pembrolizumab
Brand: Keytruda
ISMP High Alert Prototype Drug
Drug Class: PD-1 checkpoint inhibitor monoclonal antibody
Drug Family: antineoplastic
Subclass: anti-PD-1 IgG4 monoclonal antibody
Organ Systems: hematology-oncologyimmunology
Mechanism of Action
Humanized IgG4 monoclonal antibody that blocks PD-1 on T cells, preventing interaction with PD-L1/PD-L2 on tumor cells; restores T-cell-mediated anti-tumor immune activity by removing inhibitory signaling; effective in tumors with high PD-L1 expression or high tumor mutational burden.
PD-1 (programmed cell death protein 1)
Indications
- advanced/metastatic melanoma
- NSCLC (PD-L1 positive)
- head and neck squamous cell carcinoma
- Hodgkin lymphoma
- urothelial carcinoma
- MSI-high/dMMR solid tumors (tumor-agnostic approval)
- triple-negative breast cancer
- gastric/esophageal cancer
- cervical cancer
- TMB-high solid tumors
Contraindications
- pembrolizumab hypersensitivity
Adverse Effects
Common
- fatigue
- rash
- diarrhea
- musculoskeletal pain
- decreased appetite
Serious
- immune-related adverse events (irAE): pneumonitis, colitis, hepatitis, endocrinopathies (hypothyroidism, hyperthyroidism, adrenal insufficiency, type 1 diabetes), nephritis, myocarditis (rare but potentially fatal)
- infusion reactions
- severe skin reactions (TEN, SJS)
Pharmacokinetics (ADME)
| Absorption | IV infusion only |
| Distribution | limited to vascular and extravascular space |
| Metabolism | proteolytic degradation to amino acids (no CYP involvement) |
| Excretion | proteolytic catabolism |
| Half-life | 22–27 days |
| Onset | days to weeks (therapeutic response) |
| Peak | end of infusion |
| Duration | every 3 or 6 weeks |
| Protein Binding | not applicable (IgG) |
| Vd | low (4–5 L) |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| systemic corticosteroids/immunosuppressants | may reduce pembrolizumab anti-tumor efficacy; use only for irAE management, not before treatment initiation | major |
| live vaccines | immunosuppressive state increases vaccine risk | major |
Nursing Considerations
- Monitor for immune-related adverse events (irAEs) at every visit — these can occur at any time, including months after discontinuation; educate patients to report any new symptoms.
- Administer IV over 30 minutes every 3 weeks or every 6 weeks; no dose modifications are made based on body weight.
- Grade ≥3 irAEs require immediate discontinuation and high-dose systemic corticosteroids (prednisone 1–2 mg/kg/day or equivalent); grade 2 irAEs require treatment hold and possible corticosteroids.
- Monitor TSH before each cycle; thyroid dysfunction is common (hypothyroidism >hyperthyroidism) — may be permanent and require lifelong hormone replacement.
Clinical Pearls
- Pembrolizumab has the most FDA approvals of any single oncology drug in history, including the first tumor-agnostic approval (for MSI-high/dMMR solid tumors regardless of tumor type) — a historic shift in cancer classification from histology to molecular biology.
- Unlike chemotherapy, irAEs from pembrolizumab can present weeks to months after the last dose because the augmented immune response persists; patients and clinicians must maintain vigilance well beyond the treatment period.
Safety Profile
Pregnancy contraindicated
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.
Advanced/metastatic Melanoma Cervical Cancer Gastric/esophageal Cancer Head And Neck Squamous Cell Carcinoma Hodgkin Lymphoma MSI-high/dMMR Solid Tumors (tumor-agnostic Approval) NSCLC (PD-L1 Positive) PD-1 Checkpoint Inhibitor Monoclonal Antibody TMB-high Solid Tumors Triple-negative Breast Cancer Urothelial Carcinoma