pantotaj 40 mg Tablet works. However, drinking alcohol makes your stomach produce more acid than normal. This medicine can make you feel dizzy, sleepy, or affect your vision. If this happens, do not drive, cycle or use machinery or tools until you feel better. It is not usually recommended during pregnancy and breastfeeding.

USES OF PANTOTAJ TABLET

  • Gastroesophageal reflux disease (Acid reflux)
  • Peptic ulcer disease

PANTOTAJ TABLET SIDE EFFECTS

Common
  • Vomiting
  • Headache
  • Stomach pain
  • Nausea
  • Flatulence
  • Diarrhea

HOW TO USE PANTOTAJ TABLET

Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. Pantotaj 40 mg Tablet may be taken with or without food, but it is better to take it at a fixed time.

HOW PANTOTAJ TABLET WORKS

Pantotaj 40 mg Tablet is a proton pump inhibitor (PPI). It works by reducing the amount of acid in the stomach which in turn relieves acid-related indigestion and heartburn.

PANTOTAJ TABLET RELATED WARNINGS

warnings

Alcohol

CAUTION
Caution is advised when consuming alcohol with Pantotaj 40 mg Tablet. Please consult your doctor.
warnings

Pregnancy

SAFE IF PRESCRIBED
Pantotaj 40 mg Tablet is generally considered safe to use during pregnancy. Animal studies have shown low or no adverse effects on the developing baby; however, there are limited human studies.
warnings

Lactation

SAFE IF PRESCRIBED
Pantotaj 40 mg Tablet is probably safe to use during breastfeeding. Limited human data suggests that the drug does not represent any significant risk to the baby.
warnings

Driving

UNSAFE
Pantotaj 40 mg Tablet may cause side effects which could affect your ability to drive.
warnings

Kidney

SAFE IF PRESCRIBED
Pantotaj 40 mg Tablet is safe to use in patients with kidney disease. No dose adjustment of Pantotaj 40 mg Tablet is recommended.
However, the use of Pantotaj 40 mg Tablet is not advised along with other medicines used for the treatment of Helicobacter Pylori infection.
warnings

Liver

CAUTION
Pantotaj 40 mg Tablet should be used with caution in patients with severe liver disease. Dose adjustment of Pantotaj 40 mg Tablet may be needed. Please consult your doctor.

WHAT IF YOU MISS A DOSE OF PANTOTAJ TABLET?

If you miss a dose of Pantotaj 40 mg Tablet, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular schedule. Do not double the dose.

Pantoprazole Gastro-resistant Tablets 40mg (Pantotaj) Taj Pharma

  1. Name of the medicinal product

Pantoprazole 40 mg gastro-resistant tablets

  1. Qualitative and quantitative composition

Each film-coated tablet contains; Pantoprazole Sodium IP equivalent to Pantoprazole 40mg

  1. Pharmaceutical form

Gastro-resistant tablet.

  1. Clinical particulars

4.1 Therapeutic indications

Pantoprazole is indicated for use in Adults and adolescents 12 years of age and above for

− Reflux oesophagitis.

Pantoprazole is indicated for use in Adults for

− Eradication of Helicobacter pylori (H. pylori) in combination with appropriate antibiotic therapy in patients with H. pylori associated ulcers.

− Gastric and duodenal ulcer.

− Zollinger-Ellison-Syndrome and other pathological hypersecretory conditions.

4.2 Posology and method of administration

Posology

Adults and adolescents 12 years of age and above

Reflux oesophagitis

One tablet of Pantoprazole per day. In individual cases the dose may be doubled (increase to 2 tablets Pantoprazole daily) especially when there has been no response to other treatment. A 4-week period is usually required for the treatment of reflux oesophagitis. If this is not sufficient, healing will usually be achieved within a further 4 weeks.

