Paliperidone

Oral
Schizophrenia
Adult: As paliperidone base extended-release tab: Initially, 6 mg once daily. If necessary, adjust in increments of 3 mg daily at intervals of >5 days. Usual dosage range: 3-12 mg once daily.
Child: 12-17 years As paliperidone base extended-release tab: <51 kg: Initially, 3 mg once daily. Usual dosage range: 3-6 mg daily; ≥51 kg: Initially, 3 mg once daily. Usual dosage range: 3-12 mg daily. If necessary, adjust in increments of 3 mg daily at intervals of ≥5 days. Treatment recommendations may vary among countries or individual products (refer to specific product guidelines).
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
<10	Not recommended.
≥10-<50	As paliperidone base extended-release tab: Initially, 1.5 mg once daily or 3 mg every other day, may be increased to Max 3 mg once daily if necessary.
≥50-<80	As paliperidone base extended-release tab: Initially, 3 mg once daily, may be increased to Max 6 mg once daily according to response and tolerance.

Oral
Schizoaffective disorder
Adult: As monotherapy or an adjunct to mood stabilisers and/or antidepressants: As paliperidone base extended-release tab: Initially, 6 mg once daily. If necessary, adjust in increments of 3 mg daily at intervals of >4 days. Usual dosage range: 3-12 mg once daily.
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
<10	Not recommended.
≥10-<50	As paliperidone base extended-release tab: Initially, 1.5 mg once daily or 3 mg every other day, may be increased to Max 3 mg once daily if necessary.
≥50-<80	As paliperidone base extended-release tab: Initially, 3 mg once daily, may be increased to Max 6 mg once daily according to response and tolerance.

Intramuscular
Schizophrenia
Adult: Dose is expressed in terms of paliperidone palmitate. As monthly inj: 234 mg on day 1 then 156 mg on day 8. Maintenance: 39-234 mg monthly, given 5 weeks after the 1st inj. As 3-monthly inj: Give only after the patient has been adequately treated with monthly inj for ≥4 months. If the last dose of monthly inj is 78 mg, 117 mg, 156 mg, and 234 mg, initiate 3-monthly inj at 273 mg, 410 mg, 546 mg, and 819 mg, respectively. May adjust every 3 months based on tolerability and efficacy. As 6-monthly inj: Give only after the patient has been adequately treated with monthly inj for ≥4 months or 3-monthly inj for at least 1 cycle. If the last dose of monthly inj is 156 mg and 234 mg, initiate 6-monthly inj at 1,092 mg and 1,560 mg, respectively; or if the last dose of 3-monthly inj is 546 mg and 819 mg, initiate 6-monthly inj at 1,092 mg and 1,560 mg, respectively. May adjust every 6 months based on tolerability and efficacy. Refer to detailed product guideline for further information.
Renal impairment: As a 6-monthly inj: Not recommended.

CrCl (ml/min)	Dosage Recommendation
<50	Not recommended.
≥50-<80	As paliperidone palmitate: Monthly inj: 156 mg on day 1 then 117 mg on day 8, then 78 mg monthly. 3-monthly inj: Adjust dose and stabilise patient with monthly inj then transition to 3-monthly inj.

Intramuscular
Schizoaffective disorder
Adult: As monotherapy or an adjunct to mood stabilisers or antidepressants: As paliperidone palmitate (1 mg paliperidone palmitate is equivalent to approx 0.64 mg paliperidone base): As a monthly inj: 234 mg (150 mg as base) on day 1 then 156 mg (100 mg as base) on day 8. Maintenance: 78-234 mg (50-150 mg as base) monthly, given 5 weeks after the 1st inj. Refer to detailed product guidelines for further dosing information including the management of missed dose.
Renal impairment:

CrCl (ml/min)	Dosage Recommendation
<50	Not recommended.
242>50-<80	As paliperidone palmitate: As a monthly inj: 156 mg on day 1 then 117 mg on day 8, followed by monthly inj of 78 mg.

Extended-release tab: May be taken with or without food. Swallow whole with liqd, do not chew/divide/crush.

Hypersensitivity to paliperidone or risperidone. Lactation.

Patient with known CV disease (e.g. heart failure, history of MI or ischaemia), cerebrovascular disease, conditions that may predispose to hypotension (e.g. dehydration, hypovolaemia), diabetes mellitus or risk factors for diabetes (e.g. obesity, family history of diabetes), at risk for aspiration pneumonia, history of seizures or other conditions that may lower the seizure threshold, history of clinically significant low WBC/absolute neutrophil count or drug-induced leucopenia or neutropenia, possible prolactin-dependent tumours, Parkinson's disease. Patient undergoing cataract surgery. Patient who will be experiencing conditions that may cause elevation in core body temperature (e.g. strenuous exercise, exposure to extreme heat). Not indicated for the treatment of dementia-related psychosis. Avoid use in patients with congenital long QT syndrome or history of cardiac arrhythmias. Renal and severe hepatic impairment. Children and elderly. Pregnancy. Patient Counselling This drug may cause somnolence, dizziness, or blurred vision, if affected, do not drive or operate machinery. Monitoring Parameters Monitor mental status; vital signs (as clinically indicated); blood pressure (at baseline, 3 months after treatment initiation, then yearly); weight (at baseline then repeat as clinically indicated); CBC (as clinically indicated); electrolytes, renal and liver function (annually and as clinically indicated); fasting plasma glucose level/HbA_1c (at baseline, 3 months after starting therapy, then yearly); fasting lipid panel (at baseline then 3 months after initiation of therapy). Monitor for signs and symptoms of tardive dyskinesia (every 12 months; every 6 months for high-risk patients), neuroleptic malignant syndrome, autonomic instability (e.g. tachycardia, cardiac dysrhythmia). Perform ocular examination yearly in patients >40 years or every 2 years in younger patients.

