Thiola

THIOLA- tiopronin tablet, sugar coated
Mission Pharmacal Company

1 INDICATIONS AND USAGE

THIOLA is indicated, in combination with high fluid intake, alkali, and diet modification, for the prevention of cystine stone formation in adults and pediatric patients 20 kg and greater with severe homozygous cystinuria, who are not responsive to these measures alone.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

Adults: The recommended initial dosage in adult patients is 800 mg/day. In clinical studies, the average dosage was about 1,000 mg/day.

Pediatrics: The recommended initial dosage in pediatric patients weighing 20 kg and greater is 15 mg/kg/day. Avoid dosages greater than 50 mg/kg per day in pediatric patients [see Warnings and Precautions (5.1), Use in Specific Populations (8.4)].

Administer THIOLA in 3 divided doses at the same times each day at least one hour before or 2 hours after meals.

Consider starting THIOLA at a lower dosage in patients with history of severe toxicity to d-penicillamine.

2.2 Monitoring

Measure urinary cystine 1 month after starting THIOLA and every 3 months thereafter. Adjust THIOLA dosage to maintain urinary cystine concentration less than 250 mg/L.

Assess for proteinuria before treatment and every 3 to 6 months during treatment [see Warnings and Precautions (5.1)].

Discontinue THIOLA in patients who develop proteinuria, and monitor urinary protein and renal function. Consider restarting THIOLA treatment at a lower dosage after resolution of proteinuria.

3 DOSAGE FORMS AND STRENGTHS

Tablets for oral use:100 mg tablets: round, white and imprinted in red with “M” on one side

4 CONTRAINDICATIONS

THIOLA is contraindicated in patients with hypersensitivity to tiopronin or any other components of THIOLA [see Warnings and Precautions (5.2)].

5 WARNINGS AND PRECAUTIONS

5.1 Proteinuria

Proteinuria, including nephrotic syndrome, and membranous nephropathy, have been reported with tiopronin use. Pediatric patients receiving greater than 50 mg/kg of tiopronin per day may be at increased risk for proteinuria [see Dosage and Administration (2.2), Adverse Reactions (6.1, 6.2) Use in Specific Populations (8.4)]. Monitor patients for the development of proteinuria and discontinue therapy in patients who develop proteinuria [see Dosage and Administration (2.2)].

5.2 Hypersensitivity Reactions

Hypersensitivity reactions (drug fever, rash, fever, arthralgia and lymphadenopathy) have been reported [see Contraindications (4)].

6 ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the labeling:

  • Proteinuria [see Warnings and Precautions (5.1)]
  • Hypersensitivity [see Warnings and Precautions (5.2)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed in the clinical trials of the drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse reactions occurring at an incidence of ≥5% in an uncontrolled trial in 66 patients with cystinuria age 9 to 68 years are shown in the table below. Patients in group 1 had previously been treated with d-penicillamine; those in group 2 had not. Of those patients who had stopped taking d-penicillamine due to toxicity (34 out of 49 patients in group 1), 22 were able to continue treatment with THIOLA. In those without prior history of d-penicillamine treatment, 6% developed reactions of sufficient severity to require THIOLA withdrawal.

Table 1 presents adverse reactions ≥5% in either treatment group occurring in this trial.

Table 1: Adverse Reactions Occurring in One or More Patients
System Organ Class Adverse Reaction Group 1 Previously treated with d‑penicillamine (N = 49) Group 2 Naïve to d‑penicillamine (N = 17)
Blood and Lymphatic System Disorders anemia 1 (2%) 1 (6%)
Gastrointestinal Disorders nausea 12 (25%) 2 (12%)
emesis 5 (10%)
diarrhea/soft stools 9 (18%) 1 (6%)
abdominal pain 1 (6%)
oral ulcers 6 (12%) 3 (18%)
General Disorders and Administration Site Conditions fever 4 (8%)
weakness 2 (4%) 2 (12%)
fatigue 7 (14%)
peripheral (edema) 3 (6%) 1 (6%)
chest pain 1 (6%)
Metabolism and Nutrition Disorders anorexia 4 (8%)
Musculoskeletal and Connective Tissue Disorders arthralgia 2 (12%)
Renal and Urinary Disorders proteinuria 5 (10%) 1 (6%)
impotence 1 (6%)
Respiratory, Thoracic and Mediastinal Disorders cough 1 (6%)
Skin and Subcutaneous Tissue Disorders rash 7 (14%) 2 (12%)
ecchymosis 3 (6%)
pruritus 2 (4%) 1 (6%)
urticaria 4 (8%)
skin wrinkling 3 (6%) 1 (6%)

Taste DisturbanceA reduction in taste perception may develop. It is believed to be the result of chelation of trace metals by tiopronin. Hypogeusia is often self-limited.

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