Miscellaneous genitourinary tract agents
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Thiola Tablets Prescribing Information

Drug Detail:Thiola (Tiopronin [ tye-oh-proe-nin ])

Drug Class: Miscellaneous genitourinary tract agents

Contents
Uses Warnings Before Taking Dosage Side effects Interactions

Highlights of Prescribing Information

These highlights do not include all the information needed to use THIOLA® safely and effectively. See full prescribing information for THIOLA.

THIOLA (tiopronin) tablets, for oral use
Initial U.S. Approval: 1988

Indications and Usage for Thiola Tablets

THIOLA is 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. (1)

Thiola Tablets Dosage and Administration

  • The recommended initial dosage in adult patients is 800 mg/day. In clinical studies, the average dosage was about 1,000 mg/day. (2.1)
  • 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. (2.1, 5.1, 8.4)
  • Administer THIOLA in 3 divided doses at the same times each day at least one hour before or 2 hours after meals. (2.1)
  • Measure urinary cystine 1 month after initiation of THIOLA and every 3 months thereafter. (2.1)

Dosage Forms and Strengths

Tablets: 100 mg (3)

Contraindications

  • Hypersensitivity to tiopronin or any component of THIOLA (4)

Warnings and Precautions

  • Proteinuria, including nephrotic syndrome, and membranous nephropathy, has been reported with tiopronin use. Pediatric patients receiving greater than 50 mg/kg of tiopronin per day may be at increased risk for proteinuria. (2.1, 5.1, 8.4)
  • Hypersensitivity reactions have been reported during tiopronin treatment. (4, 5.2)

Adverse Reactions/Side Effects

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 Mission Pharmacal Company at toll-free phone # 1-800-298-1087 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Use In Specific Populations

  • Lactation: Breastfeeding is not recommended. (8.2)
  • Geriatric: Choose dose carefully and monitor renal function in the elderly. (8.5)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 6/2019

Related/similar drugs

penicillamine, Cuprimine, tiopronin, D-Penamine, Depen, Thiola EC

Full Prescribing Information

6. Adverse Reactions/Side Effects

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)]

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 THIOLA. In those without prior history of d-penicillamine treatment, 6% developed reactions of sufficient severity to require THIOLA withdrawal.

Table 1 presents adverse reactions ≥5% in either treatment group occurring in this trial.

Table 1:Adverse Reactions Occurring in One or More Patients
System Organ ClassAdverse ReactionGroup 1
Previously treated with
d‑penicillamine
(N = 49)		Group 2
Naïve to d‑penicillamine
(N = 17)
Blood and Lymphatic System Disordersanemia1 (2%)1 (6%)
Gastrointestinal Disordersnausea12 (25%)2 (12%)
emesis5 (10%)–
diarrhea/soft stools9 (18%)1 (6%)
abdominal pain–1 (6%)
oral ulcers6 (12%)3 (18%)
General Disorders and Administration Site Conditionsfever4 (8%)–
weakness2 (4%)2 (12%)
fatigue7 (14%)–
peripheral (edema)3 (6%)1 (6%)
chest pain–1 (6%)
Metabolism and Nutrition Disordersanorexia4 (8%)–
Musculoskeletal and Connective Tissue Disordersarthralgia–2 (12%)
Renal and Urinary Disordersproteinuria5 (10%)1 (6%)
impotence–1 (6%)
Respiratory, Thoracic and Mediastinal Disorderscough–1 (6%)
Skin and Subcutaneous Tissue Disordersrash7 (14%)2 (12%)
ecchymosis3 (6%)–
pruritus2 (4%)1 (6%)
urticaria4 (8%)–
skin wrinkling3 (6%)1 (6%)

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.

6.2 Postmarketing Experience

Adverse reactions have been reported from the literature, as well as during post-approval use of THIOLA. 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 THIOLA exposure.

Adverse reactions reported during the postmarketing use of THIOLA are listed by body system in Table 2.