Adults

Eradication of H. pylori in combination with two appropriate antibiotics

In H. pylori positive patients with gastric and duodenal ulcers, eradication of the germ by a combination therapy should be achieved. Considerations should be given to official local guidance (e.g. national recommendations) regarding bacterial resistance and the appropriate use and prescription of antibacterial agents. Depending upon the resistance pattern, the following combinations can be recommended for the eradication of H. pylori:

  1. a) twice daily one tablet Pantoprazole

+ twice daily 1000 mg amoxicillin

+ twice daily 500 mg clarithromycin

  1. b) twice daily one tablet Pantoprazole

+ twice daily 400 – 500 mg metronidazole (or 500 mg tinidazole)

+ twice daily 250 – 500 mg clarithromycin

  1. c) twice daily one tablet Pantoprazole

+ twice daily 1000 mg amoxicillin

+ twice daily 400 – 500 mg metronidazole (or 500 mg tinidazole)

In combination therapy for eradication of H. pylori infection, the second Pantoprazole tablet should be taken 1 hour before the evening meal. The combination therapy is implemented for 7 days in general and can be prolonged for a further 7 days to a total duration of up to two weeks. If, to ensure healing of the ulcers, further treatment with pantoprazole is indicated, the dose recommendations for duodenal and gastric ulcers should be considered.

If combination therapy is not an option, e.g. if the patient has tested negative for H. pylori, the following dose guidelines apply for Pantoprazole monotherapy:

Treatment of gastric ulcer

One tablet of Pantoprazole per day. In individual cases the dose may be doubled (increase to 2 tablets Pantoprazole daily) especially when there has been no response to other treatment. A 4-week period is usually required for the treatment of gastric ulcers. If this is not sufficient, healing will usually be achieved within a further 4 weeks.

Treatment of duodenal ulcer

One tablet of Pantoprazole per day. In individual cases the dose may be doubled (increase to 2 tablets Pantoprazole daily) especially when there has been no response to other treatment. A duodenal ulcer generally heals within 2 weeks. If a 2-week period of treatment is not sufficient, healing will be achieved in almost all cases within a further 2 weeks.

Zollinger-Ellison-Syndrome and other pathological hypersecretory conditions

For the long-term management of Zollinger-Ellison-Syndrome and other pathological hypersecretory conditions patients should start their treatment with a daily dose of 80 mg (2 tablets of Pantoprazole 40 mg). Thereafter, the dose can be titrated up or down as needed using measurements of gastric acid secretion to guide. With doses above 80 mg daily, the dose should be divided and given twice daily. A temporary increase of the dose above 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.

Special populations

Patients with hepatic Impairment

A daily dose of 20 mg pantoprazole (1 tablet of 20 mg pantoprazole) should not be exceeded in patients with severe liver impairment. Pantoprazole must not be used in combination treatment for eradication of H. pylori in patients with moderate to severe hepatic dysfunction since currently no data are available on the efficacy and safety of Pantoprazole in combination treatment of these patients (see section 4.4).

Patients with renal Impairment

No dose adjustment is necessary in patients with impaired renal function. Pantoprazole must not be used in combination treatment for eradication of H. pylori in patients with impaired renal function since currently no data are available on the efficacy and safety of Pantoprazole in combination treatment for these patients (see section 5.2).

Older people

No dose adjustment is necessary in elderly patients (see section 5.2).

Paediatric population

Pantoprazole is not recommended for use in children below 12 years of age due to limited data on safety and efficacy in this age group.

Method of administration

Oral use

The tablets should not be chewed or crushed, and should be swallowed whole 1 hour before a meal with some water.

4.3 Contraindications

Hypersensitivity to the active substance, substituted benzimidazoles or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

Hepatic Impairment

In patients with severe liver impairment, the liver enzymes should be monitored regularly during treatment with pantoprazole, particularly on long-term use. In the case of a rise of the liver enzymes, the treatment should be discontinued (see section 4.2).

Combination therapy

In the case of combination therapy, the summaries of product characteristics of the respective medicinal products should be observed.

Gastric malignancy

Symptomatic response to pantoprazole may mask the symptoms of gastric malignancy and may delay diagnosis.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.

Further investigation is to be considered if symptoms persist despite adequate treatment.

Co-administration with HIV protease inhibitors

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 (see section 4.5).

Influence on vitamin B12 absorption

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 in patients with reduced body stores or risk factors for reduced vitamin B12 absorption on long-term therapy or if respective clinical symptoms are observed.

