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)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Pimavanserin in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pimavanserin in adult patients.
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)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Pimavanserin in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Pimavanserin in pediatric patients.
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.
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: Adverse Reactions Occurring in ≥10% of Patients in Study 1
ODOMZO: Sonidegib's Brand name
- Table 2: Key Laboratory Abnormalities(a)
ODOMZO: Sonidegib's Brand name
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
- Risk Summary
Based on its mechanism of action and data from animal reproduction studies, Sonidegib can cause fetal harm when administered to a pregnant woman. There are no available data on the use of Sonidegib 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. 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 Novartis Pharmaceuticals Corporation at 1-888-669-6682.
The background risk of major birth defects and miscarriage for the indicated population is unknown; however, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.
- 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.
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
No data are available regarding the presence of Sonidegib in human milk, the effects of the drug on the breast fed infant, or the effects of the drug on milk production. Because of the potential for serious adverse reactions in breastfed infants from Sonidegib, advise a nursing woman not to breastfeed during treatment with Sonidegib and for 20 months after the last dose.
Pediatric Use
The safety and effectiveness of Sonidegib have not been established in pediatric patients.
- 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.
Geriatic Use
Of the 229 patients who received Sonidegib (79 patients receiving 200 mg daily and 150 patients receiving 800 mg daily) in Study 1, 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 events, Grade 3 and 4 adverse events, and adverse events 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.
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
Based on its mechanism of action and animal data, Sonidegib can cause fetal harm when administered to a pregnant woman.
- Pregnancy Testing
Verify the pregnancy status of females of reproductive potential prior to initiating Sonidegib treatment.
- Contraception
- Females
Advise females of reproductive potential to use effective contraception during treatment with Sonidegib 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 Sonidegib and for at least 8 months after the last dose. Advise males not to donate semen during treatment with Sonidegib and for at least 8 months after the last dose.
Based on findings from animal studies, female fertility may be compromised with Sonidegib.
Immunocompromised Patients
There is no FDA guidance one the use of Sonidegib in patients who are immunocompromised.
Administration and Monitoring
Administration
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.
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 are no recommendations regarding management of overdosage.
Pharmacology
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Sonidegib
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| Systematic (IUPAC) name | |
| N-[6-[(2S,6R)-2,6-Dimethylmorpholin-4-yl]pyridin-3-yl]-2-methyl-3-[4-(trifluoromethoxy)phenyl]benzamide | |
| Identifiers | |
| CAS number | ? |
| ATC code | L01 |
| PubChem | |
| Chemical data | |
| Formula | Template:OrganicBox atomTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBox atomTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBoxTemplate:OrganicBox |
| Mol. mass | 485.498 g/mol |
| SMILES | & |
| Pharmacokinetic data | |
| Bioavailability | <10% |
| Protein binding | >97% |
| Metabolism | Liver (CYP3A) |
| Half life | ~28 days |
| Excretion | Feces (~70%), urine (30%)[1] |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status |
[[Prescription drug|Template:Unicode-only]](US) |
| Routes | By mouth (capsules) |
Mechanism of Action
Sonidegib is an inhibitor of the Hedgehog pathway. Sonidegib binds to and inhibits Smoothened, a transmembrane protein involved in Hedgehog signal transduction.
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
Less than 10% of an oral dose of Sonidegib is absorbed. Following the administration of a single Sonidegib dose (100 mg to 3000 mg) under fasted conditions in patients with cancer, the median time-to-peak concentration (Tmax) was 2 to 4 hours. Sonidegib exhibited dose-proportional increases in the area under the curve (AUC) and the maximal concentration (Cmax) over the dose range of 100 mg to 400 mg, but less than dose-proportional increases at doses greater than 400 mg. Steady-state was reached approximately 4 months after starting Sonidegib and the estimated accumulation at steady-state was 19-fold. Following a dose of 200 mg once daily, the estimated mean steady-state Cmax is 1030 ng/mL, AUC(0-24h) is 22 μg*h/mL and minimal concentration (Cmin) is 890 ng/mL.
A high-fat meal (approximately 1000 calories with 50% of calories from fat) increased exposure to Sonidegib (geometric mean AUC(inf) and Cmax) by 7.4- to 7.8-fold.
The estimated apparent steady-state volume of distribution (Vss/F) was 9,166 L. Sonidegib was greater than 97% bound to human plasma proteins in vitro and the binding was concentration independent. In vitro studies suggested that sonidegib is not a substrate of P-glycoprotein, MRP2 or BCRP.
The elimination half-life (t1/2) of Sonidegib estimated from population pharmacokinetic (PK) modeling was approximately 28 days.
Sonidegib is primarily metabolized by CYP3A. The main circulating compound was unchanged sonidegib (36% of circulating radioactivity).
