Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Libtayo: cemiplimab-rwlc 350 mg/7 mL (7 mL) [contains polysorbate 80]
Pharmacology
Mechanism of Action
Cemiplimab is a recombinant human IgG4 monoclonal antibody that inhibits programmed death-1 (PD-1) activity by binding to PD-1 and blocking the interactions with the ligands PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of immune response, including anti-tumor response. PD-1 ligand upregulation may occur in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Blocking PD-1 activity has resulted in decreased tumor growth.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: 5.3 L
Excretion
Clearance: First dose: 0.32 L/day; steady state: 0.21 L/day
Half-Life Elimination
19 days
Use: Labeled Indications
Cutaneous squamous cell carcinoma, metastatic or locally advanced: Treatment of metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC in patients who are not candidates for curative surgery or curative radiation.
Contraindications
There are no contraindications listed in the manufacturer's labeling.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to cemiplimab or any component of the formulation.
Dosage and Administration
Dosing: Adult
Cutaneous squamous cell carcinoma, metastatic or locally advanced: IV: 350 mg once every 3 weeks, continue until disease progression or unacceptable toxicity.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Adjustment for Toxicity
Withhold or discontinue cemiplimab to manage any of the following adverse reactions (no dosage reduction is recommended) and institute medical management promptly.
Immune-mediated toxicities: Administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) or other appropriate therapy for grade 3 or 4 (and certain grade 2) immune-mediated adverse reactions until improvement to grade 1 or lower, then follow with a corticosteroid taper. If immune-mediated adverse reaction is not controlled with systemic corticosteroids, consider administration of other systemic immunosuppressants. Hormone replacement therapy may be required for endocrinopathies (if clinically indicated).
Endocrinopathies: Grades 2, 3 or 4: Withhold treatment if clinically necessary.
Gastrointestinal toxicity: Colitis:
Grade 2 or 3: Withhold treatment; may resume with complete or partial resolution of toxicity (grade 0 or 1) after corticosteroid taper.
Grade 4: Permanently discontinue cemiplimab.
Ocular disorders: Vogt-Koyanagi-Harada-like syndrome: May require systemic corticosteroids to reduce the risk of permanent vision loss.
Pulmonary toxicity: Pneumonitis:
Grade 2: Withhold treatment; may resume with complete or partial resolution of toxicity (grade 0 or 1) after corticosteroid taper.
Grade 3 or 4: Permanently discontinue cemiplimab.
Other immune-mediated reaction involving a major organ:
Grade 3: Withhold treatment; may resume with complete or partial resolution of toxicity (grade 0 or 1) after corticosteroid taper.
Grade 4: Permanently discontinue cemiplimab.
Recurrent or persistent immune-mediated reactions:
Recurrent grade 3 or 4: Permanently discontinue cemiplimab.
Grade 2 or 3 persistent for ≥12 weeks after the last cemiplimab dose: Permanently discontinue cemiplimab.
Requires ≥10 mg/day prednisone (or equivalent) lasting ≥12 weeks after the last cemiplimab dose: Permanently discontinue cemiplimab.
Infusion-related reactions:
Grade 1 or 2: Interrupt infusion or slow the infusion rate.
Grade 3 or 4: Permanently discontinue cemiplimab.
Reconstitution
Withdraw 7 mL from vial and dilute with NS or D5W to final concentration between 1 to 20 mg/mL. Gently invert to mix; do not shake. Do not use if solution in vial is cloudy, discolored, or contains extraneous particulate matter other than trace amounts of translucent to white particles.
Administration
IV: Infuse over 30 minutes through a 0.2 to 5 micron inline or add-on filter. Allow solution to reach room temperature prior to infusion. Monitor for infusion reactions (may require infusion rate reduction, infusion interruption, or discontinuation depending on the severity).
Storage
Store intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Store in the original carton. Protect from light. Do not shake. Solutions diluted for infusion should be stored at up to 25°C (77°F) for no more than 8 hours (from the time of preparation to the end of the infusion) or at 2°C to 8°C (36°F to 46°F) for no more than 24 hours (from the time of preparation to the end of infusion). Do not freeze. Do not shake. Allow the diluted solution to reach room temperature prior to administration.
Drug Interactions
There are no known significant interactions.
Adverse Reactions
>10%:
Central nervous system: Fatigue (29%)
Dermatologic: Skin rash (25%), dermatologic disorders (≤2%; with drug reinitiation: 22%), pruritus (15%)
Gastrointestinal: Diarrhea (22%), nausea (19%), constipation (12%)
Neuromuscular & skeletal: Musculoskeletal pain (17%)
1% to 10%:
Cardiovascular: Hypertension (grades 3/4: ≥2%)
Dermatologic: Cellulitis (grades 3/4: ≥2%), skin infection (grades 3/4: ≥2%), erythema multiforme (≤2%), pemphigoid (≤2%)
Endocrine & metabolic: Hypothyroidism (6%), hypophosphatemia (grades 3/4: 4%), hyponatremia (grades 3/4: 3%), hyperthyroidism (2%), hypercalcemia (grades 3/4: 1%), hypoalbuminemia (grades 3/4: 1%)
Gastrointestinal: Decreased appetite (10%)
Genitourinary: Urinary tract infection (grades 3/4: ≥2%)
Hematologic & oncologic: Lymphocytopenia (grades 3/4: 7%), anemia (grades 3/4: 2%), increased INR (grades 3/4: 2%)
Hepatic: Increased serum aspartate aminotransferase (grades 3/4: 3%), hepatitis (2%)
Immunologic: Antibody development (1%)
Infection: Sepsis (grades 3/4: ≥2%)
Respiratory: Pneumonia (grades 3/4: ≥2%), pneumonitis (≥2%)
Frequency not defined: Dermatologic: Stevens-Johnson syndrome, toxic epidermal necrolysis
<1%, postmarketing, and/or case reports: Adrenocortical insufficiency, aplastic anemia, arthritis, blindness, colitis, demyelinating disease, diabetes mellitus, duodenitis, encephalitis, gastritis, Guillain-Barre syndrome, hematologic disease (hemophagocytic lymphohistiocytosis), hemolytic anemia, hypophysitis, immune thrombocytopenia, increased serum amylase, increased serum lipase, infusion related reaction, iritis, lymphadenitis (Kikuchi), meningitis, myasthenia, myasthenia gravis, myelitis, myocarditis, myositis, nephritis, neuropathy (autoimmune), ophthalmic inflammation, organ transplant rejection, pancreatitis, paresis (nerve), pericarditis, polymyalgia rheumatica, renal failure syndrome, retinal detachment, rhabdomyolysis, sarcoidosis, systemic inflammatory response syndrome, uveitis, vasculitis, visual impairment, Vogt-Koyanagi-Harada syndrome
Warnings/Precautions
Concerns related to adverse effects:
- Adrenal insufficiency: Adrenal insufficiency has occurred (rarely), including grade 2 or 3 toxicity.
- Adverse events (immune-mediated): PD-1/PD-L1 blockers (including cemiplimab) remove immune response inhibition, thus allowing for the potential for breaking of peripheral tolerance and induction of immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, may occur in any tissue or organ system. While immune-mediated adverse reactions generally manifest during treatment, they may also occur following cemiplimab discontinuation. Early identification and management are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor for signs/symptoms of immune-mediated adverse reactions. Evaluate serum chemistries (including hepatic and thyroid function tests) at baseline and periodically during treatment. Institute medical management promptly and include specialty consultation if appropriate. In general, withhold cemiplimab for grade 3 or 4 and some grade 2 immune-mediated adverse events. Permanently discontinue cemiplimab for grade 4 (and some grade 3) immune-mediated adverse events. Administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) or other appropriate therapy for grade 3 or 4 (and certain grade 2) immune-mediated adverse reactions until improvement to grade 1 or lower, then follow with a corticosteroid taper. If the immune-mediated adverse reaction is not controlled with systemic corticosteroids, consider administration of other systemic immunosuppressants. Hormone replacement therapy may be required for endocrinopathies if clinically indicated.
- Dermatologic toxicity: Immune-mediated dermatologic adverse reactions, including erythema multiforme and pemphigoid, have occurred with cemiplimab, including grade 2 and 3 dermatologic toxicity. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have also been reported with cemiplimab (and with other products in the same class). Systemic corticosteroids were required in all patients with dermatologic reactions, with most requiring prednisone ≥40 mg/day (or equivalent). Dermatologic reactions resolved in one-third of patients, although over one-fifth of patients experienced recurrence of dermatologic toxicity upon re-initiation of cemiplimab.
- Diabetes mellitus: Type 1 diabetes mellitus (which may present with diabetic ketoacidosis) has occurred in a small percentage of patients, including grade 3 and 4 events. Type 1 diabetes mellitus led to permanent cemiplimab discontinuation in a small number of patients.
- GI toxicity: Immune-mediated colitis has been reported in patients treated with cemiplimab (including grade 2 and 3 colitis). Colitis led to permanent discontinuation in a small number of patients. Systemic corticosteroids were required in all patients with colitis, over half of which received prednisone ≥40 mg/day (or equivalent). Colitis resolved in most patients. Pancreatitis (including increased serum amylase and lipase levels), gastritis, and duodenitis have also been reported.
