Brentuximab Vedotin

Dosage Forms

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]

Pharmacology

Mechanism of Action

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.

Pharmacokinetics/Pharmacodynamics

Distribution

V_dss: ADC: ~6 to 10 L

Metabolism

MMAE: Minimal, primarily via oxidation by CYP3A4/5

Excretion

MMAE: Feces (~72% [of recovered MMAE], primarily unchanged); urine

Time to Peak

ADC: At end of infusion; MMAE: ~1 to 3 days after the end of infusion

Half-Life Elimination

Terminal: ADC: ~4 to 6 days; MMAE: ~3 to 4 days

Protein Binding

MMAE: 68% to 82%

Use in Specific Populations

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 ~2.3-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), relapsed: Treatment of primary cutaneous anaplastic large cell lymphoma in patients who have received prior systemic therapy

Anaplastic large cell lymphoma (systemic), previously untreated: Treatment of previously untreated systemic anaplastic large cell lymphoma (in combination with cyclophosphamide, doxorubicin, and prednisone)

Anaplastic large cell lymphoma (systemic), relapsed: Treatment of systemic anaplastic large cell lymphoma after failure of at least 1 prior multiagent chemotherapy regimen

Hodgkin lymphoma, previously untreated: Treatment of previously untreated stage III or IV classical Hodgkin lymphoma (in combination with doxorubicin, vinblastine, and dacarbazine)

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, consolidation (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, relapsed: Treatment of CD30-expressing mycosis fungoides in patients who have received prior systemic therapy

Peripheral T-cell lymphoma, CD30-expressing, previously untreated: Treatment of previously untreated CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified (in combination with cyclophosphamide, doxorubicin, and prednisone)

Contraindications

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

Dosage and Administration

Dosing: Adult

Hodgkin lymphoma, advanced, previously untreated: IV: 1.2 mg/kg (maximum dose: 120 mg) every 2 weeks (in combination with doxorubicin, vinblastine, and dacarbazine [AVD]; begin brentuximab within ~1 hour after completion of AVD) until a maximum of 12 doses, disease progression, or unacceptable toxicity (Connors 2018). Administer primary prophylaxis with G-CSF (filgrastim) beginning with cycle 1.

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), relapsed: 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)

Peripheral T-cell lymphoma (CD30-expressing), previously untreated: IV: 1.8 mg/kg (maximum dose: 180 mg) every 3 weeks for 6 to 8 doses (in combination with cyclophosphamide, doxorubicin, and prednisone). Administer primary prophylaxis with G-CSF (filgrastim) beginning with cycle 1.

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), previously untreated: IV: 1.8 mg/kg (maximum dose: 180 mg) every 3 weeks for 6 to 8 doses (in combination with cyclophosphamide, doxorubicin, and prednisone)

Systemic anaplastic large cell lymphoma, relapsed: IV: 1.8 mg/kg (maximum dose: 180 mg) every 3 weeks, continue until disease progression or unacceptable toxicities (Pro 2012)

Dosing: Geriatric

Refer to adult dosing.

Dosing: Adjustment for Toxicity

Hematologic toxicity:

Combination therapy (usual dose 1.2 mg/kg every 2 weeks or 1.8 mg/kg every 3 weeks):

Grade 3 or 4 neutropenia: Administer G-CSF prophylaxis for subsequent cycles for patients not receiving primary prophylaxis.

Single agent therapy (usual dose 1.8 mg/kg every 3 weeks):

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) every 3 weeks or discontinuing treatment

Nonhematologic toxicities:

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:

Combination therapy (usual dose 1.2 mg/kg every 2 weeks):

Grade 2: Reduce brentuximab vedotin dose to 0.9 mg/kg (maximum dose: 90 mg) every 2 weeks.

Grade 3: Withhold treatment until improves or returns to grade 2 or lower; then resume with dose reduced to 0.9 mg/kg (maximum dose: 90 mg) every 2 weeks. Also consider modifying the dose of other neurotoxic chemotherapy agents.

Grade 4: Discontinue treatment.

Combination therapy (usual dose 1.8 mg/kg every 3 weeks):

Grade 2: For grade 2 sensory neuropathy, continue treatment at the same dose. For grade 2 motor neuropathy, reduce brentuximab vedotin dose to 1.2 mg/kg (maximum dose: 120 mg) every 3 weeks.

Grade 3: For grade 3 sensory neuropathy, reduce brentuximab vedotin dose to 1.2 mg/kg (maximum dose: 120 mg) every 3 weeks. For grade 3 motor neuropathy, discontinue brentuximab vedotin.

Grade 4: Discontinue treatment.

Single agent therapy (usual dose 1.8 mg/kg every 3 weeks):

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) every 3 weeks

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

Reconstitution

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.

Administration

IV: Infuse over 30 minutes. Do not administer as IV push or bolus; do not mix or infuse with other medications.

Hodgkin lymphoma (previously untreated): When administering in combination with doxorubicin, vinblastine, and dacarbazine [AVD], begin brentuximab within ~1 hour after completion of AVD (Connors 2018).

Storage

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.

