What are the common side effects of Invega Sustenna (paliperidone palmitate)?

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Last updated: November 11, 2025View editorial policy

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Common Side Effects of Invega Sustenna (Paliperidone Palmitate)

The most common side effects of Invega Sustenna include extrapyramidal symptoms (EPS), injection site reactions, headache, insomnia, sedation, and prolactin-related effects, with EPS occurring in approximately 34% of patients during acute treatment phases.

Extrapyramidal Symptoms (Most Significant)

  • EPS-related adverse events occur in approximately 34% of patients treated with paliperidone ER during acute and continuation treatment phases, which is notably higher than olanzapine (16%) 1
  • Specific EPS manifestations include dyskinesia, akathisia, hypokinesia, tremor, and extrapyramidal disorder, each occurring in approximately 1% of patients during maintenance phases 1
  • Acute dystonia can occur as early as one day after injection and may be severe enough to cause rhabdomyolysis, though this is rare 2
  • Parkinsonism can develop, particularly with loading dose strategies, and may be severe and prolonged 3

Injection Site Reactions

  • Injection site reactions occur at rates ranging from 4% to 10% depending on the dose regimen, compared with 2% for placebo 4
  • These reactions are generally mild and do not typically require discontinuation 4

Common Neuropsychiatric Effects

  • Headache occurs in 11-18% of patients treated with paliperidone ER 5
  • Insomnia affects 4-14% of patients receiving paliperidone ER 5
  • Sedation and somnolence are commonly reported, particularly at higher doses 6
  • Dizziness occurs frequently and may be related to orthostatic effects 6
  • Tremor is a frequently reported adverse event 6

Prolactin-Related Effects

  • Prolactin-related adverse events occur in approximately 4% of patients during long-term treatment 5
  • These effects are dose-dependent and more common at higher dosage strengths 4

Gastrointestinal Effects

  • Nausea is commonly reported during treatment 6
  • Dyspepsia occurs in a subset of patients 6

Other Common Effects

  • Akathisia (restlessness) is reported as a common adverse event 6
  • Hypertonia (increased muscle tone) occurs in some patients 6
  • Agitation and anxiety may develop during treatment 6

Dosing Considerations to Minimize Side Effects

  • EPS and body weight gain may be more common at higher doses (156 mg and 234 mg), suggesting clinicians should use the lowest effective dose 4
  • Deltoid injection produces approximately 28% higher maximum plasma concentrations compared with gluteal injection, which may influence side effect profiles 4
  • Lower doses in elderly or frail patients can reduce the risk of severe EPS complications 3

Critical Safety Monitoring

  • Patients developing EPS should be evaluated for potential rhabdomyolysis, particularly if dystonia is present, as creatine kinase levels can exceed 3000 unit/L 2
  • Therapeutic drug monitoring using serum prolactin levels may be useful when plasma drug levels are unavailable, though this approach has limitations 3

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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