pembrolizumab

pembrolizumab

(pem-broe-li-zoo-mab),

Keytruda

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: monoclonal antibodies
Pregnancy Category: D

Indications

Treatment of unresectable or metastatic melanoma with disease progression despite ipilimumab and a BRAF inhibitor (if positive for the BRAF V600 mutation).

Action

Programmed death (PD) receptor-1–blocking antibody (an IgG4 kappa immunglobulin) that blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2 resuling in inhibition of T-cell proliferation and decreased cytokine production.

Therapeutic effects

Decreased spread of melanoma.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Unknown.
Half-life: 26 days.

Time/action profile (response)

ROUTEONSETPEAKDURATION
IVwithin 3 mounkmay persist for > 8.8 mos

Contraindications/Precautions

Contraindicated in: Obstetric: Pregnancy (may cause fetal harm); Lactation: Discontinue pembrolizumab or discontinue breastfeeding.
Use Cautiously in: Obstetric: Females with reproductive potential; Moderate to severe hepatic impairment; Pediatric: Safe and effective use in children has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • dizziness (most frequent)
  • fatigue (most frequent)
  • headache (most frequent)
  • insomnia (most frequent)

Respiratory

  • immune-mediated pneumonitis (life-threatening)

Gastrointestinal

  • immune-mediated colitis (life-threatening)
  • immune-mediated Hepatitis (life-threatening)
  • ↓ appetite (most frequent)
  • constipation (most frequent)
  • diarrhea (most frequent)
  • nausea (most frequent)

Genitourinary

  • immune-mediated nephritis (life-threatening)

Dermatologic

  • pruritus (most frequent)
  • rash (most frequent)
  • vitiligo

Endocrinologic

  • immune-mediated hypophysitis (life-threatening)
  • immune-mediated hyperthyroidism
  • immune-mediated hypothyroidism

Musculoskeletal

  • arthralgia (most frequent)
  • back pain (most frequent)
  • extremity pain (most frequent)
  • mylagia (most frequent)

Hematologic

  • anemia (most frequent)

Miscellaneous

  • sepsis (life-threatening)
  • other immune mediated adverse reactions

Interactions

Drug-Drug interaction

None noted.

Route/Dosage

Intravenous (Adults) 2 mg/kg every 3 wk.

Availability

Lyophilized powder for injection (requires reconstitution): 50 mg/single use vial

Nursing implications

Nursing assessment

  • Monitor for signs and symptoms of immune-mediated pneumonitis (shortness of breath, chest pain, new or worse cough) periodically during therapy. Evaluate with x-ray. Treat with corticosteroids for ≥Grade 2 pneumonitis. Withhold pembrolizumab and monitor symptoms for moderate (Grade 2) pneumonitis; resume therapy when recovery to Grade 0 to 1. Permanently discontinue for severe (Grade 3) or life-threatening (Grade 4) pneumonitis.
  • Monitor for signs and symptoms of colitis (diarrhea, abdominal pain, mucus or blood in stool, with or without fever). Treat with corticosteroids for ≥Grade 2 colitis. Withhold pembrolizumab and monitor symptoms for moderate (Grade 2) or severe (Grade 3) colitis; resume therapy when recovery to Grade 0 to 1. Permanently discontinue for life-threatening (Grade 4) colitis.
  • Assess for signs and symptoms of immune-mediated hepatitis (yellowing of skin or whites of eyes, unusual darkening of urine, unusual tiredness, pain in right upper stomach) before each dose. Treat with corticosteroids for ≥Grade 2. Withhold or discontinue pembrolizumab depending on severity of liver enzyme elevations. Resume therapy when recovery to Grade 0 to 1.
  • Monitor for clinical signs and symptoms of hypophysitis (persistent or unusual headache, extreme weakness, dizziness or fainting, vision changes) during therapy. Treat with corticosteroids for ≥Grade 2 hypophysitis. Withhold pembrolizumab and monitor symptoms for moderate (Grade 2) hypophysitis; withhold or discontinue for severe (Grade 3), and resume therapy when recovery to Grade 0 to 1. Permanently discontinue for life-threatening (Grade 4) hypophysitis.
  • Lab Test Considerations: Monitor for changes in renal function. Treat with corticosteroids for ≥Grade 2 nephritis. Withhold pembrolizumab and monitor symptoms for moderate (Grade 2) nephritis; resume therapy when recovery to Grade 0 to 1. Permanently discontinue for severe (Grade 3) or life-threatening (Grade 4) nephritis.
    • Monitor for changes in thyroid function at start of and periodically during therapy, and as indicated based on clinical evaluation. Administer corticosteroids for ≥Grade 3 hyperthyroidism, withhold pembrolizumab for severe (Grade 3) hyperthyroidism and resume therapy when recovery to Grade 0 to 1. Permanently discontinue for life-threatening (Grade 4) hyperthyroidism. Manage hypothyroidism with thyroid replacement without interruption of therapy or corticosteroids.

