Benperidol

The safety of benperidol in pregnancy has not been established, although studies in animals have not demonstrated teratogenic effects. As with other drugs, it is not advisable to administer benperidol in pregnancy.

Neonates exposed to antipsychotics (including benperidol) 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.

Butyrophenones are excreted in breast milk and are not recommended during lactation. If the use of benperidol is considered essential, breast feeding should be discontinued.

Benperidol may interfere with activities requiring mental alertness. Therefore, patients should be advised not to drive or operate machinery until their individual susceptibility is known.

The undesirable effects reported with benperidol during clinical trials and post- marketing surveillance are shown in the table below. They are listed by System-Organ Class (SOC) and in order of frequency, using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Table 1. Frequency of adverse events:

¹ Blood dyscrasias, including granulocytopenia.
² Reported effects have included oedema, skin rashes or hypersensitivity reactions such as exanthema and pruritus.
³ Hormonal effects of antipsychotic neuroleptic drugs include hyperprolactinaemia, which may cause galactorrhoea, gynaecomastia and oligo-or amenorrhoea.
⁴ In common with all neuroleptics, extrapyramidal symptoms may occur, e.g. tremor, muscle rigidity, hypersalivation, bradykinesia, akathisia, acute dystonia, oculogyric crisis and laryngeal dystonia.

Anti-Parkinson agents should only be given as required; they should not be prescribed routinely as a preventive measure.

As with all antipsychotic agents, tardive dyskinesia may appear in some patients on long-term therapy or after drug discontinuation. The syndrome is mainly characterised by rhythmical involuntary movements of the tongue, face, mouth or jaw. The manifestations may be permanent in some patients. Benperidol should be given in the minimal effective dose for the minimum possible time.

The syndrome may be masked when the treatment is reinstituted, when the dosage is increased or when a switch is made to a different antipsychotic drug. Treatment should be discontinued as soon as possible.

The potential seriousness and unpredictability of tardive dyskinesia and the fact that it has occasionally been reported to occur when neuroleptic antipsychotic drugs have been prescribed for relatively short periods in low dosage means that the prescribing of such agents requires especially careful assessment of risks versus benefit. Tardive dyskinesia can be precipitated or aggravated by anti-Parkinson drugs. Tardive dyskinesia may occur after abrupt drug withdrawal.

It has been reported that fine vermicular movements of the tongue may be an early sign of tardive dyskinesia and that the full syndrome may not develop if the medication is stopped at that time. If signs and symptoms of tardive dyskinesia appear, the discontinuation of all neuroleptic drugs should be considered.

As with other neuroleptics, rare cases of neuroleptic malignant syndrome, an idiosyncratic response characterised by hyperthermia, generalised muscle rigidity, autonomic instability, altered consciousness, coma and elevated CPK levels, have been reported. Signs of autonomic dysfunction such as tachycardia, labile arterial pressure and sweating may precede the onset of hyperthermia, acting as early warning signs. Antipsychotic treatment should be withdrawn immediately and appropriate supportive therapy and careful monitoring instituted.

Benperidol, even in low dosage in susceptible (especially non-psychotic) individuals, may cause unpleasant subjective feelings of being mentally dulled or slowed down, dizziness, headache, or paradoxical effects of excitement, agitation or insomnia.

Depression and seizures have been reported rarely. A causal relationship with benperidol has not been unequivocally established.

⁵ Dose-related hypotension can occur, particularly in the elderly who are more susceptible to the sedative and hypotensive effects.

Benign tachycardia has occasionally been reported.

As with other neuroleptics Electrocardiogram QT prolonged, ventricular arrhythmias (including ventricular fibrillation and rarely ventricular tachycardia), Torsades de Pointes and cardiac arrest may occur. In rare cases this may lead to sudden “unexplained” death.

Treatment of undesirable cardiac effects includes withdrawal of the causal agent, and correction of hypoxia, electrolyte abnormalities and acid base disturbances.

⁶ Cases of venous thromboembolism, including cases of pulmonary embolism and cases of deep vein thrombosis have been reported with antipsychotic drugs.
⁷ Transient abnormalities of liver function in the absence of jaundice have been reported.