Zelboraf
Vemurafenib · Tablet, Film Coated · Oral
Uses
1 INDICATIONS AND USAGE ZELBORAF ® 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. ( 1.1 , 2.1 ) ZELBORAF ® is indicated for the treatment of patients with Erdheim- Chester Disease with BRAF V600 mutation. ( 1.2 , 2.1 ) Limitation of Use: ZELBORAF is not indicated for treatment of patients with wild-type BRAF melanoma ( 2.1 , 5.2 ) 1.1 Unresectable or Metastatic Melanoma ZELBORAF ® is 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 [see Warnings and Precautions (5.2) ] . 1.2 Erdheim-Chester Disease ZELBORAF ® is indicated for the treatment of patients with Erdheim-Chester Disease (ECD) with BRAF V600 mutation.
Dosage and administration
Confirm the presence of BRAF V600E mutation in tumor specimens prior to initiation of treatment with ZELBORAF. ( 2.1 ) Recommended dose: 960 mg orally twice daily taken approximately 12 hours apart with or without a meal. ( 2.2 ) 2.1 Patient Selection for Treatment of Melanoma Confirm the presence of BRAF V600E mutation in melanoma tumor specimens prior to initiation of treatment with ZELBORAF [see Warnings and Precautions (5.2) ] . Information on FDA-approved tests for the detection of BRAF V600 mutations in melanoma is available at http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dose The recommended dose of ZELBORAF is 960 mg (four 240 mg tablets) orally every 12 hours with or without a meal. A missed dose can be taken up to 4 hours prior to the next dose. Treat patients with ZELBORAF until disease progression or unacceptable toxicity occurs. Do not take an additional dose if vomiting occurs after ZELBORAF administration, but continue with the next scheduled dose. Do not crush or chew the tablets. 2.3 Dose Modifications For New Primary Cutaneous Malignancies: No dose modifications are recommended. For Other Adverse Reactions: Permanently discontinue ZELBORAF for any of the following: Grade 4 adverse reaction, first appearance (if clinically appropriate) or second appearance QTc prolongation > 500 ms and increased by > 60 ms from pre-treatment values [see Warnings and Precautions (5.5) ] Withhold ZELBORAF for NCI-CTCAE (v4.0) intolerable Grade 2 or greater adverse reactions. Upon recovery to Grade 0–1, restart ZELBORAF at a reduced dose as follows: 720 mg twice daily for first appearance of intolerable Grade 2 or Grade 3 adverse reactions 480 mg twice daily for second appearance of Grade 2 (if intolerable) or Grade 3 adverse reactions or for first appearance of Grade 4 adverse reaction (if clinically appropriate) Do not dose reduce to below 480 mg twice daily. 2.4 Dose Modification for Strong CYP3A4 Inducers Avoid concomitant use of strong CYP3A4 inducers during treatment with ZELBORAF [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . If concomitant use of a strong CYP3A4 inducer is unavoidable, increase the dose of ZELBORAF by 240 mg (one tablet) as tolerated. After discontinuation of a strong CYP3A4 inducer for two weeks, resume the ZELBORAF dose that was taken prior to initiating the strong CYP3A4 inducer.
