Brentuximab vedotin
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS [see Warnings and Precautions (5.9) , Adverse Reactions (6.1) ] . WARNING: PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML) See full prescribing information for complete boxed warning. JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS ( 5.9 , 6.1 ).
Handling and access
NIOSH hazardous drug
Table 1NIOSH lists brentuximab vedotin as a hazardous drug. AHFS class: 10:00 antineoplastic agents.
- The package insert includes manufacturer's special handling information (MSHI). Follow it when preparing, administering, and disposing of this drug.
- Biologic (Biologics License Application).
Handle with the precautions your facility uses for hazardous drugs (USP <800>). NIOSH's Managing Hazardous Drug Exposures lists controls by drug form and activity.
CD30-directed Immunoconjugate
Dosing in kidney impairment
Recommended Dosage in Patients with Renal Impairment No dosage adjustment is required for mild renal impairment (CrCL greater than 50‑80 mL/min) and moderate renal impairment (CrCL 30-50 mL/min). Avoid use in patients with severe (CrCL less than 30 mL/min) renal impairment [see Warnings and Precautions ] .
Dosing in liver impairment
Recommended Dosage in Patients with Hepatic Impairment Adult patients with previously untreated Stage III or IV classical Hodgkin lymphoma Reduce the dosage of ADCETRIS to 0.9 mg/kg up to a maximum of 90 mg every 2 weeks for patients with mild hepatic impairment (Child-Pugh A). Avoid use in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment [see Warnings and Precautions ] .
Adult patients with relapsed or refractory LBCL Reduce the dosage of ADCETRIS to 0.9 mg/kg up to a maximum of 90 mg every 3 weeks for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal [ULN] and aspartate transaminase [AST] > ULN, or total bilirubin >1 to 1.5 × ULN and any AST). Avoid use in patients with moderate and severe hepatic impairment (total bilirubin >1.5 × ULN) [see Warnings and Precautions ] .
Hepatic impairment is defined per the National Cancer Institute Organ Dysfunction Working Group. All other indications Reduce the dosage of ADCETRIS to 1.2 mg/kg up to a maximum of 120 mg every 3 weeks for patients with mild hepatic impairment (Child-Pugh A). Avoid use in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment [see Warnings and Precautions ] .
Preparation and administration
Prepare this dose
Your numbers for brentuximab vedotin. Take vial strength, diluent, and limits from the label below.
Enter a dose to see draw volume, final concentration, and rates.
Instructions for Preparation and Administration Administration
Administer ADCETRIS as an intravenous infusion only.
Do not mix ADCETRIS with, or administer as an infusion with, other medicinal products. Reconstitution
Follow procedures for proper handling and disposal of hazardous drugs 1 .
Use appropriate aseptic technique for reconstitution and preparation of dosing solutions.
Determine the number of 50 mg vials needed based on the patient’s weight and the prescribed dose [see Dosage and Administration ].
Reconstitute each 50 mg vial of ADCETRIS with 10.5 mL of Sterile Water for Injection to yield a single-dose solution containing 5 mg/mL brentuximab vedotin.
Direct the stream toward the wall of vial and not directly at the cake or powder.
Gently swirl the vial to aid dissolution. DO NOT SHAKE .
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The reconstituted solution should be clear to slightly opalescent, colorless, and free of visible particulates.
Following reconstitution, dilute immediately into an infusion bag. If not diluted immediately, store the solution refrigerated at 2°C to 8°C (36°F to 46°F) and use within 24 hours of reconstitution. DO NOT FREEZE.
Discard any unused portion left in the vial. Dilution
Calculate the required volume of 5 mg/mL reconstituted ADCETRIS solution needed.
Withdraw this amount from the vial and immediately add it to an infusion bag containing 0.9% Sodium Chloride Injection, USP, 5% Dextrose Injection or Lactated Ringer's Injection to achieve a final concentration of 0.4 mg/mL to 1.8 mg/mL brentuximab vedotin.
Gently invert the bag to mix the solution.
Following dilution, infuse the ADCETRIS solution immediately. If not used immediately, store the solution refrigerated at 2°C to 8°C (36°F to 46°F) and use within 24 hours of reconstitution. DO NOT FREEZE.
Drug interactions
Check brentuximab vedotin against a medication listLabel text (2 paragraphs)
Concomitant use of strong CYP3A4 inhibitors or inducers has the potential to affect the exposure to monomethyl auristatin E (MMAE) ( 7.1 ).
7.1 Effect of Other Drugs on ADCETRIS CYP3A4 Inhibitors: Co-administration of ADCETRIS with ketoconazole, a potent CYP3A4 inhibitor, increased exposure to MMAE [see Clinical Pharmacology (12.3) ], which may increase the risk of adverse reaction. Closely monitor adverse reactions when ADCETRIS is given concomitantly with strong CYP3A4 inhibitors.
Contraindications
4 CONTRAINDICATIONS ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation) [see Adverse Reactions (6.1) ] . Concomitant use with bleomycin due to pulmonary toxicity (4) .
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
BLikelihood score B: Likely cause of clinically apparent liver injury.
Brentuximab vedotin is a chimeric mouse-human monoclonal antibody to CD30 conjugated to a microtubule inhibitor, which is used in the therapy of Hodgkin lymphoma and anaplastic large cell lymphoma. Brentuximab vedotin has been linked to mild and transient serum enzyme elevations during therapy, but has not been implicated in cases of clinically apparent acute liver injury.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary ADCETRIS can cause fetal harm based on the findings from animal studies and the drug’s mechanism of action [see Clinical Pharmacology (12.1) ] . In animal reproduction studies, administration of brentuximab vedotin to pregnant rats during organogenesis at doses similar to the clinical dose of 1.8 mg/kg every three weeks caused embryo-fetal toxicities, including congenital malformations (see Data ). The available data from case reports on ADCETRIS use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. Advise a pregnant woman of the potential risk to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Data Animal Data In an embryo-fetal developmental study, pregnant rats received 2 intravenous doses of 0.3, 1, 3, or 10 mg/kg brentuximab vedotin during the period of organogenesis (once each on Pregnancy Days 6 and 13).
Drug-induced embryo-fetal toxicities were seen mainly in animals treated with 3 and 10 mg/kg of the drug and included increased early resorption (≥99%), post-implantation loss (≥99%), decreased numbers of live fetuses, and external malformations (i.e., umbilical hernias and malrotated hindlimbs). Systemic exposure in animals at the brentuximab vedotin dose of 3 mg/kg is approximately the same exposure in patients with cHL or sALCL who received the recommended dose of 1.8 mg/kg every three weeks.
Breastfeeding (LactMed)
No information is available on the clinical use of brentuximab vedotin during breastfeeding. Because brentuximab is a large protein molecule with a molecular weight of about 153,000 Da, the amount in milk is likely to be very low. It is also likely to be partially destroyed in the infant's gastrointestinal tract and absorption by the infant is probably minimal. Vedotin (monomethyl auristatin E) is a small-molecule anticancer drug that might enter milk and be absorbed by the infant. The manufacturer recommends that breastfeeding be discontinued during brentuximab vedotin therapy.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
Not the price at the counterThese are not what a patient pays at the pharmacy counter. They are what pharmacies, health plans, and government buyers pay, before manufacturer rebates. A patient's cost depends on their insurance (copay, coinsurance, or deductible) or the pharmacy's cash price.