ELAHERE
Clinical safety rating
cautionComprehensive clinical and safety monograph for ELAHERE (ELAHERE).
Comprehensive clinical and safety monograph for ELAHERE (ELAHERE).
Treatment of adult patients with FRα-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens (FDA approved indication)
ELAHERE (mirvetuximab soravtansine) is an antibody-drug conjugate (ADC) targeting folate receptor alpha (FRα). It consists of a humanized anti-FRα antibody conjugated to the maytansinoid DM4, a microtubule inhibitor. Upon binding to FRα on tumor cells, the ADC is internalized and releases DM4, which binds to tubulin and disrupts microtubule polymerization, leading to cell cycle arrest and apoptosis.
| Metabolism | The DM4 component is primarily metabolized by CYP3A4 and, to a lesser extent, by CYP3A5 and CYP2D6. The antibody component undergoes catabolism via proteolytic degradation. |
| Excretion | Fecal (approximately 80%) as unchanged drug; renal (approximately 8%) as unchanged drug and metabolites. |
| Half-life | Terminal half-life approximately 6.2 days (range 3.7-9.5 days) after IV administration; supports every-3-week dosing interval. |
| Protein binding | Approximately 95% bound to plasma proteins (albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Mean Vd approximately 0.27 L/kg (range 0.14-0.54 L/kg), indicating distribution primarily in plasma and extracellular fluid. |
| Bioavailability | Intravenous only; oral bioavailability not applicable (0% by oral route). |
| Onset of Action | Not clinically defined; pharmacodynamic effects (receptor binding) occur within hours; antitumor response typically assessed after 2-3 cycles (6-9 weeks). |
| Duration of Action | Duration of action is sustained over the dosing interval (3 weeks) due to long half-life; clinical effect persists as long as drug remains above therapeutic threshold; typically evaluated until disease progression or unacceptable toxicity. |
| Molecular Weight | 1468.4 |
6 mg/kg adjusted ideal body weight intravenously every 3 weeks until disease progression or unacceptable toxicity.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min). |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate to severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended. Elderly patients (≥65 years) experienced higher rates of serious adverse reactions; monitor closely. |
| 1st trimester | Adequate and well-controlled studies in pregnant women are not available; based on its mechanism of action, ELAHERE can cause fetal harm when administered to a pregnant woman. There is a risk of embryo-fetal toxicity, including teratogenicity, based on animal studies. |
| 2nd trimester | Same as T1. Avoid use during second trimester unless benefit outweighs risk. |
| 3rd trimester | Same as T1. Avoid use during third trimester; may cause fetal harm. |
Clinical note
Comprehensive clinical and safety monograph for ELAHERE (ELAHERE).
| Placental transfer | Based on its mechanism of action and molecular weight, placental transfer is expected. No human data available; animal studies indicate embryo-fetal toxicity consistent with transfer. |
| Breastfeeding | It is not known whether ELAHERE or its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, advise women not to breastfeed during treatment and for at least 2 weeks after the last dose. |
| Lactation Rating | L5 - Contraindicated (Risk of serious adverse reactions in infant) |
| Teratogenic Risk | Based on its mechanism of action (folate receptor alpha-directed antibody-drug conjugate containing maytansinoid DM4, a microtubule inhibitor), ELAHERE is expected to cause embryofetal toxicity and teratogenicity. Malformations and developmental abnormalities are likely if administered during the first trimester. Second and third trimester exposure may result in fetal growth restriction, oligohydramnios, and organ dysfunction due to anti-mitotic effects. There are no adequate human data; animal studies have not been conducted. |
| Fetal Monitoring | Monitor complete blood counts (CBC) for neutropenia, thrombocytopenia; liver function tests (ALT, AST, bilirubin); serum creatinine; ocular examinations for visual disturbances (e.g., blurred vision, keratitis); and pregnancy status prior to initiation and periodically during therapy. Fetal ultrasound for growth and amniotic fluid volume if exposure occurs during pregnancy. |
| Fertility Effects | Based on animal studies with DM4 (microtubule inhibitor), ELAHERE may impair male and female fertility. May cause ovarian failure, azoospermia, or menstrual irregularities. Long-term effects on reproductive function are unknown. |
■ FDA Black Box Warning
ELAHERE is not approved for use in patients with platinum-sensitive disease due to increased toxicity and mortality observed in a clinical trial. No other black box warnings.
| Serious Effects |
None known; however, use is contraindicated in patients with severe hypersensitivity to mirvetuximab soravtansine or any of its excipients.
| Precautions | Ocular toxicity: Corneal toxicity, including keratopathy, blurred vision, dry eyes, and photophobia. Requires ophthalmic monitoring and management with prophylactic corticosteroid eye drops., Pneumonitis/Interstitial lung disease (ILD): Monitor for cough, dyspnea, or hypoxia; withhold or discontinue if severe., Peripheral neuropathy: Monitor for sensory or motor neuropathy; dose modify as needed., Embryo-fetal toxicity: Can cause fetal harm; advise patients of reproductive potential to use effective contraception. |
| Food/Dietary | Avoid grapefruit and grapefruit juice during treatment as they may increase mirvetuximab soravtansine exposure. No other significant food interactions reported. |
| Clinical Pearls | ELAHERE (mirvetuximab soravtansine) is an antibody-drug conjugate targeting folate receptor alpha (FRα). Administer premedications to reduce infusion reactions. Monitor for ocular toxicity including blurred vision, keratopathy, and dry eye; refer to ophthalmology if symptoms occur. Assess for interstitial lung disease. Use with caution in patients with hepatic impairment due to potential for hepatotoxicity. Contraception required during treatment and for 7 months after last dose. |
| Patient Advice | This drug targets a protein called folate receptor alpha found on some cancer cells. · You will receive this medication as an intravenous (IV) infusion every 3 weeks. · Common side effects include fatigue, nausea, diarrhea, and blurred vision. · Report any vision changes, shortness of breath, or yellowing of the skin/eyes immediately. · Use effective contraception during treatment and for 7 months after the last dose. · Do not breastfeed during treatment and for 1 month after the last dose. · Stay hydrated and eat small, frequent meals to manage nausea and diarrhea. · Avoid grapefruit and grapefruit juice as it may interact with this medication. |
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