PEPRIZ D

Prescribing Information

For the Use of a Registered Medical Practitioner or a Hospital or a Laboratory Only

Pantoprazole (enteric coated pellets) and Domperidone Prolonged- Release Capsules IP

PEPRIZ D

COMPOSITION

Each hard gelatin capsule contains:

Pantoprazole Sodium I. P. equivalent to Pantoprazole 40 mg (As enteric coated pellets)

Domperidone I.P. 30 mg (As prolonged-release pellets)

Excipients q.s.

CLINICAL PHARMACOLOGY

Mechanism of Action:

Pantoprazole

Pantoprazole is a proton pump inhibitor (PPI) class of antisecretory agent. Pantoprazole is a lipophilic weak base that crosses the parietal cell membrane and enters the acidic parietal cell canaliculus where it becomes protonated, producing the active metabolite sulfenamide. Sulfenamide forms an irreversible covalent bond with two sites of the H+/K+-ATPase enzyme located on the gastric parietal cell. Thus, pantoprazole suppress the final step in gastric acid (hydrochloric acid – HCl) production by covalently binding to the H+/K+- ATPase enzyme (also called as proton pump) system at the secretory surface of the gastric parietal cell. This effect leads to inhibition of both basal and stimulated gastric acid secretion, irrespective of the stimulus. The binding to the H+/K+-ATPase results in duration of antisecretory effect that persists longer than 24 hours.

Domperidone

Domperidone is a dopamine receptor (D2) antagonist. Domperidone act predominantly on peripheral dopamine receptors and produces anti-emetic and gastrokinetic effects. Domperidone does not readily cross the blood-brain barrier (BBB). Thus, in domperidone users, especially in adults, extrapyramidal side effects are very rare (unlike metoclopramide). Anti-emetic effect of domperidone is due to a combination of peripheral (gastrokinetic) effects and antagonism of dopamine receptors (D2) in the chemoreceptor trigger zone (CTZ), which lies outside the BBB in the area postrema. 10 Oral domperidone also increases lower esophageal sphincter (LES) pressure, thus, improve antroduodenal motility and accelerate gastric emptying.

PHARMACODYNAMIC PROPERTIES

Pantoprazole

With a single oral dose of 20 to 80 mg of pantoprazole, a dose-dependent decrease in gastric acid secretion occurs. Following the initial oral dose of 40 mg pantoprazole, a 51% mean inhibition was achieved by 2.5 hours. With once-a-day dosing for 7 days, the mean inhibition was increased to 85%. Acid secretion had returned to normal within a week after the last dose of pantoprazole; there was no evidence of rebound hypersecretion.

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 receptor level, it can inhibit hydrochloric acid secretion independently of stimulation by other substances (acetylcholine, histamine, and gastrin).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.

Domperidone

Prokinetic Effect: The prokinetic (gastrokinetic) properties of domperidone are related to its peripheral dopamine receptor blocking action.

Antiemetic Effect: Domperidone produces antiemetic effect by blocking dopamine receptors (D2) peripherally. Inhibition of peripheral D2 receptor signaling prevents or relieves various GI symptoms, such as nausea and vomiting, and also relieves reflux and other symptoms associated with upper GI disorders.

PHARMACOKINETIC PROPERTIES

Pantoprazole

Absorption: Like other PPIs, pantoprazole is an acid-labile drug and therefore, administered orally in the form of gastro-resistant pellets. Absorption of pantoprazole, therefore, begins in the intestine only after the pellets leave the stomach. After administration of a single or multiple oral doses of pantoprazole 40 mg, the peak plasma concentration of pantoprazole was achieved in approximately 2.5 hours, and Cmax was 2.5 mcg/ml. Peak serum concentration (Cmax) and area under the serum concentration time curve (AUC) increases in a dose-dependent manner (with dose range from 10 to 80 mg). Pantoprazole does not accumulate, and its pharmacokinetics are unaltered with multiple daily dosing. Pantoprazole undergoes little first-pass metabolism, resulting in an absolute bioavailability of approximately 77%.

Effect of Antacid / Food: Pantoprazole absorption is not affected by concomitant administration of antacids. Administration of pantoprazole with food may delay its absorption up to 2 hours or longer; however, the Cmax and the extent of pantoprazole absorption (AUC) are not altered. Thus, pantoprazole may be taken without regard to timing of meals.

