ERIVEDGE SIDE EFFECTS
- Generic Name: vismodegib
- Brand Name: Erivedge
- Drug Class:
SIDE EFFECTS
The following clinically significant adverse reactions are described elsewhere in the labeling:
- Severe Cutaneous Adverse Reactions.
- Premature Fusion of the Epiphyses.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety data described below reflect exposure to ERIVEDGE in 138 patients with advanced basal cell carcinoma (BCC) who received ERIVEDGE at doses ≥ 150 mg orally daily in four open-label, uncontrolled, dose-ranging or fixed single dose clinical trials [Study SHH3925g, SHH4437g, SHH4476g and SHH4610g]. The median age of these patients was 61 years (range 21 to 101 years), 100% were White (including Hispanics), and 64% were male. The median duration of treatment was approximately 10 months (range 21 days to 36 months); 111 patients received ERIVEDGE for 6 months or longer.
The most common adverse reactions (≥ 10%) were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, arthralgias, vomiting, and ageusia (Table 1).
Table 1: Adverse Reactions Occurring in ≥ 10% of Patients with Advanced Basal Cell Carcinoma
| Adverse Reaction | ERIVEDGE (N = 138) |
||
| All Grades1 (%) | Grade 3 (%) | Grade 4 (%) | |
| Gastrointestinal | |||
| Nausea | 30% | 0.7% | – |
| Diarrhea | 29% | 0.7% | – |
| Constipation | 21% | – | – |
| Vomiting | 14% | – | – |
| General | |||
| Fatigue | 40% | 5% | 0.7% |
| Investigations | |||
| Weight loss | 45% | 7% | – |
| Metabolism and nutrition | |||
| Decreased appetite | 25% | 2.2% | – |
| Musculoskeletal and connective tissue | |||
| Muscle spasms | 72% | 3.6% | – |
| Arthralgias | 16% | 0.7% | |
| Nervous system | |||
| Dysgeusia | 55% | – | – |
| Ageusia | 11% | – | – |
| Skin and subcutaneous tissue | |||
| Alopecia | 64% | – | – |
| 1 Grading according to National Cancer Institute-Common Terminology Criteria for Adverse Events version 3.0. | |||
Amenorrhea
Among patients from the clinical trials included in the pooled safety data analysis, 30% of 10 pre-menopausal women developed amenorrhea while receiving ERIVEDGE.
Laboratory Abnormalities
Grade 3 laboratory abnormalities observed in clinical trials were hyponatremia (4%), azotemia (2%) and hypokalemia (1%).
Additionally, in a post-approval clinical trial conducted in 1232 patients with locally advanced or metastatic BCC treated with ERIVEDGE, a subset of 29 patients had baseline values for blood creatine phosphokinase (CPK) reported. Within this subset of patients, 38% had a shift from baseline, including Grade 3 (3%) increased CPK. Grade 3 or 4 increased CPK occurred in 2.4% of the 453 patients across the entire study population with any CPK measurement.
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of ERIVEDGE. 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.
Hepatobiliary disorders: Drug-induced liver injury
Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome/toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms.
SRC: NLM .