Sepiapterin
Looking up MedlinePlus…
From MedlinePlus, U.S. National Library of Medicine
Dosing in kidney impairment
This label has no separate kidney-impairment dosing section. Check warnings and clinical pharmacology in the full label.
Preparation and administration
Recommended Dosage and Administration The recommended starting dosage of SEPHIENCE is based on the patient’s age and is administered orally once daily (see Table 1 ). Administer SEPHIENCE with food [see Clinical Pharmacology] . [See table below.] is the maximum daily dose for all patients. 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 Evaluation Period Dosage Titration in Patients Less than 2 Years of Age After initiating treatment at the starting dosage by age ( Table 1 ), check blood Phe levels to determine response to treatment within 2 weeks.
If blood Phe does not decrease, SEPHIENCE dosage may be titrated incrementally based on blood Phe levels to a maximum daily dosage of 60 mg/kg. Existing dietary protein and Phe intake should not be modified during the evaluation period. Discontinuation for Lack of Biochemical Response Discontinue SEPHIENCE in patients whose blood Phe does not decrease after 2 weeks of treatment at the maximum daily dosage of 60 mg/kg.
Dosage Modification and Monitoring Monitor blood Phe levels during treatment, and if needed, modify the daily dosage of SEPHIENCE within the range of 7.5 mg/kg to 60 mg/kg and/or dietary protein and Phe intake to ensure adequate blood Phe level control. Frequent blood Phe monitoring is recommended in the pediatric population [see Warnings and Precautions] .
Missed Dose A missed dose should be taken as soon as possible but 2 doses should not be administered on the same day. Resume the normal dosing schedule the following day.
Preparation and Administration Instructions Doses Less Than 1,000 mg ( administration based on 25 mg/mL concentration ) Determine the required number of SEPHIENCE packets and the required volume of water or apple juice to achieve a concentration of 25 mg/mL mixture (see Table 2 ). [See table below.] Calculate the prescribed dose volume to the nearest 0.2 mL.
Divide the calculated daily dose (mg) by the final concentration (25 mg/mL) of SEPHIENCE liquid mixture for doses less than 1,000 mg. Prescribed dose volume (mL) = SEPHIENCE calculated dose (mg)) 25 mg/mL Prepare a liquid mixture. Open and empty the entire content of each SEPHIENCE packet into an appropriate-size container and mix with the required volume of water or apple juice per Table 2 .
Stir the contents for 30 seconds or more until the mixture is uniformly mixed. Using a graduated oral dosing syringe, draw up the prescribed dose volume to the nearest 0.2 mL. Administer the prescribed dose volume (mL). Administer immediately. If particles are remaining in the syringe, draw up additional water or apple juice and administer the contents immediately.
Repeat if particles still remain. Discard unused portion of SEPHIENCE mixture remaining in the container. Consume additional food after administration of the prescribed dose volume. Doses 1,000 mg or Greater ( whole packet administration ) Determine the required number of SEPHIENCE packets and the required volume of water, apple juice, strawberry jam, or applesauce (see Table 3 ). [See table below.] 00 mg or Greater Abbreviations: mg, milligrams; mL, milliliters; Tbsp, tablespoons a For calculated daily doses 1,000 mg or greater, round the dose to the nearest 250 mg to determine the number of SEPHIENCE packets required. b For each 1,000 mg packet, add 2 Tbsp (30 mL) of water, apple juice, strawberry jam, or applesauce, and then add an additional quantity of 2 Tbsp (30 mL) for up to three 250 mg packet(s) and then mix.
Daily Dose (mg) Number of 1,000 mg packets a Number of 250 mg packets a Volume of water, apple juice, strawberry jam, or applesauce b 1,000 mg to 1,124 mg 1 0 2 Tbsp or 30 mL 1,125 mg to 1,374 mg 1 1 4 Tbsp or 60 mL 1,375 mg to 1,624 mg 1 2 1,625 mg to 1,874 mg 1 3 1,875 mg to 2,124 mg 2 0 2,125 mg to 2,374 mg 2 1 6 Tbsp or 90 mL 2,375 mg to 2,624 mg 2 2 2,625 mg to 2,874 mg 2 3 2,875 mg to 3,124 mg 3 0 3,125 mg to 3,374 mg 3 1 8 Tbsp or 120 mL 3,375 mg to 3,624 mg 3 2 3,625 mg to 3,874 mg 3 3 3,875 mg to 4,124 mg 4 0 4,125 mg to 4,374 mg 4 1 10 Tbsp or 150 mL 4,375 mg to 4,624 mg 4 2 4,625 mg to 4,874 mg 4 3 4,875 mg to 5,124 mg 5 0 5,125 mg to 5,374 mg 5 1 12 Tbsp or 180 mL 5,375 mg to 5,624 mg 5 2 5,625 mg to 5,874 mg 5 3 5,875 mg to 6,124 mg 6 0 Prepare a liquid or soft food mixture.
