Tiopronin 100mg Tablets
It is used to prevent kidney stones.
Drug Class
Urolitholytic agent
Pharmacologic Class
Thiol compound; Chelating agent
Pregnancy Category
Category C
FDA Approved
Aug 1988
DEA Schedule
Not Controlled
Overview
What is this medicine?
Tiopronin is a medication used to prevent kidney stones in people who have a genetic condition called cystinuria. It works by making a substance called cystine, which forms the stones, more soluble in your urine, so it's less likely to form crystals and stones.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and adhere to the guidelines below:
Take your medication on an empty stomach, either 1 hour before or 2 hours after meals, unless your doctor has advised you differently.
Take your medication at the same time every day to establish a routine.
Follow the dietary plan recommended by your doctor to ensure you're getting the nutrients you need while taking this medication.
Adhere to your doctor's guidance on the types of liquids to drink and the amount of fluid intake while taking this medication.
Storing and Disposing of Your Medication
To maintain the effectiveness and safety of your medication:
Store it at room temperature in a dry place, avoiding bathrooms and areas prone to moisture.
Keep all medications in a secure location, out of the reach of children and pets.
* Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so by your doctor or pharmacist. If you're unsure about the best way to dispose of your medication, consult your pharmacist. You may also have access to drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Avoid taking two doses at the same time or taking extra doses, as this can increase the risk of side effects.
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided to you and adhere to the guidelines below:
Take your medication on an empty stomach, either 1 hour before or 2 hours after meals, unless your doctor has advised you differently.
Take your medication at the same time every day to establish a routine.
Follow the dietary plan recommended by your doctor to ensure you're getting the nutrients you need while taking this medication.
Adhere to your doctor's guidance on the types of liquids to drink and the amount of fluid intake while taking this medication.
Storing and Disposing of Your Medication
To maintain the effectiveness and safety of your medication:
Store it at room temperature in a dry place, avoiding bathrooms and areas prone to moisture.
Keep all medications in a secure location, out of the reach of children and pets.
* Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so by your doctor or pharmacist. If you're unsure about the best way to dispose of your medication, consult your pharmacist. You may also have access to drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Avoid taking two doses at the same time or taking extra doses, as this can increase the risk of side effects.
Lifestyle & Tips
- Drink plenty of fluids (e.g., water) throughout the day and night to maintain a high urine output (aim for 3-4 liters/day).
- Limit sodium intake in your diet, as high sodium can increase cystine excretion.
- Limit animal protein intake, as it can increase acid load and cystine excretion.
- Take the medication on an empty stomach (at least 1 hour before or 2 hours after meals) to ensure proper absorption.
- Do not stop taking the medication without consulting your doctor, even if you feel well.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: 800 mg/day in 3 divided doses. Maintenance: Adjusted to achieve urinary cystine excretion < 200 mg/L.
Dose Range:
200 - 1500 mg
Condition-Specific Dosing:
Cystinuria:
Initial: 800 mg/day in 3 divided doses. Adjust dose based on 24-hour urinary cystine excretion (target < 200 mg/L). Typical maintenance dose is 600-1500 mg/day.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Initial: 15 mg/kg/day in 3 divided doses. Adjust dose based on 24-hour urinary cystine excretion (target < 200 mg/L). Max: 50 mg/kg/day or 4000 mg/day, whichever is less.
Adolescent:
Initial: 15 mg/kg/day in 3 divided doses. Adjust dose based on 24-hour urinary cystine excretion (target < 200 mg/L). Max: 50 mg/kg/day or 4000 mg/day, whichever is less.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, but monitor renal function and urinary cystine levels closely.
Moderate:
Use with caution. Consider lower initial doses and careful titration based on urinary cystine levels and renal function.
Severe:
Use with caution. Significant dose reduction may be necessary. Monitor closely for adverse effects and efficacy.
Dialysis:
Not well studied. Tiopronin is dialyzable. Consider administering after dialysis sessions and monitor closely.
Hepatic Impairment:
Mild:
No specific dose adjustment recommended.
Moderate:
Use with caution. Monitor liver function tests.
Severe:
Use with caution. Not well studied. Monitor liver function tests and for adverse effects.
Pharmacology
Mechanism of Action
Tiopronin is a thiol compound that undergoes disulfide exchange with cystine, forming a mixed disulfide of tiopronin and cysteine. This mixed disulfide is more soluble than cystine, thereby reducing the concentration of insoluble cystine in the urine and preventing the formation of cystine stones.
Pharmacokinetics
Absorption:
Bioavailability:
Variable, approximately 50-70% (oral)
Tmax:
Approximately 1-2 hours
FoodEffect:
Food significantly decreases absorption (up to 50%). Should be taken at least 1 hour before or 2 hours after meals.
