Usual Adult Dose for Anxiety

Initial dose: Amitriptyline 25 mg-perphenazine 2 to 4 mg orally 3 to 4 times a day OR amitriptyline 50 mg-perphenazine 4 mg orally 2 times a day

• Severely ill patients with schizophrenia: Amitriptyline 50 mg-perphenazine 8 mg orally 3 times a day

Maintenance dose: Amitriptyline 25 mg-perphenazine 2 mg orally 2 times a day to amitriptyline 25 mg-perphenazine 4 mg 4 times a day
Maximum dose: Amitriptyline 200 mg-perphenazine 16 mg/day

Comments:

• During initial treatment, severely ill patients with schizophrenia may be given an additional dose at bedtime.
• Maintenance doses should be the lowest dose in order to control symptoms.
• Some patients require maintenance treatment for many months.

Uses:

• Treatment of patients with moderate to severe anxiety and/or agitation and depressed mood
• Treatment of patients with depression in whom anxiety and/or agitation are severe
• Treatment of patients with depression and anxiety in association with chronic physical disease
• Patients with schizophrenia and associated depressive symptoms

Usual Adult Dose for Depression

Initial dose: Amitriptyline 25 mg-perphenazine 2 to 4 mg orally 3 to 4 times a day OR amitriptyline 50 mg-perphenazine 4 mg orally 2 times a day

• Severely ill patients with schizophrenia: Amitriptyline 50 mg-perphenazine 8 mg orally 3 times a day

Maintenance dose: Amitriptyline 25 mg-perphenazine 2 mg orally 2 times a day to amitriptyline 25 mg-perphenazine 4 mg 4 times a day
Maximum dose: Amitriptyline 200 mg-perphenazine 16 mg/day

Comments:

• During initial treatment, severely ill patients with schizophrenia may be given an additional dose at bedtime.
• Maintenance doses should be the lowest dose in order to control symptoms.
• Some patients require maintenance treatment for many months.

Uses:

• Treatment of patients with moderate to severe anxiety and/or agitation and depressed mood
• Treatment of patients with depression in whom anxiety and/or agitation are severe
• Treatment of patients with depression and anxiety in association with chronic physical disease
• Patients with schizophrenia and associated depressive symptoms

Usual Adult Dose for Agitation

Initial dose: Amitriptyline 25 mg-perphenazine 2 to 4 mg orally 3 to 4 times a day OR amitriptyline 50 mg-perphenazine 4 mg orally 2 times a day

• Severely ill patients with schizophrenia: Amitriptyline 50 mg-perphenazine 8 mg orally 3 times a day

Maintenance dose: Amitriptyline 25 mg-perphenazine 2 mg orally 2 times a day to amitriptyline 25 mg-perphenazine 4 mg 4 times a day
Maximum dose: Amitriptyline 200 mg-perphenazine 16 mg/day

Comments:

• During initial treatment, severely ill patients with schizophrenia may be given an additional dose at bedtime.
• Maintenance doses should be the lowest dose in order to control symptoms.
• Some patients require maintenance treatment for many months.

Uses:

• Treatment of patients with moderate to severe anxiety and/or agitation and depressed mood
• Treatment of patients with depression in whom anxiety and/or agitation are severe
• Treatment of patients with depression and anxiety in association with chronic physical disease
• Patients with schizophrenia and associated depressive symptoms

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Use with caution.

Dose Adjustments

Elderly, adolescent, and/or patients with conditions where anxiety predominates: Patients should begin with amitriptyline 10 mg-perphenazine 4 mg orally 3 to 4 times a day, then the dose should be adjusted to maintain adequate treatment.

Precautions

US BOXED WARNINGS:
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 17 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.
• This drug is not approved for the treatment of patients with dementia-related psychosis.

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 this drug 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.
• This drug is not approved for use in pediatric patients.

Safety and efficacy have not been established in patients younger than 18 years; this drug is not recommended for use in these patients.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Storage requirements:

• Protect from light.

General:

• For some patients, amitriptyline-perphenazine 10 mg-2 mg and 10 mg-4 mg tablets may provide more flexible dosage adjustments compared to combination tablets with higher doses of amitriptyline.

Monitoring:

• Hematologic: Periodic blood counts
• Hepatic: Periodic liver function tests
• Psychiatric: Changes in mood/behavior (e.g., depression, mania/hypomania, suicidal ideation)

Patient advice:

• Patients should be instructed to tell their healthcare provider about all of the medicines that they take, including prescription and non-prescription medicines.
• This medicine may increase the risk of suicidal thoughts and behavior. Patients should be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Patients should report any behavior of concern to their healthcare provider as soon as possible.
• Patients should be advised to speak to a healthcare provider if they are pregnant, intend to become pregnant, or are breastfeeding.
• This medicine may cause impaired judgment, thinking, or motor skills; patients should not drive a car or operate dangerous machinery until they know how this drug affects them.
• Patients and their caregivers should be told to report any signs/symptoms of tardive dyskinesia, neuroleptic malignant syndrome, respiratory depression or profound sedation.