Adcetris 50 mg

Each vial contains Brentuximab Vedotin 50 mg and sodium for approximately 13.2 mg. It also contains the following excipients: Monohydrate citric acid, sodium citrate dihydrate, α,α-trehalose dihydrate, polysorbate 80.

After reconstitution, each mL contains Brentuximab Vedotin 5 mg.

Adcetris 50 mg is an antibody-drug conjugate composed of a CD30-directed monoclonal antibody [recombinant chimeric immunoglobulin G1 (IgG1), produced by recombinant DNA technology in Chinese hamster ovary cells] that is covalently linked to the antimicrotubule agent monomethyl auristatin E (MMAE).

Classical Hodgkin Lymphoma (HL)

​Adcetris 50 mg is indicated for treatment of patients with classical HL after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates.

Classical Hodgkin Lymphoma (HL) Post-auto-HSCT Consolidation

​Adcetris 50 mg is indicated for the treatment of patients with classical HL at high risk of relapse or progression as post-auto-HSCT consolidation.

Systemic Anaplastic Large Cell Lymphoma (sALCL)

​Adcetris 50 mg is indicated for treatment of patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen.

​The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Adcetris 50 mg is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Adcetris 50 mg is used to treat Hodgkin's lymphoma or anaplastic large cell lymphoma.

Adcetris 50 mg is given after a stem cell transplant or other cancer medications have been tried without successful treatment.

Adcetris 50 mg was approved by the US Food and Drug Administration (FDA) on an "accelerated" basis. In clinical studies, Adcetris 50 mg produced complete or partial remission in many people. However, further studies are needed to determine if this medicine can lengthen survival time.

Adcetris 50 mg may also be used for purposes not listed in this medication guide.

Dosage Recommendations

Administer Adcetris 50 mg as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity. See Table 1 for the recommended starting dosage.

For classical HL post-auto-HSCT consolidation treatment, initiate Adcetris 50 mg treatment within 4–6 weeks post-auto-HSCT or upon recovery from auto-HSCT. These patients should continue treatment until a maximum of 16 cycles, disease progression, or unacceptable toxicity.

Table 1: Recommended Adcetris 50 mg Dosage

Dose Modification

Peripheral Neuropathy

For new or worsening Grade 2 or 3 neuropathy, dosing should be held until neuropathy improves to Grade 1 or baseline and then restarted at 1.2 mg/kg. For Grade 4 peripheral neuropathy, Adcetris 50 mg should be discontinued.

Neutropenia

The dose of Adcetris 50 mg should be held for Grade 3 or 4 neutropenia until resolution to baseline or Grade 2 or lower. Consider G-CSF prophylaxis for subsequent cycles in patients who experience Grade 3 or 4 neutropenia in the previous cycle. In patients with recurrent Grade 4 neutropenia despite the use of G-CSF prophylaxis, consider discontinuation or dose reduction of Adcetris 50 mg to 1.2 mg/kg.

Instructions For Preparation And Administration

Administration

• Administer Adcetris 50 mg as an intravenous infusion only.
• Do not mix Adcetris 50 mg with, or administer as an infusion with, other medicinal products.

Reconstitution

• Follow procedures for proper handling and disposal of anticancer drugs.
• 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.
• Reconstitute each 50 mg vial of Adcetris 50 mg with 10.5 mL of Sterile Water for Injection, USP, to yield a single-use solution containing 5 mg/mL Adcetris 50 mg.
• 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.
• Inspect the reconstituted solution for particulates and discoloration. 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 2–8°C (36–46°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 50 mg solution needed.
• Withdraw this amount from the vial and immediately add it to an infusion bag containing a minimum volume of 100 mL of 0.9% Sodium Chloride Injection, 5% Dextrose Injection or Lactated Ringer's Injection to achieve a final concentration of 0.4 mg/mL to 1.8 mg/mL Adcetris 50 mg.
• Gently invert the bag to mix the solution.
• Following dilution, infuse the Adcetris 50 mg solution immediately. If not used immediately, store the solution at 2–8°C (36–46°F) and use within 24 hours of reconstitution. DO NOT FREEZE.

How supplied

Dosage Forms And Strengths

For injection: 50 mg of Adcetris 50 mg as a sterile, white to off-white lyophilized, preservative-free cake or powder in a single-use vial for reconstitution.

Storage And Handling

Adcetris 50 mg (Adcetris 50 mg) for Injection is supplied as a sterile, white to off-white preservative-free lyophilized cake or powder in individually-boxed single-use vials:

NDC (51144-050-01), 50 mg Adcetris 50 mg.

Storage

Store vial at 2–8°C (36–46°F) in the original carton to protect from light.

