Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
By its mode of action, nitisinone increases tyrosine levels in all nitisinone treated patients.
Eye-related adverse reactions, such as conjunctivitis, corneal opacity, keratitis, photophobia, and eye pain, related to elevated tyrosine levels are therefore common. Other common adverse reactions include thrombocytopenia, leucopenia, and granulocytopenia. Exfoliative dermatitis may occur uncommonly.

Tabulated list of adverse reactions
The adverse reactions listed below by MedDRA system organ class and absolute frequency, are based on data from a clinical trial and post-marketing use. Frequency is defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

MedDRA system organ              Frequency                        Adverse reaction class
Blood and lymphatic system       Common                           Thrombocytopenia, disorders                                                         leucopenia, granulocytopenia
Uncommon                         Leukocytosis
Eye disorders                    Common                           Conjunctivitis, corneal opacity, keratitis,
photophobia, eye pain
Uncommon                         Blepharitis
Skin and subcutaneous            Uncommon                         Exfoliative dermatitis, tissue disorders                                                  erythematous rash, pruritus
Investigations                   Very common                      Elevated tyrosine levels 
Description of selected adverse reactions
Orfadin hard capsules treatment leads to elevated tyrosine levels. Elevated levels of tyrosine have been associated with eye-related adverse reactions, such as e.g. corneal opacities and hyperkeratotic lesions. Restriction of tyrosine and phenylalanine in the diet should limit the toxicity associated with this type of tyrosinemia by lowering tyrosine levels (see section 4.4).
In clinical studies, granulocytopenia was only uncommonly severe (<0.5x109/L) and not associated with infections. Adverse reactions affecting the MedDRA system organ class ‘Blood and lymphatic system disorders’ subsided during continued Orfadin hard capsules treatment.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il.