perphenazine
Apo-Perphenazine ◆, Trilafon

Available forms
Available by prescription only
Injection: 5 mg/ml
Oral concentrate: 16 mg/5 ml
Tablets: 2 mg, 4 mg, 8 mg, 16 mg

Indications and dosages
 Psychosis. Adults: Initially, 8 to 16 mg P.O. b.i.d., t.i.d., or q.i.d., increasing to 64 mg daily. Or administer 5 to 10 mg I.M.; change to P.O. as soon as possible.
 Mental disturbances, acute alcoholism, nausea, vomiting, hiccups. Adults: 5 to 10 mg I.M., p.r.n. Maximum dose is 15 mg daily in ambulatory patients; 30 mg daily in hospitalized patients; or 8 to 16 mg P.O. daily in divided doses.
 Perphenazine may be given slowly by I.V. drip at 1 mg/2 minutes with continuous blood pressure monitoring (rarely used). A maximum of 5 mg I.V. diluted to 0.5 mg/ml with normal saline solution may be given for severe hiccups or vomiting.

Pharmacodynamics
Antipsychotic action: Thought to exert antipsychotic effects by postsynaptic blockade of CNS dopamine receptors, thus inhibiting dopamine-mediated effects; antiemetic effects are attributed to dopamine receptor blockade in the medullary chemoreceptor trigger zone. Has many other central and peripheral effects: produces both alpha and ganglionic blockade and counteracts histamine- and serotonin-mediated activity. Most serious adverse reactions are extrapyramidal.

Pharmacokinetics
Absorption: Rate and extent of absorption vary with administration route. Oral tablet absorption erratic and variable; oral concentrate absorption much more predictable. I.M. drug absorbed rapidly.
Distribution: Distributed widely into body, including breast milk. Drug is 91% to 99% protein-bound. After oral tablet administration, steady state serum levels achieved within 4 to 7 days.
Metabolism: Metabolized extensively by liver; no active metabolites formed.
Excretion: Mostly excreted in urine via kidneys; some in feces via biliary tract.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug; in patients experiencing coma; in those with CNS depression, blood dyscrasia, bone marrow depression, liver damage, or subcortical damage; and in those receiving large doses of CNS depressants.
  Use cautiously in elderly or debilitated patients; in those with alcohol withdrawal, psychic depression, suicidal tendencies, adverse reaction to other phenothiazines, impaired renal function, or respiratory disorders; and in patients receiving other CNS depressants or anticholinergics.

Interactions
Drug-drug. Antacids that contain aluminum and magnesium, antidiarrheals: Inhibits absorption. Separate administration times by at least 2 hours.
Antihypertensives: Potentiates hypotensive effects. Monitor patient closely.
Appetite suppressants, sympathomimetics (such as ephedrine [commonly found in nasal sprays], epinephrine, phenylephrine): Decreases stimulatory and pressor effects. Monitor patient closely.
Atropine, other anticholinergics (such as antidepressants, antihistamines, antiparkinsonians, MAO inhibitors, meperidine, phenothiazines): Causes oversedation, paralytic ileus, visual changes, and severe constipation. Monitor patient closely.
Bromocriptine: Antagonizes prolactin secretion. Monitor patient closely.
CNS depressants (such as analgesics; barbiturates; epidural, general, spinal anesthetics; narcotics; tranquilizers), parenteral magnesium sulfate: Causes oversedation, respiratory depression, and hypotension. Monitor patient closely.
Lithium: Causes severe neurologic toxicity with encephalitis-like syndrome; decreases therapeutic response to perphenazine. Avoid use together.
Metrizamide: Increases risk of seizures. Monitor patient closely.
Nitrates: Causes hypotension. Monitor blood pressure.
Phenobarbital: Enhances renal excretion of perphenazine. Adjust dosage as needed.
Phenytoin: Increases or decreases phenytoin levels. Monitor patient closely.
Pimozide: Prolongs QT interval. Avoid use together.
Propranolol: Increases levels of both drugs. Use together cautiously.
Drug-herb. Yohimbe: Increases risk of alpha₂ adrenergic antagonism. Discourage use together.
Drug-food. Apple juice, caffeine: Decreases therapeutic response to perphenazine. Discourage use together.
Drug-lifestyle. Alcohol use: Causes additive effects. Discourage alcohol use.
Heavy smoking: Decreases therapeutic response to perphenazine. Discourage smoking.
Sun exposure: May cause photosensitivity reactions. Advise patient to take precautions.