Distribution: The apparent volume of distribution of pantoprazole is approximately 11 to 23.6 liters, distributing mainly in extracellular fluid. The plasma protein binding of pantoprazole is about 98%, primarily to albumin.

Metabolism: Pantoprazole is extensively metabolized in the liver through the cytochrome P450 (CYP) system. The main metabolic pathway is demethylation, by CYP2C19, with subsequent sulfation; other metabolic pathways include oxidation by CYP3A4. There is no evidence that any of the pantoprazole metabolites have significant pharmacologic activity.

Excretion: Renal elimination represents the major route of excretion (about 80 %) for the metabolites of pantoprazole, the rest is excreted with the faeces. There is no renal excretion of unchanged pantoprazole. The main metabolite in both the serum and urine is desmethyl pantoprazole which is conjugated with sulphate. Following oral administration, the serum concentration of pantoprazole declines biexponentially, with a terminal elimination half-life of approximately one hour.

Domperidone

Pharmacokinetics of domperidone in prolonged-release formulation is not available. Conventional formulation of domperidone (i.e., immediate release) has following pharmacokinetic properties:

Absorption: Domperidone is rapidly absorbed after oral administration, with peak plasma concentrations occurring at approximately 1 hour after dosing. The Cmax and AUC values of domperidone increased proportionally with dose in the 10 mg to 20 mg dose range. The low absolute bioavailability of oral domperidone (approximately 15%) is due to an extensive firstpass metabolism in the gut and liver.

Effect of Food: Domperidone's bioavailability is enhanced in normal subjects when taken after a meal. The time of peak absorption is slightly delayed and the AUC somewhat increased when domperidone is taken after a meal.

Distribution: Oral domperidone does not appear to accumulate or induce its own metabolism. The peak plasma concentration (Cmax) of 18 ng/ml to 21 ng/ml occurs 1.5 hours (Tmax) after the oral dose. Domperidone is 91 to 93% bound to plasma proteins. Distribution studies with domperidone have shown wide tissue distribution, but low brain concentration.

Metabolism: Domperidone undergoes rapid and extensive hepatic metabolism by hydroxylation and N-dealkylation. In vitro metabolism experiments with diagnostic inhibitors revealed that CYP3A4 is a major form of cytochrome P-450 involved in the N-dealkylation of domperidone, whereas CYP3A4, CYP1A2 and CYP2E1 are involved in domperidone aromatic hydroxylation.

Excretion: After oral dose, domperidone is excreted mainly by renal (31%) and biliary (66%) routes. The proportion of the drug excreted unchanged is small (10% of fecal excretion and approximately 1% of urinary excretion). The plasma half-life after a single oral dose is 7 to 9 hours in healthy subjects, but is prolonged in patients with severe renal insufficiency.

THERAPEUTIC INDICATIONS

Combination of pantoprazole and domperidone is indicated for the treatment of Gastroesophageal reflux disease (GERD) not responding adequately to pantoprazole alone.

DOSAGE AND ADMINISTRATION

For oral administration in adults.

Recommended dose is 1 capsule to be administered once daily for 4 to 8 weeks.

Combination of pantoprazole and domperidone may be administered with or without food. The capsules should be swallowed whole with water and not to be opened, chewed or crushed. Or, as prescribed by the physician.

CONTRAINDICATIONS

Combination of pantoprazole and domperidone Capsules are contraindicated in the following:

· Patients with known hypersensitivity to pantoprazole or to any substituted benzimidazole derivative or to domperidone or to any component of the formulation.

· In patients receiving rilpivirine-containing products.

· Prolactin-releasing pituitary tumor (prolactinoma).

· In patients with gastrointestinal hemorrhage, mechanical obstruction or perforation (i.e., when stimulation of the gastric motility could be harmful).

· In patients with moderate or severe hepatic impairment.

· In patients who have known existing prolongation of cardiac conduction intervals, particularly QTc.

·Patients with significant electrolyte disturbances (hypokalemia, hyperkalemia, hypomagnesemia) or underlying cardiac disease such as congestive heart failure (CHF).

· Co-administration with QT-prolonging drugs.

· Co-administration with potent CYP3A4 inhibitors.

WARNINGS AND PRECAUTIONS

Pantoprazole

Presence of Gastric Malignancy: In adults, symptomatic response to therapy with pantoprazole does not preclude the presence of gastric malignancy. Consider additional follow-up and diagnostic testing in adult patients who have a suboptimal response or an early symptomatic relapse after completing treatment with a pantoprazole.

