Sepiapterin
SEPHIENCE
What it isOral synthetic precursor converted to BH4, the cofactor for phenylalanine hydroxylase; phenylketonuria.
Why this oneUnlike sapropterin, it enters cells as a precursor and is converted through the BH4 salvage pathway.
What limits itMonitor phenylalanine to avoid excessive lowering; bleeding and a clinically important levodopa interaction require attention.
FDA-approved for
- phenylketonuria (2025)
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Phenylketonuria (PKU), age <6 months | peds <6 mo | PO 7.5 mg/kg QD with food | Adjust by blood Phe within 7.5–60 mg/kg QD | PO 60 mg/kg QD |
| PKU, age 6 months to <1 year | peds 6 mo–<1 yr | PO 15 mg/kg QD with food | Adjust by blood Phe within 7.5–60 mg/kg QD | PO 60 mg/kg QD |
| PKU, age 1 to <2 years | peds 1–<2 yr | PO 30 mg/kg QD with food | Adjust by blood Phe within 7.5–60 mg/kg QD | PO 60 mg/kg QD |
| PKU, age ≥2 years | adults & peds ≥2 yr | PO 60 mg/kg QD with food | Adjust by blood Phe within 7.5–60 mg/kg QD | PO 60 mg/kg QD |
Titration Age <2 yr: check blood Phe within 2 weeks of starting; if Phe not decreased, increase incrementally by blood Phe levels to max 60 mg/kg/day
Renal Undefined
Hepatic Undefined
60 mg/kg/day is the maximum daily dose for all ages
Instructions
- Take QD with food; consume additional food after the dose
- Maintain dietary protein and Phe-restricted diet; regular dietary assessments; obtain baseline blood Phe before starting; monitor blood Phe during treatment (frequently in peds)
- Daily doses <1,000 mg: prepare 25 mg/mL mixture in water or apple juice (each 250 mg packet + 9 mL), give exact prescribed volume with oral syringe, administer immediately
- Daily doses ≥1,000 mg: mix whole packets with water, apple juice, strawberry jam, or applesauce per label table; consume entire mixture immediately
- Stored mixture: ≤6 h room temp or ≤24 h refrigerated; re-stir before use; discard after
- Discontinue if blood Phe does not decrease after 2 weeks at 60 mg/kg/day
- Missed dose: take ASAP but never 2 doses same day; resume normal schedule next day
Cautions
- Increased bleeding risk (hematomas, prolonged bleeding, heavy menstrual bleeding); consider treatment interruption with active bleeding
- Hypophenylalaninemia, esp. pediatric patients — monitor blood Phe; prolonged low Phe associated with adverse developmental outcomes
- Levodopa interaction: seizures, over-stimulation, irritability possible — monitor neurologic status
Adverse reactions
- Diarrhea
- Headache
- Abdominal pain
- Hypophenylalaninemia (peds)
- Feces discoloration
- Oropharyngeal pain
- Bleeding events
Pregnancy Insufficient human data; uncontrolled maternal blood Phe is itself fetotoxic — maintain Phe 120–360 micromol/L during pregnancy and 3 months pre-conception; no adverse developmental effects in animal studies
Lactation No data on presence in milk; weigh benefits of breastfeeding against need for drug
NO BOXED WARNINGS
Principal riskNo FDA boxed warning.
Cost, est. cash$10,000–$20,000/month
Generic entry2039 est.
Classes and tags
Clinical profile
Legacy pregnancy categoryNot assigned — PLLR-era drug
Defining liabilityGenerally tolerated at therapeutic doses; clinically important risks are agent-specific and increase with interactions or organ impairment.
Mechanism of action: Sepiapterin ballicule
