Drug Monograph
Full clinical overview, indications, dosage references & safety notes.
Drug class: Antiurolithic (cystine-binding thiol)
Main indication: Cystine urolithiasis (prevention and dissolution)
Available forms2 forms · 3 strengths documentedShow all ↓
Oral · solid
Tablet 100 mg Thiola®; human-labeled
Delayed-release tablet 100 mg human-labeled
Delayed-release tablet 300 mg human-labeled
Human-labeled products only. There is no veterinary-labeled tiopronin product.
Overview
Tiopronin (Thiola®) is an antiurolithic agent used in dogs for the prevention and dissolution of cystine urolithiasis when dietary therapy (a low-protein, low-sodium diet), increased water intake, and urinary alkalinization are not sufficiently effective.
Tiopronin reduces cystine stone formation by forming a more water-soluble complex that is readily excreted in the urine. Its effects on cystine reduction are dose-related and typically begin within the first day of treatment.
Mechanism of Action (MOA): Tiopronin is a chelating agent that undergoes thiol-disulfide exchange with cystine to form tiopronin-cystine disulfide. This complex is more water-soluble and is more readily excreted, helping prevent the formation of cystine calculi.
Indications
Tiopronin is used in dogs for the prevention and dissolution of cystine urolithiasis when conventional management alone is insufficient.
- Prevention of cystine urolithiasis: Used when dietary therapy, increased water intake, and urinary alkalinization are not completely effective.
- Dissolution of cystine uroliths: Used as part of a treatment regimen to promote dissolution of existing cystine calculi.
- Cystine nephrolithiasis: In dogs, medical dissolution of cystine nephroliths may also be attempted, using tiopronin together with a therapeutic diet and supplemental potassium citrate.
Dosage (Reference)
Dog
In dogs, tiopronin is used for both prevention and dissolution of cystine urinary calculi as part of a comprehensive management plan that includes increased water intake and urinary alkalinization.
| Clinical use | Route | Dose | Frequency | Notes |
|---|---|---|---|---|
| Prevention of cystine uroliths | PO | 15 mg/kg | Every 12 hours | Increase water intake and urine diuresis. For prevention of canine cystine uroliths, target a urine pH of approximately 7.5, adding potassium citrate when dietary alkalinization is insufficient and adjusting treatment according to urine pH monitoring. |
| Dissolution of cystine uroliths | PO | Approximately 20 mg/kg | Every 12 hours | Reevaluate uroliths by ultrasonography or radiography every 4 weeks. |
| Cystine nephrolithiasis (dissolution) | PO | 15 mg/kg | Every 12 hours | Give with a therapeutic diet and supplemental potassium citrate as needed to maintain a urine pH of about 7.5, a higher target than the one given for urolith prevention. |
Important dosing notes (dogs):
• Preventive dosage: 15 mg/kg PO every 12 hours; a lower dosage of 5 to 10 mg/kg every 12 hours to prevent recurrent uroliths is also published.
• Increase water intake and promote urine diuresis during treatment.
• For prevention of canine cystine uroliths, target a urine pH of approximately 7.5, adding potassium citrate when dietary alkalinization is insufficient and adjusting treatment according to urine pH monitoring.
• In dogs with low cystine excretion and a low recurrence rate, the dose may be individually reduced (to less than 30 mg/kg/day) or discontinued.
• For dissolution therapy, use approximately 20 mg/kg PO every 12 hours, within a published range of 15–20 mg/kg every 12 hours, continued until the uroliths dissolve.
• Reevaluate uroliths every 4 weeks using ultrasonography or radiography.
• After successful dissolution, continue with the preventive dosage. In dogs whose uroliths re-formed during preventive treatment, the uroliths dissolved when the dose was raised back to the dissolution rate.
• If dissolution is not achieved after 2–3 months, surgery is recommended.
• Preventive dosage: 15 mg/kg PO every 12 hours; a lower dosage of 5 to 10 mg/kg every 12 hours to prevent recurrent uroliths is also published.
• Increase water intake and promote urine diuresis during treatment.
• For prevention of canine cystine uroliths, target a urine pH of approximately 7.5, adding potassium citrate when dietary alkalinization is insufficient and adjusting treatment according to urine pH monitoring.
