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)

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.

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.

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.

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.

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.

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.

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.

• Lyophilized powder for injection: 50 mg/vial;

• Monitor for signs and symptoms of peripheral neuropathy (hypoesthesia, hyperesthesia, paresthesia, discomfort, burning, neuropathic pain, weakness). For new or worsening neuropathy Grade 2:Reduce dose of vincristine per prescribing information. Continue dosing with brentuximab. If neuropathy improves to Grade ≤1 by day 8 of next cycle, then resume vincristine at full dose. For Grade 3, Discontinue vincristine. For first occurrence, delay next dose until neuropathy improves to ≤ Grade 1, then restart at brentuximab at 1.2 mg/kg up to 120 mg. For second occurrence, hold therapy until improvement to ≤ Grade 2 then restart at 0.8 mg/kg up to a maximum of 80 mg. For third 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 reaction, 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 patient prior to subsequent infusions with acetaminophen, an antihistamine, and a corticosteroid.
• Monitor for tumor lysis syndrome due to rapid reduction in tumor volume (acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or 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 first sign of rash; may be life-threatening. Stevens-Johnson syndrome 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 professional 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 increases with the number of infusions. Withhold brentuximab at first 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.

• • Verify negative pregnancy status prior to starting therapy.
  Monitor CBC prior to each dose and more frequently in patients with Grade 3 or 4 neutropenia. Prolonged (≥1 wk) severe neutropenia may occur. Hold dose of brentuximab for Grade 3 or 4 neutropenia until resolution to baseline or ≤Grade 2. Consider growth factor support for subsequent cycles for patients who developed Grade 3 or 4 neutropenia. Discontinue brentuximab or reduce dose to 1.2 mg/kg (up to 120 mg) in patients with recurrent Grade 4 neutropenia despite use of growth factors.
  • Monitor liver enzymes and bilirubin periodically during therapy. Signs of new, worsening, or recurrent hepatotoxicity may require decrease in dose, or interruption or discontinuation of therapy.
  • Monitor blood glucose frequently during therapy. May occur more frequently in patients with high body mass index or diabetes. If hyperglycemia develops, administer antihyperglycemic agents as clinically indicated.

IV Administration:

• Premedicate patients with previously untreated Stage III, IV cHL and PTCL 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.Concentration: 5 mg/mL. Solution should be clear to slightly opalescent, and colorless. Do not administer solutions that are discolored or contain a precipitate. Withdraw volume of brentuximab dose from infusion bag of at least 100 mL.
  Diluent: 0.9% NaCl, D5W, or LR.Concentration: 0.4 —1.8 mg/mL. Invert bag gently to mix. Dilute immediately into infusion bag or store solution in refrigerator; use within 24 hrs of reconstitution. Do not freeze.
• Rate: Infuse over 30 min. Do not administer as IV push or bolus.
• Y-Site Incompatibility: Do not administer with other mediations or solutions.

• 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.

• Decreased spread of lymphoma.

Adcetris