Tiopronin 300mg DR Tablets
It is used to prevent kidney stones.
Drug Class
Urological agent, cystine complexing agent
Pharmacologic Class
Thiol compound
Pregnancy Category
C
FDA Approved
Aug 1988
DEA Schedule
Not Controlled
Overview
What is this medicine?
Tiopronin is a medication used to treat a rare genetic condition called cystinuria. In cystinuria, too much of a substance called cystine builds up in the urine, leading to kidney stones. Tiopronin works by changing cystine into a more soluble form, making it easier for your body to pass it out in the urine and helping to prevent kidney stones from forming.
How to Use This Medicine
Taking Your Medication Correctly
To ensure you get the most out of your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely.
Some brands of this medication should be taken on an empty stomach, while others can be taken with or without food. It's essential to know how to take your specific brand. If your brand can be taken with or without food, take it the same way each time to maintain consistency. If you're unsure about how to take your medication, consult your doctor or pharmacist.
If you have difficulty swallowing tablets whole, some brands can be crushed and mixed with applesauce. To do this, crush one tablet at a time and mix with applesauce. The mixture can be stored in the refrigerator for up to 2 hours. After taking your dose, add water to the container, mix, and drink the contents. However, check with your doctor or pharmacist first to confirm if your brand can be crushed and mixed with applesauce.
Take your medication at the same time every day. Follow the diet plan and fluid intake instructions provided by your doctor. Adhere to the recommended type and amount of liquids to drink while taking this medication.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding the bathroom. Keep all medications in a safe 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. If you have questions about disposing of your medication, consult your pharmacist. You may also want to explore drug take-back programs in your area.
Missing 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 dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
To ensure you get the most out of your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely.
Some brands of this medication should be taken on an empty stomach, while others can be taken with or without food. It's essential to know how to take your specific brand. If your brand can be taken with or without food, take it the same way each time to maintain consistency. If you're unsure about how to take your medication, consult your doctor or pharmacist.
If you have difficulty swallowing tablets whole, some brands can be crushed and mixed with applesauce. To do this, crush one tablet at a time and mix with applesauce. The mixture can be stored in the refrigerator for up to 2 hours. After taking your dose, add water to the container, mix, and drink the contents. However, check with your doctor or pharmacist first to confirm if your brand can be crushed and mixed with applesauce.
Take your medication at the same time every day. Follow the diet plan and fluid intake instructions provided by your doctor. Adhere to the recommended type and amount of liquids to drink while taking this medication.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding the bathroom. Keep all medications in a safe 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. If you have questions about disposing of your medication, consult your pharmacist. You may also want to explore drug take-back programs in your area.
Missing 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 dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses to make up for the missed one.
Lifestyle & Tips
- Drink plenty of fluids (water) throughout the day and night to help dilute your urine and prevent stone formation. Aim for 3-4 liters per day, or as advised by your doctor.
- Maintain a low-sodium diet, as high sodium intake can increase cystine excretion.
- Limit protein intake, especially animal protein, as it can increase cystine excretion. Consult with a dietitian for specific recommendations.
- Alkalinize urine as directed by your doctor (e.g., with potassium citrate) to further increase cystine solubility, if recommended.
- Take the medication consistently as prescribed, even if you feel well. Do not stop taking it without consulting your doctor.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: 800 mg/day orally in 3 divided doses. Maintenance: Titrate based on cystine excretion, typically 800-1500 mg/day.
Dose Range:
800 - 4000 mg
Condition-Specific Dosing:
cystinuria:
Initial: 800 mg/day in 3 divided doses. Adjust dose to maintain urinary cystine excretion below 200 mg/L (100 mg/g creatinine) or 100 mg/L (50 mg/g creatinine) in patients with recurrent stone formation. Max dose: 4000 mg/day.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Initial: 15 mg/kg/day orally in 3 divided doses. Titrate based on cystine excretion. Max dose: 50 mg/kg/day or 4000 mg/day, whichever is less.
Adolescent:
Initial: 15 mg/kg/day orally in 3 divided doses. Titrate based on cystine excretion. Max dose: 50 mg/kg/day or 4000 mg/day, whichever is less.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, but monitor cystine excretion and adverse effects closely.
