Zelboraf

Last reviewed on RxList: 6/4/2020
Zelboraf Side Effects Center

What Is Zelboraf?

Zelboraf (vemurafenib) is a kinase inhibitor used to treat patients with metastatic melanoma with BRAFV600E mutation that is unable to be removed by surgery.

What Are Side Effects of Zelboraf?

Common side effects of Zelboraf include:

  • joint pain,
  • tiredness,
  • nausea,
  • hair loss,
  • rash or itching,
  • skin growths (skin tags),
  • blurred vision,
  • increased sensitivity of your eyes to light,
  • hair loss,
  • thickening skin,
  • rough scaly patches on skin,
  • dry skin,
  • skin redness,
  • muscle pain,
  • pain in extremities,
  • back pain,
  • fatigue,
  • swelling of extremities,
  • fever,
  • weakness,
  • diarrhea,
  • vomiting,
  • constipation,
  • headache,
  • changes in taste,
  • decreased appetite,
  • cough, and
  • sunburn.

Dosage for Zelboraf

The recommended dose of Zelboraf is 960 mg (four 240 mg tablets) twice daily, 12 hours apart.

What Drugs, Substances, or Supplements Interact with Zelboraf?

Zelboraf may interact with blood thinners, cyclosporine, sirolimus, tacrolimus, digoxin, theophylline, ADHD medications, antibiotics, antidepressants, antifungals, cancer medicines, ergot drugs, cough medicines, pain medications, heart or blood pressure medications, heart rhythm medications, HIV/AIDS medicines, medicines to treat psychiatric disorders, or seizure medications. Tell your doctor all medications and supplements you use.

Zelboraf During Pregnancy and Breastfeeding

Do not use Zelboraf if you are pregnant. It could harm the fetus. Use birth control, and tell your doctor if you become pregnant during treatment. It is unknown if this drug passes into breast milk or if it could harm a nursing baby. Breastfeeding is not recommended while you are using Zelboraf.

Additional Information

Our Zelboraf (vemurafenib) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

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Skin Cancer Symptoms, Types, Images See Slideshow
Zelboraf Consumer Information

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).

Seek medical treatment if you have a serious drug reaction that can affect many parts of your body. Symptoms may include: skin rash, fever, swollen glands, muscle aches, severe weakness, unusual bruising, or yellowing of your skin or eyes.

Stop using vemurafenib and call your doctor at once if you have:

  • skin changes--a new wart or lesion, a skin sore or red bump that bleeds or does not heal, or any change in the size or color of a mole;
  • unusual thickening of tissues under the skin on the palms of your hands or the soles of your feet;
  • a finger or fingers that feel tight or are bent inward;
  • fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness (like you might pass out);
  • eye problems--vision changes, eye pain or swelling, severe eye redness, small white or yellow patches on the surface of your eye; or
  • liver problems--stomach pain (upper right side), nausea, vomiting, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

  • joint pain;
  • feeling tired;
  • nausea;
  • hair loss;
  • mild rash or itching;
  • skin growths; or
  • sunburn, increased sensitivity to sunlight.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Zelboraf (Vemurafenib)

Zelboraf Professional Information

SIDE EFFECTS

The following adverse reactions are discussed in greater detail in other sections of the label:

  • New Primary Malignancies [see WARNINGS AND PRECAUTIONS]
  • Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
  • Dermatologic Reactions [see WARNINGS AND PRECAUTIONS]
  • QT Prolongation [see WARNINGS AND PRECAUTIONS]
  • Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
  • Photosensitivity [see WARNINGS AND PRECAUTIONS]
  • Ophthalmologic Reactions [see WARNINGS AND PRECAUTIONS]
  • Radiation Sensitization and Radiation Recall [see WARNINGS AND PRECAUTIONS]
  • Renal Failure [see WARNINGS AND PRECAUTIONS]
  • Dupuytren's Contracture and Plantar Fascial Fibromatosis [see WARNINGS AND PRECAUTIONS]

