INVEGA

What it is

INVEGA is paliperidone palmitate, a psychotropic agent belonging to the chemical class of benzisoxazole derivatives. INVEGA SUSTENNA is available as a white to off-white sterile modified release suspension for intramuscular injection. INVEGA SUSTENNA is available in dose strengths of 25 mg, 50 mg, 75 mg, 100 mg and 150 mg paliperidone (as palmitate).

Approved indications

— Acute and maintenance treatment of schizophrenia in adults.

Dosing overview

Recommended initiation of INVEGA SUSTENNA is with a dose of 150 mg on treatment day 1 and 100 mg one week later (day 8), both administered in the deltoid muscle. The recommended monthly maintenance dose is 75 mg; some patients may benefit from lower or higher doses within the recommended range of 25 to 150 mg based on individual patient tolerability and/or efficacy. For patients with mild renal impairment (creatinine clearance ≥ 50 mL/min to < 80 mL/min), recommended initiation of INVEGA SUSTENNA is with a dose of 100 mg on treatment day 1 and 75 mg one week later, both administered in the deltoid muscle. Thereafter, follow with monthly injections of 50 mg in either the deltoid or gluteal muscle, adjusted within the range of 25 to 100 mg based on patient tolerability and/or efficacy.

Key safety warnings

A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with antipsychotic drugs, including paliperidone. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Paliperidone causes a modest increase in the corrected QT (QTc) interval. The use of paliperidone should be avoided in combination with other drugs that are known to prolong QTc including Class 1A (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications, antipsychotic medications (e.g., chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval. A syndrome of potentially irreversible, involuntary, dyskinetic, rhythmical movements, including those of the tongue and/or face, may develop in patients treated with antipsychotic drugs. The risk of developing tardive dyskinesia and the likelihood that it will become irreversible appear to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. Weight gain has been observed with INVEGA SUSTENNA and other atypical antipsychotics. Clinical monitoring of weight is recommended. Paliperidone can induce orthostatic hypotension and syncope in some patients because of its alpha-blocking activity.

Contraindications

Hypersensitivity reactions, including anaphylactic reactions and angioedema, have been observed in patients treated with risperidone and paliperidone. Paliperidone palmitate is converted to paliperidone, which is a metabolite of risperidone and is therefore contraindicated in patients with a known hypersensitivity to either paliperidone or risperidone, or to any of the excipients in the INVEGA SUSTENNA formulation.

PBS listing

INVEGA SUSTENNA is listed on the PBS in strengths of 25 mg, 75 mg, 100 mg, 50 mg and 150 mg (as palmitate) in pre-filled syringes for intramuscular injection. All strengths are listed with streamlined authority restriction. Ex-manufacturer prices are A$76.51 (25 mg), A$199.05 (75 mg), A$244.62 (100 mg), A$153.01 (50 mg) and A$244.62 (150 mg).

Regulatory history

INVEGA SUSTENNA paliperidone (as palmitate) 25 mg, 50 mg, 75 mg and 100 mg modified release suspension for injection pre-filled syringes were first listed on the ARTG on 2010-07-28. The TGA approved INVEGA SUSTENNA on 2010-07-20 for acute and maintenance treatment of schizophrenia in adults. PBAC recommended INVEGA SUSTENNA in November 2016 for schizophrenia in patients adequately stabilised with paliperidone once monthly injection, with streamlined authority required listing.