About Syprine®
Syprine® (Trientine Hydrochloride) is a chelating compound for removal of excess copper from the body. In renal clearance studies, the urinary execretion rates of cooper demonstrated that Syprine® is effective as a cupriuretic agent in patients with Wilson’s disease. Clinical experience with Syprine is limited.1
Indications and usage
Syprine® is indicated in the treatment of patients with Wilson’s disease who are intolerant of penicillamine.1
Clinical summary of pivotal studies
Study 1
Forty-one patients between the ages of 6 and 54 who had a diagnosis of Wilson’s disease, and were intolerant of penicillamine, were treated with Syprine®. The dosage varied from 450 to 2400 mg per day. The mean duration of therapy was 48.7 months.
Of the 41 patients, 34 improved. Of the remaining patients, four had no change in clinical global response, two were lost to follow-up, and one showed deterioration in clinical condition. One of the patients who improved while on therapy with Syprine® had a recurrence of the symptoms of systemic lupus erythematosus, which had appeared originally during therapy with penicillamine. No other adverse reactions, except iron deficiency, were noted among any of these 41 patients.1
Study 2
Thirteen patients were treated with Syprine® following their development of intolerance to penicillamine. Retrospectively, these patients were compared to a separate group of 12 patients with Wilson’s disease who were both tolerant of and controlled with penicillamine, but who failed to continue any copper chelation therapy.
In the 13 patients treated with Syprine®, previous signs and symptoms relating to penicillamine intolerance disappeared in eight patients, improved in four, and were unchanged in one. Overall, neurological status in the treated group was better, and Kayser-Fleischer rings improved significantly. In terms of clinical outcome, all treated patients were alive at the data cutoff date, while 9 of the 12 untreated patients died of hepatic disease. Mean duration of therapy was 4.1 years, mean duration for patients without therapy was 2.7 years.1
Dosing considerations
Syprine® is available as 250 mg capsules for oral administration. Systematic evaluation of dose and/or interval between dose has not been done. However, the recommended initial dose is 500-700 mg/day for pediatric patients and 750-1250 mg/day for adults given in divided doses two, three, or four times daily. This may be increased to a maximum of 2000 mg/day for adults or 1500 mg/day for pediatric patients age 12 or under. The daily dose of Syprine® should be increased only when the clinical response is not adequate or the concentration of free serum copper is persistently above 20 mcg/dcL.
Syprine® should be given on an empty stomach, at least one hour before meals or two hours after meals and at least one hour apart from any other drug, food, or milk.1
Indications and Usage
SYPRINE is indicated in the treatment of patients with Wilson's disease who are intolerant of penicillamine. Clinical experience with SYPRINE is limited and alternate dosing regimens have not been well-characterized; all endpoints in determining an individual patient's dose have not been well defined. SYPRINE and penicillamine cannot be considered interchangeable. SYPRINE should be used when continued treatment with penicillamine is no longer possible because of intolerable or life endangering side effects.
Unlike penicillamine, SYPRINE is not recommended in cystinuria or rheumatoid arthritis. The absence of a sulfhydryl moiety renders it incapable of binding cystine and, therefore, it is of no use in cystinuria. In 15 patients with rheumatoid arthritis, SYPRINE was reported not to be effective in improving any clinical or biochemical parameter after 12 weeks of treatment. SYPRINE is not indicated for treatment of biliary cirrhosis.
Important Safety Information
SYPRINE® is contraindicated in patients hypersensitive to SYPRINE, or any components of the formulation. Patients should be observed closely for signs of possible hypersensitivity. Patients receiving SYPRINE should remain under regular medical supervision throughout the period of drug administration. Patients (especially women) should be closely monitored for evidence of iron deficiency anemia. Clinical experience is limited.
SYPRINE must be taken on an empty stomach, at least one hour before meals or two hours after meals and at least one hour apart from any other drug, food, or milk. The capsules should be swallowed whole with water and should not be opened or chewed.
For the first month of treatment, the patient should have his temperature taken nightly, and report any symptom such as fever or skin eruption.
The following adverse reactions have been reported from a clinical study: iron deficiency and systemic lupus erythematosus. In addition, dystonia, muscular spasm and myasthenia gravis have been reported in marketed use.
In general, mineral supplements should not be given since they may block the absorption of SYPRINE.
You are encouraged to report negative side effects of prescription drugs to FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.
Reference: 1. Syprine package insert. Lawrenceville, NJ: Aton Pharma; 2007.
