Sapropterin is a prescription medication used to manage certain metabolic conditions. It is a synthetic form of tetrahydrobiopterin (BH4), a substance that occurs naturally in the human body. This medication is designed to supplement or enhance the body’s metabolic processes. Its purpose is to address specific biochemical imbalances by supporting enzyme function.
Mechanism of Action
Sapropterin acts as a synthetic counterpart to tetrahydrobiopterin (BH4). BH4 functions as a cofactor for the phenylalanine hydroxylase (PAH) enzyme. This enzyme converts phenylalanine into tyrosine. This conversion is important because high phenylalanine levels can be detrimental to the brain and other organs.
In individuals with phenylketonuria (PKU), mutations in the PAH gene result in PAH enzyme deficiency or dysfunction. This leads to elevated phenylalanine levels in the blood and brain. Sapropterin provides an external source of BH4, which enhances the remaining activity of the faulty PAH enzyme in patients who still have some functional enzyme present. By boosting PAH activity, sapropterin helps to lower phenylalanine levels, mitigating the accumulation of this amino acid.
Use in Phenylketonuria (PKU)
Sapropterin is used to reduce high phenylalanine levels in patients with a type of phenylketonuria (PKU) that responds to this treatment. The aim is to decrease toxic phenylalanine concentrations in the blood, which can lead to neurological damage and cognitive impairments. Not all individuals with PKU will respond to sapropterin, especially those with severe genetic mutations that cause a complete loss of PAH enzyme activity.
Determining responsiveness involves a trial period where patients receive sapropterin to see if their blood phenylalanine levels decrease significantly. For neonates, a 24-hour sapropterin loading test is recommended; responsiveness is defined as a decrease in blood phenylalanine of 30% or more. For older children, adolescents, and adults, a trial of 48 hours to 7 days, or even 4 weeks, may be necessary to assess a reduction in blood phenylalanine or an improved tolerance to dietary phenylalanine. Sapropterin is often used in conjunction with a phenylalanine-restricted diet and does not eliminate its need. For responsive patients, it may allow for some liberalization of dietary phenylalanine intake compared to those relying solely on diet.
Administration and Dosage
Sapropterin is available as tablets and as a powder for oral solution. The medication should be dissolved in water or apple juice and taken with a meal for improved absorption. Tablets can be swallowed whole or dissolved in 4 to 8 ounces (120-240 mL) of liquid, consumed within 15 minutes. Tablets may be stirred or crushed for faster dissolution; small pieces floating are normal and safe to swallow.
The powder for oral solution should be dissolved in 4 to 8 ounces (120-240 mL) of water or apple juice and consumed within 30 minutes. Both forms can also be mixed into a small amount of soft food, such as applesauce or pudding. Dosage is individualized based on body weight and determined by a physician. For patients aged 7 years and older, the starting dose ranges from 10 to 20 milligrams per kilogram of body weight daily, while children 1 month to 6 years begin with 10 mg/kg daily. Regular monitoring of blood phenylalanine levels is necessary to assess response and adjust the dose, within a range of 5 to 20 mg/kg per day.
Potential Side Effects
Sapropterin can cause side effects. Common side effects include headache, runny or stuffy nose, and sore throat. Patients may also experience gastrointestinal symptoms such as diarrhea, nausea, vomiting, and stomach pain. These reactions are mild and may decrease as the body adjusts to treatment.
Less common but more serious side effects can occur, necessitating immediate medical attention. These include signs of an allergic reaction, such as rash, itching, swelling of the face, tongue, or throat, severe dizziness, or difficulty breathing. Inflammation of the esophagus or stomach (esophagitis or gastritis) has also been reported. This can manifest as burning in the chest or stomach, heartburn, or trouble swallowing. Patients should report any concerning or persistent symptoms to their healthcare provider.