brentuximab vedotin

High Alert

Classical Hodgkin lymphoma in patients who have failed autologous hematopoietic stem cell transplant or who have failed ≥2 prior multiagent chemotherapies and are not candidates for autologous hematopoietic stem cell transplant.
Previously untreated, high-risk classical Hodgkin lymphoma (in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide).
Classical Hodgkin lymphoma in patients who are at high risk of relapse or progression as autologous hematopoietic stem cell transplant consolidation.
Previously untreated stage III or IV classical Hodgkin lymphoma (in combination with doxorubicin, vinblastine, and dacarbazine).
Systemic anaplastic large cell lymphoma after failure of ≥1 multiagent 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).
Relapsed or refractory large B-cell lymphoma, including diffuse large B-cell lymphoma not otherwise specified, diffuse large B-lymphoma arising from indolent lymphoma, or high-grade B-cell lymphoma, after ≥2 lines of systemic therapy in patients who are not eligible for autologous hematopoietic stem cell transplant or chimeric antigen receptor T-cell therapy (in combination with lenalidomide and rituximab).

Action ⬆ ⬇

An antibody-drug conjugate (ADC) made up of 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.

Pharmacokinetics ⬆ ⬇

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.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

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

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Concurrent use of bleomycin (↑ risk of pulmonary toxicity);
Severe renal impairment;
Moderate or severe hepatic impairment;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

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

Adv. Reactions/Side Effects ⬆ ⬇

CV: peripheral edema

Derm: alopecia, night sweats, pruritus, rash, stevens-johnson syndrome (SJS), toxic epidermal necrolysis (TEN), dry skin

EENT: oropharyngeal pain

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, weight loss, ENTEROCOLITIS, NEUTROPENIC COLITIS, ulcer

GU: ↓fertility

Hemat: anemia, neutropenia, thrombocytopenia

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

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

Interactions ⬆ ⬇

Drug-drug:

Bleomycin may ↑ risk of pulmonary toxicity; concurrent use contraindicated.
Strong CYP3A4 inhibitors, including ketoconazole, may ↑ levels and risk of toxicity.
Strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness.

Route/Dosage ⬆ ⬇

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 hepatic impairment: 1.2 mg/kg (max dose = 120 mg) every 3 wk until disease progression or unacceptable toxicity; Moderate or severe hepatic impairment: 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 hepatic impairment: 1.2 mg/kg (max dose = 120 mg) every 3 wk until a maximum of 5 doses completed; Moderate or severe hepatic impairment: 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 postautologous hematopoietic stem cell transplant or upon recovery of autologous hematopoietic stem cell transplant.

Renal Impairment

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

Hepatic Impairment

IV (Adults ): Mild hepatic impairment: 1.2 mg/kg (max dose = 120 mg) every 3 wk until a maximum of 16 cycles completed, disease progression, or unacceptable toxicity; Moderate or severe hepatic impairment: 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 hepatic impairment: 0.9 mg/kg (max dose = 90 mg) every 2 wk until a maximum of 12 doses completed, disease progression, or unacceptable toxicity; Moderate or severe hepatic impairment: Avoid use.

Relapsed Primary Cutaneous Anaplastic Large Cell Lymphoma or CD30-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 hepatic impairment: 1.2 mg/kg (max dose = 120 mg) every 3 wk until a maximum of 16 cycles completed, disease progression, or unacceptable toxicity; Moderate or severe hepatic impairment: Avoid use.

Previously Untreated Systemic Anaplastic Large Cell Lymphoma or Other CD30-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 hepatic impairment: 1.2 mg/kg (max dose = 120 mg) every 3 wk with each cycle of chemotherapy for 6–8 doses; Moderate or severe hepatic impairment: Avoid use.

Relapsed or Refractory Large B-Cell Lymphoma

IV (Adults ): 1.2 mg/kg (max dose = 120 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 hepatic impairment: 0.9 mg/kg (max dose = 90 mg) every 3 wk until disease progression or unacceptable toxicity; Moderate or severe hepatic impairment: Avoid use.

