ELAHERE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ELAHERE (ELAHERE).
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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ELAHERE (ELAHERE).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Due to potential for serious adverse reactions (e.g., myelosuppression, neurotoxicity) in nursing infants, advise not to breastfeed during treatment and for at least 1 week after the last dose. M/P ratio unknown. |
| 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. |
■ 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 |
["Known severe hypersensitivity to mirvetuximab soravtansine or any of its components","Use in patients with platinum-sensitive disease as safety and efficacy not established and increased risk of serious adverse events"]
| 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."] |
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| 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. |