Amitriptyline Perphenazine

Dosage Forms & Strengths

amitriptyline/perphenazine

tablet

• 10mg/2mg
• 25mg/2mg
• 10mg/4mg
• 25mg/4mg
• 50mg/4mg

Anxiety or Agitation with Depression

Indicated for (1) moderate-to-severe anxiety and/or agitation and depressed mood, (2) depression in whom anxiety and/or agitation are severe, and (3) depression and anxiety associated with chronic physical disease

Initial: 25 mg/2 mg or 25 mg/4 mg PO TID/QID, OR 50 mg/4 mg PO BID

Maintenance: 2 mg/25 mg or 4 mg/25 mg PO BID/QID, OR 50 mg/4 mg PO BID

10 mg/ 2 mg and 10 mg/4 mg can be used to increase flexibility in adjusting maintenance dosage to the lowest amount consistent with relief of symptoms

Do not exceed daily dose of 200 mg/16 mg

Schizophrenia with Depression

Indicated for patients with schizophrenic who have associated depressive symptoms

Initial: 50 mg/8 mg (ie, 2 tablets of 25 mg/4 mg) PO BID/TID; if needed a fourth dose may be given at bedtime

Maintenance: 2 mg/25 mg or 4 mg/25 mg PO BID/QID, OR 50 mg/4 mg PO BID

10 mg/ 2 mg and 10 mg/4 mg can be used to increase flexibility in adjusting maintenance dosage to the lowest amount consistent with relief of symptoms

Do not exceed daily dose of 200 mg/16 mg

Dosing Considerations

Depending on the condition being treated, therapeutic response may not be observed for several days up to 2-3 weeks, or longer

After a satisfactory response is noted, dosage should be reduced to the smallest amount necessary to obtain relief from the symptoms

Not recommended

Avoid; strong anticholinergic and sedative effects; may cause orthostatic hypotension (Beers criteria)

Consider alternatives; if must use, initiate with lower initial dose such as 1 tablet (amitriptyline 10 mg/perphenazine 4 mg) three/four times daily

Black Box Warnings

Children & Antidepressants

• In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (< 24 years of age) taking antidepressants for major depressive disorders and other psychiatric illnesses. This increase was not seen in patients >24 years of age. A slight decrease in suicidal thinking was seen in adults >65 years. Risks must be weighed in children and young adults against the benefits of taking antidepressants. Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies. This should be done during the initial 1-2 months of therapy and dosage adjustments. The patient’s family should communicate to the healthcare provider any abrupt changes in behavior. Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy. This drug is not approved for use in pediatric patients.

Antipsychotics & Dementia

• Patients with dementia-related psychosis that are treated with antipsychotic drugs are at an increased risk of death as shown in short-term controlled trials. The deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. This drug is not approved for the treatment of patients with dementia-related psychosis (See WARNINGS in package insert).

Contraindications

Tricyclic Antidepressant (amitriptyline): hypersensitivity, severe cardiovascular disorder, narrow angle glaucoma, within 14 days of MAOIs (risk of serotonin syndrome), any drugs or conditions that prolong QT interval, acute recovery post-MI

Antipsychotic (perphenazine): hypersensitivity, CNS depression, neuroleptic malignant syndrome, poorly controlled seizure disorder, subcortical braine damage, coma, severe obtundation, high dose CNS depressants, blood dyscrasia, myelosuppression, liver damage

Pregnancy Category: D

Lactation: excreted in breast milk; not recommended

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Mechanism of Action

Amitriptyline: Antidepressant; neurotransmitter (especially norepinephrine and serotonin) reuptake inhibitor; elicits anticholinergic effects  

Perphenazine: Antipsychotic agent; elicits moderate anticholinergic effects, weak to moderate sedative effects, strong extrapyramidal effects, and strong antiemetic activity

Pharmacokinetics

Amitriptyline

• Onset of action: 6 weeks
• Half-life: 9-27 hr
• Peak serum time: 4 hr
• Metabolism: Hepatic (CYP2C19, CYP3A4)
• Excretion: Urine (25-50%); bile (small amounts)

Perphenazine

• Half-life: 9-12 hr
• Peak plasma time: 1-3 hr; 2-4 hr (metabolite)
• Metabolism: Hepatic P450 enzyme (CYP2D6)
• Excretion: Urine; feces