Dosage forms and strengths
Tablet: 240 mg. Tablet: 240 mg ( 3 )
Contraindications
None. 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. ( 5.1 ) 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. ( 5.1 ) Other Malignancies: Monitor patients receiving ZELBORAF closely for signs or symptoms of other malignancies ( 5.1 ). Tumor Promotion in BRAF Wild-Type Melanoma: Increased cell proliferation can occur with BRAF inhibitors ( 5.2 ). Serious Hypersensitivity Reactions including anaphylaxis and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS Syndrome): Discontinue ZELBORAF for severe hypersensitivity reactions. ( 5.3 ) Severe Dermatologic Reactions, including Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis: Discontinue ZELBORAF for severe dermatologic reactions. ( 5.4 ) 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. ( 5.5 ) Hepatotoxicity: Measure liver enzymes and bilirubin before initiating ZELBORAF and monitor monthly during treatment. ( 5.6 ) Photosensitivity: Advise patients to avoid sun exposure. ( 5.7 ) Serious Ophthalmologic Reactions: Monitor for signs and symptoms of uveitis. ( 5.8 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of the potential risk to the fetus and to use effective contraception. ( 5.9 , 8.1 , 8.3 ) Radiation Sensitization and Radiation Recall: Severe cases have been reported. ( 5.10 ). Renal Failure: Measure serum creatinine before initiating ZELBORAF and monitor periodically during treatment ( 5.11 ). Dupuytren's Contracture and plantar fascial fibromatosis: Events should be managed with dose reduction, treatment interruption, or treatment discontinuation. ( 5.12 ). 5.1 New Primary Malignancies Cutaneous Malignancies Cutaneous squamous cell carcinoma, keratoacanthoma, and melanoma occurred at a higher incidence in patients receiving ZELBORAF compared to those in the control arm in Trial 1. The incidence of cutaneous squamous cell carcinomas (cuSCC) and keratoacanthomas in the ZELBORAF arm was 24% compared to < 1% in the dacarbazine arm [see Adverse Reactions (6.1) ] . The median time to the first appearance of cuSCC was 7 to 8 weeks; approximately 33% of patients who developed a cuSCC while receiving ZELBORAF experienced at least one additional occurrence with median time between occurrences of 6 weeks. Potential risk factors associated with cuSCC observed in clinical studies using ZELBORAF included age (≥ 65 years), prior skin cancer, and chronic sun exposure. In Trial 4, in patients with ECD, the incidence of cuSCC and/or keratoacanthomas was 40.9% (9/22). The median time to first appearance of cuSCC amongst patients with at least one occurrence was 12.1 weeks. In Trial 1, in patients with unresectable or metastatic melanoma, new primary malignant melanoma occurred in 2.1% (7/336) of patients receiving ZELBORAF compared to none of the patients receiving dacarbazine. Perform dermatologic evaluations prior to initiation of therapy and every 2 months while on therapy. Manage suspicious skin lesions with excision and dermatopathologic evaluation. Consider dermatologic monitoring for 6 months following discontinuation of ZELBORAF. Non-Cutaneous Squamous Cell Carcinoma Non-cutaneous squamous cell carcinomas (non-cuSCC) of the head and neck can occur in patients receiving ZELBORAF [see Adverse Reactions (6.1) ] . Monitor patients receiving ZELBORAF closely for signs or symptoms of new non-cuSCC. Other Malignancies Based on mechanism of action, ZELBORAF may promote malignancies associated with activation of RAS through mutation or other mechanisms [see Warnings and Precautions (5.2) ] . Monitor patients receiving ZELBORAF closely for signs or symptoms of other malignancies. Cases of myeloid neoplasms amongst patients with ECD have been observed, including in patients who have received ZELBORAF. Monitoring complete blood count in ECD patients with co-existing myeloid malignancies is recommended. 5.2 Tumor Promotion in BRAF Wild-Type Melanoma In vitro experiments have demonstrated paradoxical activation of MAP-kinase signaling and increased cell proliferation in BRAF wild-type cells that are exposed to BRAF inhibitors. Confirm evidence of BRAF V600E mutation in tumor specimens prior to initiation of ZELBORAF [see Indications and Usage (1) and Dosage and Administration (2.1) ] . 5.3 Hypersensitivity Reactions Anaphylaxis and other serious hypersensitivity reactions can occur during treatment and upon re-initiation of treatment with ZELBORAF. Severe hypersensitivity reactions included generalized rash and erythema, hypotension, and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). Permanently discontinue ZELBORAF in patients who experience a severe hypersensitivity reaction [see Adverse Reactions (6.2) ] . 5.4 Dermatologic Reactions Severe dermatologic reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, can occur in patients receiving ZELBORAF. Permanently discontinue ZELBORAF in patients who experience a severe dermatologic reaction [see Adverse Reactions (6.1) ]. 5.5 QT Prolongation Concentration-dependent QT prolongation occurred in an uncontrolled, open-label QT sub-study in previously treated patients with BRAF V600E mutation-positive metastatic melanoma [see Clinical Pharmacology (12.2) ] . QT prolongation may lead to an increased risk of ventricular arrhythmias, including Torsade de Pointes.
