Side Effects of Odomzo (sonidegib)

Odomzo (sonidegib) is a cancer medication used to treat adults with basal cell carcinoma that has recurred following surgery or radiation treatment or that cannot be treated with surgery or radiation. 

Odomzo is an inhibitor of the hedgehog biological signaling pathway, a pathway that promotes the growth of both normal and cancer cells. Odomzo binds to and inhibits smoothened, a protein involved in hedgehog signaling. Inhibiting smoothened disrupts cell signaling and growth of cancer cells. 

Common side effects of Odomzo include:

• hair loss,
• weakness,
• nausea,
• decreased appetite,
• vomiting,
• taste changes,
• diarrhea,
• weight loss,
• stomach pain,
• headache,
• pain,
• muscle pain and spasms, and
• itching. 

Women taking Odomzo may experience an absence of menstrual periods (amenorrhea). It is unknown if amenorrhea is permanent. Women who wish to get pregnant in the future should talk to their doctor.

Drug interactions of Odomzo because they may result in high blood levels of Odomzo, leading to increased side effects, include:

• ketoconazole,
• itraconazole,
• voriconazole,
• certain HIV medications, and
• telithromycin. 

The following drugs may decrease blood levels of Odomzo, causing treatment failure:

• carbamazepine,
• efavirenz,
• modafinil,
• phenobarbital,
• phenytoin,
• rifampin, and
• St. John's wort. 

Use of Odomzo during pregnancy is not recommended because it may cause death and severe birth defects. Female patients who have been exposed to Odomzo during pregnancy should report their pregnancy to Novartis Pharmaceuticals Corporation by calling 1-888-669-6682. 

It is unknown if Odomzo is excreted in breast milk. Breastfeeding is not recommended while using Odomzo and for at least 20 months after the last dose because there is a potential for serious side effects in the breastfed baby. 

The most common side effects of sonidegib include:

• hair loss,
• weakness,
• nausea,
• decreased appetite,
• vomiting,
• taste changes,
• diarrhea,
• weight loss,
• stomach pain,
• headache,
• pain,
• muscle pain and spasms, and
• itching.

Women taking sonidegib may experience an absence of menstrual periods (amenorrhea). It is not known if amenorrhea is permanent. Women who wish to get pregnant in the future should talk to their doctor for advice.

The following clinically significant adverse reactions are described elsewhere in the labeling:

• Musculoskeletal Adverse Reactions.

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 of Odomzo was evaluated in BOLT, 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 was greater in patients treated with Odomzo 800 mg as compared to 200 mg, including:

• muscle spasms,
• alopecia,
• dysgeusia,
• fatigue,
• nausea,
• decreased weight,
• decreased appetite,
• myalgia,
• pain, and
• vomiting.

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 Hh 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 BOLT

Table 2: Key Laboratory Abnormalities^a in BOLT

Amenorrhea

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.

Effects Of Other Drugs On Odomzo

Strong And Moderate CYP3A Inhibitors

Avoid concomitant administration of Odomzo with strong CYP3A inhibitors.

Avoid concomitant administration of Odomzo with moderate CYP3A inhibitors. If a moderate CYP3A inhibitor must be used, administer the moderate CYP3A inhibitor for less than 14 days and monitor closely for adverse reactions particularly musculoskeletal adverse reactions.

Strong And Moderate CYP3A Inducers

Avoid concomitant administration of Odomzo with strong and moderate CYP3A inducers.