Long term treatment

In long-term treatment, especially when exceeding a treatment period of 1 year, patients should be kept under regular surveillance.

Gastrointestinal infections caused by bacteria

Treatment with Pantoprazole may lead to a slightly increased risk of gastrointestinal infections caused by bacteria such as Salmonella and Campylobacter and C. difficile.

Hypomagnesaemia

Severe hypomagnesaemia has been reported in patients treated with PPIs like pantoprazole 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 PPIs with digoxin or medicinal products that may cause hypomagnesaemia (e.g., diuretics), health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment.

Bone fractures

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 older people 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.

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, Pantoprazole treatment should be stopped for at least 5 days before CgA measurements (see section 5.1). 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

4.5 Interaction with other medicinal products and other forms of interaction

Medicinal products with pH-Dependent Absorption PharmacokineticsBecause of profound and long lasting inhibition of gastric acid secretion, pantoprazole may interfere with the absorption of other medicinal products where gastric pH is an important determinant of oral availabilitydependent e.g some azole antifungals such as ketoconazole, itraconazole, posaconazole and other medicine such as erlotinib.

HIV protease inhibtiors

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 (see section 4.4).

If the combination of HIV protease inhibitors with a proton pump inhibitor is judged unavoidable, close clinical monitoring (e.g virus load) is recommended. A pantoprazole dose of 20 mg per day should not be exceeded. Dosage of the HIV protease inhibitors may need to be adjusted.

Coumarin anticoagulants (phenprocoumon or warfarin)

Co-administration of Pantoprazole with warfarin or phenprocoumon did not affect the pharmacokinetics of warfarin, phenprocoumon or INR. However, there have been reports of increased INR and prothrombin time in patients receiving PPIs and warfarin or phenprocoumon concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding, and even death. Patients treated with pantoprazole and warfarin or phenprocoumon may need to be monitored for increase in INR and prothrombin time.

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 medicinal products 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.

An interaction of pantoprazole with other medicinal products or compounds, which are metabolized using the same enzyme system, cannot be excluded.

Results from a range of interaction studies demonstrate that pantoprazole does not affect 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 by concomitantly administering pantoprazole with the respective antibiotics (clarithromycin, metronidazole, amoxicillin) No clinically relevant interactions were found.

Medicinal products that inhibit or induce CYP2C19:

Inhibitors of CYP2C19 such as fluvoxamine could increase the systemic exposure of pantoprazole. A dose reduction may be considered for patients treated long-term with high doses of pantoprazole, or those with hepatic impairment.

Enzyme inducers affecting CYP2C19 and CYP3A4 such as rifampicin and St John´s wort (Hypericum perforatum) may reduce the plasma concentrations of PPIs that are metabolized through these enzyme systems.

4.6 Fertility, pregnancy and lactation

Pregnancy

A moderate amount of data on pregnant women (between 300-1000 pregnancy outcomes) indicate no malformative or feto/ neonatal toxicity of Pantoprazole.

Animal studies have shown reproductive toxicity (see section 5.3).

As a precautionary measure, it is preferable to avoid the use of pantoprazole during pregnancy.

Breast-feeding

Animal studies have shown excretion of pantoprazole in breast milk. There is insufficient information on the excretion of pantoprazole in human milk but excretion into human milk has been reported. A risk to the newborns/infants cannot be excluded. Therefore a decision on whether to discontinue breast-feeding or to discontinue/abstain from Pantoprazole therapy taking into account the benefit of breast- feeding to the child and the benefit of Pantoprazole therapy to women.

Fertility

There was no evidence of impaired fertility following the administration of pantoprazole in animal studies (see section 5.3).

4.7 Effects on ability to drive and use machines

Pantoprazole has no or negligible influence on the ability to drive and use machines.

Adverse drug reactions such as dizziness and visual disturbances may occur (see section 4.8). If affected, patients should not drive or operate machines.

4.8 Undesirable effects

Approximately 5 % of patients can be expected to experience adverse drug reactions (ADRs). The most commonly reported ADRs are diarrhoea and headache, both occurring in approximately 1 % of patients.