Side effects
The following adverse reactions are discussed in greater detail in other sections of the label: New Primary Malignancies [see Warnings and Precautions (5.1) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Dermatologic Reactions [see Warnings and Precautions (5.4) ] QT Prolongation [see Warnings and Precautions (5.5) ] Hepatotoxicity [see Warnings and Precautions (5.6) ] Photosensitivity [see Warnings and Precautions (5.7) ] Ophthalmologic Reactions [see Warnings and Precautions (5.8) ] Radiation Sensitization and Radiation Recall [see Warnings and Precautions (5.10) ] Renal Failure [see Warnings and Precautions (5.11) ] Dupuytren's Contracture and Plantar Fascial Fibromatosis [see Warnings and Precautions (5.12) ] Melanoma: Most common adverse reactions (≥ 30%) are arthralgia, rash, alopecia, fatigue, photosensitivity reaction, nausea, pruritus, and skin papilloma. ( 6.1 ) Erdheim-Chester Disease: Most common adverse reactions (>50%) are arthralgia, rash maculo-papular, alopecia, fatigue, electrocardiogram QT interval prolonged, and skin papilloma. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not predict the rates observed in a broader patient population in clinical practice. Unresectable or Metastatic Melanoma with BRAF V600E Mutation This section describes adverse drug reactions (ADRs) identified from analyses of Trial 1 and Trial 2 [see Clinical Studies (14) ] . Trial 1 randomized (1:1) 675 treatment-naive patients with unresectable or metastatic melanoma to receive ZELBORAF 960 mg orally twice daily or dacarbazine 1000 mg/m 2 intravenously every 3 weeks. In Trial 2, 132 patients with metastatic melanoma and failure of at least one prior systemic therapy received treatment with ZELBORAF 960 mg orally twice daily. Table 1 presents adverse reactions reported in at least 10% of unresectable or metastatic melanoma patients treated with ZELBORAF. The most common adverse reactions of any grade (≥ 30% in either study) in ZELBORAF-treated patients were arthralgia, rash, alopecia, fatigue, photosensitivity reaction, nausea, pruritus, and skin papilloma. The most common (≥ 5%) Grade 3 adverse reactions were cuSCC and rash. The incidence of Grade 4 adverse reactions was ≤ 4% in both studies. The incidence of adverse events resulting in permanent discontinuation of study medication in Trial 1 was 7% for the ZELBORAF arm and 4% for the dacarbazine arm. In Trial 2, the incidence of adverse events resulting in permanent discontinuation of study medication was 3% in ZELBORAF-treated patients. The median duration of study treatment was 4.2 months for ZELBORAF and 0.8 months for dacarbazine in Trial 1, and 5.7 months for ZELBORAF in Trial 2. Table 1 Adverse Reactions Reported in ≥ 10% of Unresectable or Metastatic Melanoma Patients Treated with ZELBORAF Adverse drug reactions, reported using MedDRA and graded using NCI-CTC-AE v 4.0 (NCI common toxicity criteria) for assessment of toxicity. ADRs Trial 1: Treatment-Naïve Patients Trial 2: Patients with Failure of at Least One Prior Systemic Therapy ZELBORAF n=336 Dacarbazine n=287 ZELBORAF n=132 All Grades (%) Grade 3 Grade 4 adverse reactions limited to gamma-glutamyltransferase increased (< 1% in Trial 1 and 4% in Trial 2). (%) All Grades (%) Grade 3 (%) All Grades (%) Grade 3 (%) Skin and subcutaneous tissue disorders Rash 37 8 2 0 52 7 Photosensitivity reaction 33 3 4 0 49 3 Alopecia 45 < 1 2 0 36 0 Pruritus 23 1 1 0 30 2 Hyperkeratosis 24 1 < 1 0 28 0 Rash maculo-papular 9 2 < 1 0 21 6 Actinic keratosis 8 0 3 0 17 0 Dry skin 19 0 1 0 16 0 Rash papular 5 < 1 0 0 13 0 Erythema 14 0 2 0 8 0 Musculoskeletal and connective tissue disorders Arthralgia 53 4 3 < 1 67 8 Myalgia 13 < 1 1 0 24 < 1 Pain in extremity 18 < 1 6 2 9 0 Musculoskeletal pain 8 0 4 < 1 11 0 Back pain 8 < 1 5 < 1 11 < 1 General disorders and administration site conditions Fatigue 38 2 33 2 54 4 Edema peripheral 17 < 1 5 0 23 0 Pyrexia 19 < 1 9 < 1 17 2 Asthenia 11 < 1 9 < 1 2 0 Gastrointestinal disorders Nausea 35 2 43 2 37 2 Diarrhea 28 < 1 13 < 1 29 < 1 Vomiting 18 1 26 1 26 2 Constipation 12 < 1 24 0 16 0 Nervous system disorders Headache 23 < 1 10 0 27 0 Dysgeusia 14 0 3 0 11 0 Neoplasms benign, malignant and unspecified (includes cysts and polyps) Skin papilloma 21 < 1 0 0 30 0 Cutaneous SCC Includes both squamous cell carcinoma of the skin and keratoacanthoma. Cases of cutaneous squamous cell carcinoma were required to be reported as Grade 3 per protocol.
