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Brentuximab vedotin: Drug information

Brentuximab vedotin: Drug information
(For additional information see "Brentuximab vedotin: Patient drug information" and see "Brentuximab vedotin: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Progressive multifocal leukoencephalopathy:

JC virus infection resulting in progressive multifocal leukoencephalopathy (PML) and death can occur in patients receiving brentuximab vedotin.

Brand Names: US
  • Adcetris
Brand Names: Canada
  • Adcetris
Pharmacologic Category
  • Antineoplastic Agent, Anti-CD30;
  • Antineoplastic Agent, Antibody Drug Conjugate;
  • Antineoplastic Agent, Antimicrotubular;
  • Antineoplastic Agent, Monoclonal Antibody
Dosing: Adult
Hodgkin lymphoma, advanced, previously untreated

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

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 cell transplantation

Hodgkin lymphoma, consolidation therapy after autologous hematopoietic cell transplantation (HCT): 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 brentuximab vedotin within 4 to 6 weeks post HCT or upon recovery from HCT.

Mycosis fungoides, relapsed

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, previously untreated

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) (Horwitz 2019). Administer primary prophylaxis with G-CSF (filgrastim) beginning with cycle 1.

Primary cutaneous anaplastic large cell lymphoma, relapsed

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, previously untreated

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

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).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

CrCl ≥30 mL/minute: Initial: No dosage adjustment necessary.

CrCl <30 mL/minute: Avoid use.

Dosing: Hepatic Impairment: Adult

Hepatic impairment at treatment initiation:

Usual dose 1.2 mg/kg every 2 weeks:

Mild impairment (Child-Pugh class A): Initial: 0.9 mg/kg (maximum dose: 90 mg) every 2 weeks.

Moderate to severe impairment (Child-Pugh class B or C): Avoid use.

Usual dose 1.8 mg/kg every 3 weeks:

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.

Hepatotoxicity during treatment:

New, worsening, or recurrent hepatotoxicity: May require brentuximab vedotin treatment delay, dose modification, or discontinuation.

Dosing: Pediatric

(For additional information see "Brentuximab vedotin: Pediatric drug information")

Hodgkin lymphoma, classic; high-risk

Hodgkin lymphoma, classic; high-risk:

Children ≥2 years and Adolescents: IV: 1.8 mg/kg/dose; maximum dose: 180 mg/dose; administer every 3 weeks with each cycle of chemotherapy up to 5 doses total. For use in previously untreated patients and administered in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide along with filgrastim. For patients weighing >100 kg, calculate dose based on a weight of 100 kg (Castellino 2022; manufacturer's labeling).

Dosing adjustment for toxicity:

Hodgkin lymphoma

Children ≥2 years and Adolescents: IV: Note: Adjustment to the vincristine dose may be necessary in some instances; refer to Vincristine monograph for details.

Brentuximab Dosing Adjustment for Toxicity in Pediatric Patients (Based on Combination Therapy Usual Dose of 1.8 mg/kg Every 3 Weeks)

Hematologic toxicity

Neutropenia, grade 3 or 4

In patients unable to start a cycle >5 weeks after the initiation of the previous cycle due to neutropenia (ie, >2-week treatment delay), reduce brentuximab dose to 1.2 mg/kg (maximum dose: 120 mg/dose) every 3 weeks.

Nonhematologic toxicity

Peripheral neuropathy: Grade 2

Continue brentuximab at current dose.

Peripheral neuropathy: Grade 3

First occurrence: Hold brentuximab until improvement to ≤ grade 2; restart at reduced dose of 1.2 mg/kg (maximum dose: 120 mg/dose).

Second occurrence: Hold brentuximab until improvement to ≤ grade 2; restart at reduced dose of 0.8 mg/kg (maximum dose: 80 mg/dose).

Third occurrence: Discontinue brentuximab treatment.

Peripheral neuropathy: Grade 4

Discontinue brentuximab treatment.

Dosing: Kidney Impairment: Pediatric

Children ≥2 years and Adolescents: IV:

CrCl ≥30 mL/minute: Initial: No dosage adjustment necessary.

CrCl <30 mL/minute: Avoid use.

Dosing: Hepatic Impairment: Pediatric

Children ≥2 years and Adolescents: IV:

Hepatic impairment at treatment initiation:

Mild impairment (Child-Pugh class A): Reduce initial dose to 1.2 mg/kg (maximum dose: 120 mg/dose) every 3 weeks.

Moderate to severe impairment (Child-Pugh class B or C): Avoid use.

Hepatotoxicity during treatment:

New, worsening, or recurrent hepatotoxicity: May require brentuximab vedotin treatment delay, dose modification, or discontinuation.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Obesity: Adult

Note: According to the prescribing information, the dose for patients weighing >100 kg should be calculated based on a weight of 100 kg (refer to "Dosing: Adult").

