Odomzo (sonidegib phosphate)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Sonidegib, a hedgehog signaling pathway inhibitor, is an antineoplastic agent.
Sonidegib is an antineoplastic agent that inhibits the hedgehog pathway by binding to and selectively inhibiting Smoothened, a transmembrane protein involved in hedgehog signal transduction. The hedgehog signaling pathway plays an important role during embryonic organ and tissue development and is a key regulator of bone development and maintenance of tissues and stem cells in adults and during postnatal development. However, genetic mutations that allow for aberrant activation of the hedgehog pathway have been implicated in the development of several malignancies such as basal cell carcinoma.
Inhibition of Smoothened by sonidegib results in inhibition of the hedgehog pathway.
Following oral administration, less than 10% of sonidegib is absorbed. Area under the serum concentration-time curve (AUC) and peak plasma concentrations of sonidegib are dose proportional over a dosage range of 100-400 mg. Peak plasma concentrations of sonidegib are achieved 2-4 hours following oral administration of a single dose of sonidegib (100 mg to 3 g) under fasting conditions in cancer patients.
Following administration of sonidegib, steady-state concentrations of the drug are achieved in approximately 4 months and the estimated accumulation is 19-fold. Administration of sonidegib with a high-fat meal (approximately 1000 calories with 50% of calories from fat) increased systemic exposure (AUC and peak plasma concentrations) of sonidegib by 7.4- to 7.8-fold. In a population pharmacokinetic analysis, administration of sonidegib with a high-fat meal increased bioavailability of the drug fivefold.
Sonidegib is metabolized in the liver principally by cytochrome P-450 (CYP) isoenzyme 3A. In vitro, sonidegib is more than 97% bound to plasma proteins. Following oral administration of sonidegib, approximately 70% of the absorbed dose is recovered in feces and 30% is recovered in urine; unchanged drug is not excreted in urine.
The estimated plasma elimination half-life of the drug is 28-29.6 days.
Population pharmacokinetic analyses indicate that age, sex, body weight, and ethnicity generally do not have clinically important effects on the exposure of sonidegib. A cross-study comparison indicates that systemic exposure following administration of sonidegib (single 200-mg dose) is increased by 1.7-fold in healthy Japanese individuals compared with individuals from Western countries.
USES: This medication is used to treat a certain type of skin cancer (basal cell carcinoma).
Generic name: sonidegib phosphate
Pronunciation: (SOE-ni-DEG-ib)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Odomzo
Indications
The following indications are listed for Odomzo:
- Basal Cell Carcinoma Of Skin
Also known as: Basal Cell Epithelioma, Basalioma.
Dosing
No dosing information is available for this tab.
Sonidegib is administered orally once daily on an empty stomach, at least 1 hour before or 2 hours after a meal.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Sonidegib is metabolized principally by cytochrome P-450 (CYP) isoenzyme 3A. In vitro studies indicate that sonidegib inhibits CYP isoenzymes 2B6 and 2C9, but does not induce CYP 1A2, 2B6, or 3A.
In vitro studies indicate that sonidegib inhibits breast cancer resistance protein (BCRP, ABCG2), but does not inhibit P-glycoprotein (P-gp, ABCB1), multidrug resistance protein 2 (MRP2, ABCC2), organic cation transporter (OCT) 1, OCT2, organic anion transporter (OAT) 1, OAT3, organic anion transport protein (OATP) 1B1, and OATP1B3. In vitro studies also indicate that the drug is not a substrate of P-gp, MRP2, or BCRP.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
The manufacturer states that there are no known contraindications to the use of sonidegib.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in 10% or more of patients with advanced basal cell carcinoma receiving sonidegib in the principal efficacy study include muscle spasms, alopecia, dysgeusia, fatigue, nausea, diarrhea, musculoskeletal pain, weight loss, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, pruritus, and arthralgia.
Laboratory abnormalities reported in more than 15% of patients receiving sonidegib include elevated concentrations of serum creatinine, elevated concentrations of serum CK, hyperglycemia, elevated concentrations of lipase, anemia, lymphopenia, elevated concentrations of aminotransferases (i.e., AST, ALT), and elevated concentrations of amylase.
Amenorrhea lasting at least 18 months also has been reported in 2 of 14 premenopausal women receiving sonidegib (200 or 800 mg once daily).
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
No enhanced messaging available.
Safety and efficacy of sonidegib have not been established in pediatric patients.
Data in animals suggest possible adverse effects on bone, teeth, reproductive tissues, and nerve fibers in juvenile rats receiving sonidegib at exposure levels of approximately 1.2 times the human exposure at the recommended dosage.
Epiphyseal disorders were reported in pediatric patients exposed to sonidegib in a clinical trial.
Sonidegib may cause fetal harm if administered to pregnant females based on its mechanism of action and animal findings.
Verify pregnancy status in all females of reproductive potential prior to initiation of sonidegib therapy. If a female patient or female partner of a male patient receiving sonidegib therapy becomes pregnant during therapy or within 20 or 8 months, respectively, after discontinuance of the drug, the clinician should notify the manufacturer at 800-406-7984.
It is not known whether sonidegib is distributed into milk. Because of the potential for serious adverse reactions to sonidegib in breast-fed infants, women should be advised to discontinue breast-feeding while receiving sonidegib and for at least 20 months after discontinuance of therapy. The effects of the drug on breast-fed infants or on milk production are unknown.
The manufacturer makes no specific dosage recommendations for geriatric patients.
In the BOLT study, 54% of patients receiving sonidegib (200 or 800 mg once daily) were 65 years of age or older and 28% were 75 years of age or older. No overall differences in efficacy were observed between geriatric and younger adults; however, grade 3 or 4 adverse effects, serious adverse effects, or adverse effects requiring interruption or discontinuance of therapy occurred more frequently in patients 65 years of age or older compared with younger adults.
The manufacturer makes no specific dosage recommendations for geriatric patients.
ICD codes
No ICD codes are available for this drug.
Formulary status
Search health-plan coverage for this drug by ZIP code.
Choose the first character of a health plan name.
Last reviewed · Source: First Databank (FDB) drug data
On this page
Actions
Sign in to save favorites
Saving this drug requires a free Physicians Office Resource account.