Cemiplimab is a medication used in the treatment of certain types of cancer. It is a monoclonal antibody that works by blocking a protein called programmed death receptor-1 (PD-1) on the surface of immune cells. By blocking PD-1, cemiplimab helps the immune system recognize and attack cancer cells more effectively.

Cemiplimab (Libtayo) is a fully human monoclonal antibody that targets immune checkpoints. It has been approved for the treatment of advanced skin cancer.

Cemiplimab (Libtayo) Use:

• Metastatic or locally advanced cutaneous squamous cell carcinoma:
  • Treatment of metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC in patients who are not candidates for curative surgery or curative radiation.

Cemiplimab (Libtayo) Dose in Adults

Cemiplimab (Libtayo) Dose in the treatment of metastatic or locally advanced cutaneous squamous cell carcinoma:

• The recommended way to take cemiplimab is through an intravenous (IV) injection, which means it's given directly into your bloodstream.
• You'll receive 350 milligrams of the medicine once every three weeks.
• You'll keep getting these injections until either the cancer gets worse or you experience side effects that are too severe to continue.

Cemiplimab (Libtayo) Dose in Childrens

Not recommended for use in children.

Pregnancy Risk Category: Not Assigned

• Cemiplimab is a type of medicine that might affect pregnancy.
• It's an antibody that can cross from a pregnant person to their baby.
• So, before starting cemiplimab treatment, doctors need to check if you're pregnant or could become pregnant.
• If you're a woman who can have children, you should use reliable birth control while taking cemiplimab and for at least four months after your last dose to avoid harming the baby.

Use of cemiplimab during breastfeeding

• We're not sure if cemiplimab can pass into breast milk.
• Because there's a chance it could harm a nursing baby, the manufacturer suggests that breastfeeding is not recommended while you're on this treatment or for at least four months after your last cemiplimab dose.

Cemiplimab (Libtayo) Dose in Kidney disease:

Before Starting Treatment:

• If your kidney function (CrCl) is 25 mL/minute or higher, no dosage adjustments are needed for cemiplimab.
• If your kidney function is less than 25 mL/minute, there are no specific dosage adjustments mentioned in the instructions.

During Treatment, if You Experience Kidney Problems:

• If you develop immune-mediated nephritis (a kidney problem related to your immune system):
  • For severe cases (grade 3 or 4), your doctor may give you corticosteroids (like prednisone) or other suitable treatment until the kidney issue improves to a lower grade (grade 1 or less).
  • For grade 3 cases, they might temporarily stop cemiplimab until the kidney problem improves (grade 0 or 1) and then restart it.
  • If it's a severe grade 4 case, cemiplimab should be stopped permanently.

Cemiplimab (Libtayo) Dose in Liver disease:

Before Starting Treatment:

• If you have mild liver impairment, no dosage adjustments are recommended for cemiplimab, as it does not significantly affect the medication's behavior.
• If you have moderate to severe liver impairment, there are no specific dosage adjustments suggested in the instructions because this hasn't been studied.

During Treatment, if You Experience Liver Problems:

• If you develop immune-mediated hepatitis (a liver problem related to your immune system):
  • For severe cases (grade 3 or 4), your doctor may prescribe corticosteroids (like prednisone) or other suitable treatment until the liver issue improves to a lower grade (grade 1 or less).
  • If your liver enzyme levels (ALT or AST) are significantly elevated (more than 3 to 10 times the upper limit of normal) or if your total bilirubin is up to 3 times the upper limit of normal, they might temporarily stop cemiplimab until the liver problem improves (grade 0 or 1) and then restart it.
  • If your liver enzyme levels (ALT or AST) are more than 10 times the upper limit of normal or if your total bilirubin is more than 3 times the upper limit of normal, cemiplimab should be stopped permanently.

Common Side Effects of Cemiplimab (Libtayo):

• Central Nervous System:
  • Fatigue
• Dermatologic:
  • Skin Rash
  • Dermatologic Disorders
  • Pruritus
• Gastrointestinal:
  • Diarrhea
  • Nausea
  • Constipation
• Neuromuscular & Skeletal:
  • Musculoskeletal Pain

Less Common Side Effects Of Cemiplimab (Libtayo):

• Cardiovascular:
  • Hypertension
• Dermatologic:
  • Cellulitis
  • Skin Infection
  • Erythema Multiforme
  • Pemphigoid
• Endocrine & Metabolic:
  • Hypothyroidism
  • Hypophosphatemia
  • Hyponatremia
  • Hyperthyroidism
  • Hypercalcemia
  • Hypoalbuminemia
• Gastrointestinal:
  • Decreased Appetite
• Genitourinary:
  • Urinary Tract Infection
• Hematologic & Oncologic:
  • Lymphocytopenia
  • Anemia
  • Increased INR
• Hepatic:
  • Increased Serum Aspartate Aminotransferase
  • Hepatitis
• Immunologic:
  • Antibody Development
• Infection:
  • Sepsis
• Respiratory:
  • Pneumonia
  • Pneumonitis

Rare Side effects of Libtayo:

• Dermatologic:
  • Stevens-Johnson Syndrome
  • Toxic Epidermal Necrolysis

Contraindications to Cemiplimab (Libtayo):

• The manufacturer's labeling does not list any specific contraindications for the use of this medication.
• This means that there are no absolute medical reasons mentioned in the official instructions that would prohibit someone from taking cemiplimab under normal circumstances.

