Tiopronin

The goal of therapy is to reduce urinary cystine concentration below its solubility limit. Tiopronin is an active reducing agent which undergoes thiol-disulfide exchange with cystine to form a mixed disulfide of tiopronin-cysteine.

• VENXXIVA is indicated, in combination with high fluid intake, alkali, and diet modification, for the prevention of cystine stone formation in adults and pediatric patients 9 years of age and older with severe homozygous cystinuria, who are not responsive to these measures alone. Additional pediatric use information is approved for Mission Pharmacal Company’s Thiola EC (tiopronin delayed-release) tablets.

• VENXXIVA is contraindicated in patients with hypersensitivity to tiopronin or any other components of VENXXIVA [see Warnings and Precautions ( 5.2 )] .contraindicated

The recommended initial dosage in adult patients is 800 mg/day. In clinical studies, the average dosage was about 1,000 mg/day. ( 2.1 ) The recommended initial dosage in pediatric patients 9 years of age and older is 15 mg/kg/day. Avoid dosages greater than 50 mg/kg per day in pediatric patients. ( 5.1 , 8.4 ) Measure urinary cystine 1 month after initiation of VENXXIVA and every 3 months thereafter. ( 2.3 ) Administer VENXXIVA in 3 divided doses at the same times each day, without food. ( 2.1 ) 2.1 Recommended Dosage Adults : The recommended initial dosage in adult patients is 800 mg/day. In clinical studies, the average dosage was about 1,000 mg/day. Pediatrics : The recommended initial dosage in pediatric patients 9 years of age and older is 15 mg/kg/day. Avoid dosages greater than 50 mg/kg per day in pediatric patients [see Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.4 )] . Administer VENXXIVA in 3 divided doses at the same times each day, without food. Consider starting VENXXIVA at a lower dosage in patients with history of severe toxicity to d-penicillamine. Additional pediatric use information is approved for Mission Pharmacal Company’s Thiola EC (tiopronin delayed-release) tablets. However, due to Mission Pharmacal Company’s marketing exclusivity rights, this drug product is not labeled with that information. 2.3 Monitoring Measure urinary cystine 1 month after starting VENXXIVA and every 3 months thereafter. Adjust VENXXIVA dosage to maintain urinary cystine concentration less than 250 mg/L.

Proteinuria, including nephrotic syndrome, and membranous nephropathy, has been reported with tiopronin use. Pediatric patients receiving greater than 50 mg/kg of tiopronin per day may be at increased risk for proteinuria. ( 2.1 , 5.1 , 8.4 ) Hypersensitivity reactions have been reported during tiopronin treatment. ( 4 , 5.2 ) 5.1 Proteinuria Proteinuria, including nephrotic syndrome, and membranous nephropathy, have been reported with tiopronin use. Pediatric patients receiving greater than 50 mg/kg of tiopronin per day may be at increased risk for proteinuria. [see Dosage and Administration ( 2.3 ), Adverse Reactions ( 6.1 , 6.2 ), Use in Specific Populations ( 8.4 )] . Monitor patients for the development of proteinuria and discontinue therapy in patients who develop proteinuria [see Dosage and Administration ( 2.3 )] . 5.2 Hypersensitivity Reactions Hypersensitivity reactions (drug fever, rash, fever, arthralgia and lymphadenopathy) have been reported [see Contraindications ( 4 )] .

The following adverse reactions are discussed in greater detail in other sections of the labeling: Proteinuria [see Warnings and Precautions ( 5.1 )] Hypersensitivity [see Warnings and Precautions ( 5.2 )] Most common adverse reactions (≥10%) are nausea, diarrhea or soft stools, oral ulcers, rash, fatigue, fever, arthralgia, proteinuria, and emesis. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Cycle Pharmaceuticals Ltd at 1-857-437-3969 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of the drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions occurring at an incidence of ≥5% in an uncontrolled trial in 66 patients with cystinuria age 9 to 68 years are shown in the table below. Patients in group 1 had previously been treated with d-penicillamine; those in group 2 had not. Of those patients who had stopped taking d-penicillamine due to toxicity (34 out of 49 patients in group 1), 22 were able to continue treatment with tiopronin. In those without prior history of d-penicillamine treatment, 6% developed reactions of sufficient severity to require tiopronin withdrawal. Table 1 presents adverse reactions ≥5% in either treatment group occurring in this trial.

