Elevated blood Phe levels can have devastating effects on PKU patients

  • Elevated Phe levels are neurotoxic and can lead to mild to severe consequences.8-10,12,14,17-19

Even mild Phe elevations can impact PKU patients

  • Mild elevations in Phe can be associated with declines in brain functioning5
    • Each 100-μmol/L increase in lifetime Phe predicted an average 1.9- to 4.1-point drop in IQ*


*Results from a systematic review and meta-analysis of 40 studies in PKU patients, over a range of blood Phe from 394 to 666 μmol/L. Lifetime Phe level was defined as the mean of 6- or 12-month median assessments for each patient from birth to the last measurement in each study.5

Recommended blood Phe levels can span a wide range and are higher than normal levels

  • The NIH Consensus Conference recommends blood Phe levels from 120 to 360 μmol/L for patients ≤12 years of age, and blood Phe levels from 120 to 900 μmol/L for patients >12 years of age19
    • Based on the lack of information on Phe levels and brain function after 12 years of age, the NIH Consensus Conference strongly encourages even lower Phe levels (from 120 to 600 μmol/L) during adolescence


*Normal values for adults: 58±15 μmol/L; for adolescents (mean age 16 years): 60±13 μmol/L; for children (mean age 8 years): 62±18 μmol/L.4

Long-term studies of neurocognitive outcomes with KUVAN treatment have not been conducted. BioMarin is implementing a trial to evaluate long-term neurocognitive outcomes in PKU patients treated with KUVAN.

Indication

KUVAN® (sapropterin dihydrochloride) Tablets is indicated to reduce blood phenylalanine (Phe) levels in patients with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU). KUVAN is to be used in conjunction with a Phe-restricted diet.

Important Safety Information

Prolonged exposure to elevated blood Phe levels in PKU patients can result in severe neurologic damage. The initiation of KUVAN therapy does not eliminate the need for careful monitoring of blood Phe levels and ongoing dietary management.

Some patients receiving KUVAN can experience significant drops in blood Phe levels. Patients should be monitored closely to ensure that blood Phe levels do not fall too low.

Not all patients with PKU respond to treatment with KUVAN. Response to treatment can only be determined by a therapeutic trial of KUVAN.

KUVAN has not been studied in patients with liver or renal impairment. Patients who have these conditions should be carefully monitored when receiving KUVAN. Caution should be used with the administration of KUVAN to patients who are receiving levodopa and drugs that affect nitric oxide–mediated vasorelaxation or folate metabolism.

The most serious adverse reactions reported during KUVAN administration (regardless of relationship to treatment) were gastritis, spinal cord injury, streptococcal infection, testicular carcinoma, and urinary tract infection. Mild to moderate neutropenia was also noted. The most common adverse reactions were headache, diarrhea, abdominal pain, upper respiratory tract infection, pharyngolaryngeal pain, vomiting, and nausea.

Please read the full Prescribing Information by clicking here.

BIOMARIN