mirvetuximab soravtansine

Absorption: IV administration results in complete bioavailability.

Distribution: Minimally distributed to tissues.

Protein Binding: >99%.

Metabolism/Excretion: The monoclonal antibody portion (mirvetuximab soravtansine) is broken down into small peptides by catabolic pathways. Unconjugated DM4 and its metabolite, S-methyl-DM4, are metabolized by the liver via the CYP3A4 isoenzyme. S-methyl DM4 and DM4-sulfo-SPDB-lysine are the main metabolites detected in urine.

Half-Life: Mirvetuximab soravtansine: 4.8 days; Unconjugated DM4: 2.8 days; S-methyl-DM4: 5 days.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion‡; 2 days after administration*; 3 days after administration‡	unknown

‡Mirvetuximab soravtansine; * Unconjugated DM4; ‡ S-methyl-DM4.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Moderate or severe hepatic impairment;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Severe renal impairment or end-stage kidney disease;
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

EENT: blurred vision, cataract, corneal disorders, dry eye, eye pain, photophobia, visual impairment, uveitis

F and E: hypokalemia, hypomagnesemia

GI: abdominal distension, abdominal pain, constipation, diarrhea, hypoalbuminemia, ↑liver enzymes, nausea, vomiting

GU: ↑serum creatinine

Hemat: anemia, leukopenia, lymphocytopenia, neutropenia, thrombocytopenia

Metab: ↓appetite

MS: arthralgia, myalgia

Neuro: fatigue, peripheral neuropathy

Resp: dyspnea, interstitial lung disease

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inhibitors may ↑ DM4 levels and the risk of toxicity.

Route/Dosage ⬆ ⬇

Adjusted body weight = Ideal body weight (kg) + 0.4 * (Actual body weight [kg] — ideal body weight [kg])

IV (Adults ): 6 mg/kg (based on adjusted body weight) every 3 wk; continue until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Solution for injection: 5 mg/mL

Assessment ⬆ ⬇

Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of therapy, every other cycle for the 1st 8 cycles, and as clinically indicated thereafter. Monitor for severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis. If superficial keratitis, a cornea epithelial defect, or 3-line or more loss in best corrected visual acuity occurs: Withhold dose until improved or resolved; then maintain at same dose level or consider dose ↓ (see Implementation). If corneal ulcer or stromal opacity or best corrected distance visual acuity 20/200 or worse occurs: Withhold dose until improved or resolved; then ↓ by one dose level (see Implementation). If corneal perforation occurs: Permanently discontinue mirvetuximab soravtansine. If uveitis (Grade 2/1 to 2+ cell or flare in anterior chamber) occurs: Withhold dose until Grade ≤1; then maintain dose at same dose level. If uveitis (Grade 3/3+ cell or flare in anterior chamber) occurs: Withhold dose until Grade ≤1; then ↓ by one dose level (see Implementation). If uveitis (Grade 4/hypopyon) occurs: Permanently discontinue mirvetuximab soravtansine.
Monitor for signs/symptoms of pneumonitis (dyspnea, cough, hypoxia, fever). CT scan or chest x-ray should be done prior to and periodically during therapy to monitor lung status. If Grade 2 pneumonitis occurs: Hold dose until Grade ≤1; then maintain at same dose level or consider dose ↓ (see Implementation). If Grade 3 or 4 pneumonitis occurs: Permanently discontinue mirvetuximab soravtansine.
Monitor for signs/symptoms of peripheral neuropathy (paresthesia, tingling or burning sensations, neuropathic pain, muscle weakness, dysesthesia). If Grade 2 peripheral neuropathy occurs: Hold dose until Grade ≤1; then ↓ by one dose level (see Implementation). If Grade 3 or 4 peripheral neuropathy occurs: Permanently discontinue mirvetuximab soravtansine.
Monitor for signs/symptoms of infusion-related reactions (fever, chills, sweating, myalgia, headache, dizziness, nausea, vomiting, urticaria, pruritus, shortness of breath, wheezing ) during and within 24 hr of infusion. Always use pretreatment therapy (acetaminophen, steroids, antihistamines, IV fluids, and/or oxygen therapy). If Grade 1 infusion-related reaction occurs: Maintain infusion rate. If Grade 2 infusion-related reaction occurs: Interrupt infusion and administer supportive care; after recovery from symptoms, resume the infusion at 50% of the previous rate, and if no further symptoms appear, ↑ rate as appropriate until infusion is completed; administer additional premedication for future cycles. If Grade 3 or 4 infusion-related reaction occurs: Immediately stop infusion and administer supportive treatment; permanently discontinue mirvetuximab soravtansine.