Warnings and precautions

Insufficiency of the adrenals:

• Adrenal insufficiency, although rare, has been reported in some cases during cemiplimab treatment.
• This condition may sometimes reach moderate (grade 2) or severe (grade 3) levels of toxicity.
• Adrenal insufficiency refers to a problem with the adrenal glands that can affect hormone production.

Negative events (immune-mediated).

• When using PD-1/PD-L1 blockers like cemiplimab, it's important to be aware that they can unleash the immune system and potentially lead to immune-mediated adverse reactions, which can be severe or even life-threatening and affect various parts of the body.
• These reactions may occur during treatment or after treatment ends.
• Early identification and management are crucial for safe use.
• Monitoring for signs of these reactions and evaluating blood tests, including liver and thyroid function, at the beginning and regularly during treatment, is recommended.
• If severe (grade 3 or 4, and some grade 2) immune-mediated adverse events occur, cemiplimab may be temporarily withheld or permanently discontinued.
• Systemic corticosteroids or other appropriate therapies are typically used to manage these reactions until they improve.
• In some cases, additional immunosuppressive treatments may be necessary, and hormone replacement therapy might be needed if there are endocrine issues.

Dermatologic toxicities:

• Cemiplimab can lead to skin problems, including immune-mediated dermatologic adverse reactions like erythema multiforme and pemphigoid, which can range from moderate (grade 2) to severe (grade 3).
• Some rare but serious conditions like Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have also been reported with cemiplimab and similar medications.
• To treat these skin reactions, patients often need systemic corticosteroids, with most requiring high doses (prednisone ≥40 mg/day or equivalent).
• While these skin problems resolved in about one-third of patients, more than one-fifth experienced a recurrence of skin issues when they restarted cemiplimab after stopping it.

Diabetes mellitus

• In some cases, while using cemiplimab, a small percentage of patients developed Type 1 diabetes mellitus, which is a condition where the body's immune system attacks the insulin-producing cells in the pancreas.
• This can sometimes lead to a severe condition called diabetic ketoacidosis.
• Some of these cases were quite severe, reaching grade 3 and 4 levels.
• Type 1 diabetes mellitus forced a few patients to permanently stop using cemiplimab.

Toxicity to the GI:

• While using cemiplimab, some patients experienced immune-mediated colitis, which is inflammation of the colon or large intestine, ranging from moderate (grade 2) to severe (grade 3).
• In a few cases, colitis was serious enough to require permanent discontinuation of cemiplimab.
• To manage colitis, patients typically needed systemic corticosteroids, with more than half of them receiving high doses (prednisone ≥40 mg/day or equivalent).
• Fortunately, colitis improved in most patients with appropriate treatment.
• Additionally, other gastrointestinal issues like pancreatitis (including elevated amylase and lipase levels), gastritis, and duodenitis have also been reported in some individuals using cemiplimab.

Hepatitis

• Some individuals using cemiplimab experienced immune-mediated hepatitis, which is inflammation of the liver due to an immune response.
• This condition could range in severity, with some cases reaching grade 3 or higher, and in some instances, it was fatal.
• For a small percentage of patients, hepatitis was severe enough to necessitate permanent discontinuation of cemiplimab.
• To manage hepatitis, systemic corticosteroids were needed in all cases, and most patients required high doses of prednisone (≥40 mg/day or equivalent).
• Thankfully, hepatitis improved in nearly two-thirds of patients with appropriate treatment.

Hypophysitis

• In rare cases, individuals using cemiplimab have experienced hypophysitis, which is inflammation of the pituitary gland in the brain, sometimes reaching grade 3 severity.
• Hypophysitis can lead to a condition called hypopituitarism, where the pituitary gland doesn't produce enough hormones.
• This can affect various bodily functions regulated by hormones and may require medical management.

Infusion reactions

• While receiving cemiplimab through an infusion, some patients have experienced infusion-related reactions, with grade 3 reactions being rare but possible.
• It's important for healthcare providers to closely monitor for any signs or symptoms of these reactions during the infusion.
• Depending on the severity of the reaction, they may need to pause or slow down the infusion, or in severe cases, permanently stop cemiplimab treatment.
• Timely recognition and appropriate management are crucial to ensure the safety and well-being of patients undergoing cemiplimab infusions.

Nephrotoxicity

• In a small number of patients receiving cemiplimab, there have been cases of immune-mediated nephritis, which is inflammation of the kidneys leading to renal dysfunction.
• This condition could range from moderate (grade 2) to severe (grade 3).
• Although it rarely resulted in permanent discontinuation of cemiplimab, all patients with nephritis required systemic corticosteroids for treatment, and a significant portion of them needed high doses of prednisone (≥40 mg/day or equivalent).
• Fortunately, nephritis resolved in all patients with appropriate treatment.
• Monitoring for signs of nephritis is important during cemiplimab treatment, and prompt medical attention is necessary if any symptoms or issues arise.

