Tiopronin is a medication primarily used to treat cystinuria, a condition where cystine stones form in the kidneys, bladder, and/or urinary tract. It helps to decrease the amount of cystine in the urine, thus reducing the formation of these stones. Tiopronin works by binding to cysteine to form a more soluble compound that can be more easily excreted in urine.

The drug is also known by its brand name, Thiola. Patients prescribed tiopronin usually need to maintain a high fluid intake to further help prevent stone formation. In addition to treating cystinuria, tiopronin has also been used for various other medical conditions including certain forms of arthritis and to protect against certain side effects of chemotherapy, though these uses are less common and can be considered off-label.

Tiopronin (Acadione) is an orphan drug. It is used in the prevention of cysteine kidney stones by inhibiting the precipitation of cysteine in urine and making it more water-soluble.

Tiopronin Uses:

• Prevention of Nephrolithiasis (cystine kidney stones):
  • used to stop the development of cystine stones in adults and children under the age of 20 who have severe homozygous cystinuria and have not responded to increased fluid intake, alkali, or dietary changes.

Note:

• Tiopronin is suggested as the drug of preference for the prevention of recurrent cystine stones in patients who are unresponsive to increased fluid intake, sodium and protein restriction, urinary alkalinization, or who have significant recurrent stone burdens based on the American Urologic Association (AUA) guidelines for the medical management of kidney stones.

Tiopronin (Acadione) Dose in Adults

Tiopronin (Acadione) Dose in the Prevention of nephrolithiasis (cystine kidney stones): Oral:

• The typical starting dose of tiopronin is 800 milligrams per day, divided into three separate doses.
• The average dose that people usually take is about 1,000 milligrams per day.
• If someone has had a bad reaction to a similar medication called d-penicillamine, doctors might start with a lower dose of tiopronin.
• The dose may be adjusted over time to make sure that the amount of cystine in the urine stays below 250 milligrams per liter, which helps prevent the formation of new stones.

Tiopronin (Acadione) Dose in Childrens

Tiopronin (Acadione) Dose in the Prevention of nephrolithiasis (cystine kidney stones):

Note: Use with high fluid intake, alkali, and dietary changes; dosage should be reduced at first in individuals with a history of severe d-penicillamine toxicity:

For preventing kidney stones in children and adolescents with cystinuria:

• Age: For children and adolescents who are at least 2 years old.
• Dose: Start with 15 mg/kg per day, divided into three doses throughout the day.
• Goal: Adjust the dose over time to ensure the cysteine level in the urine is less than 250 mg/L.
• Maximum Dose: Do not exceed 50 mg/kg per day.

Observations from Studies

• In a study with 18 patients ages 1.8 to 24 years, the average dose needed was about 24.65 mg/kg per day, but this varied widely from 13.8 to 51 mg/kg per day.
• It was noted that older children might need lower doses per kg than younger, smaller children.
• The treatment led to a significant decrease in stone episodes per year and reduced the size and number of existing stones.

Dosing adjustment for toxicity:

• Proteinuria (protein in urine): If a patient develops proteinuria, stop tiopronin. Once the proteinuria resolves, consider resuming at a lower dose.

Using tiopronin in children under 20 kg has limited data, so careful monitoring and adjustments are necessary to balance efficacy and safety.

Pregnancy Risk Category: N

• In studies conducted on animals, no harmful effects were observed on reproduction when using the drug being studied.
• This suggests that the drug did not cause any problems during the reproductive process in the animals tested.

Use during lactation:

• Tiopronin has not been studied to see if it passes into breast milk.
• However, it is known to lower prolactin levels, which is a hormone important for milk production.
• This could potentially reduce milk supply in nursing mothers.
• Because of these concerns, the manufacturer recommends against breastfeeding while taking tiopronin.

Tiopronin Dose in Renal Disease:

• The manufacturer's labeling for tiopronin does not provide specific dosage recommendations for patients with renal impairment.

Tiopronin Dose in Liver disease:

• The manufacturer's labeling for tiopronin does not include specific dosage recommendations for patients with hepatic impairment.

Common Side Effects of Tiopronin (Acadione):

• Neuromuscular & Skeletal:
  • Arthralgia
  • Asthenia
• Central Nervous System:
  • Fatigue
• Gastrointestinal:
  • Diarrhea
  • Nausea
  • Oral Mucosa Ulcer
• Dermatologic:
  • Skin Rash

Less Common Side Effects of Tiopronin (Acadione):

• Cardiovascular:
  • Chest Pain
  • Peripheral Edema
• Dermatologic:
  • Wrinkling Of Skin
  • Pruritus
  • Urticaria
  • Ecchymoses
• Gastrointestinal:
  • Vomiting
  • Anorexia
  • Abdominal Pain
• Genitourinary:
  • Proteinuria
  • Impotence
• Hematologic & Oncologic:
  • Anemia
• Respiratory:
  • Cough
• Miscellaneous:
  • Fever

Contraindication to Tiopronin (Acadione):

• If a person is hypersensitive (allergic) to tiopronin or any ingredient in the medication's formulation, they should not use tiopronin.
• Hypersensitivity reactions can include a range of symptoms from mild rashes to severe allergic reactions, making it important for patients to avoid this medication if they have known allergies to it or its components.

