Version May 2024
Basal cell carcinoma, locally advanced or metastatic: IV: 350 mg once every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months.
Cervical cancer, recurrent or metastatic (off-label use): IV: 350 mg once every 3 weeks for up to 96 weeks, with the option to repeat in patients who received 16 treatment cycles and experienced disease progression in the posttreatment follow-up phase; may continue beyond progression if a response consistent with pseudo-progression occurs and in the absence of rapid progression, worsening performance status, or unacceptable toxicity (Ref).
Cutaneous squamous cell carcinoma, metastatic or locally advanced: IV: 350 mg once every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months (Ref).
Non–small cell lung cancer, locally advanced or metastatic, first-line single-agent treatment: IV: 350 mg once every 3 weeks until disease progression or unacceptable toxicity (Ref). Note: Select patients for treatment based on PD-L1 expression (on ≥50% of tumor cells).
Non–small cell lung cancer, locally advanced or metastatic, first-line combination treatment: IV: 350 mg once every 3 weeks (in combination with platinum-based chemotherapy) until disease progression or unacceptable toxicity, or for up to 108 weeks (Ref). Note: Chemotherapy consisted of up to 4 cycles of paclitaxel in combination with either cisplatin or carboplatin, or pemetrexed in combination with either cisplatin or carboplatin; refer to protocol for further information (Ref).
Renal impairment prior to treatment initiation: Note: Kidney function estimated by Cockcroft-Gault equation.
CrCl ≥21 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; however, CrCl ≥21 mL/minute had no clinically important effect on cemiplimab pharmacokinetics.
CrCl <21 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling.
Renal toxicity during treatment:
Immune-mediated nephritis with kidney dysfunction: If cemiplimab treatment interruption or discontinuation is required, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to grade 1 or lower, then follow with a corticosteroid taper.
Grade 2 or 3 increased serum creatinine: Withhold treatment; resume with complete or partial resolution of toxicity (grade 0 or 1) after corticosteroid taper. Permanently discontinue cemiplimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
Grade 4 increased serum creatinine: Permanently discontinue cemiplimab.
Hepatic impairment prior to treatment initiation:
Mild or moderate impairment (total bilirubin >1 up to 3 × ULN): There are no dosage adjustments provided in the manufacturer’s labeling; however, mild or moderate hepatic impairment had no clinically important effect on cemiplimab pharmacokinetics.
Severe impairment (total bilirubin >3 × ULN): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Hepatotoxicity during treatment:
If cemiplimab treatment interruption or discontinuation is required, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) or other appropriate therapy for immune-mediated adverse reactions until improvement to grade 1 or lower, then follow with a corticosteroid taper. Permanently discontinue cemiplimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation.
Immune-mediated hepatitis without tumor involvement of the liver:
ALT or AST >3 up to 8 × ULN or total bilirubin >1.5 up to 3 × ULN: Withhold treatment; may resume with complete or partial resolution of toxicity (grade 0 or 1) after corticosteroid taper.
ALT or AST >8 × ULN or total bilirubin >3 × ULN: Permanently discontinue cemiplimab.
Immune-mediated hepatitis with tumor involvement of the liver:
Baseline ALT or AST >1 up to 3 × ULN and increases to >5 up to 10 × ULN or baseline ALT or AST >3 up to 5 × ULN and increases to >8 up to 10 × ULN: Withhold treatment; resume with complete or partial resolution of toxicity (grade 0 or 1) after corticosteroid taper. If ALT and AST are ≤ ULN at baseline, withhold or permanently discontinue cemiplimab based on recommendations for hepatitis without liver involvement (above).
ALT or AST >10 × ULN or total bilirubin >3 × ULN: Permanently discontinue cemiplimab.
Additional recommendations:
Grade 2 immune-mediated hepatitis: Withhold immune checkpoint inhibitor (ICI); if no improvement within 3 to 5 days after ICI is withheld, consider initiation of corticosteroids (prednisone 0.5 to 1 mg/kg/day or equivalent) (Ref).
