perphenazine

Absorption: 20% absorbed following oral administration.

Distribution: Widely distributed, high concentrations in the CNS.

Protein Binding: ≥90%.

Metabolism/Excretion: Mostly metabolized by the liver via the CYP2D6 isoenzyme;the CYP2D6 isoenzyme exhibits genetic polymorphism; ∼7% of population may be poor metabolizers and may have significantly ↑ perphenazine concentrations and an ↑ risk of adverse effects.

Half-Life: 8.4–12.3 hr.

Time/Action Profile ⬆ ⬇

(antipsychotic effect‡)

ROUTE	ONSET	PEAK	DURATION
PO	2–6 hr	unknown	6–12 hr

‡Optimal antipsychotic response may not occur for several wk.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity (cross-sensitivity with other phenothiazines may occur);
Angle-closure glaucoma;
Pre-existing bone marrow depression or blood dyscrasias;
Severe liver or cardiovascular disease;
Intestinal obstruction;
Lactation: Lactation.

Use Cautiously in:

Diabetes mellitus;
Respiratory disease;
Prostatic hyperplasia;
CNS tumors;
Seizure disorder;
At risk for falls;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Safety and effectiveness not established in children;
Geri: Appears on Beers list. risk of stroke, cognitive decline, and mortality in older adults with dementia. Avoid use in older adults, except for schizophrenia or short-term use as an antiemetic.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, tachycardia

Derm: photosensitivity, pigment changes, rash

EENT: blurred vision, dry eyes, lens opacities

Endo: galactorrhea, amenorrhea

GI: constipation, dry mouth, anorexia, ileus

GU: urinary retention, urine discoloration

Hemat: AGRANULOCYTOSIS, leukopenia

Metab: hyperthermia, weight gain

Neuro: extrapyramidal reactions, NEUROLEPTIC MALIGNANT SYNDROME, sedation, tardive dyskinesia

Misc: allergic reactions

Interactions ⬆ ⬇

Drug-drug:

Additive hypotension withantihypertensives, acute ingestion of alcohol, or nitrates.
Additive CNS depression with MAO inhibitors or other CNS depressants, including alcohol, antihistamines, opioid analgesics, sedative/hypnotics, and general anesthetics.
Additive anticholinergic effects with other drugs possessing anticholinergic properties, including antihistamines, antidepressants, atropine, disopyramide, haloperidol, and other phenothiazines.
Hypotension and tachycardia may occur with epinephrine.
↑risk of agranulocytosis with other agents that cause bone marrow suppression, including antithyroid agents.
↑risk of extrapyramidal reactions with lithium.
May mask lithium toxicity.
Antacids or lithium may ↓ absorption of perphenazine.
May ↓ antiparkinson effect of levodopa or bromocriptine.

Drug-Natural Products:

↑anticholinergic effects with angel's trumpet, jimson weed, and scopolia.

Route/Dosage ⬆ ⬇

Schizophrenia

PO (Adults ): 2–16 mg 2–4 times daily (not to exceed 64 mg/day).

Nausea/Vomiting

PO (Adults ): 8–16 mg/day in divided doses (not to exceed 24 mg/day).

Availability ⬆ ⬇

(Generic available)

