Dosing & Uses
Dosage Forms & Strengths
tablet (Thiola)
- 100mg
tablet, delayed-release (Thiola EC)
- 100mg
- 300mg
Prevention of Nephrolithiasis
Indicated, in combination with high fluid intake, alkali, and diet modification, for the prevention of cystine stone formation in adults and pediatric patients ≥20 kg with severe homozygous cystinuria, who are not responsive to these measures alone
Initial: 800 mg/day PO divided TID
Adjust dose to maintain urinary cystine <250 mg/L (average daily dose is ~1000 mg/day)
Consider starting at lower dose with history of severe toxicity to d-penicillamine
Dosing Considerations
Measure urinary cystine 1 month after initiating and every 3 months thereafter
Assess for proteinuria before treatment and every 3-6 months during treatment
Discontinue in patients who develop proteinuria and monitor urinary protein and renal function
Consider restarting treatment at a lower dosage after resolution of proteinuria
Dosage Forms & Strengths
tablet (Thiola)
- 100mg
tablet, delayed-release (Thiola EC)
- 100mg
- 300mg
Prevention of Nephrolithiasis
Indicated, in combination with high fluid intake, alkali, and diet modification, for the prevention of cystine stone formation in adults and pediatric patients ≥20 kg with severe homozygous cystinuria, who are not responsive to these measures alone
<20 kg: Safety and efficacy not established
≥20 kg
- 15 mg/kg/day PO divided TID; not to exceed 50 mg/kg/day
- Adjust dose to maintain urinary cystine levels <250 mg/L
- Consider starting at lower dose with history of severe toxicity to d-penicillamine
Dosing Considerations
Measure urinary cystine 1 month after initiating and every 3 months thereafter
Assess for proteinuria before treatment and every 3-6 months during treatment
Discontinue in patients who develop proteinuria and monitor urinary protein and renal function
Consider restarting treatment at a lower dosage after resolution of proteinuria
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
Nausea (12-25%)
Oral ulcers (12-18%)
Diarrhea/soft stools (6-18%)
Fatigue (14%)
Rash (12-14%)
Arthralgia (12%)
Weakness (4-12%)
1-10%
Emesis (10%)
Proteinuria (6-10%)
Fever (8%)
Anorexia (8%)
Urticaria (8%)
Abdominal pain (6%)
Peripheral edema (6%)
Chest pain (6%)
Impotence (6%)
Cough (6%)
Ecchymosis (6%)
Skin wrinkling (6%)
Pruritus (4-6%)
Anemia (2-6%)
Frequency Not Defined
Reduced taste perception
Hypogeusia
Postmarketing Reports
Cardiac disorders: CHF
Ear and labyrinth disorders: Vertigo
Gastrointestinal disorders: Abdominal discomfort, distension. or pain; chapped lips; diarrhea; dry mouth; dyspepsia; eructation; flatulence; gastrointestinal disorder; gastroesophageal reflux disease; nausea; vomiting; jaundice; liver transaminitis
General disorders and administration site conditions: Asthenia; chest pain; fatigue; malaise; pain; peripheral swelling; pyrexia; swelling
Investigations: GFR decreased; weight increased
Metabolism and nutrition disorders: Decreased appetite; dehydration; hypophagia
Musculoskeletal and connective tissue disorders: Arthralgia; back pain; flank pain; joint swelling; limb discomfort; musculoskeletal discomfort; myalgia; neck pain; pain in extremity
Nervous system disorders: Ageusia; burning sensation; dizziness; dysgeusia; headache; hypoesthesia
Renal and urinary disorders: Nephrotic syndrome; proteinuria; renal failure
Skin and subcutaneous tissue disorders: Dry skin; hyperhidrosis; pemphigus foliaceus; pruritus; rash; rash pruritic; skin irritation; skin texture abnormal; skin wrinkling; urticaria
Warnings
Contraindications
Hypersensitivity
Cautions
Hypersensitivity reactions reported including drug fever, rash, fever, arthralgia, and lymphadenopathy
Not recommended if breastfeeding
Proteinuria
- Proteinuria reported, including nephrotic syndrome and membranous nephropathy
- Pediatric patients receiving >50 mg/kg/day may be at increased risk
- Monitor for development of proteinuria and discontinue therapy in patients who develop proteinuria
Drug interaction overview
- Thiola EC: Tiopronin is released faster from Thiola EC in the presence of alcohol and the risk for adverse events associated when taken with alcohol is unknown
- Avoid alcohol consumption 2 hr before and 3 hr after taking Thiola EC
Pregnancy & Lactation
Pregnancy
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
Clinical considerations
- Renal stones in pregnancy may increase risk of adverse pregnancy outcomes (eg, preterm birth, low birth weight)
Animal data
- No findings of fetal malformations could be attributed to the drug in reproduction studies in mice and rats at doses up to 2 times the highest recommended human dose of 2 grams/day (based on mg/m²)
Lactation
There are no data on the presence of tiopronin in either human or animal milk or on the effects of the breastfed child
Prescribing information describes a published study suggesting tiopronin may suppress milk production
Because of the potential for serious adverse reactions, including nephrotic syndrome, advise patients that breastfeeding is not recommended during treatment
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Tiopronin is an active reducing agent which undergoes thiol-disulfide exchange with cystine to form a mixed disulfide of tiopronin-cysteine; from this reaction, a water-soluble mixed disulfide is formed and the amount of sparingly soluble cystine is reduced
Absorption
Peak plasma time: 1 hr (immediate-release); 3 hr (delayed-release)
Elimination
Excretion: Urine 48% (4 hr); 78% (72 hr)
Administration
Oral Administration
Thiola: Take at least 1 hr before meals or 2 hr after meals
Thiola EC
- May take with or without food
- Swallow tablet whole; do not chew, crush, or split
Storage
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)
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Patient Handout
Formulary
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