Warnings and precautions

Goodpasture syndrome:

• Tiopronin shares structural similarities with penicillamine, a medication that has been rarely linked to a severe condition called Goodpasture syndrome.
• This syndrome can lead to serious kidney and lung problems and, in rare cases, can be fatal.
• Because of this potential risk, if someone taking tiopronin shows signs or symptoms of Goodpasture syndrome, it's essential to stop the medication immediately.
• These signs might include blood in the urine, difficulty breathing, or other unusual symptoms.
• Prompt medical attention is necessary if any concerning symptoms arise.

Hematologic effects

• Because tiopronin shares similarities in structure with penicillamine, it carries a risk of causing hematologic (blood-related) side effects.
• These may include conditions like leukopenia (reduced white blood cell count) without eosinophilia (an increase in a type of white blood cell called eosinophils) and thrombocytopenia (low platelet count).
• Patients should be advised to promptly report any early signs or symptoms of these issues, such as fever, sore throat, mouth ulcers, infections, easy bruising, or unusual bleeding under the skin (petechiae or purpura).
• If the platelet count drops below 100,000 per cubic millimeter or the white blood cell count falls below 3,500 per cubic millimeter, tiopronin therapy should be stopped.
• Early detection and management of these hematologic effects are crucial for patient safety.

Hypersensitivity

• Hypersensitivity reactions to tiopronin, including drug fever, rash, fever, joint pain (arthralgia), and swelling of lymph nodes (lymphadenopathy), have been reported.

Myasthenia gravis:

• Because tiopronin shares structural similarities with penicillamine, a medication that has been rarely linked to fatalities related to myasthenia gravis, there is a potential risk of myasthenia gravis in patients treated with tiopronin.
• Myasthenia gravis is a neuromuscular disorder characterized by muscle weakness and fatigue.
• If a person taking tiopronin experiences signs or symptoms of myasthenia gravis, such as muscle weakness, difficulty swallowing or breathing, or drooping eyelids, it's crucial to discontinue therapy immediately and seek medical attention.
• Prompt recognition and management of these symptoms are essential for patient safety.

Pemphigus

• Because tiopronin shares structural similarities with penicillamine, a medication associated with pemphigus, there is a potential risk of pemphigus-type reactions in patients treated with tiopronin.
• Pemphigus is a group of rare autoimmune diseases characterized by blistering of the skin and mucous membranes.
• If a person taking tiopronin develops symptoms suggestive of pemphigus, such as painful blisters on the skin or in the mouth, it's essential to discontinue treatment and seek medical attention promptly.

Proteinuria:

• Proteinuria, which includes conditions like nephrotic syndrome and membranous nephropathy, has been reported in patients taking tiopronin.
• There may be an increased risk of proteinuria in pediatric patients who receive doses higher than 50 mg/kg per day.
• It's important to monitor patients for the development of proteinuria while they are taking tiopronin.
• If proteinuria occurs, treatment should be interrupted.

Tiopronin: Drug Interaction

Monitoring parameters:

• Renal Function:
  • Patients should have their kidney function assessed at the beginning of treatment.
  • Follow-up assessments should occur every 3 to 6 months thereafter.
• Urinary Protein and Urinalysis:
  • Baseline assessments of 24-hour urinary protein and urinalysis should be conducted.
  • These tests should be repeated every 3 to 6 months during treatment.
• Urinary Cystine Levels:
  • Urinary cystine levels should be measured 1 month after starting tiopronin.
  • Subsequent measurements should be performed every 3 months.
• Stone Formation Monitoring:
  • Patients should be monitored for the formation of stones.
  • Imaging tests such as X-rays or ultrasounds may be used to detect stone formation.

How to administer Tiopronin (Acadione)?

Delayed-Release Tablets:

• Take consistently, with or without meals.
• Swallow the tablets whole; do not chew, crush, or split them.

Immediate-Release (IR) Tablets:

• Take the tablets either 1 hour before or 2 hours after meals.
• This timing helps optimize the absorption of the medication.

Mechanism of action of Tiopronin (Acadione):

• Tiopronin works as an active reducing agent in the body.
• It undergoes a process called thiol-disulfide exchange with cystine, a compound that contributes to the formation of kidney stones.
• This exchange forms a new compound called tiopronin-cystine disulfide, which is more soluble in water than cystine alone.
• As a result, the amount of cystine that can form into solid crystals in the urine decreases.
• This reduction in cystine crystals helps to prevent the formation of kidney stones made of cystine, known as cystine calculi

Onset: Rapid.

Time to Peak Plasma Concentration:

• Delayed Release: Median time to peak concentration is 3 hours (range: 1 to 6 hours).
• Immediate Release: Median time to peak concentration is 1 hour (range: 0.5 to 2.1 hours).

Excretion:

• Tiopronin is primarily excreted through urine.
• Approximately 48% of the dose is excreted within 4 hours, and around 78% is excreted within 72 hours.

International Brand Names of Tiopronin:

• Acadione
• Capen
• Captimer
• Chiosol
• Epatiol
• Kai Na
• Kai Xi Lai
• Mucolysin
• Mucosyt
• Orin
• Stargen
• Sutilan
• Thiola
• Vincol

Tiopronin Brand Names in Pakistan:

No Brands Available in Pakistan.