ZELBORAF*
Manufacturer DetailsGENERIC*
USA AND CANADA
Compositions:
Vemurafenib- mg,
Vemurafenib- mg,
| Strength | Rate | Packing Style |
|---|---|---|
| mg | 0.00 | unit |
List of Related Indications:
- Treat patients with late-stage(metastatic) or unresectable (cannot be removed by surgery) melanoma, the most dangerous type of skin cancer
List Of Drugs:
- Vemurafenib- Zelboraf - @- 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:
Avoid concomitant administration of ZELBORAF with strong CYP3A4 inhibitors
or inducers.
CYP1A2 Substrates: ZELBORAF can increase concentrations of CYP1A2 substrates.
Avoid concomitant use of ZELBORAF with CYP1A2 substrates with a narrow
therapeutic window.
If coadministration cannot be avoided, monitor closely for toxicities and
consider dose reduction of CYP1A2 substrates.
Indication:
ZELBORAF (vemurafenib) tablet for oral use
Initial U.S. Approval: 2011
Drug Name- Zelboraf
Active Ingredient - Vemurafenib
To treat patients with late-stage (metastatic ) or unresectable
( cannnot be removed by surgery) melonoma, the most dangerous
type of skin cancer
Indication-
To treat patients with late-stage (metastatic ) or unresectable
( cannnot be removed by surgery) melonoma, the most dangerous
type of skin cancer
Approved by FDA on 17-8-2011 (Ref- FDA approved List- 2011)
Adverse Reaction:
Most common adverse reactions (. 30%) are arthralgia, rash, alopecia, fatigue,
photosensitivity reaction, nausea, pruritus, and skin papilloma.
Contra-Indications:
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
New Primary Cutaneous Malignancies: Perform dermatologic evaluations prior
to initiation of therapy, every 2 months while on therapy, and for up to 6 months
following discontinuation of ZELBORAF. Manage with excision and continue
treatment without dose adjustment.
New Non-Cutaneous Squamous Cell Carcinoma: Evaluate for symptoms
or clinical signs of new non-cutaneous SCC before initiation of treatment and
periodically during treatment.
Other Malignancies: Monitor patients receiving ZELBORAF closely for signs
or symptoms of other malignancies
Tumor Promotion in BRAF Wild-Type Melanoma: Increased cell proliferation can
occur with BRAF inhibitors
Serious Hypersensitivity Reactions including anaphylaxis and Drug Reaction
with Eosinophilia and Systemic Symptoms (DRESS Syndrome):
Discontinue ZELBORAF for severe hypersensitivity reactions.
Severe Dermatologic Reactions, including Stevens-Johnson Syndrome
and Toxic Epidermal Necrolysis:
Discontinue ZELBORAF for severe dermatologic reactions.
QT Prolongation: Monitor ECG and electrolytes before and during treatment.
Withhold ZELBORAF for QTc of 500 ms or greater. Correct electrolyte abnormalities
and control for cardiac risk factors for QT prolongation.
Hepatotoxicity: Monitor liver enzymes and bilirubin before initiating
ZELBORAF and monthly during treatment.
Photosensitivity: Advise patients to avoid sun exposure.
Serious Ophthalmologic Reactions: Monitor for signs and symptoms of uveitis.
Embryo-Fetal Toxicity: May cause fetal harm. Advise women of potential
risk to the fetus.
Radiation Sensitization and Radiation Recall: Severe cases have been
reported.
Dosages/ Overdosage Etc:
Indication-
To treat patients with late-stage (metastatic ) or unresectable
( cannnot be removed by surgery) melonoma, the most dangerous
type of skin cancer
INDICATIONS AND USAGE
ZELBORAFR is a kinase inhibitor indicated for the treatment of patients with
unresectable or metastatic melanoma with BRAF V600E mutation as detected
by an FDA-approved test.
Limitation of Use: ZELBORAF is not indicated for treatment of patients with
wild-type BRAF melanoma.
DOSAGE AND ADMINISTRATION
Confirm the presence of BRAF V600E mutation in tumor specimens prior to
initiation of treatment with ZELBORAF.
Recommended dose: 960 mg orally twice daily taken approximately 12 hours
apart with or without a meal.
