For the prevention of cystine kidney stone formation1

THIOLA® is an adjunctive therapy to diet modification, urinary alkalinization, and high fluid intake, or who have adverse reactions to d-penicillamine.1

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.2 The poor solubility of cystine in urine leads to stone formation.2 The accumulation of cystine causes crystallization when concentrations rise above the saturation point (approximately 250 mg cystine per liter of urine).1,2

Approximately 1 in 10,000 persons are homozygous for cystinuria.3 Patients with this disorder may present at a young age. In children, cystinuria is the cause of up to 10% of all stones.4

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

Indication

THIOLA (tiopronin) tablets is a prescription medicine used to help prevent the formation of cystine (kidney) stones in patients with severe cystinuria who were not successfully treated with alkali, dietary changes and increased fluid intake, or patients who have had side effects with the drug d‑penicillamine.

Important Safety Information

THIOLA is not for everyone. You should not take THIOLA if you:

  • Are pregnant or plan to become pregnant
  • Are breastfeeding or plan to breastfeed
  • Have a history of blood disorders including aplastic anemia (your bone marrow does not make enough new cells), agranulocytois (decrease in certain white blood cells), or thrombocytopenia (decrease in the number of platelets)

The safety and effectiveness of THIOLA have not been established in children under 9 years of age, and there are no well‑controlled studies in pregnant women. High doses of THIOLA in pregnant laboratory animals have been shown to harm the fetus, so you should talk about these risks with your doctor to determine whether THIOLA is right for you. No long‑term animal studies have been performed to see whether THIOLA can cause cancer, so you should discuss these risks with your doctor.

While you are taking THIOLA, your doctor will monitor you closely for signs and symptoms of possible complications. Your doctor will routinely do certain blood and urine tests, and yearly scans of your abdomen to look at the size and appearance of kidney stones. THIOLA should only be used under the close supervision of your doctor.

THIOLA can cause serious side effects or potential complications, and some of these could be fatal. Therefore, it is important to call your doctor right away if you have any side effects.

Side effects associated with THIOLA include a drug‑related fever that typically occurs during the first month of treatment. If this occurs, talk with your doctor, who may discontinue treatment until the fever goes away.

You may notice a reduced sense of taste while taking THIOLA, which will eventually go away. Some patients also report wrinkling or thin, fragile skin during long‑term treatment.

Other side effects of THIOLA may include an itchy rash that is found on many parts of your body. This typically occurs during the first few months of treatment, and antihistamines can help reduce the itching. The rash will usually disappear once you stop taking THIOLA. Less often, patients who take THIOLA for more than 6 months may develop a rash that is usually located on the upper body and is very itchy. It typically goes away slowly after discontinuing treatment and returns after re‑starting treatment.

Some patients may develop a drug hypersensitivity reaction to THIOLA that includes fever, joint pain, and swollen lymph nodes. If this occurs, your doctor may discontinue THIOLA.

THIOLA can cause serious and potentially fatal blood disorders, including aplastic anemia (your bone marrow does not make enough new cells), agranulocytois (decrease in certain white blood cells), or thrombocytopenia (decrease in the number of platelets). Call your doctor immediately if you have any signs or symptoms such as fever, sore throat, chills, bleeding, or if you are bruising more easily.

Although THIOLA may be less toxic than d‑penicillamine, it could potentially cause all of the serious side effects reported for d‑penicillamine. No deaths have been reported as a result of THIOLA treatment; however, fatal outcomes have 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 that causes muscles to weaken). Do not take THIOLA if you have a history of these conditions.

Additional side effects that have been reported during treatment with d‑penicillamine and that might occur during THIOLA treatment include: decreased sense of smell, nausea, vomiting, diarrhea or soft stools, loss of appetite, abdominal pain, bloating, gas, sore throat, sores in the mouth, hives, warts, swelling of the throat, difficulty breathing, shortness of breath, fatigue or weakness, muscle or joint pain, swelling in your legs or fluid build‑up in the lungs, lung or kidney problems, and blood or high amounts of protein in urine. These side effects are more likely to develop during THIOLA therapy in patients who had previous reactions to d‑penicillamine. Talk to your doctor about any unusual side effects.

Seek immediate medical attention and discontinue THIOLA if you notice symptoms such as fever, sore throat, chills, bleeding, easy bruising, 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.

Jaundice (yellow appearance of the skin and whites of the eyes) and abnormal liver function tests have been reported during THIOLA treatment for conditions unrelated to cystine stones.

To report suspected adverse events, contact Mission Pharmacal Company at 800.298.1087, or the FDA at 800.FDA.1088 or www.fda.gov/medwatch.

References: 1. THIOLA [prescribing information]. San Antonio, TX: Mission Pharmacal. 2. Biyani CS, Cartledge JJ. EAU‑EBU Update Series. 2006;4:175‑183. 3. Genetics Home Reference. http://ghr.nlm.nih.gov/condition/cystinuria. Accessed August 12, 2014. 4. Knoll T, Zollner A, Wendt‑Nordahl G, Michel MS, Alken P. Pediatr Nephrol. 2005;20:19‑24.