OPDIVO
Clinical safety rating
cautionComprehensive clinical and safety monograph for OPDIVO (OPDIVO).
Comprehensive clinical and safety monograph for OPDIVO (OPDIVO).
Unresectable or metastatic melanomaMetastatic non-small cell lung cancer (NSCLC) as first-line treatment in combination with ipilimumab for PD-L1 ≥1%, or as monotherapy for PD-L1 ≥1% after prior chemotherapyAdvanced renal cell carcinoma (RCC) as first-line treatment in combination with ipilimumab, or as monotherapy after prior anti-angiogenic therapyClassical Hodgkin lymphoma (cHL) after failure of autologous HSCT and brentuximab vedotinRecurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) after prior platinum-based therapyUrothelial carcinoma after platinum-based chemotherapy or in cisplatin-ineligible patients with high PD-L1 expressionMicrosatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer after prior fluoropyrimidine, oxaliplatin, and irinotecanHepatocellular carcinoma (HCC) after prior sorafenibAdjuvant treatment of melanoma with lymph node involvement after complete resectionUnresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma after prior fluoropyrimidine- and platinum-based chemotherapyGastric cancer or gastroesophageal junction adenocarcinoma after prior chemotherapyMalignant pleural mesothelioma in combination with ipilimumab as first-line treatment
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. |
| Molecular Weight | 146620 Da |
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 | Based on its mechanism of action as an immune checkpoint inhibitor, nivolumab may disrupt fetal immune tolerance, potentially increasing the risk of fetal loss or developmental abnormalities. Human data are lacking; however, animal studies suggest adverse effects at maternal exposures below the clinical dose. |
| 2nd trimester | Nivolumab may cross the placenta and could cause fetal harm due to its immunomodulatory effects. Use only if maternal benefit outweighs potential fetal risk. |
| 3rd trimester | Nivolumab may lead to fetal harm, including immune-mediated disorders. Late gestation exposure might increase the risk of neonatal immune dysfunction. |
Clinical note
Comprehensive clinical and safety monograph for OPDIVO (OPDIVO).
| Placental transfer | Monoclonal antibodies such as nivolumab are known to cross the placenta, especially in the second and third trimesters. The degree of transfer is expected to increase with gestational age due to active FcRn-mediated transport. |
| Breastfeeding | It is unknown whether nivolumab is excreted in human milk. Because many monoclonal antibodies are excreted in breast milk and due to potential for serious adverse reactions in nursing infants, women should be advised not to breastfeed during treatment and for at least 5 half-lives after the last dose. |
| Lactation Rating | L4 (Possibly Hazardous) |
| 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. |
| 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. |
■ 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 |
| Food/Dietary | No known food interactions. No dietary restrictions required with OPDIVO use. |
| Clinical Pearls | Monitor for immune-related adverse events (irAEs) including pneumonitis, colitis, hepatitis, endocrinopathies, and dermatitis. Administer as an IV infusion over 30 minutes. Do not co-administer with other systemic immunosuppressants unless treating irAEs. Infusion reactions are rare but manage with interruption or slowing. Pembrolizumab (Keytruda) and nivolumab are PD-1 inhibitors; consider PD-L1 expression for some indications. |
| Patient Advice | Report any new or worsening symptoms like cough, chest pain, shortness of breath, diarrhea, abdominal pain, jaundice, severe fatigue, skin rash, or changes in urine color immediately. · OPDIVO can cause inflammation of the lungs (pneumonitis), colon (colitis), liver (hepatitis), or hormone glands (thyroid, pituitary, adrenal) which may require corticosteroid treatment. · Avoid pregnancy while on OPDIVO and for at least 5 months after the last dose. Use effective contraception. · Do not receive live vaccines during treatment and for a period after treatment as directed by your doctor. · Store OPDIVO in the refrigerator at 2°C to 8°C (36°F to 46°F) and protect from light. Do not freeze or shake. |
Loading safety data…