Lab Test Considerations:

Verify negative pregnancy status before initiating therapy.
May cause hypokalemia and hypomagnesemia.
May ↑ liver enzymes.

Implementation ⬆ ⬇

Premedication: Administer a corticosteroid IV (dexamethasone 10 mg or equivalent), antihistamine PO/IV (diphenhydramine 25–50 mg), and an antipyretic PO/IV (acetaminophen 325–650 mg) ≥30 min prior to each infusion and an antiemetic PO/IV (5-HT₃ serotonin receptor antagonist or appropriate alternative) before each dose and thereafter as necessary; consider additional premedications, including corticosteroids, the day prior to administration in patients who have experienced infusion-related reactions.
Ophthalmic Premedication: Instill 1 drop of topical ophthalmic steroid in each eye 6 times daily starting the day prior to each infusion until Day 4; then administer 1 drop in each eye 4 times daily for Days 5–8 of each cycle; Instill lubricating eye drop at least 4 times daily and as needed during treatment; wait ≥10 min after ophthalmic topical steroid administration before instilling lubricating eye drops.
Dose Reduction Recommendations:1st dose ↓: 5 mg/kg adjusted body weight every 3 wk (21-day cycle). 2nd dose ↓: 4 mg/kg adjusted body weight every 3 wk (21-day cycle). Permanently discontinue mirvetuximab soravtansine in patients who cannot tolerate 4 mg/kg dose.

IV Administration:

Use double gloves and a protective gown to prepare and administer. If possible, prepare in a biological safety cabinet or a compounding aseptic containment isolator; eye, face, and respiratory protection may be needed. Prepare and administer in a closed-system drug transfer device. During administration, if there is a potential that the substance could splash or if the patient may resist, use eye and face protection. Discard IV equipment in specially designated containers.
Intermittent Infusion: Calculate the dose based on the patient’s adjusted body weight (see Route/Dosage), total volume of solution required, and the number of vials needed (>1 vial will be needed for a full dose). Diluent: Allow vials to warm to room temperature. Gently swirl (do not shake) and inspect each vial for particulate matter and discoloration prior to withdrawal of solution; should be clear to slightly opalescent, colorless. Determine the volume of D5W required to achieve the final diluted drug concentration. Either remove excess D5W from a prefilled IV bag or add the calculated volume of D5W to a sterile empty IV bag. Then add the calculated dose volume of mirvetuximab soravtansine to the bag. Discard unused remaining drug in vials. Gently mix the diluted drug solution by slowly inverting the bag several times to assure uniform mixing. Do not shake or agitate. Use within 8 hr if stored at room temperature or 12 hr if refrigerated. Concentration: 1–2 mg/mL. Rate: Using a 0.2- or 0.22-mcm polyethersulfone in-line filter, infuse the initial dose at 1 mg/min. If well tolerated after 30 min, ↑ infusion rate to 3 mg/min. If well tolerated after 30 min, ↑ infusion rate to 5 mg/min. If no infusion-related reactions occur with the previous dose, subsequent infusions should be started at the maximally tolerated rate and may be ↑ up to a maximum infusion rate of 5 mg/min, as tolerated. Following the infusion, flush the IV line with D5W to ensure delivery of the full dose.
Y-Site Incompatibility:
- Do not administer other drugs through same IV line

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy.
Emphasize importance of regular follow-ups and eye exams.
Advise patient to immediately report any visual changes and to use lubricating and ophthalmic steroid eye drops during therapy. Tell patient to avoid use of contact lenses during treatment unless directed by a health care provider.
Advise patients and family to call 911 and immediately seek treatment for signs and symptoms of hypersensitivity reactions.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Rep: May cause fetal harm. Advise patient to notify health care provider if pregnancy is suspected and to avoid breastfeeding during therapy. Advise women of reproductive potential to use effective contraception during and for 7 mo after the last dose.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