Special Handling

Adcetris 50 mg is an antineoplastic product. Follow special handling and disposal procedures.

REFERENCES

1. OSHA Hazardous Drugs. OSHA. [Accessed on 30 July 2013, from http://www.osha.gov/SLTC/hazardousdrugs/index.html]

Manufactured by: Seattle Genetics, Inc., Bothell, WA 98021 1-855-473-2436. Revised: Mar 2016

See also:
What is the most important information I should know about Adcetris 50 mg?

You should not receive Adcetris 50 mg if you are allergic to it, or if you are also receiving another cancer medicine called bleomycin (Blenoxane).

Some people receiving a Adcetris 50 mg injection have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you feel nauseated, itchy, or if you have a fever, chills, cough, or trouble breathing during the injection. Infusion reactions often occur within the first 24 hours after the start of your Adcetris 50 mg infusion.

Adcetris 50 mg can lower blood cells that help your body fight infections and help your blood clot. Your blood may need to be tested often. Avoid being near people who are sick or have infections. Avoid activities that may increase your risk of bleeding injury. Tell your doctor at once if you develop signs of infection.

While using Adcetris 50 mg, you may need frequent blood tests at your doctor's office.

Adcetris 50 mg may cause a serious viral infection of the brain that can lead to disability or death. Call your doctor right away if you notice any change in your mental state, problems with speech or walking, or decreased vision. These symptoms may start gradually and get worse quickly.

Use Adcetris 50 mg as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Adcetris 50 mg is given as an injection at your doctor's office, hospital, or clinic. Contact your health care provider if you have any questions.
• If you miss a dose of Adcetris 50 mg, contact your doctor right away.

Ask your health care provider any questions you may have about how to use Adcetris 50 mg.

Brentuximab is used to treat certain types of cancers (Hodgkin's lymphoma, systemic anaplastic large cell lymphoma). It works by slowing or stopping the growth of cancer cells.

How to use Adcetris 50 mg intravenous

This medication is given by injection into a vein over 30 minutes by a health care professional. It is given as directed by your doctor, usually once every 3 weeks.

The dosage is based on your medical condition, weight, and response to treatment.

Your health care professional will monitor you during the infusion in case you develop a reaction to brentuximab. If a rare but severe allergic reaction occurs, the infusion will be stopped and you should never receive brentuximab again. If a less serious reaction occurs, the infusion will be interrupted, you will be treated for the reaction, and the infusion will be continued. If you develop a less serious infusion reaction, you will be directed by your doctor to take certain medications (such as acetaminophen, antihistamines, corticosteroids) before each future brentuximab infusion to lessen the chance of symptoms. Consult your doctor for more details. Get medical help right away if you have symptoms such as fever, chills, rash, itching, cough, or trouble breathing within 24 hours of the infusion.

See also:
What other drugs will affect Adcetris 50 mg?

In vitro data indicate that monomethyl auristatin E (MMAE) is a substrate and an inhibitor of CYP3A4/5. In vitro data indicate that MMAE is also a substrate of the efflux transporter P-glycoprotein (P-gp).

Effect Of Other Drugs On Adcetris 50 mg

CYP3A4 Inhibitors/Inducers

MMAE is primarily metabolized by CYP3A. Co-administration of Adcetris 50 mg with ketoconazole, a potent CYP3A4 inhibitor, increased exposure to MMAE by approximately 34%. Patients who are receiving strong CYP3A4 inhibitors concomitantly with Adcetris 50 mg should be closely monitored for adverse reactions. Co-administration of Adcetris 50 mg with rifampin, a potent CYP3A4 inducer, reduced exposure to MMAE by approximately 46%.

P-gp Inhibitors

Co-administration of Adcetris 50 mg with P-gp inhibitors may increase exposure to MMAE. Patients who are receiving P-gp inhibitors concomitantly with Adcetris 50 mg should be closely monitored for adverse reactions.

Effect Of Adcetris 50 mg On Other Drugs

Co-administration of Adcetris 50 mg did not affect exposure to midazolam, a CYP3A4 substrate. MMAE does not inhibit other CYP enzymes at relevant clinical concentrations. Adcetris 50 mg is not expected to alter the exposure to drugs that are metabolized by CYP3A4 enzymes.

See also:
What are the possible side effects of Adcetris 50 mg?

Summary of the Safety Profile: The safety profile of Adcetris 50 mg is based on available clinical trial data, the named patient program (NPP), and post-marketing experience to date. Frequencies of adverse reactions described as follows and in Table 7 have been determined based on data generated from clinical studies.

