Skip to main content

fluPHENAZine (Monograph)

Brand name: Formerly available as Prolixin
Drug class: Phenothiazines
VA class: CN701
CAS number: 5002-47-1

Medically reviewed by on Nov 6, 2023. Written by ASHP.


    Increased Mortality in Geriatric Patients with Dementia-related Psychosis
  • Geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death.

  • Analyses of 17 placebo-controlled trials in geriatric patients mainly receiving atypical antipsychotic agents revealed an approximate 1.6- to 1.7-fold increase in mortality compared with that in patients receiving placebo.

  • Most fatalities appeared to result from cardiovascular-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).

  • Observational studies suggest that conventional or first-generation antipsychotic agents also may increase mortality in such patients.

  • Antipsychotic agents, including fluphenazine, are not approved for the treatment of dementia-related psychosis.


Propylpiperazine-derivative phenothiazine; conventional (prototypical, first-generation) antipsychotic agent.

Uses for fluPHENAZine

Psychotic Disorders

Symptomatic management of psychotic disorders (i.e., schizophrenia).

The long-acting decanoate ester is used mainly for maintenance therapy in patients with chronic schizophrenic disorder who cannot be relied on to take oral antipsychotic drugs; do not use for acute management of severely agitated patients.

fluPHENAZine Dosage and Administration



Administer fluphenazine hydrochloride orally or IM.

Administer fluphenazine decanoate IM or sub-Q. If used outside of psychiatric institutions, administer under direction of clinician experienced in use of psychotropic drugs, particularly phenothiazine derivatives.

Avoid skin contact with elixir, oral concentrate solution, or injection since contact dermatitis rarely occurs.

Oral Administration

Fluphenazine hydrochloride: Administer orally every 6–8 hours initially; maintenance therapy can often be administered as a single daily dose.

When oral concentrate solution is used, dilute dose with at least 60 mL of suitable diluent (e.g., water; uncaffeinated soft drinks [e.g., Seven-Up]; carbonated orange beverage; sodium chloride; milk; V-8; or pineapple, apricot, prune, orange, tomato, or grapefruit juice) just before administration. (See Compatibility under Stability.)

IM or Sub-Q Administration

Fluphenazine hydrochloride: Administer IM every 6–8 hours.

Fluphenazine decanoate: Administer IM or sub-Q using a dry syringe and needle of at least 21 gauge; use of a wet needle or syringe may cause solution to become cloudy.


Available as fluphenazine hydrochloride or fluphenazine decanoate; dosage expressed in terms of the salt.

Carefully adjust dosage according to individual requirements and response, using lowest possible effective dosage.

Periodically evaluate patients receiving long-term therapy to determine whether maintenance dosage may be decreased or drug therapy discontinued. (See Tardive Dyskinesia under Cautions.)

Conversion from oral fluphenazine hydrochloride to long-acting decanoate injection may be indicated for psychotic patients stabilized on a fixed daily oral dosage. In patients without a history of therapy with phenothiazines, administer shorter-acting form for several weeks prior to instituting therapy with fluphenazine decanoate in order to determine patient’s approximate dosage requirements and susceptibility to adverse effects.

Precise formula for converting therapy from fluphenazine hydrochloride to fluphenazine decanoate not established. An approximate conversion ratio of 12.5 mg every 3 weeks of fluphenazine decanoate for every 10 mg daily of fluphenazine hydrochloride has been used.


Psychotic Disorders

Fluphenazine hydrochloride: Initially, 2.5–10 mg daily given in divided doses every 6–8 hours. Dosage may be gradually increased, if necessary, until desired clinical effects are obtained.

Optimum therapeutic effect often occurs with oral fluphenazine hydrochloride dosages <20 mg daily. Dosages up to 40 mg may be required in severely disturbed patients, but safety of prolonged administration of such dosages not established. Use dosages >20 mg daily with caution.

After maximum response attained, reduce fluphenazine hydrochloride dosage gradually to maintenance dosage of 1–5 mg daily, often as a single dose. To avoid recurrence of psychotic symptoms, continued therapy is required following optimum therapeutic response.


Fluphenazine hydrochloride: Generally, IM dose is approximately one-third to one-half the oral dose.

Usual initial fluphenazine hydrochloride dose is 1.25 mg. Depending on severity and duration of symptoms, initial total IM dosage may range from 2.5–10 mg daily given in divided doses every 6–8 hours; may gradually increase dosage if necessary, until symptoms are controlled.

Use fluphenazine hydrochloride dosages >10 mg daily with caution.

