Active Ingredient: Sonidegib
Sonidegib 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.
For this indication, competent medicine agencies globally authorize below treatments:
Oral
200 - 200 mg
From 200 To 200 mg once every day
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 sonidegib therapy may be required for CK elevations and muscle-related adverse events.
The table below summarises recommendations for dose interruption and/or dose reduction of sonidegib therapy in the management of symptomatic CK elevations and muscle-related adverse events (such as myalgia, myopathy, and/or spasm).
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 sonidegib 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 sonidegib.
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.
In clinical trials, treatment with sonidegib 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.
It should be taken at least two hours after a meal and at least one hour before the following meal, at the same time each day.
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