sapropterin (Rx)

Brand and Other Names:Kuvan
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 100mg

powder for oral solution

  • 100mg/packet

Hyperphenylalaninemia

Indicated for hyperphenylalaninemia caused by tetrahydrobiopterin responsive phenylketonuria

10 mg/kg PO qDay initially with food; response to therapy is determined by change in blood Phe following treatment at 10 mg/kg/day for up to 1 month; blood Phe levels should be checked after 1 wk of therapy and periodically for up to a month; if blood Phe does not decrease from baseline at 10 mg/kg/day, the dose may be increased to 20 mg/kg/day; patients whose blood Phe does not decrease after 1 month of treatment at 20 mg/kg/day are non-responders and treatment should be discontinued  

Once responsiveness established, dosage may be adjusted within range of 5 to 20 mg/kg/day according to response to therapy; periodic blood Phe monitoring is recommended to assess blood Phe control

Dosing Considerations

Measure baseline blood Phe level before initiating therapy

If 20 mg/kg/day starting dose used, response to therapy is determined by change in blood Phe following therapy at 20 mg/kg/day for a period of 1 month; blood Phe levels should be checked after 1 wk of therapy and periodically during first month; treatment should be discontinued in patients who do not respond to therapy

Dosage Forms & Strengths

tablet

  • 100mg

Hyperphenylalaninemia

Indicated for hyperphenylalaninemia caused by tetrahydrobiopterin responsive phenylketonuria

1 month to 6 years: Recommended starting dose is 10 mg/kg taken once daily

≥ 7 years: 10 mg/kg PO qDay initially with food; if 10 mg/kg/day starting dose used, response to therapy is determined by change in blood Phe following treatment at 10 mg/kg/day for up to 1 month; blood Phe levels should be checked after 1 wk of therapy and periodically for up to a month; if blood Phe does not decrease from baseline at 10 mg/kg/day, the dose may be increased to 20 mg/kg/day; patients whose blood Phe does not decrease after 1 month of treatment at 20 mg/kg/day are non-responders and treatment should be discontinued  

Once responsiveness established, dosage may be adjusted within range of 5-20 mg/kg/day according to response to therapy; periodic blood Phe monitoring is recommended to assess blood Phe control

Children aged <7 years treated with doses of 20 mg/kg/day are at increased risk for low levels of blood Phe

Dosing Considerations

Measure baseline blood Phe level before initiating therapy

Nonresponders: If 20 mg/kg/day starting dose used, response to therapy is determined by change in blood Phe following therapy at 20 mg/kg/day for a period of 1 month; blood Phe levels should be checked after 1 wk of therapy and periodically during first month; treatment should be discontinued in patients who do not respond to therapy

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Interactions

Interaction Checker

and sapropterin

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            Contraindicated (0)

              Serious - Use Alternative (0)

                Monitor Closely (5)

                • avanafil

                  sapropterin, avanafil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Possible additive vasorelaxation, leading to low blood pressure.

                • betrixaban

                  sapropterin increases levels of betrixaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Decrease betrixaban dose to 80 mg PO once, then 40 mg PO qDay if coadministered with a P-gp inhibitor.

                • levodopa

                  sapropterin, levodopa. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Case reports of combination causing convulsions, over-stimulation, or irritability.

                • methotrexate

                  methotrexate decreases levels of sapropterin by Other (see comment). Use Caution/Monitor. Comment: Mechanism: Inhibition of dihydropteridine reductase (DHPR).

                • tadalafil

                  sapropterin, tadalafil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Possible additive vasorelaxation, leading to low blood pressure.

                Minor (3)

                • pyrimethamine

                  pyrimethamine decreases levels of sapropterin by Other (see comment). Minor/Significance Unknown. Comment: Mechanism: Inhibition of dihydropteridine reductase (DHPR).

                • sildenafil

                  sapropterin, sildenafil. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Possible additive vasorelaxation, leading to low blood pressure.

                • vardenafil

                  sapropterin, vardenafil. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Possible additive vasorelaxation, leading to low blood pressure.