• In dogs with low cystine excretion and a low recurrence rate, the dose may be individually reduced (to less than 30 mg/kg/day) or discontinued.
• For dissolution therapy, use approximately 20 mg/kg PO every 12 hours, within a published range of 15–20 mg/kg every 12 hours, continued until the uroliths dissolve.
• Reevaluate uroliths every 4 weeks using ultrasonography or radiography.
• After successful dissolution, continue with the preventive dosage. In dogs whose uroliths re-formed during preventive treatment, the uroliths dissolved when the dose was raised back to the dissolution rate.
• If dissolution is not achieved after 2–3 months, surgery is recommended.
Cat
Tiopronin is not recommended for routine use in cats but may be considered cautiously for recurrent cystine urolithiasis under specialist supervision. Doses of 12–20 mg/kg orally every 12 hours have been reported, but feline safety, efficacy, and an optimal regimen remain unestablished. Adverse reactions have occurred, and prevention of recurrence should not be equated with demonstrated stone dissolution.
| Clinical use | Route | Dose | Frequency | Notes |
|---|---|---|---|---|
| All indications | — | Not recommended | — | Cats reportedly do not tolerate the drug well, and dissolution of cystine uroliths has not been successful. |
Important dosing notes (cats):
• Avoid use in cats.
• Feline efficacy and safety have not been thoroughly evaluated, and the published feline dosing rests on a small number of cats.
• Avoid use in cats.
• Feline efficacy and safety have not been thoroughly evaluated, and the published feline dosing rests on a small number of cats.
Warnings & Precautions
Tiopronin should be used cautiously in patients with hematologic, renal, or hepatic abnormalities and is contraindicated in certain situations.
- Hypersensitivity: Contraindicated in patients with known hypersensitivity to tiopronin.
- Obstructive urolithiasis: Contraindicated in patients with obstructive urinary calculi.
- Hematologic disorders: Carefully evaluate the risks and benefits before use in patients with agranulocytosis, aplastic anemia, thrombocytopenia, or other significant hematologic abnormalities.
- Renal impairment: Use with caution in patients with impaired renal function.
- Hepatic impairment: Use with caution in patients with impaired hepatic function.
- Penicillamine sensitivity: Use with caution in patients with sensitivity to penicillamine.
- Previous penicillamine toxicity: In humans, a lower starting dose is recommended in patients with a history of severe toxicity to penicillamine.
- Cats: Avoid use in cats because they reportedly do not tolerate the drug well and dissolution of cystine uroliths has not been successful.
- Pregnancy: Reproductive safety information is limited. No adverse developmental outcomes were seen in rats given up to four times the recommended human dose, but skeletal defects, cleft palates and increased resorptions occurred in rats given ten times the human dose of the related drug penicillamine, which may also be of concern with tiopronin.
- Lactation: Because tiopronin may be excreted in milk, it is not recommended for use in nursing animals; a published study also suggests it may suppress milk production.
Drug Interactions
The following interaction has been reported for tiopronin.
- Nephrotoxic, hepatotoxic, or myelosuppressive drugs: Concurrent use may result in additive toxic effects. The clinical significance is unclear.
Side Effects & Overdose
Side Effects
Adverse effects associated with tiopronin may involve hematologic, hepatic, renal, dermatologic, neuromuscular, and behavioral systems.
- Proteinuria: Reported during treatment in dogs.
- Thrombocytopenia: May occur during therapy.
- Anemia: Reported in treated dogs.
- Coombs-positive regenerative spherocyte anemia: Has been associated with tiopronin treatment in dogs and is reported to be reversible; if it occurs, the drug should be discontinued and appropriate treatment started as needed, such as corticosteroids or blood component therapy.
- Increased liver enzymes and bile acids: May occur during therapy.
- Lethargy: Reported in some patients.
- Dermatologic effects: Including small skin pustules and a dry, crusty nose.
- Aggression: Behavioral changes have been reported.
- Sulfur odor of the urine: May occur during treatment.
- Myopathy: Reported as staggering and difficulty chewing.
- Frequency and time course: Information on the canine adverse-effect profile is limited. In a retrospective study of dogs treated for cystinuria, 13% experienced adverse events. They appeared between 1 month and 36 months of therapy (mean 7.8 months) and resolved when treatment was discontinued.
