brentuximab vedotin (Rx)

Brand and Other Names:Adcetris
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

  • 50mg/vial
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Classical Hodgkin Lymphoma (cHL)

Previously untreated cHL

  • First-line therapy for previously untreated Stage III or IV cHL in combination with doxorubicin, vinblastine, and dacarbazine (AVD)
  • 1.2 mg/kg IV q2Weeks (in combination with AVD); not to exceed 120 mg/dose 
  • Continue until a maximum of 12 doses, disease progression, or unacceptable toxicity

cHL consolidation

  • Indicated for cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation
  • Initiate within 4–6 weeks post-auto-HSCT or upon recovery from auto-HSCT
  • 1.8 mg/kg IV q3Weeks; not to exceed 180 mg/dose  
  • Continue until a maximum of 16 cycles, disease progression, or unacceptable toxicity

Relapsed cHL

  • Indicated for cHL after failure of auto-HSCT or after failure of at least 2 prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates
  • 1.8 mg/kg IV q3Weeks; not to exceed 180 mg/dose  
  • Continue until disease progression or unacceptable toxicity

Systemic Anaplastic Large Cell Lymphoma

Previously-untreated systemic anaplastic large cell lymphoma (sALCL)

  • Indicated for treatment of previously-untreated sALCL
  • 1.8 mg/kg IV q3Weeks for 6-8 doses; not to exceed 180 mg/dose 

Relapsed sALCL

  • Indicated for treatment of systemic anaplastic large cell lymphoma (sALCL) after failure of at least 1 prior multiagent chemotherapy regimen
  • 1.8 mg/kg IV q3Weeks; not to exceed 180 mg/dose 
  • Continue until disease progression or unacceptable toxicity

Primary Cutaneous Anaplastic Large Cell Lymphoma

Indicated for primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30 expressing mycosis fungoides (MF) who have received prior systemic therapy

1.8 mg/kg IV q3Weeks; not to exceed 180 mg/dose  

Continue until a maximum of 16 cycles, disease progression, or unacceptable toxicity

CD30-expressing Peripheral T-cell Lymphomas

Indicated in 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 (CHP)

1.8 mg/kg IV q3Weeks for 6-8 doses; not to exceed 180 mg/dose

Dosage Modifications

Renal impairment

  • 1.2 mg/kg q2Weeks or 1.8 mg/kg q3Weeks
  • Mild or moderate (CrCl 30-80 mL/min): No dosage adjustment required
  • Severe (CrCl <30 mL/min): Avoid use

Hepatic impairment

  • Mild (Child-Pugh A)
    • 1.2 mg/kg q2Weeks: 0.9 mg/kg q2Weeks; not to exceed 90 mg/dose
    • 1.8 mg/kg q3Weeks: 1.2 mg/kg q3Weeks; not to exceed 120 mg/dose
  • Moderate or severe (Child-Pugh B or C): Avoid use

Peripheral neuropathy

  • Monotherapy (1.8 mg/kg q3Weeks)
    • New or worsening Grade 2 or 3: Hold dose until neuropathy improves to Grade 1 or baseline; restart at 1.2 mg/kg (not to exceed 120 mg/dose)
    • Grade 4: Discontinue brentuximab
  • Combination therapy (1.2 mg/kg q2Weeks)
    • Grade 2: Reduce dose to 0.9 mg/kg/dose q2Weeks; not to exceed 90 mg/dose
    • Grade 3: Hold dose until neuropathy improves to Grade ≤2; restart at 0.9 mg/kg q2Weeks (not to exceed 90 mg/dose); consider modifying dose of other neurotoxic chemotherapy
    • Grade 4: Discontinue brentuximab
  • Combination therapy (1.8 mg/kg q3Weeks)
    • Grade 2 sensory neuropathy: No dosage adjustment required
    • Grade 2 motor neuropathy or Grade 3 sensory neuropathy: Reduce to 1.2 mg/kg q3Weeks (not to exceed 120 mg/dose)
    • Grade 3 motor neuropathy or Grade 4 peripheral neuropathy: Discontinue brentuximab

