Pansa DSR Capsules

Pantoprazole Gastro-resistant and Domperidone Prolonged-release Capsules IP [40 mg + 30 mg]

Each hard gelatin capsule contains :

Pantoprazole Sodium IP

equivalent to Pantoprazole 40 mg

(As Gastro-resistant pellets)

Colour : Indigo Carmine

Domperidone IP 30 mg

(As Prolonged-release pellets)

Colour : Lake of Sunset Yellow

Approved colours used in the capsule shell.

Capsule, Pantoprazole (40 mg) and Domperidone (30 mg).

4.1 Therapeutic indications

For the treatment gastro-esophageal reflux disease (GERD) not responding adequately to Pantoprazole alone.

4.2 Posology and method of administration

1 Capsule to be administered once daily.

Pansa DSR capsules should be administered on empty stomach, preferably in the morning or at least 1 hour prior to meal. The capsules should be swallowed whole with water and not to be opened, chewed or crushed.

Pediatric patients

Pansa DSR Capsules are not recommended for use in children.

4.3 Contraindications

• 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.

4.4 Special warnings and precautions for use

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 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 acid-suppressing 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 acidsuppressing 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 are higher in young children since metabolic

functions and the blood-brain 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.

4.5 Interaction with other medicinal products and other forms of interaction

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 Rilpivirine containing 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 has 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.

Concomitant use of the following drugs is contraindicated.

A. QTc-prolonging medicinal products

• Anti-arrhythmic class IA (e.g. Disopyramide, Hydroquinidine, Quinidine).
• Anti-arrhythmic 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 antihistaminic (e.g. Mequitazine, Mizolastine).
• Certain medicines used in cancer (e.g. Toremifene, Vandetanib, Vincamine).
• Other medicines (e.g. Bepridil, Diphemanil, Methadone).

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

• Protease inhibitors.
• Systemic azole antifungals.
• Some macrolides (e.g. Erythromycin, Clarithromycin and Telithromycin).

Concomitant use of the following drugs is not recommended.

• Moderate CYP3A4 inhibitors (e.g. Diltiazem, Verapamil and some macrolides).

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 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.

4.6 Use in special populations

Pregnancy

Pansa DSR capsule should be used during pregnancy only if the potential benefit justifies the possible risk to the fetus.

Breast-feeding

Pansa DSR 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.

4.7 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.

4.8 Undesirable effects

Pantoprazole

Clinical trials 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, diarrhoea, 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.

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 : Diarrhea 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

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. Healthcare professionals are asked to report any suspected adverse reactions via email to : medico@zuventus.com

Website : https://www.zuventus.co.in/drug-safety-reporting

By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Symptoms

Symptoms of overdose are agitation, altered consciousness, convulsions, disorientation, somnolence, and extrapyramidal reactions.

Treatment

There is no specific antidote, but in the event of overdose, gastric lavage as well as the administration of activated charcoal, may be useful. Close medical supervision and supportive therapy is recommended. Anticholinergic, Antiparkinson drugs may be helpful in controlling the extrapyramidal reactions.

5.1 Mechanism of action

Pantoprazole

Pantoprazole is a proton pump inhibitor (PPI) class of anti-secretory 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 anti-secretory 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 gastro-kinetic 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 (gastro-kinetic) effects and antagonism of dopamine receptors in the chemoreceptor trigger zone (CTZ), which lies outside the BBB in the area postrema. Oral Domperidone also increases lower esophageal sphincter (LES) pressure, thus, improve antroduodenal motility and accelerate gastric emptying. There is no effect on gastric secretion.

5.2 Pharmacodynamic properties

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 (gastro-kinetic) 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.

5.3 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 sustained 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 first-pass metabolism in the gut and liver.

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.

