BRIEF SUMMARY

CEMIPLIMAB- (Sep 2018)

Indn-       To treat cutaneou squamous cell carinoma (CSCC)                                                                                                                                   

Comp-    Injection: 350 mg/7 mL (50 mg/mL) solution in a single-dose vial   The recommended dosage of LIBTAYO is 350 mg as an intravenous infusion over 30 minutes every 3 weeks.

ADR-   Most common adverse reactions (incidence = 20%) were fatigue, rash and diarrhea.

CI-    None.

 WARNINGS -

 Severe and Fatal Immune-Mediated Adverse Reactions:                                           Immunemediated adverse reactions can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immunemediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions and immune-mediated nephritis and renal dysfunction

Pat Inform-

 Immune-Mediated Adverse Reactions-                                                                           Advise patients that LIBTAYO can cause immune-mediated adverse reactions including the following

  Pneumonitis:                                                                                                                   Advise patients to contact their healthcare provider immediately for signs or symptoms of pneumonitis, including new or worsening symptoms of cough, chest pain, or shortness of breath

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U.S. FDA APPROVED  DRUGS DURING 2018

Sr.No-  41

ADVERSE REACTIONS-

 Most common adverse reactions (incidence = 20%) were fatigue, rash and diarrhea.

CONTRAINDICATIONS-                                                                                                        None.

 WARNINGS AND PRECAUTIONS-

? Severe and Fatal Immune-Mediated Adverse Reactions:                                           Immunemediated adverse reactions can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immunemediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions and immune-mediated nephritis and renal dysfunction.

 Monitor for symptoms and signs of immune-mediated adverse reactions. Evaluate clinical chemistries, including liver and thyroid function, at baseline and periodically during treatment. Withhold or permanently discontinue LIBTAYO and administer corticosteroids based on the severity of reaction.

? Infusion-Related Reactions:                                                                                           Interrupt, slow the rate of infusion or permanently discontinue based on severity of reaction.

? Embryo-Fetal Toxicity:                                                                                                  Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception.

PATIENT COUNSELING INFORMATION-

 Advise the patient to read the FDA-approved patient labeling (Medication Guide).

 Immune-Mediated Adverse Reactions-                                                                           Advise patients that LIBTAYO can cause immune-mediated adverse reactions including the following

  Pneumonitis:                                                                                                                   Advise patients to contact their healthcare provider immediately for signs or symptoms of pneumonitis, including new or worsening symptoms of cough, chest pain, or shortness of breath

  Colitis:                                                                                                                             Advise patients to contact their healthcare provider immediately for signs or symptoms of colitis, including diarrhea, blood or mucus in stools, or severe abdominal pain. 

 Hepatitis:                                                                                                                           Advise patients to contact their healthcare provider immediately for signs or symptoms of hepatitis.

  Endocrinopathies:                                                                                                          Advise patients to contact their healthcare provider immediately for signs or symptoms of hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis, or type 1 diabetes mellitus.

  Nephritis:                                                                                                                         Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis. 

 Dermatologic- Adverse Reactions:                                                                               Advise patients to contact their healthcare provider immediately if they develop a new rash. Infusion-Related Reactions Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions.

Embryo-Fetal Toxicity-                                                                                                      Advise females of reproductive potential that LIBTAYO can cause harm to a fetus and to inform their healthcare provider of a known or suspected pregnancy.

Advise females of reproductive potential to use effective contraception during treatment and for at least 4 months after the last dose of LIBTAYO.

 Lactation-                                                                                                                          Advise female patients not to breastfeed while taking LIBTAYO and for at least 4 months after the last dose.

Manufactured by:

Regeneron Pharmaceuticals, Inc. 777 Old Saw Mill River Road, Tarrytown, NY 10591-6707 .U.S. License No. 1760

Marketed by: 

Regeneron Pharmaceuticals, Inc. (Tarrytown, NY 10591) and sanofi-aventis U.S. LLC (Bridgewater, NJ 08807)  ©2018 Regeneron Pharmaceuticals, Inc. / sanofi-aventis U.S. LLC. 

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CLINICAL PHARMACOLOGY-   

 1.Mechanism of Action-                                                                                                    Binding of the PD-1 ligands PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. .

2. Pharmacokinetics-                                                                                                        Cemiplimab-rwlc pharmacokinetic (PK) data were collected in 505 patients with various solid tumors, including 135 patients with CSCC. The PK of cemiplimab-rwlc was linear and dose proportional in the dose range of 1 mg/kg to 10 mg/kg administered intravenously every two weeks and 350 mg intravenously administered every three weeks.

After a dose of 350 mg LIBTAYO administered intravenously every 3 weeks, median steadystate concentrations (CV%) of cemiplimab-rwlc ranged between a maximum concentration (Cmax,ss) of 166 mcg/mL (28%) and a minimum concentration (Cmin,ss) of 59 mcg/mL (48%). Steady-state exposure is achieved after approximately 4 months of treatment.

Distribution-                                                                                                                    The volume of distribution of cemiplimab-rwlc at steady state is 5.3 L (25%).

Elimination-                                                                                                                     Cemiplimab-rwlc clearance (CV%) after the first dose is 0.32 L/day (39%) and decreases over time by 34%, resulting in a steady-state clearance (CLss) (CV%) of 0.21 L/day (39%). The elimination half-life (CV%) at steady state is 19 days (30%).

 Specific Populations-                                                                                                        The following factors have no clinically important effect on the exposure of cemiplimab-rwlc: age (27 to 96 years), sex, body weight (31 to 156 kg), race (White, Black, Asian and other), cancer type, albumin level (22 to 48 g/L), renal function (creatinine clearance determined by Cockcroft-Gault 25 to 420 mL/min) and hepatic function (total bilirubin 0.35 to 45 µmol/L).

 LIBTAYO has not been studied in patients with moderate or severe hepatic impairment.

 USE IN SPECIFIC POPULATIONS-   

 1.  Pregnancy Risk Summary-                                                                                           Based on its mechanism of action, LIBTAYO can cause fetal harm when administered to a pregnant woman.                                                                                                           There are no available data on the use of LIBTAYO in pregnant women.

Animal studies have demonstrated that inhibition of the PD1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death . Human IgG4 immunoglobulins (IgG4) are known to cross the placenta; therefore, LIBTAYO has the potential to be transmitted from the mother to the developing fetus.

 Advise women of the potential risk to a fetus.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

2. Lactation Risk Summary-                                                                                               There is no information regarding the presence of cemiplimab-rwlc in human milk, or its effects on the breastfed child or on milk production.

Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for at least 4 months after the last dose of LIBTAYO.  

3. Females and Males of Reproductive Potential Pregnancy Testing-                        Verify pregnancy status in females of reproductive potential prior to initiating LIBTAYO . Contraception LIBTAYO can cause fetal harm when administered to a pregnant woman.

 Females-                                                                                                                             Advise females of reproductive potential to use effective contraception during treatment with LIBTAYO and for at least 4 months after the last dose.

4. Pediatric Use-                                                                                                                 The safety and effectiveness of LIBTAYO have not been established in pediatric patients.

5 Geriatric Use-                                                                                                                    Of the 163 patients with metastatic and locally advanced CSCC who received LIBTAYO in clinical studies, 72% were 65 years or older and 37% were 75 years or older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.