FDA OKs New Formulation of Tiopronin for Cystinuria

Megan Brooks

July 02, 2019

The US Food and Drug Administration (FDA) has approved an enteric-coated delayed-release formulation of tiopronin (Thiola EC, Retrophin) for treatment of cystinuria, a rare inherited disorder that causes an increase in cystine levels in the urine, leading to recurring cystine kidney stones.

Thiola EC tablets can be taken with or without food, "an advancement over the original formulation (Thiola) which has limiting food restrictions, and also provides the potential to reduce the number of tablets necessary to manage cystinuria," Eric Dube, PhD, chief executive officer of Retrophin, said in a news release.

The company expects to have Thiola EC delayed-release tablets available in strengths of 100 mg and 300 mg next month.

"Thiola's utility as the treatment of choice for cystinuria is well established. However, for certain patients, the challenges of administration one hour before or two hours after meals three times a day, coupled with a high pill burden, have been challenging," David Goldfarb, MD, clinical chief, Division of Nephrology, NYU Langone Health, New York City, said in the news release.

"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.

Cystinuria occurs in roughly 1 in 7000 to 1 in 10,000 people in the United States, according to the National Organization for Rare Disorders.

The FDA approved Thiola EC tablets through the 505(b)(2) regulatory pathway, which allows the agency to reference previous findings of safety and efficacy for an already-approved product, as well as review findings from further studies of the product.

Thiola EC is indicated for the prevention of cystine stone formation in adults and pediatric patients weighing at least 20 kg who have severe homozygous cystinuria and who are not responsive to these measures alone. Thiola EC should be used in conjunction with high fluid intake, as well as alkali and diet modification.

The most common adverse reactions (≥10%) are nausea, diarrhea or soft stools, oral ulcers, rash, fatigue, fever, arthralgia, proteinuria, and emesis.

Proteinuria, including nephrotic syndrome and membranous nephropathy, has been reported with tiopronin use. Children receiving >50 mg/kg of tiopronin daily may be at increased risk for proteinuria and should be monitored for the development of proteinuria. Treatment should be discontinued in those who develop proteinuria. Hypersensitivity reactions, including fever, rash, arthralgia, and lymphadenopathy, have been reported.

Full prescribing information is available online.

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