Sepiapterin

SEPHIENCE is indicated for the treatment of hyperphenylalaninemia (HPA) in adult and pediatric patients 1 month of age and older with sepiapterin-responsive phenylketonuria (PKU). SEPHIENCE is to be used in conjunction with a phenylalanine (Phe)-restricted diet. SEPHIENCE is a phenylalanine hydroxylase (PAH) activator indicated for the treatment of hyperphenylalaninemia (HPA) in adult and pediatric patients 1 month of age and older with sepiapterin-responsive phenylketonuria (PKU).

SEPHIENCE is a precursor of the enzymatic co-factor tetrahydrobiopterin (BH 4 ) which activates PAH.

Patients treated with SEPHIENCE should be on a dietary protein and a Phe-restricted diet. Administer SEPHIENCE orally once daily with food. The recommended starting dosage of SEPHIENCE is: Age SEPHIENCE (mg/kg) per day Less than 6 months 7.5 mg/kg 6 months to less than 1 year 15 mg/kg 1 year to less than 2 years 30 mg/kg 2 years and older 60 mg/kg Important Administration Information: prepare SEPHIENCE calculated daily doses of < 1,000 mg as a liquid mixture (25 mg/mL), and administer exact prescribed dose volume (mL). See full prescribing information for complete preparation and administration instructions.

None. None.

Increased Bleeding: SEPHIENCE may increase the risk of bleeding. Consider treatment interruption in patients with active bleeding. Hypophenylalaninemia: Some pediatric PKU patients experienced hypophenylalaninemia, monitor patients blood Phe levels during treatment. Interaction with Levodopa: Seizures, over-stimulation or irritability may occur, monitor patients for a change in neurologic status.

The following clinically significant adverse reactions are described elsewhere in the labeling: Increased Bleeding. Hypophenylalaninemia. Most common adverse reactions with SEPHIENCE (≥2% and greater than placebo) were diarrhea, headache, abdominal pain, hypophenylalaninemia, feces discoloration, and oropharyngeal pain.

Dihydrofolate Reductase (DHFR) Inhibitors: Avoid concomitant use (e.g., trimethoprim, methotrexate, trimetrexate, pemetrexed, pralatrexate, raltitrexed, or piritrexim). Sepiapterin Reductase (SR) Inhibitors: Avoid concomitant use (e.g. sulfasalazine or sulfamethoxazole). Interaction with Levodopa: Monitor patients for a change in neurologic status. Drugs Affecting Nitric Oxide-Mediated Vasorelaxation: Potential for vasorelaxation, monitor blood pressure (e.g., PDE-5 inhibitors).

Store SEPHIENCE at room temperature between 20°C to 25°C (68°F to 77°F), excursion permitted between 15°C to 30°C (59°F to 86°F). Store SEPHIENCE liquid or soft food mixture either refrigerated or at controlled room temperature.