Adcetris

Name: Adcetris

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include severe forms of some of the side effects listed in this medication guide.

Stability

Storage

Parenteral

Powder for Injection

2–8°C in original package to protect from light.1

May store reconstituted drug in vial at 2–8°C; use within 24 hours.1 Protect from direct sunlight until time of use.19 Do not freeze.1

May store infusion solution at 2–8°C; use within 24 hours of reconstitution.1 Protect from direct sunlight until time of use.19 Do not freeze.1

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Compatible1

Dextrose 5% in water

Ringer’s injection, lactated

Sodium chloride 0.9%

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Brentuximab Vedotin

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, for IV infusion only

50 mg

Adcetris

Seattle Genetics

Commonly used brand name(s)

In the U.S.

  • Adcetris

Available Dosage Forms:

  • Powder for Solution

Therapeutic Class: Antineoplastic Agent

Pharmacologic Class: Antibody Drug Conjugate

Before Using Adcetris

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of brentuximab injection in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies have not been performed on the relationship of age to the effects of brentuximab injection in the geriatric population.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

  • Bleomycin

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Atazanavir
  • Boceprevir
  • Ceritinib
  • Delavirdine
  • Idelalisib
  • Indinavir
  • Nefazodone
  • Nelfinavir
  • Posaconazole
  • Saquinavir
  • Telithromycin
  • Tipranavir
  • Voriconazole

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

  • Grapefruit Juice

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Infection—May decrease your body's ability to fight an infection.
  • Kidney disease or
  • Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.
  • Lung problems (eg, cough, shortness of breath) or
  • Neutropenia (low white blood cells) or
  • Peripheral neuropathy (nerve problem) or
  • Pneumonitis (inflammation of the lung) or
  • Stomach or intestinal bleeding or
  • Stomach ulcer or
  • Thrombocytopenia (low platelets in the blood)—Use with caution. May make these conditions worse.

How is this medicine (Adcetris) best taken?

Use this medicine (Adcetris) as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • It is given as an infusion into a vein over a period of time.
  • Other drugs may be given to help with infusion side effects.
  • You may have more chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu.
  • You may bleed more easily. Be careful and avoid injury. Use a soft toothbrush and an electric razor.

What do I do if I miss a dose?

  • Call your doctor to find out what to do.

Adcetris Description

Adcetris (brentuximab vedotin) is a CD30-directed antibody-drug conjugate (ADC) consisting of three components: 1) the chimeric IgG1 antibody cAC10, specific for human CD30, 2) the microtubule disrupting agent MMAE, and 3) a protease-cleavable linker that covalently attaches MMAE to cAC10.

Brentuximab vedotin has an approximate molecular weight of 153 kDa.  Approximately 4 molecules of MMAE are attached to each antibody molecule.  Brentuximab vedotin is produced by chemical conjugation of the antibody and small molecule components.  The antibody is produced by mammalian (Chinese hamster ovary) cells, and the small molecule components are produced by chemical synthesis.

Adcetris (brentuximab vedotin) for Injection is supplied as a sterile, white to off-white, preservative-free lyophilized cake or powder in single-use vials.  Following reconstitution with 10.5 mL Sterile Water for Injection, USP, a solution containing 5 mg/mL brentuximab vedotin is produced.  The reconstituted product contains 70 mg/mL trehalose dihydrate, 5.6 mg/mL sodium citrate dihydrate, 0.21 mg/mL citric acid monohydrate, and 0.20 mg/mL polysorbate 80 and water for injection.  The pH is approximately 6.6.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies with brentuximab vedotin or the small molecule (MMAE) have not been conducted.

MMAE was genotoxic in the rat bone marrow micronucleus study through an aneugenic mechanism.  This effect is consistent with the pharmacological effect of MMAE as a microtubule disrupting agent.  MMAE was not mutagenic in the bacterial reverse mutation assay (Ames test) or the L5178Y mouse lymphoma forward mutation assay.

