SEPHIENCE-Sepiapterin powder
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anum Ijaz M.B.B.S., M.D.[2]
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Overview
SEPHIENCE-Sepiapterin powder is a phenylalanine hydroxylase (PAH) activator that is FDA approved for the treatment of hyperphenylalaninemia (HPA) in adult and pediatric patients 1 month of age and older with sepiapterin-responsive phenylketonuria (PKU). SEPHIENCE is to be used in conjunction with a phenylalanine (Phe)- restricted diet.. Common adverse reactions include diarrhea, headache, abdominal pain, hypophenylalaninemia, feces discoloration, and oropharyngeal pain..
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
FDA-labeled Indications
SEPHIENCE is indicated for the treatment of hyperphenylalaninemia (HPA) in adult with sepiapterin-responsive phenylketonuria (PKU). SEPHIENCE is to be used in conjunction with a phenylalanine (Phe)-restricted diet.
Recommended Dosage
- The recommended starting dosage of SEPHIENCE is based on the patient’s age and is administered orally once daily, as shown in the table below.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Sepiapterin powder in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Sepiapterin powder in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
FDA-labeled Indications
SEPHIENCE is indicated for the treatment of hyperphenylalaninemia (HPA) in pediatric patients 1 month of age and older with sepiapterin-responsive phenylketonuria (PKU). SEPHIENCE is to be used in conjunction with a phenylalanine (Phe)-restricted diet.
Recommended Dosage
- The recommended starting dosage of SEPHIENCE is based on the patient’s age and is administered orally once daily.
Add Dosage table.
Evaluation Period
- Dosage Titration in Patients Less than 2 Years of Age
- After initiating treatment at the starting dosage by age, 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.
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.
Dosage Forms and Strengths
Oral powder: 250 mg or 1,000 mg sepiapterin as yellow to orange powder in a unit-dose packet.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Sepiapterin powder in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Sepiapterin powder in pediatric patients.
Contraindications
None.
Warnings
Increased Bleeding
- SEPHIENCE may increase the risk of bleeding.
- Bleeding events, including superficial hematomas, prolonged bleeding, and heavy menstrual bleeding have occurred in patients treated with SEPHIENCE.
- One patient with non-traumatic superficial hematomas and prolonged bleeding was re-challenged at a lower dose of SEPHIENCE with recurrence of symptoms, which led to treatment discontinuation.
- The patient experienced symptoms 15 days after initial exposure and two days after rechallenge. The patient had normal blood counts and coagulation studies at the time of the bleeding.
- Inform the patient about the increased risk of bleeding associated with SEPHIENCE and to follow up with his/her healthcare provider if he/she experiences any signs of increased bleeding.
- Consider treatment interruption with SEPHIENCE in patients with active bleeding.
Hypophenylalaninemia
- In clinical trials of SEPHIENCE, some pediatric PKU patients experienced hypophenylalaninemia (low blood Phe), including some patients with multiple low blood Phe levels, during treatment with SEPHIENCE.
- 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.
- Monitor blood Phe levels during treatment and if needed, modify the dosage of SEPHIENCE and/or dietary protein and Phe intake to ensure adequate blood Phe level control.
- Frequent blood Phe monitoring is recommended in the pediatric population.
Interaction with Levodopa
- 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.
- Monitor patients who are receiving levodopa for changes in neurological status during treatment with SEPHIENCE.
Adverse Reactions
Clinical Trials Experience
Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- The safety of SEPHIENCE was evaluated in Trial 1 [Part 1 (open label); Part 2, (placebo-controlled)]; and Trial 2 (open-label).
- The two trials included a total of 215 SEPHIENCE-treated patients with PKU: 10 (5%) were <2 years old, 118 (55%) were ≥2 and <17 years old, and 87 (40%) were ≥17 years old.
- All patients received SEPHIENCE from 7.5 mg/kg/day up to 60 mg/kg/day and the median duration of treatment (in weeks) was 25.5.
Trial 1
- Trial 1 included a total of 157 patients (85 male and 72 female, aged 1 year to 61 years old) with PKU across both parts of the trial.
- The patients received dosages from 20 mg/kg up to 60 mg/kg daily and the median duration of treatment was 8 weeks.
- The most common adverse reactions that were reported in ≥2% of patients treated with SEPHIENCE and greater than that of the placebo group were diarrhea, headache, abdominal pain, hypophenylalaninemia, feces discoloration and oropharyngeal pain.
