tiopronin (Rx)

>10%

Nausea (12-25%)

Oral ulcers (12-18%)

Diarrhea/soft stools (6-18%)

Fatigue (14%)

Rash (12-14%)

Arthralgia (12%)

Weakness (4-12%)

1-10%

Emesis (10%)

Proteinuria (6-10%)

Fever (8%)

Anorexia (8%)

Urticaria (8%)

Abdominal pain (6%)

Peripheral edema (6%)

Chest pain (6%)

Impotence (6%)

Cough (6%)

Ecchymosis (6%)

Skin wrinkling (6%)

Pruritus (4-6%)

Anemia (2-6%)

Frequency Not Defined

Reduced taste perception

Hypogeusia

Postmarketing Reports

Cardiac disorders: CHF

Ear and labyrinth disorders: Vertigo

Gastrointestinal disorders: Abdominal discomfort, distension. or pain; chapped lips; diarrhea; dry mouth; dyspepsia; eructation; flatulence; gastrointestinal disorder; gastroesophageal reflux disease; nausea; vomiting; jaundice; liver transaminitis

General disorders and administration site conditions: Asthenia; chest pain; fatigue; malaise; pain; peripheral swelling; pyrexia; swelling

Investigations: GFR decreased; weight increased

Metabolism and nutrition disorders: Decreased appetite; dehydration; hypophagia

Musculoskeletal and connective tissue disorders: Arthralgia; back pain; flank pain; joint swelling; limb discomfort; musculoskeletal discomfort; myalgia; neck pain; pain in extremity

Nervous system disorders: Ageusia; burning sensation; dizziness; dysgeusia; headache; hypoesthesia

Renal and urinary disorders: Nephrotic syndrome; proteinuria; renal failure

Skin and subcutaneous tissue disorders: Dry skin; hyperhidrosis; pemphigus foliaceus; pruritus; rash; rash pruritic; skin irritation; skin texture abnormal; skin wrinkling; urticaria

Contraindications

Hypersensitivity

Cautions

Hypersensitivity reactions reported including drug fever, rash, fever, arthralgia, and lymphadenopathy

Not recommended if breastfeeding

Proteinuria

• Proteinuria reported, including nephrotic syndrome and membranous nephropathy
• Pediatric patients receiving >50 mg/kg/day may be at increased risk
• Monitor for development of proteinuria and discontinue therapy in patients who develop proteinuria

Drug interaction overview

• Thiola EC: Tiopronin is released faster from Thiola EC in the presence of alcohol and the risk for adverse events associated when taken with alcohol is unknown
• Avoid alcohol consumption 2 hr before and 3 hr after taking Thiola EC

Pregnancy

Available published case report data with tiopronin have not identified a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes

Clinical considerations

• Renal stones in pregnancy may increase risk of adverse pregnancy outcomes (eg, preterm birth, low birth weight)

Animal data

• No findings of fetal malformations could be attributed to the drug in reproduction studies in mice and rats at doses up to 2 times the highest recommended human dose of 2 grams/day (based on mg/m²)

Lactation

There are no data on the presence of tiopronin in either human or animal milk or on the effects of the breastfed child

Prescribing information describes a published study suggesting tiopronin may suppress milk production

Because of the potential for serious adverse reactions, including nephrotic syndrome, advise patients that breastfeeding is not recommended during treatment

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Tiopronin is an active reducing agent which undergoes thiol-disulfide exchange with cystine to form a mixed disulfide of tiopronin-cysteine; from this reaction, a water-soluble mixed disulfide is formed and the amount of sparingly soluble cystine is reduced

Absorption

Peak plasma time: 1 hr (immediate-release); 3 hr (delayed-release)

Elimination

Excretion: Urine 48% (4 hr); 78% (72 hr)

Oral Administration

Thiola: Take at least 1 hr before meals or 2 hr after meals

Thiola EC

• May take with or without food
• Swallow tablet whole; do not chew, crush, or split

Unable to swallow tablet whole

• Crush and mix with applesauce
• Administration with other liquids or foods has not been studied and not recommended

• Preparation and administration mixed in applesauce

  • For patients who can swallow semi-solid food
  • Crush tablet in a clean pill crusher or mortar and pestle; always crush 1 tablet at a time
  • Measure ~1 tablespoon of applesauce and transfer it into a container with the crushed tablet
  • Mix crushed tablet in applesauce until powder is well dispersed
  • Administer entire drug-applesauce mixture immediately
  • If this is not possible, may refrigerate mixture for up to 2 hr after adding crushed tablet to applesauce; discard any mixture that has not been given within 2 hr
  • To assure that any leftover applesauce mixture from container is recovered, add tap water to the same container, mix, and administer

Storage

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)