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
Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (1)
- ethanol
ethanol increases levels of tiopronin by Other (see comment). Modify Therapy/Monitor Closely. Comment: Tiopronin is released faster from the delayed-release product (Thiola EC) in the presence of alcohol and the risk for adverse events when taken with alcohol is unknown. Avoid alcohol consumption 2 hr before and 3 hr after taking delayed-release tiopronin.
Minor (0)
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
Unable to swallow tablet whole
- Crush and mix with applesauce
- Administration with other liquids or foods has not been studied and not recommended
-
Preparation and administration mixed in applesauce
- For patients who can swallow semi-solid food
- Crush tablet in a clean pill crusher or mortar and pestle; always crush 1 tablet at a time
- Measure ~1 tablespoon of applesauce and transfer it into a container with the crushed tablet
- Mix crushed tablet in applesauce until powder is well dispersed
- Administer entire drug-applesauce mixture immediately
- If this is not possible, may refrigerate mixture for up to 2 hr after adding crushed tablet to applesauce; discard any mixture that has not been given within 2 hr
- To assure that any leftover applesauce mixture from container is recovered, add tap water to the same container, mix, and administer
Storage
Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)
Images
Patient Handout
tiopronin oral
TIOPRONIN DELAYED-RELEASE - ORAL
(tye-OH-proe-nin)
COMMON BRAND NAME(S): Thiola EC
USES: This medication is used to prevent kidney stones in people with a certain inherited disorder (cystinuria). Cystinuria occurs when there is too much of a certain natural substance (the amino acid cystine) in the urine, leading to formation of kidney stones. Tiopronin works by making cystine more dissolvable in the urine.This medication should be used in combination with other methods to prevent kidney stones (such as drinking plenty of water, taking alkali treatment, following a special diet).
HOW TO USE: Take this medication by mouth with or without food as directed by your doctor, usually three times daily. You may take this medication with or without food, but it is important to choose one way and take this medication the same way with every dose.If you have trouble swallowing the tablets whole, you may crush the tablet and mix it with 1 tablespoonful of applesauce in a container. Do not use other foods or liquids. Crush only one tablet at a time. Mix well and take all of the mixture right away. Then add water to the container, mix, and drink the rinse water to make sure you get all of your dose. If you cannot take the crushed tablet-applesauce mixture right away, it can be kept in a refrigerator for up to 2 hours. Discard any mixture that has not been given after 2 hours.Avoid drinking alcohol 2 hours before and 3 hours after taking this medication. Drinking alcohol may increase the amount of this medication in your body which may cause serious side effects.Continue to drink plenty of water and to take the alkali medication as directed by your doctor. Closely follow the diet recommended by your doctor.The dosage is based on your medical condition, lab tests, and response to treatment. For children, the dosage may be based on their weight.Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day.Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase.Tell your doctor if your condition gets worse.
SIDE EFFECTS: Nausea, diarrhea, or decreased sense of taste/smell may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: muscle/joint pain, swollen lymph nodes, loss of appetite, tiredness, signs of kidney problems (such as change in the amount of urine, painful urination, cloudy/bloody/frothy urine), muscle weakness.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before taking tiopronin, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, kidney disease.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this medication passes into breast milk. Because of possible risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: Do not share this medication with others.Lab and/or medical tests (such as urine cystine levels, urine tests) should be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.
MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.
STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
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