Neutropenia

  • Combination therapy (1.8 mg/kg q3Weeks or 1.2 mg/kg q2Weeks)
    • Grade ≥3: Administer G-CSF prophylaxis for subsequent cycles for patients not receiving primary G-CSF prophylaxis
  • Monotherapy (1.8 mg/kg q3Weeks)
    • Grade ≥3 neutropenia: Hold dose until resolution to baseline or Grade ≤2 ; consider G-CSF prophylaxis for subsequent cycles
    • Recurrent Grade 4 (despite use of G-CSF prophylaxis): Consider discontinuing brentuximab or reduce to 1.2 mg/kg q3Weeks (not to exceed 120 mg/dose)

Dosing Considerations

Patients weighing >100 kg should be calculated based on a weight of 100 kg

Orphan Designations

Angioimmunoblastic T-cell lymphoma

Cutaneous T-cell lymphoma

Diffuse large B-cell lymphoma

Adult T-cell leukemia/lymphoma

Enteropathy-associated T-cell lymphoma

Orphan sponsor

  • Seattle Genetics, Inc; 21823 30th Drive Southeast, Bothell, WA 98021

Safety and efficacy not established

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Interactions

Interaction Checker

and brentuximab vedotin

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10% (Untreated cHL, Any Grade)

            Anemia (98%)

            Neutropenia (91%)

            Peripheral sensory neuropathy (65%)

            Constipation (42%)

            Vomiting (33%)

            Diarrhea (27%)

            Pyrexia (27%)

            Decreased weight (22%)

            Stomatitis (21%)

            Abdominal pain (21%)

            Febrile neutropenia (19%)

            Bone pain (19%)

            Insomnia (19%)

            Decreased appetite (18%)

            Back pain (13%)

            Rashes, eruptions, exanthems (13%)

            Dyspnea (12%)

            Peripheral motor neuropathy (11%)

            >10% (Untreated cHL, Grade 3 or 4)

            Neutropenia (20-62%)

            Febrile neutropenia (6-13%)

            Anemia (1-11%)

            >10% (pcALCA or MF, Any Grade)

            Anemia (62%)

            Peripheral sensory neuropathy (45%)

            Nausea (36%)

            Diarrhea (29%)

            Fatigue (29%)

            Neutropenia (21%)

            Vomiting (17%)

            Pruritus (17%)

            Pyrexia (17%)

            Alopecia (15%)

            Thrombocytopenia (15%)

            Decreased appetite (15%)

            Arthralgia (12%)

            Myalgia (12%)

            Peripheral edema (11%)

            Maculopapular rash (11%)

            Generalized pruritus (11%)

            Asthenia (11%)

            Dyspnea (11%)

            1-10% (Untreated cHL)

            Increased ALT, all grades (10%)

            Grades 3 or 4

            • Peripheral sensory neuropathy (10%)
            • Vomiting (3%)
            • Diarrhea (3%)
            • Abdominal pain (3%)
            • Increased ALT (3%)
            • Pyrexia (3%)
            • Constipation (2%)
            • Stomatitis (2%)
            • Peripheral motor neuropathy (2%)
            • Dyspnea (1%)

            1-10% (Other Indications)

            Extremity pain (10%)

            Muscle spasms (9-10%)

            Dry skin (4-10%)

            Chills (4%)

            Nausea (3–4%)

            Dyspnea (2–3%)

            Pruritus (2–5%)

            Pyrexia (2%)

            Cough (2%)

            Grade 3 or 4 (pcALCL or MF)

            • Peripheral sensory neuropathy (5%)
            • Fatigue (5%)
            • Diarrhea (3%)
            • Neutropenia (2-3%)
            • Asthenia (2%)
            • Maculopapular rash (2%)
            • Generalized pruritus (2%)
            • Nausea (2%)
            • Vomiting (2%)
            • Thrombocytopenia (2%)