- Adverse reactions were similar across both adult and pediatric populations except for hypophenylalaninemia.
Description of Selected Adverse Reactions
Increased Bleeding
- In Trial 1 Part 2, a case of heavy menstrual bleeding was reported in a SEPHIENCE-treated patient.
- Less than 2% of patients in Trial 2 experienced increased bleeding, which included heavy menstrual bleeding, non-traumatic superficial hematomas, and prolonged bleeding.
Hypophenylalaninemia
- In Trial 1 Part 2, hypophenylalaninemia was seen in 5% (2/37) of sepiapterin-treated pediatric patients and in no adult patients. Some pediatric patients in Trial 2 had multiple low blood Phe levels.
Postmarketing Experience
There is limited information regarding SEPHIENCE-Sepiapterin powder Postmarketing Experience in the drug label.
Drug Interactions
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 (BH4).
- 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 BH4.
- If concomitant use is not avoidable, monitor blood Phe levels.
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.
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).
Use in Specific Populations
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.
- 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
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 AUC0-24 at the MRHD).
- In an embryo-fetal development study in pregnant rabbits, SEPHIENCE was administered at dose levels of 100, 300, or 1,000 mg/kg/day via oral gavage to pregnant rabbits during the period of organogenesis from gestation day (GD) 7 to GD 19.
- There were no maternal or embryo-fetal developmental toxicities at doses up to 1,000 mg/kg/day (6-fold the human AUC0-24 at the MRHD).
- In the pre- and post-natal development study in rats, SEPHIENCE was administered at dose levels of 30, 100, and 300 mg/kg/day via oral gavage once daily to pregnant rats from GD 6 to lactation day 20.
- SEPHIENCE did not induce effects on maternal reproductive function or on developmental and reproductive parameters of male and female offspring up to 300 mg/kg (7-fold the human AUC0-24 at the MRHD).
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of SEPHIENCE-Sepiapterin powder in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of SEPHIENCE-Sepiapterin powder during labor and delivery.
Nursing Mothers
Risk Summary
- 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.
- The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SEPHIENCE and any potential adverse effects on the breastfed infant from SEPHIENCE or from the underlying maternal condition.
Pediatric Use
- The safety and effectiveness of SEPHIENCE have been established in pediatric patients 1 month of age and older.
- Use of SEPHIENCE 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).
- In Trial 1 Part 2, hypophenylalaninemia was seen in 5.4% (2/37) of sepiapterin-treated pediatric patients and in no adult patients. Some pediatric patients in Trial 2 had multiple low blood Phe levels.
- The safety and effectiveness of SEPHIENCE for treatment of PKU have not been established in pediatric patients younger than 1 month of age.
Geriatic Use
Clinical studies of SEPHIENCE did not include patients 65 years of age and older to determine if they respond differently from younger adult patients.
Gender
There is no FDA guidance on the use of SEPHIENCE-Sepiapterin powder with respect to specific gender populations.
Race
There is no FDA guidance on the use of SEPHIENCE-Sepiapterin powder with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of SEPHIENCE-Sepiapterin powder in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of SEPHIENCE-Sepiapterin powder in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of SEPHIENCE-Sepiapterin powder in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of SEPHIENCE-Sepiapterin powder in patients who are immunocompromised.
Administration and Monitoring
Administration
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.
Add Saphience administration table
- 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 given above.
- 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.
Add adminsitration table 2
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.
- 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.
Monitoring
There is limited information regarding SEPHIENCE-Sepiapterin powder Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of SEPHIENCE-Sepiapterin powder and IV administrations.
Overdosage
There is limited information regarding SEPHIENCE-Sepiapterin powder overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding SEPHIENCE-Sepiapterin powder Pharmacology in the drug label.
Mechanism of Action
SEPHIENCE is a precursor of the enzymatic co-factor tetrahydrobiopterin (BH4) which activates PAH.
Structure
- EPHIENCE (sepiapterin) contains the drug substance sepiapterin, a PAH activator. Sepiapterin is a yellow to orange powder.
- Sepiapterin is slightly soluble in water with the solubility at 1.4 mg/mL.
- The chemical name of sepiapterin is (S)-2-amino-6-(2-hydroxypropanoyl)-7,8-dihydropteridin-4(3H)-one.