Grade 3 or 4 immune-mediated hepatitis: Withhold ICI; initiate corticosteroids (methylprednisolone 1 to 2 mg/kg or equivalent) (Ref). Based on data from a retrospective cohort study in patients with grade 3 or 4 immune-mediated hepatitis, initial treatment with methylprednisolone 1 mg/kg/day demonstrated similar time to ALT normalization (compared with higher methylprednisolone doses), while reducing the potential for corticosteroid-related complications (Ref).
No dose reduction for cemiplimab is recommended. Concomitant chemotherapy may require dosage modification; refer to individual monographs for further information.
Immune-mediated toxicities (general information): Withhold cemiplimab for severe (grade 3) immune-mediated adverse reactions. Permanently discontinue cemiplimab for life-threatening (grade 4) adverse reactions, recurrent severe (grade 3) adverse reactions, or inability to reduce corticosteroid dose to ≤10 mg/day prednisone (or equivalent) within 12 weeks of corticosteroids. If cemiplimab requires treatment interruption or discontinuation, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone [or equivalent]) until improvement to grade 1 or lower, then follow with a corticosteroid taper (continue to taper over at least 1 month). If immune-mediated adverse reaction is not controlled with systemic corticosteroids, consider administration of other systemic immunosuppressants. Systemic corticosteroids may not be necessary for certain adverse reactions. Hormone replacement therapy may be required for endocrinopathies (if clinically indicated). See table for additional dosage modification guidance.
Additional management recommendations: Consider withholding checkpoint inhibitor therapy for most grade 2 toxicities and resume when symptoms and/or lab values resolve to ≤ grade 1; systemic corticosteroids (initial dose of 0.5 to 1 mg/kg/day prednisone [or equivalent]) may be administered if indicated for grade 2 toxicities (Ref). Refer to guideline for further information regarding management of immune-mediated adverse reactions associated with checkpoint inhibitor therapy.
|
Adverse reaction |
Severity |
Cemiplimab modification |
|---|---|---|
|
aSJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; DRESS = drug rash with eosinophilia and systemic symptoms. | ||
|
b Refer to prednisone monograph for tapering recommendations when used for immune-mediated adverse reactions associated with checkpoint inhibitor therapy. | ||
|
Immune-mediated adverse reactions | ||
|
Cardiovascular toxicity: Myocarditis |
Grade 2, 3, or 4 |
Permanently discontinue cemiplimab. |
|
Dermatologic toxicity: |
Mild or moderate nonexfoliative rash |
May be managed with topical emollients and/or topical corticosteroids. |
|
Exfoliative dermatologic conditions: Suspected SJS, TEN, or DRESSa |
Withhold treatment; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taperb. Permanently discontinue cemiplimab if no complete or partial response within 12 weeks of initiating corticosteroids or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. | |
|
Confirmed SJS, TEN, or DRESSa |
Permanently discontinue cemiplimab. | |
|
Endocrinopathies |
Grades 3 or 4 |
Withhold treatment until clinically stable or permanently discontinue cemiplimab depending on the severity. |
|
Adrenal insufficiency, ≥ grade 2 |
Initiate symptomatic management (including hormone replacement as clinically indicated). | |
|
Diabetes, type 1 |
Initiate insulin as clinically indicated. | |
|
Hypophysitis |
Withhold or discontinue cemiplimab (depending on the severity). Initiate hormone replacement therapy as clinically indicated. | |
|
Hyperthyroidism |
Withhold or discontinue cemiplimab (depending on the severity). Initiate medical management as clinically indicated. | |
|
Hypothyroidism |
Withhold cemiplimab (depending on the severity). Initiate thyroid hormone replacement therapy as clinically indicated. | |
|
GI adverse reactions: Colitis |
Grade 2 or 3 |
Withhold treatment; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taperb. Permanently discontinue cemiplimab if no complete or partial response within 12 weeks of initiating corticosteroids, or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Grade 4 |
Permanently discontinue cemiplimab. | |
|
Neurologic toxicities |
Grade 2 |
Withhold treatment; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taperb. Permanently discontinue cemiplimab if no complete or partial response within 12 weeks of initiating corticosteroids or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Grade 3 or 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; resume with complete or partial resolution of toxicity (to grade 0 or 1) after corticosteroid taperb. Permanently discontinue cemiplimab if no complete or partial response within 12 weeks of initiating corticosteroids or if unable to reduce prednisone to <10 mg/day (or equivalent) within 12 weeks of corticosteroid initiation. |
|
Grade 3 or 4 |
Permanently discontinue cemiplimab. | |
|
Other adverse reactions | ||
|
Infusion-related reactions |
Grade 1 or 2 |
Interrupt infusion or slow the infusion rate. |
|
Grade 3 or 4 |
Permanently discontinue cemiplimab. | |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidences may be reported for non-FDA approved dosing.
