Is Pembrolizumab Dialyzable?
No, pembrolizumab is not dialyzable and does not require dose adjustment in patients with end-stage renal disease on hemodialysis.
Pharmacokinetic Properties That Prevent Dialyzability
Pembrolizumab is a large monoclonal antibody (IgG4) with pharmacokinetic characteristics that make it unsuitable for removal by dialysis 1:
- Molecular weight: As a humanized IgG4 monoclonal antibody, pembrolizumab has a molecular weight of approximately 149 kDa, which far exceeds the cutoff for dialysis membranes (typically <50 kDa) 1
- Volume of distribution: The geometric mean volume of distribution at steady state is 6.0 L, indicating limited distribution outside the vascular compartment 1
- Elimination pathway: Pembrolizumab clearance is approximately 195 mL/day at steady state with a terminal half-life of 22 days, and elimination occurs through protein catabolism rather than renal excretion 1
Clinical Evidence in Dialysis Patients
Multiple case reports demonstrate successful use of pembrolizumab in patients on hemodialysis without dose modification:
- A patient with metastatic melanoma was successfully treated with pembrolizumab while on hemodialysis, representing the first reported case of this combination 2
- A patient with metastatic squamous NSCLC demonstrated a 45-month partial response to pembrolizumab monotherapy during hemodialysis without immune-related adverse events, the longest reported remission in this population 3
- A patient with ESRD and advanced NSCLC with high PD-L1 expression was successfully treated with pembrolizumab 200 mg every 3 weeks, with maintained antitumor effect for 5 months after hemodialysis initiation 4
Dosing Recommendations for Dialysis Patients
Standard dosing should be used without adjustment 1, 2, 3:
- Administer pembrolizumab 200 mg IV every 3 weeks or 400 mg IV every 6 weeks
- No dose reduction or timing adjustment relative to dialysis sessions is necessary
- Population pharmacokinetic analysis showed renal impairment (eGFR ≥15 mL/min/1.73 m²) had no clinically important effect on pembrolizumab clearance 1
Renal Toxicity Monitoring Considerations
While pembrolizumab is not nephrotoxic through direct renal excretion, immune-related nephrotoxicity can occur 5, 6:
- Incidence: Renal toxicities occur in 1.77% of pembrolizumab-treated patients 6
- Histopathologic patterns: Acute interstitial nephritis (AIN), acute tubular injury (ATI), and minimal change disease are the most common forms 6
- Monitoring: Check serum creatinine before each infusion, as early identification of increases may help prevent severe kidney damage 5
- Management: Pembrolizumab withdrawal coupled with corticosteroid therapy is most effective for kidney function recovery in cases of AIN 6
Critical Clinical Pitfall
Do not assume that dialysis will remove pembrolizumab or that timing of administration relative to dialysis sessions matters—the drug's large molecular size and protein-based elimination pathway make it completely non-dialyzable 1, 2.