Cimetidine inhibits cytochrome P450 2D6, potentially causing toxic amitriptyline concentrations; dose reduction may be necessary.
Source: NLP:perphenazine and amitriptyline hydrochloride
Brand names: Perphenazine And Amitriptyline Hydrochloride
Phenothiazine
Route: Oral
FDA Black Box Warning
WARNING Increased Mortality in Elderly Patients with Dementia-Related Psychosis Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Perphenazine and amitriptyline hydrochloride is not approved for the treatment of patients with dementia-related psychosis (see WARNINGS ). Suicidality and Antidepressant Drugs Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of perphenazine and amitriptyline or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psy
Contraindications
CONTRAINDICATIONS Perphenazine and amitriptyline hydrochloride tablets are contraindicated in depression of the central nervous system from drugs (barbiturates, alcohol, narcotics, analgesics, antihistamines); in the presence of evidence of bone marrow depression; and in patients known to be hypersensitive to phenothiazines or amitriptyline. It should not be given concomitantly with monoamine oxidase inhibitors. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressants and monoamine oxidase inhibitors simultaneously. When it is desired to replace a monoamine oxidase inhibitor with perphenazine and amitriptyline hydrochloride, a minimum of 14 days should be allowed to elapse after the former is discontinued. Perphenazine and amitriptyline hydrochloride should then be initiated cautiously with gradual increase in dosage until optimum response is achieved. Amitriptyline hydrochloride is not recommended for use during the acute recovery phase following myocardial infarction.
Pregnancy & Breastfeeding
Pregnancy Nonteratogenic Effects Neonates exposed to antipsychotic drugs, during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization. Perphenazine and amitriptyline hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
8 interactions on record
Cimetidine inhibits cytochrome P450 2D6, potentially causing toxic amitriptyline concentrations; dose reduction may be necessary.
Source: NLP:perphenazine and amitriptyline hydrochloride
Flecainide inhibits cytochrome P450 2D6, potentially causing toxic amitriptyline concentrations; dose reduction may be necessary.
Source: NLP:perphenazine and amitriptyline hydrochloride
Fluoxetine inhibits cytochrome P450 2D6 and has a long half-life; at least 5 weeks must elapse before initiating amitriptyline after fluoxetine withdrawal.
Source: NLP:perphenazine and amitriptyline hydrochloride
Propafenone inhibits cytochrome P450 2D6, potentially causing toxic amitriptyline concentrations; dose reduction may be necessary.
Source: NLP:perphenazine and amitriptyline hydrochloride
Quinidine inhibits cytochrome P450 2D6, potentially causing toxic amitriptyline concentrations; dose reduction may be necessary.
Source: NLP:perphenazine and amitriptyline hydrochloride
Paroxetine inhibits cytochrome P450 2D6; caution is indicated in coadministration with amitriptyline and dose adjustments may be necessary.
Source: NLP:perphenazine and amitriptyline hydrochloride
Sertraline inhibits cytochrome P450 2D6; caution is indicated in coadministration with amitriptyline and dose adjustments may be necessary.
Source: NLP:perphenazine and amitriptyline hydrochloride
Topiramate may increase amitriptyline concentration; amitriptyline dose adjustments should be made based on clinical response rather than plasma levels.
Source: NLP:perphenazine and amitriptyline hydrochloride