- The molecular formula is C9H11N5O3 and the molecular weight is 237.22 g/mol. The structural formula is:
Add structure image
Pharmacodynamics
Cardiac Electrophysiology At the recommended SEPHIENCE dose of 60 mg/kg orally once daily, clinically significant QTc interval prolongation was not observed.
Pharmacokinetics
- Following oral administration, sepiapterin reached the maximum concentration in plasma at 2 hours post-treatment and converted to pharmacologically active metabolite BH4 with the exposures of sepiapterin generally less than 2% of those of BH4.
- There was no accumulation for BH4 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, BH4 exposures increased less than dose proportionally (with slopes 0.87 and 0.84 for Cmax and AUC0-last, respectively) in the dose range 5 to 20 mg/kg and less than dose proportionally (with slopes 0.1957 and 0.3189 for Cmax and AUC0-last, respectively) in the dose range 20 to 60 mg/kg.
Ábsorption
- The time to maximum plasma concentration (Tmax) of sepiapterin is approximately 1 to 3 hours after oral administration.
- Plasma sepiapterin is rapidly metabolized to BH4 and peak BH4 concentrations are achieved approximately 4 hours after the oral administration of sepiapterin.
- Effect of Food: Administration of SEPHIENCE with food results in increased exposure to sepiapterin and BH4. When SEPHIENCE was administered at 20 or 60 mg/kg daily with a low-fat meal in healthy adult subjects, BH4 exposures were 169% to 172% higher for Cmax and 162% to 173% higher for AUC0-24h compared to administration under fasted conditions. When sepiapterin at 20 or 60 mg/kg was administered with a high-fat, high-calorie meal, BH4 exposures were 221% to 226% higher for Cmax and 251% to 284% higher for AUC0-24h compared to administration under fasted conditions
Distribution
- Sepiapterin mean human plasma protein binding was 15.4% in the presence of 0.1% dithiothreitol (DTT) in the concentration range of 0.1 to 10 μM.
- BH4 mean human plasma protein binding was between 24.1% and 41.3% in the concentration range 2 to 15 μM in the presence of 0.5% β-mercaptoethanol.
- Sepiapterin apparent volume of distribution could not be estimated reliably as sepiapterin is converted to BH4 post oral administration and plasma concentration declines to below lower limit of quantitation generally by 12 hours postdose.
- BH4 apparent volume of distribution is 11433 (5790) L in adult patients with PKU.
- Increase of BH4 in cerebrospinal fluid was detected after oral administration of sepiapterin 60 mg/kg QD for 7 days in healthy adult subjects.
Elimination
- Following oral administration, sepiapterin is quickly absorbed and converted to BH4.
- Sepiapterin plasma concentration is remarkably lower than BH4 and declines rapidly to below the limit of quantitation generally by 12 hours post dose.
- The terminal half-life of BH4 is approximately 5 hours and the apparent clearance is 1498 (848) L/h in adult patients with PKU.
Metabolism
- Sepiapterin is metabolized by SR/carbonyl reductase (CR) and DHFR in a 2-step unidirectional process to form pharmacologically active metabolite BH4.
- BH4 is further metabolized non-enzymatically or enzymatically mediated by aromatic amino acid hydroxylases, such as PAH, tyrosine hydroxylase (TH), tryptophan hydroxylase (TPH), pterin-4α-carbinolamine dehydratase (PCD), dihydropteridine reductase (DHPR), xanthine oxidase (XO), and nitric oxide synthase (NOS) in various tissues.
- Extensive metabolism of sepiapterin was observed in humans following a single oral dose of 14C-sepiapterin.
- Absorbed sepiapterin was converted to the active metabolite BH4, with Cmax and AUC0-24h of sepiapterin generally less than 2% of those of BH4.
Excretion
- Following a single oral dose of radiolabeled sepiapterin 4,000 mg to healthy adult subjects, a mean of 6.7% was recovered in urine and 26.2% recovered in feces with a combined total recovery of 32.9% by 240 hours.
- The low total mass recovery is likely due to formation of volatile metabolites in human intestine.
- Sepiapterin was a minor component in urine and was one of the prominent radioactive components in feces.
Pediatric Patients
The pharmacokinetics of sepiapterin and BH4 following oral administration of sepiapterin at 60 mg/kg with food in PKU patients ≥2 years old are summarized in the table below:
Add pediatric pharmacokinetics table.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis In a 6-month carcinogenicity study in Tg.rasH2 mice, sepiapterin did not increase the incidence of tumors in male or female transgenic mice at approximately 12- and 16-fold, respectively, the human exposure (AUC0-24h) at the MRHD.
