sonidegib

Adult Dosing

Locally Advanced Basal Cell Carcinoma (BCC)

Recommended dose: 200 mg PO qd
Dose should be taken on empty stomach, at least 1 hour before or 2 hours after a meal

Note:

Establish the pregnancy status of females of reproductive potential before initiating sonidegib treatment
Obtain serum creatine kinase (CK) levels and renal function tests before initiating sonidegib treatment in all patients
If a dose is missed, resume dosing with the next scheduled dose
Dose modifications: Refer package insert

Pediatric Dosing

[Outline]

Indications ⬆ ⬇

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

Contraindications ⬆ ⬇

Black Box Warnings ⬆ ⬇

Emryo-fetal toxicity: Sonidegib can cause embryo-fetal death or severe birth defects when administered to a pregnant woman and is embryotoxic, fetotoxic, and teratogenic in animals. Establish the pregnancy status of females of reproductive potential before initiating the therapy
Females of reproductive potential should be advised to use effective contraception during treatment with sonidegib and for at least 20 months after the last dose
Inform males of the potential risk of exposure through semen and advise them to use condoms with a pregnant partner or a female partner of reproductive potential during treatment and for at least 8 months after the last dose

Dosing Adjustment ⬆ ⬇

Renal Dose Adjustment

Hepatic Dose Adjustment

Mild hepatic impairment: Total bilirubin ULN and AST > ULN or Total bilirubin >1-1.5 x ULN: No dose adjustments
Moderate to severe hepatic impairment: Dose adjustments not defined

Warnings/Precautions ⬆ ⬇

Sonidegib can cause embryo-fetal death or severe birth defects in pregnant women
Pregnancy status should be verified in females of reproductive potential prior to initiating sonidegib treatment and should be advised to use effective contraception during treatment and for at least 20 months after the last dose
Advise male patients with female partners to use condoms during the treatment and for at least 8 months after the last dose, in spite of vasectomy, to avoid potential drug exposure to pregnant partners and female partners of reproductive potential
Advise patients not to donate blood or blood products while taking sonidegib and for at least 20 months after the last dose
Musculoskeletal adverse reactions, which may be accompanied by serum creatine kinase (CK) elevations occur with hedgehog pathway inhibitors. Advise patients to report promptly any new unexplained muscle pain, tenderness, or weakness occurring during treatment or that persists after discontinuing sonidegib
Obtain baseline serum CK and creatinine levels prior to initiating therapy, periodically during treatment, and as clinically indicated
Obtain serum CK and creatinine levels at least weekly in patients with musculoskeletal adverse reactions with concurrent serum CK elevation >2.5 X ULN until resolution of clinical signs and symptoms

Interactions ⬆ ⬇

Odomzo interacts with :

Pregnancy/Breast Feeding ⬆ ⬇

Pregnancy Category: Not rated

Mechanism of action and data from animal reproduction studies suggest that sonidegib can cause fetal harm when administered to a pregnant woman. However, data on its use in pregnant women are not available

Breastfeeding: Manufacturer advises not to breastfeed during treatment with sonidegib and for 20 months after the last dose

Adverse Reactions ⬆ ⬇

CNS: Dysgeusia, headache
MUSC: Muscle spasms, musculoskeletal pain, myalgia
DERM: Alopecia, pruritus
GI: Nausea, diarrhea, abdominal pain, vomiting
METABOLIC: Decreased weight, decreased appetite, hyperglycemia
HEMA: Anemia, lymphopenia
LABTESTS: Elevated serum creatinine, elevated serum CK, elevated lipase, elevated ALT, elevated AST, elevated amylase
MISC: Fatigue, pain

Clinical Pharmacology ⬆ ⬇

Hedgehog pathway inhibitor; binds to and inhibits Smoothened (a G protein-coupled receptor) which is a transmembrane protein involved in Hedgehog signal transduction
Bioavailability: Less than 10%
Metabolism: Metabolized in liver by CYP3A
Excretion: Excreted in feces (70%) and urine (30%)
Half-life: approximately 28 days

Brands and Availability ⬆ ⬇