>10%:
Cardiovascular: Hypertension (17%)
Dermatologic: Pruritus (19% to 22%), skin infection (11%), skin rash (15% to 34%)
Endocrine & metabolic: Hypothyroidism (7% to 12%)
Gastrointestinal: Abdominal pain (12%), constipation (12% to 13%), decreased appetite (11% to 14%), diarrhea (26% to 33%; grades 3/4: 1% to 4%), nausea (13% to 21%; grades 3/4: <1%), vomiting (11%; grades 3/4: <1%)
Genitourinary: Urinary tract infection (13%)
Hematologic & oncologic: Anemia (14% to 15%; grades 3/4: ≤4%), hemorrhage (18%; grades 3/4: <1%)
Nervous system: Dizziness (10% to 12%), fatigue (14% to 50%), headache (10% to 13%), peripheral neuropathy (11%)
Neuromuscular & skeletal: Musculoskeletal pain (26% to 36%)
Renal: Acute kidney injury (14%)
Respiratory: Cough (11% to 12%), dyspnea (14%), pneumonia (11%), upper respiratory tract infection (14% to 22%)
1% to 10%:
Cardiovascular: Edema (10%)
Dermatologic: Actinic keratosis (10%), dermatologic disorder (2%)
Endocrine & metabolic: Hypercalcemia (grades 3/4: 1% to 2%), hyperkalemia (grades 3/4: 4%), hypermagnesemia (grades 3/4: 2%), hyperthyroidism (3%), hypoalbuminemia (grades 3/4: 1% to 2%), hypocalcemia (grades 3/4: 4%), hypokalemia (grades 3/4: 2%), hyponatremia (grades 3/4: 3% to 6%), hypophosphatemia (grades 3/4: 2% to 4%)
Gastrointestinal: Colitis (2%)
Hematologic & oncologic: Increased INR (grades 3/4: 3%), lymphocytopenia (grades 3/4: 3% to 7%), prolonged partial thromboplastin time (grades 3/4: 2%)
Hepatic: Hepatitis (2%), increased serum alanine aminotransferase (grades 3/4: 3%), increased serum alkaline phosphatase (grades 3/4: 2%), increased serum aspartate aminotransferase (grades 3/4: 2% to 4%), increased serum bilirubin (grades 3/4: 2%)
Immunologic: Antibody development (2%)
Ophthalmic: Visual impairment (grades 3/4: >2%)
Renal: Increased serum creatinine (grades 3/4: 1%)
Respiratory: Pneumonitis (3%)
<1%:
Cardiovascular: Myocarditis, pericarditis, vasculitis
Endocrine & metabolic: Adrenocortical insufficiency, hypoparathyroidism, hypophysitis, thyroiditis, type 1 diabetes mellitus
Gastrointestinal: Duodenitis, gastritis, increased serum amylase, increased serum lipase, pancreatitis, stomatitis
Hematologic & oncologic: Aplastic anemia, hemolytic anemia, hemophagocytic lymphohistiocytosis, immune thrombocytopenia, lymphadenitis (histiocytic necrotizing lymphadenitis [Kikuchi lymphadenitis])
Hypersensitivity: Severe infusion related reaction
Immunologic: Dermatomyositis, organ transplant rejection (solid), sarcoidosis
Infection: Systemic inflammatory response syndrome
Nervous system: Demyelinating disease, encephalitis, Guillain-Barre syndrome, meningitis, myasthenia (myasthenic syndrome), myasthenia gravis (including exacerbation of myasthenia gravis), neuropathy (autoimmune), paresis (nerve)
Neuromuscular & skeletal: Myelitis, myositis, polymyositis, rhabdomyolysis
Ophthalmic: Ophthalmic inflammation (including iritis, uveitis)
Renal: Nephritis
Frequency not defined: Nervous system: Confusion, ischemic stroke
Postmarketing:
Dermatologic: Pemphigoid (SITC [Brahmer 2021]), Stevens-Johnson syndrome (SITC [Brahmer 2021]), toxic epidermal necrolysis (SITC [Brahmer 2021])
