What is the recommended dosing and treatment plan for Invega Sustenna (paliperidone palmitate) in schizophrenia?

Invega Sustenna (Paliperidone Palmitate) Dosing and Treatment Protocol

Invega Sustenna should be initiated with 234 mg (150 mg eq.) on day 1 and 156 mg (100 mg eq.) on day 8, both administered into the deltoid muscle, followed by monthly maintenance doses of 39-234 mg (recommended 117 mg/75 mg eq.) into either deltoid or gluteal muscle, with no oral supplementation required. 1

Initiation Regimen

Loading Doses

• Day 1: 234 mg (150 mg eq. paliperidone) into deltoid muscle 1
• Day 8 (±2 days acceptable): 156 mg (100 mg eq. paliperidone) into deltoid muscle 1
• No oral antipsychotic supplementation is needed with this initiation regimen, as the biphasic pharmacokinetic profile allows rapid attainment of therapeutic concentrations 2, 1

Injection Technique for Loading Doses

• Patients <90 kg: Use 1-inch, 23-gauge needle 1
• Patients ≥90 kg: Use 1.5-inch, 22-gauge needle 1
• Both loading doses must be administered into the deltoid muscle to ensure proper absorption kinetics 1

Maintenance Dosing

Monthly Administration

• Recommended dose: 117 mg (75 mg eq. paliperidone) monthly 1
• Dose range: 39-234 mg (25-150 mg eq.) based on efficacy and tolerability 3, 1
• Timing flexibility: Monthly doses may be given ±7 days without clinically significant impact on plasma concentrations 1

Injection Site Options for Maintenance

• Deltoid muscle: Weight-adjusted needle size (same as loading doses) 1
• Gluteal muscle: 1.5-inch, 22-gauge needle 1

Treatment Duration and Monitoring

Acute Phase Assessment

• Evaluate therapeutic response after at least 4 weeks at an adequate dose before determining medication efficacy 4
• Clinical response onset: Approximately 8 days after the recommended 150 mg eq. initial deltoid dose 5
• Monitor for positive symptom reduction using standardized scales (e.g., PANSS total scores) 5

Maintenance Treatment

• First-episode patients: Continue antipsychotic treatment for 1-2 years after initial episode stabilization given high relapse risk 4
• Established schizophrenia: Long-term maintenance is generally required, as approximately 65% of patients relapse within 1 year without antipsychotic treatment versus 30% with maintenance therapy 4

Special Populations

Renal Impairment

• Mild impairment (CrCl 50-80 mL/min): Dosage adjustment required 1
• Moderate to severe impairment: Use with caution; specific dosing recommendations needed 1

Hepatic Impairment

• Mild to moderate: No dose adjustment required 1
• Severe: No data available; use with extreme caution 1

Elderly Patients

• Same dosage as younger adults if renal function is normal 1
• Adjust for age-related decline in creatinine clearance if present 1

Female Patients of Childbearing Age

• Effective contraception should be used during treatment 4

Switching Strategies

From Oral Antipsychotics

• Initiate paliperidone palmitate the day after discontinuing oral antipsychotic 1
• Use standard loading dose regimen (234 mg day 1,156 mg day 8) 1

From Other Long-Acting Injectables

• Begin paliperidone palmitate at the time of the next scheduled injection of the previous LAI 1
• Continue monthly thereafter with maintenance dosing 1
• Paliperidone palmitate demonstrated noninferiority to risperidone LAI in controlled trials 5, 3

Managing Missed Doses

Re-initiation Protocol

• Last dose >6 weeks ago: Re-initiation schedule depends on duration since last injection 1
• Assess need for return to loading dose regimen versus resuming maintenance dosing 1

Clinical Context and Treatment Algorithm

Position in Treatment Algorithm

• Second-line consideration: Paliperidone (including palmitate formulation) is recommended as a second-line option after failure of a D2 partial agonist first-line treatment 4
• Long-acting injectable indication: Particularly appropriate for patients with history of poor or uncertain adherence, or those who prefer LAI formulation 4

Treatment Failure Response

• If positive symptoms persist after 4 weeks at therapeutic dose with good adherence, switch to alternative antipsychotic with different pharmacodynamic profile 4
• After failure of two adequate antipsychotic trials (at least 4 weeks each), reassess diagnosis and consider clozapine 4

Safety Monitoring

Common Adverse Effects

• Most frequent: Headache, tremor, dizziness, insomnia, akathisia, somnolence, sedation 6
• Injection site reactions: Expected with LAI formulation; monitor at each administration 5
• Weight gain and prolactin elevation: Generally greater in women than men; monitor regularly 3

Extrapyramidal Symptoms Management

• Acute dystonia: Treat with anticholinergic medication 4
• Parkinsonism: Lower dose, switch antipsychotic, or add anticholinergic 4
• Akathisia: Lower dose, switch antipsychotic, add benzodiazepine, or add beta-blocker 4

Critical Safety Considerations

• Transient excursions above therapeutic levels can cause tachycardia, hypotension, QT prolongation, and extrapyramidal symptoms 2
• Delayed therapeutic attainment or premature decline increases relapse risk 2
• The biphasic pharmacokinetic profile is integral to clinical effects; manufacturing changes can substantially alter release characteristics 2

Psychosocial Integration

Combined Treatment Approach

• Antipsychotic medication must be combined with psychosocial interventions for adequate treatment 4
• Psychoeducation for patient and family regarding illness, treatment options, and relapse prevention 4
• Social skills training, vocational programs, and community support services as indicated 4