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]. 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/m² 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*

ADRsTrial 1: Treatment - Naive PatientsTrial 2: Patients with Failure of at Least One Prior Systemic Therapy
ZELBORAF
n=336
Dacarbazine
n=287
ZELBORAF
n=132
All Grades (%)Grade 3a (%)All Grades (%)Grade 3 (%)All Grades (%)Grade 3a (%)
Skin and subcutaneous tissue disorders
Rash37820527
Photosensitivity reaction33340493
Alopecia45< 120360
Pruritus23110302
Hyperkeratosis241< 10280
Rash maculo-papular92< 10216
Actinic keratosis8030170
Dry skin19010160
Rash papular5< 100130
Erythema1402080
Musculoskeletal and connective tissue disorders
Arthralgia5343< 1678
Myalgia13< 11024< 1
Pain in extremity18< 16290
Musculoskeletal pain804< 1110
Back pain8< 15< 111< 1
General disorders and administration site conditions
Fatigue382332544
Edema peripheral17< 150230
Pyrexia19< 19< 1172
Asthenia11< 19< 120
Gastrointestinal disorders
Nausea352432372
Diarrhea28< 113< 129< 1
Vomiting181261262
Constipation12< 1240160
Nervous system disorders
Headache23< 1100270
Dysgeusia14030110
Neoplasms benign, malignant and unspecified (includes cysts and polyps)
Skin papilloma21< 100300
Cutaneous SCC†#2422< 1< 12424
Seborrheic keratosis10< 110140
Investigations
Gamma-glutamyltransferase increased5310156
Metabolism and nutrition disorders
Decreased appetite1808< 1210
Respiratory, thoracic and mediastinal disorders
Cough8070120
Injury, poisoning and procedural complications
Sunburn10000140
*Adverse drug reactions, reported using MedDRA and graded using NCI-CTC-AE v 4.0 (NCI common toxicity criteria) for assessment of toxicity.
a Grade 4 adverse reactions limited to gamma-glutamyltransferase increased (< 1% in Trial 1 and 4% in Trial 2).
† 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.

Clinically relevant adverse reactions reported in < 10% of unresectable or metastatic melanoma patients treated with ZELBORAF in the Phase 2 and Phase 3 studies include:

Skin and subcutaneous tissue disorders: palmar-plantar erythrodysesthesia syndrome, keratosis pilaris, panniculitis, erythema nodosum, Stevens-Johnson syndrome, toxic epidermal necrolysis

Musculoskeletal and connective tissue disorders: arthritis, Dupuytren's contracture Nervous system disorders: neuropathy peripheral, VIIth nerve paralysis

Neoplasms benign, malignant and unspecified (includes cysts and polyps): basal cell carcinoma, oropharyngeal squamous cell carcinoma

Infections and infestations: folliculitis

Eye disorders: retinal vein occlusion

Vascular disorders: vasculitis

Cardiac disorders: atrial fibrillation

Table 2 shows the incidence of worsening liver laboratory abnormalities in Trial 1 summarized as the proportion of patients who experienced a shift from baseline to Grade 3 or 4.

Table 2 : Change from Baseline to Grade 3/4 Liver Laboratory Abnormalities in Trial 1*

ParameterChange From Baseline to Grade 3/4
ZELBORAF (%)Dacarbazine (%)
GGT11.58.6
AST0.90.4
ALT2.81.9
Alkaline phosphatase2.90.4
Bilirubin1.90
* For ALT, alkaline phosphatase, and bilirubin, there were no patients with a change to Grade 4 in either treatment arm.

Erdheim-Chester Disease (ECD)

This section describes adverse reactions identified from analyses of Trial 4 [see Clinical Studies]. In Trial 4, 22 patients with BRAF V600 mutation-positive ECD received ZELBORAF 960 mg twice daily. The median treatment duration for ECD patients in this study was 14.2 months. Table 3 presents adverse reactions reported in at least 20% of BRAF V600 mutation-positive ECD patients treated with ZELBORAF.

