Brentuximab Vedotin

REMS

Classical Hodgkin lymphoma (cHL) in patients who have failed autologous hematopoietic stem cell transplant (auto-HSCT) or who have failed ≥2 prior multi-agent chemotherapies and are not candidates for auto-HSCT.
Previously untreated, high-risk cHL (in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide).
cHL in patients who are at high risk of relapse or progression as post-auto-HSCT consolidation.
Previously untreated stage III or IV cHL (in combination with doxorubicin, vinblastine, and dacarbazine).
Systemic anaplastic large cell lymphoma after failure of ≥1 multi-agent chemotherapy regimen.
Primary cutaneous anaplastic large cell lymphoma or CD30expressing mycosis fungoides in patients who have received prior systemic therapy.
Previously untreated systemic anaplastic large cell lymphoma or other CD30–expressing peripheral T-cell lymphoma (in combination with cyclophosphamide, doxorubicin, and prednisone).

Contraindicated in:

Concurrent use of bleomycin (↑ risk of pulmonary toxicity)
Severe renal impairment (CCr <30 mL/min)
Moderate or severe hepatic impairment
OB: Pregnancy
Lactation: Lactation.

Use Cautiously in:

Preexisting GI involvement (↑ risk of GI perforation)
High BMI or diabetes (↑ risk of hyperglycemia)
Rep: Women of reproductive potential and males with female partners of reproductive potential
Pedi: Children <2 yr (safety and effectiveness not established).

CV: peripheral edema.

Derm: alopecia, night sweats, pruritus, rash, stevens-johnson syndrome, toxic epidermal necrolysis, dry skin.

Endo: hyperglycemia.

F and E: KETOACIDOSIS.

GI: ↓ appetite, abdominal pain, bowel obstruction, constipation, diarrhea, gi hemorrhage, gi perforation, gi ulcer, hepatotoxicity, ileus, nausea, pancreatitis, vomiting, ENTEROCOLITIS, NEUTROPENIC COLITIS, ulcer.

GU: ↓ fertility.

Hemat: anemia, neutropenia, thrombocytopenia.

Metab: weight loss.

MS: arthralgia, back pain, extremity pain, myalgia, muscle spasm.

Neuro: anxiety, dizziness, fatigue, headache, insomnia, peripheral neuropathy, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML).

Resp: acute respiratory distress syndrome, cough, dyspnea, interstitial lung disease, oropharyngeal pain.

Misc: fever, lymphadenopathy, chills, INFUSION REACTIONS (INCLUDING ANAPHYLAXIS), TUMOR LYSIS SYNDROME.

Drug-Drug:

MMAE is both a substrate and inhibitor of the CYP3A4/5 enzyme system.
Bleomycin may ↑ risk of pulmonary toxicity; concurrent use contraindicated.
Strong CYP3A4 inhibitors, including ketoconazole may ↑ levels and risk of adverse reactions.
Strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness.

Lyophilized powder for injection: 50 mg/vial;

Relapsed Classical Hodgkin Lymphoma or Relapsed Systemic Anaplastic Large Cell Lymphoma

IV (Adults): 1.8 mg/kg (max dose = 180 mg) every 3 wk until disease progression or unacceptable toxicity.

Renal Impairment

IV (Adults): CCr <30 mL/min: Avoid use.

Hepatic Impairment

IV (Adults): Mild (Child-Pugh A): 1.2 mg/kg (max dose = 120 mg) every 3 wk until disease progression or unacceptable toxicity; Moderate (Child-Pugh B) or severe (Child-Pugh C): Avoid use.

Previously Untreated, High-Risk Classical Hodgkin Lymphoma

IV (Children ≥2 yr): 1.8 mg/kg (max dose = 180 mg) every 3 wk until a maximum of 5 doses completed.

Renal Impairment

IV (Children ≥2 yr): CCr <30 mL/min: Avoid use.

Hepatic Impairment

IV (Children ≥2 yr): Mild (Child-Pugh A): 1.2 mg/kg (max dose = 120 mg) every 3 wk until a maximum of 5 doses completed; Moderate (Child-Pugh B) or severe (Child-Pugh C): Avoid use.

Classical Hodgkin Lymphoma Consolidation

IV (Adults): 1.8 mg/kg (max dose = 180 mg) every 3 wk until a maximum of 16 cycles completed, disease progression, or unacceptable toxicity. Initiate therapy within 4–6 wk post-auto-HSCT or upon recovery of auto-HSCT.

Renal Impairment

IV (Adults): CCr <30 mL/min: Avoid use.

