Determining responsiveness to KUVAN

To determine if patients respond to KUVAN therapy, patients must not modify their existing dietary Phe intake during the evaluation period.¹

• Baseline blood Phe measurements should be taken just prior to initiation of a KUVAN response test

The recommended starting dose of KUVAN is 10 mg/kg/day taken once daily.¹

Response to therapy is determined by a change in blood Phe level following treatment with KUVAN at 10 mg/kg/day for a period of up to 1 month.¹

• Blood levels should be checked after 1 week of KUVAN treatment and periodically for up to 1 month

If blood Phe levels do not decrease from baseline at 10 mg/kg/day, the dose may be increased to 20 mg/kg/day.¹

• Patients whose blood Phe levels do not decrease from baseline after 1 month of treatment at 20 mg/kg/day are non-responders, and treatment with KUVAN should be discontinued in these patients

Adjusting the dose of KUVAN

Once responsiveness to KUVAN has been established, KUVAN dosage may be adjusted within the range of 5 to 20 mg/kg/day according to response to therapy. Doses above 20 mg/kg/day have not been evaluated in clinical trials.¹

After the dose of KUVAN is established, continued active management of dietary Phe intake using medical foods and natural sources of protein is required to ensure blood Phe control and adequate nutritional balance.¹

Doses above 20 mg/kg/day have not been evaluated in clinical trials.¹

• Use KUVAN in conjunction with continued active management of dietary Phe intake, using medical foods and natural sources of protein to ensure blood Phe control and adequate nutritional balance¹

Note that it is very important for patients to maintain their diet as usual during the trial period. Any fluctuation in diet can prevent the establishment of a clear response to KUVAN.¹

Not all patients respond well to KUVAN; however, for patients who do not experience a decrease in blood Phe after KUVAN administration, consider if illness, diet, change in use of medical food, or other factors affecting blood Phe levels may have affected the results, and note that the time to response varies across patients.¹ Always stress to patients that they must continue their Phe-restricted diet after KUVAN response has been established.¹

Greater decreases in blood Phe levels were seen with higher doses of KUVAN

In a Phase 3, multicenter, forced dose-titration, open-label extension study (N=80), patients aged 8–49 years who responded to KUVAN treatment received consecutive doses of KUVAN at 5, 20, and 10 mg/kg/day in 2-week intervals. Blood Phe level was monitored after 2 weeks of treatment at each dose level. Their usual diet was maintained throughout the study. The mean baseline Phe level was 844 μmol/L.¹

*Mean changes from baseline in blood Phe levels in 80 KUVAN-treated patients through Week 6 visit (PKU-004) forced-dose protocol (Week 0–Week 2, KUVAN 5 mg/kg/day;
Week 2–Week 4, KUVAN 20 mg/kg/day; and Week 4–Week 6, KUVAN 10 mg/kg/day). The mean baseline Phe level was 844 µmol/L.²⁶

KUVAN is convenient and easy to take

Each KUVAN Tablet contains 100 mg of sapropterin dihydrochloride.

Administration is once a day. KUVAN’s convenient, once-daily dosing involves dissolving the tablets in 4–8 oz of water or apple juice, which is particularly useful in small children.

KUVAN being mixed in apple juice