sapropterin

(sa-prop-te-rin) sapropterin,

Kuvan

(trade name)

Classification

Therapeutic: antihyperphenylalaninemics
Pharmacologic: synthetic bh4
Pregnancy Category: C

Indications

To reduce phenylalanine (Phe) levels in patients with hyperphenylalaninemia (HPA) caused by tetrahydrobiopterin-(BH4–) responsive phenylketonuria (PKU); used with a Phe-restricted diet.

Action

Acts as a synthetic form of the cofactor (BH4) for the enzyme phenylalanine hydoxylase (PAH). PAH converts phenylalanine to tyrosine. In PKU patients, activity of PAH is deficient. BH4 helps to activate PAH and thus reduce Phe levels.

Therapeutic effects

Preservation of brain function by lowering Phe levels.

Pharmacokinetics

Absorption: Well absorbed following oral administration; food increases absorption.Distribution: Unknown.Metabolism and Excretion: Unknown.Half-life: 6.7 hr.

Time/action profile (effect on Phe levels)

ROUTE	ONSET	PEAK	DURATION
PO	within 24 hr	up to one mo	unknown

Contraindications/Precautions

Contraindicated in: Lactation: Should not be used if breast feeding.Use Cautiously in: Hepatic or renal impairment; Concurrent use of levodopa; Obstetric: Use during pregnancy only if clearly needed; Pediatric: Safety and effectiveness in children <4 yr not established.

Adverse Reactions/Side Effects

Central nervous system

headache

Ear, Eye, Nose, Throat

pharyngolaryngeal pain

Gastrointestinal

abdominal pain
diarrhea
nausea
vomiting

Hematologic

neutropenia

Interactions

Drug-Drug interaction

Concurrent use of medications known to inhibit folate metabolism including methotrexate can ↓ BH4 levels; use cautiously.Concurrent use of medications known to affect nitric oxide-mediated vasorelaxation including sildenafil, vardenafil , or tadaloafil could ↑ risk of hypotension.Concurrent use of levodopa may ↑ risk of seizures, over-stimulation and irritatibility; use cautiously.

Route/Dosage

Oral (Adults) 10 mg/kg once daily, titrated on the basis of Phe levels (range 5–20mg/kg/day).

Availability

Tablets: 100 mg

Nursing implications

Nursing assessment

Assess diet prior to and during therapy. Provide nutritional counseling. All patients with PKU should maintain a Phe-restricted diet. During dose titration, dietary Phe intake must remain stable to determine effectiveness of sapropterin.
Monitor for signs of allergic reaction (rash).
Lab Test Considerations: Monitor blood Phe levels after 1 wk of treatment and periodically for up to 1 mo. If blood Phe does not decrease from baseline at 10 mg/kg/day dose after 1 wk, may increase to 20 mg/kg/day. Patients whose blood Phe does not decrease within 1 mo of treatment with 20 mg/kg/day dose are considered non-responders and therapy should be discontinued. Prolonged elevations of Phe in patients with PKU can result in neurologic damage including mental retardation, microcephaly, delayed speech, seizures, and behavioral abnormalities. Prolonged levels that are too low can cause catabolism and protein breakdown.

Potential Nursing Diagnoses

Imbalanced nutrition: more than body requirements (Indications)
Deficient knowledge, related to diet and medication regimen (Patient/Family Teaching)

Implementation

Oral: Administer with food to increase absorption. Dissolve tablets in 4–8 oz of water or apple juice and administer within 15 min of dissolution. Tablets may take several minutes to dissolve; stirring or crushing tablets may make dissolution faster. Small pieces floating on top of water or apple juice are normal and safe for patients to swallow. If small pieces remain in glass after drinking medicine, add more water or apple juice to make sure complete dose is administered. Protect tablets from moisture, do not remove dessicant packet. Color of tablets may change over time to light yellow; this is normal and tablets are safe. Do not use tablets that have expired.

Patient/Family Teaching

Instruct patient to take saropterin as directed at the same time each day. Take missed doses as soon as remembered that day; do not take 2 doses in the same day, omit dose if remembered next day. Instruct patient to read the Patient Information guide prior to taking sapropterin and with each Rx refill, in case of new information.
Advise patient to avoid making changes to dietary PhE without consulting health care professional; any dietary changes may affect Phe level.
Instruct patient to notify health care professional if fever or illness occurs; dose may need to be adjusted.
Advise patient to consult health care professional prior to taking other Rx, OTC, or herbal products.
Advise female patients to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

Reduction of Phe levels.