pembrolizumab (Rx)

Brand and Other Names:Keytruda
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

lyophilized powder for reconstitution

  • 50mg/vial

solution for injection

  • 100mg/4mL (25mg/mL)
more...

Melanoma

Indicated for unresectable or metastatic melanoma

2 mg/kg IV q3wk until disease progression or unacceptable toxicity

Infuse IV over 30 minutes

Non-Small Cell Lung Cancer

Also see Administration

Single-agent

  • Indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [Tumor Proportion Score (TPS) ≥50%)] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations
  • Also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy; patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab
  • 200 mg IV q3wk until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression
  • Select patients for treatment of metastatic NSCLC as a single agent based on the presence of positive PD-L1 expression
  • Information on FDA-approved tests for detection of PD-L1 expression in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics

Combination therapy

  • Indicated in combination with pemetrexed and carboplatin for first-line treatment of patients with metastatic nonsquamous NSCLC irrespective of PD-L1 expression
  • When administering in combination with chemotherapy, administer pembrolizumab before chemotherapy
  • Pembrolizumab 200 mg IV plus pemetrexed 500 mg/m² plus carboplatin (AUC 5 mg/mL/min) IV on Day 1 of each 21-day cycle for 4 cycles, THEN
  • Pembrolizumab 200 mg IV q3wk until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression

Head & Neck Squamous Cell Carcinoma

Indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy

200 mg IV q3wk infused over 30 minutes until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression

Dosing considerations (HNSCC)

  • Indication for HNSCC approved under accelerated approval based on tumor response rate and durability of response
  • Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials

Classical Hodgkin Lymphoma

Indicated for adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL) or who have relapsed after 3 or more prior lines of therapy

200 mg IV q3wk

Continue until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression

Also see Administration

Urothelial Carcinoma

Indicated for locally advanced or metastatic urothelial carcinoma (UC) in patients who are not eligible for cisplatin-containing chemotherapy; also indicated for patients with disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy

200 mg IV q3wk until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression

Microsatellite Instability-High Cancer

Indicated for unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, OR colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan

200 mg IV q3wk until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression

Dosage Modifications

Renal impairment: No dosage adjustment required

Mild hepatic impairment: No dosage adjustment required

Moderate or severe hepatic impairment: Not studied

Withhold for any of the following (may resume when recover to grade 0-1)

  • Grade 2 pneumonitis
  • Grade 2 or 3 colitis
  • Grade 3 or 4 endocrinopathies (eg, hypophysitis, hypo- or hyperthyroidism)
  • Grade 2 nephritis
  • AST or ALT >3 and up to 5 x ULN or total bilirubin >1.5 and up to 3 x ULN
  • Any other severe or grade 3 treatment-related adverse reaction

Permanently discontinue for any of the following

  • Any life-threatening adverse reaction (excluding endocrinopathies controlled with hormone replacement therapy)
  • Grade 3 or 4 pneumonitis or recurrent pneumonitis of grade 2 severity
  • Grade 3 or 4 nephritis
  • AST or ALT >5 x ULN or total bilirubin >3 x ULN
  • For patients with liver metastasis who begin treatment with grade 2 AST or ALT, discontinue if AST or ALT increases by ≥50% relative to baseline and lasts for at least 1 week
  • Grade 3 or 4 infusion-related reactions
  • Inability to reduce corticosteroid dose to ≤10 mg/day of prednisone or equivalent within 12 weeks
  • Persistent grade 2 or 3 adverse reactions that do not recover to grade 0-1 within 12 weeks after last dose of pembrolizumab
  • Any severe or grade 3 treatment-related adverse reaction that recurs

Dosing Considerations

cHL, HNSCC, urothelial carcinoma, and MSI-H

  • Indication is approved under accelerated approval based on tumor response rate and durability of response
  • Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials

Nonsquamous NSCLC

  • Indication in for first-line treatment of patients with metastatic nonsquamous NSCLC in combination with pemetrexed and carboplatin was approved under accelerated approval based on tumor response rate and progression-free survival
  • Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials

Orphan Designations

Gastric cancer, including gastroesophageal junction adenocarcinoma

Primary mediastinal B cell lymphoma

Multiple myeloma

Nasopharyngeal carcinoma

Merkel cell carcinoma

Sponsor

  • Merck, Sharp & Dohme a subsidiary of Merck & Co, Inc; One Merck Drive, Whitehouse Station, NJ 08889

Dosage Forms & Strengths

lyophilized powder for reconstitution

  • 50mg/vial

solution for injection

  • 100mg/4mL (25mg/mL)
more...