Gastrointestinal: Cholangitis (SITC [Brahmer 2021]), cholecystitis (SITC [Brahmer 2021]), esophagitis (SITC [Brahmer 2021]), xerostomia (SITC [Brahmer 2021])
Hematologic & oncologic: Neutropenia (SITC [Brahmer 2021]), pure red cell aplasia (SITC [Brahmer 2021])
Hepatic: Hepatotoxicity (Chalasani 2021)
Hypersensitivity: Infusion-related reaction (SITC [Brahmer 2021])
Immunologic: Sjögren disease (SITC [Brahmer 2021])
Neuromuscular & skeletal: Myalgia (SITC [Brahmer 2021])
Ophthalmic: Dry eye syndrome (SITC [Brahmer 2021])
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to cemiplimab or any component of the formulation.
Concerns related to adverse effects:
• Adverse events (immune-mediated): PD-1/PD-L1 blockers (including cemiplimab) remove immune response inhibition, thus potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, may occur in any tissue or organ system and may affect more than one organ system simultaneously. Immune-mediated adverse reactions may occur at any time after initiating an anti-PD-L1/PD-1 monoclonal antibody. While immune-mediated adverse reactions generally manifest during treatment, they may also occur following cemiplimab discontinuation. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of anti-PD-1/PD-L1 monoclonal antibodies. If immune-mediated adverse reaction is suspected, initiate appropriate work-up to exclude alternate etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
• Dermatologic toxicity: Cemiplimab may cause immune-mediated rash or dermatitis. Immune-mediated dermatologic adverse reaction is defined as requiring the use of systemic corticosteroids (or other immunosuppressants) and the absence of another clear etiology. Grade 2 and 3 events have been reported. Exfoliative dermatitis, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms, have occurred with anti-PD-L1/PD-1 monoclonal antibodies. Depending on the severity, dermatologic adverse reactions may require treatment interruption or permanent discontinuation. Systemic corticosteroids were required in all patients with immune-mediated dermatologic adverse reactions. Dermatologic adverse reactions led to treatment interruption or permanent discontinuation in a small percentage of patients. Immune-mediated dermatologic adverse reactions resolved in over two-thirds of patients, although over one-third of patients experienced recurrence of dermatologic toxicity upon reinitiation of cemiplimab.
• Endocrinopathies: Cemiplimab is associated with immune-mediated endocrinopathies.
– Adrenal insufficiency: Cemiplimab may cause primary or secondary adrenal insufficiency; grade 3 events have been reported. Adrenal insufficiency rarely required treatment interruption or discontinuation; however, depending on the severity, withhold cemiplimab. Systemic corticosteroids were required in most patients with adrenal insufficiency; most of those patients remained on corticosteroids; adrenal insufficiency resolved in less than one-fifth of patients.
– Diabetes mellitus: Cemiplimab has been associated with type 1 diabetes mellitus (which may present with diabetic ketoacidosis) in a small percentage of patients, including grade 4 events, treatment was withheld and reinitiated after symptom improvement. May require long-term insulin therapy.
