Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use
Monitoring of plasma tyrosine levels
It is recommended that a slit-lamp examination of the eyes is performed before initiation of Orfadin hard capsules treatment and thereafter regularly, at least once a year. A patient displaying visual disorders during treatment with Orfadin hard capsules should without delay be examined by an ophthalmologist. It should be established that the patient is adhering to his dietary regimen and the plasma tyrosine concentration should be measured. A more restricted tyrosine and phenylalanine diet should be implemented in case the plasma tyrosine level is above 500 micromol/l. It is not recommended to lower the plasma tyrosine concentration by reduction or discontinuation of Orfadin hard capsules, since the metabolic defect may result in deterioration of the patient’s clinical condition.

Liver monitoring
The liver function should be monitored regularly by liver function tests and liver imaging. It is recommended also to monitor serum alpha-fetoprotein concentration. Increase in serum alpha-fetoprotein concentration may be a sign of inadequate treatment. Patients with increasing alpha-fetoprotein or signs of nodules in the liver should always be evaluated for hepatic malignancy.

Platelet and white blood cell (WBC) monitoring
It is recommended that platelet and white cell counts are monitored regularly, as a few cases of reversible trombocytopenia and leucopenia were observed during clinical evaluation.

Monitoring visits should be performed every 6 months; shorter intervals between visits are recommended in case of adverse events.

Concomitant use with other medicinal products
Orfadin hard capsules is a moderate CYP2C9 inhibitor. Orfadin hard capsules treatment may therefore result in increased plasma concentrations of co-administered medicinal products metabolized primarily via CYP2C9. Orfadin hard capsules treated patients who are concomitantly treated with medicinal products with a narrow therapeutic window metabolized through CYP2C9, such as warfarin and phenytoin, should be carefully monitored. Dose- adjustment of these co-administered medicinal products may be needed (see section 4.5).

Effects on Driving

4.7 Effects on ability to drive and use machines
Orfadin hard capsules has minor influence on the ability to drive and use machines. Adverse reactions involving the eyes (see section 4.8) can affect the vision. If the vision is affected the patient should not drive or use machines until the event has subsided.