(bren TUX i mab ve DOE tin)
- Anti-CD30 ADC SGN-35
- Anti-CD30 Antibody-Drug Conjugate SGN-35
- Antibody-Drug Conjugate SGN-35
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous [preservative free]:
Adcetris: 50 mg (1 ea) [contains polysorbate 80]
Brand Names: U.S.
- Antineoplastic Agent, Anti-CD30
- Antineoplastic Agent, Antibody Drug Conjugate
- Antineoplastic Agent, Monoclonal Antibody
Brentuximab vedotin is an antibody drug conjugate (ADC) directed at CD30 consisting of 3 components: 1) a CD30-specific chimeric IgG1 antibody cAC10; 2) a microtubule-disrupting agent, monomethylauristatin E (MMAE); and 3) a protease cleavable dipeptide linker (which covalently conjugates MMAE to cAC10). The conjugate binds to cells which express CD30, and forms a complex which is internalized within the cell and releases MMAE. MMAE binds to the tubules and disrupts the cellular microtubule network, inducing cell cycle arrest (G2/M phase) and apoptosis.
Vdss: ADC: ~6 to 10 L
MMAE: Minimal, primarily via oxidation by CYP3A4/5
MMAE: Feces (~72% [of recovered MMAE], primarily unchanged); urine
Time to Peak
ADC: At end of infusion; MMAE: ~1 to 3 days
Terminal: ADC: ~4 to 6 days
MMAE: 68% to 82%
Special Populations: Renal Function Impairment
The exposure (AUC) of MMAE, a brentuximab vedotin component, was increased ~2-fold in patients with severe renal impairment receiving a 1.2 mg/kg dose compared to patients with normal renal function.
Special Populations: Hepatic Function Impairment
The exposure (AUC) of MMAE, a brentuximab vedotin component, was increased ~2.2-fold in patients with hepatic impairment receiving a 1.2 mg/kg dose compared to patients with normal hepatic function.
Use: Labeled Indications
Anaplastic large cell lymphoma (primary cutaneous): Treatment of primary cutaneous anaplastic large cell lymphoma in patients who have received prior systemic therapy
Anaplastic large cell lymphoma (systemic): Treatment of systemic anaplastic large cell lymphoma after failure of at least 1 prior multiagent chemotherapy regimen
Hodgkin lymphoma, relapsed or refractory: Treatment of classical Hodgkin lymphoma after failure of at least 2 prior multiagent chemotherapy regimens (in patients who are not autologous hematopoietic stem cell transplant [HSCT] candidates) or after failure of autologous HSCT
Hodgkin lymphoma (post-autologous hematopoietic stem cell transplantation): Treatment of classical Hodgkin lymphoma in patients at high risk of relapse or progression as post–autologous HSCT consolidation
Mycosis fungoides: Treatment of CD30-expressing mycosis fungoides in patients who have received prior systemic therapy
Concurrent use with bleomycin (due to pulmonary toxicity)
Canadian labeling (additional contraindications not in the US labeling): Hypersensitivity to brentuximab or any component of the formulation; patients who have or have had progressive multifocal leukoencephalopathy
Hodgkin lymphoma, relapsed or refractory: IV: 1.8 mg/kg (maximum dose: 180 mg) every 3 weeks, continue until disease progression or unacceptable toxicities (Younes 2012)
Hodgkin lymphoma, consolidation therapy after autologous hematopoietic stem cell transplantation (HSCT): IV: 1.8 mg/kg (maximum dose: 180 mg) every 3 weeks, continue until a maximum of 16 cycles, disease progression, or unacceptable toxicity (Moskowitz 2015). Begin therapy within 4 to 6 weeks post HSCT or upon recovery from HSCT.
Mycosis fungoides (CD-30 expressing): IV: 1.8 mg/kg (maximum dose: 180 mg) every 3 weeks, continue until a maximum of 16 cycles, disease progression, or unacceptable toxicity (Prince 2017)
Primary cutaneous anaplastic large cell lymphoma, relapsed (pcALCL): IV: 1.8 mg/kg (maximum dose: 180 mg) every 3 weeks, continue until a maximum of 16 cycles, disease progression, or unacceptable toxicity (Prince 2017)
Systemic anaplastic large cell lymphoma (sALCL), relapsed: IV: 1.8 mg/kg (maximum dose: 180 mg) every 3 weeks, continue until disease progression or unacceptable toxicities (Pro 2012)
Refer to adult dosing.
