INDICATIONS: THIOLA® (tiopronin) tablets are indicated for the prevention of cystine (kidney) stone formation in patients with severe homozygous cystinuria with urinary cystine  >500 mg/day, who are resistant to treatment with conservative measures of high fluid intake, alkali and diet modification, or who have adverse reactions to d-penicillamine.

Important Safety Information 

CONTRAINDICATIONS: THIOLA is contraindicated during pregnancy (except where the benefits clearly outweigh the risks), in nursing mothers, and in patients who have previously developed agranulocytosis, aplastic anemia or thrombocytopenia while on this medication.

WARNINGS AND PRECAUTIONS:

  • While no deaths have been reported with THIOLA treatment, THIOLA can potentially cause all the serious adverse reactions reported for d-penicillamine, including death. 
  • Hematologic abnormalities requiring drug discontinuation may occur: inform patients to report promptly signs or symptoms of hematologic abnormalities.
  • Proteinuria, sometimes severe enough to cause nephrotic syndrome: monitor affected patients closely.
  • Discontinue THIOLA therapy if there are findings suggestive of Goodpasture’s syndrome, myasthenic syndrome, or myasthenia gravis. If pemphigus-type reactions occur, discontinue therapy and consider steroid treatment.
  • Inform patients about potential complications; advise them to promptly report any treatment-emergent signs or symptoms.
  • To reduce the risk of serious complications, the following tests should be conducted: 
    • Peripheral blood counts, direct platelet counts, hemoglobin, serum albumin, liver function tests, 24-hour urinary protein, routine urinalysis: 3-6 month intervals
    • Urinary cystine analysis: frequently during dose optimization, and at 6 month intervals thereafter
    • Abdominal roentgenogram: annually
  • In animal studies, THIOLA has been shown to cause fetal harm. THIOLA should only be used during pregnancy if the potential benefit justifies potential risk to the fetus.
  • THIOLA should not be used in nursing mothers.
  • The safety and efficacy of THIOLA in children under 9 years of age have not been established.

ADVERSE REACTIONS:

Adverse reactions associated with THIOLA include the following:

  • Drug fever during the first month
  • Generalized rash with pruritus
  • Lupus erythematous-like drug reaction (e.g., fever, arthralgia, lymphadenopathy, positive antinuclear antibody test)
  • Hypogeusia
  • Vitamin B6 deficiency (uncommon)
  • Wrinkling and friability of skin
  • Jaundice and abnormal liver function tests (in non-cystinuric conditions)

THIOLA is associated with fewer or less severe reactions than d-penicillamine, however the following adverse reactions may occur:  

  • Gastrointestinal (nausea, emesis, diarrhea, anorexia, abdominal pain, bloating, flatus)
  • Impairment in taste or smell
  • Dermatologic (pharyngitis, oral ulcers, rash, ecchymosis, pruritus, urticaria, warts, skin wrinkling, pemphigus, elastosis perforans serpiginosa)
  • Hypersensitivity reactions (laryngeal edema, dyspnea, respiratory distress, fever, chills, arthralgia, weakness, fatigue, myalgia, adenopathy)
  • Hematologic (increased bleeding, anemia, leukopenia, thrombocytopenia, eosinophilia)
  • Renal (proteinuria, nephrotic syndrome, hematuria)
  • Pulmonary (bronchiolitis, hemoptysis, pulmonary infiltrates, dyspnea)
  • Neurologic (myasthenic syndrome)

These reactions are more likely to occur during THIOLA therapy for patients who had previously shown toxicity to d-penicillamine.

Please see full Prescribing Information.