Tiopronin Drug Information

Tiopronin Delayed-Release Tablets are 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. Tiopronin Delayed-Release Tablets are a reducing and complexing thiol 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.

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. Administer Tiopronin Delayed-Release Tablets in 3 divided doses at the same times each day, with or without food. Maintain a routine pattern with regard to meals.

Consider starting Tiopronin Delayed-Release Tablets at a lower dosage in patients with history of severe toxicity to d-penicillamine.

Preparation and

Administration Instructions For patients who cannot swallow the tablet whole, Tiopronin Delayed-Release Tablets can be crushed and mixed with applesauce. Administration of Tiopronin Delayed-Release Tablets with other liquids or foods has not been studied and is not recommended. Preparation and Administration of Tiopronin Delayed-Release Tablets Mixed in Applesauce For patients who can swallow semi-solid food, Tiopronin Delayed-Release Tablets can be crushed and mixed with applesauce: 1. Crush the Tiopronin Delayed-Release Tablet in a clean pill crusher or mortar and pestle.

Always crush one tablet at a time. 2. Measure approximately one tablespoon of applesauce and transfer it into a container with the crushed Tiopronin Delayed-Release Tablet. 3. Mix the crushed Tiopronin Delayed-Release Tablet in the applesauce until the powder is well dispersed. 4. Administer the entire Tiopronin Delayed-Release Tablets-applesauce mixture to the patient’s mouth immediately. (However, if this is not possible, the mixture can be stored in a refrigerator for up to 2 hours after adding the crushed tablet to the applesauce. Discard any mixture that has not been given within 2 hours.) 5. To assure that any leftover applesauce mixture from the container is recovered, add tap water to the same container, mix, and have the patient drink the water.

Monitoring Measure urinary cystine 1 month after starting Tiopronin Delayed-Release Tablets and

every 3 months thereafter. Adjust Tiopronin Delayed-Release Tablets dosage to maintain urinary cystine concentration less than 250 mg/L. Assess for proteinuria before treatment and every 3 to 6 months during treatment. Discontinue Tiopronin Delayed-Release Tablets in patients who develop proteinuria, and monitor urinary protein and renal function.

Consider restarting Tiopronin Delayed-Release Tablets treatment at a lower dosage after resolution of proteinuria. The recommended initial dosage in adult patients is 800 mg/day. In clinical studies, the average dosage was about 1,000 mg/day.

The recommended initial dosage in pediatric patients 20 kg and greater is 15 mg/kg/day. Avoid dosages greater than 50 mg/kg per day in pediatric patients. Measure urinary cystine 1 month after initiation of Tiopronin Delayed-Release Tablets and every 3 months thereafter Administer Tiopronin Delayed-Release Tablets in 3 divided doses at the same times each day, with or without food.

Maintain a routine pattern with regard to meals. Tiopronin Delayed-Release Tablets can be crushed and mixed with applesauce. For preparation and administration instructions, see the full prescribing information.

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. Administer Tiopronin Delayed-Release Tablets in 3 divided doses at the same times each day, with or without food. Maintain a routine pattern with regard to meals.

Consider starting Tiopronin Delayed-Release Tablets at a lower dosage in patients with history of severe toxicity to d-penicillamine.

Preparation and

Administration Instructions For patients who cannot swallow the tablet whole, Tiopronin Delayed-Release Tablets can be crushed and mixed with applesauce. Administration of Tiopronin Delayed-Release Tablets with other liquids or foods has not been studied and is not recommended. Preparation and Administration of Tiopronin Delayed-Release Tablets Mixed in Applesauce For patients who can swallow semi-solid food, Tiopronin Delayed-Release Tablets can be crushed and mixed with applesauce: 1. Crush the Tiopronin Delayed-Release Tablet in a clean pill crusher or mortar and pestle.

Always crush one tablet at a time. 2. Measure approximately one tablespoon of applesauce and transfer it into a container with the crushed Tiopronin Delayed-Release Tablet. 3. Mix the crushed Tiopronin Delayed-Release Tablet in the applesauce until the powder is well dispersed. 4. Administer the entire Tiopronin Delayed-Release Tablets-applesauce mixture to the patient’s mouth immediately. (However, if this is not possible, the mixture can be stored in a refrigerator for up to 2 hours after adding the crushed tablet to the applesauce. Discard any mixture that has not been given within 2 hours.) 5. To assure that any leftover applesauce mixture from the container is recovered, add tap water to the same container, mix, and have the patient drink the water.

Monitoring Measure urinary cystine 1 month after starting Tiopronin Delayed-Release Tablets and

every 3 months thereafter. Adjust Tiopronin Delayed-Release Tablets dosage to maintain urinary cystine concentration less than 250 mg/L. Assess for proteinuria before treatment and every 3 to 6 months during treatment. Discontinue Tiopronin Delayed-Release Tablets in patients who develop proteinuria, and monitor urinary protein and renal function.

Consider restarting Tiopronin Delayed-Release Tablets treatment at a lower dosage after resolution of proteinuria.

• 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)] Most common adverse reactions (≥10%) are nausea, diarrhea or soft stools, oral ulcers, rash, fatigue, fever, arthralgia, proteinuria, and emesis. (6) To report SUSPECTED ADVERSE REACTIONS, contact BioComp Pharma, Inc. at toll-free phone # 1-866- 762-2365 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 Tiopronin Tablets. In those without prior history of d-penicillamine treatment, 6% developed reactions of sufficient severity to require Tiopronin Tablets withdrawal. Table 1 presents adverse reactions ≥5% in either treatment group occurring in this trial. Taste Disturbance A 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. image 6.2 Postmarketing Experience Adverse reactions have been reported from the literature, as well as during post-approval use of Tiopronin Tablets. Because the post-approval reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to Tiopronin Tablets exposure. Adverse reactions reported during the postmarketing use of Tiopronin Tablets are listed by body system in Table 2. Image

Alcohol Tiopronin is released faster from Tiopronin Delayed-Release Tablets in the presence

of alcohol and the risk for adverse events associated with Tiopronin Delayed-Release Tablets when taken with alcohol is unknown. Avoid alcohol consumption 2 hours before and 3 hours after taking Tiopronin Delayed-Release Tablets.

Tiopronin Delayed-Release Tablets are contraindicated in patients with hypersensitivity to tiopronin or any other components of Tiopronin Delayed-Release Tablets. Hypersensitivity to tiopronin or any component of Tiopronin Delayed-Release Tablets

There is no information on overdosage with tiopronin.