After symptoms are controlled, oral therapy generally should replace parenteral therapy.

IM or Sub-Q

Fluphenazine decanoate: In patients with chronic schizophrenic disorder, usual initial dose is 12.5–25 mg.

Carefully adjust subsequent fluphenazine decanoate dose and dosage interval according to patient tolerance and response; if doses >50 mg are deemed necessary, increase the next and succeeding doses cautiously in increments of 12.5 mg, but do not exceed 100 mg.

When administered as maintenance therapy, a single fluphenazine decanoate injection may be effective in controlling schizophrenic symptoms for up to 4 weeks or longer; response may persist for up to 6 weeks in some patients.

Prescribing Limits


Psychotic Disorders

Fluphenazine hydrochloride: Safety of prolonged administration of dosages up to 40 mg daily not established. Use dosages >20 mg daily with caution.


Fluphenazine hydrochloride: Use dosages >10 mg daily with caution.

IM or Sub-Q

Fluphenazine decanoate: Do not exceed 100 mg.

Special Populations

Geriatric Patients

Fluphenazine hydrochloride: Initially, 1–2.5 mg orally daily; adjust subsequent dosage based on patient response. Increase dosage more gradually in debilitated, emaciated, or geriatric patients.

Cautions for fluPHENAZine




Increased Mortality in Geriatric Patients with Dementia-related Psychosis

Increased risk of death with use of either conventional (first-generation) or atypical (second-generation) antipsychotics in geriatric patients with dementia-related psychosis.

Antipsychotic agents, including fluphenazine, are not approved for the treatment of dementia-related psychosis. (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning.)

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary, dyskinetic movements, reported with use of antipsychotic agents, including fluphenazine.

Reserve long-term antipsychotic treatment for patients with chronic illness known to respond to antipsychotic agents, and for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients requiring chronic treatment, use smallest dosage and shortest duration of treatment producing a satisfactory clinical response; periodically reassess need for continued therapy.

APA recommends assessing patients receiving conventional antipsychotic agents for abnormal involuntary movements every 6 months; for patients at increased risk for tardive dyskinesia, assess every 3 months. Consider discontinuance of fluphenazine if signs and symptoms of tardive dyskinesia appear. However, some patients may require treatment despite the presence of the syndrome.

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability, reported with antipsychotic agents, including fluphenazine.

Immediately discontinue therapy and initiate supportive and symptomatic treatment if NMS occurs. Careful monitoring recommended if therapy is reinstituted following recovery; the risk that NMS can recur must be considered.

Sensitivity Reactions


Skin disorders (e.g., pruritus, erythema, urticaria, seborrhea, photosensitivity, eczema, exfoliative dermatitis) reported with phenothiazine derivatives. Contact dermatitis reported rarely.

Consider possibility of anaphylactoid reactions.


Possible cross-sensitivity with other phenothiazines; use with caution in patients who have developed cholestatic jaundice, dermatoses, or other allergic reactions to phenothiazine derivatives.

General Precautions

Use phenothiazines with caution in debilitated patients, patients with renal or hepatic disease, patients with glaucoma or prostatic hypertrophy, and patients exposed to organophosphate insecticides.

Use phenothiazines with caution in patients with hypocalcemia, since susceptibility to dystonic reactions may be increased.

Hematologic Effects

Leukopenia and neutropenia temporally related to antipsychotic agents, including fluphenazine, reported during clinical trial and/or postmarketing experience. Agranulocytosis (including fatal cases) also reported with antipsychotic agents.

Possible risk factors for leukopenia and neutropenia include preexisting low WBC count and a history of drug-induced leukopenia or neutropenia. Monitor CBC frequently during the first few months of therapy in patients with such risk factors. Discontinue fluphenazine at the first sign of a decline in WBC count in the absence of other causative factors.

Carefully monitor patients with clinically important neutropenia for fever or other signs and symptoms of infection and treat promptly if they occur. In patients with severe neutropenia (ANC <1000/mm3), discontinue fluphenazine and monitor WBC until recovery occurs.

Other blood dyscrasias, including thrombocytopenic or nonthrombocytopenic purpura, eosinophilia, and pancytopenia, reported with phenothiazine derivatives. Perform hematologic evaluations periodically.

Abrupt Withdrawal

Gastritis, nausea, vomiting, dizziness, and tremulousness reported after abrupt discontinuance of high-dose therapy; minimize symptoms by continuing concomitant antiparkinsonian agents for several weeks after phenothiazine is withdrawn.