Moderate:
No specific dose adjustment recommended, but monitor cystine excretion and adverse effects closely. Consider lower initial doses and slower titration.
Severe:
Use with caution. No specific dose adjustment recommended, but monitor cystine excretion and adverse effects closely. Consider lower initial doses and slower titration.
Dialysis:
Not available. Tiopronin is likely dialyzable due to its low molecular weight, but specific recommendations are lacking. Use with extreme caution and close monitoring.
Hepatic Impairment:
Mild:
No specific dose adjustment recommended.
Moderate:
No specific dose adjustment recommended, but monitor for adverse effects.
Severe:
Use with caution. No specific dose adjustment recommended, but monitor for adverse effects, especially those related to liver function.
Pharmacology
Mechanism of Action
Tiopronin is a thiol compound that undergoes thiol-disulfide exchange with cystine, forming a more soluble mixed disulfide (tiopronin-cysteine disulfide) and cysteine. This reaction reduces the concentration of insoluble cystine in the urine, thereby preventing the formation and growth of cystine stones.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 50%
Tmax:
Approximately 2-3 hours (for immediate release; delayed-release may vary)
FoodEffect:
Food may delay absorption but does not significantly affect the extent of absorption. Delayed-release formulation is designed to reduce GI side effects.
Distribution:
Vd:
Not available
ProteinBinding:
Not available
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 2 hours
Clearance:
Not available
ExcretionRoute:
Renal (as tiopronin-cysteine disulfide and other metabolites)
Unchanged:
<1%
Pharmacodynamics
OnsetOfAction:
Within days to weeks (reduction in urinary cystine excretion)
PeakEffect:
Within weeks to months (stabilization of urinary cystine levels)
DurationOfAction:
Dependent on continued dosing; effects diminish rapidly upon discontinuation due to short half-life.
Safety & Warnings
Side Effects
Serious Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency 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 urinate
+ 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. While 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 unusual symptoms, contact your doctor for advice:
Gastrointestinal symptoms, 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 not mentioned here. 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.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency 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 urinate
+ 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. While 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 unusual symptoms, contact your doctor for advice:
Gastrointestinal symptoms, 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 not mentioned here. 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, especially if accompanied by fever or joint pain
- Unexplained fever, chills, or sore throat (signs of infection)
- Unusual bleeding or bruising
- Yellowing of the skin or eyes (jaundice)
- Severe abdominal pain, nausea, or vomiting (pancreatitis)
- Swelling in the legs, ankles, or feet (edema)
- Significant changes in taste sensation
- Dark urine or very little urine
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, as this medication may interact with other drugs or health conditions.
Before making any changes to your medication regimen, including starting, stopping, or adjusting the dose of any drug, consult with your doctor to confirm that it is safe to do so in conjunction with this medication.
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, as this medication may interact with other drugs or health conditions.
Before making any changes to your medication regimen, including starting, stopping, or adjusting the dose of any drug, consult with your doctor to confirm that it is safe to do so in conjunction with this medication.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. As directed by your doctor, regularly have your blood work and other laboratory tests monitored. To minimize potential interactions, avoid consuming alcohol within 2 hours before and 3 hours after taking this drug. If you are pregnant or planning to become pregnant, notify your doctor immediately. You and your doctor will need to discuss the potential benefits and risks associated with using this medication during pregnancy to make an informed decision.
Overdose Information
Overdose Symptoms:
- Nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Rash
- Fever
- Arthralgia
What to Do:
In case of suspected overdose, seek immediate medical attention. Call 911 or Poison Control at 1-800-222-1222. Management is supportive and symptomatic.
Drug Interactions
Moderate Interactions
- Iron salts (may reduce absorption of tiopronin if taken concurrently, separate administration by at least 1 hour)
- Other chelating agents (potential for additive effects or altered absorption, use with caution)
Monitoring
Baseline Monitoring
24-hour urinary cystine excretion
Rationale: To establish baseline cystine levels and guide initial dosing.
Timing: Prior to initiation of therapy
Complete Blood Count (CBC) with differential
Rationale: To establish baseline hematologic parameters due to potential for agranulocytosis or aplastic anemia.
Timing: Prior to initiation of therapy
Liver Function Tests (LFTs)
Rationale: To establish baseline liver function due to potential for cholestatic jaundice.