The table below lists adverse reactions reported with pantoprazole, ranked under the following frequency classification:

Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

For all adverse reactions reported from post-marketing experience, it is not possible to apply any Adverse Reaction frequency and therefore they are mentioned with a “not known” frequency.

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Table 1. Adverse reactions with pantoprazole in clinical trials and post-marketing experience

FrequencyCommonUncommonRareVery rareNot known
System Organ Class
Blood and lymphatic system disordersAgranulocytosisThrombocytopenia; Leukopenia; Pancytopenia
Immune system disordersHypersensitivity (including anaphylactic reactions and anaphylactic shock)
Metabolism and nutrition disordersHyperlipidaemias and lipid increases (triglycerides, cholesterol); Weight changesHyponatraemia

Hypomagnesaemia. (See section 4.4); Hypocalcaemia (1) hypokalaemia

Psychiatric disordersSleep disordersDepression (and all aggravations)Disorientation (and all aggravations)Hallucination; Confusion (especially in pre-disposed patients, as well as the aggravation of these symptoms in case of pre- existence)
Nervous system disordersHeadache; DizzinessTaste disordersParasthesia
Eye disordersDisturbances in vision / blurred vision
Gastrointestinal disordersFundic gland polyps (benign)Diarrhoea; Nausea / vomiting; Abdominal distension and bloating; Constipation; Dry mouth; Abdominal pain and discomfortMicroscopic colitis
Hepatobiliary disordersLiver enzymes increased (transaminases, γ-GT)Bilirubin increasedHepatocellular injury; Jaundice; Hepatocellular failure
Skin and sub- cutaneous tissue disordersRash / exanthema / eruption; PruritusUrticaria; AngioedemaStevens-Johnson syndrome; Lyell syndrome; Erythema multiforme; Photosensitivity

Subacute cutaneous lupus erythematosus (see section 4.4).

Musculoskeletal and connective tissue disordersFracture of the hip, wrist or spine (see section 4.4)Arthralgia; MyalgiaMuscle spasm (2)
Renal and urinary disordersInterstitial Nephritis (with possible progression to renal failure)
Reproductive system and breast disordersGynaecomastia
General disorders and administration site conditionsAsthenia, fatigue and malaiseBody temperature increased; Oedema peripheral
  1. Hypocalcemia in association with hypomagnesemia
  2. 2.Muscle spasm as a consequence of electrolyte disturbance

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

There are no known symptoms of overdose 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 an overdose with clinical signs of intoxication, apart from symptomatic and supportive treatment, no specific therapeutic recommendations can be made.

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Proton pump inhibitors

Mechanism of action

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.

Pharmacodynamic effects

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, according to the studies conducted so far, the formation of carcinoid precursors (atypical hyperplasia) or gastric carcinoids as were found in animal experiments (see section 5.3) 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.

5.2 Pharmacokinetic properties

Absorption

Pantoprazole is rapidly absorbed and the maximal plasma concentration is achieved even after one single 40 mg oral dose. On average at about 2.5 h p.a. the maximum serum concentrations of about 2 – 3 µg/ml are achieved, and these values remain constant after multiple administration.

Pharmacokinetics does 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.

The absolute bioavailability from the tablet was found to be about 77 %. Concomitant intake of food had no influence on AUC, maximum serum concentration and thus bioavailability. Only the variability of the lag-time will be increased by concomitant food intake.

Distribution

Pantoprazole’s serum protein binding is about 98 %. Volume of distribution is about 0.15 l/kg

Biotransformation The substance is almost exclusively metabolized in the liver. The main metabolic pathway is demethylation by CYP2C19 with subsequent sulphate conjugation, other metabolic pathway include oxidation by CYP3A4.

Elimination

Terminal half-life is about 1 hour and clearance is about 0.1 l/h/kg. 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).

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 hours) is not much longer than that of pantoprazole.

Special populations

Poor metabolisers

Approximately 3 % of the European population lack a functional CYP2C19 enzyme and are called poor metabolisers. In these individuals the metabolism of pantoprazole is probably mainly catalysed by CYP3A4. After a single-dose administration of 40 mg pantoprazole, the mean area under the plasma concentration-time curve was approximately 6 times higher in poor metabolisers than in subjects having a functional CYP2C19 enzyme (extensive metabolisers). Mean peak plasma concentrations were increased by about 60 %. These findings have no implications for the posology of pantoprazole.

