Sapropterin

Sapropterin is a prescription medication used for the treatment of hyperphenylalaninemia caused by tetrahydrobiopterin responsive phenylketonuria.

• Sapropterin is available under the following different brand names: Kuvan

Common side effects of sapropterin include:

• nausea
• vomiting
• stomach pain
• diarrhea
• runny or stuffy nose
• cough
• headache
• flushing
• agitation
• fidgeting
• dizziness
• joint pain

Serious side effects of sapropterin include:

• seizures
• exacerbation of seizures
• dizziness
• gastrointestinal bleeding
• post-procedural bleeding
• headache
• irritability
• myocardial infarction
• overstimulation
• respiratory failure

Rare side effects of sapropterin include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Tablet

• 100 mg

Powder for oral solution

• 100 mg/packet

Hyperphenylalaninemia

Adult dosage 

• 10 mg/kg orally every day initially with food; response to therapy is determined by change in blood phenylalanine (Phe) following treatment at 10 mg/kg/day for up to 1 month; blood Phe levels should be checked after 1 week 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 is established, dosage may be adjusted within the range of 5-20 mg/kg/day according to response to therapy; periodic blood Phe monitoring is recommended to assess blood Phe control

Pediatric dosage

• Children aged 1 month to 6 years: Recommended starting dose is 10 mg/kg taken once daily
• Children aged 7 years and more: 10 mg/kg orally every day 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 week 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 is established, dosage may be adjusted within the 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 less than 7 years who are treated with doses of 20 mg/kg/day are at increased risk for low levels of blood Phe

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Sapropterin has severe interactions with no other drugs.
• Sapropterin has serious interactions with no other drugs.
• Sapropterin has moderate interactions with the following drugs:
  • avanafil
  • betrixaban
  • levodopa
  • methotrexate
  • tadalafil
• Sapropterin has minor interactions with the following drugs:
  • pyrimethamine
  • sildenafil
  • vardenafil

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical adviceor if you have health questions, , or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Sapropterin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Sapropterin?”

Cautions

• Do not discontinue ongoing Phe-restricted diet; treat all patients with a Phe-restricted diet
• Children aged less than 7 years treated with 20 mg/kg/day are at increased risk for low levels of blood Phe compared with patients aged 7 years or more.
• Treatment should be directed by physicians knowledgeable in the management of phenylketonuria (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 for the pediatric population
• Hypersensitivity reactions including anaphylaxis and rash have occurred
• Caution in renal and hepatic impairment
• Patients that show no improvement after treatment with sapropterin at 20 mg/kg/day for 1 month are considered non-responders; response to treatment cannot be predetermined 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 patients with PKU 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 patients with PKU showed a biochemical response to the 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 (such complications have been reported in the patients receiving therapy); monitor patients for signs and symptoms of upper GI mucosal inflammation
• Drug interaction overview
  • Caution in the coadministration of medications known to inhibit folate metabolism (eg, methotrexate), PDE-5 inhibitors, or levodopa
  • Monitor patients for hypotension when coadministering sapropterin with medications known to affect nitric oxide-mediated vasorelaxation

Pregnancy and Lactation

• A patient registry has been established that collects data on women who are treated during pregnancy; for information regarding the 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 the potential benefits justify the potential risks to the fetus
• Available data from the 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 Phe concentrations should be maintained between 120 and 360 micromol/L during pregnancy and during 3 months before conception to reduce the incidence of Phe-induced teratogenic effects
• Lactation
  • Not known whether the drug is present in human milk; it is present in the milk of lactating following intravenous administration but not following oral administration; consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed child from the drug or any underlying maternal condition; exercise caution while administering the drug to a nursing woman