Amitriptyline and Perphenazine

Perphenazine and amitriptyline hydrochloride tablets are recommended for treatment of patients with moderate to severe anxiety and/or agitation and depressed mood, patients with depression in whom anxiety and/or agitation are severe, and 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. Schizophrenic patients who have associated depressive symptoms should be considered for therapy with perphenazine and amitriptyline hydrochloride tablets.

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.

Since dosage for children has not been established, this product is not recommended for use in children. The total daily dose of perphenazine and amitriptyline hydrochloride tablets should not exceed 16 mg of perphenazine and 200 mg of amitriptyline hydrochloride. Initial Dosage In psychoneurotic patients when anxiety and depression are of such a degree as to warrant combined therapy, one tablet of the 2 mg/25 mg or 4 mg/25 mg three or four times a day or one tablet of the 4 mg/50 mg combination twice a day is recommended. In more severely ill patients with schizophrenia, the 4 mg/25 mg combination is recommended in an initial dose of two tablets three times a day. If necessary, a fourth dose may be given at bedtime.

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.

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. 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. Perphenazine and amitriptyline hydrochloride is not approved for the treatment of patients with dementia-related psychosis.

To date, clinical evaluation of perphenazine has not revealed any adverse reactions peculiar to the combination. The adverse reactions that occurred were limited to those that have been reported previously for perphenazine and amitriptyline. Treatment with perphenazine and amitriptyline hydrochloride is commonly associated with sedation, hypertension, neurological impairments and dry mouth. Perphenazine The common acute neurological effects of neuroleptic drugs, including perphenazine, consist of dystonia, akathisia or motor restlessness, and pseudoparkinsonism. More chronic use of neuroleptics may be associated with the development of tardive dyskinesia. The salient features of this syndrome are described in the WARNINGS section and below. The following adverse reactions have been reported and, within each category, are listed in order of decreasing severity.

Topiramate Some patients may experience a large increase in amitriptyline concentration in the presence of topiramate and any adjustments in amitriptyline dose should be made according to the patient’s clinical response and not on the basis of plasma levels. Drugs Metabolized by P450 2D6 The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called "poor metabolizers"), reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses.

Store at 20° to 25°C (68° to 77°F). Protect from light.