SIDE EFFECTS

Clinical Trials Experience in PKU

In clinical trials, Kuvan (saproterin dihydrochloride tablets) has been administered to 579 patients with PKU in doses ranging from 5 to 20 mg/kg/day for lengths of treatment ranging from 1 to 30 weeks. Patients were aged 4 to 49 years old. The patient population was nearly evenly distributed in gender, and approximately 95% of patients were Caucasian.

The most serious adverse reactions during Kuvan (saproterin dihydrochloride tablets) administration (regardless of relationship to treatment) were gastritis, spinal cord injury, streptococcal infection, testicular carcinoma, and urinary tract infection. Mild to moderate neutropenia was noted during Kuvan (saproterin dihydrochloride tablets) administration in 24 of 579 patients (4%). The most common ( ≥ 4% of patients treated with Kuvan (saproterin dihydrochloride tablets) ) across all studies (n=579) were headache, diarrhea, abdominal pain, upper respiratory tract infection, pharyngolaryngeal pain, vomiting, and nausea.

The data described below reflect exposure of 74 patients with PKU to Kuvan (saproterin dihydrochloride tablets) at doses of 10 to 20 mg/kg/day for 6 to 10 weeks in 2 double-blind, placebo-controlled clinical trials. The overall incidence of adverse reactions in patients receiving Kuvan (saproterin dihydrochloride tablets) was similar to that reported with patients receiving placebo.

Because clinical trials were conducted under varying conditions, the observed adverse reaction rates may not predict the rates observed in patients in clinical practice. Table 1 enumerates treatment-emergent adverse reactions (regardless of relationship) that occurred in at least 4% of patients treated with Kuvan (saproterin dihydrochloride tablets) in the double-blind, placebo-controlled clinical trials described above. Reported frequency of adverse reactions was classified by MedDRA terms (Table 1).

Table 1: Summary of Adverse Reactions by Preferred Term Occurring in ≥ 4% of Patients in Controlled Clinical Studies With Kuvan (saproterin dihydrochloride tablets)

In open-label, uncontrolled clinical trials in which all patients received Kuvan (saproterin dihydrochloride tablets) in doses of 5 to 20 mg/kg/day, adverse reactions were similar in type and frequency to those reported in the double-blind, placebo-controlled clinical trials.

Safety Experience From Clinical Studies for Non-PKU Indications

Approximately 800 healthy volunteers and patients with disorders other than PKU, some of whom had underlying neurologic disorders or cardiovascular disease, have been administered a different formulation of the same active ingredient (sapropterin) in approximately 19 controlled and uncontrolled clinical trials. In these clinical trials, subjects were administered sapropterin at doses ranging from 1 to 20 mg/kg/day for lengths of exposure from 1 day to 2 years. Serious and severe adverse reactions (regardless of relationship) during sapropterin administration were convulsions, exacerbation of convulsions [see Warnings and PRECAUTIONS], dizziness, gastrointestinal bleeding, post-procedural bleeding, headache, irritability, myocardial infarction, overstimulation, and respiratory failure. Common adverse reactions were headache, peripheral edema, arthralgia, polyuria, agitation, dizziness, and upper respiratory tract infection.

Post-Marketing Experience

The following adverse reactions have been identified during a 10-year post-approval safety surveillance program in Japan of another formulation of the same active ingredient (sapropterin). This safety surveillance program was conducted in 30 patients, 27 of whom had disorders other than PKU and had an underlying neurologic condition. The most common adverse reactions were convulsions and exacerbation of convulsions in 3 of the non-PKU patients [see Warnings and PRECAUTIONS], and increased gamma-glutamyltransferase (GGT) in 2 of the non-PKU patients.

Read the entire FDA prescribing information for Kuvan (Saproterin Dihydrochloride Tablets) »