GENERIC NAME OF THE MEDICINAL PRODUCT:

Pantoprazole for Injection 40mg (Pantotaj)

QUALITATIVE AND QUANTITATIVE COMPOSITION:

Each vial 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:

Dissolve the contents in Sodium Chloride injection IP (0.9% w/v).
The re-constituted solution should be used immediately after the preparation.

CAUTION & SCHEDULE:

CAUTION: If any foreign particle is visible in the vial after dissolving the contents, Please do not use the solution.
To be sold by the retail on the prescription of a registered medical practitioner only.
SCHEDULE: SCHEDULE H DRUG - To be sold by retail on the prescription of registered medical practitioner only.

STORAGE & DOSAGE:

STORAGE: Store below 25°C.
Protect from light.
Do not freeze.
DOSAGE: As directed by Physician.

Pantoprazole Sodium for Injection IP 40mg (Pantotaj) Taj Pharma

Overview

INTRODUCTION OF PANTOTAJ INJECTION

Pantotaj Injection is a prescription medicine used for the treatment of gastroesophageal reflux disease (acid reflux) and peptic ulcer disease.

Pantotaj Injection is also used for treatment and prophylaxis of reflux oesophagitis, in combination with other medicines for the eradication of Helicobacter pylori infection and Zollinger-Ellison syndrome. This medicine works by reducing the amount of acid in the stomach which helps to provide relief in acid-related indigestion and heartburn.
This injection is administered under the supervision of healthcare professional and remember intravenous administration is recommended only if oral administration is not appropriate. Take this medicine in dose and duration as advised by your doctor. Before taking this medicine it is better to inform the doctor if you have any liver disease as a dose of your medicine needs to be adjusted. Your doctor may advise for regular monitoring of liver enzymes especially when the medicine is used for a long time. In the case of the rise of the liver enzymes, you need to stop the medicine. It is better to not take this medicine along with an antacid, you may try to take it two hours before or after taking this medicine.

It is well tolerated and safe medicine with a very low incidence of any harmful effects. However, there can be side effects headache, abdominal pain, joint pain, and nausea. This medicine may cause diarrhea, so it is better to take plenty of fluids while taking this medicine as it may help to prevent dehydration. However, it is better to consult the doctor if you get watery diarrhea with fever or stomach pain that does not go away. Remember long term use of this medicine may lead to a deficiency of vitamin B12 and magnesium. This medicine may cause an increased risk for osteoporosis-related fractures of the hip, wrist or spine when used for a longer time. Thus, taking adequate supplements of calcium and magnesium can be helpful in such cases.

USES OF PANTOTAJ INJECTION

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

PANTOTAJ INJECTION SIDE EFFECTS

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

HOW TO USE PANTOTAJ INJECTION

Your doctor or nurse will give you this medicine. Kindly do not self administer.

HOW PANTOTAJ INJECTION WORKS

Pantotaj Injection 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 INJECTION RELATED WARNINGS

warnings

Alcohol

CAUTION
Caution is advised when consuming alcohol with Pantotaj Injection. Please consult your doctor.
warnings

Pregnancy

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

Lactation

SAFE IF PRESCRIBED
Pantotaj Injection 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 Injection may cause side effects which could affect your ability to drive.
warnings

Kidney

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

Liver

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

WHAT IF YOU MISS A DOSE OF PANTOTAJ INJECTION?

If you miss a dose of Pantotaj Injection, 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 Sodium for Injection 40mg (Pantotaj) Taj Pharma

  1. Name of the medicinal product

Pantoprazole 40 mg powder for solution for injection.

  1. Qualitative and quantitative composition

Each vial contains; Pantoprazole Sodium I.P. (as lyophilized Pantoprazole Sodium) Equivalent to Pantoprazole 40mg

This pack also contains 10ml plastic ampoule of Sodium Chloride Injection I.P. (0.9% w/v)

  1. Pharmaceutical form

Powder for solution for injection.

White to almost white powder.

  1. Clinical particulars

4.1 Therapeutic indications

– Reflux oesophagitis

– Gastric and duodenal ulcer

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

4.2 Posology and method of administration

Posology

Intravenous administration of Pantoprazole is recommended only if oral administration is not appropriate. Data are available on intravenous use for up to 7 days. Therefore, as soon as oral therapy is possible, treatment with Pantoprazole i.v. should be discontinued and 40 mg pantoprazole p.o. should be administered instead.

