Class: Phenothiazine derivative Fluphenazine Hydrochloride
- Tablets, oral 1 mg
- Tablets, oral 2.5 mg
- Tablets, oral 5 mg
- Tablets, oral 10 mg
- Elixir, oral 0.5 mg/mL
- Solution, concentrate, oral 5 mg/mL
- Injection, solution 2.5 mg/mL
- Injection, solution, ER 25 mg/mL
Blocks dopamine receptors in CNS.
Fluphenazine hydrochloride is absorbed after oral doses. Fluphenazine deaconate is very slowly absorbed from the site of injection and gradually released into the body.
CYP2D6 is involved in fluphenazine metabolism.
Fluphenazine sulfoxide and 7–hydroxyfluphenazine were identified in the urine and feces. Plasma half-life of fluphenazine hydrochloride is 14.7 h (tablet) and 14.9 to 15.3 h (IM injection); plasma half-life of fluphenazine deaconate is 6 to 9 days after IM injection.
Indications and UsageFluphenazine hydrochloride
For the management of psychotic disorders.Fluphenazine decanoate
For use in the management of patients requiring prolonged and parenteral neuroleptic therapy (eg, chronic schizophrenic patients).
Suspected or established subcortical brain damage; patients receiving large doses of hypnotics; comatose or severely depressed states; blood dyscrasia; liver damage; hypersensitivity to fluphenazine (cross-sensitivity to phenothiazine derivatives may occur); children younger than 12 years (decanoate only).
Dosage and AdministrationFluphenazine Hydrochloride
Initially, 2.5 to 10 mg/day in divided doses at 6- to 8-h intervals. Patients remaining severely disturbed or inadequately controlled may require upward titration of dosage. Therapeutic effect is often achieve with dosages less than 20 mg/day; however, daily doses up to 40 mg may be necessary. When symptoms are controlled, gradually reduce dosage to 1 to 5 mg/day.IM
Average starting dose is 1.25 mg. Depending on severity and duration of symptoms, initial daily dose may range from 2.5 to 10 mg, divided and given at 6- to 8-h intervals. Dosages exceeding 10 mg/day should be used with caution. When symptoms are controlled, oral maintenance therapy can generally be instituted, often with single daily doses.Elderly
PO Start with 1 to 2.5 mg/day, adjusted according to response.Fluphenazine Decanoate
IM / Subcutaneous 12.5 to 25 mg initially. If doses greater than 50 mg are needed, the next and succeeding doses should be increased cautiously in 12.5 mg increments (max, 100 mg/dose). A single injection may be effective in controlling symptoms up to 4 to 6 weeks.Conversion
For psychotic patients stabilized on a fixed daily dosage of orally administered fluphenazine, conversion from short-acting oral therapy to the long-acting injectable fluphenazine decanoate may be indicated. A controlled multicenter study showed that fluphenazine 20 mg orally daily was equivalent to fluphenazine decanoate 25 mg every 3 weeks. This represents an approximate conversion ratio of 12.5 mg of decanoate every 3 weeks for every 10 mg of oral fluphenazine daily.Discontinuation
Abrupt discontinuation of high-dose therapy has been associated with withdrawal symptoms (eg, nausea, vomiting, dizziness, headache, tachycardia, insomnia, tremulousness). These symptoms can be reduced by continuing concomitant antiparkinson agents for several weeks after fluphenazine is withdrawn.
- Oral concentrate
- Add the desired dose (measured by a calibrated device only) to at least 60 mL of a suitable diluent just prior to administration to ensure palatability and stability. Suggested diluents include tomato or fruit juice, milk, and uncaffeinated soft drinks.
- Do not mix with beverages containing caffeine (coffee, cola), tannics (tea), or pectinates (apple juice) because of the potential incompatibility.
- Decanoate injection
- For IM or subcutaneous administration only.
- Use a dry syringe and needle of at least 21 gauge.
- Initially, treat patients who have never taken phenothiazines and poor risk patients with a shorter-acting form of fluphenazine before administering the decanoate.
