IMMPHENTIV
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IMMPHENTIV (IMMPHENTIV).
IMMPHENTIV is an anti-PD-1 monoclonal antibody that binds to the PD-1 receptor on T cells, blocking its interaction with PD-L1 and PD-L2 ligands, thereby restoring antitumor T-cell function.
| Metabolism | Metabolism is not a major clearance pathway for monoclonal antibodies. It is primarily eliminated through catabolism into amino acids via general protein degradation pathways. |
| Excretion | Renal (70% as unchanged drug), biliary/fecal (30% as metabolites and unchanged drug). |
| Half-life | Terminal elimination half-life is 12-15 hours in healthy adults; prolonged to 24-30 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 98% bound to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd 2-4 L/kg; large Vd indicates extensive tissue distribution, including penetration into cerebrospinal fluid. |
| Bioavailability | Oral: 40-50% due to first-pass metabolism; IM: 80-90%; IV: 100%; rectal: 70-80%. |
| Onset of Action | Oral: 30-60 minutes; IV: immediate (within 5 minutes) for analgesic effect. |
| Duration of Action | Oral: 4-6 hours; IV: 4-6 hours; sustained-release formulations: 12-24 hours. Duration is dose-dependent and prolonged in hepatic impairment. |
4 mg/kg intravenously every 2 weeks until disease progression or unacceptable toxicity.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment recommended for mild to moderate renal impairment (eGFR ≥30 mL/min). Insufficient data for severe renal impairment (eGFR <30 mL/min) or end-stage renal disease. |
| Liver impairment | No dose adjustment recommended for mild hepatic impairment (Child-Pugh A). Insufficient data for moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. No recommended dose. |
| Geriatric use | No specific dose adjustment required based on age alone. Clinical studies included patients ≥65 years; no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for IMMPHENTIV (IMMPHENTIV).
| Breastfeeding | Unknown if excreted in human breast milk. Because of potential for serious adverse reactions in nursing infants, breastfeeding is not recommended. M/P ratio not determined. |
| Teratogenic Risk | IMMPHENTIV is contraindicated in pregnancy. First trimester: High risk of major congenital malformations, including neural tube defects and craniofacial anomalies. Second and third trimesters: Fetal growth restriction, oligohydramnios, and fetal renal impairment. Premature labor and low birth weight reported. |
| Fetal Monitoring |
■ FDA Black Box Warning
Immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin adverse reactions can occur and may be severe or fatal. Immune-mediated adverse reactions may require discontinuation or permanent cessation of therapy.
| Serious Effects |
None known.
| Precautions | Severe immune-mediated adverse events (pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatitis), infusion-related reactions, complications in patients with multiple myeloma after allogeneic HSCT, embryo-fetal toxicity. |
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| Monitor for fetal growth, amniotic fluid volume, and fetal renal function via ultrasound every 4 weeks. Monitor maternal renal function and electrolytes monthly. Assess for signs of premature labor. |
| Fertility Effects | May impair fertility in females and males. In preclinical studies, caused decreased ovarian reserve and spermatogenesis disruption. Reversibility unknown. |