In Trial 4, the most commonly reported adverse reactions (> 50%) in patients with BRAF V600 mutation-positive ECD treated with ZELBORAF were arthralgia, rash maculo-papular, alopecia, fatigue, electrocardiogram QT interval prolonged, and skin papilloma. The most common (≥ 10%) Grade ≥ 3 adverse reactions were squamous cell carcinoma of the skin, hypertension, rash maculo-papular, and arthralgia.

The incidence of adverse reactions resulting in permanent discontinuation of study medication was 32%.

Table 3 : Adverse Reactions Reported in ≥ 20% of ECD Patients Treated with ZELBORAF*

Trial 4: Patients with ECD
Body System
Adverse Reactions
n=22
All Grades (%)Grade 3-4 (%)
Skin and subcutaneous tissue disorders
Rash maculo-papular5918
Alopecia55-
Hyperkeratosis505
Dry skin45-
Photosensitivity reaction41-
Palmar-plantar erythrodysaesthesia syndrome41-
Pruritus36-
Actinic keratosis325
Keratosis pilaris32-
Rash papular23-
Musculoskeletal and connective tissue disorders
Arthralgia8214
General disorders and administration site conditions
Fatigue555
Gastrointestinal disorders
Diarrhea50-
Nausea32-
Vomiting23-
Nervous system disorders
Peripheral sensory neuropathy36-
Neoplasms benign, malignant and unspecified (incl. cysts and polyps)
Skin papilloma55-
Seborrhoeic keratosis41-
SCC of skin#3636
Melanocytic nevus23
Cardiac disorders
Electrocardiogram QT interval prolonged555
Respiratory, thoracic and mediastinal disorders
Cough36-
Vascular disorders
Hypertension3623
Injury, poisoning and procedural complications
Sunburn23-
*Adverse drug reactions, graded using NCI-CTCAE v 4.0 (NCI common toxicity criteria) for assessment of toxicity.
# Cases of cutaneous squamous cell carcinoma were required to be reported as Grade 3 per protocol.

Clinically relevant adverse reactions reported in < 20% of ECD patients treated with ZELBORAF in Trial 4 include:

Neoplasms benign, malignant and unspecified (includes cysts and polyps): keratoacanthoma

Musculoskeletal and connective tissue disorders: Dupuytren's contracture

Table 4 shows the incidence of worsening liver laboratory abnormalities in Trial 4 summarized as the proportion of ECD patients who experienced a shift from baseline to Grade 3 or 4.

Table 4 : Change from Baseline to Grade 3 Liver Laboratory Abnormalities in Trial 4

Change From Baseline to Grade 3
ParameterVemurafenib (%)
AST0
ALT9.1
Alkaline phosphatase4.5
Bilirubin0

Postmarketing Experience

The following adverse reactions have been identified during post approval use of ZELBORAF. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Neoplasms benign, malignant and unspecified (incl. cysts and polyps): Progression of pre-existing chronic myelomonocytic leukemia with NRAS mutation [see WARNINGS AND PRECAUTIONS].

Skin and subcutaneous tissue disorders: Drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) [see WARNINGS AND PRECAUTIONS].

Blood and lymphatic systems disorder: Neutropenia

Injury, poisoning and procedural complications: Radiation sensitization and recall [see WARNINGS AND PRECAUTIONS].

Gastrointestinal disorders: Pancreatitis

Renal and urinary disorders: Acute interstitial nephritis, acute tubular necrosis [see WARNINGS AND PRECAUTIONS].

Musculoskeletal and connective tissue disorders: Dupuytren's contracture and plantar fascial fibromatosis [see WARNINGS AND PRECAUTIONS].

Read the entire FDA prescribing information for Zelboraf (Vemurafenib)

© Zelboraf Patient Information is supplied by Cerner Multum, Inc. and Zelboraf Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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