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ODOMZO is a brand name for Sonidegib, supplied as a capsule. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: ODOMZO (sonidegib) is indicated for: The treatment of adult patients with histologically confirmed locally advanced basal cell carcinoma (laBCC) that is not amenable to radiation therapy or curative surgery. The indication is granted market authorization based on objective response rate (ORR) demonstrated in a…
Verbatim from this product's HC label. Tap a section to expand.
1 Dosing Considerations Verify the pregnancy status of females of reproductive potential prior to initiating ODOMZO (see Section 7 Warnings and Precautions - Reproduction). Obtain baseline serum creatine phosphokinase (CPK) levels and renal function tests prior to initiating ODOMZO in all patients (see Section 7 Warnings and Precautions - Musculoskeletal).
2 Recommended Dose and Dosage Adjustment Recommended Dose 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. Patients should be treated until disease progression or unacceptable toxicity.
ODOMZO® Product Monograph Page 6 of 35 Dosage Adjustment Dose modifications for creatine phosphokinase (CPK) elevations and muscle-related adverse events Temporary dose interruption of ODOMZO therapy may be required for CPK elevations and muscle-related adverse events.
Table 1 summarizes recommendations for dose interruption of ODOMZO therapy in the management of CPK elevations and muscle-related adverse events (such as myalgia, myopathy, and/or spasm). 5 x ULN] Continue treatment at the same dose and monitor CPK levels weekly until resolution to baseline level and then monthly thereafter.
Monitor muscle symptoms for changes until resolution to baseline. Check renal function (serum creatinine) regularly and ensure that patient is adequately hydrated. 5 x ULN - 5 x ULN] Interrupt treatment and monitor CPK levels weekly until resolution to baseline level.
Monitor muscle symptoms for changes until resolution to baseline. Upon resolution, resume treatment at the same dose level and measure CPK monthly thereafter. Check renal function (serum creatinine) regularly and ensure that patient is adequately hydrated.
If symptoms re-occur, interrupt treatment until resolution to baseline. If symptoms persist despite dose interruption, consider discontinuing treatment. Grade 2 with renal impairment (serum Cr > ULN) If renal function is impaired, interrupt treatment and ensure that the patient is adequately hydrated and evaluate other secondary causes of renal impairment.
Monitor CPK and serum creatinine levels weekly until resolution to baseline. Monitor muscle symptoms for changes until resolution to baseline. If CPK and serum creatinine levels return to baseline, treatment can be resumed. Measure CPK levels weekly for 2 months and monthly thereafter.
1 Adverse Reaction Overview The safety of ODOMZO (sonidegib) was evaluated in 229 adult patients with locally advanced BCC (laBCC) or metastatic BCC (mBCC) who were randomized to treatment with ODOMZO 200 mg/day (n=79) or ODOMZO 800 mg/day (n=150).
The data described below reflect the cohort of ODOMZO 200 mg daily in 79 patients with laBCC (n=66) or mBCC (n=13) enrolled in the BOLT trial. Overall, 98% of patients treated with ODOMZO 200 mg reported at least one adverse event. ODOMZO® Product Monograph Page 15 of 35 The most common adverse reactions occurring in ≥10% of patients treated with ODOMZO 200 mg were muscle spasms, alopecia, fatigue, dysgeusia, nausea, musculoskeletal pain, diarrhea, weight decreased, decreased appetite, myalgia, abdominal pain, headache, pain, vomiting and pruritus (Table 3).
Overall, 43% of patients treated with ODOMZO 200 mg reported Grade 3 or 4 adverse events. The most common Grade 3 adverse reactions occurring in ≥2% of patients treated with ODOMZO 200 mg were fatigue, weight decreased, muscle spasms, and hypotension (Table 3).
One death occurred in a laBCC patient while on treatment with sonidegib 200 mg which was determined by the investigator to not be related to study drug. Overall, 20% of patients treated with ODOMZO 200 mg reported serious adverse events (SAEs).
, <2%) except for pneumonia which occurred in two patients (3%). Four patients (5%) in the 200 mg experienced SAEs that were considered related by the investigator (blood CPK increased [2 patients], rhabdomyolysis, dyspnea, and hypoglycemia).
Overall, 43% of patients treated with ODOMZO 200 mg required a dose interruption or a dose adjustment due to an adverse event. The most common (≥5%) adverse events leading to a dose interruption/adjustment were nausea, vomiting, diarrhea, blood CPK increased and lipase increased.
Please see the Serious Warnings and Precautions Box at the beginning of Part I:
Health Professional Information. Carcinogenesis and Mutagenesis Patients with advanced BCC have an increased risk of developing cutaneous squamous cell carcinoma (cuSCC). Cases of cuSCC have been reported in advanced BCC patients treated with ODOMZO.