Cardiovascular Effects

Hypotension occurs rarely. Patients with pheochromocytoma, cerebral or vascular insufficiency, or severe cardiac reserve deficiency (e.g., mitral insufficiency), or psychotic patients receiving large doses of phenothiazines who are undergoing surgery may be especially prone to hypotensive effects; closely monitor such patients during therapy.

Hypertension and fluctuations in BP may occur.

Nervous System Effects

Possible risk of seizures; phenothiazines may lower seizure threshold. Use with caution in patients with a history of seizures or EEG abnormalities or in those receiving anticonvulsant agents. Maintain adequate anticonvulsant therapy.

Drowsiness or lethargy possible; may necessitate dosage reduction.

Because of CNS depressant effects of phenothiazines, use with caution in patients with chronic respiratory disorders (e.g., severe asthma, emphysema, acute respiratory tract infections).

Neurologic reactions from phenothiazine therapy may be similar to CNS manifestations accompanying certain disorders (e.g., Reye’s syndrome, encephalopathy, meningitis, tetanus); diagnosis of these disorders may be obscured or disease-associated manifestations may be incorrectly diagnosed as drug induced.

Antiemetic effect of phenothiazines may mask signs of overdosage of toxic drugs (e.g., antineoplastic agents) or may obscure cause of vomiting in various disorders (e.g., intestinal obstruction, Reye’s syndrome, brain tumor).

Phenothiazines depress hypothalamic mechanism for body temperature regulation; use caution in patients exposed to extreme heat or cold.

Extrapyramidal symptoms occur frequently and are usually reversible; persistent reactions can usually be controlled by concomitant therapy with an antiparkinsonian drug and subsequent dosage reduction.

Autonomic reactions (e.g., nausea, appetite loss, salivation, polyuria, perspiration, dry mouth, headache, constipation) may occur.

Hepatic Effects

Liver damage, manifested by cholestatic jaundice may occur, particularly during first months of therapy; discontinue immediately if liver damage occurs.

Consider possibility of liver damage in patients receiving prolonged therapy. Monitor hepatic function periodically.

Ocular Effects

Consider possibility of pigmentary retinopathy and lenticular and corneal deposits in patients receiving prolonged therapy. Periodic ophthalmic examinations recommended in patients receiving prolonged phenothiazine therapy with moderate to high dosages.


May cause elevated serum prolactin concentrations, which may persist during chronic administration and cause clinical disturbances (e.g., galactorrhea, amenorrhea, gynecomastia, impotence).

If contemplating fluphenazine therapy in a patient with previously detected breast cancer, consider that approximately one-third of human breast cancers are prolactin dependent in vitro.

Pulmonary Effects

Clinicians should be alert to possible development of “silent pneumonias” in patients receiving phenothiazines, including fluphenazine.

Use with caution in patients with chronic respiratory disorders (e.g., severe asthma, emphysema, acute respiratory tract infections).

Specific Populations


Category C.

Risk for extrapyramidal and/or withdrawal symptoms (e.g., agitation, hypertonia, hypotonia, tardive dyskinetic-like symptoms, tremor, somnolence, respiratory distress, feeding disorder) in neonates exposed to antipsychotic agents during the third trimester; monitor neonates exhibiting such symptoms. Symptoms were self-limiting in some neonates but varied in severity; some infants required intensive support and prolonged hospitalization.

Use during pregnancy only if potential benefit justifies potential risk to the fetus.


Phenothiazines are distributed into milk. Women receiving phenothiazines should not breast-feed.

Pediatric Use

Insufficient experience with fluphenazine hydrochloride to establish safety and efficacy.

Safety and efficacy of fluphenazine decanoate not established in children <12 years of age.

Geriatric Use

Geriatric patients appear to be particularly sensitive to adverse CNS (e.g., tardive dyskinesia, parkinsonian manifestations, akathisia, sedation), anticholinergic, and cardiovascular (e.g., orthostatic hypotension) effects of antipsychotic agents. (See Geriatric Patients under Dosage and Administration.)

Geriatric patients with dementia-related psychosis treated with either conventional or atypical antipsychotic agents are at an increased risk of death. (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis in Boxed Warning.)

Hepatic Impairment

Use phenothiazines with caution in patients with hepatic disease. Monitor hepatic function periodically.

Renal Impairment

Use phenothiazines with caution in patients with renal disease. Monitor renal function periodically; if BUN becomes abnormal, discontinue therapy.

