For the prevention of cystine kidney stone formation

Thiola® is an alternative therapeutic approach that helps prevent cystine (kidney) stone formation in patients who are resistant to diet modification and high fluid intake.

About cystine stones

Cystinuria is caused by a defect in intestinal and renal tubular transport of dibasic amino acids that results in excessive urinary excretion of cystine. The poor solubility of cystine in urine leads to stone formation. The accumulation of cystine causes crystallization when concentrations rise above the saturation point (approximately 250 mg cystine per liter of urine).1,2

Cystine stones typically occur in approximately 10,000 persons in the United States who are homozygous for cystinuria. Patients with this disorder may present at a young age. In children, cystinuria is the cause of up to 10% of all stones.1,2

Hypercalciuria, hyperuricosuria, and hypocitraturia frequently accompany cystinuria. These metabolic abnormalities may contribute to the formation of calcium and uric acid stones, which sometimes complicate cystine nephrolithiasis.2

Thiola® is a prescription drug that helps prevent cystine (kidney) stones from forming in patients who are resistant to treatment with a modified diet and high fluid intake, or patients who have adverse reactions to the drug d-penicillamine.

Important Safety Information

Thiola® is not for everyone. Its safety and effectiveness have not been established for patients under the age of 9, and there are no adequate and well-controlled studies in pregnant women.

Do not take Thiola® if you are pregnant or may become pregnant, unless your doctor has discussed the risks with you and determined that the prevention of stones outweighs possible risks to the fetus. If you are nursing, Thiola® may pass through your breast milk and lead to potentially serious side effects for your infant, so you should not breastfeed while taking Thiola®.

High doses of Thiola® in laboratory animals have been shown to interfere with pregnancy and survival of the fetus. Additionally, d-penicillamine has been shown to cause birth defects in animals at very high doses, so although these results were not found with Thiola®, a similar outcome is possible. No long-term animal studies have been done to examine the cancer-causing potential of Thiola®, so you should discuss the risks with your doctor and only take Thiola® if it is necessary.

Do not take Thiola® if you have a history of blood disorders such as aplastic anemia (a condition in which the body does not produce enough new blood cells), agranulocytosis (a disorder characterized by a drop in white blood cells called granulocytes), or thrombocytopenia (an abnormal decrease in the number of platelets).

If you take Thiola®, your doctor may conduct a variety of blood and urine tests to check for possible complications and perform annual abdominal scans to monitor the size and appearance of stones.

Some patients may develop a drug-induced fever while taking Thiola®, usually during the first month of treatment. If this occurs, talk with your doctor and discontinue use until the fever subsides. Your doctor may instruct you to begin taking a small dose, and then increase it gradually until you reach the appropriate dosage.

You may notice a reduced sense of taste while taking Thiola®. Some patients also experience wrinkling or fragile skin after long-term treatment.

Other side effects of Thiola® may include a generalized rash accompanied by itching, which typically occur during the first few months of treatment. Antihistamines can help reduce the itching, and the rash will normally disappear once you stop taking Thiola®. Less often, patients who take Thiola® for more than 6 months may develop a rash late in the course of treatment. This rash is usually located on the upper body and associated with intense itching. It typically goes away slowly after discontinuing treatment and returns after re-starting treatment.

No deaths have been reported as a result of Thiola® treatment; however, a fatal outcome has been reported with certain complications of d-penicillamine therapy, including reduced white blood cells, red blood cells, or platelets; Goodpasture's syndrome (an autoimmune disorder that affects the lungs and kidneys); and myasthenia gravis (an autoimmune disorder characterized by muscle weakness). Do not take Thiola® if you have a history of these conditions.

Seek immediate medical attention and discontinue use if you notice symptoms such as fever, sore throat, chills, bleeding, easy bruisability, coughing up blood, muscle weakness, blistering or raw areas on the skin or mucous membranes, joint pain, swelling of the lymph nodes, or swelling in your legs, as these may be signs of a serious reaction to the drug.

Although Thiola® is reportedly less toxic than d-penicillamine, it could potentially cause all the side effects reported for d-penicillamine. Additional side effects might include a reduced sense of smell, throat inflammation, nausea, vomiting, diarrhea or soft stools, loss of appetite, abdominal pain, bloating, gas, oral ulcers, hives, warts, swelling of the throat, difficulty breathing, respiratory distress, fatigue, muscle pain, swelling or fluid build-up in the lungs, and blood or high amounts of protein in urine. These reactions are more likely to develop during Thiola® therapy among patients who had previous reactions to d-penicillamine. Talk to your doctor about any unusual side effects.

Jaundice and abnormal liver function tests were reported during Thiola® treatment for conditions unrelated to cystine stones, however, these results were not directly linked to Thiola®.

To report negative side effects, contact Mission Pharmacal Company at 1-800-298-1087 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Important Safety Information