Renal impairment

No dose reduction is recommended when pantoprazole is administered to patients with impaired renal function (including dialysis patients). As with healthy subjects, pantoprazole’s half-life is short. Only very small amounts of pantoprazole are dialyzed. Although the main metabolite has a moderately delayed half- life (2 – 3 h), excretion is still rapid and thus accumulation does not occur.

Hepatic impairment

Although for patients with liver cirrhosis (classes A and B according to Child) the half-life values increased to between 7 and 9 h and the AUC values increased by a factor of 5 – 7, the maximum serum concentration only increased slightly by a factor of 1.5 compared with healthy subjects.

Older people

A slight increase in AUC and Cmax in elderly volunteers compared with younger counterparts is also not clinically relevant.

Paediatric population

Following administration of single oral doses of 20 or 40 mg pantoprazole to children aged 5 – 16 years AUC and Cmax were in the range of corresponding values in adults.

Following administration of single i.v. doses of 0.8 or 1.6 mg/kg pantoprazole to children aged 2 – 16 years there was no significant association between pantoprazole clearance and age or weight. AUC and volume of distribution were in accordance with data from adults.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard to humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity.

In the two-year carcinogenicity studies in rats neuroendocrine neoplasms were found. In addition, squamous cell papillomas were found in the forestomach of rats. The mechanism leading to the formation of gastric carcinoids by substituted benzimidazoles has been carefully investigated and allows the conclusion that it is a secondary reaction to the massively elevated serum gastrin levels occurring in the rat during chronic high-dose treatment. In the two-year rodent studies an increased number of liver tumors was observed in rats and in female mice and was interpreted as being due to pantoprazole’s high metabolic rate in the liver.

A slight increase of neoplastic changes of the thyroid was observed in the group of rats receiving the highest dose (200 mg/kg). The occurrence of these neoplasms is associated with the pantoprazole-induced changes in the breakdown of thyroxine in the rat liver. As the therapeutic dose in man is low, no harmful effects on the thyroid glands are expected.

In animal reproduction studies, signs of slight fetotoxicity were observed at doses above 5 mg/kg.

Investigations revealed no evidence of impaired fertility or teratogenic effects.

Penetration of the placenta was investigated in the rat and was found to increase with advanced gestation. As a result, concentration of pantoprazole in the foetus is increased shortly before birth.

  1. Pharmaceutical particulars

6.1 List of excipients

Sodium Carbonate (Anhydrous), Mannitol, Crospovidone (Type B), Hydroxypropyl Cellulose, Calcium Stearate, Hypromellose, Yellow iron oxide, Methacrylic Acid-Ethyl Acrylate copolymer (1:1) dispersion 30%, Sodium laurilsulfate, Polysorbate 80, Triethyl Citrate

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions

6.5 Nature and contents of container

Blisters of Polyamide/Aluminium/PVC-Aluminium in a blister carton, and white opaque round HDPE container with white opaque polypropylene closure.

Pack sizes:

Blister:7, 14, 15, 28, 30, 56, 60, 98, 100 and 500 gastro-resistant tablets

HDPE: 14, 28, 56, 60, 98, 100 and 500 gastro-resistant tablets

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Any unused product or waste material should be disposed of in accordance with local requirements.

  1. Manufactured in India By:
    TAJ PHARMACEUTICALS LTD.,
    Plot no. 220, Mahagujarat, Industrial Estate,
    Moraiya, Tal. Sanand, Dist. Ahmedabad, Gujarat

         Package leaflet: Information for the user
Pantoprazole 40 mg gastro-resistant tablets (Pantotaj) Taj Pharma
Pantoprazole

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it
  • If you have any further questions, ask your doctor or
  • This medicine has been prescribed for you Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
  • If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

  1. What Pantoprazole is and what it is used for
  2. What you need to know before you take Pantoprazole
  3. How to take Pantoprazole
  4. Possible side effects
  5. How to store Pantoprazole
  6. Contents of the pack and other information

 

  1. What Pantoprazole is and what it is used for

Pantoprazole contains the active substance pantoprazole. Pantoprazole is a selective “proton pump inhibitor”, a medicine which reduces the amount of acid produced

in your stomach. It is used for treating acid-related diseases of the stomach and intestine.

