SEPHIENCE

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. When administered with a high-fat, high-calorie meal in adult healthy volunteers, BH 4 exposures increased less tha...

14.1 Clinical Studies in PKU

Trial 1(NCT05099640) was a two-part trial in adult and pediatric patients who had a diagnosis of PKU with hyperphenylalaninemia with at least 2 blood Phe measurements ≥600 μmol/L. Patients in the trial were 54% male, 90% White, 5% American Indian or Alaska Native, and 4% Other by race; 16% were identified as Hispanic or Latino. The mean age of the trial patients was 17 years (range: 1 to 61 years). At trial baseline, 8% of patients had blood Phe levels at <360 μmol/L, 36% at 360-600 μmol/L, 48% at 600-1200 μmol/L, and 8% at >1200 μmol/L. In Part 1, 157 patients re...

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...

None. None. ( 4 )

Increased Bleeding : SEPHIENCE may increase the risk of bleeding. Consider treatment interruption in patients with active bleeding. ( 5.1 ) Hypophenylalaninemia : Some pediatric PKU patients experienced hypophenylalaninemia; monitor patients blood Phe levels during treatment. ( 5.2 ) Interaction with Levodopa : Seizures, over-stimulation or irritability may occur; monitor patients for a change in neurologic status. ( 5.3 ) 5.1 Increased Bleeding SEPHIENCE may increase the risk of bleeding. Bleed...

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 ) Dr...