Pronunciation: bren-TUX-i-mab ve-DOE-tin
Class: Antibody-drug conjugate
- Injection, lyophilized powder for solution 50 mg
An antibody-drug conjugate that binds to cells that express CD30. Forms a complex that is internalized within the cell and releases monomethyl auristatin E (MMAE). MMAE binds to the tubules and disrupts the cellular microtubule network, inducing cell cycle arrest and apoptosis.
T max of antibody-drug conjugate was observed close to the end of infusion and T max for MMAE was approximately 1 to 3 days. Steady state of the antibody-drug conjugate and MMAE was achieved within 21 days.
MMAE binds to human plasma ranging from 68% to 82%. Vd for antibody-drug conjugate was 6 to 10 L.
A small fraction of MMAE released from brentuximab vedotin is metabolized and occurs primarily via oxidation by CYP3A4/5.
Approximately 24% of MMAE was recovered after 1 wk (approximately 72% in feces, primarily unchanged). Antibody-drug conjugate terminal half-life was 4 to 6 days.
Special PopulationsRenal Function Impairment
The influence of renal impairment on the pharmacokinetics of MMAE has not been determined.Hepatic Function Impairment
The influence of hepatic impairment on the pharmacokinetics of MMAE has not been determined.Elderly
Age has no effect on brentuximab vedotin pharmacokinetics.Gender
Gender has no effect on brentuximab vedotin pharmacokinetics.Race
Race has no effect on brentuximab vedotin pharmacokinetics.
Indications and Usage
For treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant or after failure of at least 2 prior multiagent chemotherapy regimens in patients who are not ASCT candidates; treatment of patients with systemic anaplastic large cell lymphoma after failure of at least 1 prior multiagent chemotherapy regimen.
Concomitant use with bleomycin.
Dosage and AdministrationAdults
IV 1.8 mg/kg every 3 wk. Continue treatment until a max of 16 cycles, disease progression, or unacceptable toxicity occurs.Dosage adjustment
For new or worsening grade 2 or 3 neuropathy, dosing should be held until neuropathy improves to grade 1 or baseline and then restarted at 1.2 mg/kg. For grade 4 peripheral neuropathy, brentuximab vedotin should be discontinued.Neutropenia
Hold dose for grade 3 or 4 neutropenia until resolution to baseline or grade 2 or lower. Growth factor support should be considered in patients taking subsequent cycles who experience grade 3 or 4 neutropenia. In patients with recurrent grade 4 neutropenia despite the use of growth factors, discontinue brentuximab vedotin or consider reducing the dose to 1.2 mg/kg.
- Administer only as IV infusion over 30 minutes. Do not administer as an IV push or bolus.
- The dose for patients who weigh more than 100 kg should be calculated based on a weight of 100 kg.
- Reconstitute each vial with 10.5 mL of sterile water for injection to yield a single-use solution of 5 mg/mL. Gently swirl the vial to aid dissolution. Do not shake.
- Calculate the required volume of 5 mg/mL reconstituted brentuximab vedotin solution needed and withdraw this amount from the vial(s). Dilute to a final concentration of 0.4 to 1.8 mg/mL by immediately adding the reconstituted solution into an infusion bag containing a minimum volume of 100 mL of sodium chloride 0.9% injection, dextrose 5% injection, or Ringer's lactate injection. Gently invert bag to mix the solution.
- If anaphylaxis occurs during infusion, immediately and permanently discontinue administration. If an infusion-related reaction occurs, interrupt the infusion and institute appropriate medical management. Premedicate for subsequent infusions with acetaminophen, an antihistamine, and a corticosteroid.
- Do not mix or administer with other drugs.
Store vials between 36° and 46°F in the original carton to protect from light. Store reconstituted solution and/or diluted solution for infusion between 36° and 46°F and use within 24 hours of reconstitution. Do not freeze. Discard any unused portion left in the vial.
The risk of pulmonary toxicity may be increased. Coadministration is contraindicated.CYP3A4 inducers (eg, rifampin)
Coadministration of brentuximab vedotin with rifampin, a potent CYP3A4 inducer, reduced MMAE exposure. Coadminister with caution. Close monitoring for a decrease in clinical response is warranted.CYP3A4 inhibitors (eg, ketoconazole)
Coadministration of brentuximab vedotin with ketoconazole, a potent CYP3A4 inhibitor, increased MMAE exposure. Use with caution. Closely monitor for adverse reactions.
Supraventricular arrhythmia (3%).
Any grade neuropathy (54%); peripheral sensory neuropathy (53%); fatigue (49%); headache (19%); dizziness, insomnia, peripheral motor neuropathy (16%); anxiety (11%).
Rash (31%); pruritus (19%); alopecia (14%); night sweats (12%); dry skin (10%); Stevens-Johnson syndrome.
Nausea (42%); diarrhea (36%); abdominal pain (25%); vomiting (22%); constipation (19%).
UTI (3%); pyelonephritis (2%).
Neutropenia (55%); anemia (52%); thrombocytopenia (28%); lymphadenopathy (11%).
Decreased appetite (16%); weight decreased (12%).
Arthralgia (19%); myalgia (17%); back pain (14%); muscle spasms, pain in extremity (10%).
Upper respiratory tract infection (47%); cough (25%); dyspnea (19%); oropharyngeal pain (11%); pneumonitis, pneumothorax, pulmonary embolism (2%).
Pyrexia (38%); antibody development (30%); pain (28%); edema peripheral (16%); chills (13%); infusion-related reactions (12%); septic shock (3%); progressive multifocal leukoencephalopathy (PML); tumor lysis syndrome.
JC virus infection resulting in PML and death can occur in patients receiving brentuximab vedotin.
Monitor CBC prior to each dose and consider more frequent monitoring for patients with grade 3 or 4 neutropenia. Monitor for infusion reaction, tumor lysis syndrome, signs of neuropathy (eg, hypoesthesia, hyperesthesia, discomfort, a burning sensation, weakness, paresthesia, neuropathic pain), and PML.
Category D . Can cause fetal harm.
Safety and efficacy not established.
Safety and efficacy not established.
May occur; a higher incidence of infusion-related reactions was observed in patients who developed persistently positive antibodies.
Infusion reactions, including anaphylaxis, may occur.
Prolonged (1 wk or longer) severe neutropenia can occur; if grade 3 or 4 neutropenia develops, manage by dose delays, reductions, or discontinuation.
Treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. Patients experiencing new or worsening peripheral neuropathy may require a delay, change in dose, or discontinuation of brentuximab vedotin.
May occur; discontinue treatment and administer appropriate medical therapy.
Tumor lysis syndrome
Patients with rapidly proliferating tumor and high tumor burden may be at increased risk of tumor lysis syndrome.
- Advise patients that brentuximab vedotin can cause a peripheral neuropathy. Advise patients to report any numbness or tingling of the hands or feet or any muscle weakness to their health care provider.
- Advise patients to contact their health care provider if a fever of 100.5°F or greater or other evidence of potential infection, such as chills, cough, or pain on urination, develops.
- Advise patients to contact their health care provider if they experience signs and symptoms of infusion reactions, including fever, chills, rash, or breathing problems, within 24 hours of infusion.
- Instruct patients to immediately report if they have any of the following neurological, cognitive, or behavioral signs and symptoms: changes in mood or unusual behavior; confusion, thinking problems, loss of memory; changes in vision, speech, or walking; decreased strength or weakness on one side of the body.
- Advise women to avoid pregnancy. Advise patients to report pregnancy immediately.
- Advise patients to avoid breast-feeding.
Copyright © 2009 Wolters Kluwer Health.