A-Z Drug Facts > Perphenazine/Amitriptyline

Perphenazine / Amitriptyline

Pronouncation: (per-FEN-uh-zeen/am-ee-TRIP-tih-leen)
Class: Psychotherapeutic combination

Trade Names:
Etrafon 2-10
- Tablets 2 mg perphenazine/10 mg amitriptyline

Trade Names:
Etrafon
- Tablets 2 mg perphenazine/25 mg amitriptyline

Trade Names:
Etrafon-A
- Tablets 4 mg perphenazine/10 mg amitriptyline

Trade Names:
Etrafon-Forte
- Tablets 4 mg perphenazine/25 mg amitriptyline

Pharmacology

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Amitriptyline blocks reuptake of serotonin and norepinephrine in CNS. Perphenazine appears to block postsynaptic dopamine receptors.

Indications and Usage

Treatment of moderate-to-severe anxiety or agitation and depressed mood; moderate to severe depression and anxiety associated with chronic physical disease; treatment of patients in whom depression and anxiety cannot be clearly differentiated; treatment of schizophrenia with associated depression.

Contraindications

Hypersensitivity to phenothiazines; depression of CNS due to drugs (eg, barbiturates, alcohol, narcotics, analgesics, antihistamines); bone marrow depression; hypersensitivity to tricyclic antidepressant. Should not be given concomitantly with MAOIs, suspected or established subcortical brain damage. Not recommended for use during acute recovery phases of MI.

Dosage and Administration

Adults

PO Initially, usual dose is 2 to 4 mg perphenazine with 10 to 50 mg amitriptyline 3 to 4 times daily.

Storage/Stability

Store tablets in tightly covered, light-resistant container.

Drug Interactions

Alcohol

May result in increased CNS depression and may precipitate extrapyramidal reaction.

Amphetamines

May antagonize antipsychotic effects of perphenazine.

Anticholinergics

May reduce therapeutic effects of perphenazine and worsen anticholinergic effects. Coadministration may worsen schizophrenic symptoms and lead to tardive dyskinesia.

Barbiturate anesthetics

Frequency and severity of neuromuscular excitation and hypotension may increase.

Barbiturates, carbamazepine, charcoal

May cause decreased amitriptyline blood levels.

Cimetidine, fluoxetine, haloperidol, oral contraceptives

May cause increased amitriptyline blood levels.

Clonidine

May result in hypertensive crisis.

CNS depressants

Depressant effects may be addictive.

Guanethidine

Hypotensive action may be inhibited.

Lithium

Possible neurotoxicity with perphenazine and may increase effects of amitriptyline.

MAOIs

Do NOT use this product with MAOIs as hyperpyretic crisis, severe convulsions, and death may result. When switching from MAOIs, wait 14 days and initiate with low doses, increasing dosage gradually until desired response is achieved.

Metrizamide

Seizure risk may be increased.

Sympathomimetics

Increased pressor effects.

Laboratory Test Interactions

May discolor urine pink to red-brown. False-positive pregnancy test results may occur, but are less likely to occur with serum test. Increases in protein bound iodine have been reported.

Adverse Reactions

Cardiovascular

Orthostatic hypotension; hypertension; tachycardia; bradycardia; syncope; cardiac arrest; circulatory collapse; arrhythmias; lightheadedness; faintness; dizziness; EKG changes; palpitations.

CNS

Sedation; neurologic impairments; extrapyramidal symptoms (eg, pseudoparkinsonism); dystonia; dyskinesia, motor restlessness; oculogyric crisis; opisthotonos; hyperreflexia; tardive dyskinesia; drowsiness; headache; weakness; anxiety; agitation; mania; exacerbation of psychosis; dizziness; tremor; fatigue; slurring of speech; insomnia; vertigo, seizures; abnormalities of CSF proteins; paradoxical excitement or exacerbation of psychotic symptoms; catatonic-like states; paranoid reactions; lethargy; hyperactivity; nocturnal confusion; bizarre dreams.

Dermatologic

Photosensitivity reaction; skin pigmentation; dry skin; exfoliative dermatitis; urticarial rash; maculopapular hypersensitivity reaction; seborrhea; eczema; acne; pruritus.

EENT

Pigmentary retinopathy; glaucoma; photophobia; rhinitis; pharyngitis; tinnitus; blurred vision; nasal congestion; mydriasis; increased IOP.

GI

Dyspepsia; adynamic ileus (may cause death); constipation; nausea; vomiting; anorexia; diarrhea; peculiar taste; dry mouth or throat.

Genitourinary

Urinary hesitancy or retention; impotence; sexual dysfunction; menstrual irregularities; nocturia.

Hematologic

Agranulocytosis; eosinophilia; leukopenia; hemolytic anemia; thrombocytopenic purpura.

Hepatic

Jaundice.

Metabolic

Hyperglycemia; hypoglycemia.

Respiratory

Laryngospasm; bronchospasm; dyspnea; cough.

Miscellaneous

Increases in appetite and weight; polydipsia; breast enlargement; galactorrhea; increased prolactin levels.

Precautions

Pregnancy

Safety not established.

Lactation

Safety not established.

Elderly

More susceptible to adverse effects.

Special Risk Patients

Use caution in patients with CV disease or mitral insufficiency, history of glaucoma, EEG abnormalities or seizure disorders, prior brain damage, hepatic or renal function impairment.

CNS effects

May impair mental or physical abilities, especially during first few days of therapy.

Neuroleptic malignant syndrome (NMS)

Has occurred with agents of this class; is potentially fatal. Signs and symptoms are hyperpyrexia, muscle rigidity, altered mental status, irregular pulse, irregular blood pressure, tachycardia and diaphoresis.

Sudden death

Has been reported; predisposing factors may be seizures or previous brain damage. Flare-up of psychotic behavior may precede death.

Tardive dyskinesia

Syndrome of potentially irreversible involuntary body and facial movements may develop. Prevalence highest in elderly, especially women. Use smallest effective doses for shortest time possible.

Overdosage

Symptoms

Confusion, tachycardia, visual hallucinations, sedation, hypothermia, arrhythmias, CHF, dilated pupils, seizures, hypotension, coma, hyperpyrexia, muscle rigidity, hyperactive reflexes, death.

Patient Information

• Instruct patient to avoid intake of alcoholic beverages or other CNS depressants.
• Tell patient to use caution in driving or operating machinery.
• Advise patient that the medication may take days to weeks before having a full effect.
• Instruct patient to avoid becoming overheated.
• Caution patient to avoid exposure to sunlight and to use sunscreen or wear protective clothing to minimize photosensitivity reaction.
• Teach patient to change position slowly if dizziness occurs.
• Instruct patient to take sips of water frequently, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
• Instruct patient to report the following symptoms to health care provider: dizziness, drooling, restlessness, tremors, stiffness, or muscle spasms.
• Instruct patient to report involuntary face, tongue, mouth, or lip movements to health care provider.
• Explain that urine may turn reddish-brown.

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