ELAHERE

/ Neopharm (Israel) 1996 Ltd.

Recommended Dosage: 6 mg/kg adjusted ideal body weight (AIBW) administered once every 3 weeks (21-day cycle).
AIBW Calculation:
AIBW = Ideal Body Weight (IBW [kg]) + 0.4 * (Actual weight [kg] – IBW);
Female IBW [kg] = 0.9 * (height[cm] – 92).
Pre-treatment Requirements: Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation.
Premedication: Administer the premedications prior to each infusion to reduce the incidence and severity of infusion related reactions (IRRs), nausea, and vomiting.
See prescribing information for full details.
Ophthalmic Topical Steroids: The use of ophthalmic topical steroids is recommended. The initial prescription and renewals of any corticosteroid medication should be made only after examination with a slit lamp. Administer one drop of ophthalmic topical steroids in each eye 6 times daily starting the day prior to each infusion until day 4; then administer one drop in each eye 4 times daily for days 5-8 of each cycle.
Lubricating Eye Drops: The use of lubricating eye drops at least four times daily and as needed is recommended during treatment. Instruct patients to use lubricating eye drops and advise to wait at least 10 minutes after ophthalmic topical steroid administration before instilling lubricating eye drops.
Preparation: This medicinal product is a hazardous drug. Vials should be warmed to room temperature. Dilute with 5% Dextrose Injection to a final concentration of 1 mg/ml to 2 mg/ml. Incompatible with 0.9% Sodium Chloride.
Administration: Intravenous infusion only. Initial rate: 1 mg/min if well tolerated after 30 minutes, increase to 3 mg/min, and subsequently to a maximum of 5 mg/min.
Monitoring: Conduct ophthalmic exams every other cycle for the first 8 cycles.
See prescribing information for full details.

Treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens.

Hypersensitivity to the active substance or any of the excipients

Ocular Toxicity: The medicinal product can cause severe ocular adverse reactions, including keratopathy, visual impairment, dry eye, photophobia, eye pain and uveitis. The median time to onset for first ocular adverse reaction was 5.1 weeks. Prophylactic artificial tears (at least 4 times daily) and ophthalmic topical steroids are recommended. Avoid use of contact lenses during treatment is recommended.
Pneumonitis: Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur.
Monitor patients for pulmonary signs and symptoms of pneumonitis, which may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded through appropriate investigations. Withhold for patients who develop persistent or recurrent Grade 2 pneumonitis until symptoms resolve to ≤ Grade 1 and consider dose reduction. Permanently discontinue in all patients with Grade 3 or 4 pneumonitis.
Peripheral Neuropathy: Monitor for paresthesia, tingling or a burning sensation, neuropathic pain, muscle weakness, or dysesthesia. Dose modification, withhold dosage or discontinuation may be required based on severity.
Embryo-Fetal Toxicity: The active substance can cause fetal harm based on its mechanism of action, which affects actively dividing cells. Effective contraception is required for females during treatment and for 7 months after the last dose.
Driving and using machines: The ability to drive or operate machinery may be impaired. If blurred vision occurs, or if neuropathic symptoms such as pain, numbness, or weakness in the hands, arms, or feet develop, driving, using tools, or operating machines should be avoided until symptoms have fully resolved.
See prescribing information for full details.

Most common (≥10%): Abdominal pain, Diarrhea, Constipation, Nausea, Vomiting, Blurred vision, Keratopathy, Dry eye, Photophobia, Cataract, Fatigue, Peripheral neuropathy, Headache, Musculoskeletal pain, Decreased appetite, Pneumonitis, Arthralgia, Myalgia, Dyspnea.
Laboratory Abnormality including liver function, chemistry and hematology.
See prescribing information for full details.

Effects of Other Drugs on Mirvetuximab Soravtansine
Strong CYP3A4 Inhibitors
DM4 is a CYP3A4 substrate. Concomitant use of Mirvetuximab Soravtansine with strong CYP3A4 inhibitors may increase unconjugated DM4 exposure, which may increase the risk of adverse reactions. Closely monitor patients for adverse reactions.

Pregnancy: Based on its mechanism of action, this medical product can cause embryo-fetal harm when administered to a pregnant woman because it contains a genotoxic compound (DM4) and affects actively dividing cells. There are no available human data in pregnant women to inform a drug-associated risk.
Verify pregnancy status in females of reproductive potential prior to initiating.
Advise females of reproductive potential to use effective contraception during treatment and for 7 months after the last dose.
Lactation: There are no data on the presence of mirvetuximab soravtansine in human milk or the effects on the breastfed child or milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment and for 1 month after the last dose.