Drug interactions
Avoid concomitant administration of ZELBORAF with strong CYP3A4 inhibitors or inducers. ( 7.1 ) 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. ( 7.2 ). 7.1 Effect of Strong CYP3A4 Inhibitors or Inducers on Vemurafenib Strong CYP3A4 Inhibitors Coadministration of a strong CYP3A4 inhibitor increased vemurafenib plasma concentrations and may lead to increased toxicity. Avoid coadministration of ZELBORAF with strong CYP3A4 inhibitors. If coadministration of a strong CYP3A4 inhibitor is unavoidable, consider dose reduction of ZELBORAF, if clinically indicated. [see Dosage and Administration (2.3) , Clinical Pharmacology (12.3) ] . Strong CYP3A4 Inducers Coadministration of ZELBORAF with rifampin, a strong CYP3A4 inducer, decreased vemurafenib plasma concentrations and may result in decreased efficacy. Avoid coadministration of ZELBORAF with strong CYP3A4 inducers (e.g., phenytoin, carbamazepine, rifampin), and replace these drugs with alternative drugs when possible. If coadministration of a strong CYP3A4 inducer is unavoidable, increase the dose of ZELBORAF by 240 mg (one tablet) as tolerated [see Dosage and Administration (2.4) , Clinical Pharmacology (12.3) ] . 7.2 Effect of Vemurafenib on CYP1A2 Substrates Coadministration of ZELBORAF with tizanidine, a sensitive CYP1A2 substrate, increased tizanidine systemic exposure by 4.7-fold. Avoid concomitant use of ZELBORAF with drugs having a narrow therapeutic window that are predominantly metabolized by CYP1A2 [see Clinical Pharmacology (12.3) ] . If coadministration cannot be avoided, monitor closely for toxicities and consider a dose reduction of concomitant CYP1A2 substrates. 7.3 Concurrent Ipilimumab Increases in transaminases and bilirubin occurred in a majority of patients who received concurrent ipilimumab and ZELBORAF [see Warnings and Precautions Section 5.6 ]. 7.4 Effect of Vemurafenib on P-gp Substrates Coadministration of ZELBORAF with digoxin, a sensitive P-glycoprotein (P-gp) substrate, increased digoxin systemic exposure by 1.8-fold. Avoid concurrent use of P-gp substrates known to have narrow therapeutic indices. If use of these medications is unavoidable, consider dose reduction of P-gp substrates with narrow therapeutic indices.
