Adcetris

Name: Adcetris

How should this medicine be used?

Brentuximab vedotin injection comes as a powder to be mixed with fluid and injected over 30 minutes intravenously (into a vein) by a doctor or nurse in a medical office or hospital. It is usually injected once every 3 weeks. This treatment period is called a cycle, and the cycle may be repeated up to 16 times.

Brentuximab vedotin injection may cause serious allergic reactions, which usually occur during the infusion of the medication or within 24 hours of receiving a dose. You may receive certain medications before your infusion to prevent an allergic reaction if you had a reaction with previous treatment. Your doctor will watch you carefully while you are receiving brentuximab vedotin. If you experience any of the following symptoms, tell your doctor immediately: fever, chills, rash, hives, itching, or difficulty breathing.

Your doctor may need to delay your treatment, adjust your dose, or stop your treatment if you experience certain side effects. Be sure to tell your doctor how you are feeling during your treatment with brentuximab vedotin injection.

Indications

Classical Hodgkin Lymphoma (HL)

ADCETRIS 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 is indicated for the treatment of patients with classical HL at high risk of relapse or progression as post-auto-HSCT consolidation [see Clinical Studies].

Systemic Anaplastic Large Cell Lymphoma (sALCL)

ADCETRIS 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 [see Clinical Studies]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

How supplied

Dosage Forms And Strengths

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

Storage And Handling

ADCETRIS (brentuximab vedotin) 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 brentuximab vedotin.

Storage

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

Special Handling

ADCETRIS is an antineoplastic product. Follow special handling and disposal procedures1.

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

Warnings

Included as part of the PRECAUTIONS section.

How is brentuximab vedotin given?

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

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

Brentuximab vedotin 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.

Brentuximab vedotin 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 brentuximab vedotin. You may need to stop using the medicine for a short time.

Dosage Forms and Strengths

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

Clinical Studies

Classical Hodgkin Lymphoma

Clinical Trial in Relapsed Classical HL (Study 1)

The efficacy of Adcetris in patients with classical HL who relapsed after autologous hematopoietic stem cell transplantation was evaluated in one open-label, single-arm, multicenter trial.  One hundred two patients were treated with 1.8 mg/kg of Adcetris intravenously over 30 minutes every 3 weeks.  An independent review facility (IRF) performed efficacy evaluations which included overall response rate (ORR = complete remission [CR] + partial remission [PR]) and duration of response as defined by clinical and radiographic measures including computed tomography (CT) and positron-emission tomography (PET) as defined in the 2007 Revised Response Criteria for Malignant Lymphoma (modified).

The 102 patients ranged in age from 15–77 years (median, 31 years) and most were female (53%) and white (87%). Patients had received a median of 5 prior therapies including autologous hematopoietic stem cell transplantation.

The efficacy results are summarized in Table 4.  Duration of response is calculated from date of first response to date of progression or data cutoff date.

Table 4: Efficacy Results in Patients with Classical Hodgkin Lymphoma (Study 1)
* Not estimable † Follow up was ongoing at the time of data submission.
  N=102
  Percent (95% CI) Duration of Response, in months
Median (95% CI) Range
 CR 32 (23, 42) 20.5 (12.0, NE* ) 1.4 to 21.9†
 PR 40 (32, 49)    3.5 (2.2, 4.1)  1.3 to 18.7
 ORR 73 (65, 83) 6.7 (4.0, 14.8) 1.3 to 21.9†

Randomized Placebo-controlled Clinical Trial in Classical HL Post-auto-HSCT Consolidation (Study 3)

The efficacy of Adcetris in patients with classical HL at high risk of relapse or disease progression post-auto-HSCT was studied in a randomized, double-blind, placebo-controlled clinical trial.  Three hundred twenty-nine patients were randomized 1:1 to receive placebo or Adcetris 1.8 mg/kg intravenously over 30 minutes every 3 weeks for up to 16 cycles, beginning 30–45 days post-auto-HSCT.  Patients in the placebo arm with progressive disease per investigator could receive Adcetris as part of a separate trial.  The primary endpoint was progression-free survival (PFS) determined by IRF.  Standard international guidelines were followed for infection prophylaxis for HSV, VZV, and PCP post-auto-HSCT [see Clinical Trial Experience (6.1)].

High risk of post-auto-HSCT relapse or progression was defined according to status following frontline therapy: refractory, relapse within 12 months, or relapse ≥12 months with extranodal disease.  Patients were required to have obtained a CR, PR, or stable disease (SD) to most recent pre-auto-HSCT salvage therapy.

