A-Z Drug Facts > Perphenazine

Perphenazine

Pronouncation: (per-FEN-uh-zeen)
Class: Antidopaminergic, Phenothiazine derivative

Trade Names:
Perphenazine
- Tablets 2 mg
- Tablets 4 mg
- Tablets 8 mg
- Tablets 16 mg
- Oral concentrate 16 mg/5 mL

Apo-Perphenazine (Canada)

Pharmacology

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Effects apparently caused by postsynaptic dopamine receptor blockade in CNS.

Pharmacokinetics

Absorption

T _max is approximately 1 to 3 h (parent), 2 to 4 h (metabolite). Steady state is 72 h. C _max is 984 pg/mL (parent compound), 7-hydroxyperphenazine (509 pg/mL). C _min is 442 pg/mL (parent compound), 7-hydroxyperphenazine (350 pg/mL).

Distribution

Readily crosses placenta, distributes into breast milk. Protein binding is greater than 90%.

Metabolism

Extensively metabolized in liver to a number of metabolites mediated by CYP2D6 and is subject to genetic polymorphism (7% to 10% of white patients, low percentage of Asian patients); therefore, they are poor metabolizers of CYP2D6 and will then metabolize the drug more slowly.

Elimination

Renal and biliary, some enterohepatic recycling. Terminal t _½ is 9.9 to 18.8 h (metabolite). Plasma t _½ is 9 to 12 h (perphenazine).

Onset

Gradual, up to several weeks, varies.

Indications and Usage

Management of psychotic disorders; treatment of schizophrenia; control of severe nausea/vomiting in adults.

Contraindications

Comatose or severely depressed states; allergy to any phenothiazine; presence of large amounts of other CNS depressants; bone marrow depression or blood dyscrasias; liver damage; subcortical brain damage.

Dosage and Administration

Psychiatric
Adults Nonhospitalized patients

PO 4 to 8 mg 3 times daily, reduce as soon as possible to minimum effective dosage.

Hospitalized patients

PO 8 to 16 mg 2 to 4 times daily; avoid dosages greater than 64 mg/day.

Nausea/Vomiting
Adults

PO 8 to 16 mg/day in divided doses; 24 mg occasionally may be necessary; early dosage reduction is desirable. Give elderly and debilitated patients lower doses and observe closely.

Children 12 yr of age and older

May be given lowest limit of adult dosage.

General Advice

• Administer without regard to meals. Administer with food if GI upset occurs.
• Shake oral concentrate well before measuring dose.
• Measure prescribed dose of oral concentrate using calibrated dropper supplied with medication.
• Dilute each 5 mL of oral concentrate with 2 oz of water, saline, 7-Up , homogenized milk, carbonated orange drink, or pineapple, apricot, prune, orange, V-8 , tomato, or grapefruit juice just prior to administration. Do not prepare dilutions ahead of time and store.
• Do not dilute oral concentrate with beverages containing caffeine (eg, coffee), tannics (eg, tea), or pectinates (eg, apple juice) because physical incompatibilities may occur.

Storage/Stability

Store tablets at controlled room temperature (59° to 86°F). Store oral concentrate in refrigerator (36° to 46°F) or at controlled room temperature. Protect oral concentrate from light.

Drug Interactions

Alcohol and other CNS depressants

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

Anticholinergics

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

Barbiturate anesthetics

Frequency and severity of neuromuscular excitation and hypotension may increase.

Cisapride, sparfloxacin

The risk of life-threatening cardiac arrhythmias, including torsades de pointes, may be increased.

Guanethidine

Hypotensive action of guanethidine may be inhibited.

Metrizamide

Possibility of seizure may be increased when subarachnoid metrizamide injection is used.

Paroxetine

Plasma levels of perphenazine may be elevated, increasing the risk of adverse reactions.

Laboratory Test Interactions

May discolor urine pink to red-brown. False-positive pregnancy tests 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; ECG changes.

CNS

Lightheadedness; faintness; dizziness; pseudoparkinsonism; dystonia; dyskinesia, motor restlessness; oculogyric crisis; dystonias; hyperreflexia; tardive dyskinesia; drowsiness; headache; fatigue; abnormalities of the cerebrospinal fluid proteins; paradoxical excitement or exacerbation of psychotic symptoms; catatonic-like states; weakness; tremor; paranoid reactions; lethargy; seizures; hyperactivity; nocturnal confusion; bizarre dreams; vertigo; insomnia.

