Sepiapterin

Sepiapterin is a prescription medicine used in conjunction with a phenylalanine (Phe)-restricted diet to treat hyperphenylalaninemia (HPA) in adults and children aged one month or older with sepiapterin-responsive phenylketonuria (PKU)

• Sepiapterin is available under the following different brand names: Sephience

Common side effects of Sepiapterin include:

• headache
• abdominal pain 
• diarrhea
• yellow or orange stool
• throat pain

Serious side effects of Sepiapterin include:

• increased risk of bleeding
• hypophenylalaninemia

Rare side effects of Sepiapterin include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Oral powder

• 250 mg unit-dose packet
• 1000 mg unit-dose packet

Phenylketonuria

Adult dosage

• 60 mg/kg orally daily
• Adjust dosage within the range of 7.5-60 mg/kg orally daily based on blood Phe levels during treatment
• Discontinue therapy if blood Phe does not decrease after 2 weeks of treatment at maximum daily dosage of 60 mg/kg

Pediatric dosage

Starting dosage

• 1 to less than 6 months: 7.5 mg/kg orally daily
• 6 months to less than 1 year: 15 mg/kg orally daily
• 1 to less than 2 years: 30 mg/kg orally daily
• 2 years and older: 60 mg/kg orally daily

Maintenance dosage

• Children younger than 2 years
  • Adjust dosage within range of 7.5-60 mg/kg orally daily based on blood Phe levels during treatment
  • If blood Phe does not decrease after 2 weeks of treatment, titrate dosage incrementally to maximum dosage of 60 mg/kg orally daily
• Children aged 2 years and older
  • Adjust dosage within range of 7.5-60 mg/kg orally daily based on blood Phe levels during treatment
  • Discontinue therapy if blood Phe does not decrease after 2 weeks of treatment at maximum daily dosage of 60 mg/kg

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your doctor has directed you to use this medication, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

Drug interaction overview

• Sepiapterin reductase inhibitors
• Avoid
  • Avoid coadministration with drugs known to inhibit folate synthesis dihydrofolate reductase (DHFR) (eg, trimethoprim, methotrexate, pemetrexed, pralatrexate) while taking sepiapterin
  • Concomitant administration may reduce sepiapterin metabolism to tetrahydrobiopterin (BH4)
  • If unavoidable, monitor blood Phe levels
• Levodopa
  • Monitor
  • Sepiapterin may increase the availability of tyrosine, a precursor of levodopa
  • Neurologic events (eg, seizures, exacerbation of seizures, over-stimulation, irritability) reported in patients receiving another PAH activator and levodopa concomitantly for a non-PKU indication
  • Monitor for a change in neurologic status if coadministered with levodopa
• Drugs affecting nitric oxide-mediated vasorelaxation
  • Monitor
  • Sepiapterin and PDE-5 inhibitors induce vasorelaxation; coadministration may reduce blood pressure even further
  • Monitor for signs and symptoms of hypotension if coadministered with drugs that affect nitric oxide-mediated vasorelaxation

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Sepiapterin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Sepiapterin?”

Cautions

• Bleeding
  • May increase bleeding risk
  • Bleeding events (e.g., superficial hematomas, prolonged bleeding, heavy menstrual bleeding) reported
  • One patient with nontraumatic superficial hematomas and prolonged bleeding was rechallenged at a lower dose with recurrence of symptoms, which led to treatment discontinuation
  • Onset of symptoms typically occurred 15 days after initial exposure and 2 days after rechallenging
  • Inform patients of the risk of bleeding and to follow up with their healthcare clinician if signs of increased bleeding occur
  • Consider treatment interruption in patients with active bleeding
• Hypophenylalaninemia
  • Can cause hypophenylalaninemia, multiple instances of low blood Phe levels during treatment reported in pediatric patients
  • Prolonged hypophenylalaninemia may be associated with catabolism and endogenous protein breakdown and adverse developmental outcomes
  • Monitor blood Phe levels during treatment and if needed, modify dose and/or dietary protein and Phe intake to ensure adequate blood Phe level control
  • Frequent blood Phe monitoring is recommended in children

Pregnancy and Lactation

• Pregnancy
  • Available data on use during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes
• Clinical considerations
  • Uncontrolled blood Phe concentrations before and during pregnancy are associated with an increased risk of adverse pregnancy outcomes and fetal adverse effects
  • To reduce the risk of hyperphenylalaninemia-induced fetal adverse effects, maintain blood Phe concentrations between 120-360 micromol/L during pregnancy and 3 months before conception
  • Available data from the Maternal Phenylketonuria Collaborative Study on 468 pregnancies and 331 live births in pregnant women with PKU demonstrated that uncontrolled Phe concentrations more than 600 micromol/L are associated with an increased risk for major birth defects (eg, microcephaly, major cardiac malformations), intrauterine fetal growth retardation, and future intellectual disability with low IQ
• Lactation
  • Data are unavailable on the presence of sepiapterin in human or animal milk, or effects on breastfed infants or milk production