Use in specific populations
Lactation: Do not breastfeed while taking ZELBORAF. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on its mechanism of action, ZELBORAF can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of ZELBORAF in pregnant women to determine the drug-associated risk; however, placental transfer of vemurafenib to a fetus has been reported. Exposure to vemurafenib could not be achieved in animals at levels sufficient to fully address its potential toxicity in pregnant women. Advise pregnant women of the potential harm to a fetus. The estimated background risks of major birth defects and miscarriage for the indicated population(s) are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Vemurafenib showed no evidence of developmental toxicity in rat fetuses at doses up to 250 mg/kg/day (approximately 1.3 times the clinical exposure at 960 mg twice daily based on AUC) or rabbit fetuses at doses up to 450 mg/kg/day (approximately 0.6 times the clinical exposure at 960 mg twice daily based on AUC). Fetal drug levels were 3–5% of maternal levels, indicating that vemurafenib has the potential to be transmitted from the mother to the developing fetus. 8.2 Lactation There is no information available regarding the presence of vemurafenib in human milk, effects on the breastfed infant, or effects on milk production. Because of the potential for serious adverse reactions in a breastfed infant, including malignancy, severe dermatologic reactions, QT prolongation, hepatotoxicity, photosensitivity, and ophthalmologic toxicity, [see Warnings and Precautions (5) ] , advise women not to breastfeed during treatment with ZELBORAF and for 2 weeks after the final dose. 8.3 Females and Males of Reproductive Potential Contraception Based on its mechanism of action, ZELBORAF can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment with ZELBORAF and for 2 weeks after the final dose. 8.4 Pediatric Use The safety and effectiveness of ZELBORAF in pediatric patients have not been established. Vemurafenib was studied in 6 adolescent patients 15 to 17 years of age with unresectable or metastatic melanoma with BRAF V600 mutation. A maximum tolerated dose was not reached with doses up to vemurafenib 960 mg twice daily. No new safety signals were observed. Vemurafenib steady-state exposure in these 6 adolescent patients was generally similar to that in adults. 8.5 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. 8.6 Hepatic Impairment No formal clinical study has been conducted to evaluate the effect of hepatic impairment on the pharmacokinetics of vemurafenib. No dose adjustment is recommended for patients with mild and moderate hepatic impairment based on a population pharmacokinetic analysis [see Clinical Pharmacology (12.3) ]. The appropriate dose of ZELBORAF has not been established in patients with severe hepatic impairment. 8.7 Renal Impairment No formal clinical study has been conducted to evaluate the effect of renal impairment on the pharmacokinetics of vemurafenib. No dose adjustment is recommended for patients with mild and moderate renal impairment based on a population pharmacokinetic analysis [see Clinical Pharmacology (12.3) ]. The appropriate dose of ZELBORAF has not been established in patients with severe renal impairment.
Pregnancy
8.1 Pregnancy Risk Summary Based on its mechanism of action, ZELBORAF can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of ZELBORAF in pregnant women to determine the drug-associated risk; however, placental transfer of vemurafenib to a fetus has been reported. Exposure to vemurafenib could not be achieved in animals at levels sufficient to fully address its potential toxicity in pregnant women. Advise pregnant women of the potential harm to a fetus. The estimated background risks of major birth defects and miscarriage for the indicated population(s) are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data Vemurafenib showed no evidence of developmental toxicity in rat fetuses at doses up to 250 mg/kg/day (approximately 1.3 times the clinical exposure at 960 mg twice daily based on AUC) or rabbit fetuses at doses up to 450 mg/kg/day (approximately 0.6 times the clinical exposure at 960 mg twice daily based on AUC). Fetal drug levels were 3–5% of maternal levels, indicating that vemurafenib has the potential to be transmitted from the mother to the developing fetus.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of ZELBORAF in pediatric patients have not been established. Vemurafenib was studied in 6 adolescent patients 15 to 17 years of age with unresectable or metastatic melanoma with BRAF V600 mutation. A maximum tolerated dose was not reached with doses up to vemurafenib 960 mg twice daily. No new safety signals were observed. Vemurafenib steady-state exposure in these 6 adolescent patients was generally similar to that in adults.
Geriatric use
8.5 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.
Overdosage
There is no information on overdosage of ZELBORAF.
Description
(vemurafenib) is a kinase inhibitor available as 240 mg tablets for oral use. Vemurafenib has the chemical name propane-1-sulfonic acid {3-[5-(4-chlorophenyl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]- 2,4-difluoro-phenyl}-amide. It has the molecular formula C 23 H 18 ClF 2 N 3 O 3 S and a molecular weight of 489.9. Vemurafenib has the following chemical structure: Vemurafenib is a white to off-white crystalline solid. It is practically insoluble in aqueous media. Tablets of ZELBORAF are for oral administration. Each tablet contains 240 mg of vemurafenib. The inactive ingredients of ZELBORAF are: Tablet core: hypromellose acetate succinate, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, and hydroxypropyl cellulose. Coating: pinkish white: poly (vinyl alcohol), titanium dioxide, polyethylene glycol 3350, talc, and iron oxide red. Chemical Structure
Mechanism of action
12.1 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.
