Large variation in the catalytic activity was observed in the CYP-mediated reactions, whereas there appeared to be only small variations in the glucuronidation and carbonyl reduction pathways. Pharmacokinetic interactions occur between haloperidol and various drugs given concomitantly, for example, carbamazepine, phenytoin, phenobarbital, fluoxetine, fluvoxamine, nefazodone, venlafaxine, buspirone, alprazolam, rifampicin rifampin , quinidine and carteolol.
Overall, drug interaction studies have suggested that CYP3A4 is involved in the biotransformation of haloperidol in humans. Interactions of haloperidol with most drugs lead to only small changes in plasma haloperidol concentrations, suggesting that the interactions have little clinical significance. On the other hand, the coadministration of carbamazepine, phenytoin, phenobarbital, rifampicin or quinidine affects the pharmacokinetics of haloperidol to an extent that alterations in clinical consequences would be expected.
In vivo pharmacogenetic studies have indicated that the metabolism and disposition of haloperidol may be regulated by genetically determined polymorphic CYP2D6 activity. However, these findings appear to contradict those from studies in vitro with human liver microsomes and from studies of drug interactions in vivo. Psychotic patients who require prolonged therapy. Adults: mg I.
Experience with doses of more than mg monthly is limited. Control of tics, vocal utterances in Tourette syndrome. Adults: 0. Children ages 3 to 0. Adults: 1 to 2 mg I. Pharmacodynamics Antipsychotic action: Haloperidol is thought to exert antipsychotic effects by strong postsynaptic blockade of CNS dopamine receptors, thereby inhibiting dopamine-mediated effects; its pharmacologic effects are most similar to those of piperazine antipsychotics.
Its mechanism of action in Tourette syndrome is unknown. Haloperidol has many other central and peripheral effects; it has weak peripheral anticholinergic effects and antiemetic effects, produces both alpha and ganglionic blockade, and counteracts histamine- and serotonin-mediated activity.
Its most prominent adverse reactions are extrapyramidal. Pharmacokinetics Absorption: Rate and extent of absorption vary with route of administration. Distribution: Distributed widely into body, with high levels in adipose tissue. Contraindications and precautions Contraindicated in patients hypersensitive to drug and in those experiencing parkinsonism, coma, or CNS depression. Use haloperidol cautiously in elderly or debilitated patients; in patients with history of seizures, EEG abnormalities, CV disorders, allergies, angle-closure glaucoma, or urine retention; and in those receiving anticoagulants, anticonvulsants, antiparkinsonians, or lithium.
Interactions Drug-drug. Aluminum- and magnesium-containing antacids and antidiarrheals: Decreases drug absorption. Separate administration times by 2 hours. Antiarrhythmics, disopyramide, procainamide, quinidine: Increases risk of arrhythmias and conduction defects. Avoid use together. Anticholinergics, including antidepressants, antihistamines, antiparkinsonians, atropine, MAO inhibitors, meperidine, phenothiazines: Causes oversedation, paralytic ileus, visual changes, and severe constipation.
Use cautiously. Beta blockers: May inhibit haloperidol metabolism, increasing plasma levels and toxicity. Bromocriptine: Antagonizes therapeutic effect of bromocriptine on prolactin secretion.
Centrally acting antihypertensives such as clonidine, guanabenz, guanadrel, guanethidine, methyldopa, reserpine : Inhibits blood pressure response.
Monitor blood pressure carefully. CNS depressants, including analgesics, barbiturates, narcotics, tranquilizers, and general, spinal, or epidural anesthetics; parenteral magnesium sulfate: Increases CNS depression. Dopamine: Decreases vasoconstricting effects. Monitor patient for lack of therapeutic effect. Levodopa: Decreases effectiveness and increases toxicity of levodopa.
Lithium: May result in severe neurologic toxicity with an encephalitis-like syndrome and a decreased therapeutic response to haloperidol.
Use cautiously; monitor patient. Metrizamide: Increases risk of seizures. Nitrates: Causes hypotension. Monitor blood pressure frequently. Phenobarbital: Enhances renal excretion. Monitor patient closely. Phenytoin: Inhibits metabolism and increases toxicity of phenytoin.
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