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

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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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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            Formulary

            FormularyPatient Discounts

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            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.
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            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.