Classical Hodgkin Lymphoma

Indicated for adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL) or who have relapsed after 3 or more prior lines of therapy

2 mg/kg IV every 3wk; not to exceed 200 mg/dose

Continue until disease progression or unacceptable toxicity

Also see Administration

Microsatellite Instability-High Cancer

Indicated for unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, OR colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan 2 mg/kg IV q3wk; not to exceed 200 mg/dose

Administer until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression

Also see Administration

Dosing Considerations

Limitation of use: Safety and effectiveness in pediatric patients with MSI-H CNS cancers have not been established

cHL and MSI-H

  • Indication is approved under accelerated approval based on tumor response rate and durability of response
  • Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials
Next:

Adverse Effects

>10%

Fatigue (47%)

Anemia (55%)

Hyperglycemia (40%)

Hyponatremia (35%)

Hypoalbuminemia (34%)

Nausea (30%)

Cough (30%)

Pruritus (30%)

Rash (29%)

Decreased appetite (26%)

Hypertriglyceridemia (25%)

Increased AST (24%)

Constipation (21%)

Diarrhea (20%)

Arthralgia (20%)

Pain in extremity (18%)

Dyspnea (18%)

Peripheral edema (17%)

Vomiting (16%)

Headache (16%)

Myalgia (14%)

Chills (14%)

Insomnia (14%)

Abdominal pain (12%)

Back pain (12%)

Dizziness (11%)

Pyrexia (11%)

Upper respiratory tract infection (11%)

Vitiligo (11%)

1-10%

Sepsis (up to 10%)

Immune-mediated hypothyroidism (8.3%)

Immune-mediated pneumonitis (2.9%)

Immune-mediated hyperthyroidism (1.2%)

Immune-mediated colitis (1%)

<1%

Immune-mediated nephritis (0.7%)

Renal failure (0.5%)

Immune-mediated hepatitis (0.5%)

Immune-mediated hypophysitis (0.5%)

Postmarketing reports

Infusion-related reactions

Exfoliative dermatitis

Bullous pemphigoid

Asthenia

Lymphopenia

Previous
Next:

Warnings

Contraindications

None

Cautions

Clinical trials reported immune-mediated pneumonitis, colitis, hepatitis, nephritis and other immune-mediated adverse reactions (eg, uveitis, arthritis, myositis, pancreatitis, hemolytic anemia, partial seizures arising in a patient with inflammatory foci in brain parenchyma, myasthenic syndrome, optic neuritis, and rhabdomyolysis)

Severe dermatitis including bullous pemphigoid and exfoliative dermatitis reported

Immune-mediated endocrinopathies reported adrenal insufficiency, changes in thyroid function, and type 1 diabetes mellitus including diabetic ketoacidosis (withhold therapy in case of severe hyperglycemia until metabolic control achieved)

Infusion-related reactions, including severe and life-threatening reactions, reported; monitor patients for signs and symptoms of infusion-related reactions including rigors, chills, wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever; permanently discontinue therapy for severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions

Hypophysitis reported; monitor for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency); administer corticosteroids for Grade 2 or greater hypophysitis; withhold therapy for moderate (Grade 2) hypophysitis, withhold or discontinue for severe (Grade 3) hypophysitis, and permanently discontinue for life-threatening (Grade 4) hypophysitis

Thyroid disorders can occur; monitor patients for changes in thyroid function (at the start of treatment, periodically during treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of thyroid disorders