– Hypophysitis: Cemiplimab may rarely cause immune-mediated hypophysitis (including rare grade 2 and 3 events). Hypophysitis may present with acute mass effect-associated symptoms such as headache, photophobia, or visual field defects. Hypophysitis may cause hypopituitarism. Systemic corticosteroids were required in a majority of patients. Cemiplimab was rarely withheld due to hypophysitis and not reinitiated in those cases.
– Thyroid disorders: Cemiplimab may cause immune-mediated thyroid disorders. Hyperthyroidism occurred in a small percentage of patients, including rare grade 2 and 3 events. Discontinuation due to hyperthyroidism was not required, although treatment interruption was required in a small number of patients. Systemic corticosteroids were sometimes required. Hyperthyroidism resolved in some patients. Some patients requiring treatment interruption for hyperthyroidism reinitiated cemiplimab (after symptom improvement) and did not experience recurrence. Hypothyroidism has also occurred, including grade 2 and 3 events. Hypothyroidism may follow hyperthyroidism. Initiate hormone replacement for hypothyroidism as clinically indicated. Discontinuation due to hypothyroidism was rarely required, although treatment interruption was required in a small number of patients; systemic corticosteroids were required in a small percentage of patients with hypothyroidism. Hypothyroidism resolved in a small number of patients, although the majority of patients with hypothyroidism required long-term thyroid hormone replacement therapy. Cemiplimab was rarely reinitiated after it was withheld for hypothyroidism (following symptom improvement), but hypothyroidism did not recur. Thyroiditis occurred rarely, including grade 2 events; systemic corticosteroids were not required and cemiplimab was rarely withheld for thyroiditis, and thyroiditis resolved in some cases. Increases or decreases in blood thyroid stimulating hormone have been observed.
• GI adverse reactions: Cemiplimab may cause immune-mediated colitis, which is defined as requiring the use of systemic corticosteroids (or other immunosuppressants) and the absence of another clear etiology. The primary component of immune-mediated colitis was diarrhea. Immune-mediated colitis occurred in a small percentage of patients, including grade 2 and 3 events. Colitis led to permanent discontinuation or treatment interruption in a small number of patients. Systemic corticosteroids were required in all patients with colitis. Colitis resolved in over half of patients. Some patients requiring treatment interruption for colitis reinitiated cemiplimab, and colitis recurred in a majority of these patients. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis who received anti-PD-L1/PD-1 monoclonal antibodies. Pancreatitis (including increased serum amylase and lipase levels), gastritis, and duodenitis have also been reported.
• Hepatitis: Cemiplimab may cause immune-mediated hepatitis, which is defined as requiring the use of systemic corticosteroids (or other immunosuppressants) and the absence of another clear etiology. Immune-mediated hepatitis occurred in a small percentage of patients, including grade 2 and higher events (some fatal). Hepatitis led to permanent discontinuation or treatment interruption in a small percentage of patients. Systemic corticosteroids were required in all patients with hepatitis; some patients required additional immunosuppression (with mycophenolate). Hepatitis resolved in over one-third of patients. Recurrence was observed in one-fifth of patients who reinitiated cemiplimab (following symptom improvement).
• Infusion reactions: Severe or life-threatening infusion-related reactions have occurred (rarely) in patients receiving cemiplimab. Common symptoms of infusion reactions included nausea, fever, and vomiting.
• Nephrotoxicity: Cemiplimab may cause immune-mediated nephritis, which is defined as requiring the use of systemic corticosteroids (or other immunosuppressants) and the absence of another clear etiology. Grade 2, 3, and fatal events have occurred in a small number of patients. Nephritis led to treatment interruption or permanent discontinuation rarely. Systemic corticosteroids were required in all patients with nephritis. Nephritis resolved in most patients. Some patients requiring treatment interruption for nephritis reinitiated cemiplimab after symptom improvement, and rarely experienced recurrence.
• Ocular disorders: Ocular events, including uveitis, iritis, and other ocular inflammatory toxicities have been reported; some cases may be associated with retinal detachment. Various grades of visual impairment (including blindness) may occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome.
