Thiola
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Questions & Answers
Side Effects & Adverse Reactions
Despite apparent lower toxicity of THIOLA™, THIOLA® may potentially cause all the serious adverse reactions reported for d-penicillamine. Thus, although no death has been reported to result directly from THIOLA® treatment, a fatal outcome from THIOLA® is possible, as has been reported with d-penicillamine therapy from such complications as aplastic anemia, agranulocytosis, thrombocytopenia, Goodpasture’s syndrome or myasthenia gravis.
Leukopenia of the granulocytic series may develop without eosinophilia. Thrombocytopenia may be immunologic in origin or occur on an idiosyncratic basis. The reduction in peripheral blood white count to less than 3500/cubic mm or in platelet count to below 100,000 cubic mm mandates cessation of therapy. Patients should be instructed to report promptly the occurrence of any symptom or sign of these hematological abnormalities, such as fever, sore throat, chills, bleeding or easy bruisability.
Proteinuria, sometimes sufficiently severe to cause nephrotic syndrome, may develop from membranous glomerulopathy. A close observation of affected patients is mandatory.
The following complications, though rare, have been reported during d-penicillamine therapy and could occur during THIOLA® treatment. When there are abnormal urinary findings associated with hemoptysis and pulmonary infiltrates suggestive of Goodpasture’s syndrome, THIOLA® treatment should be stopped. Appearance of myasthenic syndrome or myasthenia gravis requires cessation of treatment. When pemphigus-type reactions develop, THIOLA® therapy should be stopped. Steroid treatment may be necessary.
Legal Issues
There is currently no legal information available for this drug.
FDA Safety Alerts
There are currently no FDA safety alerts available for this drug.
Manufacturer Warnings
There is currently no manufacturer warning information available for this drug.
FDA Labeling Changes
There are currently no FDA labeling changes available for this drug.
Uses
THIOLA® is indicated for the prevention of cystine (kidney) stone formation in patients with severe homozygous cystinuria with urinary cystine greater than 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.
Cystine stones typically occur in approximately 10,000 persons in the United States who are homozygous for cystinuria. These persons excrete abnormal amounts of cystine in urine of over 250 mg/g creatinine, as well as excessive amounts of other dibasic amino acids (lysine, arginine and ornithine). In addition, they show varying intestinal transport defects for these same amino acids. The stone formation is the result of poor aqueous solubility of cystine.
Since there are no known inhibitors of the crystallization of cystine, the stone formation is determined primarily by the urinary supersaturation of cystine. Thus, cystine stones could theoretically form whenever urinary cystine concentration exceeds the solubility limit. Cystine solubility in urine is pH-dependent, and ranges from 170-300 mg/liter at pH 5, 190-400 mg/liter at pH 7 and 220-500 mg/liter at pH 7.5.
The goal of therapy is to reduce urinary cystine concentration below its solubility limit. It may be accomplished by dietary means aimed at reducing cystine synthesis and by a high fluid intake in order to increase urine volume and thereby lower cystine concentration.
Unfortunately, the above conservative measures alone may be ineffective in controlling cystine stone formation in some homozygous patients with severe cystinuria (urinary cystine exceeding 500 mg/day). In such patients, d-penicillamine has been used as an additional therapy. Like THIOLA™, dpenicillamine undergoes thiol-disulfide exchange with cystine, thereby lowering the amount of sparingly soluble cystine in urine.
However, d-penicillamine treatment is frequently accompanied by adverse reactions, such as dermatologic complications, hypersensitivity reactions, hematologic abnormalities and renal disturbances. THIOLA® may have a particular therapeutic role in such patients.
History
There is currently no drug history available for this drug.
Other Information
THIOLA® (Tiopronin) is a reducing and complexing thiol compound. Tiopronin is N-(2-Mercaptopropionyl) glycine and has the following structure:
Tiopronin has the empirical formula C5H9NO3S and a molecular weight of 163.20. In this drug product tiopronin exists as a dl racemic mixture.
Tiopronin is a white crystalline powder which is freely soluble in water.
THIOLA® tablets are white, sugar coated tablets, each containing 100 mg. of Tiopronin and are taken orally.
Inactive ingredients: Calcium carbonate, carnauba wax, ethyl cellulose, Eudragit E 100, hydroxy-propyl cellulose, lactose, magnesium stearate, povidone, sugar, talc, titanium dioxide.
Sources
Thiola Manufacturers
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Mission Pharmacal Company
![Thiola (Tiopronin) Tablet, Sugar Coated [Mission Pharmacal Company]](/wp-content/themes/bootstrap/assets/img/loading2.gif)
Thiola | Mission Pharmacal Company
It is recommended that a conservative treatment program should be attempted first. At least 3 liters of fluid (10-10 oz. glassfuls) should be provided, including two glasses with each meal and at bedtime. The patients should be expected to awake at night to urinate; they should drink two more glasses of fluids before returning to bed. Additional fluids should be consumed if there is excessive sweating or intestinal fluid loss. A minimum urine output of 2 liters/day on a consistent basis should be sought. A modest amount of alkali should be provided in order to maintain urinary pH at a high normal range (6.5-7.0). Potassium alkali are advantageous over sodium alkali, because they do not cause hypercalciuria and are less likely to cause the complication of calcium stones.
Excessive alkali therapy is not advisable. When urinary pH increases above 7.0 with alkali therapy, the complication of calcium phosphate nephrolithiasis may ensue because of the enhanced urinary supersaturation of hydroxyapatite in an alkaline environment.
In patients who continue to form cystine stones on the above conservative program, THIOLA® may be added to the treatment program. THIOLA® may also be substituted for d-penicillamine in patients who have developed toxicity to the latter drug. In both situations, the conservative treatment program should be continued.
The dose of THIOLA® should not be arbitrary but should be based on that amount required to reduce urinary cystine concentration to below its solubility limit (generally <250 mg/liter). The extent of the decline in cystine excretion is generally dependent on the THIOLA® dosage.
THIOLA® may be begun at a dosage of 800 mg/day in adult patients with cystine stones. In a multiclinic trial, average dose of THIOLA® was about 1000 mg/day. However, some patients require a smaller dose. In children, initial dosage may be based on 15 mg/kg/day. Urinary cystine should be measured at 1 month after THIOLA® treatment, and every 3 months thereafter. THIOLA® dosage should be readjusted depending on the urinary cystine value. Whenever possible, THIOLA® should be given in divided doses 3 times/day at least one hour before or 2 hours after meals.
In patients who had shown severe toxicity to d-penicillamine, THIOLA® might be begun at a lower dosage.
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