Odomzo

Important Safety Information

Verify the pregnancy status of females of reproductive potential prior to initiating ODOMZO [see Use in Specific Populations (8.1, 8.3)].

Recommended Dosage

The recommended dosage of ODOMZO is 200 mg taken orally once daily on an empty stomach, at least 1 hour before or 2 hours after a meal, administered until disease progression or unacceptable toxicity [see Clinical Pharmacology (12.3)].

Obtain serum creatine kinase (CK) levels and renal function tests prior to initiating ODOMZO in all patients [see Dosage and Administration (2.2) and Warnings and Precautions (5.2)].

If a dose of ODOMZO is missed, resume dosing with the next scheduled dose.

Dosage Modifications for Adverse Reactions

Interrupt ODOMZO for

• Severe or intolerable musculoskeletal adverse reactions.
• First occurrence of serum CK elevation between 2.5 and 10 times upper limit of normal (ULN).
• Recurrent serum CK elevation between 2.5 and 5 times ULN.

Resume ODOMZO at 200 mg daily upon resolution of clinical signs and symptoms.

Permanently discontinue ODOMZO for

• Serum CK elevation greater than 2.5 times ULN with worsening renal function.
• Serum CK elevation greater than 10 times ULN.
• Recurrent serum CK elevation greater than 5 times ULN.
• Recurrent severe or intolerable musculoskeletal adverse reactions.

Pregnancy

Risk Summary

Based on its mechanism of action and data from animal reproduction studies, ODOMZO can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on the use of ODOMZO in pregnant women. In animal reproduction studies, oral administration of sonidegib during organogenesis at doses below the recommended human dose of 200 mg resulted in embryotoxicity, fetotoxicity, and teratogenicity in rabbits (see Data). Teratogenic effects observed included severe midline defects, missing digits, and other irreversible malformations. Advise pregnant women of the potential risk to a fetus. Report pregnancies to Sun Pharmaceutical Industries, Inc. at 1-800-406-7984.

In the U.S. general population, the estimated background risk of major birth defects is 2-4% and of miscarriage in clinically recognized pregnancies is 15-20%.

Data

Animal Data

Daily oral administration of sonidegib to pregnant rabbits resulted in abortion, complete resorption of fetuses, or severe malformations at ≥ 5 mg/kg/day (approximately 0.05 times the recommended human dose based on AUC). Teratogenic effects included vertebral, distal limb and digit malformations, severe craniofacial malformations, and other severe midline defects. Skeletal variations were observed when maternal exposure to sonidegib was below the limit of detection.

Lactation

No data are available regarding the presence of sonidegib in human milk, the effects of the drug on the breastfed infant, or the effects of the drug on milk production. Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with ODOMZO and for 20 months after the last dose.

Females and Males of Reproductive Potential

Based on its mechanism of action and animal data, ODOMZO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].

Pregnancy Testing

Verify the pregnancy status of females of reproductive potential prior to initiating ODOMZO treatment.

Contraception

Females

Advise females of reproductive potential to use effective contraception during treatment with ODOMZO and for at least 20 months after the last dose.

Males

It is not known if sonidegib is present in semen. Advise male patients to use condoms, even after a vasectomy, to avoid potential drug exposure to pregnant partners and female partners of reproductive potential during treatment with ODOMZO and for at least 8 months after the last dose.

Advise males not to donate semen during treatment with ODOMZO and for at least 8 months after the last dose.

Infertility

Based on findings from animal studies, female fertility may be compromised with ODOMZO [see Nonclinical Toxicology (13.1)].

Pediatric Use

The safety and effectiveness of ODOMZO have not been established in pediatric patients.

Epiphyseal disorders, including premature fusion of the epiphyses, have been reported in pediatric patients exposed to ODOMZO in a clinical trial. In some cases, pediatric patients treated with other Hh pathway inhibitors have experienced progression of epiphyseal fusion despite discontinuation of the Hh pathway inhibitor.

Juvenile Animal Data

In a 5-week juvenile rat toxicology study, effects of sonidegib were observed in bone, teeth, reproductive tissues, and nerves at doses ≥10 mg/kg/day (approximately 1.2 times the recommended human dose based on AUC). Bone findings included thinning/closure of bone growth plate, decreased bone length and width, and hyperostosis. Findings in teeth included missing or fractured teeth, and atrophy. Reproductive tissue toxicity was evidenced by atrophy of testes, ovaries, and uterus, partial development of the prostate gland and seminal vesicles, and inflammation and aspermia of the epididymis. Nerve degeneration was also noted.

Geriatric Use

Of the 229 patients who received ODOMZO (79 patients receiving 200 mg daily and 150 patients receiving 800 mg daily) in BOLT, 54% were 65 years and older, while 28% were 75 years and older. No overall differences in effectiveness were observed between these patients and younger patients. There was a higher incidence of serious adverse reactions, Grade 3 and 4 adverse reactions, and adverse reactions requiring dose interruption or discontinuation in patients ≥65 years compared with younger patients; this was not attributable to an increase in any specific adverse event.