            Postmarketing reports

            Blood and lymphatic system disorders: Febrile neutropenia

            Gastrointestinal disorders: Acute pancreatitis and gastrointestinal complications (including fatal outcomes)

            Hepatobiliary disorders: Hepatotoxicity

            Infections: PML, serious infections and opportunistic infections

            Metabolism and nutrition disorders: Hyperglycemia

            Respiratory, thoracic and mediastinal disorders: Noninfectious pulmonary toxicity including pneumonitis, interstitial lung disease, and ARDS (some with fatal outcomes)

            Skin and subcutaneous tissue disorders: Toxic epidermal necrolysis, including fatal outcomes

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            Warnings

            Black Box Warnings

            Progressive multifocal leukoencephalopathy

            • JC virus infection resulting in PML and death can occur; cases of progressive multifocal leukoencephalopathy (PML) reported
            • PML is a rare, but serious brain infection that can result in death
            • Signs and symptoms of PML may develop over several weeks or months and may include mood changes, unusual behavior, confusion, thinking problems, memory loss, changes in vision, speech, or walking, and a unilateral decrease in strength or weakness

            Contraindications

            Concomitant use of brentuximab with bleomycin because of pulmonary toxicity

            Cautions

            Peripheral neuropathy (predominately sensory neuropathy) and motor neuropathy reported; drug-induced peripheral neuropathy is cumulative; monitor for symptoms of neuropathy (eg, hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain, weakness)

            Fatal and serious cases of febrile neutropenia reported; monitor complete blood counts (CBC) prior to each dose

            Grade 3 or 4 thrombocytopenia or anemia can occur

            Frequency of Grade 3 adverse reactions and deaths reported to be greater in patients with severe renal or hepatic impairment compared to patients with normal renal/hepatic function

            Serious cases of hepatotoxicity, including fatal outcomes reported after first dose or after rechallenge; serious cases of hepatotoxicity, including fatal outcomes; preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase risk; monitor liver enzymes and bilirubin; patients experiencing new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of therapy

            JC virus infection resulting in progressive multifocal leukoencephalopathy (PML) and death reported (see Black Box Warnings)

            Closely monitor for emergence of bacterial, fungal or viral infections

            Events of noninfectious pulmonary toxicity (eg, pneumonitis, interstitial lung disease, acute respiratory distress syndrome [ARDS]), some with fatal outcomes, reported

            Fatal and serious cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) reported; if SJS or TEN occurs, discontinue treatment and administer appropriate medical therapy

            Acute pancreatitis, including fatal outcomes, reported

            Fatal and serious gastrointestinal (GI) complications (eg, perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus) reported; lymphoma with preexisting GI involvement may increase risk of perforation; promptly evaluate for any new or worsening GI symptoms, and treat appropriately

            Fetal harm can occur (see Pregnancy)

            Patients with rapidly proliferating tumor and high tumor burden are at risk of tumor lysis syndrome; closely monitor and treat appropriately

            Infusion-related reactions

            • Infusion-related reactions (eg, anaphylaxis), may occur
            • If anaphylaxis occurs, immediately and permanently discontinue treatment
            • If an infusion-related reaction occurs, interrupt infusion
            • After interrupting or discontinuing treatment, institute appropriate medical management
            • Premedicate patients who previously experienced infusion-related reactions for subsequent infusions
            • Premedication may include acetaminophen, an antihistamine, and a corticosteroid

            Drug interactions overview

            • Strong CYP3A4 Inhibitors
              • Coadministration with ketoconazole, a potent CYP3A4 inhibitor, increased exposure to MMAE which may increase the risk of adverse reaction
              • Closely monitor adverse reactions when concomitantly used with strong CYP3A4 inhibitors
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            Pregnancy & Lactation