Pantoprazole is used to treat Adults and adolescents 12 years of age and above for:

  • Reflux oesophagitis. An inflammation of your oesophagus (the tube which connects your throat to your stomach) accompanied by the regurgitation of stomach acid.

Pantoprazole is used to treat Adults for :

  • An infection with a bacterium called Helicobacter pylori in patients with duodenal ulcers and stomach ulcers in combination with two antibiotics

(Eradication therapy). The aim is to get rid of the bacteria and so reduce the likelihood of these ulcers returning.

  • Stomach and duodenal ulcers.
  • Zollinger-Ellison-Syndrome and other conditions producing too much acid in the stomach.
  1. What you need to know before you take Pantoprazole

Do not take Pantoprazole

  • If you are allergic to pantoprazole or any of the other ingredients of this medicine (listed in section 6).

–   If you are allergic to medicines containing other proton pump inhibitors.

Warnings and precautions

Talk to your doctor or pharmacist

before taking Pantoprazole.

–   If you have severe liver problems.

Please tell your doctor if you  ever had problems with your liver in the past. He will check your liver enzymes more frequently, especially when you are taking Pantoprazole as a long-term treatment. In the case of a rise

of liver enzymes the treatment should be stopped.

  • If you have reduced body stores or risk factors for reduced vitamin B12 and receive long-term treatment with pantoprazole. As with all acid reducing agents, pantoprazole may lead to a reduced absorption of vitamin
  • If you are taking HIV protease inhibitors such as atazanavir (for the treatment

of HIV-infection) at the same time as pantoprazole, ask your doctor for specific advice.

  • Taking a proton pump inhibitor like pantoprazole, especially over a period of more than one year, may slightly increase your risk of fracture in the hip, wrist or spine. Tell your doctor if you have osteoporosis or if you are taking corticosteroids (which can increase the risk of osteoporosis).
  • If you are on pantoprazole for more than three months it is possible that the levels of magnesium in your blood may fall. Low levels of magnesium can be seen as fatigue, involuntary muscle contractions, disorientation,

convulsions, dizziness, increased heart rate. If you get any of these symptoms, please tell your doctor promptly. Low levels of magnesium can also lead to a reduction in potassium or calcium levels in the blood. Your doctor may decide to perform regular blood tests to monitor your levels of magnesium.

  • If you have ever had a skin reaction after treatment with a medicine similar to Pantoprazole that reduces stomach acid.
  • If you get a rash on your skin, especially in areas exposed to the sun tell your doctor as soon as you can, as you

may need to stop your treatment with Pantoprazole. Remember to also mention any other ill-effects like pain in your joints.

  • If you are due to have a specific blood test (Chromogranin A)

Tell your doctor immediately, before or after taking this medicine, if you notice any of the following symptoms, which could be a sign of another, more serious, disease:

  • an unintentional loss of weight
  • vomiting, particularly if repeated
  • difficulty in swallowing or pain when swallowing
  • vomiting blood : this may appear as dark coffee grounds in your vomit
  • you look pale and feel weak (anaemia)
  • you notice blood in your stools: which may be black or tarry in appearance
  • chest pain
  • stomach pain
  • severe and/or persistent diarrhoea, because this medicine has been associated with a small increase in infectious

Your doctor may decide that you need some tests to rule out malignant disease because pantoprazole also alleviates the symptoms of cancer and could cause delay in diagnosing it. If your symptoms continue in spite of your treatment, further investigations will be considered.

If you take Pantoprazole on a long-term basis (longer than 1 year) your doctor will probably keep you under regular

surveillance. You should report any new and exceptional symptoms and circumstances whenever you see your doctor.

Children and adolescents

Pantoprazole is not recommended for use in children as it has not been proven to work in children below 12 years of age.

