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Indications/Uses
For the symptomatic management of burning in various acid peptic disorders associated with nausea and vomiting; gastro-esophageal reflux disease, non-ulcer dyspepsia, gastroparesis and idiopathic hiccup or any other peptic disease accompanied by nausea and/or vomiting.
Dosage/Direction for Use
The usual recommended dose of Pantoprazole + Domperidone (PANTOKEM-D) is one capsule daily before breakfast.
Swallow capsule as a whole, do not chew the capsule.
Swallow capsule as a whole, do not chew the capsule.
Administration
Should be taken on an empty stomach: Swallow whole, do not chew.
Contraindications
Pantoprazole: Hepatic impairment; hypersensitivity. Domperidone: History of hypersensitivity to dimenhydrinate or related compounds; GI haemorrhage, obstruction and perforation, or after surgery, pregnancy.
Special Precautions
Pantoprazole + Domperidone (PANTOKEM-D) shall be given with care to patients with renal dysfunction or hepatic dysfunction.
Pantoprazole: Not recommended in child <12 yrs. Long-term therapy may lead to bacterial overgrowth in the GIT.
Domperidone: Increases serum prolactin levels resulting to galactorrhoea in females and gynaecomastia in males. Hypertensive crisis in patients with pheochromocytoma.
Pantoprazole: Not recommended in child <12 yrs. Long-term therapy may lead to bacterial overgrowth in the GIT.
Domperidone: Increases serum prolactin levels resulting to galactorrhoea in females and gynaecomastia in males. Hypertensive crisis in patients with pheochromocytoma.
Use In Pregnancy & Lactation
Due to lack of controlled studies in pregnant and lactating women, use of Pantoprazole + Domperidone (PANTOKEM-D) is contraindicated in this group of patients.
Adverse Reactions
Pantoprazole: The adverse reactions associated with Pantoprazole include Headache, Diarrhoea, Skin rash, Pruritus, Dizziness. GIT infections; anaphylaxis, angioedema, chest pain, dyspnoea, erythema multiforme, gastroenteritis, hyperglycaemia, infection, Inj site reaction, jaundice, optic neuropathy, anterior ischaemia, pancreatitis, speech disorder.
Domperidone: Serum prolactin level may rise resulting in galactorrhea in females and less frequently gynaecomastia in males due to Domperidone. Dry mouth, thirst, headache, nervousness, insomnia, lethargy, irritability, GI disturbances, hot flushes, mastalgia, menstrual irregularities, rash, pruritus urticaria, stomatitis, conjunctivitis, urinary frequency, dysuria, oedema, palpitations, leg cramps, asthenia, drug intolerance nervousness Drowsiness, dizziness, diarrhoea, skin rashes and itching may follow treatment with Domperidone.
Domperidone: Serum prolactin level may rise resulting in galactorrhea in females and less frequently gynaecomastia in males due to Domperidone. Dry mouth, thirst, headache, nervousness, insomnia, lethargy, irritability, GI disturbances, hot flushes, mastalgia, menstrual irregularities, rash, pruritus urticaria, stomatitis, conjunctivitis, urinary frequency, dysuria, oedema, palpitations, leg cramps, asthenia, drug intolerance nervousness Drowsiness, dizziness, diarrhoea, skin rashes and itching may follow treatment with Domperidone.
Drug Interactions
Pantoprazole: Pantoprazole is metabolized through the cytochrome P450 system, primarily the CYP2C19 and CYP3A4 isoenzymes, and subsequently undergoes phase II conjugation. Based on studies evaluating possible interactions of Pantoprazole with other drugs metabolized by the cytochrome P450 system, no dosage adjustment is needed with concomitant use of the following drugs: theophylline, cisapride, antipyrine, caffeine, carbamazepine diazepam, diclofenac, digoxin, ethanol, glyburide, oral contraceptives (levonorgestrel/ethynyl estradiol), metoprolol, nifedipine, phenytoin or warfarin. Clinically relevant interactions of Pantoprazole with other drugs with the same metabolic pathways are not expected. Therefore, when co-administered with Pantoprazole, adjustment of the dosage of Pantoprazole with such drugs may not be necessary. There was also no interaction with concomitantly administered antacids.
Because of profound and long lasting inhibition of gastric acid secretion, it is theoretically possible that Pantoprazole may interfere with absorption of drugs where gastric pH is an important determinant of their bioavailability (e.g. Ketoconazole, Ampicillin esters, and iron salts).
Domperidone: Anti-cholinergic drugs may inhibit the anti-dyspeptic effects of Domperidone. Antimuscarinic agents and opioid analgesics may antagonise the effect of Domperidone. Domperidone suppresses the peripheral effects (digestive disorders, nausea and vomiting) of dopaminergic agonists. Since Domperidone has gastro-kinetic effects, it could influence the absorption of concomitant orally administered drugs, particularly those with sustained release or enteric coated formulations.
As Domperidone interferes with serum prolactin levels, it may interfere with other hypoprolactinaemic agents and with some diagnostic tests.
Antacids and anti-secretory agents lower the oral bioavailability of Domperidone. They should be taken after meals and not before meals, i.e. they should not be taken simultaneously with Domperidone. Reduced gastric acidity impairs the absorption of Domperidone.