Sonidegib and its metabolites are eliminated primarily by the hepatic route. Of the absorbed dose, approximately 70% was eliminated in the feces and 30% was eliminated in the urine. Unchanged Sonidegib was not detectable in the urine.
Specific Populations
Mild (Child-Pugh class A), moderate (Child-Pugh class B), or severe (Child-Pugh class C) hepatic impairment had no clinically meaningful effect on Sonidegib exposure as compared to subjects with normal hepatic function.
Mild (CLcr 60 to 89 mL/min) and moderate (CLcr 30 to 59 mL/min) renal impairment had no effect on Sonidegib steady-state exposure as compared to patients with normal renal function (CLcr ≥90 mL/min).
- Age, Sex, Weight and Race
Age, body weight, or sex had no clinically meaningful effect on Sonidegib steady-state exposure.
A cross study comparison suggests that geometric mean AUCinf of Sonidegib is 1.7-fold higher in Japanese healthy subjects compared to Western healthy subjects (Whites and Blacks) following a single 200 mg dose of Sonidegib.
Drug Interaction Studies
- Effects of CYP3A Inhibitors on Sonidegib
Strong CYP3A inhibitor: The geometric mean Sonidegib AUC(0-10d) increased by 2.2-fold and the Cmax increased by 1.5-fold when Sonidegib at a dose of 800 mg was taken with ketoconazole compared to Sonidegib alone. The geometric mean sonidegib steady-state AUC(0-24h) would similarly increase in cancer patients taking Sonidegib 200 mg once daily when coadministered with a strong CYP3A inhibitor for 14 days.
Moderate CYP3A inhibitor: The geometric mean sonidegib steady-state AUC(0-24h) would increase 1.8-fold when Sonidegib 200 mg once daily is coadministered with a moderate CYP3A inhibitor (erythromycin) for 14 days and would increase 2.8-fold when Sonidegib 200 mg once daily is coadministered with a moderate CYP3A inhibitor (erythromycin) for 4 months.
- Effects of CYP3A Inducers on Sonidegib
Strong CYP3A inducer: The geometric mean Sonidegib AUC(0-10d) decreased by 72% and the Cmax decreased by 54% when Sonidegib at a dose of 800 mg was taken with rifampicin compared to Sonidegib alone.
Moderate CYP3A inducer: The geometric mean Sonidegib steady-state AUC(0-24h) would decrease 56% in cancer patients taking Sonidegib 200 mg once daily when coadministered with a moderate CYP3A inducer (efavirenz) for 14 days and would decrease 69% when coadministered with a moderate CYP3A inducer (efavirenz) for 4 months.
- Effect of Sonidegib on Cytochrome P450 Enzymes and Transporters
In vitro studies suggested that Sonidegib inhibits CYP2B6 and CYP2C9 and it does not induce CYP1A2, CYP2B6 or CYP3A expression or activity.
In vitro studies suggested that Sonidegib inhibits BCRP, but not P-glycoprotein, MRP2, OATP1B1, OATP1B3, OAT1, OAT3, OCT1 or OCT2.
- Effect of Acid Reducing Agents on Sonidegib
No clinically meaningful effect on Sonidegib exposure was observed when Sonidegib at dose of 200 mg was coadministered with esomeprazole, a proton pump inhibitor.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity studies with Sonidegib have not been performed.
Sonidegib was not mutagenic in the in vitro bacterial reverse mutation (Ames) assay and was not clastogenic or aneugenic in the in vitro human chromosome aberration assay or in vivo rat bone marrow micronucleus assay.
Sonidegib resulted in a lack of fertility when administered to female rats at ≥20 mg/kg/day (approximately 1.3 times the recommended human dose based on body surface area (BSA). A reduction of the number of pregnant females, an increase in the number of early resorptions, and a decrease in the number of viable fetuses was also noted at 2 mg/kg/day (approximately 0.12 times the recommended human dose based on BSA). In addition, in a 6 month repeat-dose toxicology study in rats, effects on female reproductive organs included atrophy of the uterus and ovaries at doses of 10 mg/kg (approximately ≥2 times the exposure in humans at the recommended dose of 200 mg based on AUC). No adverse effects on fertility were noted when male rats were administered Sonidegib at doses up to 20 mg/kg/day, the highest dose tested.
Animal Toxicology and/or Pharmacology
Body tremors along with significant increases in creatine kinase were observed in rats administered oral Sonidegib for 13 weeks or longer at ≥10 mg/kg/day (approximately ≥2 times the recommended human dose based on AUC).