Other medicines and Pantoprazole Tell your doctor or pharmacist if you are taking, have recently taken or might take

any other medicines, including medicines obtained without a prescription. This is because Pantoprazole may influence the effectiveness of other medicines, so tell your doctor if you are taking

  • Medicines such as ketoconazole, itraconazole and posaconazole (used to treat fungal infections) or erlotinib (used for certain types of cancer) because Pantoprazole may stop these and other medicines from working
  • Warfarin and phenprocoumon, which affect the thickening, or thinning of the blood. You may need further
  • Medicines used to treat HIV-infection, such as
  • Methotrexate (used to treat rheumatoid arthritis, psoriasis, and cancer) – if you are taking methotrexate your doctor may temporarily stop your Pantoprazole treatment because pantoprazole can increase levels of methotrexate in the blood.
  • Fluvoxamine (used to treat depression and other psychiatric diseases – if you are taking fluvoxamine your doctor may reduce the dose.
  • Rifampicin (used to treat infections).

St John’s wort (Hypericum perforatum) (used to treat mild depression).

Pregnancy, breast-feeding and fertility There are no adequate data from the use of pantoprazole in pregnant women. Excretion into human milk has been reported.

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine

You should use this medicine, only if your doctor considers the benefit for you greater than the potential risk for your unborn child or baby.

Driving and using machines Pantoprazole has no or negligible influence on the ability to drive and use machines.

If you experience side effects like dizziness or disturbed vision, you should not drive or operate machines.

  1. How to take Pantoprazole

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Method of administration Take the tablets 1 hour before a meal without chewing or breaking them and swallow them whole with some water.

The recommended dose is:

Adults and adolescents 12 years of age and above:

To treat reflux oesophagitis

The usual dose is one tablet a day. Your doctor may tell you to increase to 2 tablets daily. The treatment period for reflux oesophagitis is usually between 4 and 8 weeks. Your doctor will tell you how long to take your medicine.

Adults:

For the treatment of an infection with a bacterium called Helicobacter pylori in patients with

duodenal ulcers and stomach ulcers in combination with two antibiotics (Eradication therapy).

One tablet, two times a day plus two antibiotic tablets of either amoxicillin, clarithromycin and

metronidazole (or tinidazole),  each to be taken two times a day with your pantoprazole tablet. Take the

first pantoprazole tablet 1 hour before breakfast and the second pantoprazole tablet 1 hour before your

evening meal. Follow your doctor’s instructions and make sure you read the package leaflets for these

antibiotics. The usual treatment period is one to two weeks.

For the treatment of stomach and duodenal ulcers.

The usual dose is one tablet a day. After consultation with your doctor, the dose may be doubled.

Your doctor will tell you how long to take your medicine. The treatment period for stomach ulcers is usually between 4 and 8 weeks. The treatment period for duodenal ulcers is usually between 2 and 4 weeks.

For the long-term treatment of Zollinger-Ellison-Syndrome and of other conditions in which too much stomach acid is produced. The recommended starting dose is usually two tablets a day.

Take the two tablets 1 hour before a meal. Your doctor may later adjust the dose, depending on the amount of stomach acid you produce. If prescribed more than two tablets a day, the tablets should be taken twice daily.

If your doctor prescribes a daily dose of more than four tablets a day, you will be told exactly when to stop taking the medicine.

Patients with kidney problems

If you have kidney problems, you should not take Pantoprazole for eradication of Helicobacter pylori.

Patients with liver problems

If you suffer from severe liver problems, you should not take more than one tablet 20 mg pantoprazole a day (for this purpose tablets containing 20 mg pantoprazole are available).

If you suffer from moderate or severe liver problems, you should not take Pantoprazole for eradication of Helicobacter pylori

Use in children and adolescents

–   These tablets are not recommended for use in children below 12 years.

If you take more Pantoprazole than you should

Tell your doctor or pharmacist. There are no known symptoms of overdose.

If you forget to take Pantoprazole

Do not take a double dose to make up for the forgotten dose. Take your next normal dose at the usual time.

If you stop taking Pantoprazole

Do not stop taking these tablets without first talking to your doctor or pharmacist.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

  1. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

If you get any of the following side effects, stop taking these tablets and tell your doctor immediately, or contact the casualty department at your nearest hospital:

  • Serious allergic reactions (frequency rare: may affect up to 1 in 1,000 people): swelling of the tongue and/

or throat, difficulty in swallowing, hives (nettle rash), difficulties in breathing, allergic facial swelling (Quincke’s oedema / angioedema), severe dizziness with very fast heartbeat and heavy sweating.

