Sephience®
Sepiapterin is a phenylalanine hydroxylase (PAH) activator.1
Sepiapterin has the following uses:
Sepiapterin is indicated for the treatment of hyperphenylalaninemia (HPA) in adults and pediatric patients 1 month of age and older with sepiapterin-responsive phenylketonuria (PKU).1 Sepiapterin is to be used in conjunction with a phenylalanine (Phe)-restricted diet.1
Sepiapterin is available in the following dosage form(s) and strength(s):
Treatment with sepiapterin should be directed by physicians knowledgeable in the management of PKU.1
Biochemical response to sepiapterin treatment cannot generally be pre-determined by laboratory testing (e.g., molecular testing), and should be determined through a therapeutic evaluation of sepiapterin.1
Obtain baseline blood Phe concentration before initiating treatment.1
All patients with PKU who are treated with sepiapterin should be on a dietary protein and Phe-restricted diet that is based on blood Phe levels.1
Prepare sepiapterin calculated daily doses of <1000 mg as a liquid mixture (25 mg/mL), and administer exact prescribed dose volume (mL).1 Prepare sepiapterin calculated daily doses ≥1000 mg as a liquid or soft food mixture, and administer the appropriate number of whole packets.1 See full prescribing information for complete preparation and administration instructions.1
The recommended starting dosage of sepiapterin in pediatric patients is based on the patient's age and is administered orally once daily (see Table 1).1
After initiating treatment at the starting dosage by age, check blood Phe levels to determine response to treatment within 2 weeks.1 If blood Phe does not decrease, dosage in patients less than 2 years of age may be titrated incrementally based on blood Phe levels to a maximum daily dosage of 60 mg/kg.1 Existing dietary protein and Phe intake should not be modified during the evaluation period.1
Discontinue therapy in patients whose blood Phe does not decrease after 2 weeks of treatment at the maximum daily dosage of 60 mg/kg.1
Age | Dose (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 |
The recommended starting dosage of sepiapterin for adults is 60 mg/kg and is administered orally once daily with food.1
After initiating treatment at the starting dosage, check blood Phe levels to determine response to treatment within 2 weeks.1 Discontinue therapy in patients whose blood Phe does not decrease after 2 weeks of treatment at the maximum daily dosage of 60 mg/kg.1
None.1
Sepiapterin may increase the risk of bleeding.1 Bleeding events, including superficial hematomas, prolonged bleeding, and heavy menstrual bleeding have occurred in patients treated with the drug.1 One patient with non-traumatic superficial hematomas and prolonged bleeding was rechallenged at a lower dose of sepiapterin with recurrence of symptoms, which led to treatment discontinuation.1 The patient experienced symptoms 15 days after initial exposure and two days after rechallenge.1 The patient had normal blood counts and coagulation studies at the time of the bleeding.1 Inform the patient about the increased risk of bleeding associated with sepiapterin and to follow up with his/her healthcare provider if he/she experiences any signs of increased bleeding.1 Consider treatment interruption with sepiapterin in patients with active bleeding.1
In clinical trials of sepiapterin, some pediatric PKU patients experienced hypophenylalaninemia (low blood Phe), including some patients with multiple low blood Phe levels, during treatment with sepiapterin.1 Prolonged levels of blood Phe that are too low have been associated with catabolism and endogenous protein breakdown, which has been associated with adverse developmental outcomes.1 Monitor blood Phe levels during treatment and if needed, modify the dosage of sepiapterin and/or dietary protein and Phe intake to ensure adequate blood Phe level control.1 Frequent blood Phe monitoring is recommended in the pediatric population.1
In a 10-year post-marketing safety surveillance program for a non-PKU indication using another drug that is a phenylalanine hydroxylase (PAH) activator, 3 patients with underlying neurological disorders experienced seizures, exacerbation of seizures, over-stimulation, and irritability during co-administration with levodopa.1 Monitor patients who are receiving levodopa for changes in neurological status during treatment with sepiapterin.1
Available data on the use of sepiapterin during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.1 Uncontrolled blood Phe concentrations before and during pregnancy are associated with an increased risk of adverse pregnancy outcomes and fetal adverse effects.1
In animal reproduction studies, oral administration of sepiapterin to pregnant rats and rabbits during organogenesis at dose exposures up to 9- and 6- times the human exposure at the maximum recommended human dose (MRHD) of 60 mg/kg, respectively, resulted in no adverse developmental effects.1
All pregnancies have a background risk of birth defects, loss, or other adverse outcomes.1 In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.1 The background risk of major birth defects and miscarriage in pregnant women with PKU who maintain blood Phe concentrations greater than 600 micromol/L during pregnancy is greater than the corresponding background risk for pregnant women without PKU.1
Uncontrolled blood Phe concentrations before and during pregnancy are associated with an increased risk of adverse outcomes and fetal adverse effects.1 To reduce the risk of hyperphenylalaninemia-induced fetal adverse effects, blood Phe concentrations should be maintained between 120 and 360 micromol/L during pregnancy and during the 3 months before conception.1
There are no data on the presence of sepiapterin in either human or animal milk, the effects on the breastfed infant, or the effects on milk production.1 The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for sepiapterin and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.1
The safety and effectiveness of sepiapterin have been established in pediatric patients 1 month of age and older.1 Use of sepiapterin for this indication is supported by evidence from one adequate and well-controlled trial in 63 pediatric patients with PKU aged 1 to <17 years old (Trial 1) and additional safety and efficacy information obtained from an ongoing open-label trial in adult and pediatric patients with PKU (Trial 2).1 In Trial 1 Part 2, hypophenylalaninemia was seen in 5.4% (2/37) of sepiapterin-treated pediatric patients and in no adult patients.1 Some pediatric patients in Trial 2 had multiple low blood Phe levels.1 The safety and effectiveness of sepiapterin for treatment of PKU have not been established in pediatric patients younger than 1 month of age.1
Clinical studies of sepiapterin did not include patients 65 years of age and older to determine if they respond differently from younger adult patients.1
Most common adverse reactions with sepiapterin (≥2% and greater than placebo) were diarrhea, headache, abdominal pain, hypophenylalaninemia, feces discoloration, and oropharyngeal pain.1
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Sepiapterin is a precursor of the enzymatic co-factor tetrahydrobiopterin (BH4) which activates phenylalanine hydroxylase (PAH).1
Additional Information
AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Powder | 250 mg | SEPHIENCE (available in single unit dose packet) | PTC Therapeutics |
1000 mg | SEPHIENCE (available in single unit dose packet) | PTC Therapeutics |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions October 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.