6.1 Animal toxicology or pharmacology

Pantoprazole

Carcinogenesis

In a 24-month carcinogenicity study, Sprague-Dawley rats were treated orally with Pantoprazole doses of 0.5 to 200 mg/kg/day, about 0.1 to 40 times the exposure on a body surface area basis of a 50 kg person dosed with 40 mg/day. In the gastric fundus, treatment with 0.5 to 200 mg/kg/day produced enterochromaffin-like (ECL) cell hyperplasia and benign and malignant neuroendocrine cell tumors in a dose-related manner. In the forestomach, treatment with 50 and 200 mg/kg/day (about 10 and 40 times the recommended human dose on a body surface area basis) produced benign squamous cell papillomas and malignant squamous cell carcinomas. Rare gastrointestinal tumors associated with Pantoprazole treatment included an adenocarcinoma of the duodenum with 50 mg/kg/day and benign polyps and adenocarcinomas of the gastric fundus with 200 mg/kg/day. In the liver, treatment with 0.5 to 200 mg/kg/day produced dose-related increases in the incidences of hepatocellular adenomas and carcinomas. In the thyroid gland, treatment with 200 mg/kg/day produced increased incidences of follicular cell adenomas and carcinomas for both male and female rats. In a 24-month carcinogenicity study, B6C3F1 mice were treated orally with doses of 5 to 150 mg/kg/day of Pantoprazole, 0.5 to 15 times the recommended human dose based on body surface area. In the liver, treatment with 150 mg/kg/day produced increased incidences of hepatocellular adenomas and carcinomas in female mice. Treatment with 5 to 150 mg/kg/day also produced gastric-fundic ECL cell hyperplasia. A 26-week p53 +/-transgenic mouse carcinogenicity study was not positive.

Domperidone

Safety margins in in vitro proarrhythmic models (isolated Langendorff perfused heart) exceeded the free plasma concentrations in humans at maximum daily dose (10 mg administered 3 times a day) by 9- up to 45-fold. In in vivo models the no effect levels for QTc prolongation in dogs and induction of arrhythmias in a rabbit model sensitized for torsade de 13 pointes exceeded the free plasma concentrations in humans at maximum daily dose (10 mg administered 3 times a day) by more than 22-fold and 435-fold, respectively. In the anesthetized guinea pig model following slow intravenous infusions, there were no effects on QTc at total plasma concentrations of 45.4 ng/ml, which are 3-fold higher than the total plasma levels in humans at maximum daily dose (10 mg administered 3 times a day). At a high, maternally toxic dose (more than 40 times the recommended human dose), teratogenic effects were seen in the rat. No teratogenicity was observed in mice and rabbits. Development abnormalities observed in rats at a high exposure. Risk of carcinogenicity, mutagenicity or sensitisation cannot be excluded.

Each capsule of Pansa DSR contains 40 mg of Pantoprazole (in a gastro-resistant form) and 30 mg of Domperidone (in a prolonged release form) for oral administration in adults.

Pantoprazole

Pantoprazole Sodium is the Sodium salt form of Pantoprazole. Pantoprazole is a substituted Benzimidazole, proton pump inhibitor (PPI) class of anti-secretory agents which suppressesgastric acid production.

Molecular weight : 405.40 g/mol

Molecular formula : C₁₆H₁₄F₂N₃NaO₄S

Chemical name : Sodium; 5-(difluoromethoxy)-2-[(3,4-dimethoxypyridin-2- yl) methylsulfinyl] benzimidazol-1-ide Domperidone Domperidone is a dopamine receptor antagonist drug with antiemetic and gastrokinetic properties. Domperidone is white or almost white powder which is slightly soluble in water. Molecular weight : 425.90 g/mol Molecular formula : C22H24ClN5O2 Chemical name : 6-chloro-3-[1-[3-(2-oxo-3H-benzimidazol-1-yl)propyl]piperidin-4-yl]-1H-benzimidazol-2-one.

8.1 Incompatibilities

Not applicable

8.2 Shelf-life

Refer on the pack.

8.3 Packaging information

Alu-Alu blister strip of 10 capsules.

8.4 Storage and handling instructions

Store protected from moisture at a temperature not exceeding 25°C.

Keep out of reach of children.

• Instruct patients to take Pansa DSR Capsule exactly as prescribed by doctor. Do not change the dose or stop therapy without consulting to your doctor.
• Instruct patients to swallow Pansa DSR Capsule as a whole with water and not to open, chew or crush the capsules.
• If you miss a dose, take it as soon as possible. If it is almost time for your next dose, do not take the missed dose. Take the next dose at your regular time. Do not take 2 capsules per doses at the same time to make up for the missed dose.
• Pregnant women can use this medicine only if essential and in consultation with their doctor.
• Advise nursing mothers to avoid use of this medicine during lactation or not to breastfeed their infants while on drug therapy.
• This medicine is not recommended for use in children.
• Instruct patients not to share this medication with other people even though symptoms are similar. It may harm them.
• Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. Pansa DSR Capsules and certain other medicines can interact with each other causing serious side effects.

04 July 2024