Distribution:
Vd:
Not available
ProteinBinding:
Not extensively protein bound
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 1.5-2 hours
Clearance:
Not available
ExcretionRoute:
Renal (primarily as metabolites and mixed disulfides)
Unchanged:
Less than 1% (renal)
Pharmacodynamics
OnsetOfAction:
Within days to weeks (reduction in urinary cystine saturation)
PeakEffect:
Weeks to months (stabilization of stone formation)
DurationOfAction:
Dependent on continued dosing due to short half-life
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of kidney problems, including:
+ Inability to pass urine
+ Changes in urine output
+ Blood in the urine
+ Sudden weight gain
Fever
Joint pain
Swollen glands
Any skin changes
Swelling in the arms or legs
Chest pain
Erectile dysfunction (inability to get or keep an erection)
Other Possible Side Effects
Like all medications, this drug can cause side effects. Although many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor:
Gastrointestinal issues, such as:
+ Diarrhea
+ Stomach pain
+ Upset stomach
+ Vomiting
+ Decreased appetite
Change in taste
Mouth sores
Cough
Feeling tired or weak
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of kidney problems, including:
+ Inability to pass urine
+ Changes in urine output
+ Blood in the urine
+ Sudden weight gain
Fever
Joint pain
Swollen glands
Any skin changes
Swelling in the arms or legs
Chest pain
Erectile dysfunction (inability to get or keep an erection)
Other Possible Side Effects
Like all medications, this drug can cause side effects. Although many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor:
Gastrointestinal issues, such as:
+ Diarrhea
+ Stomach pain
+ Upset stomach
+ Vomiting
+ Decreased appetite
Change in taste
Mouth sores
Cough
Feeling tired or weak
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- New or worsening skin rash, itching, or hives
- Fever or chills
- Joint pain or muscle aches
- Unusual bleeding or bruising
- Yellowing of skin or eyes (jaundice)
- Dark urine or pale stools
- Severe stomach pain, nausea, or vomiting
- Swelling of hands, ankles, or feet
- Changes in urination (e.g., decreased urine output, blood in urine)
- Sore throat, mouth sores, or signs of infection
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced as a result of the allergy.
If you are breastfeeding, as you should not breastfeed while taking this medication.
To ensure safe treatment, it is crucial to discuss the following with your doctor and pharmacist:
All medications you are currently taking, including prescription and over-the-counter drugs, natural products, and vitamins.
Any existing health problems you have.
Your doctor needs this information to assess potential interactions between this medication and other substances or health conditions. Do not start, stop, or change the dose of any medication without first consulting your doctor to confirm it is safe to do so.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced as a result of the allergy.
If you are breastfeeding, as you should not breastfeed while taking this medication.
To ensure safe treatment, it is crucial to discuss the following with your doctor and pharmacist:
All medications you are currently taking, including prescription and over-the-counter drugs, natural products, and vitamins.
Any existing health problems you have.
Your doctor needs this information to assess potential interactions between this medication and other substances or health conditions. Do not start, stop, or change the dose of any medication without first consulting your doctor to confirm it is safe to do so.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regular blood tests and other laboratory assessments should be conducted as directed by your doctor to monitor your condition. Certain products may require you to avoid consuming alcohol; consult your doctor or pharmacist to determine if this applies to your specific medication. If you are pregnant or planning to become pregnant, discuss the potential benefits and risks of using this medication during pregnancy with your doctor to make an informed decision.
Overdose Information
Overdose Symptoms:
- Severe nausea or vomiting
- Diarrhea
- Abdominal pain
- Skin rash
- Fatigue
- Signs of bone marrow suppression (e.g., unusual bleeding, bruising, signs of infection)
What to Do:
Seek immediate medical attention or call a poison control center (1-800-222-1222). Treatment is supportive and symptomatic. Gastric lavage or activated charcoal may be considered if ingestion is recent. Monitor vital signs and blood counts.
Drug Interactions
Major Interactions
- Oxidizing agents (e.g., hydrogen peroxide, iodine): May inactivate tiopronin.
- Iron salts: May form insoluble complexes with tiopronin, reducing absorption of both.
Moderate Interactions
- Other chelating agents (e.g., D-penicillamine): Concurrent use not recommended due to potential for additive toxicity and similar mechanism of action.
- Antacids containing aluminum or magnesium: May interfere with absorption if taken concurrently.
Monitoring
Baseline Monitoring
24-hour urinary cystine excretion
Rationale: To establish baseline cystine levels and guide initial dosing.
Timing: Before starting therapy
Complete Blood Count (CBC) with differential
Rationale: To monitor for potential hematologic abnormalities (e.g., leukopenia, thrombocytopenia, aplastic anemia).
