Metopimazine is an antiemetic medication formulated to prevent or relieve symptoms of nausea and vomiting. It belongs to the phenothiazine chemical class. It is widely utilized across several countries, particularly in Europe, Canada, and South America. The drug offers a specific pharmacological profile for patients experiencing these symptoms.
Therapeutic Applications
Metopimazine is indicated for the symptomatic treatment of nausea and vomiting arising from various causes, including conditions that affect the digestive tract and those triggered by systemic treatments. It is frequently prescribed for managing symptoms associated with postoperative recovery, where general anesthesia and surgical stress can often induce emesis. The medication is also used to address nausea and vomiting related to certain digestive disorders.
A significant application for metopimazine is in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV). It is often employed in the management of delayed CINV, which occurs more than 24 hours after a chemotherapy session. Clinical data has shown its effectiveness as an add-on therapy or as a primary option in certain protocols. Furthermore, metopimazine is currently under investigation for its potential use in treating gastroparesis.
Mechanism of Action
The antiemetic effect of metopimazine is primarily achieved through its function as a dopamine receptor antagonist. It works by blocking dopamine D2 receptors. The most relevant location for this action is the Chemoreceptor Trigger Zone (CTZ), located outside the blood-brain barrier.
By occupying and blocking the D2 receptors in the CTZ, metopimazine prevents signals that initiate the emetic reflex. This action interrupts the communication pathway leading to nausea and vomiting. Metopimazine is considered a peripherally restricted dopamine antagonist, meaning it does not readily cross the blood-brain barrier. This peripheral selectivity contributes to a lower incidence of certain neurological side effects. The drug also exhibits affinity for alpha1-adrenoceptors and histamine H1 receptors, which may augment its antiemetic efficacy.
Administration and Dosing Guidelines
Metopimazine is available in several formulations to accommodate the varying needs of patients, especially those who may be actively vomiting and unable to swallow oral medication. These forms include standard oral tablets or capsules, oral solutions, and suppositories for rectal administration. An intravenous (IV) solution is also available in some regions, which is often reserved for hospital settings or for use in severe cases like the prevention of CINV.
The standard approved daily dosage for symptomatic nausea and vomiting is typically 30 milligrams, often divided into three 10-milligram doses taken throughout the day. For optimal effect, patients are generally advised to take the medication before the anticipated onset of symptoms, such as prior to a meal or a procedure. When used for CINV, clinical trials have sometimes explored higher daily doses, with some studies demonstrating safety and tolerability up to 180 milligrams per day for short periods. It remains important for patients to strictly adhere to the specific form and dosage prescribed by their healthcare provider.
Important Safety Considerations
While generally well-tolerated, metopimazine can cause several predictable side effects, particularly those related to its peripheral anticholinergic and antihistaminic activity. Common adverse effects include mild drowsiness, fatigue, and dry mouth. Some patients may also experience dizziness or vertigo, which can affect the ability to safely operate machinery or drive.
More serious, though less frequent, safety concerns are associated with its dopamine-blocking properties. Extrapyramidal symptoms (EPS), which are movement disorders such as muscle spasms or involuntary restlessness, can occur, particularly with higher doses. Due to its effect on alpha1-adrenoceptors, orthostatic hypotension, a sudden drop in blood pressure upon standing, has been noted as a potential dose-limiting toxicity in trials using elevated dosages.
Metopimazine is generally contraindicated in individuals with a known hypersensitivity to phenothiazine medications or those with pre-existing conditions like certain forms of glaucoma or severe central nervous system depression. Caution must be exercised when the drug is combined with other central nervous system depressants, such as alcohol or sedatives, as this combination can intensify effects like drowsiness and sedation. Additionally, concurrent use with other anticholinergic drugs may exacerbate side effects such as dry mouth and constipation.