–     Serious skin conditions (frequency not known: frequency cannot

be estimated from the available data): blistering of the skin and rapid deterioration of your general condition, erosion (including slight bleeding)

of eyes, nose, mouth/lips or genitals (Stevens-Johnson-Syndrome, Lyell-

Syndrome, Erythema multiforme) and sensitivity to light.

–   Other serious conditions

       (frequency not known:

       frequency cannot be estimated from the available data): yellowing of the skin or whites of the eyes (severe damage to liver cells, jaundice) or fever, rash, and enlarged kidneys sometimes with painful urination and lower back pain (serious inflammation of

the kidneys), possibly leading to kidney failure.

  • Other side effects are:

–     Common (may affect up to 1 in 10 people)

Benign polyps in the stomach

  • Uncommon (may affect up to 1 in 100 people)

Headache; dizziness; diarrhoea; feeling sick, vomiting; bloating and flatulence (wind); constipation; dry mouth; abdominal pain and discomfort; skin rash, exanthema, eruption; itching; feeling weak, exhausted or generally unwell; sleep disorders, fracture in the hip, wrist or spine.

  • Rare (may affect up to 1 in 1,000 people)

Distortion or complete lack of the sense of taste; disturbances in vision such as blurred vision; hives; pain in the joints; muscle pains; weight changes; raised body temperature; high fever; swelling of the extremities (peripheral oedema); allergic reactions; depression; breast enlargement in males.

  • Very Rare (may affect up to 1 in 10,000 people)

Disorientation.

  • Not known (frequency cannot be estimated from the available data) Hallucination, confusion (especially in patients with a history of these

symptoms); decreased sodium level in blood, decreased magnesium level in blood (see section 2), feeling of tingling, prickling, pins and needles, burning sensation or numbnessrash, possibly with pain in the joints, Inflammation in the large bowel, that causes persistent watery diarrheoa.

Side effects identified through blood tests:

  • Uncommon (may affect up to 1 in 100 people)

an increase in liver enzymes.

  • Rare (may affect up to 1 in 1,000 people)

an increase in bilirubin; increased fat levels in blood; sharp drop in circulating granular white blood cells associated with high fever.

–     Very Rare (may affect up to 1 in 10,000 people)

a reduction in the number of blood platelets, which may cause you to bleed or bruise more than normal; a reduction in the number of white blood cells, which may lead to more frequent infections

coexisting abnormal reduction in the number of red and white blood cells, as well as platelets.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

  1. How to store Pantoprazole

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

  1. Contents of the pack and other information

What Pantoprazole contains

  • The active substance is pantoprazole. Each gastro-resistant tablet contains 40 mg of pantoprazole (as sodium sesquihydrate).
  • The other ingredients are: Core: sodium carbonate (anhydrous), mannitol, crospovidone (type B), hydroxypropylcellulose, calcium stearate. Coating: hypromellose, yellow

iron oxide, methacrylic acid-ethyl acrylate copolymer (1:1) dispersion 30%, sodium laurilsulfate, polysorbate 80, triethyl citrate.

What Pantoprazole looks like and contents of the pack

Gastro-resistant tablet.

Yellow colored, enteric coated, oval biconvex tablets plain on both the sides.

Blisters (Polyamide/Aluminium/PVC- Aluminium) in a carton:

Blister packs: 7, 14, 15, 28, 30, 56, 60, 98,

100 and 500 gastro-resistant  tablets. HDPE bottle: White opaque round HDPE container with white opaque polypropylene closure.

HDPE bottle packs: 14, 28, 56, 60, 98, 100 and 500 gastro-resistant tablets

Not all pack sizes may be marketed

  1. Manufactured in India By:
    TAJ PHARMACEUTICALS LTD.,
    Plot no. 220, Mahagujarat, Industrial Estate,
    Moraiya, Tal. Sanand, Dist. Ahmedabad, Gujarat