Sonidegib
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Martin Nino [2]
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Black Box Warning
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EMBRYO-FETAL TOXICITY
See full prescribing information for complete Boxed Warning.
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. |
Overview
Sonidegib is a hedgehog pathway inhibitor that is FDA approved for the 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. There is a Black Box Warning for this drug as shown here. Common adverse reactions include muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, and pruritus (≥10%).
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Sonidegib is indicated for the 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.
Dosage
The recommended dose of Sonidegib 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.
Verify the pregnancy status of females of reproductive potential prior to initiating Sonidegib. Obtain serum creatine kinase (CK) levels and renal function tests prior to initiating Sonidegib in all patients.
If a dose of Sonidegib is missed, resume dosing with the next scheduled dose.
Dose Modifications Interrupt Sonidegib 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 Sonidegib at 200 mg daily upon resolution of clinical signs and symptoms.
Permanently discontinue Sonidegib 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.
Off-Label Use and Dosage (Adult)
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
The safety and effectiveness of Sonidegib have not been established in pediatric patients
Off-Label Use and Dosage (Pediatric)
Contraindications
None
Warnings
|
EMBRYO-FETAL TOXICITY
See full prescribing information for complete Boxed Warning.
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. |
Embryo-fetal Toxicity
Sonidegib can cause embryo-fetal death or severe birth defects when administered to a pregnant woman. In animal reproduction studies, Sonidegib was embryotoxic, fetotoxic, and teratogenic at maternal exposures below the recommended human dose of 200 mg. Advise pregnant women of the potential risk to a fetus.
- Females of Reproductive Potential
Verify pregnancy status of females of reproductive potential prior to initiating Sonidegib treatment. Advise females to use effective contraception during treatment with Sonidegib and for at least 20 months after the last dose.
- Males
Advise male patients with female partners to use condoms, even after a vasectomy, during treatment with Sonidegib and for at least 8 months after the last dose to avoid potential drug exposure in pregnant females or females of reproductive potential.
- Blood Donation
Advise patients not to donate blood or blood products while taking Sonidegib and for at least 20 months after the last dose of Sonidegib because their blood or blood products might be given to a female of reproductive potential.
Musculoskeletal Adverse Reactions
Musculoskeletal adverse reactions, which may be accompanied by serum creatine kinase (CK) elevations, occur with Sonidegib and other drugs which inhibit the hedgehog pathway.
In a pooled safety analysis of 12 clinical studies involving 571 patients with various advanced cancers treated with Sonidegib at doses ranging from 100 mg to 3000 mg, rhabdomyolysis (defined as serum CK increase of more than ten times the baseline value with a concurrent 1.5-fold or greater increase in serum creatinine above baseline value) occurred in one patient (0.2%) treated with Sonidegib 800 mg.
In Study 1, musculoskeletal adverse reactions occurred in 68% (54/79) of patients treated with Sonidegib 200 mg daily with 9% (7/79) reported as Grade 3 or 4. The most frequent manifestations of musculoskeletal adverse reactions reported as an adverse event were muscle spasms (54%), musculoskeletal pain (32%), and myalgia (19%). Increased serum CK laboratory values occurred in 61% (48/79) of patients with 8% (6/79) of patients having Grade 3 or 4 serum CK elevations. Musculoskeletal pain and myalgia usually preceded serum CK elevation. Among patients with Grade 2 or higher CK elevations, the median time to onset was 12.9 weeks (range: 2 to 39 weeks) and the median time to resolution (to ≤ Grade 1) was 12 days (95% CI: 8 to 14 days). Sonidegib was temporarily interrupted in 8% of patients or permanently discontinued in 8% of patients for musculoskeletal adverse reactions. The incidence of musculoskeletal adverse reactions requiring medical intervention (magnesium supplementation, muscle relaxants, and analgesics or narcotics) was 29%, including four patients (5%) who received intravenous hydration or were hospitalized.
Obtain baseline serum CK and creatinine levels prior to initiating Sonidegib, periodically during treatment, and as clinically indicated (e.g., if muscle symptoms are reported). Obtain serum creatinine and CK levels at least weekly in patients with musculoskeletal adverse reactions with concurrent serum CK elevation greater than 2.5 times ULN until resolution of clinical signs and symptoms. Depending on the severity of symptoms, temporary dose interruption or discontinuation may be required for musculoskeletal adverse reactions or serum CK elevation. Advise patients starting therapy with Sonidegib of the risk of muscle-related adverse reactions. Advise patients to report promptly any new unexplained muscle pain, tenderness or weakness occurring during treatment or that persists after discontinuing Sonidegib.