Dermatologic

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

EENT

Pigmentary retinopathy; glaucoma; photophobia; blurred vision; mydriasis; increased IOP; dry mouth or throat; nasal congestion.

GI

Dyspepsia; adynamic ileus (may result in death); nausea; vomiting; constipation.

Genitourinary

Breast enlargement; galactorrhea; urinary hesitancy or retention; impotence; sexual dysfunction; menstrual irregularities.

Hematologic

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

Hepatic

Jaundice.

Metabolic

Hyperglycemia; hypoglycemia; decreased cholesterol.

Respiratory

Laryngospasm; bronchospasm; dyspnea.

Miscellaneous

Increases in appetite and weight; polydipsia; increased prolactin levels.

Precautions

Monitor Baseline tests Assess renal function, liver enzymes, and CBC with differential before starting therapy and then periodically thereafter during prolonged treatment. Myelography Ensure medication is discontinued at least 48 h before myelography and not resumed until at least 24 h after procedure to reduce chance of seizures occurring.

Pregnancy

Pregnancy category undetermined.

Lactation

Undetermined.

Children

Not recommended in children younger than 12 yr of age.

Elderly

More susceptible to effects; consider lower dose.

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, or those who will be exposed to extreme heat.

Antiemetic effects

Because of suppression of cough reflex, aspiration of vomitus possible.

CNS effects

May impair mental or physical abilities, especially during first few days of therapy. May lower convulsive threshold; dosage adjustments of anticonvulsants may be necessary.

Hepatic effects

Jaundice usually occurs between second and fourth weeks of treatment; considered hypersensitivity reaction. Usually reversible.

Hyperprolactinemia

Patients treated with antipsychotic agents often have elevation in prolactin levels; however, there is no evidence of increased breast tumor risk.

Neuroleptic malignant syndrome (NMS)

Potentially fatal NMS has occurred with agents of this class. Signs and symptoms are hyperpyrexia, muscle rigidity, altered mental status, irregular pulse, irregular BP, tachycardia, and diaphoresis.

Pulmonary

Cases of bronchopneumonia, some fatal, have occurred.

Sudden death

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

Suicide

Because of the possibility of suicide in depressed patients, avoid access to large quantities of this drug.

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 possible time period.

Overdosage

Symptoms

CNS depression, hypotension, extrapyramidal symptoms, agitation, convulsions, fever, hypothermia, ECG changes, cardiac arrhythmias.

Patient Information

• Advise patient, family, or caregiver that dose will be adjusted periodically until max benefit has been obtained.
• Advise patient, family, or caregiver not to change the dose or stop taking unless advised by health care provider.
• Instruct patient, family, or caregiver to measure prescribed dose of oral concentrate using calibrated dropper supplied with medication.
• Advise patient, family, or caregiver to dilute each 5 mL of oral concentrate with 2 oz of water, saline, 7-Up , homogenized milk, carbonated orange drink, or pineapple, apricot, prune, orange, V-8 , tomato, or grapefruit juice just prior to administration. Caution patient, caregiver, or family not to prepare dilutions ahead of time and store.
• Caution patient, family, or caregiver not to dilute oral concentrate with beverages containing caffeine (eg, coffee), tannins (eg, tea) or pectins (eg, apple juice), because physical incompatibilities may occur.
• Instruct patient not to stop taking perphenazine when feeling better.
• Instruct patient, family, or caregiver to immediately report fainting or loss of consciousness, palpitations, dizziness, high fever, muscle rigidity or unusual muscle movements, altered mental status, irregular pulse, sore throat or other signs of infection, bleeding or unusual bruising, or yellowing of the skin or eyes.
• Advise patient, family, or caregiver to notify health care provider of the following: excessive drowsiness, increased agitation or anxiety, involuntary body or facial movements.
• Advise patient to avoid strenuous activity during periods of high temperature or humidity.
• Instruct patient to avoid alcoholic beverages and other depressants while taking this medication.
• Instruct patient to get up slowly from lying or sitting position and to avoid sudden position changes to prevent postural hypotension. Advise patient to report dizziness with position changes to health care provider. Caution patient that hot tubs and hot showers or baths may worsen dizziness.
• Advise patient to take sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
• Advise patient that drug may cause drowsiness or impaired judgment or thinking skills and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
• Caution patient that medication may cause sensitivity to sunlight and to avoid unnecessary exposure to UV light (sunlight, tanning booths) and to use sunscreen and wear protective clothing when exposed to UV light until tolerance is determined.

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