ADECETRIS*
Manufacturer DetailsGENERIC*
USA AND CANADA
Compositions:
Brentuximab Vedotin - mg,
Brentuximab Vedotin - mg,
| Strength | Rate | Packing Style |
|---|---|---|
| mg | 0.00 | unit |
List of Related Indications:
- Post-Autologous Hematopoietic stem cell Transportation (Auto-HSCT) consolidation with Classical Hodgkin Lymphoma(HL)
List Of Drugs:
- Brentuximab Vedotin - Adcetris -@- Anti-cancer ( Aug 2011)
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors,
has the potential to affect the exposure to monomethyl auristatin E (MMAE)
Indication:
ADCETRIS® (brentuximab vedotin) for injection, for intravenous use
Initial U.S. approval: 2011
Drug Name- Adcetris
Active Ingredient - Brentuximab vedotin
For the treatment of Hodgkin Lymphoma and ALCL( systemic anaplastic
large cell lymphoma)
Indication-
Treatment of Hodgkin Lymphoma and ALCL( systemic anaplastic
large cell lymphoma)
Approved by FDA on 19-8-2011 (Ref- FDA approved List- 2011)
SUBSEQUENT APPROVAL
Proprietary Name- ADCETRIS*
Established Name- Brentuximab Vedotin
Applicant-
Indication- For the Post-Autologous Hematopoietic stem cell
Transportation (Auto-HSCT) consolidation treatment
of patients with Classical Hodgkin Lymphoma(HL)
at high risk of relapse or progression
Approval Date- August 17,2015
Approved by U.S.FDA as on 17-8-2015 (Ref- FDA approved List- 2015)
Adverse Reaction:
The most common adverse reactions (20%) were:
.
Relapsed classical HL and relapsed sALCL: neutropenia, peripheral
sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection,
diarrhea, pyrexia, rash, thrombocytopenia, cough, and vomiting
.
Classical HL post-auto-HSCT consolidation: neutropenia, peripheral sensory
neuropathy, thrombocytopenia, anemia, upper respiratory tract infection,
fatigue, peripheral motor neuropathy, nausea, cough, and diarrhea
Contra-Indications:
CONTRAINDICATIONS
Concomitant use with bleomycin due to pulmonary toxicity
WARNINGS AND PRECAUTIONS
.
Peripheral neuropathy: Monitor patients for neuropathy and institute dose
modifications accordingly
.
Anaphylaxis and infusion reactions: If an infusion reaction occurs,
interrupt the infusion. If anaphylaxis occurs, immediately discontinue
the infusion
.
Hematologic toxicities: Monitor complete blood counts prior to each dose of
ADCETRIS. Closely monitor patients for fever.
If Grade 3 or 4 neutropenia develops, consider dose delays, reductions,
discontinuation, or G-CSF prophylaxis with subsequent doses .
.
Serious infections and opportunistic infections: Closely monitor patients for
the emergence of bacterial, fungal or viral infections
.
Tumor lysis syndrome: Closely monitor patients with rapidly proliferating
tumor or high tumor burden
.
Hepatotoxicity: Monitor liver enzymes and bilirubin
.
Pulmonary Toxicity: Monitor patients for new or worsening symptoms
.
Serious dermatologic reactions: Discontinue if Stevens-Johnson syndrome
or toxic epidermal necrolysis occurs
.
Embryo-fetal toxicity: Fetal harm can occur. Advise pregnant women
of the potential hazard to the fetus
Dosages/ Overdosage Etc:
Indication-
Treatment of Hodgkin Lymphoma and ALCL( systemic anaplastic
large cell lymphoma)
SUBSEQUENT APPROVAL
Indication- For the Post-Autologous Hematopoietic stem cell
Transportation (Auto-HSCT) consolidation treatment
of patients with Classical Hodgkin Lymphoma(HL)
at high risk of relapse or progression
Approval Date- August 17,2015
INDICATIONS AND USAGE
ADCETRIS is a CD30-directed antibody-drug conjugate indicated for treatment
of patients with:
Classical Hodgkin lymphoma (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 HL at high risk of relapse or progression as post-auto-HSCT
consolidation
Systemic anaplastic large cell lymphoma (sALCL) after failure of at
least one prior multi-agent chemotherapy regimen
. Accelerated approval was granted for the sALCL indication based on overall
response rate.
Continued approval for this indication may be contingent upon verification and
description of clinical benefit in confirmatory trials.
DOSAGE AND ADMINISTRATION
Administer only as an intravenous infusion over 30 minutes every 3 weeks.
The recommended dose is 1.8 mg/kg .
Reduce dose in patients with mild hepatic impairment
DOSAGE FORMS AND STRENGTHS
For injection: 50 mg lyophilized powder in a single-use vial
Patient Information:
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
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
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
Hepatotoxicity
Advise patients to report symptoms that may indicate liver injury, including
fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice
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
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
Pancreatitis
Advise patients to contact their health care provider if they develop severe
abdominal pain
Pharmacology/ Pharmacokinetics:
1 Mechanism of Action
Brentuximab vedotin is an ADC. The antibody is a chimeric IgG1 directed against CD30.
The small molecule, MMAE, is a microtubule disrupting agent. MMAE is covalently
attached to the antibody via a linker.
Nonclinical data suggest that the anticancer activity of ADCETRIS is due to the
binding of the ADC to CD30-expressing cells, followed by internalization
of the ADC-CD30 complex, and the release of MMAE via proteolytic cleavage.
Binding of MMAE to tubulin disrupts the microtubule network within the cell,
subsequently inducing cell cycle arrest and apoptotic death of the cells.
2. Pharmacokinetics
The pharmacokinetics of brentuximab vedotin were evaluated in early
development trials, including dose-finding trials, and in a population
pharmacokinetic analysis of data from 314 patients.
The pharmacokinetics of three analytes were determined: the ADC, MMAE,
and total antibody. Total antibody had the greatest exposure and had
a similar PK profile as the ADC.
Hence, data on the PK of the ADC and MMAE have been summarized
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1 Pregnancy
Pregnancy Category D
Risk Summary
There are no adequate and well-controlled studies with ADCETRIS in pregnant women.
However, based on its mechanism of action and findings in animals,
ADCETRIS can cause fetal harm when administered to a pregnant woman.
If this drug is used during pregnancy, or if the patient becomes pregnant
while receiving this drug, the patient should be apprised of the potential
hazard to the fetus.
2. Nursing Mothers
It is not known whether brentuximab vedotin is excreted in human milk.
Because many drugs are excreted in human milk and because of the potential
for serious adverse reactions in nursing infants from ADCETRIS a decision
should be made whether to discontinue nursing or to discontinue the drug,
taking into account the importance of the drug to the mother.
3. Pediatric Use
The safety and effectiveness of ADCETRIS have not been established in
the pediatric population. Clinical trials of ADCETRIS included only
9 pediatric patients and this number is not sufficient to determine whether
they respond differently than adult patients.
4. Geriatric Use
Clinical trials of ADCETRIS did not include sufficient numbers of patients
aged 65 and over to determine whether they respond differently from
younger patients. Safety and efficacy have not been established.
