Version May 2024
Sonidegib can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. Sonidegib is embryotoxic, fetotoxic, and teratogenic in animals.
Verify the pregnancy status of females of reproductive potential prior to initiating therapy. Advise females of reproductive potential to use effective contraception during treatment with sonidegib and for at least 20 months after the last dose. Advise males of the potential risk of exposure through semen and to use condoms with a pregnant partner or a female partner of reproductive potential during treatment with sonidegib and for at least 8 months after the last dose.
Basal cell carcinoma, locally advanced: Oral: 200 mg once daily until disease progression or unacceptable toxicity (Ref).
Missed doses: If a dose is missed, skip the missed dose and resume dosing with the next scheduled dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
CrCl 30 to 89 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, mild or moderate impairment had no clinically meaningful effect on sonidegib exposure (compared to patients with normal renal function). No need for dosage adjustment is expected (Ref).
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling.
Hemodialysis: No need for dosage adjustment is expected (Ref).
Mild, moderate, or severe impairment (Child-Pugh classes A, B, and C): There are no dosage adjustments provided in the manufacturer's labeling; however, hepatic impairment had no clinically meaningful effect on sonidegib exposure (compared to patients with normal hepatic function). No need for dosage adjustment is expected (Ref).
Withhold treatment for any of the following (may resume at 200 mg daily upon resolution of toxicity):
Creatine kinase (CK) serum elevation between 2.5 and 10 times ULN (first occurrence) or between 2.5 and 5 times ULN (recurrent).
Musculoskeletal adverse reactions, severe or intolerable.
Permanently discontinue therapy for:
CK serum elevation >2.5 times ULN with worsening renal function.
CK serum elevation >10 times ULN.
CK serum elevation >5 times ULN (recurrent).
Musculoskeletal adverse reactions, severe or intolerable (recurrent).
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Dermatologic: Alopecia (53%)
Endocrine & metabolic: Hyperglycemia (51%), weight loss (30%)
Gastrointestinal: Abdominal pain (18%), decreased appetite (23%), diarrhea (32%; grade 3: 1%), dysgeusia (46%), increased serum amylase (16%), increased serum lipase (43%), nausea (39%; grade 3: 1%), vomiting (11%; grade 3: 1%)
Hematologic & oncologic: Anemia (32%), lymphocytopenia (28%, grades 3/4: 3%)
Hepatic: Increased serum alanine aminotransferase (19%), increased serum aspartate aminotransferase (19%)
Nervous system: Fatigue (41%), headache (15%), pain (14%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (61%), muscle spasm (54%), musculoskeletal pain (32%), myalgia (19%)
Renal: Increased serum creatinine (92%)
1% to 10%: Dermatologic: Pruritus (10%)
<1%: Neuromuscular & skeletal: Rhabdomyolysis
Frequency not defined:
Endocrine & metabolic: Amenorrhea
Nervous system: Asthenia
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to sonidegib or any component of the formulation; pregnancy or females at risk of becoming pregnant; breastfeeding; male patients or female patients of childbearing potential who do not comply with the ODOMZO Pregnancy Prevention Program; children and adolescents <18 years of age.
Concerns related to adverse effects:
• Musculoskeletal toxicity: Musculoskeletal toxicity occurred in more than two-thirds of patients treated with sonidegib (including grade 3 and 4 events). Muscle spasms, musculoskeletal pain, and myalgia were the most frequently reported musculoskeletal adverse reactions. Increased serum creatine kinase (CK) levels were also commonly observed (some events were grade 3 or 4); CK elevations were usually preceded by musculoskeletal pain and myalgia. When CK elevations were grade 2 or higher, the median time to symptom onset was ~13 weeks (range: 2 to 39 weeks), and the median time to resolution (to ≤ grade 1) was 12 days. More than one-quarter of patients required medical management for musculoskeletal toxicity (eg, magnesium supplementation, muscle relaxants, and analgesics/opioids); several patients required intravenous hydration or hospitalization. Rhabdomyolysis was observed in 1 patient in clinical trials (at a dose higher than the FDA-approved dose).
Disease-related concerns:
• Renal impairment: Increased serum creatinine was observed in the majority of patients receiving sonidegib, although the measurement remained within the normal range in more than 75% of patients.
Special populations:
• Older adult: Patients ≥65 years of age experienced a higher incidence of serious adverse reactions (grade 3 or 4) compared to patients <65 years of age.
