OPDIVO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OPDIVO (OPDIVO).
Nivolumab is a fully human monoclonal antibody that blocks the interaction between programmed death-1 (PD-1) receptor and its ligands PD-L1 and PD-L2, thereby enhancing T-cell responses and restoring anti-tumor immune activity.
| Metabolism | Nivolumab is a monoclonal antibody degraded by general protein catabolism; no specific metabolic pathways or enzymes are involved. It is not metabolized by CYP450 enzymes. |
| Excretion | Nivolumab is eliminated primarily via catabolism. No significant renal or biliary excretion; renal clearance accounts for <1% of total clearance. |
| Half-life | Terminal elimination half-life is approximately 26.7 days (range: 19.5–44.8 days), supporting every-2-week or every-4-week dosing intervals. |
| Protein binding | Approximately 89% bound to plasma proteins (primarily albumin and IgG). |
| Volume of Distribution | Volume of distribution at steady state (Vss) is approximately 6.8 L (about 0.1 L/kg), indicating limited extravascular distribution. |
| Bioavailability | Bioavailability: Not applicable (administered intravenously); 100% systemic availability after IV infusion. |
| Onset of Action | Intravenous: Time to clinical response may vary; median time to objective response is approximately 2.1–2.8 months in clinical trials. |
| Duration of Action | Duration of action is prolonged due to long half-life; sustained receptor occupancy may persist for months after treatment discontinuation. |
OPDIVO (nivolumab) 240 mg IV every 2 weeks or 480 mg IV every 4 weeks for most indications; dose and schedule may vary by indication (e.g., 3 mg/kg IV every 2 weeks for classical Hodgkin lymphoma).
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min); use with caution. |
| Liver impairment | Mild hepatic impairment (Child-Pugh A): no adjustment. Moderate (Child-Pugh B) or severe (Child-Pugh C): not studied; use only if benefit outweighs risk. |
| Pediatric use | Weight-based dosing for patients ≥12 years: 3 mg/kg IV every 2 weeks (up to 240 mg) for Hodgkin lymphoma. Other indications: not established in pediatric patients <18 years. |
| Geriatric use | No specific dose adjustment; pharmacokinetics similar to younger adults. Monitor for immune-related adverse events, which may be more frequent in elderly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OPDIVO (OPDIVO).
| Breastfeeding | Human data are not available. The M/P ratio is unknown. Nivolumab is a large monoclonal antibody (IgG4) and is expected to be present in breast milk at low concentrations. However, due to potential for immunosuppression and adverse effects in the nursing infant, breastfeeding is not recommended during treatment and for at least 5 months after the last dose. |
| Teratogenic Risk | Based on its mechanism of action as a PD-1 inhibitor, nivolumab may disrupt immune tolerance to the fetus, which is a semi-allograft. In animal studies, immune checkpoint inhibition has been associated with increased fetal loss and developmental abnormalities. Human data are limited; however, the drug should be avoided in pregnancy unless the benefit outweighs the risk. First trimester exposure may increase risk of miscarriage. Second and third trimester exposure may increase risk of immune-mediated fetal injury, including neonatal immune-mediated disorders. |
■ FDA Black Box Warning
WARNING: IMMUNE-MEDIATED ADVERSE REACTIONS. Nivolumab can cause severe and fatal immune-mediated adverse reactions, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, skin adverse reactions, and encephalitis. Monitor for symptoms and signs; administer corticosteroids and withhold or discontinue as appropriate.
| Serious Effects |
None known.
| Precautions | ["Immune-mediated pneumonitis","Immune-mediated colitis","Immune-mediated hepatitis","Immune-mediated endocrinopathies (including adrenal insufficiency, hypophysitis, hypothyroidism, hyperthyroidism, and type 1 diabetes mellitus)","Immune-mediated nephritis and renal dysfunction","Immune-mediated skin adverse reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis)","Immune-mediated encephalitis","Infusion-related reactions","Embryo-fetal toxicity","Increased mortality in patients with multiple myeloma when combined with thalidomide analogue and dexamethasone"] |
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| Fetal Monitoring | Monitor for immune-mediated adverse events, including pneumonitis, colitis, hepatitis, nephritis, endocrinopathies, and dermatologic reactions. During pregnancy, monitor fetal growth and well-being via ultrasound. Assess for signs of fetal immune-mediated damage, such as unexplained hydrops or growth restriction. Monitor maternal thyroid function, liver enzymes, and renal function. If used in pregnancy, consider monitoring for neonatal immune-related adverse effects after delivery. |
| Fertility Effects | Nivolumab may impair fertility. Animal studies have shown alterations in male and female reproductive organs, including reduced testicular weight and effects on spermatogenesis. The clinical relevance in humans is uncertain, but reversible or irreversible impairment of fertility may occur. |