It has not been determined whether cuSCC is related to ODOMZO treatment. Therefore, all patients should be monitored routinely while taking ODOMZO and cuSCC should be treated according to the standard of care. , if muscle symptoms are reported).
5 times ULN until resolution of clinical signs and symptoms (see Section 7 Warnings and Precautions - Musculoskeletal). For pregnancy test requirements for Females of Childbearing Potential (FCBP), see Section 7 Warnings and Precautions - Sexual Health, Reproduction.
Musculoskeletal Skeletal muscle toxicity Musculoskeletal adverse reactions, which may be accompanied by serum creatine phosphokinase (CPK) elevations, occur with ODOMZO and other drugs which inhibit the hedgehog pathway. Muscle spasms, myalgia, and cases of CPK elevations were very commonly observed in the BOLT trial.
The majority of patients treated with ODOMZO 200 mg daily who had Grade 2 or higher CPK elevations developed muscle symptoms prior to the CPK elevations. For most patients, muscle symptoms and CPK elevations resolved with appropriate management.
In the pivotal trial (BOLT), at the 42-month analysis, musculoskeletal adverse reactions occurred in 76% (60/79) of patients treated with ODOMZO 200 mg daily with 5% (4/79) reported as Grade 3 or 4. The most frequent manifestations of musculoskeletal adverse reactions reported as an adverse event were muscle spasms (56%), musculoskeletal pain (39%), and myalgia (19%).
Overall, 6% of patients treated with ODOMZO 200 mg were discontinued from the study due to musculoskeletal events. Increased serum CPK laboratory values occurred in 61% (48/79) of patients with 8% (6/79) of patients having Grade 3 or 4 serum CPK elevations (see Section 8 Adverse Reactions).
1 Pregnant Women). 2 Breast- feeding). Female patients of childbearing potential who do not comply with the ODOMZO Pregnancy Prevention Program (see Section 7 Warnings and Precautions). ODOMZO® Product Monograph Page 5 of 35 Serious Warnings and Precautions ODOMZO (sonidegib) should be initiated and monitored only under the supervision of a physician qualified in the use of cancer therapies and with a full understanding of the risks of ODOMZO therapy and monitoring requirements.
1 Pregnant Women). ODOMZO has not been studied in patients with severe renal impairment (see Section 4 Dosage and Administration). ODOMZO is available only through a controlled distribution program called the ODOMZO Pregnancy Prevention Program.
3 Pediatrics, and Section 16 Non-Clinical Toxicology). Male patients who do not comply with the contraceptive measures of the ODOMZO Pregnancy Prevention Program (see Section 7 Warnings and Precautions). 3 Pediatrics). Patients who are hypersensitive to sonidegib or to any ingredient in the formulation (see Section 6 Dosage Forms, Strengths, Composition and Packaging for a complete listing).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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If symptoms persist despite dose interruption, discontinue treatment permanently. Grade 3 or 4 without renal impairment (serum Cr ≤ ULN) [Grade 3 (CPK elevation >5 x ULN - 10 x ULN)] [Grade 4 (CPK elevation >10 x ULN)] Interrupt treatment and monitor CPK levels weekly until resolution to baseline.
Monitor muscle symptoms for changes until resolution to baseline. Check renal function (serum creatinine) regularly and ensure that patient is adequately hydrated. If renal function is not impaired and CPK resolves to baseline, treatment can be resumed.
CPK levels should be measured weekly for 2 months after re-administration of ODOMZO and monthly thereafter. If symptoms persist despite dose interruption, consider discontinuing treatment. ODOMZO® Product Monograph Page 7 of 35 Severity of CPK elevation Dose modifications* and management recommendations Grade 3 or 4 with renal impairment (serum Cr > ULN) If renal function is impaired, discontinue treatment and ensure that the patient is adequately hydrated and evaluate other secondary causes of renal impairment.
Monitor CPK and serum creatinine levels weekly until resolution to baseline. Monitor muscle symptoms for changes until resolution to baseline. 03. CPK: creatine phosphokinase; Cr: creatinine; ULN: upper limit of normal. Other dose interruptions Management of severe or intolerable adverse reactions may require temporary dose interruption or treatment discontinuation.
When dose interruption is required, consider resuming ODOMZO at the same dose after resolution of the adverse reaction to ≤ Grade 1. 3 Pharmacokinetics). Special Populations Patients with hepatic impairment No initial dose adjustment is necessary in patients with hepatic impairment.
Based on a single dose PK study, sonidegib half-life was prolonged in subjects with moderate or severe hepatic impairment when compared to subjects with normal hepatic function (see Section 10 Action and Clinical Pharmacology – Pharmacokinetics - Special Populations and Conditions).