Adverse Reactions
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The safety of Sonidegib was evaluated in Study 1, a randomized, double-blind, multiple cohort trial in which 229 patients received Sonidegib at either 200 mg (n=79) or 800 mg (n=150) daily. The frequency of common adverse reactions including muscle spasms, alopecia, dysgeusia, fatigue, nausea, decreased weight, decreased appetite, myalgia, pain, and vomiting was greater in patients treated with Sonidegib 800 mg as compared to 200 mg.
The data described below reflect exposure to Sonidegib 200 mg daily in 79 patients with locally advanced BCC (laBCC; n=66) or metastatic BCC (mBCC; n=13) enrolled in Study 1. Patients were followed for at least 18 months unless discontinued earlier. The median duration of treatment with Sonidegib was 11.0 months (range 1.3 to 33.5 months). The study population characteristics were: median age of 67 years (range 25 to 92; 59% were ≥65 years), 61% male, and 90% white. The majority of patients had prior surgery (75%), radiotherapy (24%), systemic chemotherapy (4%), or topical or photodynamic therapies (18%) for treatment of BCC. No patient had prior exposure to a hedgehog pathway inhibitor.
Sonidegib was permanently discontinued in 34% of patients or temporarily interrupted in 20% of patients for adverse reactions. Adverse reactions reported in at least two patients that led to discontinuation of the drug were: muscle spasms and dysgeusia (each 5%), asthenia, increased lipase, and nausea (each 4%), fatigue, decreased appetite, alopecia, and decreased weight (each 3%). Serious adverse reactions occurred in 18% of patients.
The most common adverse reactions occurring in ≥10% of patients treated with Sonidegib 200 mg were muscle spasms, alopecia, dysgeusia, fatigue, nausea, musculoskeletal pain, diarrhea, decreased weight, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting, and pruritus (Table 1).
The key laboratory abnormalities are described in Table 2.
TABLE 1
TABLE 2
- Amenorrhea
Amenorrhea lasting for at least 18 months occurred in two of 14 pre-menopausal women treated with Sonidegib 200 mg or 800 mg once daily.
Postmarketing Experience
There is limited information regarding Sonidegib Postmarketing Experience in the drug label.
Drug Interactions
Effects of Other Drugs on Sonidegib
- Strong and Moderate CYP3A Inhibitors
Avoid concomitant administration of Sonidegib with strong CYP3A inhibitors, including but not limited to saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole and nefazodone.
Avoid concomitant administration of Sonidegib with moderate CYP3A inhibitors, including but not limited to atazanavir, diltiazem, and fluconazole. If a moderate CYP3A inhibitor must be used, administer the moderate CYP3A inhibitor for less than 14 days and monitor closely for adverse reactions particularly musculoskeletal adverse reactions.
- Strong and Moderate CYP3A Inducers
Avoid concomitant administration of Sonidegib with strong and moderate CYP3A inducers, including but not limited to carbamazepine, efavirenz, modafinil, phenobarbital, phenytoin, rifabutin, rifampin and St. John’s Wort (Hypericum perforatum).
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Sonidegib in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Sonidegib in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Sonidegib during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Sonidegib in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Sonidegib in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Sonidegib in geriatric settings.
Gender
There is no FDA guidance on the use of Sonidegib with respect to specific gender populations.
Race
There is no FDA guidance on the use of Sonidegib with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Sonidegib in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Sonidegib in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Sonidegib in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Sonidegib in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Sonidegib Administration in the drug label.
Monitoring
There is limited information regarding Sonidegib Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Sonidegib and IV administrations.
Overdosage
There is limited information regarding Sonidegib overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Sonidegib Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Sonidegib Mechanism of Action in the drug label.
Structure
There is limited information regarding Sonidegib Structure in the drug label.
Pharmacodynamics
There is limited information regarding Sonidegib Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Sonidegib Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Sonidegib Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Sonidegib Clinical Studies in the drug label.
How Supplied
There is limited information regarding Sonidegib How Supplied in the drug label.
Storage
There is limited information regarding Sonidegib Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Sonidegib Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Sonidegib interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Sonidegib Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Sonidegib Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.