Keytruda | Pharmacology Mentor

Generic Name

Pembrolizumab (Keytruda)

Mechanism

Pembrolizumab (Keytruda) is a humanized monoclonal antibody that selectively binds to the programmed death‑1 (PD‑1) receptor on T cells and NK cells.
• Blockade of PD‑1/PD‑L1 interaction restores T‑cell activity against tumor cells, enhancing antitumor immune responses.
• Unlike small‑molecule inhibitors, Keytruda’s binding is reversible yet long‑lasting, allowing durable tumor control.

Pharmacokinetics

Administration: Intravenous infusion (standard 30‑60 min).
Distribution: Large volume of distribution (~90 L).
Metabolism: Proteolytic catabolism, no significant CYP450 involvement.
Half‑life: ~26 days; steady‑state achieved by cycle 4.
Elimination: Primarily through proteolytic pathways; negligible renal excretion of unchanged drug.
Dose‑response: Linear pharmacokinetics up to 200 mg Q3 wk; 10 mg/kg Q2–Q3 wk can be used in clinical settings.

Indications

Melanoma (unresectable metastatic or recurrent after BRAF‑inhibitor therapy).
Non‑small cell lung cancer (NSCLC) (PD‑L1‑positive).
Head and neck squamous cell carcinoma (recurrent/metastatic).
Urothelial carcinoma (prior platinum‑based therapy).
Hodgkin lymphoma (relapsed/refractory).
Esophageal/gastric cancers (PD‑L1‑positive).
Colorectal cancer (MSI‑H/dMMR).
Others (basal cell carcinoma, hepatocellular carcinoma, cervical, ovarian, and others as approved in specific regions).

Contraindications

Hypersensitivity to any component of Keytruda or other PD‑1 inhibitors.
Autoimmune disorders (e.g., severe connective‑tissue disease, uncontrolled IBD).
Active infections (TB, HIV with uncontrolled viral load).
Pregnancy: Potential teratogenicity—avoid pregnancy unless benefits outweigh risks.
Cardiac dysfunction: Contraindicated in uncontrolled congestive heart failure.
Adverse reactions**: Listing to prevent immune‑related adverse events (irAEs) in patients with existing organ autoimmunity.

Dosing

Condition	Dose	Schedule	Notes
Standard regimen	200 mg	IV over 30 min Q3 weeks	For adult patients; weight‑based dosing not required unless <200 mg body‑weight.
Weight‑based regimen	10 mg/kg	IV over 30 min Q2–Q3 weeks	Preferred for patients <54 kg or in clinical trials.
Paediatric patients	10 mg/kg (≤150 kg)	IV over 30 min Q2–Q3 weeks	Supported by phase III trial data.

*Infusions should be administered in a setting prepared to manage potential irAEs (e.g., severe infusion reactions).*

Adverse Effects

Common (≥ 10 %):
• Fatigue
• Diarrhea
• Injection site reactions
• Nausea, pruritus
• Rash

Serious (≥ 1 %):
• Immune‑mediated colitis, hepatitis, pneumonitis, endocrinopathies (hypophysitis, thyroiditis), nephritis
• Severe allergic reactions (anaphylaxis)
• Infusion‑related reactions (fever, chills)

*Incidence varies with indication and concurrent therapies.*

Monitoring

Baseline: CBC, CMP, LFTs, thyroid panel, autoimmune markers (ANA, anti‑dsDNA) if indicated.
Every 3 months (or sooner if symptomatic):
CBC, CMP, LFTs, fasting glucose, HbA1c, thyroid function tests.
Pulmonary function tests if pulmonary comorbidity or symptoms.
Imaging: CT/MRI every 6–8 weeks for first year; thereafter per clinical response.
Special: Pregnancy tests for women of childbearing age; TB screening before initiation.

Clinical Pearls

1. Dosing Flexibility – The 200 mg Q3 weeks schedule offers logistical and cost advantages for many institutions, yet weight‑based dosing preserves PK consistency in smaller patients.

2. IrAE Management – Early corticosteroid therapy (prednisone 0.5–1 mg/kg) for grade 2+ toxicity can prevent progression and allow continuation.

3. Combination Therapy – Concomitant ipilimumab (CTLA‑4) requires heightened vigilance for colitis; consider delaying the second agent until irAEs resolve.

4. Biomarker Guidance – PD‑L1 tumor proportion score (≥ 1 %) predicts response in NSCLC; MSI‑H/dMMR status is essential for colorectal indications.

5. Immunogenicity and Allergic Risk – Pre‑infusion diphenhydramine or methylprednisolone may reduce infusion reactions in patients with prior hypersensitivity to monoclonal antibodies.

6. Patient Education – Empower patients to report new symptoms (dyspnea, abdominal pain, neurologic changes) early; prompt evaluation can mitigate severe organ damage.

7. Pregnancy & Lactation – There is insufficient safety data; discuss contraception and consider deferring therapy.

8. Drug Interactions – No CYP450 interactions; however, concurrent agents that depress immunity (e.g., rituximab) may amplify irAE risk.

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• *This drug card serves as a quick‑reference guide for clinicians and students; always consult the latest FDA label and institutional protocols.*