Acute Interstitial Nephritis: Acute interstitial nephritis has been observed in patients taking pantoprazole. Acute interstitial nephritis may occur at any point during pantoprazole therapy and is generally attributed to an idiopathic hypersensitivity reaction. Discontinue pantoprazole if acute interstitial nephritis develops. Clostridium Difficile-Associated Diarrhea (CDAD): Published observational studies suggest that pantoprazole therapy may be associated with an increased risk of CDAD, especially in hospitalized patients. This diagnosis should be considered for diarrhea that does not improve.

Risk of Bone Fractures: Proton pump inhibitors (PPIs), 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. Patients should use the lowest dose and shortest duration of PPI therapy appropriate to the condition being treated. 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.

Cutaneous and Systemic Lupus Erythematosus: Cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE) have been reported in patients taking PPIs, including pantoprazole. These events have occurred as both new onset and an exacerbation of existing autoimmune disease. The most common form of CLE reported in patients treated with PPIs was subacute CLE (SCLE) and occurred within weeks to years after continuous drug therapy in patients ranging from infants to the elderly. The occurrence of CLE with previous PPI treatment may increase the risk of CLE with other PPIs. Systemic lupus erythematosus (SLE) is less commonly reported than CLE in patients receiving PPIs. The 3 majority of patients presented with rash. If lesions occur, especially in sun-exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical help promptly and pantoprazole therapy should be stopped immediately. Most patients improve with discontinuation of the PPI alone in 4 to 12 weeks.

Cyanocobalamin (Vitamin B12) Deficiency: Generally, daily treatment with any acidsuppressing medication over a long period of time (e.g., longer than 3 years) may lead to malabsorption of vitamin B12 caused by hypo- or achlorhydria. Rare reports of cyanocobalamin deficiency occurring with acid-suppressing therapy have been reported in the literature. This diagnosis should be considered if clinical symptoms consistent with cyanocobalamin deficiency are observed.

Hypomagnesemia: Hypomagnesemia, symptomatic and asymptomatic, has been reported rarely in patients treated with PPIs for at least 3 months, in most cases after a year of therapy. Serious adverse events include tetany, arrhythmias, and seizures. In most patients, treatment of hypomagnesemia required magnesium replacement and discontinuation of the PPI. For patients expected to be on prolonged treatment or who take PPIs with medications such as digoxin or drugs that may cause hypomagnesemia (e.g., diuretics), monitoring of magnesium levels prior to initiation of PPI treatment and periodically thereafter should be considered.

Domperidone

Cardiovascular Effects: Domperidone has been associated with prolongation of the QT interval on the electrocardiogram. During post-marketing surveillance, there have been very rare cases of QT prolongation and torsades de pointes in patients taking domperidone. These reports included patients with confounding risk factors, electrolyte abnormalities and concomitant treatment which may have been contributing factors.

Epidemiological studies showed that domperidone was associated with an increased risk of serious ventricular arrhythmias or sudden cardiac death. A higher risk was observed in patients older than 60 years, patients taking daily doses greater than 30 mg, and patients concurrently taking QT-prolongation drugs or CYP3A4 inhibitors.

Domperidone is contraindicated in patients with known existing prolongation of cardiac conduction intervals, particularly QTc, in patients with significant electrolyte disturbances (hypokalaemia, hyperkalaemia, hypomagnesaemia), or bradycardia, or in patients with underlying cardiac diseases such as congestive heart failure (CHF) due to increased risk of ventricular arrhythmia. Electrolyte disturbances or bradycardia are known to be conditions increasing the proarrythmic risk. Treatment with domperidone should be stopped if signs or symptoms occur that may be associated with cardiac arrhythmia, and the patients should consult their physician. Patients should be advised to promptly report any cardiac symptoms.

Use with Apomorphine: Domperidone is contraindicated with QT prolonging drugs including apomorphine, unless the benefit of the co-administration with apomorphine outweighs the risks.

Use in Infants and Children: Although neurological side effects are rare, the risk of neurological side effects is higher in young children since metabolic functions and the bloodbrain barrier are not fully developed in the first months of life. Overdosing may cause extrapyramidal symptoms in children, but other causes should be taken into consideration.

DRUG INTERACTIONS

Pantoprazole

Antiretroviral Drugs: The effect of PPIs on antiretroviral drugs is variable. The clinical importance and the mechanisms behind these interactions are not always known.