A total of 329 patients were enrolled and randomized (165 Adcetris, 164 placebo); 327 patients received study treatment.  Patient demographics and baseline characteristics were generally balanced between treatment arms.  The 329 patients ranged in age from 18–76 years (median, 32 years) and most were male (53%) and white (94%).  Patients had received a median of 2 prior systemic therapies (range, 2–8) excluding autologous hematopoietic stem cell transplantation.

The efficacy results are summarized in Table 5. PFS is calculated from randomization to date of disease progression or death (due to any cause).  The median PFS follow-up time from randomization was 22 months (range, 0–49).  Study 3 demonstrated a statistically significant improvement in IRF-assessed PFS and increase in median PFS in the Adcetris arm compared with the placebo arm.  At the time of the PFS analysis, an interim overall survival analysis demonstrated no difference.

Table 5: Efficacy Results in Patients with Classical HL Post-auto-HSCT Consolidation (Study 3)
* Estimates are unreliable † Not estimable
Progression-free Survival Adcetris
N=165
Placebo
N=164
Independent Review Facility    
            Number of events (%)  60 (36) 75 (46)
            Median months (95% CI) 42.9* (30.4, 42.9*) 24.1 (11.5, NE†)
            Stratified Hazard Ratio (95% CI) 0.57 (0.40, 0.81)
            Stratified Log-Rank Test P-value P=0.001

Systemic Anaplastic Large Cell Lymphoma

Clinical Trial in Relapsed sALCL (Study 2)

The efficacy of Adcetris in patients with relapsed sALCL was evaluated in one open-label, single-arm, multicenter trial.  This trial included patients who had sALCL that was relapsed after prior therapy.  Fifty-eight patients were treated with 1.8 mg/kg of Adcetris administered intravenously over 30 minutes every 3 weeks.  An IRF performed efficacy evaluations which included overall response rate (ORR = complete remission [CR] + partial remission [PR]) and duration of response as defined by clinical and radiographic measures including computed tomography (CT) and positron-emission tomography (PET) as defined in the 2007 Revised Response Criteria for Malignant Lymphoma (modified).

The 58 patients ranged in age from 14–76 years (median, 52 years) and most were male (57%) and white (83%).  Patients had received a median of 2 prior therapies; 26% of patients had received prior autologous hematopoietic stem cell transplantation.  Fifty percent (50%) of patients were relapsed and 50% of patients were refractory to their most recent prior therapy.  Seventy-two percent (72%) were anaplastic lymphoma kinase (ALK)-negative.

The efficacy results are summarized in Table 6.  Duration of response is calculated from date of first response to date of progression or data cutoff date.

Table 6: Efficacy Results in Patients with Systemic Anaplastic Large Cell Lymphoma (Study 2)
* Not estimable † Follow up was ongoing at the time of data submission.
  N=58
  Percent (95% CI) Duration of Response, in months
Median (95% CI) Range
CR 57 (44, 70) 13.2 (10.8, NE* ) 0.7 to 15.9†
PR  29 (18, 41)  2.1 (1.3, 5.7) 0.1 to 15.8†
ORR 86 (77, 95) 12.6 (5.7, NE* ) 0.1 to 15.9†

References

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

How Supplied/Storage and Handling

How Supplied

Adcetris (brentuximab vedotin) 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 brentuximab vedotin.

Storage

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

Special Handling

Adcetris is an antineoplastic product.  Follow special handling and disposal procedures1.

Patient Counseling Information

• Peripheral neuropathy

Advise patients that Adcetris can cause a peripheral neuropathy. They should be advised to report to their health care provider any numbness or tingling of the hands or feet or any muscle weakness [see Warnings and Precautions (5.1)].

• Fever/Neutropenia
Advise patients to contact their health care provider if a fever of 100.5°F or greater or other evidence of potential infection such as chills, cough, or pain on urination develops [see Warnings and Precautions (5.3)].

• Infusion reactions

Advise patients to contact their health care provider if they experience signs and symptoms of infusion reactions including fever, chills, rash, or breathing problems within 24 hours of infusion [see Warnings and Precautions (5.2)].

• Hepatotoxicity

Advise patients to report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice [see Warnings and Precautions (5.8)].