Drug Interactions

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bleomycin: Brentuximab Vedotin may enhance the adverse/toxic effect of Bleomycin. Specifically, the risk for pulmonary toxicity may be increased. Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

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

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

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

Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Avoid combination

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 and Ivacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor and Ivacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. 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

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). 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

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination

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. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

Adverse Reactions

>10%:

Cardiovascular: Peripheral edema (11%)

Central nervous system: Neuropathy (62%), peripheral sensory neuropathy (45% to 56%; grade 3: 5% to 10%), fatigue (24% to 29%), peripheral motor neuropathy (23%; grade 3: 6%), headache (11%)

Dermatologic: Pruritus (11% to 17%; infusion-related: 2% to 5%), alopecia (15%), maculopapular rash (11%)

Endocrine & metabolic: Weight loss (19%)

Gastrointestinal: Nausea (22% to 36%; infusion-related: 3% to 4%), diarrhea (20% to 29%), vomiting (16% to 17%), decreased appetite (12% to 15%), abdominal pain (14%), constipation (13%)

Hematologic & oncologic: Neutropenia (21% to 78%; grade 3: 3% to 30%; grade 4: 2% to 9%), anemia (27% to 62%; grade 3: 4%), thrombocytopenia (15% to 41%; grade 3: 2%; grade 4: 2% to 4%)

Immunologic: Antibody development (7% to 30%)

Neuromuscular & skeletal: Arthralgia (12% to 18%), myalgia (11% to 12%), asthenia (11%), muscle spasm (11%)

Respiratory: Upper respiratory tract infection (26%), cough (21%; infusion-related: 2%), dyspnea (11% to 13%; infusion-related: 2% to 3%)

Miscellaneous: Fever (17% to 19%; infusion-related: 2%)

1% to 10%:

Central nervous system: Chills (10%; infusion-related: 4%)

Dermatologic: Cellulitis (3%)

Endocrine & metabolic: Hyperglycemia (8%)

Hepatic: Hepatotoxicity (2%)

Respiratory: Pulmonary toxicity (5%), pneumonia (4%)

Frequency not defined:

Immunologic: Antibody development (neutralizing)

<1%, postmarketing, and/or case reports: Acute pancreatitis, acute respiratory distress syndrome, anaphylaxis, bacteremia, enterocolitis, exacerbation of diabetes mellitus, febrile neutropenia, gastrointestinal erosion, gastrointestinal hemorrhage, gastrointestinal perforation, gastrointestinal ulcer, increased serum bilirubin, increased serum transaminases, interstitial pulmonary disease, intestinal obstruction, JC virus infection, ketoacidosis, neutropenic enterocolitis, opportunistic infection, pancreatitis, pneumonitis, progressive multifocal leukoencephalopathy, sepsis, septic shock, serious infection, severe hepatotoxicity, Stevens-Johnson syndrome, toxic epidermal necrolysis

Warnings/Precautions

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 (sometimes fatal) 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. Administer primary prophylaxis with G-CSF (filgrastim) beginning with cycle 1 in patients receiving brentuximab vedotin in combination with chemotherapy for previously untreated Hodgkin lymphoma or previously untreated peripheral T-cell lymphomas (PTCL).
• 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.
• Hyperglycemia: Hyperglycemia, including new-onset hyperglycemia, exacerbation of pre-existing diabetes mellitus, and ketoacidosis (including fatalities) have been reported, including grade 3 and 4 events. The median time to hyperglycemia onset was 1 month (range: up to 10 months). Hyperglycemia occurred more frequently in patients with increased body mass or diabetes. Monitor serum glucose; if hyperglycemia is observed, administer antihyperglycemics as clinically indicated.
• 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. In patients receiving brentuximab as a single agent, the median time to onset of neuropathy (any grade) was 3 months (range: up to 12 months), and the median time from onset to resolution or improvement of any grade was 5 months (range: up to 45 months). In patients receiving brentuximab in combination with chemotherapy, the median time to onset of neuropathy (any grade) was 2 months (range: up to 7 months), and the median time from onset to resolution or improvement of any grade was 2 to 4 months (range: up to 45 months). Neuropathy completely resolved in approximately one-half of patients receiving brentuximab in combination with chemotherapy; ~12% to 24% had partial improvement. 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.

Disease-related concerns:

• 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.

Special populations:

• Elderly: Patients ≥65 years of age may be at higher risk for grade 3 or higher adverse events and neutropenic fever when brentuximab vedotin is used in combination with chemotherapy.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.

Monitoring Parameters

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.

Pregnancy

Pregnancy Considerations

Based on the mechanism of action and on animal data, brentuximab vedotin may cause fetal harm if administered to a pregnant woman.

Evaluate pregnancy status prior to use in females of reproductive potential. Females of reproductive potential and males 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.

Patient Education

What is this drug used for?

• It is used to treat lymphoma.

Frequently reported side effects of this drug

• Headache
• Nausea
• Vomiting
• Abdominal pain
• Constipation
• Diarrhea
• Bone pain
• Joint pain
• Muscle pain
• Back pain
• Dry skin
• Hair loss
• Fatigue
• Loss of strength and energy
• Muscle spasms
• Lack of appetite
• Weight loss
• Night sweats
• Trouble sleeping
• Anxiety
• Common cold symptoms

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Progressive multifocal leukoencephalopathy like confusion, depression, trouble with memory, behavioral changes, change in strength on one side, trouble speaking, change in balance, or vision changes
• Infection
• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit
• Severe pulmonary disorder like lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse
• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes
• Swollen glands
• Severe dizziness
• Passing out
• Chest pain
• Coughing up blood
• Burning or numbness feeling
• Muscle weakness
• Swelling
• Bruising
• Bleeding
• Tumor lysis syndrome like fast heartbeat or abnormal heartbeat; any passing out; unable to pass urine; muscle weakness or cramps; nausea, vomiting, diarrhea or lack of appetite; or feeling sluggish
• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes
• Signs of a significant reaction like 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. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.