            Pregnancy

            Based on the findings from animal studies and mechanism of action, brentuximab may cause fetal harm

            Available data from case reports in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes

            Animal data

            • In animal reproduction studies, administration of brentuximab vedotin to pregnant rats during organogenesis at doses similar to the clinical dose (1.8 mg/kg q3weeks) caused embryo-fetal toxicities, including congenital malformation

            Contraception

            • Verify pregnancy status of females of reproductive potential prior to initiation
            • Advise females of reproductive potential to avoid pregnancy during treatment and for at least 6 months after final dose; immediately report pregnancy
            • May damage spermatozoa and testicular tissue, resulting in possible genetic abnormalities
            • Use effective contraception in males with female sexual partners of reproductive potential during treatment and for at least 6 months after final dose

            Fertility

            • Based on findings in rats, male fertility may be compromised by brentuximab

            Lactation

            There is no information related to the presence of brentuximab vedotin in human milk, the effects on the breastfed child, or the effects on milk production

            Owing to the potential for serious adverse reactions in a breastfed child from brentuximab, including cytopenias and neurologic or gastrointestinal toxicities, breastfeeding is not recommended during treatment

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            CD30-directed antibody-drug conjugate (ADC) consisting of chimeric IgG1 antibody cAC10, specific for human CD30 and the microtubule disrupting agent, monomethyl auristatin E (MMAE, or vedotin)

            Conjugate binds to cell expressing the CD30 antigen and forms a complex that is internalized within the cell and MMAE is released; MMAE induces cell cycle (G2/M phase) arrest by binding to tubules and disrupting cellular microtubule network

            Absorption

            Peak plasma time: 20-30 min (ADC); 1-3 days (MMAE)

            Steady-state: 21 days (1.8 mg/kg q3Weeks); 56 days (1.2 mg/kg q2Weeks)

            Distribution

            Protein Bound: 68-82% (MMAE)

            Vd: 6-10 L (ADC)

            Metabolism

            Data indicated MMAE metabolism occurs primarily via oxidation by CYP3A4/5

            Excretion

            Half-life: 4-6 days

            Excretion: Feces and urine (24% of the total MMAE [72% unchanged and recovered in feces])

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            Administration

            IV Incompatibilities

            Do not mix or administer with other medicinal products

            IV Compatibilities

            0.9% NaCl

            D5W

            Lactated Ringer’s (LR)

            IV Preparation

            Adhere to proper handling, dispensing, and administration of anticancer drugs

            Reconstitution

            • Reconstitute with 10.5 mL sterile water for injection to yield 5 mg/mL
            • Direct stream toward vial wall and not directly at cake or powder to prevent foaming
            • Do not shake vial; gently swirl vial to aid dissolution
            • Reconstituted solution should be clear to slightly opalescent, colorless, and free of visible particulates
            • Discard any unused portion left in vial

            Dilution

            • Calculate dosage volume (mL) and withdraw dose from vial(s)
            • Patients weighing >100 kg should be calculated for 100 kg
            • Dilute reconstituted solution in at least 100 mL of 0.9% NaCl, D5W, or LR (final concentration: 0.4-1.8 mg/mL)
            • Gently invert bag to mix solution
            • Contains no bacteriostatic preservatives, use immediately or refrigerate solution and use within 24 hr

            IV Administration

            Infuse over 30 minutes

            Do not administer as an IV push or bolus

            Recommended prophylactic medications

            • Previously untreated Stage III or IV cHL who are treated with brentuximab + AVD or previously untreated PTCL who are treated with brentuximab + CHP, administer G-CSF beginning with Cycle 1

            Storage

            Unopened vials: Refrigerate at 2-8°C (36-46°F) in original carton to protect from light

            Diluted solutions or reconstituted vials: Refrigerate at 2-8°C (36-46°F) for up to 24 hr

            Do not freeze

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            Images

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.