Timing: Before starting therapy
Liver Function Tests (LFTs)
Rationale: To monitor for potential hepatotoxicity.
Timing: Before starting therapy
Renal Function Tests (serum creatinine, BUN)
Rationale: To assess baseline renal function and guide dosing.
Timing: Before starting therapy
Urinalysis (including microscopy)
Rationale: To assess for proteinuria, hematuria, and crystalluria.
Timing: Before starting therapy
Routine Monitoring
24-hour urinary cystine excretion
Frequency: Every 1-3 months initially, then every 6-12 months once stable
Target: < 200 mg/L (or individualized target)
Action Threshold: If above target, consider dose adjustment or adherence issues.
Complete Blood Count (CBC) with differential
Frequency: Every 2-4 weeks for the first 6 months, then every 3-6 months
Target: Within normal limits
Action Threshold: Significant decrease in WBC, platelets, or hemoglobin; consider dose reduction or discontinuation.
Liver Function Tests (LFTs)
Frequency: Every 3-6 months
Target: Within normal limits
Action Threshold: Significant elevation in transaminases or bilirubin; consider dose reduction or discontinuation.
Renal Function Tests (serum creatinine, BUN)
Frequency: Every 3-6 months
Target: Within normal limits
Action Threshold: Significant increase in creatinine; consider dose adjustment or discontinuation.
Urinalysis (including microscopy)
Frequency: Every 3-6 months
Target: No significant proteinuria or hematuria
Action Threshold: New onset or worsening proteinuria/hematuria; investigate and consider drug-induced nephropathy.
Symptom Monitoring
- Skin rash (maculopapular, pruritic, urticarial)
- Fever
- Arthralgia
- Myalgia
- Proteinuria
- Hematuria
- Gastrointestinal upset (nausea, vomiting, diarrhea)
- Loss of taste (dysgeusia)
- Fatigue
- Sore throat or signs of infection (due to potential leukopenia)
Special Patient Groups
Pregnancy
Category C. Use only if the potential benefit justifies the potential risk to the fetus. Cystinuria can worsen during pregnancy, increasing stone risk. Close monitoring of urinary cystine levels and renal function is essential.
Trimester-Specific Risks:
First Trimester:
Potential for teratogenicity, though human data are limited. Weigh risks vs. benefits.
Second Trimester:
Continued risk of adverse effects, but may be necessary to prevent maternal complications.
Third Trimester:
Continued risk of adverse effects, but may be necessary to prevent maternal complications.
Lactation
L3 (Moderately safe). Tiopronin is excreted into breast milk in small amounts. Monitor breastfed infants for adverse effects (e.g., rash, GI upset, signs of bone marrow suppression). Consider alternative therapies or temporary discontinuation of breastfeeding if concerns arise.
Infant Risk:
Low to moderate risk. Potential for mild GI upset or rash in infant. Long-term effects unknown.
Pediatric Use
Tiopronin is used in pediatric patients with cystinuria. Dosing is weight-based. Close monitoring for adverse effects, especially hematologic and renal, is crucial. Long-term safety and efficacy data are available.
Geriatric Use
No specific dose adjustments are typically required based on age alone. However, geriatric patients may have reduced renal function, which necessitates careful monitoring of renal function and potential dose adjustment based on creatinine clearance. Increased susceptibility to adverse effects should be considered.
Clinical Information
Clinical Pearls
- Tiopronin is a second-line agent for cystinuria, typically used when hydration and alkalinization are insufficient or not tolerated, or when D-penicillamine is not tolerated.
- Adherence to dietary modifications (low sodium, low animal protein) and high fluid intake is crucial for optimal treatment outcomes with tiopronin.
- The extended-release formulation (Thiola EC) may improve patient adherence due to less frequent dosing and reduced GI side effects.
- Patients should be educated on the importance of taking the medication on an empty stomach to maximize absorption.
- Regular monitoring of urinary cystine excretion is essential to ensure therapeutic efficacy and guide dose adjustments.
- Close monitoring for adverse effects, particularly dermatologic, hematologic, and renal, is critical, especially during the initial months of therapy.
Alternative Therapies
- High fluid intake (hydration)
- Urinary alkalinization (e.g., potassium citrate, sodium bicarbonate)
- D-penicillamine (another thiol compound, often first-line if pharmacologic therapy is needed)
- Alpha-mercaptopropionylglycine (MPG) - older name for Tiopronin
- Cystine-binding agents (e.g., alpha-lipoic acid - investigational)
Cost & Coverage
Average Cost:
$1000 - $3000+ per 100 tablets (100mg)
Generic Available:
Yes
Insurance Coverage:
Specialty Tier (requires prior authorization)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist for more information. If you have any questions or concerns about this medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred.