Side Effects of Prolixin (fluphenazine)

Does Prolixin (fluphenazine) cause side effects?

Prolixin (fluphenazine) is an older, first-generation piperazine phenothiazine antipsychotic medication used to manage schizophrenia

Although the exact mechanism of phenothiazine antipsychotics is unknown, scientists believe that they may work by blocking the action of dopamine in the brain. Dopamine is a neurotransmitter (chemical) that nerves use to communicate with one another. Phenothiazine antipsychotics are used when patients do not respond to other antipsychotics.

Common side effects of Prolixin include extrapyramidal side effects such as

Serious side effects of Prolixin include

Drug interactions of Prolixin include medications such as procainamide, sotalol, amiodarone, and dofetilide that affect heart rate and rhythm because it can cause abnormal heartbeats.

  • Antidepressants such as fluoxetine, sertraline, amitriptyline, and nortriptyline can cause an abnormal heart rate and rhythm; combining them with Prolixin increases the risk of abnormal heartbeats.
  • Prolixin should not be combined with other antipsychotics such as aripiprazole and risperidone because such combinations can cause abnormal muscle contractions, difficulty breathing and swallowing, and neck spasms.
  • Prolixin may increase lithium levels in the body. Patients may experience increased side effects of lithium.
  • Prolixin should be used with caution with medications that depress the central nervous system and cause sedation or drowsiness such as alprazolam, clonazepam, zolpidem, codeine, morphine, and alcohol. Such combinations can cause excessive sedation, drowsiness, weakness, confusion, speech impairment, and in severe cases coma or death. 

Safe and effective use of Prolixin is not established in pregnant females; however, it should be avoided to prevent harm to the unborn. 

Prolixin enters breast milk; therefore, it should be avoided in females who are breastfeeding.

What are the important side effects of Prolixin (fluphenazine)?

Fluphenazine causes extrapyramidal side effects such as:

  • Abnormal muscle contractions
  • Difficulty breathing and swallowing
  • Neck spasms

Other side effects include:

Tardive dyskinesia (movement abnormalities of the face, arms, and legs) can result from fluphenazine treatment.

Neuroleptic malignant syndrome (NMS) which includes symptoms such as

  • fever,
  • muscle rigidity,
  • altered mental status,
  • irregular blood pressure, and
  • irregular heart rate and rhythm.

These side effects can be severe so patients must seek medical help.

Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death, and fluphenazine should not be used for treating patients with dementia related psychosis.

Prolixin (fluphenazine) side effects list for healthcare professionals

Central Nervous System

The side effects most frequently reported with phenothiazine compounds are extrapyramidal symptoms including

Most often these extrapyramidal symptoms are reversible; however, they may be persistent (see below). With any given phenothiazine derivative, the incidence and severity of such reactions depend more on individual patient sensitivity than on other factors, but dosage level and patient age are also determinants.

Extrapyramidal reactions may be alarming, and the patient should be forewarned and reassured. These reactions can usually be controlled by administration of antiparkinsonian drugs such as benztropine mesylate or intravenous caffeine and sodium benzoate injection, and by subsequent reduction in dosage.

Tardive Dyskinesia

  • The syndrome is characterized by involuntary choreoathetoid movements which variously involve
    • the tongue,
    • face,
    • mouth,
    • lips, or jaw (e.g., protrusions of the tongue, puffing of cheeks, puckering of the mouth, chewing movements),
    •  trunk and
    • extremities.
  • The severity of the syndrome and the degree of impairment produced vary widely.
  • The syndrome may become clinically recognizable either during treatment, upon dosage reduction, or upon withdrawal of treatment. Early detection of tardive dyskinesia is important. To increase the likelihood of detecting the syndrome at the earliest possible time, the dosage of neuroleptic drugs should be reduced periodically (if clinically possible) and the patient observed for signs of the disorder. This maneuver is critical, since neuroleptic drugs may mask the signs of the syndrome.

Other CNS Effects

  • Occurrences of neuroleptic malignant syndrome (NMS) have been reported in patients on neuroleptic therapy. Leukocytosis, elevated CPK, liver function abnormalities, and acute renal failure may also occur with NMS.
  • Drowsiness or lethargy, if they occur, may necessitate a reduction in dosage; the induction of a catatonic-like state has been known to occur with dosages of fluphenazine far in excess of the recommended amounts. As with other phenothiazine compounds, reactivation or aggravation of psychotic processes may be encountered.
  • Phenothiazine derivatives have been known to cause, in some patients, restlessness, excitement, or bizarre dreams.

Autonomic Nervous System

Metabolic and Endocrine

  • Weight change, peripheral edema, abnormal lactation, gynecomastia, menstrual irregularities, false results on pregnancy tests, impotency in men and increased libido in women have all been known to occur in some patients on phenothiazine therapy.

Allergic Reactions


  • Routine blood counts are advisable during therapy since blood dyscrasias including the following have been observed with phenothiazine derivatives:
  • Furthermore, if any soreness of the mouth, gums, or throat, or any symptoms of upper respiratory infection occur and confirmatory leukocyte count indicates cellular depression, therapy should be discontinued and other appropriate measures instituted immediately.


  • Liver damage as manifested by cholestatic jaundice may be encountered, particularly during the first months of therapy; treatment should be discontinued if this occurs.
  • An increase in cephalin flocculation, sometimes accompanied by alterations in other liver function tests, has been reported in patients receiving fluphenazine hydrochloride who have had no clinical evidence of liver damage.


  • Sudden, unexpected and unexplained deaths have been reported in hospitalized psychotic patients receiving phenothiazines.
  • Previous brain damage or seizures may be predisposing factors; high doses should be avoided in known seizure patients. Several patients have shown sudden flare-ups of psychotic behavior patterns shortly before death.
  • Autopsy findings have usually revealed
  • Although this is not a general feature of fluphenazine, potentiation of central nervous system depressants (opiates, analgesic, antihistamines, barbiturates, alcohol) may occur.

The following adverse reactions have also occurred with phenothiazine derivatives:

What drugs interact with Prolixin (fluphenazine)?

No information provided.


Prolixin (fluphenazine) is an older, first-generation piperazine phenothiazine antipsychotic medication used to manage schizophrenia. Common side effects of Prolixin include extrapyramidal side effects (such as abnormal muscle contractions, difficulty breathing and swallowing, neck spasms, low blood pressure, constipation, dry mouth, blurred vision, seizures, dizziness, and drowsiness. Safe and effective use of Prolixin is not established in pregnant females; however, it should be avoided to prevent harm to the unborn. Prolixin enters breast milk; therefore, it should be avoided in females who are breastfeeding.

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