Oral bioavailability is decreased by prior administration of Cimetidine or Sodium Carbonate.
Because of profound and long lasting inhibition of gastric acid secretion, it is theoretically possible that Pantoprazole may interfere with absorption of drugs where gastric pH is an important determinant of their bioavailability (e.g. Ketoconazole, Ampicillin esters, and iron salts).
Domperidone: Anti-cholinergic drugs may inhibit the anti-dyspeptic effects of Domperidone. Antimuscarinic agents and opioid analgesics may antagonise the effect of Domperidone. Domperidone suppresses the peripheral effects (digestive disorders, nausea and vomiting) of dopaminergic agonists. Since Domperidone has gastro-kinetic effects, it could influence the absorption of concomitant orally administered drugs, particularly those with sustained release or enteric coated formulations.
As Domperidone interferes with serum prolactin levels, it may interfere with other hypoprolactinaemic agents and with some diagnostic tests.
Antacids and anti-secretory agents lower the oral bioavailability of Domperidone. They should be taken after meals and not before meals, i.e. they should not be taken simultaneously with Domperidone. Reduced gastric acidity impairs the absorption of Domperidone.
Oral bioavailability is decreased by prior administration of Cimetidine or Sodium Carbonate.
Storage
Store at temperatures not exceeding 30°C. Protect from light and moisture.
Action
Pharmacology: Pharmacodynamics: Mechanism of Action: Pantoprazole, a benzimidazole sulphoxide derived prodrug, is an irreversible proton pump inhibitor. Pantoprazole, being a weak base, is highly ionized at low pH and readily accumulated in the highly acidic canalicular lumen of the stimulated parietal cell in the stomach. In this acidic environment, it is protonated and rapidly converted to a cationic cyclic sulphonamide. The sulphonamide binds covalently to cysteine residues on the luminal (acidic) surface of H+/K+-ATPase to form a mixed disulphide; thus causing irreversible inhibition of the gastric proton pump. This inhibition of the gastric proton pump or H+/K+-ATPase (which represents the final step in the secretory process), suppresses gastric secretion.
Domperidone, a benzimidazole derivative (structurally related to the butyrophenones), acts by selectively antagonizing the peripheral dopaminergic D2 receptors in the gastrointestinal (G.I.) wall, thereby enhancing gastrointestinal peristalsis and motility and increasing Lower Esophageal Sphincter (LES) tone.
Rationale of Combination: The mode of action of both Pantoprazole and Domperidone are different and complimentary to each other. Upper G.I. disorders are frequently associated with a combination of hyperacidity and dysmotility. As a result, acidic chime may either stagnate in stomach and duodenum or may be evacuated by reverse peristalsis (vomiting or nausea). Reflux of acid contents of stomach cause erosions of lower part of esophagus which may further aggravate nausea and vomiting. Since both hyperacidity and dysmotility are present at the same time in disorders like Gastro Esophageal Reflux Disease (GERD) and Non Ulcer Dyspepsia (NUD), a combination of drugs which will take care of both would be ideal.
Pantoprazole is a potent gastric inhibitor that blocks the final stage of acid secretion. Hence, whatever may be the stimulus, hyperacidity will be controlled by Pantoprazole. In contrast, Domperidone increases G.I. motility, thereby facilitating the movement of acid contents further down in the intestine preventing reflux esophagitis and thereby controlling nausea and vomiting. Hence, the pharmacology of pantoprazole and Domperidone corroborates their use in combined form for the treatment of GERD, NUD and related disorders.
Domperidone is usually administered at a dose of 10-20 mg, 2-3 times daily before meals. In order to enhance patient compliance, Pantoprazole + Domperidone (PANTOKEM-D) has been designed for single dose administration, each containing 30mg of Domperidone pellets in sustained release form. Bioavailability studies conducted on human volunteers have shown biphasic release profile of Domperidone, which allows once daily administration. This helps in improving patient compliance without compromising on the efficacy.
Pharmacokinetics: Pantoprazole: Pantoprazole is rapidly absorbed after oral administration, with peak plasma concentrations (cMAX) of 1.1 to 3.1 (mean 2.1) mg/L occurring within 2 to 4 (mean 2.7) hours (tmax) after ingestion of an enteric coated 40 mg capsule. The volume of distribution is low (mean 0.16 L/kg at steady state) due to high degree of plasma protein binding (~98%). Plasma Pantoprazole concentrations decline monophasically after oral administration, with a mean plasma terminal half-life (t1/2β) of 0.9 to 1.9 hours. However, since inhibition of acid secretion is non-competitive or irreversible, there is no correlation between plasma levels and the duration of action of Pantoprazole. Concomitant intake of food has no influence on the bioavailability of Pantoprazole, and any possible retardant effect of food on the rate of drug absorption is not of clinical relevance, considering the prolonged antisecretory action of Pantoprazole. The enteric coating does not influence the bioav of Pantoprazole. Pantoprazole undergoes extensive hepatic metabolism via cytochrome P450 oxidase followed by sulphate conjugation. Elimination of Pantoprazole is predominantly enal, with ~80% of an oral dose being excreted as urinary metabolite; the remainder is excreted in the faeces and originates primary from biliary secretion.
