Alcohol
Tiopronin is released faster from THIOLA EC in the presence of alcohol and the risk for adverse eventsassociated with THIOLA EC when taken with alcohol is unknown. Avoid alcohol consumption 2 hours beforeand 3 hours after taking THIOLA EC [see Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Available published case report data with tiopronin have not identified a drug-associated risk for major birthdefects, miscarriage, or adverse maternal or fetal outcomes. Renal stones in pregnancy may result in adversepregnancy 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 organogenesisat doses up to 2 times a 2 grams/day human dose (based on mg/m2). The estimated background risk of major
birth defects and miscarriage for the indicated population is unknown. All pregnancies have a backgroundrisk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated backgroundrisk of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to
20%, 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 andlow birth weight.
Data
Animal Data
No findings of fetal malformations could be attributed to the drug in reproduction studies in mice and rats atdoses up to 2 times the highest recommended human dose of 2 grams/day (based on mg/m2).
8.2 Lactation
Risk Summary
There are no data on the presence of tiopronin in either human or animal milk or on the effects of thebreastfed child. A published study suggests that tiopronin may suppress milk production. Because of thepotential for serious adverse reactions, including nephrotic syndrome, advise patients that breastfeeding is notrecommended during treatment with THIOLA EC.
8.4 Pediatric Use
THIOLA EC is indicated in pediatric patients weighing 20 kg or more with severe homozygous cystinuria, incombination with high fluid intake, alkali, and diet modification, for the prevention of cystine stone formationwho 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 daymay be at greater risk [see Dosage and Administration (2.1, 2.2), Warnings and Precautions (5.1) and Adverse
Reactions (6.1)].
THIOLA EC tablets are not approved for use in pediatric patients weighing less than 20 kg or in pediatricpatients unable to swallow tablets [see Recommended Dosage (2.1)].
8.5 Geriatric Use
This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drugmay be greater in patients with impaired renal function. Because elderly patients are more likely to havedecreased renal function, care should be taken in dose selection, and it may be useful to monitor renalfunction.
10 OVERDOSAGE
There is no information on overdosage with tiopronin.
11 DESCRIPTION
THIOLA EC (tiopronin) delayed-release tablets are a reducing and cystine-binding thiol drug (CBTD) for oraluse. Tiopronin is N-(2-Mercaptopropionyl) gly |