Hepatic Impairment

IV (Adults): Mild (Child-Pugh A): 1.2 mg/kg (max dose = 120 mg) every 3 wk until a maximum of 16 cycles completed, disease progression or unacceptable toxicity; Moderate (Child-Pugh B) or severe (Child-Pugh C): Avoid use.

Previously Untreated Stage III or IV Classical Hodgkin Lymphoma

IV (Adults): 1.2 mg/kg (max dose = 120 mg) every 2 wk until a maximum of 12 doses completed, disease progression or unacceptable toxicity.

Renal Impairment

IV (Adults): CCr <30 mL/min: Avoid use.

Hepatic Impairment

IV (Adults): Mild (Child-Pugh A): 0.9 mg/kg (max dose = 90 mg) every 2 wk until a maximum of 12 doses completed, disease progression or unacceptable toxicity; Moderate (Child-Pugh B) or severe (Child-Pugh C): Avoid use.

Relapsed Primary Cutaneous Anaplastic Large Cell Lymphoma or CD-30 Expressing Mycosis Fungoides

IV (Adults): 1.8 mg/kg (max dose = 180 mg) every 3 wk until a maximum of 16 cycles completed, disease progression, or unacceptable toxicity.

Renal Impairment

IV (Adults): CCr <30 mL/min: Avoid use.

Hepatic Impairment

IV (Adults): Mild (Child-Pugh A): 1.2 mg/kg (max dose = 120 mg) every 3 wk until a maximum of 16 cycles completed, disease progression, or unacceptable toxicity; Moderate (Child-Pugh B) or severe (Child-Pugh C): Avoid use.

Previously Untreated Systemic Anaplastic Large Cell Lymphoma or Other CD-30 Expressing Peripheral T-Cell Lymphomas

IV (Adults): 1.8 mg/kg (max dose = 180 mg) every 3 wk with each cycle of chemotherapy for 6–8 doses.

Renal Impairment

IV (Adults): CCr <30 mL/min: Avoid use.

Hepatic Impairment

IV (Adults): Mild (Child-Pugh A): 1.2 mg/kg (max dose = 120 mg) every 3 wk with each cycle of chemotherapy for 6–8 doses; Moderate (Child-Pugh B) or severe (Child-Pugh C): Avoid use.

An antibody-drug conjugate made up three parts: an antibody specific for human CD30 (cAC10, a cell membrane protein of the tumor necrosis factor receptor), a microtubule disrupting agent monomethyl auristatin (MMAE), and a protease-cleavable linker that attaches MMAE covalently to cAC10. The combination disrupts the intracellular microtubule network causing cell-cycle arrest and apoptotic cellular death.

Therapeutic Effects:

Decreased spread of lymphoma.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: drug-antibody conjugates

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Small amounts of MMAE that are released are metabolized by the liver and eliminated mostly by the kidneys.

Half-life: ADC: 4–6 days.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV (ADC)	unknown	end of infusion	3 wk
IV (MMAE)	unknown	1–3 days	3 wk

Instruct patient to notify health care professional of any numbness or tingling of hands or feet or any muscle weakness.
Advise patient to notify health care professional immediately if signs and symptoms of infection (fever of ≥100.5°F, chills, cough, pain on urination), hepatotoxicity (fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice), PML (changes in mood or usual behavior, confusion, thinking problems, loss of memory, changes in vision, speech, or walking, decreased strength or weakness on one side of body), pulmonary toxicity, GI complications or pancreatitis (abdominal pain, nausea, vomiting, diarrhea, rash), or infusion reactions (fever, chills, rash, breathing problems within 24 hr of infusion) occur.
Educate patient about signs and symptoms of hyperglycemia (blurred vision; drowsiness; dry mouth; flushed, dry skin; fruit-like breath odor; increased urination; ketones in urine; loss of appetite; stomachache; nausea or vomiting; tiredness; rapid, deep breathing; unusual thirst; unconsciousness). Advise patient to notify health care professional if symptoms occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: May cause fetal harm. Advise females of reproductive potential and males with a partner of reproductive potential to use effective contraception during therapy and for at least 6 mo after last dose and to avoid breast feeding during therapy. If pregnancy is suspected, notify health care professional promptly. Inform male patients therapy may impair fertility.

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Indications ⬇

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US Brand Names ⬆ ⬇

Action ⬆ ⬇

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Pharmacokinetics ⬆ ⬇

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Patient/Family Teaching ⬆ ⬇

Pronunciation ⬆