Modifier of Upper Gastrointestinal Motility
Action And Clinical Pharmacology: Domperidone is a peripheral dopamine antagonist structurally related to the butyrophenones with antiemetic and gastroprokinetic properties.
Domperidone effectively increases esophageal peristalsis and lower esophageal sphincter pressure (LESP), increases gastric motility and peristalsis, enhances gastroduodenal coordination and consequently facilitates gastric emptying and decreases small bowel transit time.
The mechanism of action of domperidone is related to its peripheral dopamine-receptor-blocking properties. Emesis induced by apomorphine, hydergine, morphine or levodopa through stimulation of the chemoreceptor trigger zone (situated outside the blood-brain barrier) can be blocked by domperidone. There is indirect evidence that emesis is also inhibited at the gastric level, since domperidone also inhibits emesis induced by oral levodopa, and local gastric wall concentrations following oral domperidone are much greater than those of the plasma and other organs. Domperidone does not readily cross the blood-brain barrier and therefore is not expected to have central effects.
Domperidone elevates serum prolactin levels but has no effect on circulating aldosterone levels.
Pharmacokinetics: In man, peak plasma levels of domperidone occur within 10 to 30 minutes following i.m. injection and 30 minutes after oral (fasted) administration. Plasma concentrations 2 hours after oral administration are lower than following i.m. injection, and this is likely the result of hepatic first-pass and gut wall metabolism. Peak plasma concentrations are 40 ng/mL following an i.m. injection of 10 mg, 20 ng/mL after a single 10 mg tablet, and 70 to 100 ng/mL after oral doses of 60 mg (tablets or oral drops). The half-life was calculated as approximately 7 hours in each case. The degree of human plasma protein binding was calculated from tritiated domperidone concentrations of 10 and 100 ng/mL as 91.7 and 93%, respectively. The major metabolic pathways for domperidone in man are hydroxylation and oxidative N-dealkylation, the products of which are hydroxy-domperidone and 2,3 dihydro-2-oxo-1-H-benzimidazole-1-propionic acid, respectively. After oral administration of 40 mg 4-domperidone to healthy volunteers, 31% of the radioactivity is excreted in the urine and 66% in the feces over a period of 4 days.
Indications And Clinical Uses: In the symptomatic management of upper gastrointestinal motility disorders associated with chronic and subacute gastritis and diabetic gastroparesis. Domperidone may also be used to prevent gastrointestinal symptoms associated with the use of dopamine agonist antiparkinsonian agents.
Contra-Indications: In patients with known sensitivity or intolerance to the drug. Domperidone should not be used whenever gastrointestinal stimulation might be dangerous, i.e., gastrointestinal hemorrhage or mechanical obstruction. tag_WarningWarnings
Manufacturers’ Warnings In Clinical States: Dopamine-receptor-blocking agents elevate prolactin levels; the elevation persists during chronic administration. Tissue culture experiments indicate that approximately one third of human breast cancers are prolactin dependent in vitro, a factor of potential importance if the prescription of these drugs is contemplated in a patient with a previously detected breast cancer. Although disturbances such as galactorrhea, amenorrhea, gynecomastia, and impotence have been reported, the clinical significance of elevated serum prolactin levels is unknown for most patients. An increase in mammary neoplasms has been found in rodents after chronic administration of dopamine-receptor-blocking agents. Neither clinical studies nor epidemiologic studies conducted to date, however, have shown an association between chronic administration of these drugs and mammary tumorigenesis. The available evidence is considered too limited to be conclusive at this time.
Pregnancy: While animal studies have not shown drug related teratogenic or primary embryotoxic effects on animal fetuses, comparable studies have not been performed in pregnant women. For this reason, domperidone should not be used in pregnant women unless the expected benefit outweighs the potential hazard.
Lactation: Domperidone is excreted in breast milk in very low concentrations. Caution should be exercised when domperidone is administered to nursing mothers.
Children: The safety and efficacy of domperidone in children have not been established. Therefore, domperidone should not be used in children.
Precautions: In the event that the patient develops galactorrhea and/or gynecomastia, withdrawal of the drug will result in alleviation of these symptoms.
Drug Interactions: The concomitant administration of anticholinergic drugs may compromise the beneficial effects of domperidone.
Since domperidone enhances gastric and small intestinal motility, it may accelerate absorption of drugs from the small bowel while slowing absorption of drugs taken up from the stomach.
Care should be exercised when domperidone is administered in combination with MAO inhibitors.
The concomitant administration of domperidone with antacids or H2-receptor blockers does not decrease the absorption of domperidone.
Adverse Reactions: In clinical studies with oral domperidone the overall incidence of side effects was
CNS (4.6%): dry mouth (1.9%), headache/migraine (1.2%), insomnia, nervousness, dizziness, thirst, lethargy, irritability (all
Gastrointestinal (2.4%): abdominal cramps, diarrhea, regurgitation, changes in appetite, nausea, heartburn, constipation (all
Endocrinological (1.3%): hot flushes, mastalgia, galactorrhea, gynecomastia, menstrual irregularities.
Mucocutaneous (1.1%): rash, pruritus, urticaria, stomatitis, conjunctivitis.
Urinary (0.8%): urinary frequency, dysuria.
Cardiovascular (0.5%): edema, palpitations.
Musculoskeletal (0.1%): leg cramps, asthenia.
Miscellaneous (0.1%): drug intolerance.
Laboratory parameters: elevated serum prolactin, elevation of AST, ALT and cholesterol (all
Symptoms And Treatment Of Overdose: Symptoms: There has been no experience with overdosage of domperidone. However, based on the pharmacological properties of domperidone, CNS effects (dyskinesias) and cardiovascular effects (arrhythmia, hypotension) might possibly occur. tag_Treatment
Treatment: Treatment is gastric lavage with close observation and supportive therapy.
Dosage And Administration: Upper Gastrointestinal Motility Disorders: The usual dosage in adults is 10 mg orally 3 to 4 times a day, 15 to 30 minutes before meals and at bedtime if required. In severe or resistant cases the dose may be increased to a maximum of 20 mg 3 to 4 times a day.
Nausea and Vomiting Associated with Dopamine Agonist Antiparkinsonian Agents: The usual dosage in adults is 20 mg orally 3 to 4 times a day. Higher doses may be required to achieve symptom control while titration of the antiparkinsonian medication is occurring.
Availability And Storage: Each white, round, biconvex, film-coated tablet engraved “APO” over “10” on one side, contains: domperidone maleate equivalent to domperidone 10 mg. Nonmedicinal ingredients: colloidal silicon dioxide, croscarmellose sodium, fumaric acid, hydroxypropyl methylcellulose, magnesium stearate, microcrystalline cellulose, polyethylene glycol and titanium dioxide. Bottles of 100 and 500. Store at room temperature 15 to 30Â°C. Protect from light and moisture.
APOÂ®-DOMPERIDONE Apotex Domperidone Maleate Modifier of Upper Gastrointestinal Motility
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