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m2: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full, weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or kidney impairment) are sufficiently resolved, AND if performance status has markedly improved or is considered adequate (ASCO [Griggs 2021]).

Dosing: Adjustment for Toxicity: Adult

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 brentuximab vedotin immediately and permanently (and administer appropriate medical intervention).

Hyperglycemia: Administer antihyperglycemics as clinically indicated.

Infusion reaction: Interrupt brentuximab vedotin 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 brentuximab vedotin if PML diagnosis confirmed.

Pulmonary toxicity ( new-onset or worsening pulmonary symptoms ): Withhold treatment until symptomatic improvement; perform prompt diagnostic evaluation and management.

Stevens-Johnson syndrome or toxic epidermal necrolysis: Discontinue brentuximab vedotin and administer appropriate medical intervention.

Dosage Forms: US

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]

Generic Equivalent Available: US

No

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Adcetris: 50 mg (1 ea) [contains polysorbate 80]

Administration: Adult

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).

Administration: Pediatric

IV: Infuse over 30 minutes. Do not administer as IV push or bolus; do not mix or infuse with other medications. Refer to protocol regarding timing of brentuximab dose in relation to chemotherapy.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

Anaplastic large cell lymphoma (primary cutaneous), relapsed: Treatment of primary cutaneous anaplastic large cell lymphoma in adults who have received prior systemic therapy.

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

Anaplastic large cell lymphoma (systemic), relapsed: Treatment of systemic anaplastic large cell lymphoma in adults 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 adults (in combination with doxorubicin, vinblastine, and dacarbazine).

Treatment of previously untreated high risk classical Hodgkin lymphoma in pediatric patients ≥2 years of age (in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide).

Hodgkin lymphoma, relapsed or refractory: Treatment of classical Hodgkin lymphoma in adults after failure of at least 2 prior multiagent chemotherapy regimens (in patients who are not autologous hematopoietic cell transplant [HCT] candidates) or after failure of autologous HCT.

Hodgkin lymphoma, consolidation (post-autologous hematopoietic cell transplantation): Treatment of classical Hodgkin lymphoma in adults at high risk of relapse or progression as post-autologous HCT consolidation.

Mycosis fungoides, relapsed: Treatment of CD30-expressing mycosis fungoides in adults 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) in adults, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified (in combination with cyclophosphamide, doxorubicin, and prednisone).

Medication Safety Issues
Sound-alike/look-alike issues:

Brentuximab vedotin may be confused with belantamab mafodotin, bendamustine, bevacizumab, bezlotoxumab, polatuzumab vedotin, rituximab.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults on monotherapy regimens, unless otherwise noted.

>10%:

Cardiovascular: Peripheral edema (11%)

Dermatologic: Alopecia (15%), maculopapular rash (11%), pruritus (11% to 17%)

Endocrine & metabolic: Weight loss (19%)

Gastrointestinal: Abdominal pain (14%), constipation (13%), decreased appetite (12% to 15%), diarrhea (20% to 29%; grade 3: 2% to 3%), nausea (22% to 36%; grade 3: 2% to 3%), vomiting (16% to 17%; grade 3: 2%)

Hematologic & oncologic: Anemia (27% to 62%; grade 3: 4%), neutropenia (21% to 78%; grades 3/4: 2% to 30%), thrombocytopenia (15% to 41%; grades 3/4: 2% to 4%)

Hypersensitivity: Infusion-related relation (≤13%)

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

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

Respiratory: Cough (21%), dyspnea (11% to 13%), upper respiratory tract infection (26%)

Miscellaneous: Fever (17% to 19%)

1% to 10%:

Dermatologic: Cellulitis (serious: 3%)

Endocrine & metabolic: Hyperglycemia (≤8%)

Hepatic: Severe hepatotoxicity (2%; including increased serum bilirubin, increased serum transaminases)

Nervous system: Chills (10%)

Respiratory: Pneumonia (serious: 4%), pulmonary toxicity (5%; including acute respiratory distress syndrome, interstitial lung disease, pneumonitis)

Frequency not defined:

Hypersensitivity: Anaphylaxis

Immunologic: Antibody development (can be neutralizing)

Nervous system: Paresthesia

Postmarketing (monotherapy or combination therapy):

Dermatological: Stevens-Johnson syndrome, toxic epidermal necrolysis

Endocrine & metabolic: Exacerbation of diabetes mellitus, ketoacidosis

Gastrointestinal: Acute pancreatitis, enterocolitis, gastrointestinal erosion, gastrointestinal hemorrhage, gastrointestinal perforation, gastrointestinal ulcer, intestinal obstruction, neutropenic enterocolitis

Hematologic & oncologic: Febrile neutropenia

Infection: Bacteremia, JC virus infection (resulting in progressive multifocal leukoencephalopathy), opportunistic infection, sepsis, septic shock, serious infection

Contraindications

Concurrent use with bleomycin (due to pulmonary toxicity [eg, interstitial infiltration and/or inflammation]).

