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 prevent the formation of cystine stones in adults and pediatric patients ≥20 kg having severe homozygous cystinuria who have been tried to treat with high fluid intake or alkali and diet modification but are resistant.

Note:

• Based on the American Urologic Association (AUA) guidelines for the medical management of kidney stones, tiopronin is recommended as the drug of choice for the prevention of recurrent cystine stones in patients that are unresponsive to increased fluid intake, restriction of sodium and protein intake, urinary alkalinization or who have large recurrent stone burdens.

Tiopronin (Acadione) Dose in Adults

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

• Initial: 800 mg/day divided in 3 doses; average dose: 1,000 mg/day. The dose should be low initially in patients with prior history of severe toxic reaction with d-penicillamine.
• Maintenance: dose should be adjusted accordingly to reduce urinary cystine level to <250 mg/L.

Tiopronin (Acadione) Dose in Childrens

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

Note: Use in combination with high fluid intake, alkali, and diet modification; dose should be low initially in patients with a history of severe toxicity to d-penicillamine:

• Children ≥2 years and Adolescents:

  • Initial: 15 mg/kg/day in 3 divided doses; adjust dose accordingly to keep urinary cysteine level to less than 250 mg/L.
  • The maximum daily dose: 50 mg/kg/day.
  • In one trial, patients with cystinuria (n=18, ages: 1.8 to 24 years), 16 patients received tiopronin along with urinary alkalinization to prevent nephrolithiasis or reduce the size of current stones. Mean dose required was 24.65 mg/kg/day (range: 13.8 to 51 mg/kg/day).
  • Older children need lower mg/kg dosing than younger children.
  • Stone incidence decreased from 0.28 per year to 0.03 per year and many patients had reductions in size and number of pre-existing stones.

• Dosing adjustment for toxicity:

  • Proteinuria:

    • Consider discontinuing the drug in patients who develop proteinuria, however, it can be resumed with a low dose once proteinuria settles.

Pregnancy Risk Category: N

• In animal reproduction studies, no adverse events were observed.

Use during lactation:

• It is unknown if breast milk contains tiopronin.
• Tiopronin may cause a drop in prolactin levels which can lead to decreased milk production in lactating mothers.
• Manufacturers do not recommend that you use this product during lactation.

Dose in Renal Disease:

There are no dosage recommendations provided in the manufacturer's labeling.

Dose in Liver disease:

There are no dosage recommendations provided in the manufacturer's labeling.

Common Side Effects of Tiopronin (Acadione):

• Central Nervous System:

  • Fatigue

• Dermatologic:

  • Skin Rash

• Gastrointestinal:

  • Nausea
  • Oral Mucosa Ulcer
  • Diarrhea

• Neuromuscular & Skeletal:

  • Arthralgia
  • Asthenia

Less Common Side Effects of Tiopronin (Acadione):

• Cardiovascular:

  • Chest Pain
  • Peripheral Edema

• Dermatologic:

  • Urticaria
  • Ecchymoses
  • Wrinkling Of Skin
  • Pruritus

• Gastrointestinal:

  • Vomiting
  • Anorexia
  • Abdominal Pain

• Genitourinary:

  • Proteinuria
  • Impotence

• Hematologic & Oncologic:

  • Anemia

• Respiratory:

  • Cough

• Miscellaneous:

  • Fever

Contraindication to Tiopronin (Acadione):

• Hypersensitivity/allergic reaction in past to tiopronin or any other component of the formulation.

Warnings and precautions

• Goodpasture syndrome:

  • Tiopronin has structural similarities to penicillamine.
  • Penicillamine has not been linked to Goodpasture Syndrome fatalities; therefore, it is possible for tiopronin-treated people to develop Goodpasture Syndrome. If you notice any symptoms or signs, discontinue treatment.

• Hematologic effects

  • Penicillamine has been associated with hematologic toxicities, tiopronin being structurally similar to penicillamine causes hematological effects as well.
  • Toxicity signs include thrombocytopenia or leukopenia with no eosinophilia.
  • Patients should promptly report any symptoms such as fever, sore throats, mouth ulcers or infections.
  • If the platelet count drops below 100,000./mm3 or WBC falls below 3,500/mm3, treatment must be stopped.

• Hypersensitivity

  • There have been hypersensitivity reactions such as drug fever, rash and fever, and lymphadenopathy.

• Myasthenia gravis:

  • Tiopronin has structural similarities to penicillamine. Penicillamine has not been linked to myasthenia Gravis. Therefore, it is possible for tiopronin-treated people to develop myasthenia graveis. Therapy should be stopped immediately if symptoms or signs appear.

• Pemphigus

  • Tiopronin has structural similarities to penicillamine. Pemphigus has been linked to penicillamine. If pemphigus-type reactions occur, stop treatment. Additional therapy may be offered.

• Proteinuria:

  • There have been reports of proteinuria that can be caused by nephrotic syndrome or membranous neuropathy.
  • Children who receive >50 mg/kg/day are at greater risk
  • Patients with proteinuria should be closely monitored. If they do, discontinue therapy.

Tiopronin: Drug Interaction

Monitoring parameters:

• Renal function,
• 24-hour urinary protein and urinalysis at baseline then every 3 to 6 months,
• urinary cystine 1 month after treatment begins then every 3 months;
• monitor for stone formation (eg, X-ray, ultrasound).

How to administer Tiopronin (Acadione)?

Oral:

• Delayed-release tablets:
  • Administer consistently with or without regard to meals. Swallow tablets whole; do not chew, crush, or split.
• IR tablets:
  • ​​​​​​​Administer 1 hour before or 2 hours after meals.

Mechanism of action of Tiopronin (Acadione):

• Tiopronin, an active reducing agent undergoes thiol–disulfide exchanging with cystine to create tiopronin–cystine disolvide.
• This is more water-soluble then cystine. The urine has a lower level of cystine, which is less soluble.
• There is also a lesser number of cystine calculi.
• InitialRapid.

Plasma peak time:

• Delayed release: 3 Hours (median), (range: 1 - 6 hours); Immediate Release: 1 Hour (median), (range: 0.0.5 - 2.1 hours).

Excretion:

• Urine (48% within 4 hours; 78% 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.