- Stopping and restarting: If adverse reactions occur, stop treatment for 4 weeks and check blood and urine analysis every 1 to 2 weeks until the signs resolve. Treatment can then be restarted, gradually increasing the dose from 10–15 mg/kg every 12 hours. If the reactions reappear despite a lowered dose, tiopronin has to be abandoned.
- Other reported effects: Glomerulonephritis, lymphadenopathy, cutaneous hypersensitivity and delayed wound healing are also reported for the cystine-binding agents.
- Feline reports: In cats, gastrointestinal signs, liver disease and anemia have been reported.
- Human safety data: In people, the common adverse effects are dermatologic (ecchymosis, itching, rashes, mouth ulcers, jaundice) and gastrointestinal upset. Less frequently reported are allergic reactions, arthralgia, dyspnea, fever, hematologic abnormalities, edema and nephrotic syndrome.
Overdose
Limited information is available regarding tiopronin overdose.
- Limited information available: There is little information regarding overdose in animals.
- Management: Contact an animal poison control center for further guidance in suspected overdose cases.
Key Notes
Practical clinical points that may help optimize the use of tiopronin in dogs:
- Adjunctive therapy: Tiopronin is intended to be used in combination with dietary modification, increased water intake, and urinary alkalinization rather than as a sole treatment.
- Rapid onset of effect: Reduction in cystine concentration is typically observed within the first day of treatment, and cystine excretion rises again on the first day after the drug is withdrawn.
- Short duration of action: The drug has a relatively short duration of effect, disappearing within about 10 hours in people, which supports twice-daily dosing.
- Primarily eliminated by the kidneys: Elimination occurs mainly through renal excretion.
- Administration timing: Give at the same time each day, at least 1 hour before or 2 hours after meals.
- Long-term follow-up is recommended: Re-examinations are recommended at 1, 3, 6, and 12 months after initiating therapy and, if well controlled, every 6–12 months thereafter.
- What to monitor: Each re-examination should include physical examination, ultrasonography or radiography of the urinary tract, urinalysis with sediment on a first morning sample, a CBC with platelet count, and liver enzymes (ALP, ALT).
- Cost and availability: There is no veterinary-labeled tiopronin product. Cost and availability can be problematic. The brand is an orphan drug supplied by a single distributor, generic tiopronin may have to be obtained from a compounding pharmacy, and it is not distributed in many countries.
- Other names: Tiopronin is also known as 2-MPG or N-(2-mercaptopropionyl)-glycine.
- Storage: Store tablets in tight containers at room temperature, 25°C (77°F), with excursions permitted to 15–30°C (59–86°F).
- Giving the tablet: The human label for the delayed-release product states that, for patients who cannot swallow the tablet whole, it may be crushed and mixed with applesauce, and that administration with other liquids or foods has not been studied.
- What the diet contributes: The canine therapeutic diet reduces urinary cystine excretion, promotes alkaline urine and lowers urine concentration, and the combination of diet and tiopronin dissolves uroliths more effectively than either alone.
- Time to dissolution: In one hospital series the mean time to dissolution was 78 days, with a range of 11 to 211 days.
- Why urine pH matters: Cystine solubility depends on urine pH. It is about 250 mg/L up to pH 7, roughly doubles to 500 mg/L at pH 7.5, and triples at pH 8 or higher.
- Castration in male dogs: Some cases of canine cystinuria are androgen dependent, and in male dogs castration lowers urinary cystine and reduces recurrence, so neutering is recommended as part of prevention.
- Recurrence: Cystine uroliths tend to recur within a year if prevention is not maintained, and may recur despite it, although recurrence does not affect every cystinuric dog and cat.
- Compared with penicillamine: Tiopronin is the recommended cystine-binding agent. It has fewer adverse effects than penicillamine, current recommendations prefer it to that drug, and it has a higher oxidation-reduction potential and may be more effective.
- No metal chelation: Unlike penicillamine, tiopronin does not appreciably increase urinary excretion of metals, so there is no risk of renal losses of biologically important metals.
- Compliance: Counsel owners on the importance of consistent daily dosing and on the clinical signs of adverse effects to watch for.
