Usage
Nivolumab is prescribed for various cancers, including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma, classical Hodgkin lymphoma, head and neck squamous cell carcinoma, urothelial carcinoma, esophageal squamous cell carcinoma, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer, hepatocellular carcinoma, and certain types of gastric, gastroesophageal junction, and esophageal cancers. It is also used in adjuvant settings for melanoma, urothelial carcinoma and esophageal or gastroesophageal junction cancer. Nivolumab’s pharmacological classification is as an antineoplastic immunomodulatory agent, specifically a checkpoint inhibitor. It works by blocking the programmed cell death protein 1 (PD-1) receptor, an immune checkpoint that normally suppresses T-cell activity. By inhibiting PD-1, nivolumab enhances T-cell responses against tumor cells.
Alternate Names
Nivolumab is also known internationally by its brand name, Opdivo®. There are no widely recognized alternate generic names.
How It Works
Pharmacodynamics: Nivolumab binds to the PD-1 receptor on activated T-cells, preventing its interaction with ligands PD-L1 and PD-L2. This blockade releases the “brake” on the immune system, allowing T-cells to recognize and attack cancer cells more effectively.
Pharmacokinetics: Administered intravenously, nivolumab exhibits dose-proportional pharmacokinetics over a range of 0.1 to 10 mg/kg every two weeks. Body weight influences clearance, with higher body weight leading to increased clearance, supporting weight-based dosing in some cases. Age, gender, race, baseline lactate dehydrogenase (LDH), and PD-L1 status appear to have no clinically significant impact on nivolumab clearance. It is predominantly eliminated through metabolic pathways, with minimal renal excretion.
Mode of Action: Nivolumab specifically targets the PD-1 receptor on T-cells, a key immune checkpoint. By binding to PD-1, it inhibits the interaction between PD-1 and its ligands PD-L1 and PD-L2, which are often expressed on tumor cells. This blockade prevents the downregulation of T-cell activity, promoting antitumor immunity.
Elimination Pathways: Nivolumab is primarily cleared through metabolic processes, rather than renal or hepatic excretion. The specific metabolic pathways haven’t been fully elucidated, but it likely involves proteolytic degradation, similar to other IgG antibodies.
Dosage
Standard Dosage
Adults: 240 mg intravenously every 2 weeks OR 480 mg intravenously every 4 weeks. Dosages are based on indication, so variations exist for specific conditions. For instance, in combination with ipilimumab for melanoma, it’s 1 mg/kg every 3 weeks for 4 doses, followed by 240 mg every 2 weeks or 480 mg every 4 weeks.
Children (≥12 years): For melanoma and MSI-H/dMMR colorectal cancer, children weighing less than 40 kg: 3 mg/kg intravenously every 2 weeks or 6 mg/kg every 4 weeks. Those weighing 40 kg or more: 240 mg every 2 weeks OR 480 mg intravenously every 4 weeks.
Special Cases:
- Elderly Patients: No dose adjustment is typically required.
- Patients with Renal Impairment: No dose adjustment is typically required.
- Patients with Hepatic Dysfunction: Limited data is available for severe hepatic impairment but dosage modifications might be considered based on individual patient factors.
- Patients with Comorbid Conditions: Dosage adjustments might be necessary depending on the specific comorbidity and its potential interaction with nivolumab or its impact on patient tolerance.
Clinical Use Cases
Nivolumab’s dosing is primarily determined by the cancer type and treatment setting (e.g., adjuvant, metastatic), rather than specific clinical scenarios like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its use in these scenarios would be determined by the underlying cancer for which it is indicated.
Dosage Adjustments
Dose adjustments are not generally needed for age or renal impairment. For patients with hepatic impairment, there’s limited data for severe cases, warranting caution. The most common dosage adjustments are based on the specific cancer being treated, the patient’s weight (particularly in pediatrics) and combined use with other drugs, such as ipilimumab.
Side Effects
Common Side Effects
Fatigue, rash, pruritus, diarrhea, nausea, musculoskeletal pain, decreased appetite, cough, constipation, and pyrexia.
Rare but Serious Side Effects
Pneumonitis, colitis, hepatitis, nephritis, endocrinopathies (e.g., hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis), encephalitis, myocarditis, Stevens-Johnson syndrome, toxic epidermal necrolysis, Guillain-Barré syndrome, myasthenia gravis, and infusion reactions.
Long-Term Effects
Long-term effects can include chronic inflammatory conditions related to immune-mediated adverse events, such as persistent pneumonitis, colitis, or hypothyroidism.
