TIOPRONIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TIOPRONIN (TIOPRONIN).
Tiopronin is a thiol compound that reduces cystine excretion by forming a soluble disulfide complex with cystine, thereby preventing cystine stone formation in patients with cystinuria. It also has antioxidant and anti-inflammatory properties, possibly through metal chelation and free radical scavenging.
| Metabolism | Tiopronin is extensively metabolized, primarily through oxidation and disulfide formation. The metabolic pathways involve conversion to tiopronin disulfide and mixed disulfides with other thiols. CYP450 involvement is minimal. |
| Excretion | Renal: ~80% as unchanged drug and metabolites, primarily via glomerular filtration and active tubular secretion. Biliary/fecal: minimal (<5%). |
| Half-life | Terminal elimination half-life is approximately 1.5-2 hours in adults with normal renal function. May be prolonged in renal impairment. |
| Protein binding | Approximately 60-70% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Approximately 0.2-0.3 L/kg, indicating distribution primarily within extracellular fluid. |
| Bioavailability | Oral bioavailability is approximately 50-70% (first-pass metabolism). |
| Onset of Action | Oral: Onset of clinical effect (reduction of cystine excretion) occurs within 2-3 hours after a single dose. |
| Duration of Action | Duration of effect is 6-12 hours, necessitating multiple daily dosing (typically every 6-8 hours) to maintain therapeutic effect. |
500-1000 mg orally three times daily for cystinuria; for rheumatoid arthritis: 250 mg orally four times daily, titrated up to 500 mg four times daily.
| Dosage form | TABLET, DELAYED RELEASE |
| Renal impairment | For GFR <50 mL/min: avoid use; for GFR 50-80 mL/min: reduce dose by 50%. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: contraindicated. |
| Pediatric use | For cystinuria: 10-15 mg/kg/day in 4 divided doses; for rheumatoid arthritis: 3-5 mg/kg/day in 4 divided doses. |
| Geriatric use | Initiate at lower end of dosing range due to increased risk of renal impairment and adverse effects; monitor renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TIOPRONIN (TIOPRONIN).
| Breastfeeding | No data available on excretion into breast milk; caution is advised. Use while breastfeeding only if potential benefit justifies risk. |
| Teratogenic Risk | Limited human data; animal studies have shown embryotoxicity and teratogenicity at high doses. Use only if clearly needed. Risk cannot be excluded. |
| Fetal Monitoring | Monitor maternal renal function and liver function tests; fetal ultrasound for growth and anomalies if used in pregnancy. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to tiopronin","History of agranulocytosis or aplastic anemia from tiopronin therapy","Lactation (relative, caution advised)"]
| Precautions | ["Nephrotic syndrome","Thrombotic thrombocytopenic purpura","Pharmacological pyridoxine deficiency","Drug-induced lupus erythematosus","Severe hypersensitivity reactions","Renal function monitoring required"] |
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| Fertility Effects | No data on human fertility; animal studies do not indicate impairment. |