DRUG INTERACTIONS

Effect of LUNSUMIO on CYP450 Substrates LUNSUMIO causes release of cytokines  that may suppress activity of CYP450 enzymes, resulting in increased exposure of CYP450 substrates.

Increased exposure of CYP450 substrates is more likely to occur after the first dose of LUNSUMIO on Cycle 1 Day 1 and up to 14 days after the second 60 mg dose on Cycle 2 Day 1 and during and after CRS

 Monitor for toxicity or concentrations of drugs that are CYP450 substrates where minimal concentration changes may lead to serious adverse reactions.

Consult the concomitant CYP450 substrate drug prescribing information for recommended dosage modification.

BRIEF SUMMARY

MOSUNETUZNAB- axgb- (Dec 2022)

Indn-  To treat adults with  elapsed or  refractory    follicular lymphoma a type of non                    Hodgkin Kymphoma 

Comp-   Injection: 1 mg/mL solution in a single-dose vial. (3) • 30 mg/30 mL (1 mg/mL) solution in a single-dose vial.                                                                                     Recommended dosage: o Cycle 1 Day 1 – 1 mg  Cycle 1 Day 8 – 2 mg  Cycle 1 Day 15 – 60 mg  Cycle 2 Day 1 – 60 mg  Cycle 3+ Day 1 – 30 mg

ADR-  The most common adverse reactions (= 20%) are cytokine release syndrome, fatigue, rash, pyrexia, and headache

CI-  None.  

WARNINGS -                                                                                                          Neurologic Toxicity: - Can cause serious neurologic toxicity, including Immune Effec tor Cell-Associated Neurotoxicity Syndrome (ICANS). Monitor patients for signs and symptoms of neurologic toxicity during treatment; withhold or permanently discontinue based on severity.

• Infections: Can cause serious or fatal infections. Monitor patients for signs and symptoms of infection, including opportunistic infections, and treat as needed.

Pat Inform-

Cytokine Release Syndrome (CRS) – Discuss the signs and symptoms associated with CRS, including fever, chills, hypotension, tachycardia, hypoxia, and headache. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.

Advise patients who experience symptoms that impair consciousness not to drive and refrain from operating heavy or potentially dangerous machinery until events resolve

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U.S.  APPROVED DRUGS DURING 2022                                        

Serial No 34

Name-        LUNSUMIO

Acive  Ingredient -  Mosuntuzmab-axgb

Pharmacological clssificiation-        To treat adults with  elapsed or  refractory                                                                          follicular lymphoma a type of non                                                                                    Hodgkin Kymphoma     

 Date of  Approval-         22/12/2022    

HIGHLIGHTS OF PRESCRIBING INFORMATION-

These highlights do not include all  the information needed to use                        LUNSUMIO safely and effectively.                                                                                  See full prescribing information for LUNSUMIO. LUNSUMIO™ (mosunetuzumab-axgb) injection, for intravenous use

.Initial U.S. Approval: 2022

WARNING:                                                                                                                 CYTOKINE RELEASE SYNDROME See full prescribing information for complete boxed warning. Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving LUNSUMIO. Initiate treatment with the LUNSUMIO step-up dosing schedule to reduce the risk of CRS. Withhold LUNSUMIO until CRS resolves or permanently discontinue based on severity.

 INDICATIONS AND USAGE-

 LUNSUMIO is a bispecific CD20-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.

This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

 ADVERSE REACTIONS-

 The most common adverse reactions (= 20%) are cytokine release syndrome, fatigue, rash, pyrexia, and headache. The most common Grade 3 to 4 laboratory abnormalities (= 10%) are decreased lymphocyte count, decreased phosphate, increased glucose, decreased neutrophil count, increased uric acid, decreased white blood cell count, decreased hemoglobin, and decreased platelets.

 CONTRAINDICATIONS -                                                                                               None. 

 WARNINGS AND PRECAUTIONS

 • Neurologic Toxicity:                                                                                                       Can cause serious neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). Monitor patients for signs and symptoms of neurologic toxicity during treatment; withhold or permanently discontinue based on severity.

• Infections:                                                                                                                  Can cause serious or fatal infections. Monitor patients for signs and symptoms of infection, including opportunistic infections, and treat as needed.

 • Cytopenias: Monitor complete blood cell counts during treatment.

 • Tumor Flare: Can cause serious tumor flare reactions. Monitor patients at risk for complications of tumor flare.

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

DOSAGE AND ADMINISTRATION-                                                                                 

 • Premedicate to reduce risk of cytokine release syndrome and infusionrelated reactions. (2.3, 5.1) • Administer only as an intravenous infusion.

• Recommended dosage: o Cycle 1 Day 1 – 1 mg o Cycle 1 Day 8 – 2 mg o Cycle 1 Day 15 – 60 mg o Cycle 2 Day 1 – 60 mg o Cycle 3+ Day 1 – 30 mg

 DOSAGE FORMS AND STRENGTHS -                                                                             Injection: • 1 mg/mL solution in a single-dose vial. (3) • 30 mg/30 mL (1 mg/mL) solution in a single-dose vial. 

PATIENT COUNSELING INFORMATION-

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

Cytokine Release Syndrome (CRS) – Discuss the signs and symptoms associated with CRS, including fever, chills, hypotension, tachycardia, hypoxia, and headache. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.