• Progressive multifocal leukoencephalopathy

Instruct patients receiving Adcetris to immediately report if they have any of the following neurological, cognitive, or behavioral signs and symptoms or if anyone close to them notices these signs and symptoms [see Boxed Warning, Warnings and Precautions (5.9)]:

      • changes in mood or usual behavior
      • confusion, thinking problems, loss of memory
      • changes in vision, speech, or walking
      • decreased strength or weakness on one side of the body

• Pulmonary Toxicity

Instruct patients to report symptoms that may indicate pulmonary toxicity, including cough or shortness of breath [see Warnings and Precautions (5.10)].

• Pancreatitis

Advise patients to contact their health care provider if they develop severe abdominal pain [see Adverse Reactions (6.2)].

• Gastrointestinal Complications

Advise patients to contact their health care provider if they develop severe abdominal pain, chills, fever, nausea, vomiting, or diarrhea [see Warnings and Precautions (5.12)].

• Females and Males of Reproductive Potential

Adcetris can cause fetal harm.  Advise women receiving Adcetris to avoid pregnancy during Adcetris treatment and for at least 6 months after the final dose of Adcetris.

Advise males with female sexual partners of reproductive potential to use effective contraception during Adcetris treatment and for at least 6 months after the final dose of Adcetris [see Use in Specific Populations (8.3)].

Advise patients to report pregnancy immediately [see Warnings and Precautions (5.13)].

• Lactation

Advise patients to avoid breastfeeding while receiving Adcetris [see Use in Specific Populations (8.2)].

Manufactured by:
Seattle Genetics, Inc.
Bothell, WA 98021
1-855-473-2436
U.S. License 1853

Adcetris, Seattle Genetics and  are US registered trademarks of Seattle Genetics, Inc. © 2016 Seattle Genetics, Inc., Bothell, WA 98021.  All rights reserved.

Package label

NDC 51144-050-01

Adcetris®

(brentuximab vedotin)
FOR INJECTION

50 mg/vial

Single-use vial.

Discard unused portion.

Reconstitution and dilution required

For intravenous use only

Rx Only

SeattleGenetics®

Adcetris  
brentuximab vedotin injection, powder, lyophilized, for solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:51144-050
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Brentuximab Vedotin (Brentuximab Vedotin) Brentuximab Vedotin 50 mg  in 10.5 mL
Inactive Ingredients
Ingredient Name Strength
Trehalose Dihydrate  
Trisodium Citrate Dihydrate  
Citric Acid Monohydrate  
Polysorbate 80  
Product Characteristics
Color WHITE (off-white) Score     
Shape Size
Flavor Imprint Code
Contains     
Packaging
# Item Code Package Description
1 NDC:51144-050-01 1 VIAL, SINGLE-DOSE in 1 BOX
1 10.5 mL in 1 VIAL, SINGLE-DOSE
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
BLA BLA125388 08/25/2011
Labeler - Seattle Genetics, Inc. (028484371)
Establishment
Name Address ID/FEI Operations
PIERRE FABRE MEDICAMENT PRODUCTION 504638276 analysis(51144-050), manufacture(51144-050)
Establishment
Name Address ID/FEI Operations
BSP Pharmaceuticals Srl 857007830 analysis(51144-050), manufacture(51144-050)
Establishment
Name Address ID/FEI Operations
Seattle Genetics, Inc. 028484371 analysis(51144-050)
Establishment
Name Address ID/FEI Operations
Covance Laboratories 213137276 analysis(51144-050)
Revised: 09/2016   Seattle Genetics, Inc.

What should i avoid while receiving brentuximab vedotin (adcetris)?

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

What is Adcetris?

Adcetris (brentuximab vedotin) is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

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

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

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

For the Consumer

Applies to brentuximab: intravenous powder for solution

Along with its needed effects, brentuximab (the active ingredient contained in Adcetris) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking brentuximab:

More common
  • Black, tarry stools
  • bleeding gums
  • blood in the urine or stools
  • body aches or pain
  • burning, numbness, tingling, or painful sensations
  • chills
  • cough
  • difficult or labored breathing
  • difficulty with breathing
  • ear congestion
  • fever
  • headache
  • loss of voice
  • lower back or side pain
  • pain
  • painful or difficult urination
  • pale skin
  • pinpoint red spots on the skin
  • sneezing
  • sore throat
  • stuffy or runny nose
  • swollen, painful, or tender lymph glands in the neck, armpit, or groin
  • tightness in the chest
  • troubled breathing with exertion
  • ulcers, sores, or white spots in the mouth
  • unsteadiness or awkwardness
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • weakness in the arms, hands, legs, or feet
Less common
  • Anxiety
  • back pain
  • bladder pain
  • blistering, peeling, or loosening of the skin
  • bloating or swelling of the face, arms, hands, lower legs, or feet
  • blurred vision
  • chest pain
  • cloudy urine
  • confusion
  • convulsions
  • diarrhea
  • dizziness or lightheadedness
  • drowsiness
  • fainting
  • fast heartbeat
  • frequent urge to urinate
  • general feeling of discomfort or illness
  • irregular heartbeat
  • itching
  • joint pain, stiffness, or swelling
  • muscle pain
  • rapid weight gain
  • red skin lesions, often with a purple center
  • red, irritated eyes
  • severe pain in the chest
  • stomach pain
  • sudden onset of severe breathing difficulty
  • sudden shortness of breath or troubled breathing
  • thickening of bronchial secretions
  • unusual weight gain or loss
Incidence not known
  • Bloody stools
  • heartburn
  • indigestion
  • nausea
  • severe abdominal pain, cramping, or burning
  • severe constipation
  • severe vomiting
  • vomiting of material that looks like coffee grounds

Some side effects of brentuximab may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Decreased appetite or weight
  • difficulty having a bowel movement (stool)
  • difficulty with moving
  • hair loss or thinning of the hair
  • muscle spasms
  • muscle stiffness
  • night sweats
  • pain in the arms or legs
  • rash
  • trouble sleeping
  • vomiting
Less common
  • Dry skin

For Healthcare Professionals

Applies to brentuximab: intravenous powder for injection

Dermatologic

Very common (10% or more): Rash (up to 31%), pruritus (up to 19%), alopecia (up to 14), night sweats (up to 12%), dry skin (up to 10%)
Rare (less than 0.1%): : Stevens-Johnson syndrome (SJS) (including fatal outcomes), toxic epidermal necrolysis (including fatal outcomes)[Ref]

Gastrointestinal

Very common (10% or more): Nausea (up to 42%), diarrhea (up to 36%), abdominal pain (up to 25%), vomiting (up to 22%), constipation (up to 19%)
Postmarketing reports: Pancreatitis (including fatal outcomes)[Ref]

Hematologic

Very common (10% or more): Neutropenia (any grade) (up to 78%), anemia (up to 52%), thrombocytopenia (up to 41%), lymphadenopathy (up to 11%)
Postmarketing reports: Febrile neutropenia[Ref]

Hypersensitivity

Frequency not reported: Anaphylactic reaction[Ref]

Metabolic

Very common (10% or more): Weight decreased (up to 19%), decreased appetite (up to 11%)
Common (1% to 10%): Hyperglycemia[Ref]

Musculoskeletal

Very common (10% or more): Arthralgia (up to 19%), myalgia (up to 17%), back pain (up to 14%), pain in extremity (up to 10%)
Common (1% to 10%): Muscle spasms[Ref]

Nervous system

Very common (10% or more): Peripheral sensory neuropathy (up to 56%), peripheral motor neuropathy (up to 23%), headache (up to 19%), dizziness (up to 16%)
Common (1% to 10%): Demyelinating polyneuropathy
Frequency not reported: Progressive multifocal leukoencephalopathy[Ref]

Other

Other side effects have included infusion related reactions (12%) including chills, nausea, dyspnea, pruritus, pyrexia and cough.[Ref]

Psychiatric

Very common (10% or more): Insomnia (up to 16%), anxiety (up to 11%)[Ref]

Respiratory

Very common (10% or more): Upper respiratory infection (up to 47%), cough (up to 25%), dyspnea (up to 17%), oropharyngeal pain (up to 11%)
Postmarketing reports: Noninfectious pulmonary toxicity (including fatal outcomes)[Ref]

Hepatic

Common (1% to 10%): Alanine aminotransferase/aspartate aminotransferase (ALT/AST) increased
Postmarketing reports: Hepatotoxicity[Ref]

Immunologic

Very common (10% or more): Infection
Common (1% to 10%): Sepsis/septic shock, pneumonia, herpes zoster
Uncommon (0.1% to 1%): Oral candidiasis, pneumocystis jiroveci pneumonia, staphylococcal bacteremia
Postmarketing reports: Serious opportunistic infections[Ref]

Oncologic

Uncommon (0.1% to 1%): Tumor lysis syndrome[Ref]

Some side effects of Adcetris may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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