Dosing: Renal Impairment
CrCl ≥30 mL/minute: Initial: No dosage adjustment necessary.
CrCl <30 mL/minute: Avoid use.
Dosing: Hepatic Impairment
Mild impairment (Child-Pugh class A): Initial: 1.2 mg/kg (maximum dose: 120 mg) every 3 weeks.
Moderate to severe impairment (Child-Pugh class B or C): Avoid use.
Dosing: Adjustment for Toxicity
Grade 3 or 4 neutropenia: Withhold treatment until resolves to baseline or ≤ grade 2, consider growth factor support in subsequent cycles.
Recurrent grade 4 neutropenia (despite the use of growth factor prophylaxis): Consider reducing the dose to 1.2 mg/kg (maximum dose: 120 mg) or discontinuing treatment
Anaphylaxis: Discontinue immediately and permanently
Infusion reaction: Interrupt infusion and administer appropriate medical intervention. Premedicate subsequent infusions with acetaminophen, an antihistamine, and/or a corticosteroid.
Peripheral neuropathy, new or worsening grade 2 or 3: Withhold treatment until improves or returns to grade 1 or baseline; then resume with dose reduced to 1.2 mg/kg (maximum dose: 120 mg)
Peripheral neuropathy, grade 4: Discontinue treatment
Progressive multifocal leukoencephalopathy (PML): Withhold treatment with new-onset symptoms suggestive of PML; discontinue if PML diagnosis confirmed
Pulmonary toxicity: Withhold treatment with new-onset or worsening pulmonary symptoms during evaluation and until symptomatic improvement
Stevens-Johnson syndrome or toxic epidermal necrolysis: Discontinue and administer appropriate medical intervention
Reconstitute each 50 mg vial with 10.5 mL sterile water for injection (SWFI), resulting in a concentration of 5 mg/mL. Direct SWFI toward the vial wall; do not direct toward the cake or powder. Swirl gently to dissolve, do not shake. Reconstituted solution should be clear to slightly opalescent without visible particles. Further dilute in at least 100 mL of either NS, D5W, or LR to a final concentration of 0.4 to 1.8 mg/mL; gently invert bag to mix. Do not mix with other medications. Use within 24 hours of initial reconstitution.
IV: Infuse over 30 minutes. Do not administer as IV push or bolus; do not mix or infuse with other medications.
Store intact vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton. Protect from light. Reconstituted solution should be diluted immediately in NS, D5W, or LR; however, may be stored refrigerated for up to 24 hours; do not freeze. Solutions diluted for infusion should be used immediately after preparation; however, may be stored for 24 hours refrigerated (do not freeze); use within 24 hours of initial reconstitution.
BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination
Belimumab: Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. Avoid combination
Bleomycin: Brentuximab Vedotin may enhance the adverse/toxic effect of Bleomycin. Specifically, the risk for pulmonary toxicity may be increased. Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification
Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification
Lumacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination
Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification
Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be decreased. Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy
Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination
Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy
Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Avoid combination
Cardiovascular: Peripheral edema (16%)
Central nervous system: Neuropathy (62%), peripheral sensory neuropathy (52% to 56%), fatigue (24% to 49%), pain (28%), peripheral motor neuropathy (16% to 23%), headache (11% to 19%), insomnia (14% to 16%), dizziness (11% to 16%), chills (10% to 13%; infusion-related: 4%), anxiety (11%)
Dermatologic: Skin rash (27% to 31%), pruritus (12% to 19%; infusion-related: 2% to 5%), alopecia (13% to 14%), night sweats (12%)
Endocrine & metabolic: Weight loss (12% to 19%)
Gastrointestinal: Nausea (22% to 42%; infusion-related: 3% to 4%), diarrhea (20% to 36%), abdominal pain (14% to 25%), vomiting (16% to 22%), constipation (13% to 19%), decreased appetite (11% to 16%)
Hematologic & oncologic: Neutropenia (54% to 78%; grade 3: 12% to 30%; grade 4: 6% to 9%), anemia (27% to 52%; grade 3: 2% to 8%; grade 4: 2%), thrombocytopenia (16% to 41%; grade 3: 5% to 7%; grade 4: 2% to 5%), lymphadenopathy (10% to 11%)
Immunologic: Antibody development (7% to 30%; neutralizing: 62%)
Neuromuscular & skeletal: Arthralgia (18% to 19%), myalgia (11% to 17%), back pain (10% to 14%), muscle spasm (10% to 11%)
Respiratory: Upper respiratory tract infection (12% to 47%), cough (17% to 25%; infusion-related: 2%), dyspnea (13% to 19%; infusion-related: 2%), oropharyngeal pain (11%)