Availability ⬆ ⬇

Lyophilized powder for injection: 50 mg/vial

Assessment ⬆ ⬇

Monitor for signs and symptoms of peripheral neuropathy (hypoesthesia, hyperesthesia, paresthesia, discomfort, burning, neuropathic pain, weakness). If new or worsening Grade 2 peripheral neuropathy occurs,↓ dose of vincristine per prescribing information. Continue dosing with brentuximab. If neuropathy improves to Grade ≤1 by day 8 of next cycle, resume vincristine at full dose. If Grade 3 peripheral neuropathy occurs, discontinue vincristine. For 1st occurrence, delay next dose of brentuximab until neuropathy improves to Grade ≤1; then restart at 1.2 mg/kg (max dose = 120 mg). For 2nd occurrence, hold brentuximab until improvement to Grade ≤2; then restart at 0.8 mg/kg (max dose = 80 mg). For 3rd occurrence, discontinue brentuximab. If Grade 4 peripheral neuropathy occurs, discontinue brentuximab and vincristine.
Monitor temperature periodically during therapy, especially if neutropenic.
Assess for signs and symptoms of infusion-related reactions, including anaphylaxis (rash, pruritus, dyspnea, swelling of face and neck). If anaphylaxis occurs, discontinue infusion immediately; do not restart. Treat other infusion-related reactions by stopping and treating symptoms. Premedicate patients who have experienced a prior infusion-related reaction with acetaminophen, an antihistamine, and a corticosteroid prior to subsequent infusions.
Monitor for tumor lysis syndrome due to rapid ↓ in tumor volume (acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, hypophosphatemia). Risks are higher in patients with greater tumor burden and rapidly proliferating tumors; may be fatal. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis, as indicated.
Assess for skin rash frequently during therapy. Discontinue at 1st sign of rash; may be life-threatening. SJS or TEN may develop. Treat symptomatically; may recur once treatment is stopped.
Assess for any new signs or symptoms that may be suggestive of PML, an opportunistic infection of the brain caused by the JC virus that leads to death or severe disability; withhold dose and notify health care provider promptly. PML symptoms may begin gradually but usually worsen rapidly. Symptoms vary depending on which part of brain is infected (mental function declines rapidly and progressively, causing dementia; speaking becomes increasingly difficult; partial blindness; difficulty walking; rarely, headaches and seizures occur). Diagnosis is usually made via gadolinium-enhanced MRI and CSF analysis. Risk of PML ↑ with the number of infusions. Withhold brentuximab at 1st sign of PML.
Monitor for signs and symptoms of pulmonary toxicity (cough, dyspnea) during therapy. If new or worsening pulmonary symptoms occur, hold brentuximab during assessment and until symptoms improve.
Monitor for severe abdominal pain during therapy; may cause pancreatitis.

Lab Test Considerations:

Verify negative pregnancy status before starting therapy.
- Monitor CBC before each dose and more frequently in patients with Grade 3 or 4 neutropenia. Prolonged (≥1 wk) severe neutropenia may occur. If Grade 3 or 4 neutropenia occurs, hold dose of brentuximab until resolution to Grade ≤2. Consider growth factor support for subsequent cycles for patients who developed Grade 3 or 4 neutropenia. If recurrent Grade 4 neutropenia occurs despite use of growth factors, discontinue brentuximab or ↓ dose to 1.2 mg/kg (max dose = 120 mg).
- Monitor liver enzymes and bilirubin periodically during therapy. Signs of new, worsening, or recurrent hepatotoxicity may require ↓ in dose or interruption or discontinuation of therapy.
- Monitor blood glucose frequently during therapy; hyperglycemia may occur more frequently in patients with high BMI or diabetes. If hyperglycemia develops, administer antihyperglycemic agents as clinically indicated.

Implementation ⬆ ⬇

IV Administration:

Premedicate patients with previously untreated stage III or IV classical Hodgkin lymphoma, peripheral T-cell lymphoma, or relapsed or refractory large B-cell lymphoma who are treated with brentuximab in combination with chemotherapy with G-CSF beginning with Cycle 1.
Intermittent Infusion: Calculate dose and number of brentuximab vials needed. Calculate for 100 kg for patients weighing >100 kg. Reconstitution: Reconstitute each 50 mg vial with 10.5 mL of sterile water for injection. Direct stream to side of vial. Swirl gently; do not shake. Solution should be clear to slightly opalescent and colorless. Do not administer solutions that are discolored or contain a precipitate. Dilute immediately into infusion bag or store solution in refrigerator; use within 24 hr of reconstitution. Concentration: 5 mg/mL. Diluent: Withdraw volume of brentuximab dose from infusion bag of >100 mL. Dilute appropriate volume of reconstituted drug in 0.9% NaCl, D5W, or LR. Concentration: 0.4–1.8 mg/mL. Invert bag gently to mix. Do not freeze. Infuse the diluted solution immediately or store solution in refrigerator; use within 24 hr of reconstitution.
Rate: Infuse over 30 min. Do not administer as IV push or bolus.
Y-Site Incompatibility: Do not administer other drugs through same IV line.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise to read Patient Information before starting therapy.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Instruct patient to notify health care provider of any numbness or tingling of hands or feet or any muscle weakness.
Advise patient to notify health care provider 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; ↓ 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; ↑ urination; ketones in urine; loss of appetite; stomachache; nausea or vomiting; tiredness; rapid, deep breathing; unusual thirst; unconsciousness). Advise patient to notify health care provider if symptoms occur.
Rep: May cause fetal harm. Advise women of reproductive potential and men with female partners of reproductive potential to use effective contraception during therapy and for >6 mo after last dose and to avoid breastfeeding during therapy. If pregnancy is suspected, notify health care provider promptly. Inform men that therapy may impair fertility.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

Code ⬆