· Decreased exposure of some antiretroviral drugs (e.g., rilpivirine atazanavir, and nelfinavir) when used concomitantly with pantoprazole may reduce antiviral effect and promote the development of drug resistance. Concomitant use of rilpivirinecontaining products with pantoprazole is contraindicated. Also, concomitant use of nelfinavir with pantoprazole should be avoided.

· Increased exposure of other antiretroviral drugs (e.g., saquinavir) when used concomitantly with pantoprazole may increase toxicity.

· There are other antiretroviral drugs which do not result in clinically relevant interactions with pantoprazole.

Coumarin Anticoagulants/Warfarin: There have been post-marketing reports of increased international normalized ratio (INR) and prothrombin time in patients receiving PPIs, including pantoprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even death. Monitor INR and prothrombin time and adjust the dose of warfarin, if needed, to maintain the target INR range.

Clopidogrel: Concomitant administration of pantoprazole and clopidogrel in healthy subjects had no clinically important effect on exposure to the active metabolite of clopidogrel or clopidogrel-induced platelet inhibition. No dose adjustment of clopidogrel is necessary when administered with an approved dose of pantoprazole.

Methotrexate: Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose) may elevate and prolong serum levels of methotrexate and/or its metabolite, possibly leading to methotrexate toxicities. A temporary withdrawal of pantoprazole therapy may be considered in some patients receiving high-dose of methotrexate.

Drugs for Which Gastric pH Can Affect Bioavailability (iron salts, erlotinib, dasatinib, nilotinib, mycophenolate mofetil, and ketoconazole): Pantoprazole causes long-lasting inhibition of gastric acid secretion. Therefore, pantoprazole may reduce absorption of other drugs where gastric pH is an important determinant of their bioavailability.

Mycophenolate Mofetil (MMF): Co-administration of pantoprazole sodium in healthy subjects and in transplant patients receiving MMF has been reported to reduce the exposure to the active metabolite, mycophenolic acid (MPA), possibly due to a decrease in MMF solubility at an increased gastric pH. The clinical relevance of reduced MPA exposure on organ rejection has not been established in transplant patients receiving pantoprazole therapy and MMF.

Use pantoprazole with caution in transplant patients receiving MMF.

Drug/Laboratory Tests Interactions

False Positive Urine Tests for THC: There have been reports of false positive urine screening tests for tetrahydrocannabinol (THC) in patients receiving PPIs, including pantoprazole. An alternative confirmatory method should be considered to verify positive results.

Increased Chromogranin A (CgA) Level: Increase in CgA may interfere with investigations for neuroendocrine tumours. To avoid this interference, pantoprazole treatment should be stopped for at least 5 days before CgA measurements. If CgA and gastrin levels have not returned to reference range after initial measurement, measurements should be repeated 14 days after cessation of pantoprazole treatment.

Domperidone

The main metabolic pathway of domperidone is through CYP3A4. In vitro data suggest that the concomitant use of drugs that significantly inhibit this enzyme may result in increased plasma levels of domperidone. There is increased risk of occurrence of QT-interval prolongation, due to pharmacodynamic and/or pharmacokinetic interactions.

1) Concomitant use of the following drugs is contraindicated.

i. QTc-prolonging medicinal products:

· Anti-arrhythmics class IA (e.g., disopyramide, hydroquinidine, quinidine).

· Anti-arrhythmics class III (e.g., amiodarone, dofetilide, dronedarone, ibutilide, sotalol).

· Certain antipsychotics (e.g., haloperidol, pimozide, sertindole).

· Certain antidepressants (e.g., citalopram, escitalopram).

· Certain antibiotics (e.g., erythromycin, levofloxacin, moxifloxacin, spiramycin).

· Certain antifungal agents (e.g., pentamidine).

· Certain antimalarial agents (e.g., halofantrine, lumefantrine).

· Certain gastrointestinal medicines (e.g., cisapride, dolasetron, prucalopride).

· Certain antihistaminics (e.g., mequitazine, mizolastine).

· Certain medicines used in cancer (e.g., toremifene, vandetanib, vincamine).

· Other medicines (e.g., bepridil, diphemanil, methadone).

ii. Potent CYP3A4 inhibitors (regardless of their QT prolonging effects):

· Protease inhibitors.

· Systemic azole antifungals.

