THIOLA EC
Clinical safety rating: caution
Comprehensive clinical and safety monograph for THIOLA EC (THIOLA EC).
THIOLA EC (tiopronin) is a reducing agent that breaks disulfide bonds in cystine, forming a mixed disulfide of tiopronin-cysteine, which is more soluble than cystine, thereby reducing cystine stone formation in the urine.
| Metabolism | Primarily hepatic metabolism; tiopronin undergoes oxidation and conjugation to form disulfide metabolites. |
| Excretion | Renal: 80% as unchanged drug; biliary/fecal: <5% |
| Half-life | Terminal half-life: 6-12 hours in patients with normal renal function; may be prolonged in renal impairment (up to 30 hours in severe CKD) |
| Protein binding | Negligible (<5%); not significantly bound to plasma proteins |
| Volume of Distribution | 1.2 L/kg; indicates distribution primarily into body water |
| Bioavailability | Oral: ~50-70% (first-pass metabolism reduces absolute bioavailability) |
| Onset of Action | Oral: 1-2 hours for peak effect on urinary cystine levels |
| Duration of Action | 12-24 hours; requires dosing every 6-12 hours to maintain therapeutic effect |
Oral administration of 300 mg (1 capsule) three times daily, 1 hour before meals and at bedtime.
| Dosage form | TABLET, DELAYED RELEASE |
| Renal impairment | For GFR < 50 mL/min: avoid use; for GFR 50-80 mL/min: no adjustment required, but monitor renal function. |
| Liver impairment | No specific guidelines; use with caution in severe hepatic impairment (Child-Pugh C) due to potential for altered metabolism. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established; not recommended for use. |
| Geriatric use | No specific dose adjustment; monitor renal function closely due to age-related decrease in GFR. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for THIOLA EC (THIOLA EC).
| Breastfeeding | It is not known whether tiopronin is excreted in human milk. Due to potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. M/P ratio: unknown. |
| Teratogenic Risk | FDA Pregnancy Category C. Animal studies have shown teratogenic effects (skeletal abnormalities) at doses 13 times the human dose. However, no adequate human studies exist. In the first trimester, risk cannot be ruled out; use only if benefit outweighs risk. Second and third trimester: limited data; may cause fetal harm if used in conditions with potential for metabolic acidosis. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["History of hypersensitivity to tiopronin or any component of the formulation."]
| Precautions | ["Monitor for proteinuria and renal function due to risk of nephrotoxicity.","Monitor for hematologic abnormalities (e.g., leukopenia, thrombocytopenia).","Skin rash and drug fever may occur.","Potential for autoimmune reactions (e.g., lupus-like syndrome)."] |
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| Fetal Monitoring | Monitor renal function, urinalysis for proteinuria, and liver function tests. During pregnancy, monitor fetal growth via ultrasound and assess for signs of metabolic acidosis. Also monitor complete blood count for possible bone marrow suppression. |
| Fertility Effects | No adequate studies on fertility effects in humans. In animal studies, tiopronin did not impair fertility in rats at doses up to 2 times the human dose. |