Thiola (US)Prevention of cystine (kidney) stone formation in pts with severe homozygous cystinuria (urinary cystine >500mg/day), who are resistant to treatment with conservative measures of high fluid intake, alkali and diet modification, or who have adverse reactions to d-penicillamine
New molecular entity
Development and Regulatory status
Jul 19Launched in the US. Available as 100mg and 300mg tablets .
Jul 19US FDA approved Thiola EC (tiopronin) delayed-release tablets in combination with high fluid intake, alkali, and diet modification, for the prevention of cystine stone formation in adults and pediatric pts 20 kg and greater with severe homozygous cystinuria, who are not responsive to these measures alone. [3,4]
Nov 18US FDA accepted for review the New Drug Application (NDA) for a new formulation of tiopronin for treatment of cystinuria with target action date of 30 June 2019 .
Chelating agent - binds to cystine to form a soluble disulfide. Kidney stones prevented from forming due to a lower concentration of urinary cystine.
The worldwide prevalence of the disease is believed to be one in 7,000. Considered a rare condition. 
Prevention of cystine (kidney) stone formation in pts with severe homozygous cystinuria (urinary cystine >500mg/day), who are resistant to treatment with conservative measures of high fluid intake, alkali and diet modification, or who have adverse reactions to d-penicillamine
Trial or other data
Jul 19Tiopronin (Thiola®) is widely available drug (but not UK), approved in 1988 for treatment of cystinuria. A new formulation of tiopronin as delayed release enteric coated tablets of 100mg and 300mg is being developed for the treatment of cystinuria [1-3].
Jul 19Tiopronin is noted to have some serious side effects. Serious adverse reactions reported for Thiola as seen with d-penicillamine, including death and haematologic abnormalities and proteinuria which require drug discontinuance. It should be discontinued if there are findings suggestive of Goodpasture syndrome, myasthenic syndrome, myasthenia gravis or ´drug fever´. Monitoring of peripheral blood counts, direct platelet count, hemoglobin, serum albumin, liver function tests, 24-hour urinary protein and routine urinalysis is recommendaded. Other potential associated adverse reactions include: gastrointestinal side effects, impairment in taste and smell, hypersensitivity reactions, hematologic abnormalities, renal complications, pulmonary manifestations, wrinkling and friability of skin, and neurological complications. The most common adverse reactions in clinical trials include: diarrhea (2%), and the following at 1%: reflux esophagitis, malaise, skin lesion, nausea, abdominal pain, intestinal polyp, urinary tract infection, and peripheral neuropathy.[2,3]