KADCYLA INJECTION*
Manufacturer DetailsSIRION THERAPEUTICS INC.
Compositions:
Ado-trantuzumab -mg injection,
Ado-trantuzumab -mg injection,
| Strength | Rate | Packing Style |
|---|---|---|
| mg | 0.00 | unit injection |
List of Related Indications:
- Single Agent for the treatment of Patients with HER2- Positive, Metastatic Breast Cancer who previously received Transtuzumab and a Taxane, separately or in combination.
List Of Drugs:
- 5/13.Ado-transtuzumab emtansine- Kadeyla - (Feb 2013)- Chemotherapeutic agents
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
No formal drug-drug interaction studies with KADCYLA have been conducted.
In vitro studies indicate that DM1, the cytotoxic component of KADCYLA,
is metabolized mainly by CYP3A4 and to a lesser extent by CYP3A5.
Concomitant use of strong CYP3A4 inhibitors (e.g.,ketoconazole, itraconazole,
clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir,ritonavir, saquinavir,
telithromycin, and voriconazole) with KADCYLA should be avoided due
to the potential for an increase in DM1 exposure and toxicity.
Consider an alternate medication with no or minimal potential to inhibit CYP3A4.
If concomitant use of strong CYP3A4 inhibitors is unavoidable, consider delaying
KADCYLA treatment until the strong CYP3A4 inhibitors have cleared from the
circulation (approximately 3 elimination half-lives of the inhibitors) when possible.
If a strong CYP3A4 inhibitor is coadministered and KADCYLA treatment cannot
be delayed, patients should be closely monitored for adverse reactions
Indication:
KADCYLA. (ado-trastuzumab emtansine) for injection, for intravenous use
Initial U.S. Approval: {YYYY}
WARNING: HEPATOTOXICITY, CARDIAC TOXICITY,
EMBRYO-FETAL TOXICITY
See full prescribing information for complete boxed warning
Do not substitute KADCYLA for or with trastuzumab.
Hepatotoxicity, liver failure and death have occurred in KADCYLA-treated
patients.
Monitor hepatic function prior to initiation and prior to each dose.
Institute dose modifications or permanently discontinue as appropriate.
KADCYLA may lead to reductions in left ventricular ejection fraction (LVEF).
Assess LVEF prior to initiation. Monitor and withhold dosing or discontinue
as appropriate.
Can cause fetal harm. Advise women of potential risk to the fetus.
Drug Name- Kadcyla
Active Ingredient - Ado-transtuzuzumab emtanasine
For patients with HER-2 postive ,late-stage (metastatic ) breast cancer
Indication-
Metastatic breast cancer
Approved by FDA on 22-2--2013 (Ref- FDA approved List- 2013)
Proprietary Name- KADCYLA INJECTION*
Established Name- Ado-Transtuzumab Emtansine
Applicant- GENTECH INC.
Indication- For use as single agent for the treatment of patients with
HER2- positive, metastatic breast cancer who previously
received transtuzumab and a taxane, separately or
in combination.
Patients should have either received prior therapy for
metastatic disease or developed disease recurrence
during or within six months of completeing adjuvant
therapy
Approval Date- February 22,2013
Approved by US FDA (Ref- FDA approved list- 2013)
Adverse Reaction:
The most common adverse drug reactions (frequency > 25%) with
KADCYLA (n=884 treated patients) were-
fatigue, nausea, musculoskeletal pain, thrombocytopenia, headache,
increased transaminases, and constipation.
Contra-Indications:
CONTRAINDICATIONS
None.
WARNINGS AND PRECAUTIONS
Pulmonary Toxicity: Permanently discontinue KADCYLA in patients diagnosed
with interstitial lung disease or pneumonitis.
Infusion-Related Reactions, Hypersensitivity Reactions: Monitor for signs and
symptoms during and after infusion. If significant infusion-related reactions
or hypersensitivity reactions occur, slow or interrupt the infusion and
administer appropriate medical therapies.
Permanently discontinue KADCYLA for life threatening infusion-related
reaction.
Thrombocytopenia: Monitor platelet counts prior to each KADCYLA dose.
Institute dose modifications as appropriate.
Neurotoxicity: Monitor for signs or symptoms. Withhold dosing temporarily
for patients experiencing Grade 3 or 4 peripheral neuropathy.
HER2 Testing: Perform using FDA-approved tests by laboratories with
demonstrated proficiency.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
KADCYLA is a HER2-targeted antibody and microtubule inhibitor conjugate
indicated, as a single agent, for the treatment of patients with HER2-positive,
metastatic breast cancer who previously received trastuzumab and a taxane,
separately or in combination. Patients should have either:
Received prior therapy for metastatic disease, or Developed disease
recurrence during or within six months of completing adjuvant therapy.