· Some macrolides (e.g., erythromycin, clarithromycin, and telithromycin).

2) Concomitant use of the following drugs is not recommended.

· Moderate CYP3A4 inhibitors (e.g., diltiazem, verapamil, and some macrolides).

3) Concomitant use of the following drugs requires caution.

· Caution with bradycardia and hypokalaemia-inducing drugs, as well as with the following macrolides involved in QT-interval prolongation: Azithromycin and roxithromycin.

Ketoconazole/Erythromycin and QTc Prolongation: Separate in vivo pharmacokinetic/pharmacodynamic interaction studies with oral ketoconazole or oral erythromycin in healthy subjects confirmed a marked inhibition of domperidone's CYP3A4 6 mediated first pass metabolism by these drugs (as both of these drugs significantly inhibit CYP3A4 enzyme). Both the Cmax and AUC of domperidone at steady state were increased approximately three-fold in each of these interaction studies. In these studies, concomitant use of domperidone and ketoconazole or erythromycin resulted in increase in QTc, over the observation period.

USE IN SPECIAL POPULATIONS

Pregnant Women

Pantoprazole:

Pregnancy Category C; Domperidone: Pregnancy Category C. Reproduction studies have been performed in rats at oral doses up to 88- times the recommended human dose and in rabbits at oral doses up to 16-times the recommended human dose and have revealed no evidence of impaired fertility or harm to the fetus due to pantoprazole. There are limited post-marketing data on the use of domperidone in pregnant women. Studies in animals have shown reproductive toxicity at maternally toxic doses.

There are however, no adequate and well controlled studies available for use of pantoprazole with domperidone combination therapy in pregnant women. Because animal reproduction studies are not always predictive of human response, Pantoprazole & Domperidone combination Capsules should be used during pregnancy only if the potential benefit justifies the possible risk to the fetus.

Lactating Women

Animal studies have shown that pantoprazole and its metabolites are excreted in the milk. Excretion of pantoprazole in human milk has also been reported (insufficient information). However, the clinical relevance of this finding is not known. Many drugs which are excreted in human milk have a potential for serious adverse reactions in nursing infants. Similarly, with pantoprazole, a risk to the newborns/infants cannot be excluded.

Domperidone is excreted in human milk and breast-fed infants receive less than 0.1 % of the maternal weight-adjusted dose. Occurrence of adverse effects, in particular cardiac effects cannot be excluded after exposure via breast milk. Caution should be exercised in case of QTc prolongation risk factors in breast-fed infants. Pantoprazole & Domperidone combination capsules should not be used during breast feeding. Accordingly, a decision should be made whether to discontinue nursing or to discontinue/abstain from therapy, taking into account the benefit of the drug to the mother.

Paediatric Patients

Safety and efficacy of pantoprazole with domperidone combination therapy has not been established in paediatric patients. Thus, pantoprazole with domperidone combination Capsules are not recommended for use in children and adolescents below 18 years of age.

Geriatric Patients

No overall differences in safety or effectiveness were observed between elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out. Elderly patients may be given the same dose as recommended for adults. No dose adjustment is necessary in these patients.

Renal Impairment

Patients Dosage modification is not necessary when pantoprazole is administered to patients with impaired renal function. On repeated administration, the elimination half-life of domperidone is prolonged in patients with severe renal impairment. Pantoprazole with domperidone capsules can be administered in patients with mild to moderate renal dysfunction. However, in patients with severe renal impairment, Pantoprazole with domperidone Capsules should be used with caution and dose/dosage frequency may need to be reduced depending on the severity of the renal dysfunction.

Hepatic Impairment

Patients In patients with severe liver impairment, a daily dose of pantoprazole 20 mg should not be exceeded. With domperidone, no dosage adjustment is necessary in patients with mild hepatic impairment. Thus, Pantoprazole with domperidone capsules can be administered in patients with mild hepatic dysfunction. If used in these patients, the liver enzymes should be monitored regularly, particularly on long-term therapy. In the case of a rise in liver enzymes, the treatment should be discontinued. Pantoprazole with domperidone capsules are contraindicated in patients with moderate or severe hepatic impairment.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES

Both, pantoprazole and domperidone have no or negligible influence on the ability to drive and use machines. However, adverse reactions such as dizziness and visual disturbances may occasionally occur in patients on PPIs drug therapy. If affected, patients should not drive or use machines.

