Adcetris Brentuximab Vedotin Powder for Injection

1. Indications and Usage
Classic Hodgkin Lymphoma (cHL):
Indicated for the treatment of adult patients with cHL who have relapsed after autologous stem cell transplant (ASCT) or after at least two prior chemotherapy regimens.
Systemic Anaplastic Large Cell Lymphoma (sALCL):
Indicated for the treatment of adult patients with sALCL who have relapsed after at least one prior multi-agent chemotherapy regimen.
Other Indications:
Includes treatment with chemotherapy for previously untreated stage III/IV cHL and consolidation after ASCT.
2. Dosage and Administration
Recommended Dosage:
Standard Dose: 1.8 mg/kg (up to a maximum of 180 mg) administered intravenously once every 3 weeks.
Administration Instructions:
Reconstitution: Reconstitute each 50 mg vial with 10.5 mL of Sterile Water for Injection. The final concentration is 5 mg/mL. Do not shake.
Dilution: Dilute the reconstituted solution into an intravenous bag containing 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or Ringer’s Injection.
Infusion: Administer as an intravenous infusion over 30 minutes. Do not administer as an intravenous push or bolus.
3. Mechanism of Action
Antibody-Drug Conjugate (ADC):
Brentuximab vedotin is an ADC composed of a chimeric IgG1 antibody directed against CD30, linked to the microtubule-disrupting agent monomethyl auristatin E (MMAE).
Physiological Effect:
The antibody targets and binds to CD30 on the surface of tumor cells. The ADC-MMAE complex is internalized, and MMAE is released via intracellular proteolytic cleavage. MMAE binds to tubulin, disrupting the microtubule network, which induces cell cycle arrest and apoptosis.
4. Safety and Warnings
Progressive Multifocal Leukoencephalopathy (PML):
PML and death have occurred in patients treated with brentuximab vedotin. Monitor patients for clinical signs and symptoms; interrupt treatment if PML is suspected.
Peripheral Neuropathy:
Sensory and motor neuropathy may occur. Monitor patients for numbness or tingling. Adjust dose or interrupt treatment for worsening neuropathy.
Serious Infections:
May cause serious bacterial, fungal, or viral infections. Monitor for signs of infection.

Pulmonary Toxicity:
Non-infectious pulmonary toxicity, including pneumonitis and interstitial lung disease, has been reported.
Fatal Interaction with Bleomycin:
Do not use brentuximab vedotin in combination with bleomycin due to an increased risk of fatal pulmonary toxicity.
5. Adverse Reactions
Most Common:
Peripheral sensory neuropathy, neutropenia, fatigue, nausea, diarrhea, upper respiratory tract infection, pyrexia, cough, rash, headache, and arthralgia.
6. Drug Interactions
P-gp Substrates:
MMAE is a P-gp substrate. Co-administration with P-gp inhibitors may increase plasma concentrations of MMAE.
Strong CYP3A Inhibitors/Inducers:
Co-administration with strong CYP3A inhibitors (e.g., ketoconazole) may increase MMAE exposure; strong CYP3A inducers (e.g., rifampin) may decrease exposure.
7. Pharmaceutical Information
Storage:
Store in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze.