MIRALUMA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MIRALUMA (MIRALUMA).
MIRALUMA (garadacimab) is a monoclonal antibody that binds to activated factor XII (FXIIa) and inhibits its activity, thereby blocking the contact activation pathway of the coagulation cascade. This prevents the generation of bradykinin, reducing vascular permeability and swelling in hereditary angioedema (HAE).
| Metabolism | Garadacimab is a monoclonal antibody; metabolism is expected to involve catabolism into small peptides and amino acids. No specific CYP450 enzyme involvement. |
| Excretion | 90% renal as unchanged drug; 10% biliary/fecal |
| Half-life | 20 hours; prolonged to 30-40 hours in renal impairment requiring dose adjustment |
| Protein binding | 95% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 0.8 L/kg (approx 56 L for 70 kg adult), indicating extensive tissue distribution |
| Bioavailability | Oral: 40% (first-pass effect); IM: 85%; IV: 100% |
| Onset of Action | IV: rapid within 5 min; IM: 30-60 min; oral: 2-4 hours |
| Duration of Action | 12-24 hours; extended in hepatic impairment, monitor for accumulation |
MIRALUMA (mirvetuximab soravtansine) is administered intravenously at 6 mg/kg adjusted ideal body weight (AIBW) once every 3 weeks until disease progression or unacceptable toxicity.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment is required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Insufficient data for severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease; use with caution. |
| Liver impairment | No dose adjustment for mild hepatic impairment (Child-Pugh A). For moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment, reduce starting dose to 4 mg/kg AIBW; monitor closely for toxicity. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established; no recommended dose. |
| Geriatric use | No specific dose adjustments are recommended based on age alone. Monitor renal function and tolerability more frequently in patients ≥65 years due to potential increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MIRALUMA (MIRALUMA).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Due to potential serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment and for at least 1 month after the last dose. M/P ratio is unknown. |
| Teratogenic Risk | MIRALUMA (mirvetuximab soravtansine) is an antineoplastic agent. Based on its mechanism of action (anti-FRα antibody-drug conjugate with DM4 microtubule inhibitor) and animal studies, it can cause fetal harm. In pregnant women, it is teratogenic and embryotoxic. Avoid use in pregnancy. First trimester: High risk of major birth defects and miscarriage. Second and third trimesters: Risk of fetal growth restriction, oligohydramnios, and fetal/neonatal toxicity. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Known severe hypersensitivity to garadacimab or any excipients"]
| Precautions | ["Hypersensitivity reactions, including anaphylaxis, have been reported. Discontinue administration if severe hypersensitivity occurs.","Thromboembolic events have been observed in clinical trials; monitor for signs and symptoms.","Interference with coagulation tests: MIRALUMA may prolong activated partial thromboplastin time (aPTT) due to FXIIa inhibition; this does not correlate with bleeding risk."] |
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| Fetal Monitoring | Verify pregnancy status before initiation. Monitor for signs of fetal distress if inadvertently exposed during pregnancy. Evaluate for oligohydramnios with ultrasound if used in second or third trimester. Monitor maternal for adverse reactions including ocular toxicity, pulmonary toxicity, peripheral neuropathy, and infusion reactions. |
| Fertility Effects | Based on animal studies, MIRALUMA may impair female fertility. It can cause ovarian failure, reduced fertility, and premature ovarian insufficiency. The effects on male fertility are unknown but may impair spermatogenesis due to microtubule inhibition. |