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                Adverse Effects

                >10%

                Rhinorrhea (11%)

                Headache (15%)

                1-10%

                Diarrhea (8%)

                Pharyngolaryngeal pain (10%)

                Cough (7%)

                Nasal congestion (4%)

                Vomiting (8%)

                Nausea (8%)

                <1%

                Gastritis

                Gastrointestinal bleeding

                Thrombocytopenia

                Spinal cord injury

                Abdominal pain

                Decreased appetite

                Respiratory tract infection

                Peripheral edema

                Postmarketing Reports

                Gastrointestinal reactions: Esophagitis, oropharyngeal pain, pharyngitis, esophageal pain, and dyspepsia

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                Warnings

                Contraindications

                None

                Cautions

                Do not eliminate ongoing Phe-restricted diet; treat all patients with a Phe-restricted diet

                Children aged <7 yr treated with 20 mg/kg/day are at increased risk for low levels of blood Phe compared with patients aged ≥7 yr

                Treatment should be directed by physicians knowledgeable in management of PKU;. prolonged elevations in blood Phe levels in patients with PKU can result in severe neurologic damage, including severe mental retardation, microcephaly, delayed speech, seizures, and behavioral abnormalities; prolonged levels of blood Phe that are too low are associated with catabolism and protein breakdown; active management of dietary Phe intake while receiving therapy is required to ensure adequate Phe control and nutritional balance; monitor blood Phe levels during treatment to ensure adequate blood Phe level control; frequent blood monitoring is recommended in pediatric population

                Hypersensitivity reactions including anaphylaxis and rash have occurred

                Caution in renal and hepatic impairment

                Patients that show no improvement after treating at 20 mg/kg/day for 1 month are considered nonresponders; response to treatment cannot be pre-determined by laboratory testing (eg, molecular testing), and can only be determined by therapeutic trial

                Some patients with PKU do not show biochemical response (reduction in blood Phe) with treatment; in two clinical trials at a dose of 20 mg/kg per day, 56% to 75% of pediatric PKU patients showed a biochemical response to therapy, and in one clinical trial at a dose of 10 mg/kg per day, 20% of adult and pediatric PKU patients showed a biochemical response to drug

                Hyperactivity behavior reported (rare)

                Gastrointestinal (GI) adverse reactions suggestive of upper GI mucosal inflammation reported with therapy; serious adverse reactions included esophagitis and gastritis; if left untreated, these could lead to severe sequelae including esophageal stricture, esophageal ulcer, gastric ulcer, and bleeding and such complications have been reported in patients receiving therapy; monitor patients for signs and symptoms of upper GI mucosal inflammation

                Drug interaction overview

                • Caution in coadministration of medications known to inhibit folate metabolism (eg, methotrexate), PDE-5 inhibitors, or levodopa
                • Monitor patients for hypotension when coadministering drug with medications known to affect nitric oxide-mediated vasorelaxation
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                Pregnancy & Lactation

                Pregnancy

                A patient registry has been established that collects data on women who are treated during pregnancy; for information regarding registry program call 1-800-983-4587

                There are no adequate and well-controlled studies in pregnant women; therapy should be administered during pregnancy only if potential benefit justifies potential risk to fetus

                Available data from maternal Phenylketonuria Collaborative Study in PKU-affected women demonstrated that uncontrolled Phe levels above 600 micromol/L are associated with a very high incidence of neurological, cardiac, facial dysmorphism, and growth anomalies; blood phenylalanine concentrations should be maintained between 120 and 360 micromol/L during pregnancy and during 3 months before conception to reduce incidence of Phe-induced teratogenic effects

                Animal data

                • An embryo-fetal development study in rats using oral doses up to 3 times maximum recommended human dose (MRHD) given during period of organogenesis showed no effects; in a rabbit study using oral administration of sapropterin dihydrochloride during period of organogenesis, a rare defect, holoprosencephaly, was noted at 10 times the MRHD

                Lactation

                Not known whether drug is present in human milk; it is present in milk of intravenously, but not orally, treated lactating rats; consider developmental and health benefits of human milk feeding along with mother’s clinical need for therapy and any potential adverse effects on human milk-fed child from drug or from underlying maternal condition; exercise caution when drug is administered to a nursing woman

                Pregnancy Categories

                A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                NA: Information not available.

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                Pharmacology

                Mechanism of Action

                Synthetic tetrahydrobiopterin (BH4), for phenylalanine hydroxylase (PAH); PAH hydroxylates Phe to form tyrosine; BH4 activates residual PAH enzyme, improving oxidative metabolism of Phe and thereby decreasing Phe blood levels

                Pharmacokinetics

                Half-Life: 7 hr; range: 3.9-17 hr

                Onset: 24 hr; up to 2 month (maximum effect)

                Peak Plasma Time: stable over 24-hr period

                Duration: 24 hr

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                Administration

                Oral Preparation

                Tablet

                • Tablets may be swallowed either as whole tablets or dissolved
                • Dissolve in 4-8 oz (120-240 mL) water or apple juice and take within 15 minutes of dissolution
                • To make the tablets dissolve faster, stir or crush them
                • Tablets may not dissolve completely; small tablet pieces may float on top of the water or apple juice, this is normal and safe to swallow
                • If after drinking the medicine, add more water or apple juice to glass and drink to ensure the entire dose is taken

                Powder for oral solution

                • Weight >10 kg
                  • Dissolve powder in 4-8 oz (120-240 mL) of water or apple juice and drink within 30 minutes of dissolution
                  • Alternatively, powder may be stirred in a small amount of soft foods (eg, apple sauce, pudding)
                • Infants weighing <10 kg
                  • Can be dissolved in as little as 5 mL of water or apple juice and a portion of this solution corresponding to a 10 mg/kg dose may be administered PO via an oral dosing syringe
                  • Administer within 30 minutes of dissolution

                Oral Administration

                Take with food

                Missed dose: Take missed dose as soon as possible, but do not take 2 doses on the same day

                Storage

                Tablets

                • Store at 20-25ºC (68-77ºF); excursions allowed between 15-30ºC (59-86ºF)
                • Keep container tightly closed
                • Protect from moisture

                Powder for oral solution

                • Store at 20-25ºC (68-77ºF); excursions allowed between 15-30ºC (59-86ºF)
                • Keep container tightly closed
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                Images

                BRAND FORM. UNIT PRICE PILL IMAGE
                sapropterin oral
                -
                100 mg tablet
                Kuvan oral
                -
                100 mg tablet
                Kuvan oral
                -
                100 mg powder

                Copyright © 2010 First DataBank, Inc.

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                Patient Handout

                Patient Education
                sapropterin oral

                SAPROPTERIN POWDER PACKET - ORAL

                (SAP-roe-TER-in)

                COMMON BRAND NAME(S): Kuvan

                USES: This medication is used along with diet changes for long-term treatment of a certain inherited disorder (phenylketonuria-PKU). It helps remove a certain chemical (phenylalanine) from the body. Too much phenylalanine in the body can cause brain damage.

                HOW TO USE: Read the Patient Information Leaflet and Instructions for Use if available from your pharmacist before you start taking sapropterin and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take this medication by mouth with a meal as directed by your doctor, usually once daily. The dosage is based on your medical condition, age, weight, lab tests, and response to treatment.Open the packet and pour its contents into 120 to 240 milliliters (4 to 8 ounces) of water or apple juice. Stir well until the powder dissolves completely (2 to 3 minutes). Drink all of the mixture within 30 minutes of mixing. You may also mix the powder in a small amount of soft food (such as apple sauce or pudding). Eat all of the mixture right away. Do not prepare a supply in advance.If the dose is less than a full packet, ask your doctor or pharmacist how much water or apple juice you should use to mix with the dose. Mix the entire contents of the packet in water or apple juice as directed by your doctor. Mix well and measure the dose using a special measuring device. Do not use a household spoon because you may not get the correct dose. Take the dose within 30 minutes of mixing. Discard any unused medication.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.Tell your doctor if you do not get better or if you get worse.

                SIDE EFFECTS: Runny/stuffy nose or sore throat may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: trouble swallowing, pain in the throat, stomach/abdominal pain that doesn't go away, nausea/vomiting that doesn't stop, black stools, blood in your vomit, signs of hyperactivity (such as not being able to sit still).A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

                PRECAUTIONS: Before taking sapropterin, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.

                DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

                OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

                NOTES: Do not share this medication with others.Lab and/or medical tests (such as phenylalanine blood levels) should be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.

                MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

                STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

                Information last revised December 2019. Copyright(c) 2021 First Databank, Inc.

                IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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                Formulary

                FormularyPatient Discounts

                Adding plans allows you to compare formulary status to other drugs in the same class.

                To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

                Adding plans allows you to:

                • View the formulary and any restrictions for each plan.
                • Manage and view all your plans together – even plans in different states.
                • Compare formulary status to other drugs in the same class.
                • Access your plan list on any device – mobile or desktop.

                The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
                PA Prior Authorization
                Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                QL Quantity Limits
                Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
                ST Step Therapy
                Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
                OR Other Restrictions
                Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.