Brentuximab vedotin

What is Brentuximab vedotin?

• Brentuximab vedotin (Adcetris) is a CD30-directed antibody-drug conjugate used for the treatment of classical Hodgkin lymphoma (cHL),systemic anaplastic large cell lymphoma, peripheral T-cell lymphomas (PTCL), primary cutaneous anaplastic large cell lymphoma (pcALCL).

What are the uses of this medicine?

This medicine is used:

• for the treatment of adult patients with previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine.
• for the treatment of adult patients with classical Hodgkin lymphoma (cHL) at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation.
• for the treatment of adult patients with classical Hodgkin lymphoma (cHL) after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates.
• for the treatment of adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone.
• for the treatment of adult patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen.
• for the treatment of adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing MF who have received prior systemic therapy.

How does this medicine work?

• Brentuximab vedotin is an ADC.
• The antibody is a chimeric IgG1 directed against CD30.
• The small molecule, MMAE, is a microtubule-disrupting agent.
• MMAE is covalently attached to the antibody via a linker.
• Nonclinical data suggest that the anticancer activity of Adcetris is due to the binding of the ADC to CD30-expressing cells, followed by internalization of the ADC‑CD30 complex, and the release of MMAE via proteolytic cleavage.
• Binding of MMAE to tubulin disrupts the microtubule network within the cell, subsequently inducing cell cycle arrest and apoptotic death of the cells.
• Additionally, in vitro data provide evidence for antibody-dependent cellular phagocytosis (ADCP).

Who Should Not Use this medicine ?

This medicine cannot be used in patients who:

• use bleomycin

What drug interactions can this medicine cause?

• Co-administration of Adcetris with ketoconazole, a potent CYP3A4 inhibitor may increase the risk of adverse reaction. Closely monitor adverse reactions when Adcetris is given concomitantly with strong CYP3A4 inhibitors.

Is this medicine FDA approved?

• Initial U.S. approval: 2011

How should this medicine be used?

Recommended dosage:

• The recommended dose as monotherapy is 1.8 mg/kg up to a maximum of 180 mg every 3 weeks.
• The recommended dose in combination with chemotherapy for previously untreated Stage III or IV cHL is 1.2 mg/kg up to a maximum of 120 mg every 2 weeks for a maximum of 12 doses.
• The recommended dose in combination with chemotherapy for previously untreated PTCL is 1.8 mg/kg up to a maximum of 180 mg every 3 weeks for 6 to 8 doses.
• Reduce dose in patients with mild hepatic impairment.

Administration:

• Administer Adcetris as an intravenous infusion only.
• Do not mix Adcetris with, or administer as an infusion with, other medicinal products.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As injection: 50 mg lyophilized powder in a single-dose vial

This medicine is available in fallowing brand namesː

• Adcetris

What side effects can this medication cause?

The most common side effects of this medicine include:

• peripheral neuropathy
• fatigue
• nausea
• diarrhea
• neutropenia
• upper respiratory tract infection
• pyrexia
• constipation
• vomiting
• alopecia
• decreased weight
• abdominal pain
• anemia
• stomatitis
• lymphopenia
• mucositis

What special precautions should I follow?

• Adcetris treatment causes a peripheral neuropathy that is predominantly sensory. Monitor patients for neuropathy and institute dose modifications accordingly.
• Infusion-related reactions, including anaphylaxis, have occurred with Adcetris. If an infusion reaction occurs, interrupt the infusion. If anaphylaxis occurs, immediately discontinue the infusion.
• Fatal and serious cases of febrile neutropenia have been reported with Adcetris. Monitor complete blood counts. Monitor for signs of infection. Manage using dose delays and growth factor support.
• Serious infections and opportunistic infections such as pneumonia, bacteremia, and sepsis or septic shock (including fatal outcomes) have been reported in patients treated with Adcetris. Closely monitor patients for the emergence of bacterial, fungal or viral infections.
• Patients with rapidly proliferating tumor and high tumor burden may be at increased risk of tumor lysis syndrome. Closely monitor patients with rapidly proliferating tumor or high tumor burden.
• The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment compared to patients with normal renal function. Avoid the use of Adcetris in patients with severe renal impairment [creatinine clearance (CrCL) <30 mL/min].
• Avoid the use of Adcetris in patients with moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment.
• Fatal and serious cases of hepatotoxicity have occurred in patients receiving Adcetris. Monitor liver enzymes and bilirubin.
• Fatal cases of JC virus infection resulting in PML have been reported in Adcetris-treated patients. Monitor patients for new or worsening symptoms.
• Fatal and serious events of noninfectious pulmonary toxicity including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome (ARDS), have been reported.
• Fatal and serious events of acute pancreatitis have been reported.
• Serious events of hyperglycemia, such as new-onset hyperglycemia, exacerbation of pre-existing diabetes mellitus, and ketoacidosis (including fatal outcomes) have been reported in Adcetris-treated patients. Monitor patients for new or worsening hyperglycemia. Manage with anti-hyperglycemic medications as clinically indicated.
• Based on the mechanism of action and findings in animals, Adcetris can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of Adcetris in pregnant women. Advise females of reproductive potential of the potential risk to a fetus and to avoid pregnancy.

What to do in case of emergency/overdose?

Management of overdosage:

• There is no known antidote for overdosage of Adcetris.
• In case of overdosage, the patient should be closely monitored for adverse reactions, particularly neutropenia, and supportive treatment should be administered.

Can this medicine be used in pregnancy?

• Based on the mechanism of action and findings in animals, Adcetris can cause fetal harm when administered to a pregnant woman.
• There are no adequate and well-controlled studies of Adcetris in pregnant women.

Can this medicine be used in children?

• Safety and effectiveness of Adcetris have not been established in pediatric patients.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• Brentuximab Vedotin

Inactive ingredients:

• Trehalose Dihydrate
• Trisodium Citrate Dihydrate
• Citric Acid Monohydrate
• Polysorbate 80

Who manufactures and distributes this medicine?

Manufactured by: Seagen Inc. Bothell, WA

What should I know about storage and disposal of this medication?

• Store vial at 2–8°C (36–46°F) in the original carton to protect from light.

Handling

• Adcetris is an antineoplastic product. Follow special handling and disposal procedures.

• Dailymed label info on Brentuximab vedotin
• FDA Brentuximab vedotin

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