U.S. FDA APPROVED  DRUGS DURING 2020

Sr.No-  30

ADVERSE REACTIONS

 The most common adverse reactions (=20%) are neutropenia, fatigue, anemia, diarrhea, thrombocytopenia, cough, pyrexia, peripheral edema, respiratory tract infection, and decreased appetite.

CONTRAINDICATIONS-                                                                                              None. 

WARNINGS AND PRECAUTIONS

Infusion-Related Reactions:                                                                                  Monitor patients frequently during infusion. Interrupt or discontinue infusion based on severity.

 Myelosuppression:                                                                                               Monitor complete blood counts. Manage using dose modifications and growth factor support. Interrupt or discontinue MONJUVI based on severity.

 Infections:                                                                                                        Bacterial, fungal and viral infections can occur during and following MONJUVI. Monitor patients for infections.

 Embryo-Fetal Toxicity:                                                                                                    May 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 (Patient Information).

Infusion-Related Reactions-                                                                                  Advise patients to contact their healthcare provider if they experience signs and symptoms of infusionrelated reactions 

Myelosuppression-                                                                                                 Inform patients about the risk of myelosuppression. Advise patients to immediately contact their healthcare provider for a fever of 100.4°F (38°C) or greater or signs or symptoms of bruising or bleeding.

Advise patients of the need for periodic monitoring of blood counts.

Infections-                                                                                                                       Inform patients about the risk of infections.                                                                        Advise patients to immediately contact their healthcare provider for a fever of 100.4°F (38°C) or greater or signs or symptoms of infection

 Embryo-Fetal Toxicity-                                                                                               Advise pregnant women of the potential risk to a fetus.                                                  Advise females of reproductive potential to inform their healthcare provider of a known or suspected pregnancy .

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

Advise patients that lenalidomide has the potential to cause fetal harm and has specific requirements regarding contraception, pregnancy testing, blood and sperm donation, and transmission in sperm.

Lenalidomide is only available through a REMS program 

Lactation-                                                                                                                        Advise women not to breastfeed during treatment with MONJUVI and for at least 3 months after the last dose.

Manufactured by: MORPHOSYS US INC. Boston, MA 02210 U.S. License No. 2152 Marketed by: MORPHOSYS US INC. and INCYTE Corporation.

MONJUVI is a registered trademark of MorphoSys AG Copyright © 2020 MorphoSys AG. All rights reserved. Product of Germany

Reference ID: 4650017       PATIENT INFORMATION MONJUVI® (mon-JOO-vee) (tafasitamab-cxix) for injection What is MONJUV

 CLINICAL PHARMACOLOGY

1. Mechanism of Action-                                                                                        Tafasitamab-cxix is an Fc-modified monoclonal antibody that binds to CD19 antigen expressed on the surface of pre-B and mature B lymphocytes and on several B-cell malignancies, including diffuse large B-cell lymphoma (DLBCL).

Upon binding to CD19, tafasitamab-cxix mediates B-cell lysis through apoptosis and immune effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

In studies conducted in vitro in DLBCL tumor cells, tafasitamab-cxix in combination with lenalidomide resulted in increased ADCC activity compared to tafasitamab-cxix or lenalidomide alone.

2. Pharmacodynamics-                                                                                         Tafasitamab-cxix reduced peripheral blood B cell counts by 97% after eight days of treatment in patients with relapsed or refractory DLBCL. Nadir with a reduction of 100% was reached within 16 weeks of treatment.

3. Pharmacokinetics-                                                                                             Mean trough concentrations (± standard deviation) were 179 (± 53) µg/mL following administration of MONJUVI at 12 mg/kg on Days 1, 8, 15, and 22 in Cycle 1-3 (plus an additional dose on Cycle 1 Day 4), and 153 (± 68) µg/mL following administration of MONJUVI at 12 mg/kg on Days 1 and 15 from Cycle 4 onwards.

Overall maximum tafasitamab-cxix serum concentrations were 483 (±109) µg/mL.

Distribution-                                                                                                               The total volume of distribution for tafasitamab-cxix was 9.3 L (95% CI: 8.6, 10 L).

Elimination-                                                                                                                The clearance of tafasitamab-cxix was 0.41 L/day (CV: 32%) and terminal elimination half-life was 17 days (95% CI: 15, 18 days).

Specific Populations-                                                                                              Body weight (40 to 163 kg) has a significant effect on the pharmacokinetics of tafasitamab-cxix, with higher clearance and volume of distribution expected with higher body weight.

No clinically meaningful differences in the pharmacokinetics of tafasitamab-cxix were observed based on age (16 to 90 years), sex, mild to moderate renal impairment (CLcr 30-89 mL/min estimated by the Cockcroft-Gault equation), and mild hepatic impairment (total bilirubin = ULN and AST > ULN, or total bilirubin 1 to 1.5 times ULN and any AST).

The effect of severe renal impairment to end-stage renal disease (CLcr < 30 mL/min), moderate to severe hepatic impairment (total bilirubin > 1.5 times ULN and any AST), and race/ethnicity on tafasitamab-cxix pharmacokinetics is unknown.

Drug Interaction Studies-                                                                                           No clinically meaningful differences in tafasitamab-cxix pharmacokinetics were observed when used concomitantly with lenalidomide.

 USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary-                                                                                 Based on its mechanism of action, MONJUVI may cause fetal B-cell depletion when administered to a pregnant woman 

There are no available data on MONJUVI use in pregnant women to evaluate for a drug-associated risk. Animal reproductive toxicity studies have not been conducted with tafasitamab-cxix.

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.

 MONJUVI is administered in combination with lenalidomide for up to 12 cycles. Lenalidomide can cause embryo-fetal harm and is contraindicated for use in pregnancy. Refer to the lenalidomide prescribing information for additional information. Lenalidomide is only available through a REMS program.

Clinical Considerations-                                                                                    Fetal/Neonatal Adverse Reactions- Immunoglobulin G (IgG) monoclonal antibodies are transferred across the placenta. Based on its mechanism of action,

MONJUVI may cause depletion of fetal CD19 positive immune cells. Defer administering live vaccines to neonates and infants exposed to tafasitamab-cxix in utero until a hematology evaluation is completed.

2. Lactation Risk Summary -                                                                                    There are no data on the presence of tafasitamab-cxix in human milk or the effects on the breastfed child or milk production. Maternal immunoglobulin G is known to be present in human milk.

The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed infant to MONJUVI are unknown. Because of the potential for serious adverse reactions in the breastfed child, advise women not to breastfeed during treatment with MONJUVI and for at least 3 months after the last dose. Refer to lenalidomide prescribing information for additional information.

3. Females and Males of Reproductive Potential-                                            MONJUVI can cause fetal B-cell depletion when administered to a pregnant woman 

Pregnancy Testing-                                                                                                  Refer to the prescribing information for lenalidomide for pregnancy testing requirements prior to initiating the combination of MONJUVI with lenalidomide.

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

Additionally, refer to the lenalidomide prescribing information for additional recommendations for contraception.

Males-                                                                                                                      Refer to the lenalidomide prescribing information for recommendations.

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

5. Geriatric Use-                                                                                                                Among 81 patients who received MONJUVI and lenalidomide in L-MIND, 72% were 65 years and older, while 38% were 75 years and older.

Clinical studies of MONJUVI did not include sufficient numbers of patients aged 65 and older to determine whether effectiveness differs compared to that of younger subjects. Patients 65 years and older had more serious adverse reactions (57%) than younger patients (39%).