THIOLA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for THIOLA (THIOLA).

How it works

Thiola (tiopronin) acts as a reducing agent, breaking disulfide bonds in cystine stones and decreasing cystine excretion by forming a soluble disulfide complex with cystine, thereby reducing urinary cystine concentration.

What the body does with it

Metabolism	Hepatic; partially metabolized to disulfide metabolites.
Excretion	Primarily renal: approximately 60-70% of an administered dose is excreted in urine as unchanged drug or as the disulfide dimer. Minor biliary/fecal excretion accounts for <10%.
Half-life	Terminal elimination half-life is approximately 4-5 hours in adults with normal renal function. In patients with renal impairment, half-life may be prolonged, requiring dose adjustment.
Protein binding	Approximately 70-80% bound to plasma proteins, primarily albumin.
Volume of Distribution	Approximately 0.5-0.7 L/kg, indicating moderate distribution into total body water.
Bioavailability	Oral bioavailability is approximately 70-80%, with peak plasma concentrations achieved 1-2 hours after oral administration.
Onset of Action	Oral administration: clinical effect (reduction in urinary cystine levels) typically observed within 2-4 hours, with maximal effect by 4-6 hours.
Duration of Action	Duration of effect is approximately 8-12 hours, supporting a recommended dosing interval of every 6-12 hours. Continuous therapy is required for sustained efficacy.

Classification & Brands

Dosing & administration

300 mg orally three times daily (total daily dose 900 mg) 1 hour before meals and at bedtime.

Dosage form	TABLET
Renal impairment	GFR 30-50 mL/min: 300 mg twice daily; GFR <30 mL/min: 300 mg once daily; hemodialysis: 300 mg once daily on non-dialysis days.
Liver impairment	No specific dosage adjustment recommended for hepatic impairment; use with caution in severe hepatic disease.
Pediatric use	Safety and efficacy not established; no FDA-approved pediatric dosing guidelines.
Geriatric use	No specific dose adjustment; monitor renal function and adjust dose based on creatinine clearance.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for THIOLA (THIOLA).

Breastfeeding	Excreted into breast milk; M/P ratio unknown. Not recommended during breastfeeding due to potential risks of hematologic toxicity and hypersensitivity in neonates.
Teratogenic Risk	FDA Pregnancy Category C. In animal studies, tiopronin (active metabolite) caused teratogenic effects (cleft palate, skeletal abnormalities) in rats and rabbits at doses 0.5-2 times human dose. No adequate human studies. First trimester: potential teratogenic risk (organogenesis). Second/third trimester: unknown effects on fetal growth; use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of agranulocytosis, aplastic anemia, or thrombocytopenia with penicillamine","History of severe adverse reactions to penicillamine","Pregnancy (may cause fetal harm based on animal data)"]

Clinical Precautions

Precautions

["Monitor for proteinuria and hematuria due to possible nephrotoxicity","Monitor complete blood counts for agranulocytosis, aplastic anemia, thrombocytopenia","Skin rashes, drug fever, lupus-like reactions may occur","Use with caution in elderly or patients with renal impairment"]

Clinical Tips & Counseling

Drug interactions

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THIOLA

Clinical safety rating: caution

Comprehensive clinical and safety monograph for THIOLA (THIOLA).

How it works

What the body does with it

Metabolism	Hepatic; partially metabolized to disulfide metabolites.
Excretion	Primarily renal: approximately 60-70% of an administered dose is excreted in urine as unchanged drug or as the disulfide dimer. Minor biliary/fecal excretion accounts for <10%.
Half-life	Terminal elimination half-life is approximately 4-5 hours in adults with normal renal function. In patients with renal impairment, half-life may be prolonged, requiring dose adjustment.
Protein binding	Approximately 70-80% bound to plasma proteins, primarily albumin.
Volume of Distribution	Approximately 0.5-0.7 L/kg, indicating moderate distribution into total body water.
Bioavailability	Oral bioavailability is approximately 70-80%, with peak plasma concentrations achieved 1-2 hours after oral administration.
Onset of Action	Oral administration: clinical effect (reduction in urinary cystine levels) typically observed within 2-4 hours, with maximal effect by 4-6 hours.
Duration of Action	Duration of effect is approximately 8-12 hours, supporting a recommended dosing interval of every 6-12 hours. Continuous therapy is required for sustained efficacy.

Classification & Brands

Dosing & administration

300 mg orally three times daily (total daily dose 900 mg) 1 hour before meals and at bedtime.

Dosage form	TABLET
Renal impairment	GFR 30-50 mL/min: 300 mg twice daily; GFR <30 mL/min: 300 mg once daily; hemodialysis: 300 mg once daily on non-dialysis days.
Liver impairment	No specific dosage adjustment recommended for hepatic impairment; use with caution in severe hepatic disease.
Pediatric use	Safety and efficacy not established; no FDA-approved pediatric dosing guidelines.
Geriatric use	No specific dose adjustment; monitor renal function and adjust dose based on creatinine clearance.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for THIOLA (THIOLA).

Breastfeeding	Excreted into breast milk; M/P ratio unknown. Not recommended during breastfeeding due to potential risks of hematologic toxicity and hypersensitivity in neonates.
Teratogenic Risk	FDA Pregnancy Category C. In animal studies, tiopronin (active metabolite) caused teratogenic effects (cleft palate, skeletal abnormalities) in rats and rabbits at doses 0.5-2 times human dose. No adequate human studies. First trimester: potential teratogenic risk (organogenesis). Second/third trimester: unknown effects on fetal growth; use only if benefit outweighs risk.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["History of agranulocytosis, aplastic anemia, or thrombocytopenia with penicillamine","History of severe adverse reactions to penicillamine","Pregnancy (may cause fetal harm based on animal data)"]