DOSAGE AND ADMINISTRATION
For intravenous infusion only. Do not administer as an intravenous push
or bolus. Do not use Dextrose (5%) solution.
The recommended dose of KADCYLA is 3.6 mg/kg given as an intravenous
infusion every 3 weeks (21-day cycle) until disease progression or
unacceptable toxicity. Do not administer KADCYLA at doses greater
than 3.6 mg/kg. Do not substitute KADCYLA for or with trastuzumab.
Management of adverse events (infusion-related reactions, hepatotoxicity,
left ventricular cardiac dysfunction, thrombocytopenia, pulmonary toxicity or
peripheral neuropathy) may require temporary interruption, dose reduction,
or treatment discontinuation of KADCYLA.
DOSAGE FORMS AND STRENGTHS
Lyophilized powder in single-use vials containing 100 mg per vial or
160 mg per vial.
Patient Information:
PATIENT COUNSELING INFORMATION
1. Inform patients of the possibility of severe liver injury and advise patients to immediately
seek medical attention if they experience symptoms of acute hepatitis such as nausea,
vomiting, abdominal pain (especially RUQ abdominal pain), jaundice, dark urine,
generalized pruritus, anorexia, etc.
2. Advise patients to contact a health care professional immediately for any of the following:
new onset or worsening shortness of breath, cough, swelling of the ankles/legs, palpitations,
weight gain of more than 5 pounds in 24 hours, dizziness or loss of consciousness
3. Advise pregnant women and females of reproductive potential that KADCYLA exposure can result in fetal harm, including embryo-fetal death or birth defects .
4. Advise females of reproductive potential to use effective contraception while receiving
KADCYLA and for 6 months following the last dose of KADCYLA.
5. Advise nursing mothers treated with KADCYLA to discontinue nursing or discontinue
KADCYLA, taking into account the importance of the drug to the mother
6. Encourage women who are exposed to KADCYLA during pregnancy to enroll in the
MotHER Pregnancy Registry by contacting 1-800-690-6720
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Ado-trastuzumab emtansine is a HER2-targeted antibody-drug conjugate.
The antibody is the humanized anti-HER2 IgG1, trastuzumab.
The small molecule cytotoxin, DM1, is a microtubule 462 inhibitor.
Upon binding to sub-domain IV of the HER2 receptor, ado-trastuzumab
emtansine undergoes receptor-mediated internalization and subsequent
lysosomal degradation, resulting in intracellular release of DM1-containing
cytotoxic catabolites.
Binding of DM1 to tubulin disrupts microtubule networks in the cell, which
results in cell cycle arrest and apoptotic cell death.
2.Pharmacokinetics
The pharmacokinetics of KADCYLA was evaluated in a phase 1 study and
in a population pharmacokinetic analysis for the ado-trastuzumab emtansine
conjugate (ADC) using pooled data from 5 trials in patients with breast cancer.
A linear two-compartment model with first-order elimination from the central
compartment adequately describes the ADC concentration-time profile.
In addition to ADC, the pharmacokinetics of total antibody (conjugated and
unconjugated trastuzumab), DM1 were also determined.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category D
Risk Summary
KADCYLA can cause fetal harm when administered to a pregnant woman. There are no
adequate and well-controlled studies of KADCYLA in pregnant women
If KADCYLA is administered during pregnancy, or if a patient becomes pregnant
while receiving KADCYLA, apprise the patient of the potential hazard to the fetus.
Patients should be advised to use effective contraception during treatment
with KADCYLA and for 6 months following the last dose of KADCYLA.
2. Nursing Mothers
It is not known whether KADCYLA, specifically, is excreted in human milk,
but IgG is known to be 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 KADCYLA, a decision
should be made whether to discontinue nursing or discontinue KADCYLA,
taking into account the importance of the drug to the mother
3. Pediatric Use
Safety and effectiveness of KADCYLA have not been established in pediatric patients.
4. Geriatric Use
2 Of 495 patients who were randomized to KADCYLA in the randomized trial (Study 1)
Studies 65 patients (13%) were . 65 years of age and 11 patients (2%) were .
75 years of age. In patients . 65 years old (n=138 across both treatment arms)
the hazard ratios for progression-free survival (PFS) and Overall Survival (OS)
were 1.06 (95% CI: 0.68, 1.66) and 1.05 (95% CI: 0.58, 1.91), respectively.
If KADCYLA is administered during pregnancy or if a patient becomes pregnant
while receiving KADCYLA, immediately report exposure to the Genentech Adverse
Event Line at 1-888-835371 2555. Encourage women who may be exposed during
pregnancy to enroll in the MotHER 372 Pregnancy Registry by contacting
1-800-690-6720
