INVEGA HAFYERA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for INVEGA HAFYERA (INVEGA HAFYERA).
Paliperidone palmitate is an atypical antipsychotic that antagonizes D2 and 5-HT2A receptors, with additional antagonism at alpha2, alpha1, and H1 receptors.
| Metabolism | Paliperidone is metabolized via O-dealkylation, aliphatic hydroxylation, and dehydroxylation; it is a substrate of CYP2D6 and CYP3A4. |
| Excretion | Primarily renal: 59% of paliperidone excreted unchanged in urine; 32% as metabolites; 6-12% fecal. Biliary excretion is minimal. |
| Half-life | Terminal elimination half-life is 25-49 days (mean ~36 days) due to slow dissolution from intramuscular depot. Steady-state reached after 4-5 monthly injections. |
| Protein binding | 74% bound to albumin and α1-acid glycoprotein. |
| Volume of Distribution | Vd approximately 3900 L (55 L/kg for a 70 kg person), indicating extensive tissue distribution. |
| Bioavailability | IM: 100% bioavailability with a controlled release profile. Oral: Not applicable (IM only). |
| Onset of Action | IM: Initial release begins within 1-2 days, achieving therapeutic plasma levels by day 3. Maximal clinical effect observed by 2-3 weeks. |
| Duration of Action | IM: Single injection provides therapeutic coverage for 6 months. After last injection, therapeutic levels persist for 6-12 months due to long half-life. |
INVEGA HAFYERA (paliperidone palmitate) is dosed once weekly via intramuscular injection in the gluteal or deltoid muscle. The recommended starting dose is 1,092 mg (deltoid or gluteal) or 1,560 mg (gluteal only) on treatment day 1 and day 8, both given in the deltoid muscle. Subsequent maintenance doses are administered once monthly. Note: INVEGA HAFYERA is only for once-weekly administration; once-monthly formulations (INVEGA SUSTENNA) are also available.
| Dosage form | SUSPENSION, EXTENDED RELEASE |
| Renal impairment | INVEGA HAFYERA is not recommended in patients with moderate to severe renal impairment (eGFR < 50 mL/min/1.73 m²). For mild impairment (eGFR 50-79 mL/min/1.73 m²), use lower doses: initiate with 819 mg (deltoid) and 1,092 mg (deltoid) on days 1 and 8, then monthly maintenance dose of 546 mg. For eGFR ≥ 80 mL/min/1.73 m², no adjustment needed. |
| Liver impairment | No dosage adjustment is necessary for mild to moderate hepatic impairment (Child-Pugh class A or B). INVEGA HAFYERA has not been studied in severe hepatic impairment (Child-Pugh class C) and should be used with caution. |
| Pediatric use | INVEGA HAFYERA is not approved for use in pediatric patients (<18 years of age). Safety and efficacy have not been established. |
| Geriatric use |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for INVEGA HAFYERA (INVEGA HAFYERA).
| Breastfeeding | Paliperidone is excreted in human breast milk. The milk-to-plasma ratio (M/P) is not specifically reported for paliperidone; for risperidone, the M/P ratio is approximately 0.5. Limited data suggest low infant exposure (relative infant dose <10% of maternal weight-adjusted dose). However, monitor infant for drowsiness, irritability, and abnormal movements. Use caution and consider benefits of breastfeeding versus potential risk. |
| Teratogenic Risk | Paliperidone (the active metabolite of risperidone) is classified as FDA Pregnancy Category C. First trimester exposure: limited human data, but animal studies show increased fetal mortality and skeletal abnormalities at doses less than human therapeutic doses. Second and third trimester exposure: risk of extrapyramidal symptoms and withdrawal symptoms in neonates, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder. Use only if potential benefit justifies potential risk. |
■ FDA Black Box Warning
Increased mortality in elderly patients with dementia-related psychosis.
| Serious Effects |
["Hypersensitivity to paliperidone, risperidone, or any component","Concurrent administration with strong CYP2D6 inhibitors (relative)"]
| Precautions | ["Cerebrovascular adverse events in elderly with dementia","Neuroleptic malignant syndrome (NMS)","Tardive dyskinesia","QT prolongation","Hyperglycemia and diabetes","Weight gain","Orthostatic hypotension","Seizures","Priapism","Leukopenia/neutropenia"] |
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| Elderly patients (≥65 years) generally require lower doses due to reduced renal function and increased sensitivity. Initiate with 819 mg (deltoid) and 1,092 mg (deltoid) on days 1 and 8, then monthly maintenance dose of 546 mg. Monitor for orthostatic hypotension and extrapyramidal symptoms. Consider dose adjustment based on renal function. |
| Fetal Monitoring | Monitor maternal: body weight, blood pressure (orthostatic hypotension), glucose and lipid profiles, prolactin levels, and signs of extrapyramidal symptoms. Fetal/neonatal: monitor for extrapyramidal symptoms and withdrawal symptoms (e.g., agitation, hypertonia, hypotonia, tremor, respiratory distress) after birth. Consider therapeutic drug monitoring of paliperidone levels if available. |
| Fertility Effects | Paliperidone may cause hyperprolactinemia, which can suppress gonadotropin-releasing hormone, leading to menstrual irregularities, anovulation, and reduced fertility in females. In males, hyperprolactinemia may cause decreased libido, erectile dysfunction, and impaired spermatogenesis. Effects are reversible upon dose reduction or discontinuation. |