PERPHENAZINE AND AMITRIPTYLINE HYDROCHLORIDE- perphenazine and amitriptyline hydrochloride tablet, film coated
Mylan Pharmaceuticals Inc.
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 psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Perphenazine and amitriptyline hydrochloride is not approved for use in pediatric patients. (See WARNINGS: Clinical Worsening and Suicide Risk, PRECAUTIONS: Information for Patients and PRECAUTIONS: Pediatric Use.)
DESCRIPTION
Perphenazine and amitriptyline hydrochloride, a broad spectrum psychotherapeutic agent for the management of outpatients and hospitalized patients with psychoses or neuroses characterized by mixtures of anxiety or agitation with symptoms of depression, is a combination of perphenazine and amitriptyline hydrochloride. Since such mixed syndromes can occur in patients with various degrees of intensity of mental illness, perphenazine and amitriptyline hydrochloride tablets are provided in multiple combinations to afford dosage flexibility for optimum management.
CLINICAL PHARMACOLOGY
Perphenazine
In common with all members of the piperazine group of phenothiazine derivatives, perphenazine has greater behavioral potency than phenothiazine derivatives of other groups without a corresponding increase in autonomic, hematologic, or hepatic side effects.
Extrapyramidal effects, however, may occur more frequently. These effects are interpreted as neuropharmacologic. They usually regress after discontinuation of the drug.
Perphenazine is a potent tranquilizer and also a potent antiemetic. Orally, its milligram potency is about 5 or 6 times that of chlorpromazine with respect to behavioral effects. It is capable of alleviating symptoms of anxiety, tension, psychomotor excitement, and other manifestations of emotional stress without apparent dulling of mental acuity.
Amitriptyline Hydrochloride
Amitriptyline hydrochloride is an antidepressant with sedative effects. Its mechanism of action in man is not known. It is not a monoamine oxidase inhibitor and it does not act primarily by stimulation of the central nervous system.
INDICATIONS AND USAGE
Perphenazine and amitriptyline hydrochloride tablets are recommended for treatment of (1) patients with moderate to severe anxiety and/or agitation and depressed mood, (2) patients with depression in whom anxiety and/or agitation are severe, and (3) patients with depression and anxiety in association with chronic physical disease. In many of these patients, anxiety masks the depressive state so that, although therapy with a tranquilizer appears to be indicated, the administration of a tranquilizer alone will not be adequate.
