Antipsychotic Medications Anti-psychotic Drugs fluphenazine, Prolixin, Anatensol

Antipsychotic: fluphenazine, Prolixin, Anatensol

Generic Name: fluphenazine
Brand Name(s): Prolixin, Anatensol
Common Use: Antipsychotic

The effects of fluphenazine decanoate are the same as those of fluphenazine HCl; however, the slow release of the decanoate derivative of fluphenazine from the site of injection results in a prolonged duration of action. Once released in the blood, fluphenazine decanoate is rapidly hydrolyzed by blood esterases with no attenuation of its antipsychotic action. Long-acting parenteral preparations for the management of manifestations of schizophrenia.

Contraindications
In patients with marked cerebral atherosclerosis, suspected or established subcortical brain damage, with or without hypothalamic damage, since a hyperthermic reaction with temperatures above 40°C may occur, sometimes not until 14 to 16 hours after drug administration.

Phenothiazines should not be used in patients receiving large doses of hypnotics, due to the possibility of potentiation. In comatose or severely depressed patients, and in the presence of blood dyscrasias, liver damage, renal insufficiency, pheochromocytoma or in patients with severe cardiovascular disorders. Patients who have shown hypersensitivity to other phenothiazines, including fluphenazine, should not be given fluphenazine decanoate as cross-sensitivity reactions may occur.

Adverse Effects

CNS:
Extrapyramidal Symptoms:
The side effects most frequently reported with phenothiazine compounds are extrapyramidal symptoms including pseudoparkinsonism (tremor, rigidity, etc.), dystonia, dyskinesia, akathisia, oculogyric crises, opisthotonos, and hyperreflexia. Fluphenazine decanoate produces a higher incidence of extrapyramidal reactions than the less potent piperazine derivatives or the straight-chain phenothiazines such as chlorpromazine. Extrapyramidal reactions tend to occur in the first few days after an injection. Caution should be exercised in those who have marked extrapyramidal reactions to oral phenothiazines or similar drugs, particularly elderly females. Extrapyramidal reactions may be alarming, and the patient should be forewarned and reassured. These reactions are often dose related and tend to subside when the dose is reduced or the drug temporarily withdrawn. However, antiparkinsonian medication may be required to control serious reactions. The use of prophylactic antiparkinson medication may be considered, although its therapeutic value has not yet been established.

Tardive Dyskinesia:
The syndrome is characterized by rhythmical involuntary movements of the tongue, face, mouth, or jaw (e.g., protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). These may be accompanied by involuntary movements of the trunk and the extremities. As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or may occur upon dosage reduction or after drug therapy has been discontinued. The risk seems to be greater in elderly patients on high dose therapy, especially females. The symptoms are persistent and in some patients appear to be irreversible.
There is no known effective treatment for tardive dyskinesia; antiparkinsonian agents usually do not alleviate the symptoms of this syndrome.
Neuroleptic drugs should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Reducing the dose to the lowest effective level or discontinuing the drug for as long as possible continues to be the most rational approach. In patients who require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.
Other CNS Effects:
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 high dosages of fluphenazine. As with other phenothiazine compounds, reactivation or aggravation of psychotic processes may be encountered. In some patients, phenothiazine derivatives have been known to cause restlessness, excitement, or bizarre dreams.
Rare occurrences of neuroleptic malignant syndrome (NMS) have been reported in patients on neuroleptic therapy. The syndrome is characterized by hyperthermia, muscular rigidity, autonomic instability (labile blood pressure, tachycardia, diaphoresis), akinesia, and altered consciousness, sometimes progressing to stupor or coma. Leukocytosis, elevated CPK, liver function abnormalities, and acute renal failure may also occur. Neuroleptic therapy should be discontinued immediately and vigorous symptomatic treatment implemented since the syndrome is potentially fatal.

Autonomic Nervous System:
Hypotension, hypertension and fluctuations in blood pressure have been reported with fluphenazine. Patients with pheochromocytoma, cerebral vascular or renal insufficiency, or a severe cardiac reserve deficiency such as mitral insufficiency, appear to be particularly prone to hypotensive reactions with phenothiazine compounds and should therefore be observed closely when the drug is administered. If severe hypotension should occur, supportive measures including the use of i.v. vasopressor drugs should be instituted immediately. Levarterenol bitartrate injection, USP is the most suitable drug for this purpose; epinephrine should not be used since phenothiazine derivatives can reverse its action, resulting in a further lowering of blood pressure.
Autonomic reactions including nausea and loss of appetite, salivation, polyuria, perspiration, dry mouth, headache, and constipation may occur. Autonomic effects can usually be controlled by reducing or temporarily discontinuing dosage.
In some patients, phenothiazine derivatives have caused blurred vision, glaucoma, bladder paralysis, fecal impaction, paralytic ileus, tachycardia, or nasal congestion.

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

Allergic Reactions:
Skin disorders such as itching, erythema, urticaria, seborrhea, photosensitivity, eczema and exfoliative dermatitis have been reported with phenothiazine derivatives. The possibility of anaphylactoid reactions should be borne in mind.

Hematologic:
Leukopenia, agranulocytosis, thrombocytopenic or nonthrombocytopenic purpura, eosinophilia, and pancytopenia have been observed with phenothiazine derivatives. 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.

Hepatic:
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 the enanthate ester of fluphenazine (a closely related compound) who have had no clinical evidence of liver damage.

Others:
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 flare-ups of psychotic behaviour patterns shortly before death. Autopsy findings have usually revealed acute fulminating pneumonia or pneumonitis, aspiration of gastric contents or intramyocardial lesions. Potentiation of CNS depressants (opiates, analgesics, antihistamines, barbiturates, alcohol) may occur.
The following adverse reactions have also occurred with phenothiazine derivatives: systemic lupus erythematosus like syndrome, hypotension severe enough to cause fatal cardiac arrest, altered ECG and EEG tracings, altered CSF proteins, cerebral edema, asthma, disturbances of body temperature (hypo- or hyperthermia), laryngeal edema, and angioneurotic edema. Skin pigmentation, and lenticular and corneal opacities have been seen with long-term use. Injections of fluphenazine decanoate are well tolerated, local tissue reactions occur only rarely.

Overdose

Symptoms Will likely be manifested as extrapyramidal signs, hypotension and sedation. Initial hospitalization may be required in cases of large overdose and close medical supervision should be maintained throughout the duration of drug action.

Treatment should be Supportive and symptomatic

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