Lactation: Breastfeeding is not recommended. ( 8.2 ) Geriatric: Choose dose carefully and monitor renal function in the elderly. ( 8.5 ) Additional pediatric use information is approved for Mission Pharmacal Company’s Thiola EC (tiopronin delayed-release) tablets. However, due to Mission Pharmacal Company’s marketing exclusivity rights, this drug product is not labeled with that information. 8.1 Pregnancy Risk Summary Available published case report data with tiopronin have not identified a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Renal stones in pregnancy may result in adverse pregnancy 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 organogenesis at doses up to 2 times a 2 grams/day human dose (based on mg/m 2 ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively.

Metabolism

Absorption VENXXIVA Tablets When tiopronin IR and VENXXIVA single doses were given to fasted healthy subjects, the median time to peak plasma levels (T max ) was 1 (range: 0.5 to 2.1) and 3 (range: 1.0 to 6.0) hours, respectively. The peak exposure (C max ) and total exposure (AUC 0-t ) of tiopronin from VENXXIVA tablets were decreased by 22% and 7% respectively compared to tiopronin IR tablets.

There is no information on overdosage with tiopronin.

• Aug 11, 1988NDANDA019569Mission Pharma
• Jun 28, 2019NDANDA211843Mission Pharmacal
• Apr 26, 2021ANDAANDA214326Teva Pharms Usa Inc
• Feb 24, 2023ANDAANDA217219Ph Health
• Aug 15, 2023ANDAANDA216278Amneal
• Jan 30, 2024ANDAANDA216990Torrent
• Jul 22, 2024ANDAANDA216456Teva Pharms Inc

1. 1Drug Ineffective75031%
2. 2Drug Dose Omission25711%
3. 3Nausea1867.8%
4. 4Rash1285.3%
5. 5Pain1184.9%
6. 6Fatigue1174.9%
7. 7Pyrexia1144.8%
8. 8Nephrolithiasis913.8%
9. 9Arthralgia853.5%
10. 10Vomiting833.5%
11. 11Headache783.3%
12. 12Diarrhoea743.1%
13. 13Pruritus733.0%
14. 14Dyspepsia562.3%
15. 15Malaise542.3%

Recent PubMed references pinned to Tiopronin as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Comparative analysis of surgical costs vs. theoretical tiopronin therapy in pediatric cystinuria: a single-center experience from Türkiye.
  The Turkish journal of pediatrics · 2026 · Sözduyar S, Ulman H, Tekin A, et al.
  PMID 41871560DOI 10.24953/turkjpediatr.2026.6198
• Tiopronin safety in cystinuria: first real-world pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS): an EAU YAU and Endourology sections review.
  Pediatric nephrology (Berlin, Germany) · 2026 · Ergül RB, Gürlek IT, Özervarlı MF, et al.
  PMID 41263948DOI 10.1007/s00467-025-07043-2
• Theoretical assessment of Au(32) nanocluster as tiopronin drug agent: DFT calculation and MD simulation; with solvent effect.
  Journal of molecular graphics & modelling · 2026 · Alotaibi HF, Kumar A, Jadeja Y, et al.
  PMID 41192201DOI 10.1016/j.jmgm.2025.109209
• Disruptions in Tiopronin therapy: impacts on clinical outcomes of pediatric cystinuria patients during the COVID-19 pandemic.
  Urolithiasis · 2025 · Önal HG, Nalçacioğlu H, Karali DT, et al.
  PMID 40445369DOI 10.1007/s00240-025-01767-4
• Exploring tiopronin adsorption on pristine and Al/Ga-doped boron nitride nanoclusters: A DFT approach for enhanced drug delivery.
  Journal of molecular graphics & modelling · 2025 · Khodayar E, Abyaz B, Zare M, et al.
  PMID 40056691DOI 10.1016/j.jmgm.2025.109002
• Tiopronin-induced Membranous Nephropathy Presenting with IgG4-predominant Staining Pattern.
  Internal medicine (Tokyo, Japan) · 2025 · Yamashita J, Hirakawa Y, Sato Y, et al.
  PMID 39261067DOI 10.2169/internalmedicine.4047-24
• Evaluate the value of prolonging the duration of tiopronin for injection administration in preventing hepatotoxicity.
  Scientific reports · 2024 · Yang H, Lin M, Liu M, et al.
  PMID 38351216DOI 10.1038/s41598-024-54314-3
• Addressing the Binding Mechanism of the Meprin and TRAF-C Homology Domain of the Speckle-Type POZ Protein Using Protein Engineering.
  International journal of molecular sciences · 2023 · Diop A, Pietrangeli P, Pennacchietti V, et al.
  PMID 38139193DOI 10.3390/ijms242417364