Miscellaneous: Fever (19% to 38%; infusion-related: 2%)
1% to 10%:
Cardiovascular: Septic shock (3%), supraventricular cardiac arrhythmia (3%), pulmonary embolism (2%)
Dermatologic: Xeroderma (10%)
Genitourinary: Urinary tract infection (3%)
Hepatic: Hepatotoxicity (2%)
Neuromuscular & skeletal: Limb pain (10%)
Renal: Pyelonephritis (2%)
Respiratory: Pulmonary toxicity (5%), pneumothorax (2%)
<1%, postmarketing, and/or case reports: Anaphylaxis, bacteremia, enterocolitis, febrile neutropenia, gastrointestinal erosion, gastrointestinal hemorrhage, gastrointestinal perforation, gastrointestinal ulcer, hyperglycemia, increased serum bilirubin, increased serum transaminases, intestinal obstruction, JC virus infection, neutropenic enterocolitis, opportunistic infection, pancreatitis, pneumonia, sepsis, serious infection, severe hepatotoxicity, Stevens-Johnson syndrome, toxic epidermal necrolysis
Concerns related to adverse effects:
• Bone marrow suppression: Grade 3 or 4 neutropenia, thrombocytopenia, and anemia may occur. Neutropenia may be severe and/or prolonged (≥1 week). Neutropenic fever also has been reported. Monitor blood counts prior to each dose; consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. May require growth factor support, dose interruption, reduction, or discontinuation.
• Dermatologic toxicity: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported (some fatal). Discontinue (and begin appropriate management) if SJS or TEN occur.
• GI toxicity: Acute pancreatitis (some fatal) has been observed. Other serious and fatal GI complications (including hemorrhage, obstruction, perforation, erosion, ulcer, enterocolitis, neutropenic colitis, and ileus) have also been reported. The risk for GI complications may be increased in patients with lymphoma with preexisting GI involvement. Prompt diagnostic evaluation and management should be performed if new or worsening GI symptoms (including severe abdominal pain) occur.
• Hepatotoxicity: Serious hepatotoxicity, including fatalities, has occurred; cases were consistent with hepatocellular injury, with elevations of transaminases and/or bilirubin. Some have occurred after the initial dose or after rechallenge. The risk for hepatotoxicity may be increased with preexisting liver disease, elevated baseline liver enzymes, and concurrent medications. Monitor liver enzymes and bilirubin. Treatment delay, dose reduction, or discontinuation may be required for new, worsening, or recurrent hepatotoxicity.
• Infection: Serious infection, including opportunistic infections (eg, pneumonia, bacteremia, sepsis/septic shock) have been reported (some fatal); monitor for signs or symptoms of bacterial, fungal, or viral infections.
• Infusion reactions/anaphylaxis: Infusion reactions, including anaphylaxis have been reported. Monitor during infusion. For anaphylaxis, immediately and permanently discontinue and administer appropriate medical intervention. For infusion-related reaction, interrupt infusion and administer appropriate medical intervention; premedicate for subsequent infusions (with acetaminophen, an antihistamine, and/or a corticosteroid).
• Peripheral neuropathy: Peripheral neuropathy is common and is generally cumulative. Neuropathy is usually sensory, although motor neuropathy has also been observed. Neuropathy completely resolved in over half of patients receiving brentuximab vedotin as monotherapy; almost one-quarter had partial improvement. Neuropathy did not improve in some patients. The median time to onset of neuropathy (any grade) was 13 weeks (range: up to 52 weeks), and the median time from onset to resolution or improvement of any grade was 21 weeks (range: up to 195 weeks). Monitor for symptoms of neuropathy (hypoesthesia, hyperesthesia, paresthesia, discomfort, burning sensation, neuropathic pain, or weakness). Dose interruption, reduction or discontinuation may be recommended for new or worsening neuropathy.
• Progressive multifocal leukoencephalopathy: [US Boxed Warning]: Cases of progressive multifocal leukoencephalopathy (PML) and death due to JC virus infection have been reported. Immunosuppression due to prior chemotherapy treatments or underlying disease may also contribute to PML development. New-onset signs/symptoms of central nervous system abnormalities (eg, changes in mood, memory, cognition, motor incoordination and/or weakness, speech and/or visual disturbances) should receive prompt evaluation with neurology consultation, brain MRI, and lumbar puncture or brain biopsy. The time to initial symptom onset varies from treatment initiation, with some cases occurring within 3 months of initial drug exposure. Withhold treatment with new-onset symptoms suggestive of PML; discontinue if diagnosis of PML is confirmed.