Administer corticosteroids for Grade 3 or greater hyperthyroidism; withhold treatment for severe (Grade 3) hyperthyroidism, and permanently discontinue for life-threatening (Grade 4) hyperthyroidism; isolated hypothyroidism may be managed with replacement therapy without treatment interruption and without corticosteroids

Renal failure reported

Embryofetal toxicity is likely, based on the drug’s mechanism of action; women of reproductive potential should use highly effective contraception during treatment and for 4 months after the last dose

Previous
Next:

Pregnancy & Lactation

Pregnancy Category: D

Animal models link the PD-1/PDL-1 signaling pathway with maintenance of pregnancy through induction of maternal immune tolerance to fetal tissue

If this drug is used during pregnancy, or if the patient becomes pregnant while taking pembrolizumab, apprise the patient of the potential hazard to a fetus

Lactation: Unknown if distributed in human breast milk; not recommended

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

more...
Previous
Next:

Pharmacology

Mechanism of Action

Monoclonal antibody to programmed cell death-1 protein (PD-1); blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2

PD-1 and PD-L1

  • PD-1 and related target PD-ligand 1 (PD-L1) are expressed on the surface of activated T cells under normal conditions; PD-L1/PD-1 interaction inhibits immune activation and reduces T-cell cytotoxic activity when bound
  • This negative feedback loop is essential for maintaining normal immune responses and limits T-cell activity to protect normal cells during chronic inflammation
  • Tumor cells may circumvent T-cell–mediated cytotoxicity by expressing PD-L1 on the tumor itself or on tumor-infiltrating immune cells, resulting in the inhibition of immune-mediated killing of tumor cells

Pharmacokinetics

Steady-state concentration reached by 18 weeks of q3wk dosing

Half-life: 26 days

Clearance: 0.22 L/day

Previous
Next:

Administration

IV Compatibilities

0.9% NaCl

Dextrose 5%

IV Preparation

Reconstitute vial by adding 2.3 mL of sterile water for injection by injecting the water along the walls of the vial and not directly on the lyophilized powder (resulting concentration 25 mg/mL)

Slowly swirl the vial; allow up to 5 minutes for the bubbles to clear

Do NOT shake the vial

Visually inspect reconstituted solution for particulate matter and discoloration prior to administration

Reconstituted solution is a clear to slightly opalescent, colorless to slightly yellow solution; discard reconstituted vial if extraneous particulate matter other than translucent to white proteinaceous particles is observed

IV infusion preparation

  • Dilute the solution for injection or reconstituted lyophilized powder before IV administration
  • Withdraw the required volume from the vial(s) and transfer into IV bag containing 0.9% NaCl or D5W; mix diluted solution by gentle inversion
  • Final concentration of the diluted solution should be between 1 mg/mL to 10 mg/mL
  • Discard any unused portion left in the vial

IV Administration

Administer IV infusion over 30 minutes through an IV line containing a sterile, nonpyrogenic, low-protein binding 0.2-5 micron in-line or add-on filter

Do not coadminister other drugs through the same infusion line

Storage

Unopened vials (lyophilized powder or solution for injection): Refrigerate between 2-8°C (36-46°F)

Does not contain preservatives

Do not freeze

Reconstituted/diluted solution

  • Diluted solution from 100 mg/4 mL (25 mg/mL) vial or from 50 mg vial lyophilized powder
  • Room temperature: No to exceed 6 hr from time of reconstitution; this includes room temperature storage of reconstituted vials and/or dilution, and duration of infusion
  • Refrigerate at 2-8°C (36-46°F): Not to exceed 24 hr from time of reconstitution/dilution
  • If refrigerated, allow the diluted solution to come to room temperature prior to administration
Previous
Next:

Images

Previous
Next:

Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
Additional Offers
Email to Patient

From:

To:

The recipient will receive more details and instructions to access this offer.

By clicking send, you acknowledge that you have permission to email the recipient with this information.

Email Forms to Patient

From:

To:

The recipient will receive more details and instructions to access this offer.

By clicking send, you acknowledge that you have permission to email the recipient with this information.

Previous