Sonidegib Capsules
Name: Sonidegib Capsules
Side effects
The following serious adverse reactions are discussed in greater detail in other sections of the label:
- Musculoskeletal Adverse Reactions [see WARNINGS AND PRECAUTIONS].
Clinical Trial 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 of ODOMZO was evaluated in Study 1, a randomized, double-blind, multiple cohort trial in which 229 patients received ODOMZO at either 200 mg (n=79) or 800 mg (n=150) daily. The frequency of common adverse reactions including muscle spasms, alopecia, dysgeusia, fatigue, nausea, decreased weight, decreased appetite, myalgia, pain, and vomiting was greater in patients treated with ODOMZO 800 mg as compared to 200 mg.
The data described below reflect exposure to ODOMZO 200 mg daily in 79 patients with locally advanced BCC (laBCC; n=66) or metastatic BCC (mBCC; n=13) enrolled in Study 1. Patients were followed for at least 18 months unless discontinued earlier. The median duration of treatment with ODOMZO was 11.0 months (range 1.3 to 33.5 months). The study population characteristics were: median age of 67 years (range 25 to 92; 59% were ≥ 65 years), 61% male, and 90% white. The majority of patients had prior surgery (75%), radiotherapy (24%), systemic chemotherapy (4%), or topical or photodynamic therapies (18%) for treatment of BCC. No patient had prior exposure to a hedgehog pathway inhibitor.
ODOMZO was permanently discontinued in 34% of patients or temporarily interrupted in 20% of patients for adverse reactions. Adverse reactions reported in at least two patients that led to discontinuation of the drug were: muscle spasms and dysgeusia (each 5%), asthenia, increased lipase, and nausea (each 4%), fatigue, decreased appetite, alopecia, and decreased weight (each 3%). Serious adverse reactions occurred in 18% of patients.
The most common adverse reactions occurring in ≥ 10% of patients treated with ODOMZO 200 mg were muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, and pruritus (Table 1).
The key laboratory abnormalities are described in Table 2.
Table 1: Adverse Reactions Occurring in ≥ 10% of Patients in Study 1
| Adverse Reaction | ODOMZO 200 mg (N=79) | |
| All Gradesa % | Grade 3% | |
| Musculoskeletal and connective tissue disorders | ||
| Muscle spasms | 54 | 3 |
| Musculoskeletal pain | 32 | 1 |
| Myalgia | 19 | 0 |
| Skin and subcutaneous tissue disorder | ||
| Alopecia | 53 | 0 |
| Pruritus | 10 | 0 |
| Nervous system disorders | ||
| Dysgeusia | 46 | 0 |
| Headache | 15 | 1 |
| General disorders and administration site conditions | ||
| Fatigue | 41 | 4 |
| Pain | 14 | 1 |
| Gastrointestinal disorders | ||
| Nausea | 39 | 1 |
| Diarrhea | 32 | 1 |
| Abdominal pain | 18 | 0 |
| Vomiting | 11 | 1 |
| Investigations | ||
| Decreased weight | 30 | 3 |
| Metabolism and nutrition disorders | ||
| Decreased appetite | 23 | 1 |
| a No Grade 4 adverse reactions were reported. | ||
Table 2: Key Laboratory Abnormalitiesa
| Laboratory Test | ODOMZO 200 mg (N=79) | |
| All Grades % | Grades 3-4% | |
| Chemistry | ||
| Increased serum creatinine | 92b | 0 |
| Increased serum creatine kinase (CK) | 61 | 8 |
| Hyperglycemia | 51 | 4 |
| Increased lipase | 43 | 13 |
| Increased alanine aminotransferase | 19 | 4 |
| Increased aspartate aminotransferase | 19 | 4 |
| Increased amylase | 16 | 1 |
| Hematology | ||
| Anemia | 32 | 0 |
| Lymphopenia | 28 | 3 |
| a Based on worst post-treatment laboratory value regardless of baseline; grading by CTCAE v4.03. b The serum creatinine level remained within normal range in 76% (60/79) of patients. | ||
Amenorrhea lasting for at least 18 months occurred in two of 14 pre-menopausal women treated with ODOMZO 200 mg or 800 mg once daily.