Invega Sustenna
Invega Sustenna
Generic Name
Invega Sustenna
Mechanism
- D₂/D₃ receptor antagonist: Inhibits dopamine signaling in mesolimbic pathways, reducing psychotic symptoms.
- Partial agonist at serotonin 5‑HT₂A receptors: Modulates serotonergic tone, contributing to antipsychotic efficacy with lower extrapyramidal risk.
- Additional activity at 5‑HT₁A, D₄, and α₁‑adrenergic receptors: These interactions help mitigate negative symptoms and improve cognitive deficits.
- Slow-release intramuscular depot: Palmitate conjugation prolongs systemic exposure, maintaining therapeutic paliperidone levels for several weeks.
Pharmacokinetics
- Absorption: Linear release from intramuscular depot; peak plasma concentration 0.5–1 weeks after injection.
- Distribution: High plasma protein binding (~99 %); tissue penetration predictable in CNS.
- Metabolism: CYP2D6 and CYP3A4 mediated oxidative metabolism; clearance is dose‑independent over therapeutic range.
- Elimination: Mean terminal half‑life 25–34 days, allowing once‑monthly dosing.
- Food interaction: Minimal; can be administered with or without food.
Indications
- Maintenance treatment of schizophrenia in patients who have responded to oral antipsychotics and require sustained symptom control.
- Indicated in both first‑episode and chronic schizophrenia when long‑acting form enhances adherence.
Contraindications
- Contraindicated in patients with known hypersensitivity to paliperidone or any component of the formulation.
- Warnings:
- Neuroleptic malignant syndrome: advise prompt medical evaluation for hyperthermia and rigidity.
- Hyperprolactinemia: monitor prolactin; consider alternative antipsychotic if symptomatic.
- Elevated prolactin can lead to galactorrhea, amenorrhea, and sexual dysfunction.
- Possible increase in blood glucose, lipids, and weight—screen for metabolic syndrome.
- Elevated risk of sedation and orthostatic hypotension; caution in elderly or polypharmacy patients.
Dosing
| Stage | Dose | Schedule | Notes |
| Initial | 120 mg *paliperidone palmitate* (150 mg paliperidone base) | 1 st injection | Usually combined with 1‑week oral paliperidone 12 mg for smooth transition. |
| Second injection | 75 mg (75 mg IM) | 2–3 weeks after 1st | 1‑week gap reduces peak concentration spikes. |
| Maintenance | 150 mg (150 mg IM) | Monthly | Adjust if breakthrough psychosis; use 200 mg if tolerance and metabolism permit. |
| Breakthrough | 1 week oral paliperidone 12 mg × 1–2 weeks | As needed | Bridging therapy until depot drug reaches therapeutic levels. |
Route: Intramuscular injection, preferably in the gluteal or deltoid muscle.
Adverse Effects
Common (≥10 %)
• Injection‑site reactions (pain, erythema, swelling)
• Somnolence, sedation
• Weight gain (mean 2–4 kg over 6 months)
• Hyperprolactinemia symptoms (galactorrhea, menstrual irregularities)
Serious (<10 %)
• Extrapyramidal symptoms, tardive dyskinesia
• Neuroleptic malignant syndrome
• Metabolic derangements (hyperglycemia, dyslipidemia, hypertension)
• Cardiovascular events (QT prolongation in susceptible patients)
• Hypersensitivity reactions (anaphylaxis)
Monitoring
- Baseline: CBC, CMP, fasting glucose, lipid profile, prolactin, ECG (if QT risk).
- After initiation:
- Weeks 2–4: Recheck CBC, CMP, prolactin, fasting glucose/lipid.
- Monthly: Weight, BMI, blood pressure, prolactin.
- Every 3 months: Full metabolic panel, monitor for injection‑site complications.
- At any sign of neuroleptic malignant syndrome: Immediate assessment and potential drug discontinuation.
Clinical Pearls
- Smooth transition from oral to LAI: Initiate with oral paliperidone for 1 week (12 mg) to reduce first‑dose withdrawal and sedation.
- Dose‑adjustment in renal impairment: No dose change is normally required; however, monitor for accumulation if creatinine clearance *Reference:* Paliperidone palmitate (Invega Sustenna) prescribing information, FDA label, 2024.