Description and Composition of Perbloc-DSR
Perbloc-DSR is a combination of two drugs which are rabeprazole 20 mg and domperidone 30 mg. These two drugs composition are its active pharmaceutical ingredients. In addition, it contains inactive ingredients called excipients in sufficient quantities.
Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H2 recepter antagonist properties but suppress gastric acid secretion by inhibiting the gastric H+K+ ATPase at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell rabeprazole has been characterized as a gastric proton pump inhibitor. Rabeprazole blocks the final step of gastric acid secretion. In gastric parietal cells, rabeprazole is protonated, accumulates, and is transformed to an active sulfenamide.
Domperidone is a derivative of benzimidazole that possesses both prokinetic and antiemetic properties due to its inhibitory action at dopamine D2 receptors.
Pharmacology and Mechanism of Action of Perbloc-DSR
How does Perbloc-DSR work?
Rabeprazole as a proton pump inhibitor suppress gastric acid secretion by inhibiting the gastric H+K+ ATPase at the secretory surface of the gastric parietal cell. Rabeprazole blocks the final step of gastric acid secretion. In gastric parietal cells, rabeprazole is protonated, accumulates, and is transformed to an active sulfenamide. When studied in vitro, rabeprazole is chemically activated at pH 1.2 with a half of 78 seconds, It inhibits acid transport in porcine gastric vesicles with a half-life of 90 seconds. The anti-secretory effects of rabeprazole begins within one hour after an oral administration of 20 mg Of it. The median inhibitory effect of it on 24 hour gastric acidity is 88% of maximal after the first dose. Rabeprazole 20 mg inhibits basal and peptone meal-stimulated acid secretion versus placebo by 86% and 95%, respectively, and increases the percent of 24-hour period that the gastric pH>3 from 10% to 65%. This relatively prolonged pharmacodynamic action compared to the short pharmacokinetic half-life (1-2 hours) reflects the sustained inactivation of the H+, K+ATPase.
Other effects on humans treated with rabeprazole for up to one year, no systemic effects have been observed on the central nervous, lymphoid, hematopoietic, renal, hepatic, cardiovascular, or respiratory systems. However, no data are available on long-term treatment with rabeprazole and ocular effects.
Domperidone is a dopamine antagonist with anti-emetic properties . Domperidone does not readily cross the blood-brain barrier. Its and-emetic effect may be due to a combination of peripheral (gastrokinetic) effects and antagonism of dopamine receptors in the chemoreceptor trigger zone, which lies outside the blood-brain barrier in the area postrema. Animal studies, together with the low concentrations found in the brain, indicate a predominantly peripheral effect of domperidone on dopamine receptors. Studies in man have shown oral domperidone to increase lower esophageal pressure, improve antroduodenal motility and accelerate gastric emptying. There is no effect on gastric secretion
Uses and Indications of Perbloc-DSR
PERBLOC-DSR is indicated for the relief of symptoms of:
- Nausea associated with acid peptic disorders
- Post-operative nausea and vomiting
- Chronic gastritis
Dosage and Administration of Perbloc-DSR
Perbloc-DSR is taken one capsule once daily or as directed by the physician.
Contraindications of Perbloc-DSR
- PERBLOC-DSR is contraindicated in patients with known hypersensitivity to rabeprazole, substituted benzimidazole, domperidone or to any component of the formulation.
- It should not be used whenever stimulation of gastric motility is to be avoided or could be harmful, e.g. in the presence of gastro-intestinal hemorrhage, obstruction or perforation.
- It is also contraindicated in patients with prolactin-releasing pituitary tumor (prolactinoma).
Warnings and Precautions
- Bone Fracture
Several published observational studies suggest that proton pump inhibitors therapy may be associated with an increased risk for osteoporosis-related fractures of the hip, wrist, or spine. The risk of fracture was increased in patients who received high dose, defined as multiple daily doses, and long-term PPI therapy (a year or longer). Patients should use the lowest dose and shortest duration of PP therapy appropriate to the condition being treated. Patients at risk for osteoporosis-related fractures should be managed according to the established treatment guidelines.
Drug Interactions with Perbloc-DSR
Rabeprazole is metabolized by the cytochrome P450 (CYP450) drug metabolizing enzyme system.
Rabeprazole does not have clinically significant interactions with other drugs metabolized by the CYP450 system, such as warfarin, theophylline, diazepam and phenytoin.
Rabeprazole produces sustained inhibition of gastric acid secretion. An interaction with compounds which are dependent on gastric pH for absorption like ketoconazole may occur due to the magnitude of acid suppression observed with rabeprazole. Therefore, patients may need to be monitored when such drugs are taken concomitantly with rabeprazole.
Co-administration of rabeprazole and antacids produced no clinically relevant changes in plasma rabeprazole concentrations
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. In vivo interaction studies with Ketoconazole revealed a marked inhibition of domperidone’s CYP3A4 mediated first pass metabolism by ketoconazole. A pharmacokinetic study has demonstrated that the AUC and the peak plasma concentration of domperidone is increased by a factor of 3 when oral ketoconazole is administered concomitantly (at steady state). A slight QT-prolonging effect (mean less than 10msec) of this combination was detected, which was greater than the one seen with ketoconazole alone. A QT prolonging effect could not be detected when domperidone was given alone in patients with no co-morbidity, even at high oral doses (up to 160mg/day).
The results of this interaction study should be taken into account when prescribing domperidone concomitantly with strong CYP3A4 inhibitors: for example: ketoconazole, ritonavir and erythromycin. While adverse interactions have not been reported in general clinical use, domperidone has the potential to interact with dopamine agonist (e.g. bromocriptine), antimuscarinics and opioid analgesics. It may also enhance the absorption of concomitantly administered drugs especially in cases of delayed gastric emptying.
General Point to Note
Symptomatic response to therapy with rabeprazole does not preclude the presence of gastric malignancy
PERBLOC-DSR should be used with caution in patients with renal impairment or in those at risk of fluid retention. In patients with severe renal insufficiency (serum creatinine more 6 mg/100 mL, i.e. more than 0.6 mmol/L) the elimination half-life of domperidone was increased, The dosing frequency should be altered depending on the severity of impairment, and the dose may need to be reduced. Patients on prolonged therapy should be reviewed regularly
Since domperidone is highly metabolized in the liver, this drug Should be used not be used in patients with hepatic impairment.
There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Since many drugs are excreted in milk caution should be exercised when this drug is administered to a nursing mother.
The safety and effectiveness of rabeprazole and domperidone in pediatric patients have not been established
There has been no experience with large overdoses with rabeprazole. In the event of overdosage, treatment should be symptomatic and supportive.
Domperidone Symptoms of overdosage may include drowsiness, disorientation and extrapyramidal reactions, especially in children. There is no specific antidote to domperidone, 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, anti-parkinson drugs may be helpful in controlling extrapyramidal reactions.
STORAGE AND HANDLING INSTRUCTIONS
Store below 30°C. Protect from sunlight.
PERBLOC-DSR is available in a ALU-ALU STRIP OF 10X1X10 capsules.