Pembrolizumab (Keytruda)

PD-1 Inhibitor Immunotherapy Monoclonal Antibody
Written by: Dr. Lisa Rodriguez, PharmD, BCOP | Reviewed by: Dr. Michael Chen, MD | Last updated: January 24, 2026

⚠️ Black Box Warning

Immune-Mediated Adverse Reactions: Pembrolizumab can cause severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and skin reactions. Monitor closely and discontinue or withhold for severe reactions.

Overview

Pembrolizumab (brand name: Keytruda) is a humanized monoclonal antibody that works as an immune checkpoint inhibitor. It belongs to a class of drugs called PD-1 (programmed death-1) inhibitors that help the immune system recognize and attack cancer cells.

Key Facts

  • Generic Name: Pembrolizumab
  • Brand Name: Keytruda
  • Manufacturer: Merck & Co., Inc.
  • FDA First Approval: September 2014
  • Drug Type: Humanized IgG4 monoclonal antibody
  • Route: Intravenous infusion
  • Half-life: Approximately 26 days

Mechanism of Action

How Pembrolizumab Works

Step 1: Cancer cells express PD-L1/PD-L2 ligands

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Step 2: These ligands bind to PD-1 receptors on T cells

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Step 3: This binding "turns off" the T cell response

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Step 4: Pembrolizumab blocks PD-1 receptors

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Step 5: T cells remain active and can attack cancer

By blocking the PD-1 pathway, pembrolizumab prevents cancer cells from evading the immune system, allowing T cells to recognize and destroy tumor cells.

FDA-Approved Indications

Melanoma

FDA Approved
  • Unresectable or metastatic melanoma
  • Adjuvant treatment following resection

Non-Small Cell Lung Cancer

FDA Approved
  • First-line for PD-L1 ≥1%
  • With chemotherapy regardless of PD-L1

Head and Neck Cancer

FDA Approved
  • Recurrent or metastatic HNSCC
  • First-line with chemotherapy

Classical Hodgkin Lymphoma

FDA Approved
  • Relapsed or refractory cHL
  • Adult and pediatric patients

Urothelial Carcinoma

FDA Approved
  • Locally advanced or metastatic
  • BCG-unresponsive NMIBC

MSI-H/dMMR Tumors

FDA Approved
  • Any solid tumor with MSI-H/dMMR
  • Tissue agnostic indication

Triple-Negative Breast Cancer

FDA Approved
  • PD-L1 positive (CPS ≥10)
  • With chemotherapy

Renal Cell Carcinoma

FDA Approved
  • First-line with axitinib
  • Adjuvant monotherapy

Additional Approved Indications: Gastric cancer, esophageal cancer, cervical cancer, hepatocellular carcinoma, Merkel cell carcinoma, endometrial carcinoma, TMB-H tumors, cutaneous squamous cell carcinoma

Dosing & Administration

Standard Dosing Regimens

Indication Dose Frequency Infusion Time
Most adult indications 200 mg Every 3 weeks 30 minutes
Alternative adult dosing 400 mg Every 6 weeks 30 minutes
Pediatric (≥12 years) 2 mg/kg (max 200 mg) Every 3 weeks 30 minutes
Melanoma adjuvant 200 mg Every 3 weeks x 1 year 30 minutes

Administration Guidelines

  • Administer as IV infusion over 30 minutes
  • Use 0.2-5 micron in-line filter
  • Do not co-administer other drugs through same line
  • Store in refrigerator; do not freeze
  • Dilute in NS or D5W to 1-10 mg/mL
  • Use within 6 hours at room temperature or 96 hours refrigerated

Dose Modifications

No dose reductions recommended. Management of adverse reactions may require withholding or discontinuation:

  • Grade 2: Withhold until ≤Grade 1
  • Grade 3: Withhold; may resume if recovers to ≤Grade 1
  • Grade 4: Permanently discontinue (except endocrinopathies)

Side Effects

Common Side Effects (≥20%)