How supplied
(vemurafenib) is supplied as 240 mg film-coated tablets with VEM debossed on one side. The following packaging configurations are available: NDC 50242-090-01 single bottle of 120 count NDC 50242-090-02 single bottle of 112 count Storage and Stability: Store at room temperature 20°C–25°C (68°F–77°F); excursions permitted between 15°C and 30°C (59°F and 86°F), See USP Controlled Room Temperature. Store in the original container with the lid tightly closed. Disposal of unused/expired medicines: The release of pharmaceuticals in the environment should be minimized. Medicines should not be disposed of via wastewater and disposal through household waste should be avoided. Use established "collection systems," if available in your location.
Storage
Storage and Stability: Store at room temperature 20°C–25°C (68°F–77°F); excursions permitted between 15°C and 30°C (59°F and 86°F), See USP Controlled Room Temperature. Store in the original container with the lid tightly closed.
Patient information
Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Healthcare 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: Evidence of BRAF V600E mutation in the tumor specimen with an FDA approved test is necessary to identify patients with melanoma for whom treatment with ZELBORAF is indicated [see Dosage and Administration (2.1) ] . ZELBORAF increases the risk of developing new primary cutaneous malignancies. Advise patients of the importance of contacting their healthcare provider immediately for any changes in their skin [see Warnings and Precautions (5.1) ] . Anaphylaxis and other serious hypersensitivity reactions can occur during treatment and upon re- initiation of treatment with ZELBORAF. Advise patients to stop taking ZELBORAF and to seek immediate medical attention for symptoms of anaphylaxis or hypersensitivity [see Warnings and Precautions (5.3) ] . 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 [see Warnings and Precautions (5.4) ] . 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 [see Warnings and Precautions (5.5) ] . 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 [see Warnings and Precautions (5.6) ] . 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 [see Warnings and Precautions (5.7) ] . Ophthalmologic reactions can occur in patients treated with ZELBORAF. Advise patients to contact their health-care provider immediately for ophthalmologic symptoms [see Warnings and Precautions (5.8) ] . Embryo-fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus [see Warnings and Precautions (5.9) and Use in Special Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment with ZELBORAF and for 2 weeks after the final dose [see Warnings and Precautions (5.9) and Use in Special Populations (8.1 , 8.3) ] . Advise female patients to contact their health-care provider immediately with a known or suspected pregnancy [see Warnings and Precautions (5.9) and Use in Special Populations (8.1 , 8.3) ] . Lactation Advise a woman not to breastfeed during treatment with ZELBORAF and for 2 weeks after the final dose [see Use in Specific Populations (8.2) ] . Radiation sensitization and recall can occur in patients treated with radiation prior to, during, or subsequent to ZELBORAF treatment. Advise patients to inform their health care provider if they have had or are planning to receive radiation therapy [see Warnings and Precautions (5.10) , Adverse Reactions (6.2) ]. Renal failure can occur in patients treated with ZELBORAF. Advise patients of the importance of monitoring serum creatinine prior to and during ZELBORAF treatment [see Warnings and Precautions (5.11) , Adverse Reactions (6.2) ]. Advise patients to contact their health care provider for symptoms of Dupuytren's contracture or plantar fascial fibromatosis [see Warnings and Precautions (5.12) ] .
Label text from the FDA structured product label by Genentech, Inc. (revised Aug 28, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Vemurafenib in 1 product
Zelboraf NDC products (1)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50242-090 | Vemurafenib 240 mg/1 Tablet, Film Coated | Genentech, Inc. | NDA |
Frequently asked questions
What is Zelboraf used for?
1 INDICATIONS AND USAGE ZELBORAF ® 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. ( 1.1 , 2.1 ) ZELBORAF ® is indicated for the treatment of patients with Erdheim- Chester Disease with BRAF V600 mutation. ( 1.2 , 2.1 ) Limitation of Use: ZELBORAF is not indicated for treatment of…
What are the side effects of Zelboraf?
The following adverse reactions are discussed in greater detail in other sections of the label: New Primary Malignancies [see Warnings and Precautions (5.1) ] Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Dermatologic Reactions [see Warnings and Precautions (5.4) ] QT Prolongation [see Warnings and Precautions (5.5) ] Hepatotoxicity [see Warnings and Precautions (5.6) ]… See the full label for the complete list.
Who makes Zelboraf?
Zelboraf is listed by 1 labeler in the FDA NDC directory, including Genentech, Inc..