Nivolumab | Pharmacology Mentor

Generic Name

Nivolumab

Mechanism

Binds to PD‑1 on T‑cells → prevents interaction with PD‑L1/L2 on tumor or antigen‑presenting cells.
Restores T‑cell effector function → increases cytokine production (IFN‑γ, TNF‑α) and promotes tumor cell killing.
Induces durable immune memory → long‑lasting antitumor activity, explaining late tumor responses and extended survival.

Pharmacokinetics

Parameter	Typical Value	Notes
Absorption	Intravenous only	No oral formulation
Distribution	Volume of distribution ≈ 10–15 L	Similar to other IgG antibodies
Half‑life	12–20 days (median ~12.5 days)	Linear kinetics up to 10 mg/kg
Clearance	0.28 mL/min/kg (≈5 mL/kg/day)	Predominantly catabolism via reticuloendothelial system
Metabolism	Proteolytic degradation to peptides/amino acids	Not renal or hepatic clearance dominant
Special Populations	No dose adjustment for age, weight, race, mild–moderate CKD, or mild liver impairment

> Key point: Because it’s a monoclonal antibody, drug–drug interactions are minimal but monoclonal antibody–related infusion reactions can occur.

Indications

Indication	Approved Status	Typical Patient Population
Metastatic melanoma	Approved (FDA 2014)	Adults with unresectable or metastatic disease
Non‑small cell lung cancer (NSCLC)	Approved (combo or monotherapy)	Stage IV or unresectable, PD‑L1 ≥1%
Renal cell carcinoma (RCC)	Approved (combo with axitinib)	Metastatic clear‑cell RCC
Classic Hodgkin lymphoma (cHL)	Approved (post‑relapse)	Adults, refractory/relapsed disease
Urothelial carcinoma	Approved (combination)	Advanced or metastatic disease
Colorectal cancer with MSI‑H/dMMR	FDA‑approved (2018)	Refractory or metastatic
Head & neck squamous cell carcinoma	FDA‑approved (combo)	Recurrent/metastatic
Pancreatic adenocarcinoma	Investigational	Phase II trials (combination)

> Note: Indications are continuously expanded as clinical trials progress.

Contraindications

Absolute contraindication: Known IgG‑mediated hypersensitivity to nivolumab or any excipient.
Relative contraindication: Patients with autoimmune disorders requiring systemic immunosuppression; consider risk–benefit.
Warnings:
Immune‑related adverse events (irAEs) such as colitis, hepatitis, endocrinopathies, pneumonitis, nephritis, or dermatitis.
Infusion reactions: Immediate monitoring during first infusion.
Neuro‑toxicities: Rare but possible (neurologic irAEs).
Liver dysfunction: Monitor ALT/AST; severe hepatotoxicity may necessitate discontinuation.

> Key tip: Avoid use in patients with untreated brain metastases or serious uncontrolled infections.

Dosing

Adults (≥18 y):
Fixed dose regimen: 240 mg IV every 2 weeks (ECHO‑Rapid) or 240 mg IV on day 1, 15, 29 (standard).
Weight‑based (optional): 3 mg/kg IV every 2 weeks.
Pediatrics (≥12 y, ≥37 kg): 3 mg/kg IV every 2 weeks (dose ≤ 240 mg).
Infusion Protocol:
Pre‑medication: antihistamine (optional) or corticosteroid (if prior reactions).
4–6 h infusion, slower pace on subsequent cycles if tolerated.
Duration: Typically 2–4 years or until disease progression or unacceptable toxicity.

> Tip: Use the fixed 240 mg on day 1, 15, 29 schedule to avoid weight‑based calculations, yet weight‑based dosing may be preferred for patients >70 kg or <45 kg.

Adverse Effects

Category	Incidence (≥Grade 3)**	Representative Toxicities
Cutaneous	5–15%	Pruritus, rash, vitiligo
Gastro‑intestinal	10–12%	Diarrhea, colitis
Hepatic	3–7%	Hepatitis, hepatotoxicity
Endocrine	2–5%	Hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis
Pulmonary	2–4%	Pneumonitis (dyspnea, cough)
Renal	1–3%	Nephritis
Neurologic	0.5–2%	Encephalitis, peripheral neuropathy

> Serious irAEs: Must be recognized promptly; may necessitate high‑dose corticosteroids or immunosuppressants.

Common side effects (any grade): fatigue, pruritus, nausea, rash, arthralgia, dizziness.

> Remember: “Immune‑system onslaught” pattern: fever, rash, GI upset, endocrine abnormalities often appear within first 6–12 weeks.

Monitoring

Baseline labs (pre‑cycle): CBC, CMP, liver enzymes, bilirubin, INR, PT/INR, creatinine, thyroid panel, cortisol/adrenal axis if indicated.
During therapy:
Every cycle: CBC, CMP, LFTs, creatinine, electrolytes.
Every 4–6 weeks: Thyroid function, cortisol (early).
Symptom‑driven: Prompt imaging for suspected pneumonitis or colitis.
Assess for irAEs: Skin exam, neurologic check, abdominal exam.
Imaging: CT/MRI every 8–12 weeks to assess tumor response per RECIST or iRECIST.

> Clinical audit: Document all adverse events, grade, management outcomes, and rechallenge decision.

Clinical Pearls

1. Start with a 240 mg fixed dose to simplify scheduling; weigh only if >70 kg for weight-based.

2. Monitor thyroid early—thyrotoxicosis often presents first; treat with beta‑blocker + levothyroxine titration.

3. Infusion first‑time: Consider a 2‑hour infusion with pre‑medicated antihistamine; second infusion can be 1‑hour if tolerated.

4. IrAE algorithm:
• Low‑grade (1–2): Symptomatic treatment + continue therapy.
• High‑grade (≥3) or life‑threatening: Hold drug, start prednisone ≥1 mg/kg/d. If no improvement in 48 h, add infliximab or tacrolimus.

5. Rechallenge: Only after resolution to grade 1 or less and with prophylactic steroids if prior irAE occurred.

6. Elderly patients: No dose reduction, but increased monitoring of renal/hepatic function due to frailty.

7. Drug‑drug interactions: minimal, but concomitant immunomodulators or biologics increase toxicity risk.

8. Pediatric oncology: Data limited; use weight‑based dosing within clinical trial or compassionate protocols.

9. Vaccinations: Live vaccines contraindicated; advise booster timing relative to nivolumab schedule.

Bottom line: Nivolumab harnesses the immune system to fight cancer, but vigilant monitoring for immune‑mediated toxicities is essential to maximize benefit while minimizing harm.

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• *(All information is current as of 2026‑01‑02. For the most recent guidelines, consult NCCN and FDA updates.)*