Fluphenazine

The safety for the use of this drug during pregnancy has not been established; therefore, the possible hazards should be weighed against the potential benefits when administering this drug to pregnant patients.

Neonates exposed to antipsychotics (including fluphenazine) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully.

Breast feeding is not recommended during treatment with depot fluphenazines, owing to the possibility that fluphenazine is excreted in the breast milk.

The use of fluphenazine may impair the mental and physical abilities required for driving a car or operating heavy machinery.

Side effects

Acute dystonic reactions occur infrequently, as a rule within the first 24-48 hours, although delayed reactions may occur. In susceptible individuals they may occur after only small doses. These may include such dramatic manifestations as oculogyric crises and opisthotonos. They are rapidly relieved by intravenous administration of an anti-parkinsonian agent such as procyclidine.

Parkinsonian-like states may occur particularly between the second and fifth days after each injection, but often decrease with subsequent injection. These reactions may be reduced by using smaller doses more frequently, or by the concomitant use of anti-parkinsonian drugs such as trihexyphenidyl, benzatropine or procyclidine. Anti-parkinsonian drugs should not be prescribed routinely, because of the possible risks of aggravating anti-cholinergic side effects or precipitating toxic confusional states, or of impairing therapeutic efficacy.

With careful monitoring of the dose the number of patients requiring anti-parkinsonian drugs can be minimised.

Tardive Dyskinesia

As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long term therapy or may occur 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.

The syndrome is characterised by rhythmical involuntary movements of the tongue, face, mouth or jaw (eg. protrusion of tongue, puffing of cheeks, puckering of mouth, chewing movements). Sometimes these may be accompanied by involuntary movements of the extremities. There is no known effective treatment for tardive dyskinesia: anti-parkinsonian agents usually do not alleviate the symptoms of this syndrome. It is suggested that all antipsychotic agents be discontinued if these symptoms appear. Should it be necessary to reinstitute treatment, or increase the dosage of the agent, or switch to a different antipsychotic agent, the syndrome may be masked. It has been reported that fine vermicular movements of the tongue may be an early sign of the syndrome and if the medication is stopped at that time, the syndrome may not develop.

Other Undesirable Effects

As with other phenothiazines, drowsiness, lethargy, blurred vision, dryness of the mouth, constipation, urinary hesitancy or incontinence, mild hypotension, impairment of judgement and mental skills, and epileptiform attacks are occasionally seen.

Headache, nasal congestion, vomiting, agitation, excitement and insomnia, and hyponatraemia have also been observed during phenothiazine therapy.

Blood dyscrasias have rarely been reported with phenothiazine derivatives. Blood counts should be performed if the patient develops signs of persistent infection. Transient leucopenia and thrombocytopenia have been reported. Antinuclear antibodies and SLE have been reported very rarely.

Jaundice has rarely been reported. Transient abnormalities of liver function tests may occur in the absence of jaundice.

A transient rise in serum cholesterol has been reported rarely in patients on oral fluphenazine.

Abnormal skin pigmentation and lens opacities have sometimes been seen following long-term administration of high doses of phenothiazines.

Phenothiazines are known to cause photosensitivity reactions but this has not been reported for fluphenazine. Skin rashes, hypersensitivity and anaphylactic reactions have occasionally been reported.

Elderly patients may be more susceptible to the sedative and hypotensive effects.

The effects of phenothiazines on the heart are dose-related. ECG changes with prolongation of the QT interval and T-Wave changes have been reported commonly in patients treated with moderate to high dosage; they have been reported to precede serious arrhythmias, including ventricular tachycardia and fibrillation, which have also occurred after overdosage. Sudden, unexpected and unexplained deaths have been reported in hospitalised psychotic patients receiving phenothiazines.

Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs – Frequency unknown.

Phenothiazines may impair body temperature regulation. Elderly or hypothyroid patients may be particularly susceptible to hypothermia. The hazard of hyperpyrexia may be increased by especially hot or humid weather, or by drugs such as anti-parkinsonian agents, which impair sweating.

Rare occurrences of neuroleptic malignant syndrome (NMS) have been reported in patients on neuroleptic therapy. The syndrome is characterised by hyperthermia, together with some or all of the following: muscular rigidity, autonomic instability (labile blood pressure, tachycardia, diaphoresis), akinesia, and altered consciousness, sometimes progressing to stupor or coma. Leucocytosis, 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.

Hormonal effects of phenothiazines include hyperprolactinaemia, which may cause galactorrhoea, gynaecomastia and oligomenorrhoea or amenorrhoea. Sexual function may be impaired, and false results may be observed with pregnancy tests. Syndrome of inappropriate anti-diuretic hormone secretion has also been observed.

Oedema has been reported with phenothiazine medication.

Pregnancy, puerperium and perinatal conditions; drug withdrawal syndrome neonatal – Frequency not known.