Therefore, higher drug accumulation and exposures at steady state of sonidegib following repeated doses are expected. Patients with baseline hepatic impairment should be closely monitored for sonidegib toxicity and hepatic function.
ODOMZO should be permanently discontinued if liver function deteriorates. No efficacy and safety data are available in patients with severe hepatic impairment. Patients with renal impairment ODOMZO has not been studied in a dedicated pharmacokinetic study in patients with renal impairment.
Based on the available data, ODOMZO elimination via the kidney is negligible. A population pharmacokinetic analysis found that mild or moderate renal impairment did not have a significant effect on the exposure of ODOMZO, suggesting that dose adjustment is not necessary in those patients.
No clinical data are available in patients with severe renal impairment. Geriatric (≥65 years) Safety and efficacy data in patients aged 65 years and older […]
Overall, 30% of patients in the 200 mg group with laBCC or mBCC discontinued due to an adverse event. The most common (≥2%) adverse events leading to discontinuation were muscle spasms, asthenia, dysgeusia, nausea, fatigue, decreased weight and decreased appetite.
2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. Patients were followed for at least 42 months unless discontinued earlier. 2 months). The study population characteristics for patients in the sonidegib 200 mg group were: median age of 67 years (range 25 to 92; 60% were ≥65 years), 61% male, and 90% White.
0, except grouped terms where indicated; the frequency of an adverse reaction is derived from all treatment-emergent adverse events. No Grade 4 adverse reactions were reported. 03. b Abdominal pain includes abdominal pain and abdominal pain upper.
c Fatigue includes asthenia, fatigue, lethargy, and malaise. d Pain includes ear pain, eye pain, facial pain, gingival pain, oral pain, oropharyngeal pain, pain, and pain of skin. e Muscle spasms includes muscle spasms and muscle tightness.
f Musculoskeletal pain includes arthralgia, back pain, musculoskeletal chest pain, musculoskeletal pain, pain in extremity, and pain in jaw. g Myopathy includes muscular weakness. h Dysgeusia includes ageusia. i Alopecia includes alopecia and madarosis.
j Pruritus includes pruritus, pruritus generalized, and eye pruritus. k Rash includes dermatitis acneiform, dry skin, rash, and rash pruritic. Amenorrhea Amenorrhea lasting for at least 18 months occurred in 2 of 14 pre-menopausal women treated with ODOMZO 200 mg or 800 mg once daily.
4 Abnormal Laboratory Findings: Hematologic, Clinical Chemistry and Other Quantitative Data Changes in laboratory […]
Musculoskeletal pain and myalgia usually preceded serum CPK elevation. Among patients with Grade 2 or higher CPK elevations, the median time to onset was 13 weeks (range: 2 to 39 weeks) and the median time to resolution (to ≤ Grade 1) was 12 days (95% confidence interval [CI]: 8 to 14 days).
Rhabdomyolysis was reported in 1 patient (1%) in the 200 mg cohort and 5 patients (3%) in the 800 mg cohort. At least 5 cases of rhabdomyolysis were reported in patients treated with above the clinically recommended dose in 2 Phase I studies.
Some cases were reported as serious, leading to treatment discontinuation. 5-fold increase in serum creatinine from the pre-treatment or baseline level, or >10x upper limit of normal if no baseline level reported. No reported cases in the BOLT study were confirmed based on this definition.
One reported case in a patient treated with ODOMZO 800 mg in a Phase I study was confirmed. , if muscle symptoms are reported). 5 times ULN until resolution of clinical signs and symptoms. 2 Recommended Dose). Advise patients starting therapy with ODOMZO 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 ODOMZO. Sexual Health Reproduction Embryo-fetal death or severe birth defects ODOMZO 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 (see Section 16 Non-Clinical Toxicology). Because of the risk of embryo-fetal toxicity, female patients of childbearing potential must not be given ODOMZO until pregnancy is excluded.
ODOMZO is only available through a controlled distribution program called the ODOMZO Pregnancy Prevention Program (OPPP). The OPPP is designed to assist healthcare professionals and patients to avoid embryo-fetal exposure to ODOMZO.
Female of Childbearing Potential (FCBP) Definition of FCBP in the OPPP A FCBP is defined as a female who meets at least one of the following criteria: Is menstruating, Is amenorrhoeic and has not entered clinically confirmed menopause, Is pre-menopausal, and Does not qualify as a Female of Non-Childbearing Potential (FNCBP).
, in natural menopause for ≥12 months), or Has had a hysterectomy and/or a bilateral oophorectomy, or Has premature ovarian failure confirmed by a gynecologist, or Has one of the following: o An XY genotype, ODOMZO® Product Monograph Page 11 of 35 o Turner’s syndrome, or o Uterine agenesis For FCBP, ODOMZO is contraindicated unless ALL of the following conditions […]