Recommended dose

Gastric and duodenal ulcer, reflux oesophagitis

The recommended intravenous dose is one vial of Pantoprazole (40 mg pantoprazole) per day.

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 Pantoprazole. 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.

In case a rapid acid control is required, a starting dose of 2 x 80 mg Pantoprazole is sufficient to manage a decrease of acid output into the target range (<10 mEq/h) within one hour in the majority of patients.

Special populations

Pediatric population

The safety and efficacy of Pantoprazole in children aged under 18 years have not been established. Therefore, Pantoprazole is not recommended for use in patients below 18 years of age.

Currently available data are described in section 5.2 but no recommendation on a posology can be made.

Hepatic Impairment

A daily dose of 20 mg pantoprazole (half a vial of 40 mg pantoprazole) should not be exceeded in patients with severe liver impairment (see section 4.4).

Renal Impairment

No dose adjustment is necessary for patients with impaired renal function.

Elderly

No dose adjustment is necessary for elderly patients.

Method of administration

This medicine should be administered by a healthcare professional and under appropriate medical supervision.

A ready-to-use solution is prepared in 10 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection. For instructions for preparation of the medicinal product before administration, see section 6.6. The prepared solution may be administered directly or maybe administered after mixing it with 100 ml sodium chloride 9 mg/ml (0.9 %) solution for injection or glucose 55 mg/ml (5 %) solution for injection.

After preparation, the solution must be used within 12 hours.

The medicinal product should be administered intravenously over 2 – 15 minutes.

For instructions on reconstitution and dilution of the medicinal product before administration, see section 6.6.

4.3 Contraindications

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

4.4 Special warnings and precautions for use

In the presence of alarm symptoms

In the presence of any alarm symptom (e. g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis, anemia 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, liver enzymes should be monitored during therapy. In the case of a rise of the liver enzymes, the treatment should be discontinued (see section 4.2).

Co-administration with atazanavir

Co-administration of atazanavir with proton pump inhibitors is not recommended (see section 4.5). 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 such as Salmonella and Campylobacter or C. difficile.

Hypomagnesaemia

Severe hypomagnesemia 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 drugs that may cause hypomagnesemia (e.g., diuretics), health care professionals should consider measuring magnesium levels before starting PPI treatment and periodically during treatment.

The 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.

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 elderly or in presence of other recognized 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.

Interference with laboratory tests

Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumors. 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.

This medicine contains less than 1 mmol sodium (23 mg) per maximum daily dose, that is to say, ‘sodium-free’.

4.5 Interaction with other medicinal products and other forms of interaction

Medicinal products with pH-Dependent Absorption Pharmacokinetics

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

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 co-administration of proton pump inhibitors with atazanavir is not recommended (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. The dosage of the HIV protease inhibitor may need to be adjusted.

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. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. 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.

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 ethinyloestradiol 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 metabolized 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.

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.

Methotrexate

Concomitant use of high dose methotrexate (e.g. 300 mg) and proton pump inhibitors have 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

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. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown. Pantoprazole should not be used during pregnancy unless clearly necessary.

Breast-feeding

Animal studies have shown excretion of pantoprazole in breast milk. There is insufficient information on the excretion into human milk but excretion into human milk has been reported. A risk to the newborn/infant cannot be excluded. Therefore, a decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Pantoprazole should be made taking into account the benefit of breast-feeding to the child and the benefit of Pantoprazole therapy to the woman.

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 ADR is injection site thrombophlebitis. Diarrhea and headache occurred 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)

Hypocalcemia (1); Hypokalaemia

Psychiatric disordersSleep disordersDepression (and all aggravations)Disorientation (and all aggravations)Hallucination; Confusion (especially in predisposed patients, as well as the aggravation of these symptoms in case of pre-existence)
Nervous system disordersHeadache, DizzinessTaste disordersParaesthesia
Eye disordersDisturbances in vision/ blurred vision
Gastrointestinal disordersFundic gland polyps (benign)Diarrhea; 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; Hepato-cellular failure
Skin and subcutaneous tissue disordersRash / exanthema / eruption; PruritusUrticaria; AngioedemaStevens-John-son 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 conditionsInjection site thrombo-phlebitisAsthenia, fatigue, and malaiseBody temperature increased; Oedema peripheral
  1. Hypocalcemia in association with hypomagnesemia
  2. Muscle spasm as a consequence of electrolyte disturbance

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization 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 was well tolerated.

