Drug Detail:Adcetris (Brentuximab vedotin [ bren-tux-i-mab-ve-doe-tin ])
Generic Name: Brentuximab Vedotin 50mg in 10.5mL
Dosage Form: injection, powder, lyophilized, for solution
Drug Class: CD30 monoclonal antibodies
2.1 Recommended Dosage
The recommended ADCETRIS dosage is provided in Table 1. Administer ADCETRIS as a 30-minute intravenous infusion.
For recommended dosage for patients with renal or hepatic impairment, see Dosage and Administration (2.2 and 2.3).
For dosing instructions of combination agents administered with ADCETRIS, see Clinical Studies (14.1 and 14.2) and the manufacturer’s prescribing information.
| * The dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg | ||
| Indication | Recommended Dose* | Frequency and Duration |
| Adult patients with previously untreated Stage III or IV classical Hodgkin lymphoma | 1.2 mg/kg up to a maximum of 120 mg in combination with chemotherapy |
Administer every 2 weeks until a maximum of 12 doses, disease progression, or unacceptable toxicity |
| Pediatric patients with previously untreated high risk classical Hodgkin lymphoma | 1.8 mg/kg up to a maximum of 180 mg in combination with chemotherapy |
Administer every 3 weeks with each cycle of chemotherapy for a maximum of 5 doses |
| Adult patients with classical Hodgkin lymphoma consolidation |
1.8 mg/kg up to a maximum of 180 mg |
Initiate ADCETRIS treatment within 4-6 weeks post-auto-HSCT or upon recovery from auto-HSCT. Administer every 3 weeks until a maximum of 16 cycles, disease progression, or unacceptable toxicity |
| Adult patients with relapsed classical Hodgkin lymphoma | 1.8 mg/kg up to a maximum of 180 mg | Administer every 3 weeks until disease progression or unacceptable toxicity |
| Adult patients with previously untreated systemic ALCL or other CD30-expressing peripheral T-cell lymphomas | 1.8 mg/kg up to a maximum of 180 mg in combination with chemotherapy |
Administer every 3 weeks with each cycle of chemotherapy for 6 to 8 doses |
| Adult patients with relapsed Systemic ALCL | 1.8 mg/kg up to a maximum of 180 mg |
Administer every 3 weeks until disease progression or unacceptable toxicity |
| Adult patients with relapsed primary cutaneous ALCL or CD30-expressing mycosis fungoides | 1.8 mg/kg up to a maximum of 180 mg | Administer every 3 weeks until a maximum of 16 cycles, disease progression, or unacceptable toxicity |
2.2 Recommended Dosage in Patients with Renal Impairment
No dosage adjustment is required for mild renal impairment (CrCL greater than 50-80 mL/min) and moderate renal impairment (CrCL 30-50 mL/min).
Avoid use in patients with severe (CrCL less than 30 mL/min) renal impairment [see Warnings and Precautions (5.6)].
2.3 Recommended Dosage in Patients with Hepatic Impairment
Adult patients with previously untreated Stage III or IV classical Hodgkin lymphoma
Reduce the dosage of ADCETRIS to 0.9 mg/kg up to a maximum of 90 mg every 2 weeks for patients with mild hepatic impairment (Child-Pugh A).
Avoid use in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment [see Warnings and Precautions (5.7)].
All other indications
Reduce the dosage of ADCETRIS to 1.2 mg/kg up to a maximum of 120 mg every 3 weeks for patients with mild hepatic impairment (Child-Pugh A).
Avoid use in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment [see Warnings and Precautions (5.7)].
2.4 Recommended Prophylactic Medications
In adult patients with previously untreated Stage III or IV cHL who are treated with ADCETRIS + doxorubicin, vinblastine, and dacarbazine (AVD), administer G‑CSF beginning with Cycle 1.
In pediatric patients with previously untreated high risk cHL who are treated with ADCETRIS + doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide (AVEPC), administer G-CSF beginning with Cycle 1.
In adult patients with previously untreated PTCL who are treated with ADCETRIS + cyclophosphamide, doxorubicin, and prednisone (CHP), administer G-CSF beginning with Cycle 1.