Adverse Drug Reactions (ADR)
Clinically significant ADRs include any severe immune-related adverse events, such as pneumonitis, colitis, hepatitis, or myocarditis. These require prompt intervention, which may involve corticosteroids and/or other immunosuppressants and nivolumab discontinuation.
Contraindications
Absolute contraindication is hypersensitivity to nivolumab. While not an absolute contraindication, nivolumab should be used with caution in patients with active autoimmune disease due to the potential for exacerbation. Patients with multiple myeloma are advised not to use nivolumab due to observed increased mortality risk.
Drug Interactions
Nivolumab has shown limited clinically significant drug interactions. However, concurrent use of corticosteroids or other immunosuppressants should be avoided or minimized due to potential interference with nivolumab’s efficacy. Always consult a comprehensive drug interaction checker before co-administering any medication with nivolumab.
Pregnancy and Breastfeeding
Nivolumab can cause fetal harm and should not be used during pregnancy unless clearly needed. Women of childbearing potential should use effective contraception during and for 5 months after treatment. Nivolumab is present in human milk at potentially clinically significant levels. Breastfeeding is not recommended during and for at least 5 months following the last dose.
Drug Profile Summary
- Mechanism of Action: PD-1 immune checkpoint inhibitor, enhances T-cell activity against tumor cells.
- Side Effects: Fatigue, rash, pruritus, diarrhea; rarely pneumonitis, colitis, endocrinopathies.
- Contraindications: Hypersensitivity to nivolumab, multiple myeloma, caution in active autoimmune diseases.
- Drug Interactions: Limited clinically significant interactions; caution with corticosteroids, immunosuppressants.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy unless benefits outweigh risks; not recommended while breastfeeding.
- Dosage: Varies depending on cancer type; 240 mg IV every 2 weeks OR 480 mg every 4 weeks are common.
- Monitoring Parameters: Monitor for immune-related adverse events, including pulmonary, gastrointestinal, hepatic, endocrine, and neurological symptoms. Regular blood counts, liver function tests, and thyroid function tests are also important.
Popular Combinations
Nivolumab is often combined with ipilimumab (another checkpoint inhibitor) for certain melanomas. It may also be used in combination with chemotherapy regimens for other cancer types, like NSCLC, and in combination with cabozantinib for RCC. The specific combinations and their dosing regimens depend on the cancer type and treatment setting.
Precautions
- General Precautions: Screen for autoimmune diseases, evaluate organ function, and educate patients about potential immune-related side effects.
- Specific Populations: Avoid in pregnancy unless benefits outweigh risks, discontinue breastfeeding, caution in patients with active autoimmune disease.
- Lifestyle Considerations: No specific lifestyle restrictions are typically associated with nivolumab therapy. However, patients should be cautioned about potential fatigue and other side effects that could impair driving or operating machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Nivolumab?
A: The dosage depends on the indication. Common regimens include 240 mg IV every 2 weeks or 480 mg every 4 weeks for adults. Pediatric and combination therapy dosing differs.
Q2: What are the most common side effects?
A: Fatigue, rash, pruritus, diarrhea, nausea, musculoskeletal pain, decreased appetite, cough, constipation and pyrexia are common side effects.
Q3: What are the serious side effects to watch for?
A: Serious side effects can include immune-related adverse events such as pneumonitis, colitis, hepatitis, nephritis, endocrinopathies, and neurological effects. These necessitate prompt evaluation and management.
Q4: Can Nivolumab be used during pregnancy or breastfeeding?
A: Nivolumab is contraindicated during pregnancy and breastfeeding due to potential fetal harm and its presence in breast milk.
Q5: How is Nivolumab administered?
A: Nivolumab is administered intravenously as an infusion.
Q6: Are there any drug interactions with Nivolumab?
A: While limited, concurrent corticosteroid or other immunosuppressant use requires caution. Always consult a drug interaction checker.
Q7: How does Nivolumab differ from other cancer treatments like chemotherapy?
A: Nivolumab, as an immunotherapy, targets the immune system to fight cancer, whereas chemotherapy directly kills cancer cells, leading to a different side effect profile.
Q9: How long is a typical treatment course with Nivolumab?
A: Treatment duration varies, often continuing until disease progression or unacceptable toxicity occurs. In adjuvant settings, there may be a defined treatment period, such as up to one year.
Q10: What should patients be monitored for during treatment?
A: Monitor for immune-related adverse events, as well as standard parameters like blood counts and organ function.