Clinical Studies
The safety and effectiveness of Sonidegib were evaluated in a single, multicenter, double-blind, multiple cohort clinical trial conducted in patients with locally advanced basal cell carcinoma (laBCC) (n=194) or metastatic basal cell carcinoma (mBCC) (n=36) (Study 1). Patients were randomized (2:1) to receive either Sonidegib 800 mg or 200 mg orally, once daily, until disease progression or intolerable toxicity. Randomization was stratified by stage of disease (locally advanced or metastatic), laBCC disease histology (aggressive vs. non-aggressive), and geographic region. Patients with laBCC were required to have lesions for which radiotherapy was contraindicated or inappropriate (e.g., Gorlin syndrome or limitations because of location of tumor), that had recurred after radiotherapy, that were unresectable or for which surgical resection would result in substantial deformity, or that had recurred after prior surgical resection.
The major efficacy outcome measure of the trial was objective response rate (ORR) as determined by blinded central review according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) for patients with laBCC or RECIST version 1.1 for patients with mBCC. Duration of response (DoR), determined by blinded central review, was a key secondary outcome measure.
For patients with laBCC, the evaluation of tumor response was based on a composite assessment that integrated tumor measurements obtained by radiographic assessments of target lesions (per RECIST 1.1), digital clinical photography, and histopathology assessments (via punch biopsies). All modalities used must have demonstrated absence of tumor to achieve a composite assessment of complete response (CR). Response by digital clinical photography was evaluated by World Health Organization (WHO) adapted criteria [partial response (PR): ≥50% decrease in the sum of the product of perpendicular diameters (SPD) of the lesions, CR: disappearance of all lesions, progressive disease (PD): ≥25% increase in the SPD of the lesions]. Multiple punch biopsies of target lesions were performed to confirm a CR or when a response assessment was confounded by presence of lesion ulceration, cyst, and or scarring/fibrosis.
A total of 66 patients randomized to Sonidegib 200 mg daily had laBCC. Three of these patients had a diagnosis of Gorlin Syndrome. The demographic characteristics of the 66 patients with laBCC were: median age of 67 years (range: 25 to 92 years; 58% were ≥65 years); 58% male, 89% white, and ECOG performance status of 0 (67%). Seventy-six percent of patients had prior therapy for treatment of BCC; this included surgery (73%), radiotherapy (18%), and topical/photodynamic therapies (21%). Approximately half of these patients (56%) had aggressive histology.
Patients with laBCC randomized to receive Sonidegib 200 mg daily were followed for at least 12 months unless discontinued earlier. The ORR was 58% (95% confidence interval: 45, 70), consisting of 3 (5%) complete responses and 35 (53%) partial responses. A pre-specified sensitivity analysis using an alternative definition for complete response, defined as at least a PR according to MRI and/or photography and no evidence of tumor on biopsy of the residual lesion, yielded a CR rate of 20%. Among the 38 patients with an objective response, 7 (18%) patients experienced subsequent disease progression with 4 of these 7 patients having maintained a response of 6 months or longer. The remaining 31 patients (82%) have ongoing responses ranging from to 1.9+ to 18.6+ months and the median duration of response has not been reached.
A total of 128 patients randomized to Sonidegib 800 mg daily had laBCC. Twelve of these patients had a diagnosis of Gorlin Syndrome. There was no evidence of better antitumor activity (ORR) among patients with laBCC randomized to receive Sonidegib 800 mg daily and followed for at least 12 months unless discontinued earlier.
How Supplied
Each Sonidegib capsule has an opaque pink color with ‘SONIDEGIB 200MG’ printed on the capsule body and ‘NVR’ printed on the cap in black ink. Sonidegib capsules are supplied as follows:
Bottle of 30 capsules (NDC 0078-0645-15)
Storage
Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling.
Embryo-Fetal Toxicity
- Advise female patients of the potential risk to a fetus.
- 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, even those with prior vasectomy, to use condoms, to avoid potential drug exposure in both pregnant partners and female partners of reproductive potential during treatment with Sonidegib and for at least 8 months after the last dose.
- Advise female patients and female partners of male patients to contact their healthcare provider with a known or suspected pregnancy.
- Advise females who may have been exposed to Sonidegib during pregnancy, either directly or through seminal fluid, to contact the Novartis Pharmaceuticals Corporation at 1-888-669-6682.
Advise patients not to donate blood or blood products while taking Sonidegib and for 20 months after stopping treatment.
Musculoskeletal Adverse Reactions
Advise patients to contact their healthcare provider immediately for new or worsening signs or symptoms of muscle toxicity, dark urine, decreased urine output, or the inability to urinate.
Administration Instructions
Advise patients to take Sonidegib on an empty stomach, at least 1 hour before or 2 hours after a meal.
Lactation
Advise women not to breastfeed during treatment with Sonidegib and for up to 20 months after the last dose.
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
ODOMZO®
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.
- ↑ "Odomzo (sonidegib) Capsules, for Oral Use. Full Prescribing Information" (PDF). Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936. Retrieved 2 October 2016.