Adult: Prevention of cystine stone formation in patients with severe homozygous cystinuria who are resistant to treatment with high fluid intake or alkali and diet modification: Initially, 800 mg daily. Average dose: 1,000 mg daily. Administer in 3 divided doses, along with adequate hydration and alkalinisation of the urine. Adjust dose to reduce urinary cystine level to <250 mg/L. May initiate treatment at a lower dose in patients with history of severe d-penicillamine toxicity. Child: ≥2 years Prevention of cystine stone formation in ≥20 kg patients with severe homozygous cystinuria who are resistant to treatment with high fluid intake or alkali and diet modification: Initially, 15 mg/kg daily. Max: 50 mg/kg daily. Administer in 3 divided doses, along with adequate hydration and alkalinisation of the urine. Adjust dose to reduce urinary cystine level to <250 mg/L. May initiate treatment at a lower dose in patients with history of severe d-penicillamine toxicity.
Administration
immediate-release: Should be taken on an empty stomach. Take at least 1 hr before or 2 hr after meals & at the same time each day. Ensure adequate fluid intake. delayed-release: May be taken with or without food. Take consistently w/ or w/o meals & at the same time each day. Ensure adequate fluid intake.
Contraindications
History of blood dyscrasias. Lactation.
Special Precautions
Children and elderly. Pregnancy.
Adverse Reactions
Significant: Proteinuria including nephrotic syndrome and membranous nephropathy, pemphigus, haematologic effects (e.g. leucopenia without eosinophilia, thrombocytopenia), hypersensitivity reactions (e.g. drug fever, rash, fever, arthralgia, lymphadenopathy). Blood and lymphatic system disorders: Anaemia, eosinophilia. Gastrointestinal disorders: Nausea, vomiting, diarrhoea, abdominal pain, flatulence, bloating, oral ulcer. General disorders and admin site conditions: Fatigue, malaise, asthenia, peripheral oedema. Hepatobiliary disorders: Jaundice. Investigations: Decreased GFR. Metabolism and nutrition disorders: Anorexia, dehydration. Musculoskeletal and connective tissue disorders: Myalgia, back pain, joint swelling. Nervous system disorders: Ageusia, dysgeusia, headache, vertigo. Renal and urinary disorders: Haematuria. Respiratory, thoracic and mediastinal disorders: Dyspnoea, cough, pharyngitis. Skin and subcutaneous tissue disorders: Rash, pruritus, erythema, skin wrinkling. Potentially Fatal: Rare: Goodpasture syndrome, myasthenia gravis.
Ensure adequate fluid intake while you are being treated with this drug.
Monitoring Parameters
Monitor renal function tests, 24-hour urinary protein and urinalysis at baseline and every 3-6 months thereafter; urinary cystine 1 month after treatment initiation and every 3 months thereafter; stone formation (e.g. X-ray, ultrasound); LFTs, CBC with differential, platelet count, and Hb.
Food Interaction
May increase bioavailability with alcohol. Delayed-release tab: Released faster from its formulation with alcohol.
Action
Description: Tiopronin is sulfhydryl compound acting as a chelator and active reducing agent with properties similar to penicillamine. It undergoes thiol-disulfide exchange with cystine to form tiopronin-cystine disulfide which is more water soluble than cystine, thereby resulting in the decrease of the amount of sparingly soluble cystine in the urine, and reduction of the formation of cystine calculi. Onset: Rapid. Pharmacokinetics: Absorption: Absorbed from the gastrointestinal tract. Time to peak plasma concentration: Approx 1 hour (immediate-release tab); approx 3 hours (delayed-release tab). Excretion: Via urine (approx 48% within 4 hours; approx 78% within 72 hours).
Chemical Structure
Tiopronin Source: National Center for Biotechnology Information. PubChem Database. Tiopronin, CID=5483, https://pubchem.ncbi.nlm.nih.gov/compound/Tiopronin (accessed on Jan. 23, 2020)
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