ADVERSE EFFECTS

PANTOPRAZOLE

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug may not reflect the rates observed in clinical practice.

Common adverse reactions reported with pantoprazole therapy in clinical trials with frequency > 2% include: Headache, diarrhea, nausea, abdominal pain, vomiting, flatulence, dizziness, and arthralgia.

Additional adverse reactions reported in clinical trials with a frequency of ≤ 2% include: Body as a Whole: Allergic reaction, pyrexia, photosensitivity reaction, facial edema.

Gastrointestinal: Constipation, dry mouth, hepatitis. Hematologic: Leukopenia, thrombocytopenia. Metabolic/Nutritional: Elevated creatine kinase (CK), generalized edema, elevated triglycerides, elevated liver enzymes.

Musculoskeletal: Myalgia. Nervous: Depression, vertigo. Skin and Appendages: Urticaria, rash, pruritus. Special Senses: Blurred vision.

Post-Marketing Experience :

Acute kidney injury as an adverse drug reaction reported with the use of proton pump inhibitors. The following adverse reactions have been identified during post-approval use of pantoprazole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

General Disorders and Administration Conditions: Asthenia, fatigue, malaise.

Hematologic: Pancytopenia, agranulocytosis.

Hepatobiliary Disorders: Hepatocellular damage leading to jaundice and hepatic failure.

Immune System Disorders: Anaphylaxis (including anaphylactic shock), SLE.

Infections and Infestations: Clostridium difficile-associated diarrhea.

Investigations: Weight changes.

Metabolism and Nutritional Disorders: Hyponatremia, hypomagnesemia.

Musculoskeletal Disorders: Rhabdomyolysis, bone fracture.

Nervous System: Ageusia, dysgeusia.

Psychiatric Disorders: Hallucination, confusion, insomnia, somnolence.

Renal and Urinary Disorders: Interstitial nephritis.

Skin and Subcutaneous Tissue Disorders: Severe dermatologic reactions, including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), angioedema (Quincke’s edema) and CLE.

Domperidone

Central Nervous System: As the pituitary gland is outside the blood-brain barrier, domperidone may cause an increase in prolactin levels. In rare cases this hyperprolactinaemia may lead to neuro-endocrinological side effects such as galactorrhoea, gynaecomastia and amenorrhoea. Extrapyramidal side effects are very rare in neonates and infants, and exceptional in adults. These side effects reverse spontaneously and completely as soon as the treatment is stopped. Other central nervous system-related effects of convulsion, agitation and somnolence also are very rare and primarily reported in infants and children.

The adverse drug reactions are ranked below by frequency, using the following convention: Very common (≥ 1/10), common (≥ 1/100 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000), not known (cannot be estimated from available data).

General Disorders:

Uncommon: Asthenia.

Immune System Disorder: Not known: Anaphylactic reactions including anaphylactic shock and angioedema. Psychiatric Disorders:

Uncommon: Anxiety, loss of libido;

Not known: Agitation, nervousness.

Nervous System Disorders:

Uncommon: Somnolence, headache;

Not known: Extrapyramidal disorder, convulsions.

Eye Disorders: Not known: Oculogyric crisis.

Cardiac Disorders: Not known: Ventricular arrhythmias, QTc prolongation, Torsade de Pointes, sudden cardiac death.

Gastrointestinal Disorders:

Common: Dry mouth;

Uncommon: Diarrhoea.

Skin and Subcutaneous Tissue Disorders:

Uncommon: Rash, pruritus;

Not known: Urticaria, angioedema.

Reproductive System and Breast Disorders:

Uncommon: Breast pain, breast tenderness, galactorrhoea;

Not known: Gynaecomastia, amenorrhoea.

Renal and Urinary Disorders: Not known: Urinary retention.

Investigations: Not known: Abnormal liver function test, increased blood prolactin

OVERDOSAGE

Experience in patients taking very high doses of pantoprazole (> 240 mg) is limited. Pantoprazole is not removed by hemodialysis. In case of overdose, treatment should be symptomatic and supportive.

INCOMPATIBILITIES :

Not Applicable

STORAGE

Store at a temperature below 25°C.

Protect from moisture.

Keep the medicine out of reach of children.

PRESENTATION

Strip of 10 Capsules

MANUFACTURED BY

Pinnacle Life Science Pvt. Ltd.

(Subsidiary of Aarti Drugs Ltd.)

At D-42, IIE SIDCUL, Selaqui,