Special Warning : אזהרת שימוש

4.4     Special warnings and precautions for use
Patients who do not have a nonsense mutation
Patients must have a nonsense mutation in the dystrophin gene as part of their underlying disease state, as determined by genetic testing. Patients who do not have a nonsense mutation should not receive ataluren.

Renal impairment
An increase in ataluren exposure and in ataluren metabolite has been reported in patients with severe renal impairment (eGFR <30 ml/min). The toxicity of the metabolite is unknown.
Higher ataluren exposure was associated with potential decrease in efficacy. Therefore, patients with severe renal impairment or end-stage renal disease should be treated with ataluren only if the anticipated clinical benefit outweighs the potential risk, and should be closely monitored for possible metabolite toxicity and decrease in efficacy. A lower ataluren dose should be considered.

Treatment should not be initiated in previously untreated patients with eGFR <30 ml/min (see sections 4.2 and 5.2).

Changes in lipid profile
Because changes in lipid profile (increased triglycerides and cholesterol) were reported for some patients in clinical trials, it is recommended that total cholesterol, LDL, HDL, and triglycerides be monitored on an annual basis in nonsense mutation Duchenne muscular dystrophy (nmDMD) patients receiving ataluren, or more frequently as needed based on the patient’s clinical status.

Hypertension with use of concomitant systemic corticosteroids
Because hypertension with use of concomitant systemic corticosteroids was reported for some patients in clinical trials, it is recommended that resting systolic and diastolic blood pressure be monitored every 6 months in nmDMD patients receiving ataluren concomitantly with corticosteroids, or more frequently as needed based on the patient’s clinical status.

Renal function monitoring
Because small increases in mean serum creatinine, blood urea nitrogen (BUN), and cystatin C were observed in the controlled studies of nmDMD, it is recommended that serum creatinine, BUN, and cystatin C be monitored every 6 to 12 months in nmDMD patients receiving ataluren, or more frequently as needed based on the patient’s clinical status.

Potential interactions with other medicinal products
Caution should be exercised when ataluren is co-administered with medicinal products that are inducers of UGT1A9, or substrates of OAT1or OAT3 (see section 4.5).

Aminoglycosides
Aminoglycosides have been shown to reduce the readthrough activity of ataluren in vitro.
In addition, ataluren was found to increase nephrotoxicity of intravenous aminoglycosides.
The co-administration of these medicinal products with ataluren should be avoided (see section 4.3).
Since the mechanism by which ataluren increases nephrotoxicity of intravenous aminoglycosides is not known, concomitant use of other nephrotoxic medicinal products with ataluren is not recommended.
If this is unavoidable (e.g. vancomycin to treat MRSA) careful monitoring of renal function is advised (see section 4.5).

Effects on Driving

4.7     Effects on ability to drive and use machines

The effect of ataluren on driving, on cycling, or on using machines has not been tested.
Patients who experience dizziness should use caution when driving, cycling or using machines.