• Pulmonary toxicity: Noninfectious pulmonary toxicity (eg, pneumonitis, interstitial lung disease, acute respiratory distress syndrome), some fatal, has been reported in patients receiving brentuximab vedotin. Monitor for signs/symptoms of pulmonary toxicity (eg, cough, dyspnea). Withhold treatment and perform prompt diagnostic evaluation and management for new or worsening pulmonary symptoms.
• Tumor lysis syndrome: Tumor lysis syndrome (TLS) may occur; risk of TLS is higher in patients with a high tumor burden or with rapid tumor proliferation. Monitor closely.
• Hepatic impairment: Avoid use in patients with moderate to severe hepatic impairment (Child-Pugh classes B and C). A reduced dose is required in patients with mild impairment (Child-Pugh class A). The frequency of grade 3/4 toxicities (and deaths) was increased in patients with moderate or severe impairment (compared to patients with normal hepatic function). A component of brentuximab vedotin, the microtubule-disrupting agent monomethylauristatin E (MMAE) is excreted hepatically. MMAE exposure is increased ~2.2-fold in patients with hepatic impairment.
• Renal impairment: Avoid use in patients with severe renal impairment (CrCl <30 mL/minute). The frequency of grade 3/4 toxicities (and deaths) was increased in patients with severe impairment (compared to patients with normal renal function). A component of brentuximab vedotin, the microtubule-disrupting agent MMAE is excreted renally; MMAE exposure is increased in patients with severe impairment.
Concurrent drug therapy issues:
• Bleomycin: Due to the risk for pulmonary injury, concurrent use with bleomycin is contraindicated. In a study comparing brentuximab combined with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) to brentuximab combined with AVD (doxorubicin, vinblastine, and dacarbazine), the occurrence of pulmonary toxicity was higher in the brentuximab/ABVD group. Pulmonary symptoms/toxicities reported with brentuximab in combination with ABVD consisted of cough, dyspnea, and interstitial infiltration/inflammation; most patients responded to corticosteroids.
• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
CBC with differential prior to each dose (more frequently if clinically indicated); liver and renal function tests. Pregnancy test (in women of reproductive potential) prior to treatment initiation. Monitor for infusion reaction, tumor lysis syndrome, signs/symptoms of progressive multifocal leukoencephalopathy (PML), and for signs of neuropathy (hypoesthesia, hyperesthesia, paresthesia, discomfort, burning sensation, or neuropathic pain or weakness), dermatologic toxicity, pulmonary toxicity, GI toxicity, or infection.
Adverse events were observed in animal reproduction studies. Based on the mechanism of action and on animal data, brentuximab vedotin may cause fetal harm if administered to a pregnant woman. In women of reproductive potential, verify pregnancy prior to treatment initiation. Women of reproductive potential and men with female partners of reproductive potential should avoid pregnancy during treatment and for at least 6 months after the final dose. Brentuximab vedotin treatment may compromise fertility in males.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience joint pain, headache, nausea, vomiting, abdominal pain, constipation, diarrhea, back pain, dry skin, hair loss, muscle spasms, lack of appetite, weight loss, night sweats, insomnia, or anxiety. Have patient report immediately to prescriber signs of progressive multifocal leukoencephalopathy (confusion, depression, memory impairment, behavioral changes, change in strength on one side, difficulty speaking, change in balance, or vision changes), signs of infection, signs of a severe pulmonary disorder (lung or breathing problems like difficulty breathing, shortness of breath, or a cough that is new or worse), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of bowel problems (black, tarry, or bloody stools; fever; mucus in stools; vomiting; vomiting blood; severe abdominal pain; constipation; or diarrhea), enlarged lymph nodes, severe dizziness, passing out, severe loss of strength and energy, angina, coughing up blood, burning or numbness feeling, muscle pain, muscle weakness, swelling of arm or leg, bruising, bleeding, signs of tumor lysis syndrome (tachycardia or abnormal heartbeat; any passing out; urinary retention; muscle weakness or cramps; nausea, vomiting, diarrhea or lack of appetite; or feeling sluggish), or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
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- Drug class: CD30 monoclonal antibodies
Other brands: Adcetris