Significant: QT prolongation, extrapyramidal symptoms (including tardive dyskinesia), dyslipidaemia, significant weight gain, hyperprolactinaemia, orthostatic hypotension, syncope, leucopenia, neutropenia, agranulocytosis, somnolence, motor and sensory instability, seizures, priapism, oesophageal dysmotility/aspiration, hyperglycaemia, diabetes mellitus (including exacerbation of pre-existing diabetes; ketoacidosis [very rarely], and diabetic coma [rarely]), impaired core body temperature regulation, hypersensitivity reactions (including anaphylactic reactions and angioedema). Cardiac disorders: Tachycardia, bradycardia, atrioventricular block, conduction disorder. Eye disorders: Blurred vision. Gastrointestinal disorders: Abdominal pain or discomfort, nausea, vomiting, constipation, diarrhoea, dyspepsia, toothache, dry mouth. General disorders and administration site conditions: Pyrexia, asthenia, fatigue; inj site reactions (IM). Infections and infestations: Influenza. Investigations: Decreased weight, increased transaminases. Metabolism and nutrition disorders: Decreased or increased appetite. Musculoskeletal and connective tissue disorders: Musculoskeletal pain, back pain, arthralgia. Nervous system disorders: Sedation, dizziness, tremor, headache. Psychiatric disorders: Insomnia, agitation, anxiety, depression, mania. Renal and urinary disorders: UTI. Reproductive system and breast disorders: Amenorrhoea, galactorrhoea. Respiratory, thoracic and mediastinal disorders: Cough, nasal congestion, upper respiratory tract infection, bronchitis, sinusitis, pharyngolaryngeal pain. Skin and subcutaneous tissue disorders: Pruritus, rash. Vascular disorders: Hypertension.
Potentially Fatal: Neuroleptic malignant syndrome (NMS).

Symptoms: Extrapyramidal symptoms, gait unsteadiness, drowsiness, somnolence, tachycardia, hypotension, QT prolongation. Torsades de pointes and ventricular fibrillation may also occur. Management: Supportive and symptomatic treatment. For acute overdose, establish and maintain clear airway and ensure adequate oxygenation and ventilation. Initiate CV monitoring (e.g. ECG) immediately. Consider administration of activated charcoal together with a laxative. Hypotension and circulatory collapse may be treated with IV fluids and/or sympathomimetic agents (do not use epinephrine and dopamine). Administer an anticholinergic agent in cases of severe extrapyramidal symptoms.

Increased risk of QT prolongation with class IA (e.g. quinidine, procainamide) or class III (e.g. amiodarone, sotalol) antiarrhythmics, other antipsychotics (e.g. chlorpromazine, thioridazine), antibiotics (e.g. gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QT interval; avoid concomitant use. May result in additive paliperidone exposure when administered concomitantly with risperidone. Enhanced CNS effects with centrally acting drugs. Concomitant use with psychostimulants (e.g. methylphenidate) may result in extrapyramidal symptoms upon change of either or both treatments. May antagonise the effect of levodopa and other dopamine agonists. Strong CYP3A4/P-glycoprotein (P-gp) inducers (e.g. carbamazepine) may reduce paliperidone concentration. Co-administration of valproate semisodium increases the concentration of oral paliperidone. Additive hypotensive effect may occur when given with drugs that have potential for inducing orthostatic hypotension.

Enhanced CNS effects with alcohol.

Paliperidone is a benzisoxazole derivative atypical antipsychotic, which is the major active metabolite of risperidone. The exact mechanism for its antipsychotic action is unclear but may involve mixed central dopaminergic (D₂ receptor) and serotonergic (5-HT_2A receptor) antagonism. It is also an active antagonist at adrenergic (α₁ and α₂) and histaminergic (H₁) receptors. Synonym: 9-hydroxyrisperidone.
Absorption: Bioavailability: 28% (oral). Time to peak plasma concentrations: Oral: Approx 24 hours; IM: Approx 13 days (monthly inj), 30-33 days (3-monthly inj), 29-32 days (6-monthly inj).
Distribution: Enters breast milk. Volume of distribution: Oral: 487 L; IM: 391 L (monthly inj), 1,960 L (3- and 6-monthly inj). Plasma protein binding: 74%, mainly to α₁-acid glycoprotein and albumin.
Metabolism: Undergoes dealkylation, hydroxylation, dehydrogenation, and benzisoxazole scission.
Excretion: Via urine (approx 80%; approx 59% as unchanged drug, 32% as metabolites); faeces (11%). Elimination half-life: Oral: Approx 23 hours; IM: 25-49 days (monthly inj); 84-95 days (3-monthly inj [deltoid]), 118-139 days (3-monthly inj [gluteal]); 148-159 days (6-monthly inj).

Intramuscular: Store between 15-30°C. Oral: Store between 15-30°C. Protect from moisture.

Antipsychotics

N05AX13 - paliperidone ; Belongs to the class of other antipsychotics.