Mutagenesis
- Based on the weight of evidence, SEPHIENCE is not genotoxic. SEPHIENCE was negative in the Ames assay. SEPHIENCE was positive in an in vitro chromosomal aberration assay without metabolic activation but not with metabolic activation. * SEPHIENCE was negative in the in vivo (micronucleus and comet) assays in rats.
Impairment of Fertility SEPHIENCE was found to have no effect on fertility and reproductive function of male and female rats when given prior to and throughout mating in male and female rats and continuing to gestation day (GD) 7 in females at oral doses up to 300 mg/kg/day (approximately 7.5-fold the plasma exposure (AUC) at MRHD).
Clinical Studies
- 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 received open-label treatment with SEPHIENCE: 7.5 mg/kg orally in patients 0 to <6 months of age, 15 mg/kg in patients 6 to <12 months of age, 30 mg/kg in patients 12 months to <2 years of age, or 60 mg/kg in patients ≥2 years of age per day for 14 days.
- In Part 1, 66% of PKU patients showed a biochemical response to SEPHIENCE with a >30% or greater reduction in Phe level.
- In Part 2, after the 2-week washout period from Part 1, 98 patients aged 2 years and older who demonstrated a ≥30% reduction in blood Phe levels to SEPHIENCE treatment in Part 1 were randomized in a double-blind fashion to either SEPHIENCE 20 mg/kg daily for Weeks 1 and 2, 40 mg/kg daily for Weeks 3 and 4, 60 mg/kg daily for Weeks 5 and 6 (N=49), or placebo (N=49) for 6 weeks to assess efficacy.
- Twelve additional patients who had shown a 15% to 30% reduction in blood Phe during Part 1 were enrolled in Part 2 but were not included in the primary efficacy analysis.
- In Part 2, the primary efficacy was assessed in patients who demonstrated a ≥30% reduction in blood Phe levels during Part 1 (N=98) by the mean change in blood Phe level from baseline to Weeks 5 and 6 in the SEPHIENCE-treated group as compared to the mean change in the placebo group.
- In Part 2 of Trial 1, 55 patients in the SEPHIENCE group and 54 patients in the placebo group completed the treatment period. One patient in the SEPHIENCE group discontinued treatment.
The table below displays a reduction in blood Phe level from baseline to Weeks 5 and 6 in Part 2 of Trial 1 for SEPHIENCE-treated patients relative to placebo.
Efficacy endpoints table Add Sephience graph
How Supplied
- SEPHIENCE (sepiapterin) oral powder is supplied as a yellow to orange powder in a unit-dose heat-sealed laminated aluminum foil packet. Each packet contains:
- 250 mg sepiapterin per packet:
NDC 52856-201-03 Carton of 30-unit dose packets
NDC 52856-201-01 Single unit dose packet
- 1,000 mg sepiapterin per packet:
NDC 52856-301-03 Carton of 30-unit dose packets
NDC 52856-301-01 Single unit dose packet
Storage
- 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.
Images
Drug Images
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Package and Label Display Panel
Add Prinicpal Display {{#ask: Label Page::SEPHIENCE-Sepiapterin powder |?Label Name |format=template |template=DrugLabelImages |mainlabel=- |sort=Label Page }}
Patient Counseling Information
- Advise the patient and/or caregiver to read the FDA-approved patient labeling (Patient Information and Instructions for Use).
- Increased Bleeding
Inform the patient about the increased risk of bleeding associated with SEPHIENCE and to follow up with his/her healthcare provider if he/she experiences any symptoms of increased bleeding.
- Drug Interactions
Advise the patient to inform his/her healthcare provider if he/she is taking, or plan to take, any prescription or over-the-counter medications and supplements because of the potential for drug interactions.
- Feces Discoloration
Advise patients that SEPHIENCE may cause feces to have a yellow or orange discoloration.
Precautions with Alcohol
Alcohol-Sepiapterin powder interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
SEPHIENCE (seh-FIGH-ence)
Look-Alike Drug Names
There is limited information regarding SEPHIENCE-Sepiapterin powder Look-Alike Drug Names in the drug label.
Price
References
The contents of this FDA label are provided by the National Library of Medicine.