Drug Interactions between metoclopramide and thiethylperazine

CONTRAINDICATED: Coadministration of metoclopramide with phenothiazines, neuroleptics, or other antidopaminergic agents (e.g., tetrabenazine) may increase the frequency and severity of extrapyramidal reactions (i.e., acute dystonic reactions, tardive dyskinesia, akathisia, Parkinson-like symptoms) due to additive antidopaminergic effects. By itself, metoclopramide can cause acute dystonic reactions in approximately 0.2% of patients treated with the usual adult dosages of 30 to 40 mg/day. These reactions are typically seen during the first 24 to 48 hours of treatment, occur more frequently in pediatric and adult patients less than 30 years of age, and are increased with higher dosages. Symptoms may include involuntary movements of limbs, facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech, trismus, opisthotonus (tetanus-like reactions), and rarely, stridor and dyspnea due to laryngospasm. Dystonic reactions usually respond to treatment with anticholinergic agents such as diphenhydramine or benztropine. Tardive dyskinesia (TD) is a potentially irreversible and disfiguring disorder characterized most frequently by involuntary movements of the tongue, face, mouth, or jaw, and less frequently by involuntary movements of the trunk and/or extremities. Movements may be choreoathetotic in appearance. Although the risk of TD with metoclopramide has not been extensively studied, a prevalence of 20% has been reported in one study among patients treated for at least 12 weeks. The risk is increased in the elderly, women, and diabetic populations; however, it is not possible to predict which patients will develop TD. Both the risk of developing TD and the likelihood that TD will become irreversible increase with duration of treatment and total cumulative dose. There is no known effective treatment. In some patients, TD may remit, partially or completely, within several weeks to months after metoclopramide is withdrawn. Akathisia, or motor restlessness, consist of feelings of anxiety, agitation, jitteriness, and insomnia, as well as inability to sit still, pacing, and foot tapping. Symptoms may disappear spontaneously or respond to a reduction in dosage. Parkinsonian-like symptoms may include bradykinesia, tremor, cogwheel rigidity, and mask-like facies. These symptoms most commonly occur within the first 6 months of metoclopramide therapy and subside within 2 to 3 months following drug discontinuation.

MANAGEMENT: Due to the potential for increased risk of serious and potentially irreversible extrapyramidal reactions, metoclopramide should not be prescribed in combination with other antidopaminergic agents. In addition, metoclopramide should not be used for longer than 12 weeks except in rare cases where therapeutic benefit is anticipated to outweigh the risk of developing tardive dyskinesia.

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