Brentuximab vedotin


Concise Prescribing Info
Indications/Uses
Listed in Dosage.
Dosage/Direction for Use
Adult : IV Hodgkin’s disease In patients with previously untreated CD-30 positive cases combined with doxorubicin, vinblastine, and dacarbazine: 1.2 mg/kg over 30 minutes on days 1 and 15 for each 28-day cycle for 6 cycles. In patients with increased risk of relapsed or progression or with relapsed or refractory cases following ASCT: 1.8 mg/kg  over 30 minutes every 3 weeks. CD-30 positive cutaneous T-cell lymphoma; Systemic or relapsed anaplastic large cell lymphoma 1.8 mg/kg over 30 minutes every 3 weeks. Patient weighing >100 kg: Use 100 kg in dose calculation. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Dosage Details
Intravenous
Hodgkin's disease
Adult: In patients with previously untreated CD-30 positive cases in combination with doxorubicin, vinblastine, and dacarbazine: 1.2 mg/kg via infusion over 30 minutes on days 1 and 15 for each 28-day cycle for 6 cycles. In patients with increased risk of relapsed or progression or with relapsed or refractory cases following autologous stem cell transplant (ASCT): 1.8 mg/kg  given via infusion over 30 minutes every 3 weeks. Max: 16 cycles. Patient weighing >100 kg: Use 100 kg in dose calculation. Continue treatment until disease progression or unacceptable toxicity. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).

Intravenous
Anaplastic large cell lymphoma
Adult: In patients with relapsed or refractory cases: 1.8 mg/kg via infusion over 30 minutes every 3 weeks up. Min: 8 cycles. Max: 16 cycles. Patient weighing >100 kg: Use 100 kg in dose calculation. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).

Intravenous
CD-30 positive cutaneous T-cell lymphoma
Adult: In patient with at least 1 prior systemic therapy: 1.8 mg/kg via infusion over 30 minutes every 3 weeks. Max: 16 cycles. Patient weighing >100 kg: Use 100 kg in dose calculation. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Renal Impairment
CrCl (mL/min)  Dosage
 <30 As monotherapy: Initially, 1.2 mg/kg via infusion over 30 minutes every 3 weeks. In combination with chemotherapy: Contraindicated.
Hepatic Impairment
As monotherapy: Initially, 1.2 mg/kg via infusion over 30 minutes every 3 weeks. In combination with chemotherapy: Mild (Child-Pugh A): 0.9 mg/kg via infusion over 30 minutes every 3 weeks. Moderate to severe (Child-Pugh B or C): Contraindicated.
Reconstitution
Reconstitute vial labelled as containing 50 mg with 10.5 mL sterile water for injection to a final concentration of 5 mg/mL.
Contraindications
Severe renal and moderate or severe hepatic impairment in combination with chemotherapy. Co-administration with bleomycin. Lactation.
Special Precautions
Patient with antibodies to brentuximab vedotin; pre-existing gastrointestinal involvement of underlying lymphoma; previous therapies or underlying diseases causing immunosuppression; rapidly proliferating tumour and high tumour burden or risk factors for tumour lysis syndrome; elevated baseline liver enzymes; elevated BMI with or without history of diabetes mellitus. Mild to moderate renal and mild hepatic impairment.
Adverse Reactions
Significant: Immediate and delayed infusion-related reactions, anaphylactic reactions; tumour lysis syndrome, peripheral neuropathy (sensory and motor), haematological toxicities (e.g. Grade 3 or 4 anaemia, thrombocytopenia, prolonged neutropenia); febrile neutropenia; hyperglycaemia; increased serum transaminase levels.
Cardiac disorders: Dyspnoea, supraventricular arrhythmia.
Gastrointestinal disorders: Nausea, diarrhoea, vomiting, constipation, abdominal pain, stomatitis (combination therapy).
General disorders and admin site conditions: Fatigue, pyrexia.
Investigations: Increased ALT/AST, decreased weight.
Metabolism and nutrition disorders: Hyperglycaemia, decreased appetite (combination therapy), peripheral oedema.
Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, back pain, muscle spasms, chills.
Nervous system disorders: Headache.
Psychiatric disorders: Insomnia.
Respiratory, thoracic and mediastinal disorders: Upper respiratory tract infection, cough.
Skin and subcutaneous tissue disorders: Rash, pruritus, alopecia.
Potentially Fatal: John Cunningham virus reactivation resulting to progressive multifocal leukoencephalopathy; acute pancreatitis; pulmonary toxicity (e.g. pneumonitis, interstitial lung disease, acute respiratory distress syndrome); serious infections (e.g. pneumonia, septic shock); Stevens-Johnson syndrome, toxic epidermal necrolysis; hepatotoxicity; gastrointestinal complications (e.g. intestinal obstruction, ileus, enterocolitis, neutropenic colitis, erosion, ulcer, perforation, haemorrhage.
Patient Counseling Information
This drug may cause dizziness, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor complete CBC with differential prior to each dose; LFT and renal function. Perform pregnancy test to women of reproductive potential prior to treatment initiation. Monitor for tumour lysis syndrome; signs or symptoms of leukoencephalopathy and neuropathy, dermatologic toxicity, infusion reaction, pulmonary toxicity (e.g. cough, dyspnoea), gastrointestinal toxicity, infection.
Drug Interactions
Increased serum concentration of MMAE with strong CYP3A4 and P-gp inhibitors (e.g. ketoconazole). Decreased serum concentration of MMAE with strong CYP3A4 inducers (e.g. rifampicin). May diminish therapeutic effect of live vaccines.
Potentially Fatal: Pulmonary toxicity with bleomycin.
Action
Description: Brentuximab vedotin is an antibody drug conjugate (ADC) which binds to CD30-expressing tumour cells. It forms a complex which is internalised within the cells and releases monomethylauristatin E (MMAE) via proteolytic cleavage. MMAE binds to tubules and disrupts microtubule network thereby inducing cell cycle arrest and apoptotic death of CD30-expressing tumour cells.
Pharmacokinetics:
Absorption: Time to peak plasma concentration: At the end of infusion (ADC); approx 1-3 days after the end of infusion (MMAE).
Distribution: Volume of distribution: Approx 6-10 L (ADC). Plasma protein binding: 68-82% (MMAE).
Metabolism: Metabolised primarily via oxidation by CYP3A4/5 (small fraction of MMAE).
Excretion: Via faeces (approx 72% as MMAE); urine (approx 24% as MMAE). Elimination half-life: Approx 4-6 days (ADC); approx 3-4 days (MMAE).
Storage
Store between 2-8°C. Do not freeze. Protect from light.
ATC Classification
L01XC12 - brentuximab vedotin ; Belongs to the class of monoclonal antibodies, other antineoplastic agents. Used in the treatment of cancer.
References
Adcetris Lyophilized Powder for Solution (Seattle Genetics, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 04/06/2019.

Anon. Brentuximab Vedotin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 04/06/2019.

Brentuximab Vedotin. Drugs and Lactation Database (LactMed) [Internet]. Bethesda, MD. U.S. National Library of Medicine. https://www.ncbi.nlm.nih.gov/books/NBK501922/. Accessed 20/06/2019.

Buckingham R (ed). Brentuximab Vedotin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/06/2019.

Joint Formulary Committee. Brentuximab Vedotin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 13/06/2019.

Disclaimer: This information is independently developed by MIMS based on Brentuximab vedotin from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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