- Hepatitis: Immune-mediated hepatitis has been reported, including grade 3 and higher events (some fatal). Hepatitis led to permanent discontinuation in a small percentage of patients. Systemic corticosteroids were required in all patients with hepatitis; most patients required prednisone ≥40 mg/day (or equivalent). Hepatitis resolved in nearly two-thirds of patients.
- Hypophysitis: Hypophysitis (including grade 3 events) has occurred (rarely). Hypophysitis may result in hypopituitarism.
- Infusion reactions: Infusion-related reactions (grade 3) have occurred (rarely) in patients receiving cemiplimab. Monitor for signs/symptoms of infusion-related reactions. Based on the severity of the infusion reaction, interrupt or slow the rate of infusion or permanently discontinue cemiplimab.
- Nephrotoxicity: Immune-mediated nephritis with renal dysfunction has occurred in a small number of patients receiving cemiplimab, including grade 2 and 3 events. Nephritis led to permanent cemiplimab discontinuation rarely. Systemic corticosteroids were required in all patients with nephritis, including two-thirds of patients requiring prednisone ≥40 mg/day (or equivalent). Nephritis resolved in all patients.
- Ocular disorders: Ocular events, including uveitis, iritis, visual impairment (various grades; may include blindness), and other ocular inflammatory toxicities have been reported; some cases may be associated with retinal detachment. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome; may require systemic corticosteroids to reduce the risk of permanent vision loss.
- Pneumonitis: Immune-mediated pneumonitis has been reported with cemiplimab, including grade 2 and higher events (some fatal). Pneumonitis led to permanent discontinuation in a small percentage of patients. Systemic corticosteroids were required in all patients with pneumonitis, most of which received prednisone ≥40 mg/day (or equivalent). Pneumonitis resolved in over half of patients.
- Thyroid disorders: Hypothyroidism occurred in patients receiving cemiplimab, including grade 2 and 3 hypothyroidism (no patients discontinued hormone replacement therapy). Hyperthyroidism has also occurred, including grade 2 and 3 hyperthyroidism, and resolved in over one-third of patients.
- Other immune-mediated toxicities: Other clinically significant immune-mediated adverse reactions have been reported with cemiplimab or with other medications in the same class (some have been severe or fatal). Events have included meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis, Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy, myocarditis, pericarditis, vasculitides, myositis, rhabdomyolysis (and associated sequelae including renal failure), arthritis, polymyalgia rheumatica, hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia (formerly known as immune thrombocytopenic purpura), and solid organ transplant rejection.
Dosage form specific issues:
- Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Monitoring Parameters
Evaluate serum chemistries, hepatic function tests and thyroid function tests (at baseline and periodically during treatment). Pregnancy test (prior to therapy in females of reproductive potential). Monitor for signs/symptoms of adrenal insufficiency, dermatologic toxicity, diabetes mellitus, diarrhea/colitis, hepatitis, hypophysitis, ocular disorders, pneumonitis, thyroid disorders, and other immune-mediated adverse reactions. Monitor for signs/symptoms of infusion-related reactions.
Pregnancy
Pregnancy Considerations
Cemiplimab is a recombinant human immunoglobulin (IgG4) monoclonal antibody; human IgG4 is known to cross the placenta. Based on the mechanism of action and information from animal reproduction studies, use of cemiplimab during pregnancy may cause fetal harm.
Evaluate pregnancy status prior to therapy. Females of reproductive potential should use effective contraception during therapy and for at least 4 months after the last cemiplimab dose.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience back pain, diarrhea, constipation, lack of appetite, or nausea. Have patient report immediately to prescriber signs of thyroid, pituitary, or adrenal gland problems (mood changes, behavioral changes, weight changes, constipation, deeper voice, dizziness, passing out, cold sensation, severe fatigue, hair loss, persistent headache, or decreased sex drive), signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit), signs of infusion reaction, signs of colitis (black, tarry, or bloody stools; diarrhea; or severe abdominal pain), signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes), signs of kidney problems (unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin), signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), confusion, fatigue, severe loss of strength and energy, sensing things that seem real but are not, trouble with memory, seizures, stiff neck, severe headache, severe dizziness, passing out, vision changes, severe muscle pain, severe joint pain, muscle weakness, chest pain, abnormal heartbeat, sweating a lot, burning or numbness feeling, bruising, bleeding, enlarged glands, vision changes, eye pain, or severe eye irritation (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
