What are the recommendations for managing insufficient absorption of Thiola (tiopronin) in patients with cystinuria?

From the Guidelines

For patients with cystinuria experiencing insufficient absorption of Thiola (tiopronin), the most effective management strategy is to increase fluid intake to at least 3 liters daily and consider dividing the total daily Thiola dose into smaller, more frequent administrations. This approach helps to dilute urine and reduce cystine concentration, thereby enhancing the absorption of Thiola 1. Taking Thiola on an empty stomach, 30 minutes before meals, may also improve absorption. If these measures are insufficient, the physician might gradually increase the dose while monitoring urinary cystine levels, with typical adult doses ranging from 800-1200 mg daily 1. Dietary modifications to reduce sodium and animal protein intake can complement medication therapy by decreasing urinary cystine 1. Some key points to consider in managing insufficient absorption of Thiola include:

• Increasing fluid intake to help dilute urine and reduce cystine concentration
• Dividing the total daily Thiola dose into smaller, more frequent administrations to maintain consistent blood levels
• Taking Thiola on an empty stomach to improve absorption
• Gradually increasing the dose while monitoring urinary cystine levels if necessary
• Implementing dietary modifications to reduce sodium and animal protein intake Regular monitoring of urinary cystine levels is essential to assess treatment effectiveness 1. Thiola works by forming a soluble complex with cystine, preventing crystal formation and stone development 1. If absorption issues persist despite these interventions, alternative thiol-binding medications like D-penicillamine might be considered, though Thiola generally has fewer side effects 1.

From the FDA Drug Label

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 9 years of age and older is 15 mg/kg/day. Avoid dosages greater than 50 mg/kg per day in pediatric patients. Administer tiopronin tablets in 3 divided doses at the same times each day at least one hour before or 2 hours after meals.

The FDA drug label does not provide specific recommendations for managing insufficient absorption of Thiola (tiopronin) in patients with cystinuria. The label provides information on the recommended dosage and administration of tiopronin, but it does not address the issue of insufficient absorption directly. Therefore, no conclusion can be drawn, and no specific guidance can be provided on this topic based on the available information 2, 2.

From the Research

Insufficient Absorption of Thiola (Tiopronin) in Patients with Cystinuria

• The management of insufficient absorption of Thiola (tiopronin) in patients with cystinuria involves adjusting the dose of tiopronin based on the urinary concentration of free cysteine 3.
• Monitoring urinary cystine concentration is necessary to achieve adequate individualized doses of tiopronin, as tiopronin may interfere with cystine metabolism in a complex way 3.
• The effects of tiopronin on cystine metabolism can be evaluated by calculating the total urinary excretion of cystine as the sum of free cystine and the amount of cystine corresponding to the cysteine content of the tiopronin-cysteine disulfide 3.

Factors Affecting Cystine Excretion

• Sodium intake can affect cystine excretion, with a sodium-restricted diet resulting in decreased cystine excretion 4.
• The use of sodium bicarbonate can also impact cystine excretion, with withdrawal of sodium bicarbonate resulting in decreased cystine excretion 4.
• Urine volume, pH, and cystine excretion are strongly correlated with cystine capacity, which can be measured using a solid-phase assay 5.

Use of Cystine-Binding Thiol Drugs

• Cystine-binding thiol drugs (CBTDs), such as tiopronin, can lower the urinary supersaturation of cystine and improve cystine capacity 6.
• CBTDs can be effective in preventing cystine stone formation and are generally well-tolerated, although side effects can occur 7, 3.
• The minimum effective dose of CBTDs can be prescribed by monitoring the response to the drug and measuring cystine capacity 6.