Ocular disorders

• Cemiplimab use has been associated with various ocular (eye-related) issues, including uveitis, iritis, visual impairment of different grades (which may even lead to blindness), and other inflammatory problems affecting the eyes, with some cases involving retinal detachment.
• If uveitis occurs along with other immune-related adverse reactions, it might be reminiscent of a condition called Vogt-Koyanagi-Harada-like syndrome, and treatment might involve systemic corticosteroids to reduce the risk of permanent vision loss.
• It's crucial to promptly address any eye-related symptoms or issues while using cemiplimab and seek medical attention to protect your vision.

Pneumonitis

• There have been reports of immune-mediated pneumonitis while using cemiplimab, including cases of moderate (grade 2) and more severe events, with some resulting in fatalities.
• Although it only led to permanent discontinuation in a small percentage of patients, all patients with pneumonitis needed systemic corticosteroids for treatment, and most of them required high doses of prednisone (≥40 mg/day or equivalent).
• Fortunately, pneumonitis improved in over half of the affected patients with appropriate treatment.

Thyroid disorders

• Thyroid-related issues have been observed in patients using cemiplimab.
• This includes cases of hypothyroidism, which can range from moderate (grade 2) to severe (grade 3).
• However, no patients needed to discontinue hormone replacement therapy due to these thyroid problems.
• Additionally, hyperthyroidism has also occurred, with some cases reaching grade 2 or 3 severity.
• In more than one-third of these patients, hyperthyroidism resolved on its own.

Other immune-mediated toxicities

• Cemiplimab and similar medications in its class have been associated with various other immune-mediated adverse reactions that can be clinically significant, and some of these reactions have been severe or even fatal.
• These events encompass a wide range of immune-related issues affecting different parts of the body and systems, including the central nervous system (e.g., meningitis, encephalitis, myelitis, demyelination), neuromuscular system (e.g., myasthenic syndrome/myasthenia gravis, Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy), heart (myocarditis, pericarditis), blood vessels (vasculitides), muscles (myositis, rhabdomyolysis), joints (arthritis, polymyalgia rheumatica), blood (hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis), immune system (systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis), lungs (sarcoidosis), platelet disorders (immune thrombocytopenia), and even the risk of rejection in solid organ transplants.
• These immune-mediated reactions underscore the importance of careful monitoring and early intervention during treatment with cemiplimab to manage potential adverse events.

Monitoring parameters:

Blood Tests and Evaluation:

• Regularly check blood chemistry levels.
• Assess liver function with hepatic function tests.
• Monitor thyroid function through thyroid function tests.
• Perform a pregnancy test before starting treatment in women who can become pregnant.

Signs and Symptoms Monitoring:

• Keep an eye out for signs of adrenal insufficiency.
• Watch for any skin-related issues (dermatologic toxicity).
• Be alert to symptoms of diabetes.
• Be vigilant for signs of diarrhea or colitis.
• Monitor for signs of hepatitis.
• Be aware of symptoms of hypophysitis.
• Pay attention to any eye problems (ocular disorders).
• Be on the lookout for breathing issues (pneumonitis).
• Keep an eye on thyroid-related symptoms.
• Be aware of any other potential immune-related reactions.
• Monitor for signs of infusion-related reactions during treatment.

How to administer Cemiplimab (Libtayo)?

How to Infuse:

• Infuse it slowly over 30 minutes.
• Use a special filter with tiny holes (0.2 to 5 micron) either as part of the IV line or added separately.
• Make sure the solution isn't too cold; let it reach room temperature before starting the infusion.

During Infusion:

• Keep a close watch for any signs of infusion reactions.
• Depending on how severe the reaction is, you may need to slow down the infusion, pause it for a bit, or even stop it altogether. Your healthcare provider will decide what to do.

Mechanism of action of cemiplimab (Libtayo):

• Cemiplimab works by blocking the activity of a protein called PD-1.
• PD-1 is a part of our immune system that can inhibit or slow down the body's response against threats, including cancer cells.
• Cemiplimab binds to PD-1, preventing it from interacting with other molecules called PD-L1 and PD-L2.
• These interactions usually inhibit the immune system's ability to fight against tumors.
• Some tumors can increase the production of PD-1 ligands, which makes it harder for the immune system to recognize and attack them.
• By blocking PD-1, cemiplimab helps the immune system overcome this inhibition, allowing it to respond more effectively against cancer cells and slowing down tumor growth.

Distribution:

• Volume of Distribution (V): 5.3 liters.
• This tells us how widely the medication is distributed throughout the body.

Half-life Elimination:

• Half-life elimination: 19 days.
• This is the time it takes for half of the medication to be cleared from the body.
• A longer half-life means the drug stays in the body for a more extended period.

Excretion:

• Clearance:
  • First dose: 0.32 liters per day. This is the rate at which the drug is removed from the body after the initial dose.
  • Steady state: 0.21 liters per day. This is the rate at which the drug is removed from the body once it has reached a stable level in the bloodstream.

International Brands of Cemiplimab:

• Libtayo

Cemiplimab Brand Names in Pakistan:

Not available.