Flupenthixol is readily absorbed from the gastrointestinal tract and is probably subject to first-pass metabolism in the gut wall. It is also extensively metabolised in the liver and is excreted in the urine and faeces in the form of numerous metabolites; there is evidence of enterohepatic recycling. Owing to the first-pass effect, plasma concentrations following oral administration are much lower than those following estimated equivalent doses of the intramuscular depot preparation. Moreover, there is very wide intersubject variation in plasma concentrations of flupenthixol, but in practice, no simple correlation has been found between plasma concentrations of flupenthixol and its metabolites, and the therapeutic effect. Paths of metabolism of flupenthixol include sulphoxidation, side-chain N-dealkylation, and glucuronic acid conjugation. It is widely distributed in the body, and crosses the blood-brain barrier. Flupenthixol passes the placental barrier and small amounts have been detected in breast milk.
The decanoate ester of flupenthixol is very slowly absorbed from the site of intramuscular injection and is therefore suitable for depot injection. It is gradually released into the blood stream where it is rapidly hydrolysed to flupenthixol.
SCHIZOPHRENIA AND RELATED PSYCHOTIC CONDITIONS: Initially 3-9mg b.i.d., adjusted according to response. Max 18mg/day DEPRESSIONS, PSYCHOSOMATIC DISORDERS 0.5mg b.i.d. Increase upto 3-5mg daily. Elderly: Start at half the adult dose and increase gradually.
Children: not recommended
MAINTENANCE IN SCHIZOPHRENIA AND OTHER PSYCHOSES: 20-40MG DEEP IM as depot injection every 2-4 weeks
Flupenthixol exerts its neuroleptic effect by mixed blockade of dopamine d1 and d2 receptors in the limbic system (antipsychotic effects) and the striatal system (extrpyramidal effects). Increases prolactin secretion (hypothalamic action) and has antiemetic action. Flupenthixol produces calmness and reposiveness. Aggressive behaviour is reduced while hallucinations and delusions disappear. Has antidepressant effect.
The most common interactions encountered with phenothiazines are adverse effects resulting from concomitant administration of drugs with similar pharmacological actions. When given with other drugs that produce orthostatic hypotension dosage adjustments may be necessary. However, it should be noted that phenothiazines have been reported to reduce the antihypertensive action of guanethidine and other adrenergic neurone blockers. As many phenothiazines possess antimuscarinic actions they may potentiate the adverse effects of other drugs with antimuscarinic actions, including tricyclic antidepressants and the antimuscarinic antiparkinsonian drugs that may be given to treat phenothiazine-induced extrapyramidal effects. In theory, antipsychotics with dopamine-blocking activity and dopaminergic drugs such as those used to treat parkinsonism may be mutually antagonistic. Concomitant administration of metoclopramide may increase the risk of antipsychotic-induced extrapyramidal effects.
There is an increased risk of arrhythmias when antipsychotics are used with drugs which prolong the QT interval including certain antiarrhythmics, antihistamines, antimalarials, and cisapride. There is also an increased risk of arrhythmia when tricyclic antidepressants are used with antipsychotics which prolong the QT interval. Because of an increased risk of seizures the US manufacturers recommend discontinuation of chlorpromazine before the use of metrizamide for radiographic procedures. Symptoms of CNS depression may be enhanced by other drugs with CNS-depressant properties including alcohol, general anaesthetics, hypnotics, anxiolytics, and opioids.
Effect & Precaution
Neuroleptic Malignant Syndrome, nausea epigastric distress, dyskinesia and restlessness.
Precaution: Severe hepatic, cardiac and renal disease. With other CNS depressants and ethanol. Epilepsy and has to be tapered off gradually.
Breast Feeding: Contraindicated.
Man: May be given in reduced dose