KEYTRUDA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KEYTRUDA (KEYTRUDA).
Pembrolizumab is a humanized monoclonal antibody that binds to the programmed death-1 (PD-1) receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including antitumor immune responses.
| Metabolism | Pembrolizumab is a monoclonal antibody that is degraded into small peptides and amino acids via catabolic pathways. No specific metabolic enzymes are involved. |
| Excretion | Pembrolizumab is not metabolized; elimination occurs primarily via catabolism to small peptides and amino acids. Less than 1% is excreted unchanged in urine. No significant biliary or fecal elimination. |
| Half-life | Terminal elimination half-life is approximately 22 days (range 14–27 days) based on population pharmacokinetics, consistent with its IgG4 monoclonal antibody structure. This long half-life supports the every-3-week or every-6-week dosing interval. |
| Protein binding | Pembrolizumab binds to the programmed death-1 (PD-1) receptor; plasma protein binding data are not specifically reported, but as a monoclonal antibody, it is not bound to albumin or other serum proteins in a clinically significant manner. |
| Volume of Distribution | Volume of distribution at steady state is approximately 6.1 L (range 3.0–9.5 L), which approximates plasma volume. In body weight-based dosing, typical Vd is about 0.09 L/kg. |
| Bioavailability | Pembrolizumab is administered only intravenously; bioavailability is 100% by this route. |
| Onset of Action | Following intravenous administration, the time to clinical effect is variable, often requiring 8–16 weeks (2–4 cycles) to achieve radiographic response in solid tumors. Some responses may occur later. |
| Duration of Action | The duration of action (clinical benefit) depends on tumor type and response; median duration of response ranges from months to years. Treatment is typically continued until disease progression or unacceptable toxicity. |
| Action Class | Programmed Cell Death 1 (PD-1) Checkpoint Inhibitors |
KEYTRUDA (pembrolizumab) 200 mg intravenously every 3 weeks or 400 mg intravenously every 6 weeks. Infuse over 30 minutes.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Severe renal impairment (creatinine clearance <30 mL/min) has not been studied; use with caution. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment has not been studied; use with caution. |
| Pediatric use | For pediatric patients aged 2 years and older: 2 mg/kg (up to a maximum of 200 mg) intravenously every 3 weeks. Safety and efficacy in patients younger than 2 years not established. |
| Geriatric use | No specific dose adjustments based on age. Clinical studies included patients ≥65 years; no overall differences in safety or efficacy observed compared to younger patients. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KEYTRUDA (KEYTRUDA).
| Breastfeeding | No data on human milk secretion. Pembrolizumab is a large protein molecule; excretion into milk is likely low, but systemic absorption in the infant is possible. The M/P ratio is unknown. Due to potential for adverse effects (e.g., immunosuppression), advise against breastfeeding during treatment and for at least 4 months after the last dose. |
| Teratogenic Risk | Pembrolizumab is an IgG4 monoclonal antibody; IgG crosses the placenta during the second and third trimesters. Based on its mechanism of action (PD-1 blockade), there is a potential risk of fetal harm, including immune-mediated disorders and intrauterine growth restriction. Animal studies have not been conducted, but human experience is limited. Avoid use during pregnancy unless the benefit outweighs risks. No data for first trimester specifically. |
■ FDA Black Box Warning
WARNING: IMMUNE-MEDIATED PNEUMONITIS: KEYTRUDA can cause immune-mediated pneumonitis, including fatal cases. Monitor patients for signs and symptoms of pneumonitis. Withhold or permanently discontinue KEYTRUDA depending on severity.
| Serious Effects |
None known.
| Precautions | ["Immune-mediated pneumonitis","Immune-mediated colitis","Immune-mediated hepatitis","Immune-mediated endocrinopathies (hypophysitis, thyroid disorders, type 1 diabetes mellitus)","Immune-mediated nephritis and renal dysfunction","Immune-mediated skin adverse reactions (including Stevens-Johnson syndrome and toxic epidermal necrolysis)","Infusion-related reactions","Complications of allogeneic hematopoietic stem cell transplantation","Embryofetal toxicity"] |
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| Fetal Monitoring | Monitor maternal hepatic function, renal function, and thyroid function tests periodically. Monitor for immune-related adverse events (e.g., pneumonitis, colitis, hepatitis, endocrinopathies). During pregnancy, fetal monitoring by ultrasound for growth and well-being is recommended; consider screening for immune-related complications in the neonate after delivery. |
| Fertility Effects | No dedicated human studies. In animal studies, no adverse effects on male or female fertility were observed at doses up to 200 mg/kg in monkeys. However, due to potential effects on immune function, may theoretically affect fertility. No specific recommendations. |