Do not administer to patients with allergy to any component of the formulation. Patients with mild-to-moderate allergy (e.g. rash) should be evaluated for risk vs benefit prior to continuing therapy. Not studied in hepatic impairment (hepatic damage associated with impaired phenylalanine metabolism). Low levels of phenylalanine associated with catabolism and protein breakdown. Not studied in renal impairment (use with caution). Folic acid antagonists may decrease BH~4~ levels via dihydropteridine reductase enzyme inhibition. In sapropterin clinical studies for a non-PKU use, seizure, over-stimulation, and irritability reported in patients also receiving levodopa (use caution). Use with caution with medications that affect nitric oxide-mediated vasorelaxation, including PDE-5 inhibitors (risk of hypotension). Response to sapropterin treatment established through treatment (cannot be predetermined by lab testing). Patients whose phenylalanine levels do not decrease after treatment at 20 mg/kg/day for 1 month are considered nonresponders.