Serious infections and opportunistic infections have been reported in patients treated with this medicine. In the phase 2 population, 16% of patients reported an event term that referred to an infection.

Serious adverse drug reactions in the phase 2 population were: Neutropenia, thrombocytopenia, constipation, diarrhea, vomiting, pyrexia, peripheral motor neuropathy and peripheral sensory neuropathy, hyperglycemia, demyelinating polyneuropathy, TLS and Stevens-Johnson syndrome.

The most frequently observed adverse reactions in the phase 2 population were: Peripheral sensory neuropathy, fatigue, nausea, diarrhea, neutropenia, vomiting, pyrexia and upper respiratory tract infection.

In the phase 2 population, adverse reactions led to treatment discontinuation in 19% of patients receiving Adcetris 50 mg. Serious adverse reactions that led to treatment discontinuation in ≥2 HL or sALCL patients were peripheral sensory neuropathy (6%) and peripheral motor neuropathy (2%).

The safety data in patients with relapsed or refractory HL who had not received an ASCT and were treated with the recommended dose of 1.8 mg/kg every 3 weeks in the phase 1 dose escalation and clinical pharmacology studies (n=15 patients) and in the NPP (n=26 patients) were consistent with the safety profile of the pivotal clinical studies.

Tabulated List of Adverse Reactions: Adverse reactions for Adcetris 50 mg are listed by MedDRA system organ class and preferred term. Within each system organ class, adverse reactions are listed under frequency categories of: Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Description of Selected Adverse Reactions: Adverse reactions that led to dose delays of up to 3 weeks in >5% of patients were neutropenia (14%) and peripheral sensory neuropathy (11%).

The adverse reaction that led to a dose reduction in >5% of patients was peripheral sensory neuropathy (8%). Ninety percent (90%) of patients in the phase 2 studies remained at the recommended dose of 1.8 mg/kg while on treatment.

Severe and prolonged (≥1 week) neutropenia can occur with this treatment which may increase the risk of patients developing serious infections. The median duration of grade 3 or 4 neutropenia was limited (1 week); 2% of patients had grade 4 neutropenia that lasted ≥7 days. Less than ½ of the patients in the phase 2 population with grade 3 or 4 neutropenia had temporally associated infections and the majority of temporally associated infections were grade 1 or 2.

Among patients who experienced peripheral neuropathy, the median follow-up time from end of treatment until last evaluation was approximately 10 weeks. At the time of last evaluation, 62% of the 84 patients who experienced peripheral neuropathy had resolution or improvement of their peripheral neuropathy symptoms. The median time from onset to resolution or improvement for all events was 6.6 weeks (range from 0.3-54.4 weeks).

PML has been reported outside of the pivotal phase 2 clinical trials.

Acute pancreatitis (including fatal outcomes) has been reported outside of the pivotal phase 2 clinical trials. Consider the diagnosis of acute pancreatitis for patients presenting with new or worsening abdominal pain.

Anaphylactic reactions have been reported outside of the pivotal phase 2 clinical trials. Symptoms of an anaphylactic reaction may include, but are not limited to, urticaria, angioedema, hypotension and bronchospasm.

Febrile neutropenia has been reported outside of the pivotal phase 2 clinical trials. A patient enrolled in a phase 1 dose escalation trial experienced grade 5 febrile neutropenia after receiving a single dose of 3.6 mg/kg of Adcetris 50 mg.

Immunogenicity: Patients with relapsed or refractory HL or sALCL in two phase 2 studies were tested for antibodies to Adcetris 50 mg every 3 weeks using a sensitive electrochemiluminescent immunoassay. Approximately 35% of patients in these studies developed antibodies to Adcetris 50 mg. Of these patients, the majority became positive prior to dose 2, 7% were persistently antitherapeutic antibodies (ATA)-positive, and 62% of the ATA-positive patients had neutralizing antibodies. One percent (1%) of patients experienced adverse reactions consistent with infusion-related reactions that led to discontinuation of treatment.

The presence of antibodies to Adcetris 50 mg did not correlate with a clinically meaningful reduction in serum Adcetris 50 mg levels and did not result in a decrease in the efficacy of Adcetris 50 mg. While the presence of antibodies to Adcetris 50 mg does not necessarily predict the development of an IRR, there was a higher incidence of IRRs observed in patients with persistently positive ATA (30%) relative to patients with transiently positive ATA (12%) and never positive ATA (7%).

Reporting of Suspected Adverse Reactions: Reporting suspected adverse reactions after authorization of Adcetris 50 mg is important. It allows continued monitoring of the benefit/risk balance of Adcetris 50 mg. Healthcare professionals are asked to report any suspected adverse reactions to the marketing authorization holder.