Risperone
Risperidone

Presentation: Tab 1 mg (white, film coated, half-scored, oblong) 10tabs x 6 strips, 2mg (orange, film coated, half-scored, oblong) 10tabs x 6 strips

Action: Risperidone is a novel antipsychotic belonging to a new class of antipsychotic, the benzisoxazole class.

Pharmacodynamic: Risperidone is a selective monoaminergic antagonist with high affinity for serotoninergic 5-HT₂ and dopaminergic D₂ receptors. Risperidone binds also to alpha, adrenergic receptors, with lower affinity to H₁, histaminergic and alpha₂ adrenergic receptors. Risperidone has no affinity for cholinergic receptors.

Pharmacokinetics: Risperidone is completely absorbed after oral administration, reaching peak plasma concentration within 1 to 2 hours. The absorption is not affected by food. Risperidone is metabolised by cytochrome P-450 IID6 to 9-hydroxy-risperidone which has similar pharmacological properties as risperidone. Elimination half-life of' risperidone is about 3 hours while that of 9-hydroxy-risperidone and the anlipsychotic fraction is 24 hours. Steady state of risperidone is usually I day and of 9-hydroxy-risperidone is 4-5 days. A slower elimination is expected in renal insufficiency patients and in the elderly.

Indications: Risperidone is indicated for the treatment of schizophrenia including first episode psychoses, acute schizophrenia exacerbations, chronic schizophrenia and other psychotic conditions in which positive symptoms and/or negative symptoms are present. Risperidone also alleviates affective symptoms like depression, anxiety and guilt feelings associated with schizophrenia.

Dosage and administration: Schizophrenia: adults should start with 2mg/day in 2 divided doses and titrated accordingly to between 4-6mg per day. Some patients may benefit from a lower optimal dose. For sonic patients such as first episode patients, a slower titration phase and a lower starting and maintenance dose may be appropriate. Doses above 10mg/day generally have not been shown to provide additional efficacy and may increase risk of extrapyramidal symptoms. Use of Risperone in children below 15 years is not established.

For patients with renal and liver disease or elderly: a starting dose of 0.5mg twice a day is recommended with of 0.5mg bd increments to 1-2mg bd per day.

Contraindications: Patients with a known hypersensitivity to risperidone or any other ingredients in the product.

Warning and Precautions: Risperone is not recommended for the treatment of behavioural symptoms of dementia due to an increased risk of cerebrovaseular events. Treatment of acute psychoses in patients with a history of dementia should be limited to short term only. Caution to be taken when treating patients with known cardiovascular disease or associated risk factors. Orthostalic hypotension may occur in the initial dose titration phase.

All antipsychotic drugs should be discontinued if signs and symptoms of tardive dyskinesia (rhythmical involuntary movement, predominantly of face and tongue) or neuroleptic malignant syndrome (hyperthermia, muscle rigidity, autonomic instability, altered consciousness and elevated CPK levels) occur.

Risperone should be used with caution in patients with known cardiovascular disease, renal and liver disease, Parkinson's disease and epilepsy. It is recommended to halve both the starting and subsequent dose increments in geriatric patients and patients with renal or Beer insufficiency. Hyperglycaemia or exacerbation of pre-existing diabetes has been reported very rarely. Patients are advised not to drive or operate machineries if Risperone interfere with their mental alertness.

Gradual withdrawal of antipsychotics are advised to minimise the recurrence of psychotic symptoms and the emergence of involuntary movement disorders.

Interactions: Caution if used in combination with other centrally acting drugs including alcohol. Hepatic enzyme inducers like carbamazepine may reduce the plasma level of risperidone. Phenotiazines, tricyclic antidepressants and some beta-blockers may increase the plasma concentration of risperidone. Fluoxetine and paroxetine, CYP2D6 inhibitors may increase the plasma concentration of risperidone but less of the active antipsychotic fraction. The same interaction may occur with haloperidol.

Amitriptyline does not affect the pharmacokinetics of risperidone. Cimetidine and ranitidine increase the bioavailability of risperidone but marginally of the antipsychotic fraction. Erythromycin, a CYP 3A4 inhibitor, does not change the pharmacokinetics of risperidone and the active antipsychotic fraction.

When taken with other highly bound drugs, there is no clinically relevant displacement of either drug. Risperone does not show a clinically relevant effect on the pharmacokinetics of valproate. In patients on long term lithium and older/typical neuroleptic therapy, there is no significant change in the pharmacokinetics of lithium after substitution of the concomitant neuroleptic with risperidone. Food does not affect the absorption of risperidone.

Use in pregnancy and lactation: The safety of risperidone for use in human pregnancy has not been established. In animal studies, although no teratogenic effects were noted, some prolactin and CNS-mediated effects such as delayed oestrus and changes in mating and nursing behaviour were observed in rats. Risperidone and 9-hydroxyrisperidone are excreted in human breast milk. Therefore, women receiving Risperone should not breast feed.

Adverse events: Generally, risperidone is well tolerated and in many instances it has been difficult to differentiate adverse events from symptoms of the underlying disease. Common side effects are insomnia, agitation, anxiety and headache. Less common: somnolence, fatigue, dizziness, impaired concentration, constipation, dyspepsia, nausea/vomiting, abdominal pain, blurred vision, priapsim, erectile dysfunction, ejaculatory dysfunction, orgasmic dysfunction, urinary incontinence, rhinitis, rash and other allergic reactions. In some cases, extrapyramidal symptoms may occur. Occasionally, orthostatic hypotension and cerebrovascular accidents has been observed.

Risperidone can induce a dose-dependent increase in plasma prolactin concentration with possibly galactorrhoea, gynaecomastia, disturbances of the menstrual cycle and amenorrhoea.

Weight gain, oedema, increased hepatic enzyme levels decrease in neutrophil and/or thrombocyte count as well as hyperglycaemia have been observed during treatment. As with classical neuroleptics, rare cases of the following have been reported in schizophreia patients: water intoxication with hyponatraemia, either due to polydipsia or to the syndrome of inappropriate secretion of antidiuretic hormone; tardive dyskinesia, body temperature dysregulation and seizures. Sedation, generally transient and mild has been reported more frequently in children and adolescents.

Symptoms and treatment for overdose: Symptoms include drowsiness, sedation, tachycardia and hypotension, and extrapyramidal symptoms and rare eases of QT prolongation. There is no specific antidote.

Appropriate supportive treatment including gastric larvage and administration of activated charcoal and laxative should be considered. Cardiovascular monitoring should include continuous electrocardiography monitoring.

Storage: Store below 25C in a dry place. Keep out of reach of children.