Tiopronin 100mg DR Tablets
It is used to prevent kidney stones.
Drug Class
Urolitholytic agent
Pharmacologic Class
Thiol compound
Pregnancy Category
Not available
FDA Approved
Apr 2019
DEA Schedule
Not Controlled
Overview
What is this medicine?
Tiopronin is a medication used to prevent kidney stones in people with a genetic condition called cystinuria. It works by making a substance called cystine, which forms the stones, more soluble in your urine. This helps to reduce the formation of new stones and may help dissolve existing ones.
How to Use This Medicine
Taking Your Medication Correctly
To ensure you get the most benefit from 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 well, and drink. 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 check if there are 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 dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses.
To ensure you get the most benefit from 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 well, and drink. 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 check if there are 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 dose, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses.
Lifestyle & Tips
- Maintain a very high fluid intake (e.g., 3-4 liters per day) to ensure high urine output and dilute cystine.
- Follow a low-sodium diet as directed by your doctor or dietitian.
- Follow a low-methionine diet (which means limiting high-protein foods) as advised by your healthcare provider.
- Take the medication consistently as prescribed, usually divided into 3 doses throughout the day.
- If advised by your doctor, take urine alkalinizing agents (e.g., potassium citrate) to increase urine pH, which further increases cystine solubility.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
Initial 800 mg/day, divided into 3 doses. Adjust based on 24-hour urinary cystine excretion.
Dose Range:
800 - 2000 mg
Condition-Specific Dosing:
cystinuria:
Adjust dose to achieve urinary cystine excretion of <200-250 mg/L. Usual maintenance dose is 800-1500 mg/day. Maximum dose 2000 mg/day.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Initial 15 mg/kg/day, divided into 3 doses. Adjust based on 24-hour urinary cystine excretion. Maximum dose 50 mg/kg/day or 2000 mg/day, whichever is less. Safety and efficacy established in pediatric patients 9 years and older.
Adolescent:
Same as adult or child dosing based on weight and clinical status.
Dose Adjustments
Renal Impairment:
Mild:
No specific dose adjustment recommended, but monitor renal function and cystine excretion closely.
Moderate:
No specific dose adjustment recommended, but monitor renal function and cystine excretion closely.
Severe:
No specific dose adjustment recommended, but monitor renal function and cystine excretion closely. Use with caution.
Dialysis:
Not specifically studied. Tiopronin is approximately 50-70% protein bound, suggesting limited removal by dialysis. Monitor clinical response and adverse effects.
Hepatic Impairment:
Mild:
No specific dose adjustment recommended. Use with caution.
Moderate:
No specific dose adjustment recommended. Use with caution.
Severe:
No specific dose adjustment recommended. Use with caution.
Pharmacology
Mechanism of Action
Tiopronin is a thiol compound that undergoes thiol-disulfide exchange with cystine, forming a mixed disulfide of tiopronin and cysteine. This mixed disulfide is approximately 50 times more soluble than cystine, thereby reducing the urinary concentration of cystine and preventing the formation of cystine stones.
Pharmacokinetics
Absorption:
Bioavailability:
Not explicitly quantified as a percentage, but well absorbed.
Tmax:
Approximately 2-3 hours (delayed-release formulation).
FoodEffect:
High-fat meal delays Tmax by approximately 2 hours and decreases Cmax by approximately 20%, but AUC is similar. Can be administered without regard to food.
Distribution:
Vd:
Not explicitly stated.
ProteinBinding:
Approximately 50-70%.
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 2-3 hours.
Clearance:
Not explicitly stated as a rate.
ExcretionRoute:
Primarily renal (as unchanged drug and metabolites).
Unchanged:
Approximately 20-30% excreted unchanged in urine.
Pharmacodynamics
OnsetOfAction:
Reduction in urinary cystine excretion can be observed within days of initiating therapy.
PeakEffect:
Optimal reduction in urinary cystine excretion and clinical benefit achieved with stable dosing over several weeks.
DurationOfAction:
Requires multiple daily doses due to its relatively 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 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 (difficulty getting or maintaining 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 symptoms that bother you or do not go away, contact your doctor:
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. 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 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 (difficulty getting or maintaining 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 symptoms that bother you or do not go away, contact your doctor:
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. 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:
- Severe or spreading skin rash, hives, or itching
- Fever, chills, or signs of infection (e.g., persistent sore throat, unusual fatigue)
- Unexplained joint pain or muscle pain
- Unusual bleeding or bruising
- Yellowing of the skin or eyes (jaundice)
- Dark urine or pale stools
- Severe nausea, vomiting, or diarrhea
- Significant decrease in urine output
- Swelling of the face, lips, tongue, or throat (signs of allergic reaction)
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 allergic reaction you experienced, including any symptoms that occurred.
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 (OTC) 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, consult with your doctor to confirm it is safe to:
Start taking a new medication
Stop taking a medication
* Change the dosage of any 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 allergic reaction you experienced, including any symptoms that occurred.
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 (OTC) 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, consult with your doctor to confirm it is safe to:
Start taking a new medication
Stop taking a medication
* Change the dosage of any 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 promptly. 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:
- Severe nausea
- Vomiting
- Diarrhea
- Abdominal pain
- Potentially severe allergic reactions
- Bone marrow suppression (e.g., severe fatigue, easy bruising, signs of infection)
What to Do:
Seek immediate medical attention. Call 911 or your local poison control center (e.g., 1-800-222-1222 in the US). Treatment is supportive and symptomatic.