Open and empty the entire content of each SEPHIENCE packet into a container. Mix with the required amount of water, apple juice, strawberry jam, or applesauce per Table 3 . Stir the contents for 30 seconds or more when mixing SEPHIENCE with water or apple juice or 60 seconds or more when mixing SEPHIENCE with strawberry jam or applesauce until the mixture is uniform.
Administer the dose. Consume the entire mixture immediately. If particles are remaining in the container, add additional water or juice to the container and administer the contents immediately. Repeat if particles still remain. Consume additional food after administration of the entire mixture.
Storage Instructions for the Liquid and Soft Food Mixtures If the SEPHIENCE liquid or soft food mixture is not administered immediately, cover and store the mixture at controlled room temperature between 20°C to 25°C (68°F to 77°F) for up to 6 hours or refrigerate between 2°C to 8°C (36°F to 46°F) for up to 24 hours. If the liquid or soft food mixture is stored, stir for at least 30 or 60 seconds, respectively, prior to administration of the prescribed dose.
Discard unused SEPHIENCE mixture after 6 hours at controlled room temperature or after 24 hours if refrigerated.
| *For calculated daily doses less than 1,000 mg, the final concentration of prepared SEPHIENCE liquid mixture is 25 mg/mL [see Dosage and Administration (2.3)]. **60 mg/kg is the maximum daily dose for all patients. | |
| 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 |
| Abbreviations: mg, milligrams; mL, milliliters a For calculated daily doses less than 1,000 mg, round the dose up to the nearest 250 mg to determine the number of SEPHIENCE packets and prepare each 250 mg packet with 9 mL of water or apple juice. | |||
| Daily Dose (mg) | Number of 1,000 mg packetsa | Number of 250 mg packetsa | Volume of water or apple juice (mL) |
| 250 mg or less | 0 | 1 | 9 mL |
| 251 mg to 500 mg | 0 | 2 | 18 mL |
| 501 mg to 750 mg | 0 | 3 | 27 mL |
| 751 mg to 999 mg | 1 | 0 | 36 mL |
| Abbreviations: mg, milligrams; mL, milliliters; Tbsp, tablespoons a For calculated daily doses 1,000 mg or greater, round the dose to the nearest 250 mg to determine the number of SEPHIENCE packets required. b For each 1,000 mg packet, add 2 Tbsp (30 mL) of water, apple juice, strawberry jam, or applesauce, and then add an additional quantity of 2 Tbsp (30 mL) for up to three 250 mg packet(s) and then mix. | |||
| Daily Dose (mg) | Number of 1,000 mg packetsa | Number of 250 mg packetsa | Volume of water, apple juice, strawberry jam, or applesauceb |
| 1,000 mg to 1,124 mg | 1 | 0 | 2 Tbsp or 30 mL |
| 1,125 mg to 1,374 mg | 1 | 1 | 4 Tbsp or 60 mL |
| 1,375 mg to 1,624 mg | 1 | 2 | |
| 1,625 mg to 1,874 mg | 1 | 3 | |
| 1,875 mg to 2,124 mg | 2 | 0 | |
| 2,125 mg to 2,374 mg | 2 | 1 | 6 Tbsp or 90 mL |
| 2,375 mg to 2,624 mg | 2 | 2 | |
| 2,625 mg to 2,874 mg | 2 | 3 | |
| 2,875 mg to 3,124 mg | 3 | 0 | |
| 3,125 mg to 3,374 mg | 3 | 1 | 8 Tbsp or 120 mL |
| 3,375 mg to 3,624 mg | 3 | 2 | |
| 3,625 mg to 3,874 mg | 3 | 3 | |
| 3,875 mg to 4,124 mg | 4 | 0 | |
| 4,125 mg to 4,374 mg | 4 | 1 | 10 Tbsp or 150 mL |
| 4,375 mg to 4,624 mg | 4 | 2 | |
| 4,625 mg to 4,874 mg | 4 | 3 | |
| 4,875 mg to 5,124 mg | 5 | 0 | |
| 5,125 mg to 5,374 mg | 5 | 1 | 12 Tbsp or 180 mL |
| 5,375 mg to 5,624 mg | 5 | 2 | |
| 5,625 mg to 5,874 mg | 5 | 3 | |
| 5,875 mg to 6,124 mg | 6 | 0 | |
Drug interactions
Check sepiapterin against a medication listLabel text (4 paragraphs)
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 )