Adverse reactions
CNS: neuroleptic malignant syndrome, extrapyramidal reactions, tardive dyskinesia, sedation, pseudoparkinsonism, EEG changes, dizziness, adverse behavioral effects, seizures, drowsiness.
CV: orthostatic hypotension, tachycardia, ECG changes, cardiac arrest.
EENT: ocular changes, blurred vision, nasal congestion.
GI: dry mouth, constipation, nausea, vomiting, diarrhea, ileus.
GU: urine retention, dark urine, menstrual irregularities, inhibited ejaculation.
Hematologic: leukopenia, galactorrhea, agranulocytosis, eosinophilia, hemolytic anemia, thrombocytopenia.
Hepatic: jaundice.
Metabolic: hyperglycemia, hypoglycemia, weight gain.
Skin: mild photosensitivity, allergic reactions, pain at I.M. injection site, sterile abscess.
Other: gynecomastia, SIADH.

Effects on lab test results
• May increase or decrease serum glucose level.
• May increase liver function test values and eosinophil count. May decrease hemoglobin, hematocrit, and WBC, granulocyte, and platelet counts.

Overdose and treatment
CNS depression is characterized by deep, unarousable sleep and possible coma, hypotension or hypertension, extrapyramidal symptoms, dystonia, abnormal involuntary muscle movements, agitation, seizures, arrhythmias, ECG changes, hypothermia or hyperthermia, and autonomic nervous system dysfunction.
 Treatment is symptomatic and supportive, including maintaining vital signs, airway, stable body temperature, and fluid and electrolyte balance.
 Induce vomiting in a conscious patient with ipecac syrup even if spontaneous vomiting has occurred. Don’t induce vomiting in patients with impaired consciousness. Use gastric lavage, then activated charcoal and sodium chloride cathartics; dialysis is usually ineffective. Regulate body temperature as needed. Treat hypotension with I.V. fluids. Don’t give epinephrine. Treat seizures with parenteral diazepam or barbiturates; arrhythmias with parenteral phenytoin (1 mg/kg with rate titrated to blood pressure); and extrapyramidal reactions with benztropine at 1 to 2 mg or parenteral diphenhydramine at 10 to 50 mg.

Special considerations
• Oral formulations may cause stomach upset; administer with food or fluid.
• Dilute the concentrate in 2 to 4 oz (60 to 118 ml) of liquid (water, caffeine-free carbonated drinks, fruit juice, tomato juice, milk, or puddings). Dilute every 5 ml of concentrate with 60 ml of suitable fluid. Shake oral concentrate before administration.
• Liquid formulation may cause rash upon contact with skin.
• I.M. injection may cause skin necrosis; avoid extravasation.
• Administer I.M. injection deep into upper outer quadrant of buttocks. Massaging injection site may prevent formation of abscesses.
• Don’t administer drug for injection if it’s excessively discolored or contains precipitate.
• Monitor blood pressure before and after parenteral administration.
• After abrupt withdrawal of long-term therapy, patient may experience gastritis, nausea, vomiting, dizziness, tremor, feeling of warmth or cold, diaphoresis, tachycardia, headache, and insomnia.
• Perphenazine causes false-positive test results for urinary porphyrins, urobilinogen, amylase, and 5-hydroxyindoleacetic acid because of darkening of urine by metabolites; also causes false-positive urine pregnancy test results using human chorionic gonadotropin.
Breast-feeding patients
• Drug appears widely in breast milk. Use cautiously in breast-feeding women. Potential benefits to mother should outweigh potential harm to infant.
Pediatric patients
• Drug isn’t recommended for children younger than age 12.
Geriatric patients
• Use lower doses in elderly patients, and adjust to effect; 30% to 50% of the usual dose may be effective. Elderly patients have an increased risk of adverse effects, especially tardive dyskinesia and other extrapyramidal effects.

Patient education
• Explain risks of dystonic reactions and tardive dyskinesia, and tell patient to report abnormal body movements.
• Instruct patient to avoid sun exposure and to wear sunscreen when going outdoors to prevent photosensitivity reactions and to avoid using sun lamps and tanning beds, which may cause burning of the skin or skin discoloration.
• Tell patient to avoid spilling liquid; contact with skin may cause rash and irritation.
• Warn patient not to take extremely hot or cold baths and to avoid exposure to temperature extremes; drug may cause thermoregulatory changes.
• Advise patient to take drug exactly as prescribed and not to double missed doses.
• Inform patient that interactions with many other drugs are possible. Advise patient to seek medical approval before taking herbal or OTC products.
• Instruct patient not to stop taking drug suddenly; any adverse reactions may be alleviated by a dosage reduction. Patient should promptly report difficulty urinating, sore throat, dizziness, or fainting.
• Tell patient to avoid hazardous activities that require alertness until drug’s effect is known. Reassure patient that sedative effects of drug should become tolerable within a few weeks.
• Tell patient not to drink alcohol or take other drugs that may cause excessive sedation.
• Explain which fluids are appropriate for diluting the concentrate (not apple juice or drinks containing caffeine); explain dropper technique of measuring dose.
• Recommend sugarless hard candy or chewing gum, ice chips, or artificial saliva to relieve dry mouth.
• Tell patient not to crush or chew sustained-release form.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use