New Formulation of Tiopronin Receives FDA Approval for Treatment of Cystinuria
Retrophin's enteric-coated formulation allows administration with or without food.
Officials with the FDA have approved a new enteric-coated formulation of tiopronin (Thiola EC, Retrophin) 100 mg and 300 mg tablets, for the treatment of cystinuria, a rare inherited disorder that causes a buildup of cystine levels in the urine, resulting in the formation of recurring cystine kidney stones.
According to Retrophin, these new tablets are expected to be available in July 2019.
“This new formulation provides patients with the freedom to administer Thiola EC with or without food, an advancement over the original formulation which has limiting food restrictions, and also provides the potential to reduce the number of tablets necessary to manage cystinuria. We look forward to working with the cystinuria community as we make the new formulation available next month,” said Eric Dube, PhD, chief executive officer of Retrophin, in a prepared statement.
The recommended initial dosage of tiopronin in adult patients is 800 mg per day. In clinical studies the average dose of tiopronin was approximately 1000 mg, or 10 pills per day. The original formulation of Retrophin’s tiopronin 100 mg product is recommended to be administered at least 1 hour before or 2o hours after meals. The enteric-coated formulation of tiopronin is recommended to be administered with or without food.
Dr David S. Goldfarb, Clinical Chief, Division of Nephrology at NYU Langone Health, said tiopronin’s utility as the treatment of choice for cystinuria is well established, but certain patients find it challenging to adhere to administration 1 hour before or 2 hours after meals 3 times a day, coupled with a high pill burden.
“Having a new treatment option with the flexibility of dosing with or without food, as well as one that provides an opportunity for patients to take fewer pills, should meaningfully improve convenience and compliance,” he added, in a prepared statement.
Retrophin’s enteric-coated tiopronin tablets were approved through the 505(b)(2) regulatory pathway which allows the FDA to reference previous findings of safety and efficacy for an already-approved product, combined with reviewing findings from further studies of the product.
The most commonly reported adverse reactions (≥10%) are nausea, diarrhea or soft stools, oral ulcers, rash, fatigue, fever, arthralgia, proteinuria, and emesis.
In addition, proteinuria, including nephrotic syndrome and membranous nephropathy, have been reported with tiopronin use. Pediatric patients receiving >50 mg/kg of tiopronin per day may be at increased risk for proteinuria.
Retrophin Announces FDA Approval of THIOLA® EC (tiopronin) 100mg and 300mg Tablets for the Treatment of Cystinuria [news release]. San Diego, CA; June 28, 2019: Retrophin website. http://ir.retrophin.com/news-releases/news-release-details/retrophin-announces-fda-approval-thiolar-ec-tiopronin-100mg-and. Accessed June 2019.