Sapropterin

INTRODUCTION

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 hydroxylase (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.

Adverse Reactions/Side Effects

CNS: headache. EENT: pharyngolaryngeal pain. GI: abdominal pain, diarrhea, nausea, vomiting. Hemat: neutropenia.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Assess any pain in the laryngeal or pharyngeal areas. Report severe or prolonged pharyngeal or laryngeal pain.

• Monitor signs of neutropenia, including fever, sore throat, and signs of infection. Report these signs to the physician.

Patient/Client-Related Instruction

• Instruct patient to report other bothersome side effects such as severe or prolonged headache or GI problems (nausea, vomiting, diarrhea, abdominal pain).

Pharmacokinetics

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

Distribution: Unknown.

Metabolism and Excretion: Unknown.

Half-life: 6.7 hr.

Contraindications/Precautions

Contraindicated in: Lactation: Should not be used if breast-feeding.

Use Cautiously in: Hepatic or renal impairment; Concurrent use of levodopa; OB: Use during pregnancy only if clearly needed; Pedi: Safety and effectiveness in children <4 yr not established.

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

Route/Dosage

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

Availability

Tablets: 100 mg.