Thiola (Page 2 of 2)

ADVERSE REACTIONS

Some patients may develop drug fever, usually during the first month of therapy. THIOLA ® treatment should be discontinued until the fever subsides. It may be reinstated at a small dose, with a gradual increase in dosage until the desired level is achieved.

A generalized rash (erythematous, maculopapular or morbilliform) accompanied by pruritis may develop during the first few months of treatment. It may be controlled by antihistamine therapy, typically recedes when THIOLA ® treatment is discontinued, and seldom recurs when THIOLA ® treatment is restarted at a lower dosage. Less commonly, rash may appear late in the course of treatment (of more than 6 months). Located usually in the trunk, the late rash is associated with intense pruritis, recedes slowly after discontinuing treatment, and usually recurs upon resumption of treatment.

A drug reaction simulating lupus erythematous, manifested by fever, arthralgia and lymphadenopathy may develop. It may be associated with a positive antinuclear antibody test, but not necessarily with nephropathy. It may require discontinuance of THIOLA ® treatment.

A reduction in taste perception may develop. It is believed to be the result of chelation of trace metals by THIOLA . Hypogeusia is often self-limiting.

Unlike during d-penicillamine therapy, vitamin B6 deficiency is uncommonly associated with THIOLA ® treatment.

Some patients may complain of wrinkling and friability of skin. This complication usually occurs after long-term treatment, and is believed to result from the effect of THIOLA ® on collagen.

A multiclinic trial involving 66 cystinuric patients in the United States indicated that THIOLA ® is associated with fewer or less severe adverse reactions than d-penicillamine. Among those who had to stop taking d-penicillamine due to toxicity, 64.7% could take THIOLA ®. In those without prior history of d-penicillamine treatment, only 5.9% developed reactions of sufficient severity to require THIOLA ® withdrawal. A review of available literature supports the findings from this trial.

Despite this apparent reduced toxicity to THIOLA ® relative to d-penicillamine, THIOLA ® treatment may potentially be associated with all the adverse reactions reported with d-penicillamine. They include:
           Gastrointestinal side-effects (nausea, emesis, diarrhea or softstools, anorexia, abdominal pain, bloating or flatus) in about 1 in 6 patients;
           Impairment in taste and smell in about 1 in 25 patients;
           Dermatologic complications (pharyngitis, oral ulcers, rash, ecchymosis, prurites, uritcaria, warts, skin wrinkling, pemphigus, elastosis perforans serpiginosa) in about 1 in 6 patients;
           Hypersensitivity reactions (laryngeal edema, dyspnea, respiratory distress, fever, chills, arthralgia, weakness, fatigue, myalgia, adenopathy) in about 1 in 25 patients;
           Hematologic abnormalities (increased bleeding, anemia, leukopenia, thrombocytopenia, eosinophilia) in about 1 in 25 patients;
           Renal complications (proteinuria, nephrotic syndrome, hematuria) in about 1 in 20 patients;
           Pulmonary manifestations (bronchiolitis, hemoptysis, pulmonary infiltrates, dyspnea) in about 1 in 50 patients;
           Neurologic complications (myasthenic syndrome) in about 1 in 50 patients.

These reactions are more likely to develop during THIOLA ® therapy among patients who had previously shown toxicity to d-penicillamine.

In patients who had previously manifested adverse reactions to d-penicillamine, adverse reactions to THIOLA ® are more likely to occur than in patients who took THIOLA ® for the first time. A close supervision with a careful monitoring of potential side effects is mandatory during THIOLA ® treatment. Patients should be told to report promptly any symptoms suggesting toxicity. The treatment with THIOLA ® should be stopped if severe toxicity develops.

Jaundice and abnormal liver function tests have been reported during THIOLA ® therapy for non-cystinuric conditions. A direct cause and effect relationship, based upon these foreign reports, has not been established. Although such complications were not encountered in the small multi-center trials in the United States, patients should be carefully monitored and if any abnormalities are noted, the drug should be discontinued and the patient treated by appropriate measures.

DOSAGE AND ADMINISTRATION

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.

HOW SUPPLIED

THIOLA ® (NDC 0178-0900-01), is available for oral administration as 100 mg. round, white, sugar coated tablets in bottles of 100 tablets each. Each tablet is imprinted in red with “M” on one side and blank on the other side. Store at 25°C (77°F); excursions permitted to 15- 30°C (59-86°F) [see USP Controlled Room Temperature].

C05 Rev 010060

MISSION PHARMACAL COMPANY, San Antonio, TX 78230 1355

THIOLA ® Label
NDC: 0178-0900-01

Thiola Label NDC 0178-0900-01
(click image for full-size original)
THIOLA
tiopronin tablet, sugar coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:0178-0900
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
TIOPRONIN (TIOPRONIN) TIOPRONIN 100 mg
Inactive Ingredients
Ingredient Name Strength
SUCROSE 123 mg
CALCIUM CARBONATE 42.7 mg
LACTOSE 39 mg
DIMETHYLAMINOETHYL METHACRYLATE — BUTYL METHACRYLATE — METHYL METHACRYLATE COPOLYMER 28.8 mg
ETHYLCELLULOSES 20 mg
MAGNESIUM SILICATE 14.4 mg
MAGNESIUM STEARATE 5.4 mg
TITANIUM DIOXIDE 1.7 mg
CARNAUBA WAX 0.05 mg
FD&C RED NO. 40
ALUMINUM OXIDE
POVIDONE, UNSPECIFIED
HYDROXYPROPYL CELLULOSE (70000 WAMW)
Product Characteristics
Color white Score no score
Shape ROUND Size 8mm
Flavor Imprint Code M
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:0178-0900-01 100 TABLET, SUGAR COATED in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
NDA NDA019569 08/11/1988
Labeler — Mission Pharmacal Company (008117095)
Registrant — Mission Pharmacal Company (927726893)
Establishment
Name Address ID/FEI Operations
Mission Pharmacal Company 927726893 manufacture (0178-0900)

Revised: 01/2024 Mission Pharmacal Company

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