Dosage Modifications for Adverse Reactions
| Recommended ADCETRIS Dosage from Table 1* | Monotherapy or Combination Therapy | Severity | Dosage Modification |
| * The dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg | |||
| Peripheral Neuropathy | |||
| 1.2 mg/kg up to a maximum of 120 mg every 2 weeks |
In combination with chemotherapy | Grade 2 | Reduce dose to 0.9 mg/kg up to a maximum of 90 mg every 2 weeks |
| Grade 3 | Hold ADCETRIS dosing until improvement to Grade 2 or lower Restart at 0.9 mg/kg up to a maximum of 90 mg every 2 weeks Consider modifying the dose of other neurotoxic chemotherapy agents |
||
| Grade 4 | Discontinue dosing | ||
| 1.8 mg/kg up to a maximum of 180 mg every 3 weeks |
As monotherapy | New or worsening Grade 2 or 3 |
Hold dosing until improvement to baseline or Grade 1 Restart at 1.2 mg/kg up to a maximum of 120 mg every 3 weeks |
| Grade 4 | Discontinue dosing | ||
| In combination with chemotherapy | Grade 2 | Sensory neuropathy: Continue treatment at same dose Motor neuropathy: Reduce dose to 1.2 mg/kg up to a maximum of 120 mg every 3 weeks |
|
| Grade 3 | Sensory neuropathy: Reduce dose to 1.2 mg/kg, up to a maximum of 120 mg every 3 weeks Motor neuropathy: Discontinue dosing | ||
| Grade 4 | Discontinue dosing | ||
| Neutropenia | |||
| 1.2 mg/kg up to a maximum of 120 mg every 2 weeks |
In combination with chemotherapy | Grade 3 or 4 | Administer G‑CSF prophylaxis for subsequent cycles for patients not receiving primary G‑CSF prophylaxis |
| 1.8 mg/kg up to a maximum of 180 mg every 3 weeks |
In combination with chemotherapy | Grade 3 or 4 | Administer G-CSF prophylaxis in subsequent cycles for patients not receiving primary G-CSF |
| 1.8 mg/kg up to a maximum of 180 mg* every 3 weeks |
As monotherapy | Grade 3 or 4 | Hold dosing until improvement to baseline or Grade 2 or lower Consider G-CSF prophylaxis for subsequent cycles |
| Recurrent Grade 4 despite G‑CSF prophylaxis | Consider discontinuation or dose reduction to 1.2 mg/kg up to a maximum of 120 mg every 3 weeks | ||
| * The dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg. † Peripheral neuropathy was assessed using the Balis scale. |
||
| Recommended ADCETRIS Dosage from Table 1* |
Severity | Dosage Modification |
| Peripheral Neuropathy† | ||
| 1.8 mg/kg up to a maximum of 180 mg every 3 weeks |
Grade 2† | Reduce dose of vincristine per prescribing information Continue dosing with ADCETRIS If neuropathy improves to Grade ≤1 by day 8 of next cycle, then resume vincristine at full dose |
| Grade 3† | Discontinue vincristine First Occurrence: Hold ADCETRIS dosing until improvement to ≤ Grade 2 then restart at 1.2 mg/kg up to a maximum of 120 mg Second Occurrence: Hold until improvement to ≤ Grade 2 then restart at 0.8 mg/kg up to a maximum of 80 mg Third Occurrence: Discontinue ADCETRIS |
|
| Grade 4† | Discontinue ADCETRIS and vincristine | |
| Neutropenia | ||
| 1.8 mg/kg up to a maximum of 180 mg every 3 weeks |
Grade 3 or 4 | Reduce dose to 1.2 mg/kg up to a maximum of 120 mg every 3 weeks in patients who are unable to start a cycle > 5 weeks after the start of the previous cycle (> 2-week delay) due to neutropenia |
Instructions for Preparation and Administration
Administration
- Administer ADCETRIS as an intravenous infusion only.
- Do not mix ADCETRIS with, or administer as an infusion with, other medicinal products.
Reconstitution
- Follow procedures for proper handling and disposal of hazardous drugs [see References (15)].
- Use appropriate aseptic technique for reconstitution and preparation of dosing solutions.
- Determine the number of 50 mg vials needed based on the patient’s weight and the prescribed dose [see Dosage and Administration (2.1)].
- Reconstitute each 50 mg vial of ADCETRIS with 10.5 mL of Sterile Water for Injection, USP, to yield a single-dose solution containing 5 mg/mL brentuximab vedotin.
- Direct the stream toward the wall of vial and not directly at the cake or powder.
- Gently swirl the vial to aid dissolution. DO NOT SHAKE.
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The reconstituted solution should be clear to slightly opalescent, colorless, and free of visible particulates.
- Following reconstitution, dilute immediately into an infusion bag. If not diluted immediately, store the solution at 2° to 8°C (36° to 46°F) and use within 24 hours of reconstitution. DO NOT FREEZE.
- Discard any unused portion left in the vial.
Dilution
- Calculate the required volume of 5 mg/mL reconstituted ADCETRIS solution needed.
- Withdraw this amount from the vial and immediately add it to an infusion bag containing 0.9% Sodium Chloride Injection, USP, 5% Dextrose Injection, USP or Lactated Ringer's Injection, USP to achieve a final concentration of 0.4 mg/mL to 1.8 mg/mL brentuximab vedotin.
- Gently invert the bag to mix the solution.
- Following dilution, infuse the ADCETRIS solution immediately. If not used immediately, store the solution at 2° to 8°C (36° to 46°F) and use within 24 hours of reconstitution. DO NOT FREEZE.
