Sepiapterin

Brand Names: Sephience

Drug Class: General Prescription

Overview

11 DESCRIPTION SEPHIENCE (sepiapterin) contains the drug substance sepiapterin, a PAH activator. Sepiapterin is a yellow to orange powder. Sepiapterin is slightly soluble in water with the solubility at 1.4 mg/mL. The chemical name of sepiapterin is (S) -2-amino-6-(2-hydroxypropanoyl)-7,8-dihydropteridin-4 (3H) -one. The molecular formula is C 9 H 11 N 5 O 3 and the molecular weight is 237.

Mechanism of Action

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action SEPHIENCE is a precursor of the enzymatic co-factor tetrahydrobiopterin (BH 4 ) which activates PAH. 12.2 Pharmacodynamics Cardiac Electrophysiology At the recommended SEPHIENCE dose of 60 mg/kg orally once daily, clinically significant QTc interval prolongation was not observed. 12.3 Pharmacokinetics Following oral administration, sepiapterin reached the maximum concentration in plasma at 2 hours post-treatment and converted to pharmacologically active metabolite BH 4 with the exposures of sepiapterin generally less than 2% of those of BH 4 ( Table 5 ). There was no accumulation for BH 4 following repeated once daily dose up to 60 mg/kg administered in adult healthy volunteers.

Indications

  • 1 INDICATIONS AND USAGE 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 to be used in conjunction with a phenylalanine (Phe)- restricted diet. ( 1 )

Common Doses

  • 7.5 mg
  • 15 mg
  • 30 mg
  • 60 mg

Dosage

2 DOSAGE AND ADMINISTRATION Patients treated with SEPHIENCE should be on a dietary protein and a Phe-restricted diet. ( 2.1 ) Administer SEPHIENCE orally once daily with food. ( 2.2 ) The recommended starting dosage of SEPHIENCE is: ( 2.2 ) 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

Contraindications

  • 4 CONTRAINDICATIONS None. None. ( 4 )

Side Effects

  • 6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Increased Bleeding [see Warnings and Precautions ( 5.1 )] . Hypophenylalaninemia [see Warnings and Precautions ( 5.2 )] . Most common adverse reactions with SEPHIENCE (≥2% and greater than placebo) were diarrhea, headache, abdominal pain, hypophenylalaninemia, feces discoloration, and oropharyngeal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact PTC Therapeutics, Inc. at 1-866-562-4620 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.

Interactions

  • 7 DRUG INTERACTIONS Dihydrofolate Reductase (DHFR) Inhibitors : Avoid concomitant use (e.g., trimethoprim, methotrexate, trimetrexate, pemetrexed, pralatrexate, raltitrexed, or piritrexim). ( 7.1 ) Sepiapterin Reductase (SR) Inhibitors : Avoid concomitant use (e.g. sulfasalazine or sulfamethoxazole). ( 7.1 ) Interaction with Levodopa : Monitor patients for a change in neurologic status. ( 7.2 ) Drugs Affecting Nitric Oxide-Mediated Vasorelaxation : Potential for vasorelaxation; monitor blood pressure (e.g., PDE-5 inhibitors). ( 7.2 ) 7.