Introduction: Cystinuria is a rare cause of stone formation which can require long term medication with chelating agents to prevent or reduce the frequency and/or severity of stone episodes. These medications have a range of significant side effects which can limit tolerability with penicillamine reported to have a worse side effect profile than tiopronin.
Methods: The database of 218 cystinuric patients attending a single centre specialist clinic was used to identify patients who were or had been on either penicillamine, tiopronin at any point. These were then categorised according to whether they were still taking or had discontinued, if they had tried both medications and side effects.
Results: There were 63 patients identified with more male 34 (54%) than female 29 (46%) patients. Two thirds had a mutation in SLC3A1. 28/63 (44%) had penicillamine – 18/28 (64%) continued taking 10/28 (36%) stopped due to one or more side effects; nausea and dizziness (7), loss of taste and smell (2), hair loss (2), peripheral oedema (2), bruising (1), mouth ulcers (1) and nephrotic syndrome (1). 22/63 (35%) had tiopronin - 16/23 (70%) continued taking 7/23 (30%) stopped due to one or more side effects ; nausea (2), rash (2), swelling of tongue (1), ulcers and diarrhoea (1), nephrotic syndrome (1). 12 of the 63 patients had tried both medications with 8/12 trying penicillamine and when they had side effects switched to tiopronin. Of these 8 patients who were unable to take penicillamine, 4 (50%) who were given tiopronin 2nd line tolerated it. Likewise 4 of the 12 patients had tried tiopronin first and when unable to tolerate it had been switched to penicillamine 2nd line. 2 of the 4 (50%) were able to tolerate penicillamine. So 6 of the 12 patients (50%) who could not tolerate the first chelating agent they were given went on to successfully tolerate the second line regardless of which order the drugs were given, 50% could not tolerate either drug.
Conclusions: Chelating agents used for cystinuria have a range of troublesome side effects that leads to frequent discontinuation of the medication. However in our series, unlike previous reports, the incidence of these side effects is not markedly different with penicillamine when compared with tiopronin. Our results also demonstrate a benefit in trying the alternative medication if the other is not tolerated regardless of the order in which they are taken.