DOSAGE FORMS AND STRENGTHS
Tablet: 240 mg
Patient Information:
PATIENT COUNSELING INFORMATION
Health care providers should advise patients of the potential benefits and risks
of ZELBORAF and instruct their patients to read the Medication Guide before
starting ZELBORAF therapy.
Inform patients of the following:
1. Evidence of BRAF V600E mutation in the tumor specimen with an FDA approved tes
is necessary to identify patients for whom treatment with ZELBORAF is indicated
2.ZELBORAF increases the risk of developing new primary cutaneous malignancies.
Advise patients of the importance of contacting their health care provider immediately
for any changes in their skin
3. Anaphylaxis and other serious hypersensitivity reactions can occur during treatment
and upon reinitiation of treatment with ZELBORAF. Advise patients to stop taking
ZELBORAF and to seek immediate medical attention for symptoms of anaphylaxis
or hypersensitivity
4.Severe dermatologic reactions can occur in patients receiving ZELBORAF.
Advise patients to stop taking ZELBORAF and to contact their health care provider
for severe dermatologic reactions
5.ZELBORAF can prolong QT interval, which may result in ventricular arrhythmias.
Advise patients of the importance of monitoring of their electrolytes and the electrical
activity of their heart (via an ECG) during ZELBORAF treatment
6.Liver injury leading to functional hepatic impairment, including coagulopathy
or other organ dysfunction, can occur with ZELBORAF.
Advise patients of the importance of laboratory monitoring of their liver during
ZELBORAF treatment and to contact their health care provider for relevant
symptoms
7. ZELBORAF can cause mild to severe photosensitivity. Advise patients to avoid
sun exposure, wear protective clothing, and use a broad spectrum UVA/UVB
sunscreen and lip balm (SPF . 30) when outdoors to help protect against sunburn
8. Ophthalmologic reactions can occur in patients treated with ZELBORAF.
Advise patients to contact their health care provider immediately for
ophthalmologic symptoms
9.ZELBORAF can cause fetal harm when administered to a pregnant woman
based on its mechanism of action. Advise women of childbearing potential
and men to use appropriate contraceptive measures during ZELBORAF
therapy and for at least 2 months after discontinuation of ZELBORAF.
Patients to contact their health care provider immediately if they become pregnant
Pharmacology/ Pharmacokinetics:
1 Mechanism of Action
Vemurafenib is a low molecular weight, orally available inhibitor of some mutated forms
of BRAF serine-threonine kinase, including BRAF V600E. Vemurafenib also inhibits
other kinases in vitro such as CRAF, ARAF, wild-type BRAF, SRMS, ACK1, MAP4K5,
and FGR at similar concentrations.
Some mutations in the BRAF gene including V600E result in constitutively activated
BRAF proteins, which can cause cell proliferation in the absence of growth factors
that would normally be required for proliferation. Vemurafenib has anti-tumor effects in
cellular and animal models of melanomas with mutated BRAF V600E.
2.Pharmacokinetics
The pharmacokinetics of vemurafenib were determined in patients with BRAF
mutation-positive metastatic melanoma following 15 days of 960 mg twice
daily with dosing approximately 12 hours apart. The population
pharmacokinetic analysis pooled data from 458 patients. At steady-state,
vemurafenib exhibits linear pharmacokinetics within the 240 mg to
960 mg dose range.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1 Pregnancy
Pregnancy Category D
ZELBORAF can cause fetal harm when administered to a pregnant woman based
on its mechanism of action.
There are no adequate and well controlled studies in pregnant women.
Women of childbearing potential and men should be advised to use appropriate
contraceptive measures during ZELBORAF therapy and for at least 2 months
after discontinuation of ZELBORAF.
If this drug is used during pregnancy or if the patient becomes pregnant while taking
this drug, the patient should be apprised of the potential hazard to a fetus.
2. Nursing Mothers
It is not known whether vemurafenib is excreted in human milk. Because many
drugs are excreted in human milk and because of the potential for serious
adverse reactions from ZELBORAF in nursing infants, 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
Safety and efficacy in pediatric patients below the age of 18 have not been established.
4. Geriatric Use
Clinical studies of ZELBORAF did not include sufficient numbers of subjects aged 65
and over to determine whether they respond differently from younger subjects.