• Pneumonitis: Cemiplimab may cause immune-mediated pneumonitis, which is defined as requiring the use of systemic corticosteroids (or other immunosuppressants) and the absence of another clear etiology. In patients who received other anti-PD-L1/PD-1 monoclonal antibodies, the incidence of pneumonitis was higher in patients who received prior thoracic radiation. Grade 2 to 4 events have been observed. Pneumonitis led to permanent discontinuation or treatment interruption in a small percentage of patients. Systemic corticosteroids were required in all patients with pneumonitis. Pneumonitis resolved in over half of patients. Of the patients who reinitiated cemiplimab (following symptom improvement), some experienced recurrence of pneumonitis.
• Other immune-mediated toxicities: Other clinically significant immune-mediated adverse reactions have been reported rarely with cemiplimab or with other anti-PD-L1/PD-1 monoclonal antibodies (some have been severe or fatal). Events have included meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy, myocarditis, pericarditis, vasculitis, myositis/polymyositis/dermatomyositis, rhabdomyolysis (and associated sequelae including renal failure), arthritis, polymyalgia rheumatica, hypoparathyroidism, 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.
Disease-related concerns:
• Hematopoietic stem cell transplant: Fatal and other serious complications may occur in patients who receive allogeneic hematopoietic stem cell transplant (HSCT) before or after treatment with an anti-PD-L1/PD-1 monoclonal antibody. Transplant-related complications included hyperacute graft-versus-host disease (GVHD), acute or chronic GVHD, hepatic veno-occlusive disease (also known as sinusoidal obstruction syndrome) after reduced-intensity conditioning, and steroid-requiring febrile syndrome (with no identified infectious etiology). These complications may occur despite intervening therapy between PD-L1/PD-1 blockade and HSCT. Manage early signs/symptoms of transplant-related complications promptly. Assess the risks/benefits of treatment with an anti-PD-L1/PD-1 monoclonal antibody prior to or after an allogenic HSCT.
• Myasthenia gravis: Checkpoint inhibitors may worsen or precipitate new myasthenia gravis (MG), especially within the first 16 weeks of treatment; use with caution. Patients with well-controlled MG may be considered for checkpoint inhibitor therapy if MG treatment is maintained (or reinitiated in patients whose MG is in remission), combination therapy (eg, anti–CTLA-4 with anti–PD-a/PD-L1 monoclonal antibodies) is avoided, and respiratory and bulbar function are closely followed. In patients who develop overt MG during checkpoint inhibitor therapy, early aggressive treatment with plasma exchange or IVIG in combination with high-dose corticosteroids may be required (AAN [Narayanaswami 2021]).
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.
Other warnings/precautions:
• Appropriate use: Select patients for first-line single-agent treatment of locally advanced (unresectable) or metastatic non–small cell lung cancer based on PD-L1 expression (≥50%) on tumor cells. Information on approved tests for detection of PD-L1 expression may be found at http://www.fda.gov/companiondiagnostics.
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]
No
Solution (Libtayo Intravenous)
350 mg/7 mL (per mL): $1,713.92
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Libtayo: 250 mg/5 mL ([DSC]); 350 mg/7 mL (7 mL) [contains polysorbate 80]
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).
Non-small cell lung cancer, combination therapy: When administered in combination with platinum-based chemotherapy, the chemotherapy agents should be administered first, followed by cemiplimab on the same day, using separate infusion bags and separate filters for each product (Ref).
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Libtayo: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761097s016lbl.pdf#page=36
Basal cell carcinoma, locally advanced or metastatic: Treatment of locally advanced or metastatic basal cell carcinoma in patients previously treated with a hedgehog pathway inhibitor or when a hedgehog pathway inhibitor is not appropriate.
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.
Non–small cell lung cancer, locally advanced or metastatic:
First-line treatment (single-agent therapy) of non–small cell lung cancer in adults whose tumors have high PD-L1 expression (Tumor Proportion Score ≥50%) as determined by an approved test, with no EGFR, ALK, or ROS1 aberrations, and with locally advanced (in patients who are not candidates for surgical resection or definitive chemoradiation) or metastatic disease.