Advise patients who experience symptoms that impair consciousness not to drive and refrain from operating heavy or potentially dangerous machinery until events resolve 

Neurologic Toxicity – Discuss the signs and symptoms associated with neurologic toxicity, including ICANS, headache, peripheral neuropathy, dizziness, or mental status changes.

Advise patients to immediately contact their healthcare provider if they experience any signs or symptoms of neurologic toxicity.

Advise patients who experience neurologic toxicity that impairs consciousness to refrain from driving or operating heavy or potentially dangerous machinery until neurologic toxicity resolves].

Infections – Discuss the signs or symptoms associated with infection..

Cytopenias – Discuss the signs and symptoms associated with cytopenias, including neutropenia and febrile neutropenia, anemia, and thrombocytopenia..

Tumor Flare – Inform patients of the potential risk of tumor flare reaction and to report any signs and symptoms associated with this event to their healthcare provider for evaluation].

Embryo-Fetal Toxicity – Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to inform their healthcare provider if they are pregnant or become pregnant.

Advise females of reproductive potential to use effective contraception during treatment with LUNSUMIO and for 3 months after the last dose.

Lactation – Advise women not to breastfeed during treatment with LUNSUMIO and for 3 months after the last dose

LUNSUMIO is a trademark of Genentech, Inc. ©2022 Genentech, Inc.                 Man- by: Genentech, Inc. A Member of the Roche Group 1 DNA Way South San Francisco, CA 94080-4990 U.S. License No.: 1048

CLINICAL PHARMACOLOGY-                                                                                   

1. Mechanism of Action-                                                                                  Mosunetuzumab-axgb is a T-cell engaging bispecific antibody that binds to the CD3 receptor expressed on the surface of T-cells and CD20 expressed on the surface of lymphoma cells and some healthy B-lineage cells.

2. Pharmacodynamics-                                                                                                      After administration of the recommended dosage of LUNSUMIO, peripheral B-cell counts decreased to undetectable levels (< 5 cells/microliter) in most patients (92%) by Cycle 2 Day 1 and the depletion was sustained at later cycles including at Cycle 4 and Cycle 8..

Distribution-                                                                                                                      The mean (CV%) volume of distribution of mosunetuzumab-axgb was 5.49 L (31%). 

Elimination-                                                                                                                   The steady-state geometric mean (CV%) terminal elimination half-life of mosunetuzumab-axgb was 16.1 (17.3%) days.

The geometric mean (CV%) clearance at baseline and at steady state are 1.08 L/day (63%) and 0.584 L/day (18%), respectively.

Specific Populations-                                                                                               There were no clinically significant differences in the pharmacokinetics of mosunetuzumab-axgb based on age (19 to 96 years), sex, race (Asian and Non-Asian), ethnicity (Hispanic/Latino and not Hispanic/Latino), mild or moderate renal impairment (estimated Creatinine clearance [CrCL] by Cockcroft-Gault formula: 30 to 89 mL/min), or mild hepatic impairment (total bilirubin less than or equal to upper limit of normal [ULN] with AST greater than ULN or total bilirubin greater than 1 to 1.5 times ULN with any AST).

The effects of severe renal impairment (CrCL 15 to 29 mL/min) or moderate to severe hepatic impairment (total bilirubin greater than 1.5 times ULN with any AST) on the pharmacokinetics of mosunetuzumab-axgb are unknown.

Drug Interaction Studies-                                                                                              No clinical studies evaluating the drug interaction potential of mosunetuzumab-axgb have been conducted. 12.6 Immunogenicity The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay.

Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the study described below with the incidence of anti-drug antibodies in other studies, including those of mosunetuzumab-axgb.

 USE IN SPECIFIC POPULATIONS

1 Pregnancy Risk Summary-                                                                                     Based on the mechanism of action, LUNSUMIO may cause fetal harm when administered to a pregnant woman

 There are no available data on the use of LUNSUMIO in pregnant women to evaluate for a drug-associated risk. No animal reproductive or developmental toxicity studies have been conducted with mosunetuzumab-axgb.

Human immunoglobulin G (IgG) is known to cross the placenta; therefore, LUNSUMIO has the potential to be transmitted from the mother to the developing fetus.

Advise women of the potential risk to the fetus.

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

2 Lactation Risk Summary-                                                                                      There is no information regarding the presence of mosunetuzumab-axgb in human milk, the effect on the breastfed child, or milk production.

Because human IgG is present in human milk, and there is potential for mosunetuzumab-axgb absorption leading to B-cell depletion, advise women not to breastfeed during treatment with LUNSUMIO and for 3 months after the last dose.

3 Females and Males of Reproductive Potential-                                                     LUNSUMIO may cause fetal harm when administered to a pregnant woman

 Pregnancy Testing-                                                                                                    Verify pregnancy status in females of reproductive potential prior to initiating LUNSUMIO.

 Contraception Females -                                                                                        Advise females of reproductive potential to use effective contraception during treatment with LUNSUMIO and for 3 months after the last dose.

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

5. Geriatric Use-                                                                                                              Among the 90 patients with relapsed or refractory follicular lymphoma treated with LUNSUMIO, 33% were 65 years of age or older, and 8% were 75 years of age or older.

There is an insufficient number of patients 65 years of age or older and 75 years of age or older to assess whether there are differences in safety or effectiveness in patients 65 years of age and older compared to younger adult patients.