Prazole Plus

Prazole Plus

Manufacturer:

Multicare

Distributor:

Zuellig
Full Prescribing Info
Contents
Pantoprazole, domperidone.
Description
Each capsule contains pantoprazole sodium sesquihydrate equivalent to pantoprazole 40 mg as enteric-coated pellets and domperidone 30 mg as sustained-release (SR) pellets.
It also contains the following excipients: Colors: Lake of indigo carmine, red ferric oxide, yellow ferric oxide and titanium dioxide (approved colors used in capsule shell).
Prazole Plus is a fixed-dose combination of pantoprazole and domperidone.
Action
Pharmacology: Mechanism of Action: Pantoprazole, a benzimidazole sulfoxide 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 sulfonamide. The sulfonamide binds covalently to cysteine residues on the luminal (acidic) surface of H+/K+-ATPase to form a mixed disulfide; 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 acid secretion. Domperidone, a benzimidazole derivative (structurally related to the butyrophenones), acts by selectively antagonizing the peripheral dopaminergic, receptors in the gastrointestinal 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 gastrointestinal disorders are frequently associated with a combination of hyperacidity and dysmotility. As a result, acidic chyme 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 gastroesophageal reflux disease (GERD) and nonulcer dyspepsia (NUD), a combination of drugs which will take care of both would be ideal. Pantoprazole is a potent gastric acid 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 gastrointestinal 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, without compromising on its efficacy, domperidone SR is developed. Domperidone SR (30 mg) is for once-daily administration since its plasma t½ is otherwise 12-16 hrs.
Pharmacokinetics: Pantoprazole: Pantoprazole is rapidly absorbed after oral administration, with peak plasma concentrations (Cmax) of 1.1-3.1. (mean 2.1) mg/L occurring within 2-4 (mean 2.7) hrs (tmax) after ingestion of an enteric-coated 40 mg tablet. 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 t½ (ty,P) of 0.9-1.9 hrs. However, since inhibition of acid secretion is noncompetitive 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 bioavailability of pantoprazole. Pantoprazole undergoes extensive hepatic metabolism via cytochrome P450 (CYP450) oxidase followed by sulfate conjugation. Elimination of pantoprazole is predominantly renal, with -80% of an oral dose being excreted as urinary metabolite; the remainder is excreted in the feces 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 20-mg oral dose is in the range of 15-19 ng/mL. The mean elimination t½ ranges from 12-16 hrs 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 min 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.
Special Populations: Pantoprazole: Hepatic Impairment: There is a slight increase (1.5-fold) in maximum drug concentrations in patients with mild to severe hepatic impairment. No dosage adjustment is needed in patients with mild to severe hepatic impairment.
Renal Impairment: Pharmacokinetic parameters for pantoprazole in patients with severe renal impairment are similar to those of healthy subjects. No dosage adjustment is needed in patients with renal impairment.
Gender: No dosage adjustment is needed based on gender.
Pediatrics: The pharmacokinetics of pantoprazole have not been investigated in patients <18 years.
Geriatrics: No dosage adjustment is recommended based on age.
Domperidone: Hepatic Impairment: There is no published pharmacokinetic data in patients with hepatic impairment. Because domperidone is extensively metabolized, response to Prazole Plus should be carefully monitored in this patient population.
Neonates: Domperidone is not recommended for use in neonates.
Lactation: Domperidone may precipitate galactorrhea and improve postnatal lactation. It is secreted in breast milk in very small quantities and thus insufficient to be considered harmful.
Pediatrics: Domperidone is not recommended other than for treatment of nausea and vomiting in patients undergoing cancer therapy. There may be an increased risk for extrapyramidal reactions in young children because of an incompletely developed blood-brain barrier.
Pregnancy: The safety of domperidone has not been proven, therefore its use is not recommended in pregnant women.
Geriatrics: No special precautions are necessary in older patients.
Prazole Plus should be used with caution in conditions where the individual drugs have been used with precautionary approach.
Indications/Uses
Management of GERD; gastritis, NUD, gastric or duodenal ulcer, dyspepsia, bloating, fullness, belching, nonsteroidal anti-inflammatory drug (NSAID)-induced dyspepsia.
Dosage/Direction for Use
Usual Recommended Dose: 1 capsule daily before breakfast.
Administration: Swallow capsule whole, do not chew the capsule. The content of the vial needs to be reconstituted with 0.9% sodium chloride injection w/v 10 mL before injection. This freshly prepared solution should be administered IV over 2-15 min, either as a slow injection or it may be further diluted with 0.9% sodium chloride injection w/v 100 mL or 5% glucose injection and administered as a short-term infusion. The duration of administration should be 2-15 min. The reconstituted solution must be used within 12 hrs of preparation.
Overdosage
In the event of overdosage, gastric lavage should be performed. Symptomatic and supportive measures are recommended.
Contraindications
Known hypersensitivity to pantoprazole, domperidone or any of the excipients of Prazole Plus.
Due to lack of controlled studies in pregnant and lactating women, use of Prazole Plus is contraindicated in pregnancy and lactation.
Special Precautions
Prazole Plus shall be given with care to patients with renal or hepatic dysfunction.
Use In Pregnancy & Lactation
Due to lack of controlled studies in pregnant and lactating women, use of Prazole Plus is contraindicated in pregnancy and lactation.
Adverse Reactions
Pantoprazole: The adverse reactions associated with pantoprazole include headache, diarrhea, skin rash, pruritus and dizziness. Domperidone: Serum prolactin level may rise resulting in galactorrhea in females and less frequently gynecomastia in males due to domperidone. Dry mouth, thirst, headache, nervousness, drowsiness, diarrhea, skin rashes and itching may follow treatment with domperidone.
Drug Interactions
Pantoprazole: Pantoprazole is metabolized through the CYP450 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 CYP450 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, ethynylestradiol), 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 (eg, ketoconazole, ampicillin esters and iron salts).
Domperidone: Anticholinergic drugs may inhibit the antidyspeptic effects of domperidone. Antimuscarinic agents and opioid analgesics may antagonize the effect of domperidone. Domperidone suppresses the peripheral effects (digestive disorders, nausea and vomiting) of dopaminergic agonists. Since domperidone has gastrokinetic 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 hypoprolactinemic agents and with some diagnostic tests. Antacids and antisecretory agents lower the oral bioavailability of domperidone. They should be taken after meals and not before meals ie, 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 a temperature below 25°C. Protect from light and moisture.
MIMS Class
Antacids, Antireflux Agents & Antiulcerants / GIT Regulators, Antiflatulents & Anti-Inflammatories
ATC Classification
A02BC02 - pantoprazole ; Belongs to the class of proton pump inhibitors. Used in the treatment of peptic ulcer and gastro-oesophageal reflux disease (GERD).
Presentation/Packing
Cap (hard-gelatin, transparent size "1", filled with blue and brown to yellowish-brown spherical pellets) 30's.
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