Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Sun Pharmaceutical Industries Europe B.V., Polarisavenue 87, 2132JH Hoofddorp, Netherlands
Odomzo is indicated for the treatment of adult patients with locally advanced basal cell carcinoma (BCC) who are not amenable to curative surgery or radiation therapy.
Odomzo should only be prescribed by or under the supervision of a specialist physician experienced in the management of the approved indication.
The recommended dose is 200 mg sonidegib taken orally once daily at least two hours after a meal and at least one hour before the following meal, at the same time each day.
Treatment should be continued as long as clinical benefit is observed or until unacceptable toxicity develops.
Temporary dose interruption and/or dose reduction of Odomzo therapy may be required for CK elevations and muscle-related adverse events.
Table 1 summarises recommendations for dose interruption and/or dose reduction of Odomzo therapy in the management of symptomatic CK elevations and muscle-related adverse events (such as myalgia, myopathy, and/or spasm).
Table 1. Recommended dose modifications and management for symptomatic CK elevations and muscle-related adverse events:
| Severity of CK elevation (CK) | Dose modifications* and management recommendations |
|---|---|
| Grade 1 [CK elevation >ULN – 2.5 x ULN] | Continue treatment at the same dose and monitor CK 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. | |
| Grade 2 without renal impairment (serum Cr ≤ ULN) [CK elevation >2.5 x ULN – 5 x ULN] | Interrupt treatment and monitor CK 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 CK 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. Re-introduce sonidegib at 200 mg every other day and follow the same monitoring recommendations. If symptoms persist despite alternate-day dosing, consider discontinuing treatment. | |
| Grade 3 or 4 without renal impairment (serum Cr ≤ ULN) [Grade 3 (CK elevation >5 x ULN – 10 x ULN)] [Grade 4 (CK elevation >10 x ULN)] | Interrupt treatment and monitor CK 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 CK resolves to baseline, consider resuming treatment at 200 mg every other day. CK levels should be measured weekly for 2 months after re-administration of sonidegib and monthly thereafter. | |
| Grade 2, 3 or 4 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 CK and serum creatinine levels weekly until resolution to baseline. Monitor muscle symptoms for changes until resolution to baseline | |
| If CK and serum creatinine levels return to baseline consider resuming treatment at 200 mg every other day and measure CK levels weekly for 2 months and monthly thereafter; otherwise discontinue treatment permanently |
* The above recommendations for dose modifications are based on the Common Terminology Criteria for Adverse Events (CTCAE) v4.03, developed by the National Cancer Institute (USA). The CTCAE is a standardised classification of side effects used in assessing medicinal products for cancer therapy.
Cr: creatinine; ULN: upper limit of normal
Management of severe or intolerable adverse reactions may require temporary dose interruption (with or without a subsequent dose reduction) or discontinuation.
When dose interruption is required, consider resuming Odomzo at the same dose after resolution of the adverse reaction to ≤ grade 1.
If dose reduction is required, then the dose should be reduced to 200 mg every other day. If the same adverse drug reaction occurs following the switch to alternate daily dosing and does not improve, consider discontinuing treatment with Odomzo.
Due to the long half-life of sonidegib the full effect of a dose interruption or dose adjustment of sonidegib on several adverse events is expected to generally occur after a few weeks (see section 5.2).
In clinical trials, treatment with Odomzo was continued until disease progression or until unacceptable toxicity. Treatment interruptions of up to 3 weeks were allowed based on individual tolerability.
Benefit of continued treatment should be regularly assessed, with the optimal duration of therapy varying for each individual patient.
Sonidegib has not been studied in a dedicated pharmacokinetic study in patients with renal impairment. Based on the available data, sonidegib 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 apparent clearance (CL/F) of sonidegib, suggesting that dose adjustment is not necessary in patients with renal impairment (see section 5.2). No efficacy and safety data are available in patients with severe renal impairment.
No dose adjustment is necessary in patients with hepatic impairment (see section 5.2).
Safety and efficacy data in patients aged 65 years and older do not suggest that a dosage adjustment is required in these patients (see section 5.2).
The safety and efficacy of Odomzo in children and adolescents aged below 18 years with basal cell carcinoma have not been established. No data are available.
Odomzo is for oral use. The capsules must be swallowed whole. They must not be chewed or crushed. The capsules must not be opened due to risk of teratogenicity (see section 5.3).
Odomzo must be taken at least two hours after a meal and at least one hour before the following meal to prevent increased risk of adverse events due to higher exposure of sonidegib when taken with a meal (see section 5.2). If vomiting occurs during the course of the treatment, then no re-dosing of the patient is allowed before the next scheduled dose.
If a dose is missed, it should be taken as soon as this is realised, unless more than six hours have passed since it was scheduled to be taken; in this case, the patient should wait and take the next scheduled dose.
In dose escalation studies, Odomzo was administered at doses up to 3000 mg orally once daily. Patients should be monitored closely for adverse events and given appropriate supportive measures in all cases of overdose.
5 years.
Do not store above 30°C.
Store in the original package in order to protect from moisture.
10 × 1 hard capsule in PCTFE/PVC/Alu perforated unit-dose blisters.
Each pack contains either 10 or 30 hard capsules.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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