Starting dosage Starting dosage

Start your patients on the right THIOLA dosage

The dosage of THIOLA should not be arbitrary; dosage should be based on the amount required to reduce cystine below its solubility limit, generally <250 mg/L. The recommended starting dosage in adults is 800 mg/day.1

Recommended starting dosage of THIOLA1

Adults:

May begin at
800 mg/day

Children ≥9 years of age:

May begin at 15
mg/kg/day

Patients with a history of severe toxicity to d-penicillamine may start at a lower dose.

Talk to your patients about the importance of taking THIOLA at least 1 hour before or 2 hours after meals, in divided doses, 3 times per day if possible.1

The reduction in urinary cystine is proportional to the THIOLA dosage1
Adult dosage1
1 g/day
2 g/day
Potential reduction in urinary cystine1
250 to 350 mg/day
500 mg/day

The dosing calculator can assist you in determining the appropriate dosage for your patients.

Advise patients

Advise patients taking THIOLA on the importance of continuing with a conservative treatment program consisting of high fluid intake and alkali and diet modification to achieve their goals of treatment.1

Learn more

Dosing calculator Dosing calculator

THIOLA adult dosing calculatora

This calculator is an aid to assist with dose calculation. It is important to consider other factors such as previous exposure to d-penicillamine, lifestyle, etc, when determining an appropriate dose.

In a multicenter trial, average dose of THIOLA was approximately 1000 mg/day.1

Calculator

The solubility limit of 250 mg/L is based on a urinary pH target goal of 6.5 to 7.0.1

Calculator

Cystine solubility is dependent on pH values.1

Calculator

A minimum urine output of at least 2 L/day on a consistent basis should be sought.1

Monitoring response Monitoring response

The importance of monitoring THIOLA response

A 24-hour urine collection to measure urinary cystine levels should be performed1,2:

Calendar

1 month

after starting THIOLA

Months

Every 3 months

thereafter

THIOLA dosage should be readjusted depending on the urinary cystine value.1

Successful management focused on routine measurements of cystine levels is associated with improved patient adherence and reduced need for surgical interventions.3

Adjusting dosage Adjusting dosage

Adjusting THIOLA dosage

Routine monitoring of patients’ cystine levels is critically important to ensuring they are on the right dosage of THIOLA.1,2 As patients’ 24-hour cystine and urinary output fluctuate, THIOLA dosage may need to be adjusted.1

While on THIOLA, patients should continue with a conservative treatment program and maintain a urine pH between 6.5 and 7.0.1

24-hour urine test

Using the 24-hour urine test to measure urinary output and cystine levels is a critical step in determining THIOLA dosage adjustments.1,2

References:  1. THIOLA [package insert]. San Antonio, TX: Mission Pharmacal Company.  2. Knoll T, Zöllner A, Wendt-Nordahl G, Michel MS, Alken P. Cystinuria in childhood and adolescence: recommendations for diagnosis, treatment, and follow-up. Pediatr Nephrol. 2005;20(1):19-24. doi:10.1007/s00467-004-1663-1.  3. Claes DJ, Jackson E. Cystinuria: mechanisms and management. Pediatr Nephrol. 2012;27(11):2031-2038. doi:10.1007/s00467-011-2092-6.  

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.