paliperidone: clinical use

Prescribing considerations

• Confirm the licensed indication, formulation suitability and previous response or tolerability to paliperidone or risperidone before selecting the injection.
• Assess renal function because elimination is predominantly renal and formulation restrictions differ.
• Consider cardiovascular disease, QT risk, hypotension, seizure risk, diabetes, thromboembolism risk, Parkinson’s disease, Lewy body dementia and prolactin-dependent tumours.
• Oral prolonged-release tablets may be unsuitable with severe gastrointestinal narrowing, dysphagia or substantially shortened gastrointestinal transit.
• Document current or previous paliperidone use before cataract surgery.
• The injection is unsuitable when immediate control of severe acute agitation or psychosis is required.

Contraindications and cautions

• Hypersensitivity to paliperidone, risperidone or a formulation excipient.

Monitoring

• Clinical response, adherence and adverse effects
• Weight and features of metabolic disturbance, including hyperglycaemia
• Blood pressure and cardiovascular status; consider ECG assessment where QT or cardiac risk is present
• Extrapyramidal symptoms, tardive dyskinesia and sedation
• Prolactin-related symptoms; assess prolactin where clinically indicated
• Renal function
• White-cell count in patients with relevant previous leucopenia or neutropenia, and promptly if infection symptoms arise
• Injection-site reactions for the injectable formulation

Clinical pharmacology

Paliperidone is risperidone’s principal active metabolite. It antagonises dopamine D2 and serotonin 5-HT2 receptors, with additional alpha-adrenergic and histamine H1 activity. Hepatic CYP metabolism has a limited role, while renal elimination is clinically important. Paliperidone palmitate is a poorly soluble prodrug slowly hydrolysed after intramuscular injection.

Formulation and product differences

• Oral prolonged-release tablets use a non-absorbable controlled-release shell and must be swallowed whole; food substantially affects exposure, so administration should be consistent.
• The injection contains paliperidone palmitate and must be administered intramuscularly by a healthcare professional.
• Injectable paliperidone remains in the body for a prolonged period, so adverse effects and treatment changes may persist longer than with tablets.
• The injection is not recommended in moderate or severe renal impairment; the tablet formulation also requires renal-function-based prescribing and is not recommended in very severe renal impairment.

Modified-release tablet

Route: Oral

Strengths: 3 mg, 6 mg, 9 mg

Injection

Route: Parenteral

Strengths: 75 mg, 100 mg, 150 mg