Tablets: 2 mg; 4 mg; 8 mg; 16 mg

Assessment ⬆ ⬇

Assess mental status (orientation, mood, behavior) prior to and periodically during therapy.
- Assess fasting blood glucose, cholesterol level, weight, and BMI, initially and periodically throughout therapy. Refer as appropriate for nutritional/weight management and medical management.
- Assess positive (hallucinations, delusions, agitation) and negative (social withdrawal) symptoms of schizophrenia.
- Monitor BP (sitting, standing, lying), ECG, pulse, and respiratory rate prior to and periodically during the period of dose adjustment. May cause Q-wave and T-wave changes in ECG.
- Observe patient carefully when administering medication to ensure that medication is actually taken and not hoarded or cheeked.
- Assess fluid intake and bowel function. Increased bulk and fluids in the diet may help minimize constipation.
- Monitor patient for onset of akathisia (restlessness or desire to keep moving) and extrapyramidal side effects (parkinsonian: difficulty speaking or swallowing, loss of balance control, pill rolling of hands, mask-like face, shuffling gait, rigidity, tremors; and dystonic: muscle spasms, twisting motions, twitching, inability to move eyes, weakness of arms or legs) every 2 mo during therapy and 8–12 wk after therapy has been discontinued. Report these symptoms; reduction in dose or discontinuation of medication may be necessary. Trihexyphenidyl, diphenhydramine, or benztropine may be used to control these symptoms. Benzodiazepines may alleviate akathisia.
- Monitor for tardive dyskinesia (uncontrolled rhythmic movement of mouth, face, and extremities; lip smacking or puckering; puffing of cheeks; uncontrolled chewing; rapid or worm-like movements of tongue, excessive eye blinking). Notify health care professional immediately if these symptoms occur, as these side effects may be irreversible.
- Monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, convulsions, diaphoresis, hypertension or hypotension, pallor, tiredness, severe muscle stiffness, loss of bladder control). Notify health care professional immediately if these symptoms occur.
- Assess for falls risk. Drowsiness, orthostatic hypotension, and motor and sensory instability increase risk. Institute prevention if indicated.
Antiemetic: Assess nausea and vomiting prior to and following perphenazine administration.
- Monitor intake and output. Patients with severe nausea and vomiting may require IV fluids with electrolytes in addition to antiemetics.

Lab Test Considerations:

Evaluate CBC, liver function tests, and ocular examinations periodically during therapy. May cause ↓ hematocrit, hemoglobin, leukocytes, granulocytes, or platelets. May cause ↑ bilirubin, AST, ALT, and alkaline phosphatase. Agranulocytosis occurs after 4–10 wk of therapy, with recovery 1–2 wk following discontinuation. May recur if medication is restarted. Liver function abnormalities may require discontinuation of therapy.
- May cause false-positive or false-negative pregnancy test results and false-positive urine bilirubin test results.

Implementation ⬆ ⬇

PO: Administer without regard to meals.

Patient/Family Teaching ⬆ ⬇

Advise patient to take medication as directed and not to skip doses or double up on missed doses. Take missed doses as soon as remembered unless almost time for the next dose. If more than 2 doses/day are ordered, the missed dose should be taken within 1 hr of the scheduled time or omitted. Abrupt withdrawal may lead to gastritis, nausea, vomiting, dizziness, headache, tachycardia, and insomnia.
Inform patient of possibility of extrapyramidal symptoms and tardive dyskinesia. Instruct patient to report these symptoms immediately.
Advise patient to make position changes slowly to minimize orthostatic hypotension. Protect from falls.
Medication may cause drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
Caution patient to avoid taking alcohol or other CNS depressants concurrently with this medication.
Advise patient to use sunscreen and protective clothing when exposed to the sun. Exposed surfaces may develop a blue-gray pigmentation, which may fade following discontinuation of the medication. Extremes in temperature should also be avoided, because this drug impairs body temperature regulation.
Instruct patient to use frequent mouth rinses, good oral hygiene, and sugarless gum or candy to minimize dry mouth. Consult health care professional if dry mouth continues for >2 wk.
Advise patient not to take perphenazine within 2 hr of antacids or antidiarrheal medication.
Inform patient that this medication may turn urine a pink to reddish-brown color.
Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
Instruct patient to notify health care professional promptly if sore throat, fever, unusual bleeding or bruising, rash, weakness, tremors, visual disturbances, dark-colored urine, or clay-colored stools occur.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding. Advise patients that use during 3rd trimester may cause extrapyramidal and/or withdrawal symptoms (agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder).
Emphasize the importance of routine follow-up exams to monitor response to medication and detect side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