Thiola Ec Drug Information

THIOLA EC is indicated, in combination with high fluid intake, alkali, and diet modification, for the prevention of cystine stone formation in adults and pediatric patients 20 kg and greater with severe homozygous cystinuria, who are not responsive to these measures alone.

Recommended Dosage Adults

The recommended initial dosage in adult patients is 800 mg/day. In clinical studies, the average dosage 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. Administer THIOLA EC in 3 divided doses at the same times each day, with or without food. Maintain a routine pattern with regard to meals.

Consider starting THIOLA EC at a lower dosage in patients with history of severe toxicity to d-penicillamine.

Preparation and Administration Instructions

For patients who cannot swallow the tablet whole, THIOLA EC can be crushed and mixed with applesauce. Administration of THIOLA EC with other liquids or foods has not been studied and is not recommended. Preparation and Administration of THIOLA EC Mixed in Applesauce For patients who can swallow semi-solid food, THIOLA EC can be crushed and mixed with applesauce: Crush the THIOLA EC tablet in a clean pill crusher or mortar and pestle.

Always crush one tablet at a time. Measure approximately one tablespoon of applesauce and transfer it into a container with the crushed THIOLA EC tablet. Mix the crushed THIOLA EC tablet in the applesauce until the powder is well dispersed.

Administer the entire THIOLA EC-applesauce mixture to the patient’s mouth immediately. (However, if this is not possible, the mixture can be stored in a refrigerator for up to 2 hours after adding the crushed tablet to the applesauce. Discard any mixture that has not been given within 2 hours.) To assure that any leftover applesauce mixture from the container is recovered, add tap water to the same container, mix, and have the patient drink the water.

Monitoring

Measure urinary cystine 1 month after starting THIOLA EC and every 3 months thereafter. Adjust THIOLA EC dosage to maintain urinary cystine concentration less than 250 mg/L. Assess for proteinuria before treatment and every 3 to 6 months during treatment.

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.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of the drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Patients in group 1 had previously been treated with d-penicillamine; those in group 2 had not. In those without prior history of d-penicillamine treatment, 6% developed reactions of sufficient severity to require THIOLA withdrawal.

Table 1 presents adverse reactions ≥5% in either treatment group occurring in this trial. Taste Disturbance A reduction in taste perception may develop. It is believed to be the result of chelation of trace metals by tiopronin.

Hypogeusia is often self-limited.

Postmarketing Experience

Adverse reactions have been reported from the literature, as well as during post-approval use of THIOLA. Because the post-approval reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to THIOLA exposure. Adverse reactions reported during the postmarketing use of THIOLA are listed by body system in Table 2.

Alcohol Tiopronin is released faster from THIOLA EC in the presence of alcohol and the risk for adverse events associated with THIOLA EC when taken with alcohol is unknown. Avoid alcohol consumption 2 hours before and 3 hours after taking THIOLA EC.

Pregnancy Risk Summary Available published case report data with tiopronin have not identified a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Renal stones in pregnancy may result in adverse pregnancy outcomes (see Clinical Considerations ). In animal reproduction studies, there were no adverse developmental outcomes with oral administration of tiopronin to pregnant mice and rats during organogenesis at doses up to 2 times a 2 grams/day human dose (based on mg/m 2 ).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are respectively.

Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Renal stones in pregnancy may increase the risk of adverse pregnancy outcomes, such as preterm birth and low birth weight. Data Animal Data No findings of fetal malformations could be attributed to the drug in reproduction studies in mice and rats at doses up to 2 times the highest recommended human dose of 2 grams/day (based on mg/m 2 ).

Pediatric Use THIOLA EC is indicated in pediatric patients weighing 20 kg or more with severe homozygous cystinuria, in combination with high fluid intake, alkali, and diet modification, for the prevention of cystine stone formation who are not responsive to these measures alone. This indication is based on safety and efficacy data from a trial in patients 9 years to 68 years of age and clinical experience. Proteinuria, including nephrotic syndrome, has been reported in pediatric patients.

Pediatric patients receiving greater than 50 mg/kg tiopronin per day may be at greater risk. THIOLA EC tablets are not approved for use in pediatric patients weighing less than 20 kg.

THIOLA EC is contraindicated in patients with hypersensitivity to tiopronin or any other components of THIOLA EC. Hypersensitivity to tiopronin or any component of THIOLA EC

There is no information on overdosage with tiopronin.