IOLA EC is indicated, in combination with high fluid intake, alkali, and diet modification, for the prevention ofcystine stone formation in adults and pediatric patients 20 kg and greater with severe homozygous cystinuria,who are not responsive to these measures alone.
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosage
Adults: The recommended initial dosage in adult patients is 800 mg/day. In clinical studies, the averagedosage was about 1,000 mg/day.
Pediatrics: The recommended initial dosage in pediatric patients weighing 20 kg and greater is 15 mg/kg/day.
Avoid dosages greater than 50 mg/kg per day in pediatric patients [see Warnings and Precautions (5.1),
Pediatric Use (8.4)].
Administer THIOLA EC in 3 divided doses at the same times each day, with or without food. Maintain a routinepattern with regard to meals. Swallow THIOLA EC tablets whole.
Consider starting THIOLA EC at a lower dosage in patients with history of severe toxicity to d-penicillamine.
2.2 Monitoring
Measure urinary cystine 1 month after starting THIOLA EC and every 3 months thereafter. Adjust THIOLA ECdosage to maintain urinary cystine concentration less than 250 mg/L.
Assess for proteinuria before treatment and every 3 to 6 months during treatment [see Warnings andPrecautions (5.1)].
Discontinue THIOLA EC in patients who develop proteinuria, and monitor urinary protein and renal function.
Consider restarting THIOLA EC treatment at a lower dosage after resolution of proteinuria.
3 DOSAGE FORMS AND STRENGTHS
Tablets for oral use:
100 mg tablets: round, white to off-white and imprinted in red with “T1” on one side
300 mg tablets: round, white to off-white and imprinted in red with “T3” on one side
4 CONTRAINDICATIONS
THIOLA EC is contraindicated in patients with hypersensitivity to tiopronin or any other components of THIOLAEC [see Warnings and Precautions (5.2)].
5 WARNINGS AND PRECAUTIONS
5.1 Proteinuria
Proteinuria, including nephrotic syndrome, and membranous nephropathy, have been reported with tioproninuse. Pediatric patients receiving greater than 50 mg/kg of tiopronin per day may be at increased risk forproteinuria. [see Dosage and Administration (2.2), Adverse Reactions (6.1, 6.2) Pediatric Use (8.4)]. Monitor
patients for the development of proteinuria and discontinue therapy in patients who develop proteinuria [seeDosage and Administration (2.2)].
5.2 Hypersensitivity Reactions
Hypersensitivity reactions (drug fever, rash, fever, arthralgia and lymphadenopathy) have been reported [seeContraindications (4)].
6 ADVERSE REACTIONS
The following adverse reactions are discussed in greater detail in other sections of the labeling:
• Proteinuria [see Warnings and Precautions (5.1)]
• Hypersensitivity [see Warnings and Precautions (5.2)]
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed inthe clinical trials of the drug cannot be directly compared to rates in the clinical trials of another drug and maynot reflect the rates observed in practice.
Adverse reactions occurring at an incidence of ≥5% in an uncontrolled trial in 66 patients with cystinuriaage 9 to 68 years are shown in the table below. Patients in group 1 had previously been treated withd-penicillamine; those in group 2 had not. Of those patients who had stopped taking d-penicillamine due to
toxicity (34 out of 49 patie |
