50/20. Margentuximab-(MARGENZA)- (Dec 2020)- To treat Herz and Breast Cancer
Drug Name:50/20. Margentuximab-(MARGENZA)- (Dec 2020)- To treat Herz and Breast Cancer
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
DRUG INTERACTIONS- summary-
Anthracyclines Patients who receive anthracyclines less than 4 months after stopping MARGENZA may be at increased risk of cardiac dysfunction.
While this interaction has not been studied with MARGENZA, clinical data from other HER2-directed antibodies warrants consideration. Avoid anthracycline-based therapy for up to 4 months after stopping MARGENZA.
If concomitant use is unavoidable, closely monitor patient’s cardiac function.
Indication:
U.S. FDA APPROVED DRUGS DURING 2020
Sr.No- 50
Adverse Reaction:
ADVERSE REACTIONS-
- The most common adverse drug reactions (>10%) with MARGENZA in combination with chemotherapy are fatigue/asthenia, nausea, diarrhea, vomiting, constipation, headache, pyrexia, alopecia, abdominal pain, peripheral neuropathy, arthralgia/myalgia, cough, decreased appetite, dyspnea, infusion-related reactions, palmar-plantar erythrodysesthesia, and extremity pain.
Contra-Indications:
CONTRAINDICATIONS- • None.
WARNINGS AND PRECAUTIONS- • Infusion-Related Reactions (IRRs): Monitor for signs and symptoms. If a significant infusion-associated reaction occurs, slow or interrupt the infusion and administer appropriate medical therapies.
Dosages/ Overdosage Etc:
On days when both MARGENZA and chemotherapy are to be administered, MARGENZA may be administered immediately after chemotherapy completion.
DOSAGE FORMS AND STRENGTHS- Injection: 250 mg/10 mL (25 mg/mL) in a single-dose vial.
Patient Information:
PATIENT COUNSELING INFORMATION-
Left Ventricular Dysfunction- Advise patients to contact a health care professional immediately for any of the following: new onset or worsening shortness of breath, cough, swelling of the ankles/legs, swelling of the face, palpitations, weight gain of more than 5 pounds in 24 hours, dizziness or loss of consciousness
Embryo-Fetal Toxicity- Advise pregnant women and females of reproductive potential that exposure to MARGENZA during pregnancy or within 4 months prior to conception can result in fetal harm.
Advise female patients to contact their healthcare provider with a known or suspected pregnancy
Advise females of reproductive potential to use effective contraception during treatment with MARGENZA and for 4 months following the last dose
Manufactured by: MARGENZATM is a trademark of MacroGenics, Inc. MacroGenics, Inc. ©2020 MacroGenics, Inc. 9704 Medical Center Drive Rockville, MD 20850-3343 U.S. License No. 2139
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY -
1. Mechanism of Action- Margetuximab-cmkb binds to the extracellular domain of the human epidermal growth factor receptor 2 protein (HER2). Upon binding to HER2-expressing tumor cells, margetuximab-cmkb inhibits tumor cell proliferation, reduces shedding of the HER2 extracellular domain and mediates antibody-dependent cellular cytotoxicity (ADCC).
2. Pharmacodynamics- The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of margetuximab-cmkb have not been fully characterized.
3. Pharmacokinetics - Following the approved recommended dosage, the steady-state geometric mean (% CV) Cmax of margetuximab-cmkb is 466 (20%) µg/mL and AUC0-21d is 4120 (21%) µg.day/mL in patients with HER2-positive relapsed or refractory advanced breast cancer.
Margetuximab undergoes both linear and nonlinear elimination. After a single dose, margetuximab-cmkb Cmax and AUC0- 21d increase in an approximately dose proportional manner from 10 to 18 mg/kg (0.67 to 1.2 times the approved recommended dose).
Distribution - Margetuximab-cmkb geometric mean (%CV) steady-state volume of distribution is 5.47 L (22%).
Elimination- The geometric mean (%CV) terminal half-life of margetuximab-cmkb is 19.2 days (28%) and clearance is 0.22 L/day (24%). Four months after margetuximab-cmkb discontinuation, concentrations decrease to approximately 3% of the steady-state trough serum concentration.
Metabolism- Margetuximab-cmkb is expected to be metabolized into small peptides by catabolic pathways.
Specific Populations- No clinically significant differences in margetuximab-cmkb PK were observed based on age (29 to 83 years), sex, race (Caucasian, Black, Asian), mild to moderate (CLcr 30 to 89 mL/min estimated using the Cockcroft-Gault equation) renal impairment, mild hepatic impairment .
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS-
1. Pregnancy Risk Summary- Based on findings in animals and mechanism of action, MARGENZA can cause fetal harm when administered to a pregnant woman.
There are no available data on use of MARGENZA in pregnant women to inform the drug-associated risk.
In postmarketing reports, use of a HER2- directed antibody during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.
Advise patients of potential risks to a fetus.
There are clinical considerations if MARGENZA is used during pregnancy or within 4 months prior to conception.
Estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
In the U.S. general population, background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 - 4% and 15 - 20%, respy.
2. Lactation Risk Summary- There is no information regarding presence of MARGENZA in human milk, effects on the breastfed child, or effects on milk production.
Published data suggest human IgG is present in human milk but does not enter neonatal or infant circulation in substantial amounts.
Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for MARGENZA treatment and any potential adverse effects on the breastfed child from MARGENZA or from the underlying maternal condition.
This consideration should also take into account the MARGENZA washout period of 4 months
3. Females and Males of Reproductive Potential- MARGENZA can cause fetal harm when administered to a pregnant woman.
Pregnancy Testing- Verify pregnancy status of females of reproductive potential prior to initiation of MARGENZA.
Contraception- Females- Advise females of reproductive potential to use effective contraception during treatment and for 4 months following the last dose of MARGENZA.
4 Pediatric Use- Safety and effectiveness of MARGENZA have not been established in pediatric patients.
5 Geriatric Use - Of the 266 patients treated with MARGENZA 20% were 65 years of age or older and 4% were 75 years or older. No overall differences in efficacy were observed between patients =65 years of age compared to younger patients.
There was a higher incidence of Grade = 3 adverse reactions observed in patients age 65 years or older (56%) compared to younger patients (47%), as well as adverse reactions associated with potential cardiotoxicity (35% vs 18%).
