ODOMZO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ODOMZO (ODOMZO).
Hedgehog pathway inhibitor; binds to Smoothened (SMO), a G protein-coupled receptor, to inhibit downstream signaling
| Metabolism | Metabolized primarily by CYP3A4; also involves CYP2C8 and CYP2C9 |
| Excretion | Primarily hepatic metabolism via CYP3A4; 70% excreted in feces (as unchanged drug and metabolites), 20% in urine (mostly metabolites). |
| Half-life | Terminal elimination half-life is approximately 90 hours (range 70–120 h), supporting once-daily dosing due to sustained Hh pathway inhibition. |
| Protein binding | >99.5% bound to human plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 9.1 L/kg, indicating extensive extravascular distribution and high tissue binding. |
| Bioavailability | Oral bioavailability is about 40–50% under fasted conditions; increased by 2-fold with a high-fat meal (recommended with food). |
| Onset of Action | Clinical effect on tumor growth observed within 4–8 weeks of continuous oral dosing. |
| Duration of Action | Pharmacodynamic effect persists for 2–3 weeks after last dose due to slow elimination; continuous daily dosing required for maintained efficacy. |
200 mg orally once daily, taken with food.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild-to-moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or ESRD. |
| Liver impairment | Child-Pugh A: no dose adjustment. Child-Pugh B: reduce dose to 200 mg every other day. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients (<18 years). |
| Geriatric use | No specific dose adjustment required based on age; monitor for increased risk of adverse effects due to potential age-related renal function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ODOMZO (ODOMZO).
| Breastfeeding | It is unknown if sonidegib or its metabolites are excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, including potential for tumor development, women should not breastfeed during treatment and for at least 20 months after the last dose. No M/P ratio is available. |
| Teratogenic Risk | ODOMZO (sonidegib) is contraindicated in pregnancy. Based on its mechanism of action (Hedgehog pathway inhibitor), it is expected to cause embryofetal toxicity, including severe birth defects and fetal loss. There are no adequate data in pregnant women; animal studies show teratogenicity at clinically relevant exposures. All trimesters are at risk; exposure should be avoided. |
■ FDA Black Box Warning
None
| Serious Effects |
["None known"]
| Precautions | ["Embryo-fetal toxicity: Can cause fetal harm; verify pregnancy status, advise effective contraception","Musculoskeletal adverse reactions: Arthralgia, muscle spasms, musculoskeletal pain","Fatigue","Increased creatine phosphokinase (CPK)","Renal toxicity: Monitor renal function","Hepatic impairment: Avoid in severe impairment"] |
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| Fetal Monitoring | Pregnancy status should be verified before starting ODOMZO. Women of reproductive potential must use effective contraception during treatment and for at least 20 months after the last dose. Males with female partners should use condoms during treatment and for 8 months after the last dose to avoid exposure to semen. Monthly pregnancy testing is recommended. |
| Fertility Effects | Animal studies have shown impairment of female fertility with sonidegib. Reversible menstrual irregularities have been observed in clinical studies. Effects on male fertility are unknown; testicular toxicity (hypospermia, reduced sperm motility) was seen in animal studies. The clinical significance in humans is not established. |