Common Adverse Effects

Extrapyramidal reactions (e.g., pseudo-parkinsonism, dystonia, dyskinesia, akathisia, oculogyric crises, opisthotonos, hyperreflexia), drowsiness, lethargy, weight gain.

Drug Interactions

Specific Drugs and Laboratory Tests

Drug or Test




Phenothiazines may lower seizure threshold, but CNS depressant effects do not potentiate anticonvulsant activity of anticonvulsants

Dosage adjustment of anticonvulsant may be necessary to maintain seizure control during concomitant use


Possible potentiated effects of atropine in some patients receiving fluphenazine because of added anticholinergic effects

CNS depressants (e.g., alcohol, analgesics, antihistamines, barbiturates, general anesthetics, opiates)

Possible additive effects or potentiated action of other CNS depressants

Use concomitantly with caution to avoid excessive sedation or CNS depression (see Contraindications)

During surgery in patients receiving high fluphenazine dosages, may need to reduce dosages of anesthetics or other CNS depressants


Reversal of epinephrine action

Do not use epinephrine for phenothiazine-induced hypotension; further lowering of BP may result


An acute encephalopathic syndrome reported occasionally, especially when high serum lithium concentrations present

Observe patients receiving combined therapy for evidence of adverse neurologic effects; promptly discontinue if such signs or symptoms appear

Test for phenylketonuria (PKU)

False-positive test results may occur during phenothiazine use

Tests for pregnancy

False-positive results reported in some patients receiving phenothiazines

Tests for urobilinogen, amylase, uroporphyrins, porphobilinogens, 5-hydroxyindolacetic acid

Urinary metabolites of phenothiazines may cause urine to darken and result in false-positive test results

fluPHENAZine Pharmacokinetics



Rapidly absorbed from GI tract and from parenteral sites. Peak serum concentrations were attained within 1.5–2 or 0.5 hours after IM or oral administration, respectively, of fluphenazine hydrochloride.


Fluphenazine hydrochloride: Usually occurs within 1 hour following oral or IM administration.

Fluphenazine decanoate: Within 24–72 hours.


Fluphenazine hydrochloride: 6–8 hours following oral or IM administration.

Fluphenazine decanoate: Usually 1–6 weeks (average: 2 weeks).



Not fully elucidated; reportedly crosses blood-brain barrier.

Phenothiazines cross the placenta and are distributed into milk.



Metabolic fate not fully elucidated.

Elimination Route

Excreted in feces and urine as unchanged drug, fluphenazine sulfoxide, and 7-hydroxyfluphenazine following IM administration of fluphenazine decanoate in 1 patient studied; also excreted in urine as metabolite conjugates.


Fluphenazine hydrochloride: 14.7–15.3 hours following IM or oral administration.

Fluphenazine decanoate: 6.8–9.6 days following IM administration.





Tightly closed containers at 20–25°C. Protect from light.


Tightly closed containers at 20–25°C, unless otherwise specified by manufacturer; avoid freezing. Protect from light.

Solution, Concentrate

Tightly closed containers at 20–25°C, unless otherwise specified by manufacturer; avoid freezing. Protect from light.



Fluphenazine decanoate: 20–25°C. Protect from light.

Fluphenazine hydrochloride: 20–25°C ; avoid freezing. Protect from light.



Do not mix oral concentrate solution with beverages containing caffeine (e.g., coffee, cola), tannic acid (e.g., tea), or pectinates (e.g., apple juice), since physical incompatibility may result. (See Oral Administration under Dosage and Administration.)


Drug Compatibility (for Fluphenazine Hydrochloride)
Syringe Compatibilityh


Benztropine mesylate

Diphenhydramine HCl

Hydroxyzine HCl


Advice to Patients


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

fluPHENAZine Decanoate


Dosage Forms


Brand Names




25 mg/mL*

Fluphenazine Decanoate Injection

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

fluPHENAZine Hydrochloride


Dosage Forms


Brand Names




2.5 mg/5 mL*

Fluphenazine Hydrochloride Elixir

Solution, concentrate

5 mg/mL*

Fluphenazine Hydrochloride Concentrate


1 mg*

Fluphenazine Hydrochloride Tablets

2.5 mg*

Fluphenazine Hydrochloride Tablets

5 mg*

Fluphenazine Hydrochloride Tablets

10 mg*

Fluphenazine Hydrochloride Tablets


Injection, for IM use only

2.5 mg/mL*

Fluphenazine Hydrochloride Injection

AHFS DI Essentials™. © Copyright 2024, Selected Revisions November 15, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

Reload page with references included