• Pediatric: Premature fusion of the epiphyses has been reported in pediatric patients exposed to sonidegib and other Hedgehog pathway inhibitors; the fusion progressed after discontinuation in some cases following use of other Hedgehog pathway inhibitors. Sonidegib is not indicated for use in pediatric patients.
Dosage form specific issues:
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.
Other warnings/precautions:
• Blood donations: Advise patients not to donate blood or blood products during sonidegib treatment and for at least 20 months after the last sonidegib dose.
• Conversion: One 200 mg sonidegib capsule is equivalent to 281 mg of the diphosphate salt of sonidegib.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Odomzo: 200 mg
No
Capsules (Odomzo Oral)
200 mg (per each): $528.39
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule, Oral:
Odomzo: 200 mg
Oral: Administer on an empty stomach at least 1 hour before or 2 hours after a meal.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Sonidegib may cause teratogenicity, reproductive toxicity, and has a structural or toxicity profile similar to existing hazardous agents.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Odomzo: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/205266s009lbl.pdf#page=14
Basal cell carcinoma, locally advanced: Treatment of adult patients with locally advanced basal cell carcinoma (BCC) that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy.
Odomzo may be confused with Opdivo
Sonidegib be confused with glasdegib, SORAfenib, sotorasib, vismodegib
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Sonidegib. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Sonidegib. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May increase the serum concentration of Sonidegib. Management: Avoid concomitant use of sonidegib and moderate CYP3A4 inhibitors when possible. When concomitant use cannot be avoided, limit CYP3A4 inhibitor use to less than 14 days and monitor for sonidegib toxicity (particularly musculoskeletal adverse reactions). Risk D: Consider therapy modification
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Sonidegib. Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Taking sonidegib with a high-fat meal (~1,000 calories with 50% fat content) will increase systemic exposure (7- to 8-fold). Management: Do not administer with food; must be taken on an empty stomach, at least 1 hour before and 2 hours after food.
Verify the pregnancy status of patients who may become pregnant prior to initiating therapy. Patients who may become pregnant should use effective contraception during treatment and for at least 20 months after the last sonidegib dose. Amenorrhea lasting for at least 18 months was observed in some premenopausal patients.
It is not known if sonidegib is present in semen. Advise patients of the potential risk of exposure through semen and to use condoms with a pregnant partner or a partner who may become pregnant, during treatment and for at least 8 months after the last sonidegib dose. Condoms should be used even following a vasectomy. Advise patients not to donate sperm during sonidegib treatment and for at least 8 months after the last sonidegib dose.
In utero exposure to sonidegib may cause fetal harm. Sonidegib is embryotoxic, fetotoxic, and teratogenic in animals. Embryo-fetal death or severe birth defects may occur if administered to a pregnant patient.
Data collection to monitor pregnancy and infant outcomes following exposure to sonidegib is ongoing. Health care providers should notify the manufacturer of pregnancies which may occur following exposure to sonidegib (800-406-7984).
It is not known if sonidegib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for at least 20 months after the last sonidegib dose.
Serum creatine kinase (CK) and serum creatinine (baseline, periodically during treatment, and at least weekly with musculoskeletal toxicity and CK elevations >2.5 times ULN until resolution), liver function. Verify pregnancy status of patients who may become pregnant prior to therapy initiation. Monitor for signs/symptoms of musculoskeletal adverse reactions, and advise patients to promptly report new, unexplained muscle pain, tenderness, or weakness (either occurring during therapy or persisting after discontinuation).
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Basal cell cancer is associated with mutations in Hedgehog pathway components. Hedgehog regulates cell growth and differentiation in embryogenesis; while generally not active in adult tissue, Hedgehog mutations associated with basal cell cancer can activate the pathway resulting in unrestricted proliferation of skin basal cells (Von Hoff 2009). Sonidegib is a selective Hedgehog pathway inhibitor which binds to and inhibits Smoothened homologue (SMO), the transmembrane protein involved in Hedgehog signal transduction.
Absorption: <10%; AUCinf and Cmax are increased by 7.4- to 7.8-fold, respectively, when administered with a high-fat meal (~1,000 calories with 50% fat content)
Distribution: 9,166 L
Protein binding: >97%
Metabolism: Primarily hepatic through CYP3A
Bioavailability: <10% of an oral dose is absorbed
Half-life elimination: ~28 days
Time to peak: 2 to 4 hours
Excretion: Feces (~70%); urine (30%)
Race/ethnicity: Following a single 200 mg dose, exposure (AUCinf) is 1.7-fold higher in Japanese healthy subjects as compared to Western healthy subjects.
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