Pantoprazole is extensively protein bound, it is not readily dialyzable.

In the case of 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: Drugs for acid related disorders, Proton pump inhibitors

Mechanism of action

Pantoprazole is a substituted benzimidazole that inhibits the secretion of hydrochloric acid in the stomach by specific action on 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.

The 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 tumors.

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 the reference range.

5.2 Pharmacokinetic properties

General Pharmacokinetics

Pharmacokinetics do not vary after single or repeated administration. In the dose range of 10 to 80 mg, the plasma kinetics of pantoprazole is linear after both oral and intravenous administration.

Distribution

Pantoprazole’s serum protein binding is about 98%. The 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 sulfate conjugation, other metabolic pathways 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 feces. The main metabolite in both the serum and urine is desmethylpantoprazole which is conjugated with sulfate. The half-life of the main metabolite (about 1.5 hours) is not much longer than that of pantoprazole.

Special populations

Poor metabolizers

Approximately 3 % of the European population lacks a functional CYP2C19 enzyme and is called poor metabolizers. In these individuals, the metabolism of pantoprazole is probably mainly catalyzed 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 metabolizers than in subjects having a functional CYP2C19 enzyme (extensive metabolizers). 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 (incl. 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 time 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.

Pediatric population

Following administration of single intravenous 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

Pre-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 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 side effects to 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.

The 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 fetus is increased shortly before birth.

  1. Pharmaceutical particulars

6.1 List of excipients

None.

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.

6.3 Shelf life

18 months.

After reconstitution, or reconstitution and dilution, chemical and physical in-use stability has been demonstrated for 12 hours at 25°C.

From a microbiological point of view, unless the method of opening and dilution precludes the risk of microbial contamination, the product should be used immediately.

If not used immediately, in-use storage times and conditions are the responsibility of the user.

6.4 Special precautions for storage

Store below 25°C.

For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

6.5 Nature and contents of the container

10 ml type-I tubular colorless glass vial with a grey bromobutyl rubber stopper, sealed with a red flip-off tear-off aluminum seal.

Pantoprazole 40 mg powder for solution for injection is supplied in packs containing 1, 5, 10 or 50 vials.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

A ready-to-use solution is prepared by injecting 10 ml of sodium chloride 9 mg/ml (0.9 %) solution for injection into the vial containing the powder. The appearance of the product after reconstitution is a clear colorless solution, practically free from particles. This solution may be administered directly or maybe administered after mixing it with 100 ml sodium chloride 9 mg/ml (0.9 %) solution for injection or glucose 55 mg/ml (5 %) solution for injection. Glass or plastic containers should be used for dilution.

Pantoprazole should not be prepared or mixed with solvents other than those stated.

The medicine should be administered intravenously over 2-15 minutes.

The contents of the vial are for single use only. Any product that has remained in the container or the visual appearance of which has changed (e.g. if cloudiness or precipitation is observed) should be disposed of in accordance with local requirements.

  1. Manufactured in India by:
    TAJ PHARMACEUTICALS LTD.
    At: Survey No. 622/2/1/4, Dedhrota, Himatnagar-Vijapur Highway,
    Dist: Sabarkantha, Gujarat, India

         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 that 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 esophagus (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 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 (anemia)
  • you notice blood in your stools: which may be black or tarry in appearance
  • chest pain
  • stomach pain
  • severe and/or persistent diarrhea, 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 Takes 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 the 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 the 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 edema/ angioedema), severe dizziness with a 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; diarrhea; 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 edema); 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 the blood, decreased magnesium level in the blood (see section 2), feeling of tingling, prickling, pins, and needles, burning sensation or numbness, rash, possibly with pain in the joints, Inflammation in the large bowel, that causes persistent watery diarrhea.

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 the blood; a sharp drop in circulating granular white blood cells associated with a 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), hydroxypropyl cellulose, calcium stearate. Coating: hypromellose, yellow

iron oxide, methacrylic acid ethyl acrylate copolymer (1:1) dispersion 30%, sodium lauryl sulfate, 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 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.
    At: Survey No. 622/2/1/4, Dedhrota, Himatnagar-Vijapur Highway,
    Dist: Sabarkantha, Gujarat, India