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Zelboraf (Vemurafenib) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in another section of the label:

  • Cutaneous Squamous Cell Carcinoma [see Warnings and Precautions]
  • Hypersensitivity Reactions [see Warnings and Precautions]
  • Dermatologic Reactions [see Warnings and Precautions]
  • QT Prolongation [see Warnings and Precautions]
  • Liver Laboratory Abnormalities [see Warnings and Precautions]
  • Photosensitivity [see Warnings and Precautions]
  • Ophthalmologic Reactions [see Warnings and Precautions]
  • New Primary Malignant Melanoma [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.

The adverse drug reactions (ADRs) described in this section were identified from Trial 1 and Trial 2 [see Clinical Studies]. In Trial 1, treatment naive patients with unresectable or metastatic melanoma (n=675) were allocated to ZELBORAF 960 mg orally twice daily or to dacarbazine 1000 mg/m2 intravenously every 3 weeks. In Trial 2, (n=132) patients with metastatic melanoma and failure of at least one prior systemic therapy received treatment with ZELBORAF 960 mg orally twice daily. Adverse reactions reported in at least 10% of patients treated with ZELBORAF are presented in Table 2. The most common adverse reactions of any grade (≥ 30% in either study) reported 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 2 Adverse Reactions Reported in ≥ 10% of Patients Treated with ZELBORAFAdverse drug reactions, reported using MedDRA and graded using NCI-CTC-AE v 4.0 (NCI common toxicity criteria) for assessment of toxicity.
Trial 1: Treatment Naive Patients Trial 2: Patients with Failure of at Least One Prior Systemic Therapy
ZELBORAF
n= 336
Dacarbazine
n= 287
ZELBORAF
n= 132
ADRs All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%)
Skin and subcutaneous tissue disorders
Rash 37 8 - 2 - - 52 7 -
Photosensitivity reaction 33 3 - 4 - - 49 3 -
Alopecia 45 <1 - 2 - - 36 - -
Pruritus 23 1 - 1 - - 30 2 -
Hyperkeratosis 24 1 - <1 - - 28 - -
Rash maculo-papular 9 2 - <1 - - 21 6 -
Actinic keratosis 8 - - 3 - - 17 - -
Dry skin 19 - - 1 - - 16 - -
Rash papular 5 <1 - - - - 13 - -
Erythema 14 - - 2 - - 8 - -
Musculoskeletal and connective tissue disorders
Arthralgia 53 4 - 3 <1 - 67 8 -
Myalgia 13 <1 - 1 - - 24 <1 -
Pain in extremity 18 <1 - 6 2 - 9 - -
Musculoskeletal pain 8 - - 4 <1 - 11 - -
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 - - 23 - -
Pyrexia 19 <1 - 9 <1 - 17 2 -
Asthenia 11 <1 - 9 <1 - 2 - -
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 - - 16 - -
Nervous system disorders
Headache 23 <1 - 10 - - 27 - -
Dysgeusia 14 - - 3 - - 11 - -
Neoplasms benign, malignant and unspecified (includes cysts and polyps)
Skin papilloma 21 <1 - - - - 30 - -
Cutaneous SCCIncludes both squamous cell carcinoma of the skin and keratoacanthoma. All cases of cutaneous squamous cell carcinoma were to be reported as Grade 3 per instructions to study investigators and no dose modification or interruption was required. 24 22 - <1 <1 - 24 24 -
Seborrheic keratosis 10 <1 - 1 - - 14 - -
Investigations
Gamma-glutamyltransferase increased 5 3 <1 1 - - 15 6 4
Metabolism and nutrition disorders
Decreased appetite 18 - - 8 <1 - 21 - -
Respiratory, thoracic and mediastinal disorders
Cough 8 - - 7 - - 12 - -
Injury, poisoning and procedural complications
Sunburn 10 - - - - - 14 - -

Clinically relevant adverse events reported in < 10% of patients treated with ZELBORAF in the Phase 2 and Phase 3 studies include:

Skin and subcutaneous tissue disorders: palmar-plantar erythrodysaesthesia syndrome, keratosis pilaris, erythema nodosum, Stevens-Johnson syndrome

Musculoskeletal and connective tissue disorders: arthritis

Nervous system disorders: dizziness, neuropathy peripheral, VIIth nerve paralysis

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

Infections and infestations: folliculitis

Investigations: weight decreased

Eye disorders: retinal vein occlusion, uveitis

Vascular disorders: vasculitis

Cardiac disorders: atrial fibrillation

Table 3 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 3 Change From Baseline to Grade 3/4 Liver Laboratory AbnormalitiesFor ALT, alkaline phosphatase and bilirubin, there were no patients with a change to grade 4 in either treatment arm.
Change From Baseline to Grade 3/4
Parameter ZELBORAF (%) Dacarbazine (%)
GGT 11.5 8.6
AST 0.9 0.4
ALT 2.8 1.9
Alkaline phosphatase 2.9 0.4
Bilirubin 1.9 -



REPORTS OF SUSPECTED ZELBORAF SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Zelboraf. The information is not vetted and should not be considered as verified clinical evidence.

Possible Zelboraf side effects / adverse reactions in 58 year old male

Reported by a consumer/non-health professional from United States on 2011-10-11

Patient: 58 year old male weighing 84.8 kg (186.6 pounds)

Reactions: Vomiting, Pain, Lack of Satiety, Abasia, Pyrexia, Headache, Eating Disorder, Malaise, Dysstasia, Chest Pain, Insomnia, Vision Blurred, Asthenia, Decreased Appetite, Muscle Spasms

Adverse event resulted in: life threatening event, hospitalization

Suspect drug(s):
Zelboraf



Possible Zelboraf side effects / adverse reactions in 54 year old female

Reported by a pharmacist from United States on 2011-10-28

Patient: 54 year old female

Reactions: Rash Generalised

Suspect drug(s):
Zelboraf



Possible Zelboraf side effects / adverse reactions in 54 year old female

Reported by a pharmacist from United States on 2011-11-14

Patient: 54 year old female weighing 76.0 kg (167.2 pounds)

Reactions: Drug Eruption, Angioedema, Arthralgia, Rash Maculo-Papular, Renal Failure Acute

Adverse event resulted in: hospitalization

Suspect drug(s):
Zelboraf



See index of all Zelboraf side effect reports >>

Drug label data at the top of this Page last updated: 2011-08-01

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