Invega - Drug Monograph

Introduction

Invega (paliperidone) is an atypical antipsychotic medication approved by the FDA in 2006. It is the major active metabolite of risperidone and belongs to the benzisoxazole derivatives class. Invega is primarily used in the treatment of schizophrenia and schizoaffective disorder, offering both immediate-release and extended-release formulations that provide steady-state plasma concentrations with once-daily dosing.

Mechanism of Action

Paliperidone exerts its therapeutic effects through antagonism of dopamine D₂ and serotonin 5-HT₂A receptors. The drug demonstrates high affinity for these receptors, with approximately 10 times greater affinity for 5-HT₂A than D₂ receptors. This dual mechanism is thought to contribute to its efficacy in treating both positive and negative symptoms of schizophrenia while potentially reducing extrapyramidal side effects compared to typical antipsychotics. Paliperidone also exhibits antagonism at α₁ and α₂ adrenergic receptors and H₁ histaminergic receptors, which contributes to its side effect profile.

Indications

• Treatment of schizophrenia in adults and adolescents (12-17 years)
• Monotherapy and adjunctive therapy for schizoaffective disorder in adults
• Maintenance treatment of schizophrenia (as extended-release formulation)

Dosage and Administration

• Renal impairment: Dose adjustment required (CrCl 50-80 mL/min: max 6 mg daily; CrCl 10-49 mL/min: max 3 mg daily)
• Hepatic impairment: No dosage adjustment required
• Elderly: Consider renal function; initial dose reduction may be necessary

• Take with or without food
• Swallow tablet whole; do not chew, crush, or divide
• Should be administered in the morning

Pharmacokinetics

Contraindications

• Hypersensitivity to paliperidone, risperidone, or any components
• Known hypersensitivity reactions to other antipsychotics
• Severe renal impairment (CrCl <10 mL/min) due to decreased clearance

Warnings and Precautions

• Cerebrovascular adverse events in elderly patients with dementia
• Neuroleptic malignant syndrome (NMS)
• Tardive dyskinesia
• Metabolic changes (hyperglycemia, dyslipidemia, weight gain)
• Hyperprolactinemia
• Orthostatic hypotension and syncope
• Leukopenia, neutropenia, and agranulocytosis
• Potential for cognitive and motor impairment
• Seizures
• Dysphagia and esophageal dysmotility
• Suicide ideation and behavior
• Priapism

Drug Interactions

• Strong CYP3A4/P-glycoprotein inducers (e.g., carbamazepine, rifampin): May decrease paliperidone concentrations
• Other CNS depressants: Additive sedative effects
• Drugs that prolong QT interval: Additive effects possible
• Antihypertensive agents: Enhanced hypotensive effects
• Levodopa and dopamine agonists: Antagonistic effects

• CYP450 inhibitors: Unlikely to significantly affect paliperidone concentrations due to minimal hepatic metabolism

Adverse Effects

• Extrapyramidal symptoms (14%)
• Headache (12%)
• Somnolence (9%)
• Anxiety (7%)
• Insomnia (6%)
• Tachycardia (5%)

• Neuroleptic malignant syndrome (<0.1%)
• Tardive dyskinesia (0.1%)
• QT prolongation
• Seizures (0.3%)
• Hyperglycemia/diabetes mellitus
• Significant weight gain (≥7% body weight in 9% of patients)

Monitoring Parameters

• Complete medical and psychiatric history
• Physical examination
• BMI, waist circumference
• Blood pressure, heart rate
• Fasting blood glucose, HbA1c
• Lipid profile
• CBC with differential
• Renal function tests
• ECG (if cardiac risk factors present)
• Assessment for movement disorders

• Mental status and symptom improvement
• Weight and BMI (every visit)
• Blood pressure (regularly)
• Fasting glucose (at 3 months, then annually)
• Lipid profile (at 3 months, then annually)
• Signs of extrapyramidal symptoms
• Prolactin levels (if symptomatic)
• Treatment adherence assessment

Patient Education

• Take medication exactly as prescribed at the same time each day
• Do not crush, chew, or break tablets
• Report any new or worsening symptoms immediately
• Be aware of potential sedation; avoid alcohol and CNS depressants
• Rise slowly from sitting/lying position to prevent dizziness
• Report any involuntary movements, muscle stiffness, or fever
• Monitor weight regularly and maintain healthy lifestyle
• Keep all follow-up appointments
• Do not stop medication abruptly without medical supervision
• Use effective contraception; notify provider if pregnant or planning pregnancy
• Be aware of potential impact on driving or operating machinery

References

1. FDA Prescribing Information: Invega (paliperidone) Extended-Release Tablets 2. Kane JM, et al. Efficacy and safety of paliperidone extended-release tablets: results of a 6-week, randomized, placebo-controlled study. Biol Psychiatry. 2007;62(12):1363-1370. 3. Canuso CM, et al. Randomized, double-blind, placebo-controlled study of paliperidone extended-release and quetiapine in adults with schizophrenia. J Clin Psychopharmacol. 2010;30(3):235-244. 4. Berwaerts J, et al. Efficacy and safety of the 3-month formulation of paliperidone palmitate vs placebo for relapse prevention of schizophrenia: a randomized clinical trial. JAMA Psychiatry. 2015;72(8):830-839. 5. Marder SR, et al. Paliperidone for schizophrenia. Expert Opin Pharmacother. 2008;9(4):633-643. 6. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Schizophrenia. 3rd ed. 2020. 7. Lehman AF, et al. The Schizophrenia Patient Outcomes Research Team (PORT): updated treatment recommendations 2009. Schizophr Bull. 2010;36(1):94-103.