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

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.

• Dermatologic toxicity: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported (some fatal).

• 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.

• Hepatic impairment: The incidence of ≥ grade 3 adverse reactions may be increased in patients with moderate or severe impairment (compared to patients with normal hepatic function).

• 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.

• 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.

• Infection: Serious infection, including opportunistic infections (eg, pneumonia, bacteremia, sepsis/septic shock) have been reported (some fatal).

• Infusion reactions/anaphylaxis: Infusion reactions, including anaphylaxis have been reported.

• Peripheral neuropathy: Peripheral neuropathy is common and is generally cumulative; grades 1 to 4 neuropathy have been reported. 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. Symptoms of neuropathy include hypoesthesia, hyperesthesia, paresthesia, discomfort, burning sensation, neuropathic pain, or weakness.

• Progressive multifocal leukoencephalopathy: 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 include changes in mood, memory, cognition, motor incoordination and/or weakness, speech and/or visual disturbances. The time to initial symptom onset varies from treatment initiation, with some cases occurring within 3 months of initial drug exposure.

• Pulmonary toxicity: Noninfectious pulmonary toxicity (eg, pneumonitis, interstitial lung disease, acute respiratory distress syndrome), some fatal, has been reported in patients receiving brentuximab vedotin.

• Renal impairment: Due to higher exposure of monomethylauristatin E (MMAE; the microtubule disrupting agent component), the incidence of ≥ grade 3 adverse reactions may be increased in patients with severe impairment (compared to patients with normal kidney function).

• 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.

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.

Special populations:

• Older adult: 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.

Metabolism/Transport Effects

Substrate of CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

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

BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

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

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

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

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

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

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

Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: 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. Risk C: 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. Risk C: 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. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

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

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

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

Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

Evaluate pregnancy status prior to use in patients who could become pregnant. Patients who could become pregnant and patients with partners who could become pregnant should avoid pregnancy during treatment and for 6 months after the final brentuximab vedotin dose. Brentuximab vedotin treatment may compromise fertility in males.

Pregnancy Considerations

Based on the mechanism of action and on animal data, in utero exposure to brentuximab vedotin may cause fetal harm.

Breastfeeding Considerations

It is not known if brentuximab vedotin is present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer does not recommend breastfeeding during brentuximab vedotin treatment.

Monitoring Parameters

CBC with differential prior to each dose (monitor more frequently in patients with grade 3 or 4 neutropenia); liver and renal function tests. Verify pregnancy status (in females of reproductive potential) prior to treatment initiation. Monitor for infusion reaction. Monitor for signs/symptoms of progressive multifocal leukoencephalopathy (evaluate with MRI, and lumbar puncture or brain biopsy), neuropathy (hypoesthesia, hyperesthesia, paresthesia, discomfort, burning sensation, or neuropathic pain or weakness), dermatologic toxicity, pulmonary toxicity (new or worsening symptoms such as cough or dyspnea), GI toxicity, tumor lysis syndrome, and/or infection (bacterial, fungal, or viral).

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

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

Distribution: Vdss: ADC: ~6 to 10 L

Protein binding: MMAE: 68% to 82%

Metabolism: MMAE: Minimal, primarily via oxidation by CYP3A4/5

Half-life elimination: Terminal: ADC: ~4 to 6 days; MMAE: ~3 to 4 days

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

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

Pharmacokinetics: Additional Considerations

Altered kidney function: 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.

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.

Pricing: US

Solution (reconstituted) (Adcetris Intravenous)

50 mg (per each): $12,093.60

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Adcetris (AR, AT, AU, BB, BE, BR, CH, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HK, HR, HU, ID, IE, IL, IS, JP, KR, LB, LT, LU, LV, MT, MY, NL, NO, PH, PL, PT, RO, SA, SE, SG, SI, SK, TH, TW)


For country code abbreviations (show table)
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  2. Adcetris (brentuximab vedotin) [prescribing information]. Bothell, WA: Seagen Inc; November 2022.
  3. Adcetris (brentuximab vedotin) [product monograph]. Mississauga, Ontario, Canada: Seagen Canada Inc; June 2021.
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  12. Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
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  16. Prince HM, Kim YH, Horwitz SM, et al; ALCANZA study group. Brentuximab vedotin or physician's choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial. Lancet. 2017;390(10094):555-566. doi: 10.1016/S0140-6736(17)31266-7 [PubMed 28600132]
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  19. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. http://www.cdc.gov/niosh/topics/antineoplastic/pdf/hazardous-drugs-list_2016-161.pdf. Updated September 2016. Accessed October 19, 2016.
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