fluphenazine decanoate
Modecate ◆, Prolixin Decanoate

fluphenazine enanthate
Moditen Enanthate ◆, Prolixin Enanthate

fluphenazine hydrochloride
Permitil, Prolixin

Available forms
Available by prescription only
fluphenazine decanoate
Depot injection: 25 mg/ml
fluphenazine enanthate
Depot injection: 25 mg/ml
fluphenazine hydrochloride
Elixir: 2.5 mg/5 ml (with 14% alcohol)
I.M. injection: 2.5 mg/ml
Oral concentrate: 5 mg/ml (Prolixin contains 14% alcohol and Permitil contains 1% alcohol)
Tablets: 1 mg, 2.5 mg, 5 mg, 10 mg

Indications and dosages
 Psychotic disorders. Adults: Initially, 0.5 to 10 mg fluphenazine hydrochloride P.O. daily in divided doses q 6 to 8 hours; may increase cautiously to 20 mg. Maintenance dosage is 1 to 5 mg P.O. daily. I.M. doses are one-third to one-half that of oral doses; the usual starting dose is 1.25 mg I.M. The initial total daily dose is 2.5 to 10 mg divided and given every 6 to 8 hours. For the enanthate and decanoate formulations, 12.5 to 25 mg I.M. q 3 to 6 weeks.
Elderly patients: Use lower doses (1 to 2.5 mg P.O. daily).

Pharmacodynamics
Antipsychotic action: Fluphenazine is thought to exert antipsychotic effects by postsynaptic blockade of CNS dopamine receptors, thereby inhibiting dopamine-mediated effects.
Fluphenazine has many other central and peripheral effects; it produces both alpha and ganglionic blockade and counteracts histamine- and serotonin-mediated activity. Its most prominent adverse reactions are extrapyramidal.

Pharmacokinetics
Absorption: Rate and extent of absorption vary with route of administration; oral tablet absorption is erratic and variable.
Distribution: Distributed widely into the body, including breast milk. CNS levels of drug are usually higher than those in plasma. Drug is 91% to 99% protein-bound.
Metabolism: Metabolized extensively by the liver, but no active metabolites are formed; duration of action is about 6 to 8 hours after oral administration; 1 to 6 weeks (average, 2 weeks) after I.M. depot administration.
Excretion: Mostly excreted in urine via the kidneys; some is excreted in feces via the biliary tract.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and patients experiencing coma, CNS depression, bone marrow suppression, other blood dyscrasia, subcortical damage, or liver damage.
  Use cautiously in elderly or debilitated patients and in those with pheochromocytoma, severe CV disease, peptic ulcer disease, exposure to extreme hot or cold (including antipyretic therapy), exposure to phosphorus insecticides, respiratory or seizure disorders, hypocalcemia, severe reaction to insulin or electroconvulsive therapy, mitral insufficiency, glaucoma, or prostatic hyperplasia. Use parenteral form cautiously in patients with asthma and those allergic to sulfites.

Interactions
Drug-drug. Aluminum- and magnesium-containing antacids and antidiarrheals: Decreases absorption. Monitor patient.
Antiarrhythmics, disopyramide, procainamide, quinidine: Increases risk of arrhythmias and conduction defects. Avoid use together.
Anticholinergics, including antidepressants, antihistamines, antiparkinsonians, atropine, MAO inhibitors, meperidine, phenothiazines: Causes oversedation, paralytic ileus, visual changes, and severe constipation. Avoid use together.
Beta blockers: Increases plasma levels and toxicity. Monitor patient closely.
Bromocriptine: Antagonizes therapeutic effect of bromocriptine on prolactin secretion. Monitor patient for drug effect.
Centrally acting antihypertensives, such as clonidine, guanabenz, guanadrel, guanethidine, methyldopa, and reserpine: Inhibits blood pressure response. Monitor patient closely.
CNS depressants, including analgesics, barbiturates, narcotics, parenteral magnesium sulfate, tranquilizers, and general, spinal, or epidural anesthetics: May cause additive effects of oversedation, respiratory depression, and hypotension. Avoid use together.
Dopamine: Decreases vasoconstricting effects. Monitor patient carefully.
Levodopa: Decreases effectiveness and increases toxicity of levodopa. Monitor patient carefully.
Lithium: May cause severe neurologic toxicity with an encephalitis-like syndrome and a decreased therapeutic response to fluphenazine. Monitor patient closely.
Metrizamide: Increases risk of seizures. Observe patient closely.
Nitrates: May result in hypotension. Check blood pressure frequently.
Phenobarbital: Enhances renal excretion. Monitor patient closely.
Phenytoin, tricyclic antidepressants: Inhibits metabolism and increases toxicity of these drugs. Monitor patient closely.
Propylthiouracil: Increases risk of agranulocytosis. Monitor patient carefully.
Sympathomimetics including ephedrine, epinephrine, and phenylephrine (common in nasal sprays) and appetite suppressants: Decreases stimulatory and pressor effects of these drugs. Use together cautiously.
Drug-food. Caffeine: Increases fluphenazine metabolism. Discourage caffeine use.
Drug-lifestyle. Alcohol use: May increase CNS depression. Discourage alcohol use.
Smoking: Increases fluphenazine metabolism. Discourage smoking.
Sun exposure: Increases risk of photosensitivity. Advise patient to take precautions.