  • Fatigue (26-35%)
  • Musculoskeletal pain (20-25%)
  • Decreased appetite (22%)
  • Pruritus (20%)
  • Diarrhea (20%)
  • Nausea (20%)
  • Rash (20%)
  • Cough (18%)
  • Constipation (15%)

Immune-Related Adverse Events (irAEs)

Serious irAEs Requiring Immediate Attention

  • Pneumonitis (2-5%): Cough, dyspnea, chest pain
  • Colitis (1-3%): Diarrhea, abdominal pain, blood in stool
  • Hepatitis (1-2%): Elevated liver enzymes, jaundice
  • Nephritis (0.3%): Elevated creatinine, decreased urine
  • Endocrinopathies (10%): Thyroid disorders, adrenal insufficiency, diabetes
  • Skin reactions (2%): SJS/TEN, severe rash
  • Myocarditis (<1%): Chest pain, heart failure

Management of irAEs

Severity Management
Grade 1 Continue pembrolizumab, monitor closely
Grade 2 Hold pembrolizumab, corticosteroids if needed
Grade 3-4 Discontinue, high-dose corticosteroids, may need additional immunosuppression

Monitoring Requirements

Before Each Dose

  • Symptoms assessment
  • Liver function (AST, ALT, bilirubin)
  • Renal function (creatinine)
  • Thyroid function (TSH)

Every 3-6 Cycles

  • Complete metabolic panel
  • Free T4 if TSH abnormal
  • Cortisol if indicated
  • Blood glucose

As Clinically Indicated

  • Chest imaging for pneumonitis
  • Colonoscopy for severe colitis
  • Cardiac workup if symptoms
  • Endocrine consultation

Drug Interactions

⚠️ Corticosteroids

Systemic corticosteroids may decrease pembrolizumab efficacy. Avoid at treatment initiation unless for management of irAEs or as premedication for chemotherapy.

Other Considerations

  • Other immunosuppressants: May decrease efficacy
  • Live vaccines: Avoid during treatment
  • No known CYP interactions: Antibody not metabolized by CYP450

Patient Information

Before Starting Treatment

  • Review all medications including OTC and supplements
  • Discuss vaccination status
  • Report any autoimmune conditions
  • Pregnancy/breastfeeding counseling
  • Understand immune side effects

During Treatment

What to Report Immediately

  • New or worsening cough, shortness of breath
  • Severe diarrhea or abdominal pain
  • Yellowing of skin or eyes
  • Unusual fatigue or weakness
  • Chest pain or irregular heartbeat
  • Severe headaches or vision changes
  • Skin rash or blistering

Lifestyle Considerations

  • Carry medical alert card about immunotherapy
  • Inform all healthcare providers about treatment
  • Use effective contraception during and 4 months after
  • Avoid live vaccines
  • Stay hydrated
  • Report any new symptoms promptly

Cost & Access

Financial Considerations

Average wholesale price: Approximately $10,000-12,000 per infusion

Annual cost: $150,000-200,000 (varies by dosing schedule)

Financial Assistance Programs

  • Merck Access Program
  • Patient assistance programs
  • Co-pay assistance for eligible patients
  • Foundation support programs

Insurance Coverage: Generally covered for FDA-approved indications. Prior authorization typically required.

Clinical Pearls

  • irAEs can occur at any time, even after discontinuation
  • Endocrinopathies may be permanent, requiring hormone replacement
  • PD-L1 testing may be required for certain indications
  • Can be combined with chemotherapy or other targeted agents
  • Response may take longer than with chemotherapy (pseudo-progression possible)
  • Some patients achieve durable responses lasting years

Important Safety Information

This is not a complete list of side effects or drug information. Always consult the full prescribing information and discuss with your oncology team. Report side effects to FDA at 1-800-FDA-1088.

References

  1. Keytruda (pembrolizumab) [prescribing information]. Merck & Co., Inc.; 2026.
  2. NCCN Guidelines. Management of Immunotherapy-Related Toxicities. Version 1.2026.
  3. FDA Oncology Drug Approvals. Pembrolizumab indication updates.