Domperidone: Domperidone is rapidly and almost completely (93%) absorbed after oral administration. Peak plasma concentrations occur within 30 min. after oral administration. The peak plasma concentration value after a 20mg oral dose is in the range of 15 to 19 ng/ml. The mean elimination half life ranges from 12 -16 hours for an oral dose. Oral bioavailability of Domperidone is 13 - 17% because of extensive presystemic metabolism in gut wall and liver.
Administration of Domperidone 90 minutes after a meal increases bioavailability whereas Cimetidine or alkali pretreatment reduces bioavailability. Domperidone is strongly bound to plasma proteins (90 – 93%). Domperidone undergoes extensive biotransformation with <1% excreted unchanged in urine.
Domperidone, a benzimidazole derivative (structurally related to the butyrophenones), acts by selectively antagonizing the peripheral dopaminergic D2 receptors in the gastrointestinal (G.I.) wall, thereby enhancing gastrointestinal peristalsis and motility and increasing Lower Esophageal Sphincter (LES) tone.
Rationale of Combination: The mode of action of both Pantoprazole and Domperidone are different and complimentary to each other. Upper G.I. disorders are frequently associated with a combination of hyperacidity and dysmotility. As a result, acidic chime may either stagnate in stomach and duodenum or may be evacuated by reverse peristalsis (vomiting or nausea). Reflux of acid contents of stomach cause erosions of lower part of esophagus which may further aggravate nausea and vomiting. Since both hyperacidity and dysmotility are present at the same time in disorders like Gastro Esophageal Reflux Disease (GERD) and Non Ulcer Dyspepsia (NUD), a combination of drugs which will take care of both would be ideal.
Pantoprazole is a potent gastric inhibitor that blocks the final stage of acid secretion. Hence, whatever may be the stimulus, hyperacidity will be controlled by Pantoprazole. In contrast, Domperidone increases G.I. motility, thereby facilitating the movement of acid contents further down in the intestine preventing reflux esophagitis and thereby controlling nausea and vomiting. Hence, the pharmacology of pantoprazole and Domperidone corroborates their use in combined form for the treatment of GERD, NUD and related disorders.
Domperidone is usually administered at a dose of 10-20 mg, 2-3 times daily before meals. In order to enhance patient compliance, Pantoprazole + Domperidone (PANTOKEM-D) has been designed for single dose administration, each containing 30mg of Domperidone pellets in sustained release form. Bioavailability studies conducted on human volunteers have shown biphasic release profile of Domperidone, which allows once daily administration. This helps in improving patient compliance without compromising on the efficacy.
Pharmacokinetics: Pantoprazole: Pantoprazole is rapidly absorbed after oral administration, with peak plasma concentrations (cMAX) of 1.1 to 3.1 (mean 2.1) mg/L occurring within 2 to 4 (mean 2.7) hours (tmax) after ingestion of an enteric coated 40 mg capsule. The volume of distribution is low (mean 0.16 L/kg at steady state) due to high degree of plasma protein binding (~98%). Plasma Pantoprazole concentrations decline monophasically after oral administration, with a mean plasma terminal half-life (t1/2β) of 0.9 to 1.9 hours. However, since inhibition of acid secretion is non-competitive or irreversible, there is no correlation between plasma levels and the duration of action of Pantoprazole. Concomitant intake of food has no influence on the bioavailability of Pantoprazole, and any possible retardant effect of food on the rate of drug absorption is not of clinical relevance, considering the prolonged antisecretory action of Pantoprazole. The enteric coating does not influence the bioav of Pantoprazole. Pantoprazole undergoes extensive hepatic metabolism via cytochrome P450 oxidase followed by sulphate conjugation. Elimination of Pantoprazole is predominantly enal, with ~80% of an oral dose being excreted as urinary metabolite; the remainder is excreted in the faeces and originates primary from biliary secretion.
Domperidone: Domperidone is rapidly and almost completely (93%) absorbed after oral administration. Peak plasma concentrations occur within 30 min. after oral administration. The peak plasma concentration value after a 20mg oral dose is in the range of 15 to 19 ng/ml. The mean elimination half life ranges from 12 -16 hours for an oral dose. Oral bioavailability of Domperidone is 13 - 17% because of extensive presystemic metabolism in gut wall and liver.
Administration of Domperidone 90 minutes after a meal increases bioavailability whereas Cimetidine or alkali pretreatment reduces bioavailability. Domperidone is strongly bound to plasma proteins (90 – 93%). Domperidone undergoes extensive biotransformation with <1% excreted unchanged in urine.
MedsGo Class
Antacids, Antireflux Agents & Antiulcerants / GIT Regulators, Antiflatulents & Anti-Inflammatories
Features
Dosage
40mg / 30mg
Ingredients
- Domperidone
- Pantoprazole
Packaging
Capsule 30's
Generic Name
Pantoprazole Sodium Sesquihydrate / Domperidone
Registration Number
DRP-4926-02
Classification
Prescription Drug (RX)
Product Questions
Questions