Fertility studies with brentuximab vedotin or MMAE have not been conducted.  However, results of repeat-dose toxicity studies in rats indicate the potential for brentuximab vedotin to impair male reproductive function and fertility.  In a 4-week repeat-dose toxicity study in rats with weekly dosing at 0.5, 5, or 10 mg/kg brentuximab vedotin, seminiferous tubule degeneration, Sertoli cell vacuolation, reduced spermatogenesis, and aspermia were observed.  Effects in animals were seen mainly at 5 and 10 mg/kg of brentuximab vedotin.  These doses are approximately 3 and 6-fold the human recommended dose of 1.8 mg/kg, respectively, based on body weight.

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

Monitor patients for peripheral neuropathy and institute dose modifications accordingly (see Dosage Modifications)

If an infusion reaction occurs, the infusion should be interrupted and appropriate medical management instituted (higher incidence in patients who developed persistently positive antibodies)

If anaphylaxis occurs, the infusion should be discontinued immediately and appropriate medical management instituted

If Stevens-Johnson syndrome or toxic epidermal necrolysis occurs, discontinue and administer appropriate medical therapy

Monitor CBC prior to each dose; if Grade 3 or 4 neutropenia develops, manage by dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses (see Dosage Modifications)

Patients with rapidly proliferating tumor and high tumor burden are at risk of tumor lysis syndrome; monitored closely and take appropriate measures

Fetal harm can occur; advise pregnant women of the potential hazard to the fetus; advise females of reproductive potential to avoid pregnancy during treatment and for at least 6 months after final dose

Coadministration of strong CYP3A4 inhibitors may increase risk for toxicity

Avoid use with severe renal impairment (CrCl <30 mL/min); frequency of Grade 3 adverse reactions and deaths reported to be greater in patients with severe renal impairment compared to patients with normal renal function, possibly due to higher MMAE exposure

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

Decrease dose with mild hepatic impairment and avoid use with moderate or severe hepatic impairment (see Dosage Modifications)

JC virus infection resulting in progressive multifocal leukoencephalopathy (PML) and death reported in brentuximab-treated patients; consider the diagnosis of PML in any patient presenting with new onset signs and symptoms of CNS abnormalities; hold dosing for any suspected case of PML and discontinue drug dosing if a diagnosis of PML is confirmed

Events of noninfectious pulmonary toxicity including pneumonitis, interstitial lung disease, and acute respiratory distress syndrome (ARDS), some with fatal outcomes, reported; monitor patients for new or worsening symptoms

Closely monitor patients for emergence of bacterial, fungal or viral infections

Fatal and serious gastrointestinal (GI) complications including perforation, hemorrhage, erosion, ulcer, intestinal obstruction, enterocolitis, neutropenic colitis, and ileus reported; lymphoma with preexisting GI involvement may increase risk of perforation; perform prompt diagnostic evaluation in the event of new or worsening GI symptoms, and treat appropriately

Important information

You should not receive Adcetris if you are also receiving another cancer medicine called bleomycin (Blenoxane).

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

How is Adcetris given?

Adcetris is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting.

Before you receive Adcetris, you may be given other medications to prevent certain side effects that brentuximab vedotin can cause.

Adcetris is usually given once every 3 weeks for up to 16 treatment cycles, or until your body no longer responds to the medication. Follow your doctor's dosing instructions very carefully.

Adcetris can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests.

If you need surgery, tell the surgeon ahead of time that you are using this medicine. You may need to stop using the medicine for a short time.

What other drugs will affect Adcetris?

Many drugs can interact with brentuximab vedotin. Not all possible interactions are listed here. Tell your doctor about all your medications and any you start or stop using during treatment with Adcetris, especially:

  • St. John's wort;

  • an antibiotic or antifungal medicine;

  • antiviral medicine to treat hepatitis, HIV, or AIDS;

  • heart medication;

  • seizure medicine; or

  • tuberculosis medications.

This list is not complete and many other drugs can interact with brentuximab vedotin. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.

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