7.1 Effects of Other Drugs on SEPHIENCE Avoid concomitant use of drugs known to inhibit folate synthesis dihydrofolate reductase (DHFR) (e.g., trimethoprim, methotrexate, trimetrexate, pemetrexed, pralatrexate, raltitrexed, and piritrexim) while taking SEPHIENCE. Concomitant administration of such drugs may reduce sepiapterin metabolism to tetrahydrobiopterin (BH 4 ). If concomitant use is not avoidable, monitor blood Phe levels. Avoid concomitant use of sepiapterin reductase (SR) inhibitors with SEPHIENCE. Concomitant administration of such drugs may reduce sepiapterin metabolism to BH 4 . If concomitant use is not avoidable, monitor blood Phe levels.
7.2 Effects of SEPHIENCE on Other Drugs SEPHIENCE may increase the availability of tyrosine, a precursor of levodopa. Neurologic events were reported postmarketing in patients receiving another PAH activator and levodopa concomitantly for a non-PKU indication. Monitor patients for a change in neurologic status when levodopa is administered with SEPHIENCE [see Warnings and Precautions ( 5.3 )] .
7.3 Drugs Affecting Nitric Oxide-Mediated Vasorelaxation SEPHIENCE and PDE-5 inhibitors induce vasorelaxation, thus concomitant use of SEPHIENCE with PDE-5 inhibitors may reduce blood pressure even further. Monitor for signs and symptoms of hypotension with concomitant use of SEPHIENCE with drugs that affect nitric oxide-mediated vasorelaxation (e.g., PDE-5 inhibitors such as sildenafil, vardenafil, or tadalafil).
Contraindications
None. None. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
LiverTox has no chapter for sepiapterin. Check the label's hepatic warnings.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Available data on the use of SEPHIENCE during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Uncontrolled blood Phe concentrations before and during pregnancy are associated with an increased risk of adverse pregnancy outcomes and fetal adverse effects ( see Clinical Considerations ) .
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 ( see Data ). All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. 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.
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. Clinical Considerations Disease-Associated Maternal and/or Embryofetal Risk Uncontrolled blood Phe concentrations before and during pregnancy are associated with an increased risk of adverse outcomes and fetal adverse effects ( see Data ).
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 [see Dosage and Administration ( 2.2 )] . Data Human Data 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 above 600 micromol/L are associated with an increased risk for major birth defects (including microcephaly, major cardiac malformations), intrauterine fetal growth retardation, and future intellectual disability with low IQ.
Animal Data In an embryo-fetal development study in rats, SEPHIENCE was administered at dose levels of 100, 300, or 1,000 mg/kg/day via oral gavage to pregnant rats during the period of organogenesis from gestation day (GD) 7 to GD 17. There were no maternal or embryo-fetal developmental toxicities noted at doses up to 1,000 mg/kg/day (9-fold the human AUC 0-24 at the MRHD). In an embryo-fetal development study in pregnant rabbits,…
Breastfeeding (LactMed)
No information is available on the use of sepiapterin during breastfeeding. If a mother requires sepiapterin, it is not a reason to discontinue breastfeeding. However, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
Not the price at the counterThese are not what a patient pays at the pharmacy counter. They are what pharmacies, health plans, and government buyers pay, before manufacturer rebates. A patient's cost depends on their insurance (copay, coinsurance, or deductible) or the pharmacy's cash price.