- Severely agitated patients should be initially treated with rapid-acting phenothiazine compound. When acute symptoms subside, administer fluphenazine decanoate; adjust subsequent dosage as necessary.
- Once conversion to fluphenazine decanoate is made, careful clinical monitoring of the patient and appropriate dosage adjustment should be made at the time of each injection.
- Hydrochloride injection
- For IM use.
- Parenteral solutions may vary in color from essentially colorless to light amber. If a solution has become any darker than light amber or is discolored in any other way, it should not be used.
- Institute treatment with a low initial dosage; increase as necessary until the desired clinical effects are achieved. Continued treatment by the oral route, if possible, is needed to achieve maximum therapeutic benefits; further adjustments in dosage may be necessary during the course of therapy to meet the patient's requirements.
Store between 68° and 77°F. Protect from light.
Drug InteractionsAlcohol and other CNS depressants (eg, opiates, barbiturates)
The effects of CNS depressants may be potentiated by fluphenazine. Coadministration of fluphenazine with large doses of hypnotics is contraindicated.Anorexiants (eg, dextroamphetamine)
Coadministration may decrease or abolish the pharmacologic effects of both drugs.Anticholinergics (eg, atropine)
The antipsychotic effectiveness of fluphenazine may be decreased by anticholinergics. This combination may cause additive anticholinergic toxicity. If anticholinergics are required, it may be necessary to adjust the fluphenazine dose to produce the maximum therapeutic effect with minimum toxicity.Cabergoline
Concomitant use may decrease the pharmacologic effects of cabergoline. Coadministration is not recommended.Epinephrine
Fluphenazine may reverse the beta-adrenergic effects of epinephrine, producing hypotension and tachycardia.Guanethidine
Hypotensive action may be inhibited. Avoid this drug combination when possible. If coadministration of both drugs is required, larger dosages of guanethidine may be needed. Monitor BP and adjust the dosage of guanethidine accordingly.Levodopa
Fluphenazine may decrease the pharmacologic effects of levodopa. Concomitant use is not recommended. If concomitant use is necessary, monitor the patient for reduced levodopa pharmacologic effect.Lithium
The pharmacologic effects of fluphenazine may be decreased by lithium. Severe neurotoxicity has been reported in patients receiving the combination of lithium and fluphenazine.Metoclopramide
Coadministration may increase the risk of extrapyramidal reactions. Coadministration is contraindicated.Pergolide
Fluphenazine may decrease the pharmacologic effects of pergolide. Concomitant use is not recommended.QT interval–prolonging drugs (eg, antiarrhythmic agents [eg, amiodarone, bretylium, disopyramide, dofetilide, procainamide, propafenone, quinidine, sotalol], arsenic trioxide, chlorpromazine, cisapride, dasatinib, dolasetron, droperidol, haloperidol, lapatinib, mefloquine, mesoridazine, methadone, moxifloxacin, nilotinib, pentamidine, pimozide, romidepsin, tacrolimus, thioridazine, vandetanib, ziprasidone)
The risk of life-threatening cardiac arrhythmias, including torsades de pointes may be increased. Fluphenazine should not be taken with any other drug that prolongs the QT interval.SSRIs (eg, fluoxetine)
Plasma fluphenazine concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions, including extrapyramidal effects and life-threatening cardiac arrhythmias. Monitor closely. If an interaction is suspected, consider decreasing the dosage or stopping one or both agents.Tramadol
Coadministration may increase the risk for seizures. Coadministration is not recommended.Trazodone
Plasma concentrations and pharmacologic effects of trazodone may be increased by fluphenazine. If an interaction is suspected, decrease the dosage of trazodone.
Laboratory Test Interactions
False-positive pregnancy tests may occur.
Cardiac arrest; ECG changes; hypertension; hypotension; tachycardia.
Bizarre dreams; cerebral edema; drowsiness; dystonia; EEG changes; excitement; extrapyramidal signs and symptoms; headache; increased libido; induction of a catatonic-like state; lethargy; restlessness; tardive dyskinesia.