Drug Interactions
Moderate Interactions
- Iron salts (e.g., ferrous sulfate): May reduce absorption of tiopronin. Separate administration by at least 1 hour.
- Other chelating agents: Potential for additive effects or altered pharmacokinetics, though not well studied.
Monitoring
Baseline Monitoring
24-hour urinary cystine excretion
Rationale: To establish baseline cystine excretion and guide initial dosing.
Timing: Before initiating therapy.
Renal function (serum creatinine, eGFR)
Rationale: To assess baseline kidney function.
Timing: Before initiating therapy.
Complete Blood Count (CBC)
Rationale: To assess baseline hematologic status and monitor for potential myelosuppression.
Timing: Before initiating therapy.
Urinalysis
Rationale: To check for proteinuria, hematuria, and other urinary abnormalities.
Timing: Before initiating therapy.
Routine Monitoring
24-hour urinary cystine excretion
Frequency: Every 1-3 months initially, then every 6-12 months once stable.
Target: <200-250 mg/L (or as per clinical guidelines)
Action Threshold: If cystine excretion remains high, consider dose increase, adherence check, or re-evaluation of dietary/fluid intake.
Renal function (serum creatinine, eGFR)
Frequency: Every 3-6 months.
Target: Normal for age and baseline.
Action Threshold: Significant decline in renal function, consider dose adjustment or investigation.
Complete Blood Count (CBC)
Frequency: Every 3-6 months.
Target: Normal.
Action Threshold: Significant abnormalities (e.g., leukopenia, thrombocytopenia, anemia), consider dose reduction, discontinuation, or further investigation.
Urinalysis
Frequency: Every 3-6 months.
Target: Normal.
Action Threshold: New onset or worsening proteinuria/hematuria, investigate.
Liver function tests (LFTs)
Frequency: Periodically, if clinically indicated or symptoms suggest hepatic dysfunction.
Target: Normal.
Action Threshold: Significant elevations, investigate.
Symptom Monitoring
- Skin rash (e.g., maculopapular, urticarial)
- Fever
- Arthralgia (joint pain)
- Myalgia (muscle pain)
- Gastrointestinal upset (nausea, vomiting, diarrhea, abdominal pain)
- Taste disturbances (dysgeusia)
- Fatigue
- Signs of infection (e.g., sore throat, fever, chills) due to potential leukopenia
- Unusual bleeding or bruising
- Yellowing of skin or eyes (jaundice)
- Dark urine
- Significant decrease in urine output
Special Patient Groups
Pregnancy
There are no available data on tiopronin use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, oral administration of tiopronin to pregnant rats and rabbits during organogenesis resulted in adverse developmental outcomes (increased post-implantation loss, decreased fetal body weight, and skeletal variations) at doses associated with maternal toxicity. Use only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential for increased post-implantation loss, decreased fetal body weight, and skeletal variations observed in animal studies during organogenesis.
Second Trimester:
Continued potential for adverse developmental outcomes.
Third Trimester:
Potential for continued growth restriction and skeletal effects.
Lactation
There are no data on the presence of tiopronin in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for tiopronin and any potential adverse effects on the breastfed infant from tiopronin or from the underlying maternal condition. Caution is advised.
Infant Risk:
Unknown, but potential for adverse effects based on drug's systemic absorption and mechanism of action. Monitor breastfed infant for adverse reactions.
Pediatric Use
Safety and efficacy of tiopronin delayed-release tablets have been established in pediatric patients 9 years and older. Dosing is weight-based. Limited data for children younger than 9 years.
Geriatric Use
No specific dose adjustment is recommended based on age alone. However, geriatric patients may have decreased renal function, which should be considered. Use with caution, generally starting at the lower end of the dosing range, and monitor for adverse effects.
Clinical Information
Clinical Pearls
- Tiopronin is often considered an alternative to D-penicillamine for cystinuria, particularly in patients who experience intolerable side effects with D-penicillamine, as tiopronin may have a better side effect profile.
- Adherence to high fluid intake (e.g., >3 liters/day) and dietary modifications (low sodium, low methionine) is paramount for successful management of cystinuria, even with medication.
- Regular monitoring of 24-hour urinary cystine excretion is crucial to guide dose adjustments and ensure therapeutic efficacy.
- Taste disturbances (dysgeusia) are a common, though usually mild, side effect.
- The delayed-release formulation helps to improve patient adherence by allowing for less frequent dosing compared to immediate-release formulations.
Alternative Therapies
- D-penicillamine (another thiol compound)
- High fluid intake (primary non-pharmacological therapy)
- Dietary modifications (low sodium, low methionine)
- Urinary alkalinization (e.g., potassium citrate, sodium bicarbonate) to increase cystine solubility
Cost & Coverage
Average Cost:
$5,000 - $10,000+ per 90-180 tablets (monthly supply)
Insurance Coverage:
Specialty Tier, typically requires prior authorization and may have step therapy requirements.
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, 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 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 medical attention. When seeking help, be prepared to provide details about the medication, including the amount taken and the time it happened, to facilitate prompt and effective treatment.