Regulatory Decision Summary for NITISINONE TABLETS

This submission was based on demonstration of bioequivalence of Nitisinone Tablets to foreign authorized Orfadin capsules, allowing bridging between the Nitisinone Tablet formulation and the product used in studies reported in the literature. This provided evidence of the safety and efficacy of Nitisinone Tablets, which was combined with literature studies and post market safety data for Orfadin.

Uncertainties included the effects of advanced age, chronic treatment, renal impairment, hepatic impairment, race, and genetic polymorphisms on the pharmacokinetics of nitisinone, and safety when used during pregnancy and lactation.

A Risk Management Plan was reviewed by the Marketed Health Products Directorate. Risk minimization measures include ongoing post-marketing surveillance and adequate labelling of all identified safety issues, including the lack of data in some subpopulations, the potential risk from use during pregnancy and lactation, and the potential risk to the fetus and mother from discontinuing nitisinone during pregnancy.

The evidence of the benefit provided by nitisinone for the treatment of hereditary tyrosinemia type 1, a serious and often fatal disorder, outweighs the associated risks.