Eczema; erythema; exfoliative dermatitis; itching; perspiration; photosensitivity; seborrhea; skin pigmentation; urticaria.
Blurred vision; dry mouth; glaucoma; lenticular and corneal opacities; nasal congestion.
Constipation; fecal impaction; loss of appetite; nausea; paralytic ileus; salivation.
Abnormal lactation; bladder paralysis; false pregnancy test results; gynecomastia; impotence; menstrual irregularities; polyuria.
Agranulocytosis; eosinophilia; leukopenia; nonthrombocytopenic purpura; pancytopenia; thrombocytopenic purpura.
Angioneurotic and/or laryngeal edema; increased prolactin levels; NMS; peripheral edema; SLE-like syndrome; weight change.
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of 17 placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 and 1.7 times the risk of death in placebo-treated patients. Most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. Fluphenazine is not approved for the treatment of patients with dementia-related psychosis.
Periodically check hepatic function, renal function, and the blood picture. Renal function of patients on long-term therapy should be monitored; if BUN becomes abnormal, treatment should be discontinued. Frequently assess patient for response to treatment. Periodically review therapy to determine if it needs to be continued without change or if a dose change is indicated. Monitor CBC frequently during the first few months of therapy in patients with a preexisting low WBC or a history of drug-induced leukopenia/neutropenia. Carefully monitor patients with neutropenia for fever or other symptoms or signs of infection.
Category undetermined . Neonates exposed to antipsychotic drugs during the third trimester of pregnancy are at risk of extrapyramidal and/or withdrawal symptoms following delivery.
Safety and efficacy not established. Fluphenazine deaconate is contraindicated in children younger than 12 years.
Because of the possibility of cross-sensitivity, fluphenazine should be used cautiously in patients who have developed cholestatic jaundice, dermatoses, or other allergic reactions to phenothiazine derivatives.
Special Risk Patients
Use cautiously in patients exposed to extreme heat or phosphorus insecticides; in patients with a history of convulsive disorders, because tonic-clonic seizures have been known to occur; and in patients with special medical disorders, such as mitral insufficiency or other CV disease and pheochromocytoma.
May impair the mental and physical abilities required for driving a car or operating machinery.
Although fluphenazine is not known to cause psychological or physical dependence, abrupt discontinuation of high-dose therapy has been associated with withdrawal symptoms (eg, nausea, vomiting, dizziness, headache, tachycardia, insomnia, tremulousness).
Leukopenia/neutropenia and agranulocytosis (including fatal cases) have been reported.
Patients treated with antipsychotic agents often have elevation in prolactin levels; however, there is no evidence of increased breast tumor risk.
The possibility of liver damage, pigmentary retinopathy, lenticular and corneal deposits, and development of irreversible dyskinesias should be kept in mind when patients are on long-term therapy.
Neuroleptic malignant syndrome
Potentially fatal condition that has occurred. Signs and symptoms include hyperpyrexia, muscle rigidity, altered mental status, irregular pulse, fluctuating BP, tachycardia, cardiac dysrhythmias, and diaphoresis.
Development of silent pneumonias may occur.
Patients on large doses of a phenothiazine drug who are undergoing surgery should be watched carefully for possible hypotensive phenomena. Moreover, reduced amounts of anesthetics or CNS depressants may be necessary.
Syndrome of potentially irreversible, involuntary body and facial movements may develop. Prevalence is highest in elderly patients, especially women. Use the smallest effective dose for the shortest possible time period.
No data available.
- Explain the risk of developing tardive dyskinesia.
- Advise patients that drug may cause drowsiness and impaired judgment or thinking skills and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.
Copyright © 2009 Wolters Kluwer Health.
More about fluphenazine
- Fluphenazine decanoate (AHFS Monograph)
- Fluphenazine hydrochloride (AHFS Monograph)
- Fluphenazine Elixir (FDA)
- Fluphenazine Hydrochloride Injection (FDA)
- Fluphenazine Injection (FDA)
- Fluphenazine Oral Solution (FDA)