Cognitive problems may develop in patients following a
Phe-restricted diet but who have elevated Phe

Multiple Studies Show Cognitive Risk Due to Elevated Phe

In addition to elevated Phe, variability in Phe levels can significantly impact cognitive function

  • In a recent study of 46 children with PKU (mean age 7.5 years) who were managed early and continuously to maintain levels in the recommended 120–360 μmol/L range, the impact of fluctuations in Phe control was evaluated13
    • Mean lifetime blood Phe was 312 ± 132 (126–852) μmol/L, and mean standard deviation in blood Phe was 181.8 ± 72 (96–336) μmol/L
    • The correlation between mean lifetime blood Phe and IQ in this study was not significant (P=0.34), but the correlation between deviation in blood Phe and IQ was (P=0.04)
  • Results suggest that stability of blood Phe may be important to cognitive function in continuously managed patients13

Improving Phe control can improve cognitive function in PKU patients

  • In a study of 19 early managed adult PKU patients with Phe levels above target (mean 1320 μmol/L), 4–5 weeks of more strict Phe control (mean 630 μmol/L)20
    • Significantly improved sustained attention
    • Significantly improved reaction time
  • This study showed a partial reversibility in some cognitive measures that were affected by elevated Phe20

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.

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