Potential Nursing Diagnoses

Diarrhea (Adverse Reactions)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • Intravenous Administration
  • Intermittent Infusion: Reconstitute by injecting 2.3 mL of Sterile Water for Injection along vial walls; swirl slowly, do not shake. Allow up to 5 min for bubbles to clear. Solution is clear to slightly opalescent, colorless to slightly yellow; do not administer solution if discolored or contains particulate matter other than translucent to white proteinaceous particles. Solution is stable at room temperature for up to 4 hr and 24 hr if refrigerated. Diluent: 0.9% NaCl. Mix using gently inversion. Concentration: 1 mg/mL to 10 mg/mL.
  • Rate: Infuse through a sterile, non-pyrogenic, low-protein binding 0.2 micron to 0.5 micron in-line or add-on filter over 30 min.
  • Y-Site Incompatibility: Do not administer other drugs through same infusion line.

Patient/Family Teaching

  • Explain purpose of pembrolizumab to patient.
  • Advise patient to notify health care professional immediately if signs and symptoms of pneumonitis, colitis, hepatitis, kidney problems (change in amount or color of urine), hormone gland problems (rapid heart beat, weight loss, increased sweating, weight gain, hair loss, feeling cold, constipation, deepening of voice, muscle aches, dizziness or fainting, persistent or unusual headache) occur.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Advise female patient of reproductive potential to use highly effective contraception during and for 4 mo after last dose; may cause fetal harm. Avoid breastfeeding during therapy.
  • Emphasize importance of keeping scheduled appointments for blood work or other laboratory tests.

Evaluation/Desired Outcomes

  • ↓ spread of melanoma.
References in periodicals archive ?
Pembrolizumab is a humanized monoclonal antibody that works by increasing the ability of the body's immune system to help detect and fight tumor cells.
Abstract #505) Oral Presentation: Pembrolizumab in Combination with Lenalidomide and Low-Dose Dexamethasone for Relapsed/Refractory Multiple Myeloma (RRMM): Keynote-023.
Robert C, Schachter J, Long GV, et al Pembrolizumab versus ipilimumab in advanced melanoma.
This mechanism is also suggested as a predictive factor for responsiveness to the new immuno- oncology drugs that act through PD-1 and PD-L1 such as nivolumab, pembrolizumab and pidilizumab.
It's becoming clear that ipilimumab, which thwarts CTLA-4, is not as potent as either of the drugs that target PD-1--nivolumab and pembrolizumab.
The findings were statistically significant and may have treatment implications for the use in recently pregnant women of antibodies against PD-1 cell-surface receptors, a class of biologies that include nivolumab and pembrolizumab, both approved in 2014 for advanced melanoma.
The nine new antineoplastic agents and their indications are belinostat (Beleodaq) for peripheral T-cell lymphoma; blinatumomab (Blincyto) for acute lymphoblastic leukemia; ceritinib (Zykadia) for non-small cell lung cancer; idelalisib (Zydelig) for some types of leukemia and lymphoma; nivolumab (Opdivo) for metastatic melanoma; olaparib (Lynparza) for ovarian cancer; pembrolizumab (Keytruda) for unresectable or metastatic melanoma; ramucirumab (Cyramza) for gastric or gastroesophageal adenocarcinoma and metastatic non-small cell lung cancer; and siltuximab (Sylvant) for multicentric Castleman disease.
The Merck drug pembrolizumab shrank tumors in 66 percent of 29 patients with Hodgkin's, with 21 percent having a complete response.
Pembrolizumab was tested on melanoma - the most dangerous form of skin cancer - because the prospects for patients with advanced forms of this disease are so bleak.
One study will present the design of a phase 1b/2 study to evaluate the efficacy and safety of eribulin in combination with pembrolizumab in patients with metastatic triple-negative breast cancer.
The collaboration has been expanded for evaluating the safety and efficacy of the combination of Lilly's Alimta, or pemetrexed for injection, and Merck's Keytruda, or pembrolizumab, in a pivotal Phase III study in first-line nonsquamous non-small cell lung cancer (NSCLC).