The 6 most recently updated of 6 ClinicalTrials.gov registrations naming Tiopronin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• The Effects of Tiopronin on 3-Aminopropanal Level & Neurologic Outcome After Aneurysmal Subarachnoid Hemorrhage
  Completed · Phase 2 · Interventional · 60 enrolled · E. Sander Connolly
  NCT01095731updated 2025-10-29
• Registry of Thiola EC Therapy
  Completed · Observational · 25 enrolled · NYU Langone Health
  NCT05048563updated 2024-02-29
• Effect of Increasing Doses of Tiopronin on Cystine Capacity in Patients With Cystinuria
  Completed · Phase 2 · Interventional · 10 enrolled · NYU Langone Health
  NCT03663855updated 2021-12-17
• Effect of Increasing Doses of Cystine Binding Thiol Drugs on Cystine Capacity in Patients With Cystinuria
  Completed · Phase 4 · Interventional · 10 enrolled · NYU Langone Health
  NCT02125721updated 2021-08-23
• Cystine Capacity Clinical Study (CysCap)
  Completed · Observational · 30 enrolled · NYU Langone Health
  NCT02120105updated 2018-12-03
• Efficacy and Safety Study of Magnesium Isoglycyrrhizinate Injection in Subjects With Acute Drug-induced Liver Injury
  Completed · Phase 2 · Interventional · 174 enrolled · Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
  NCT02734966updated 2016-09-27

Frequently asked questions

How does Tiopronin work?

The goal of therapy is to reduce urinary cystine concentration below its solubility limit. Tiopronin is an active reducing agent which undergoes thiol-disulfide exchange with cystine to form a mixed disulfide of tiopronin-cysteine.

What is Tiopronin used for?

According to FDA labeling, Tiopronin carries indications including: VENXXIVA is indicated, in combination with high fluid intake, alkali, and diet modification, for the prevention of cystine stone formation in adults and pediatric patients 9 years of age and older with severe homozygous cystinuria, who are not responsive to these measures alone. Additional pediatric use information is approved for Mission Pharmacal Company’s Thiola EC (tiopronin delayed-release) tablets.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Tiopronin?

Tiopronin is classified as Other urologicals, Reducing and Complexing Thiol, Cystine Disulfide Reduction, Increased Organic Ion Degradation.

What are the brand names for Tiopronin?

Tiopronin is marketed under brand names including Thiola, Venxxiva.

What are the contraindications for Tiopronin?

Tiopronin labeling lists contraindications including: VENXXIVA is contraindicated in patients with hypersensitivity to tiopronin or any other components of VENXXIVA [see Warnings and Precautions ( 5.2 )] .. Always consult the full prescribing information and a clinician.