Timing: Prior to initiation of therapy
Renal Function (BUN, creatinine)
Rationale: To establish baseline renal function.
Timing: Prior to initiation of therapy
Urinalysis (proteinuria)
Rationale: To establish baseline for potential nephrotic syndrome.
Timing: Prior to initiation of therapy
Routine Monitoring
24-hour urinary cystine excretion
Frequency: Every 1-3 months initially, then every 3-6 months once stable
Target: <200 mg/L (or <100 mg/L in recurrent stone formers)
Action Threshold: If cystine excretion remains high, consider dose adjustment or adherence issues.
Complete Blood Count (CBC) with differential
Frequency: Every 2 weeks for the first 3 months, then monthly for 6 months, then every 3-6 months
Target: Within normal limits
Action Threshold: Significant decrease in WBC, neutrophils, or platelets; consider drug discontinuation.
Liver Function Tests (LFTs)
Frequency: Every 3-6 months or as clinically indicated
Target: Within normal limits
Action Threshold: Significant elevation in liver enzymes; investigate and consider drug discontinuation.
Urinalysis (proteinuria)
Frequency: Every 3-6 months or as clinically indicated
Target: Negative or trace protein
Action Threshold: New or worsening proteinuria; investigate for nephrotic syndrome.
Symptom Monitoring
- Skin rash
- Fever
- Joint pain (arthralgia)
- Sore throat or signs of infection (agranulocytosis)
- Unusual bleeding or bruising (aplastic anemia)
- Abdominal pain, nausea, vomiting (pancreatitis)
- Yellowing of skin or eyes (jaundice)
- Changes in taste (dysgeusia)
- Fatigue, weakness, pallor (anemia)
- Swelling (edema, related to nephrotic syndrome)
Special Patient Groups
Pregnancy
Category C. Animal studies have shown adverse effects on the fetus, but there are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus. Cystinuria can worsen during pregnancy, increasing stone risk.
Trimester-Specific Risks:
First Trimester:
Potential for teratogenicity based on animal data; use with caution.
Second Trimester:
Monitor for maternal and fetal complications; continue if benefits outweigh risks.
Third Trimester:
Monitor for maternal and fetal complications; continue if benefits outweigh risks.
Lactation
L3 (Moderately Safe). It is not known whether tiopronin is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Infant Risk:
Potential for unknown adverse effects; monitor infant for rash, fever, or other signs of toxicity.
Pediatric Use
Tiopronin is approved for use in pediatric patients with cystinuria. Dosing is weight-based (15 mg/kg/day initially, up to 50 mg/kg/day or 4000 mg/day). Close monitoring for adverse effects, especially hematologic and renal, is crucial.
Geriatric Use
No specific dose adjustments are generally required based on age alone. However, elderly patients may have decreased renal function, which warrants careful monitoring of cystine excretion and adverse effects. Start with lower doses and titrate slowly, as with other medications in this population.
Clinical Information
Clinical Pearls
- Tiopronin is an alternative to D-penicillamine for cystinuria, especially in patients who cannot tolerate D-penicillamine due to side effects.
- Delayed-release formulation (Thiola EC) is designed to improve gastrointestinal tolerability and may be taken with or without food.
- Adherence to high fluid intake and dietary modifications (low sodium, moderate protein) is critical for treatment success, even with medication.
- Regular monitoring of 24-hour urinary cystine excretion is essential to ensure adequate dosing and therapeutic efficacy.
- Patients should be educated on the importance of reporting any new or unusual symptoms, especially rash, fever, sore throat, or signs of bleeding/bruising, due to potential serious adverse effects.
Alternative Therapies
- D-penicillamine (another thiol compound, often first-line but with higher side effect profile)
- High fluid intake (cornerstone of management)
- Urinary alkalinization (e.g., potassium citrate, sodium bicarbonate)
- Dietary modifications (low sodium, moderate protein)
Cost & Coverage
Average Cost:
Check current per 30 tablets
Generic Available:
Yes
Insurance Coverage:
Tier 3 or Specialty Tier (requires prior authorization)
General Drug Facts
If your symptoms or health issues persist or worsen, it's 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 be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to discuss them with 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 seeking help, be prepared to provide detailed information about the overdose, including the medication taken, the amount, and the time it occurred.