sapropterin

Absorption: Well absorbed following oral administration; food ↑ absorption.

Distribution: Unknown.

Metabolism/Excretion: Unknown.

Half-Life: 6.7 hr.

Time/Action Profile ⬆ ⬇

(effect on Phe levels)

ROUTE	ONSET	PEAK	DURATION
PO	within 24 hr	up to 1 mo	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Lactation: Lactation.

Use Cautiously in:

Hepatic or renal impairment;
Concurrent use of levodopa;
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Children <4 yr (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash

EENT: pharyngolaryngeal pain, rhinitis

GI: abdominal pain, diarrhea, esophagitis, gastritis, nausea, vomiting

Hemat: neutropenia

Neuro: headache, hyperactivity

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Interactions ⬆ ⬇

Drug-drug:

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 avanafil, sildenafil, vardenafil , or tadalafil could ↑ risk of hypotension.
Concurrent use of levodopa may ↑ risk of seizures, over-stimulation and irritability; use cautiously.

Route/Dosage ⬆ ⬇

PO (Adults and Children ≥7 yr): 10–20 mg/kg once daily, titrated on the basis of Phe levels (range 5–20 mg/kg/day).
PO (Children 1 mo-6 yr): 10 mg/kg once daily, titrated on the basis of Phe levels (range 5–20 mg/kg/day).

Availability ⬆ ⬇

(Generic available)

Powder for oral solution: 100 mg/pkt; 500 mg/pkt
Tablets: 100 mg

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 and symptoms of upper gastrointestinal mucosal inflammation (esophagitis, gastritis, oropharyngeal pain, pharyngitis, esophageal pain, abdominal pain, dyspepsia, nausea, vomiting) during therapy. May lead to severe sequelae (esophageal stricture, esophageal ulcer, gastric ulcer, bleeding).
Monitor for signs of allergic reaction (wheezing, dyspnea, coughing, hypotension, flushing, nausea, rash). Discontinue therapy and initiate symptomatic therapy.

Lab Test Considerations:

Monitor blood Phe levels after 1 wk of treatment and periodically for up to 1 mo. If blood Phe does not ↓ from baseline at 10 mg/kg/day dose after 1 wk, may ↑ to 20 mg/kg/day. Patients whose blood Phe does not ↓ 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.

Implementation ⬆ ⬇

PO: Administer with food to increase absorption. Swallow tablets whole or dissolve 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 desiccant 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.
- Dissolve powder for oral solution in 4 to 8 oz. (120 240 mL) of water or apple juice and consume within 30 minutes. Powder should dissolve rapidly and completely; powder is off-white to yellow in color.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take sapropterin 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.
Advise patient to notify health care professional if signs and symptoms of gastritis (severe upper stomach-area (abdominal) discomfort or pain, nausea, vomiting, blood in vomit or stool, black, tarry stools) or hyperactivity (fidgeting, moving around too much, talking too much) occur.
Instruct patient to notify health care professional if fever or illness occurs; dose may need to be adjusted.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. To reduce risk of hyperphenylalaninemia-induced fetal adverse effects, maintain blood phenylalanine concentrations between 120 and 360 micromol/L during pregnancy and during the 3 mo before conception. Advise women who become pregnant while taking sapropterin to enroll in Pregnancy Registry to monitor pregnancy outcomes. For more information about the registry program call 1-800-983-4587.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