First-line treatment (in combination with platinum-based chemotherapy) of non–small cell lung cancer in adults whose tumors have no EGFR, ALK, or ROS1 aberrations, and with locally advanced (in patients who are not candidates for surgical resection or definitive chemoradiation) or metastatic disease.
Cervical carcinoma, recurrent or metastatic
Cemiplimab may be confused with caplacizumab, cenegermin, certolizumab, cetuximab, dostarlimab, nivolumab.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetaminophen: May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Antibiotics: May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Corticosteroids (Systemic): May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Management: Carefully consider the need for corticosteroids, at doses of a prednisone-equivalent of 10 mg or more per day, during the initiation of immune checkpoint inhibitor therapy. Use of corticosteroids to treat immune related adverse events is still recommended Risk D: Consider therapy modification
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Inhibitors of the Proton Pump (PPIs and PCABs): May diminish the therapeutic effect of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor therapy
Ketoconazole (Systemic): Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies) may enhance the hepatotoxic effect of Ketoconazole (Systemic). Risk C: Monitor therapy
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Evaluate pregnancy status prior to therapy. Patients who could become pregnant should use effective contraception during therapy and for at least 4 months after the last cemiplimab dose.
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.
It is not known if cemiplimab is present in breast milk.
Due to the potential for adverse events in the breastfed infant, the manufacturer does not recommended breastfeeding during therapy or for at least 4 months after the last cemiplimab dose.
PD-L1 expression (for first-line single-agent treatment of metastatic or locally advanced non –small cell lung cancer). Evaluate serum chemistries, hepatic function tests, serum creatinine, and thyroid function tests (at baseline and periodically during treatment). Monitor blood glucose (for hyperglycemia). Evaluate pregnancy status (prior to therapy in patients who could become pregnant). Monitor closely for signs/symptoms of immune-mediated adverse reactions, including adrenal insufficiency, dermatologic toxicity, diabetes mellitus, diarrhea/colitis (consider initiating or repeating infectious workup in patients with corticosteroid-refractory immune-mediated colitis to exclude alternative causes), hepatitis, hypophysitis, ocular disorders, pneumonitis, thyroid disorders, and other immune-mediated adverse reactions. Monitor for signs/symptoms of infusion-related reactions. If received/receiving hematopoietic stem cell transplant, monitor closely for early signs/symptoms of transplant-related complications.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Additional suggested monitoring (ASCO [Schneider 2021]): Prior to therapy: CBC with differential; creatine kinase; comprehensive clinical assessment including performance status, weight, body mass index, heart rate, BP, and oxygen saturation; consider chest x-ray, electrocardiogram, and CT scan; assess history of autoimmune conditions, organ-specific disease, endocrinopathies, neuropathy, and infectious disease; assess bowel habits, respiratory symptoms, skin (for rash), arthralgias, and neurologic symptoms. During therapy: Assess BP, weight, heart rate, and oxygen saturation; assess for infections; screen for hyperglycemia/diabetes (polyuria, polydipsia, weight loss); eye exam (including intraocular pressure after 6 weeks); CBC with differential; creatine kinase; monitor bone mineral density (with long-term therapy).
Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017]). Obtain baseline ECG, natriuretic peptides, and troponins in all patients; obtain a baseline echocardiogram in high-risk patients; consider serial ECGs and cardiac troponins prior to doses 2, 3, and 4, and if normal, reduce to every 3 doses until completion of therapy; cardiovascular risk assessment every 6 to 12 months in high-risk patients who require long-term (>12 months therapy, consider cardiovascular risk assessment every 6 to 12 months in all patients requiring long-term therapy) (ESC [Lyon 2022]). Refer to a cardiologist when clinically indicated.
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.
Distribution: Vd: 5.9 L.
Half-life elimination: 22 days.
Excretion: Clearance: First dose: 0.25 L/day; steady state: 0.22 L/day.
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