Adverse reactions
CNS: neuroleptic malignant syndrome, extrapyramidal reactions, tardive dyskinesia, sedation, pseudoparkinsonism, EEG changes, drowsiness,seizures, dizziness.
CV: orthostatic hypotension, tachycardia, ECG changes.
EENT: ocular changes, blurred vision, nasal congestion.
GI: dry mouth, constipation.
GU: urine retention, dark urine, menstrual irregularities, inhibited ejaculation.
Hematologic: leukopenia, agranulocytosis, eosinophilia, hemolytic anemia, aplastic anemia, thrombocytopenia.
Hepatic: cholestatic jaundice.
Metabolic: elevated protein-bound iodine level, weight gain, increased appetite.
Skin: mild photosensitivity, allergic reactions.
Other: gynecomastia.

Effects on lab test results
• May increase liver function test values and eosinophil count. May decrease hemoglobin 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. Don’t induce vomiting: Drug inhibits cough reflex, and aspiration may occur. Use gastric lavage and then activated charcoal and saline cathartics; dialysis doesn’t help. 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 adjusted to blood pressure), and extrapyramidal reactions with benztropine 1 to 2 mg or parenteral diphenhydramine at 10 to 50 mg.

Special considerations
• Prolixin Concentrate and Permitil Concentrate are 10 times more concentrated than Prolixin elixir (5 mg/ml versus 0.5 mg/ml). Order carefully.
• Oral liquid and parenteral forms can cause contact dermatitis. Wear gloves and avoid contact with skin and clothing.
• Protect drug from light. Slight yellowing of injection or concentrate is common and doesn’t affect potency. Discard markedly discolored solutions.
• Dilute liquid concentrate with water, fruit juice, milk, or semisolid food just before administration.
• For long-acting forms (decanoate and enanthate), which are oil preparations, use a dry needle of at least 21G. Allow 24 to 96 hours for onset of action.
• Monitor patient for tardive dyskinesia, which may occur after prolonged use. It may not appear until months or years later and may disappear spontaneously or persist for life, despite ending drug.
 ALERT Watch for evidence of neuroleptic malignant syndrome (extrapyramidal effects, hyperthermia, autonomic disturbance), which is rare but commonly fatal. It may not be related to length of drug use or type of neuroleptic; however, more than 60% of affected patients are men.
• Monitor therapy with weekly bilirubin tests during first month, periodic blood tests (CBCs and liver function tests), and periodic renal function and ophthalmic tests (long-term use).
• Drug causes false-positive test results for urinary porphyrins, urobilinogen, amylase, and 5-hydroxyindoleacetic acid because of darkening of urine by metabolites; it also causes false-positive results for urine pregnancy tests that use human chorionic gonadotropin.
• Withhold dose if symptoms of blood dyscrasia (fever, sore throat, infection, cellulitis, weakness) or persistent extrapyramidal reactions (longer than a few hours) develop, especially in children and pregnant women.
• Don’t withdraw drug abruptly unless serious adverse reactions occur.
• After abrupt withdrawal of long-term therapy, gastritis, nausea, vomiting, dizziness, tremor, feeling of warmth or cold, diaphoresis, tachycardia, headache, or insomnia may occur.
• Depot injection (25 mg/ml) and I.M. injection (2.5 mg/ml) aren’t interchangeable.
• Depot injection isn’t recommended for patients who aren’t stabilized on a phenothiazine. This form has a prolonged elimination; its action couldn’t be terminated in case of adverse reactions.
Breast-feeding patients
• Drug appears in breast milk. Use cautiously; potential benefits to mother should outweigh potential harm to infant.
Pediatric patients
• Safety and efficacy in children younger than age 12 haven’t been established.

Patient education
• Inform patient that drug may cause dizziness or drowsiness. Advise patient to avoid hazardous tasks that require alertness until CNS response to drug is established.
• Tell patient to avoid ingestion of alcohol and to seek medical approval before taking other drugs.
• Instruct patient to promptly report rash or hives, anxiety, nervousness, anorexia (especially in underweight patients), suspicion of pregnancy, or intent to become pregnant.

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