Table 2:Adverse Reactions Reported for THIOLA Pharmacovigilance by System Organ Class and Preferred Term
System Organ ClassPreferred Term
Cardiac Disorderscongestive heart failure
Ear and Labyrinth Disordervertigo
Gastrointestinal Disordersabdominal discomfort; abdominal distension; abdominal pain; chapped lips; diarrhea; dry mouth; dyspepsia; eructation; flatulence; gastrointestinal disorder; gastroesophageal reflux disease; nausea; vomiting; jaundice; liver transaminitis
General Disorders and Administration Site Conditionsasthenia; chest pain; fatigue; malaise; pain; peripheral swelling; pyrexia; swelling
Investigationsglomerular filtration rate decreased; weight increased
Metabolism and Nutrition Disordersdecreased appetite; dehydration; hypophagia
Musculoskeletal and Connective Tissue Disordersarthralgia; back pain; flank pain; joint swelling; limb discomfort; musculoskeletal discomfort; myalgia; neck pain; pain in extremity
Nervous System Disordersageusia; burning sensation; dizziness; dysgeusia; headache; hypoesthesia
Renal and Urinary Disordersnephrotic syndrome; proteinuria; renal failure
Skin and Subcutaneous Tissue Disordersdry skin; hyperhidrosis; pemphigus foliaceus; pruritus; rash; rash pruritic; skin irritation; skin texture abnormal; skin wrinkling; urticaria

8. Use In Specific Populations

8.1 Pregnancy

Risk Summary
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. Renal stones in pregnancy may result in adverse pregnancy outcomes (see Clinical Considerations). In animal reproduction studies, there were no adverse developmental outcomes with oral administration of tiopronin to pregnant mice and rats during organogenesis at doses up to 2 times a 2 grams/day human dose (based on mg/m2). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively.

Clinical Considerations
Disease-associated maternal and/or embryo/fetal risk
Renal stones in pregnancy may increase the risk of adverse pregnancy outcomes, such as preterm birth and low birth weight.

Data
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).

8.2 Lactation

Risk Summary
There are no data on the presence of tiopronin in either human or animal milk or on the effects of the breastfed child. A published study suggests that 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 with THIOLA.

8.4 Pediatric Use

THIOLA is indicated in pediatric patients weighing 20 kg or more with severe homozygous cystinuria, in combination with high fluid intake, alkali, and diet modification, for the prevention of cystine stone formation who are not responsive to these measures alone. This indication is based on safety and efficacy data from a trial in patients 9 years to 68 years of age and clinical experience. Proteinuria, including nephrotic syndrome, has been reported in pediatric patients. Pediatric patients receiving greater than 50 mg/kg tiopronin per day may be at greater risk [see Dosage and Administration (2.1, 2.2), Warnings and Precautions (5.1) [see Adverse Reactions (6.1)].

THIOLA tablets are not approved for use in pediatric patients weighing less than 20 kg or in pediatric patients unable to swallow tablets [see Dosage and Administration (2.1)].

8.5 Geriatric Use

This drug is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

THIOLA
tiopronin tablet, sugar coated
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:0178-0900
Route of AdministrationORAL
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
TIOPRONIN (UNII: C5W04GO61S) (TIOPRONIN - UNII:C5W04GO61S) TIOPRONIN100 mg
Inactive Ingredients
Ingredient NameStrength
POVIDONE, UNSPECIFIED (UNII: FZ989GH94E)
HYDROXYPROPYL CELLULOSE (70000 WAMW) (UNII: 66O7AQV0RT)
SUCROSE (UNII: C151H8M554) 123 mg
CALCIUM CARBONATE (UNII: H0G9379FGK) 42.7 mg
LACTOSE (UNII: J2B2A4N98G) 39 mg
DIMETHYLAMINOETHYL METHACRYLATE - BUTYL METHACRYLATE - METHYL METHACRYLATE COPOLYMER (UNII: 905HNO1SIH) 28.8 mg
ETHYLCELLULOSES (UNII: 7Z8S9VYZ4B) 20 mg
MAGNESIUM SILICATE (UNII: 9B9691B2N9) 14.4 mg
MAGNESIUM STEARATE (UNII: 70097M6I30) 5.4 mg
TITANIUM DIOXIDE (UNII: 15FIX9V2JP) 1.7 mg
CARNAUBA WAX (UNII: R12CBM0EIZ) 0.05 mg
FD&C RED NO. 40 (UNII: WZB9127XOA)
ALUMINUM OXIDE (UNII: LMI26O6933)
Product Characteristics
ColorWHITEScoreno score
ShapeROUNDSize8mm
FlavorImprint CodeM
Contains
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:0178-0900-01100 in 1 BOTTLE; Type 0: Not a Combination Product08/11/1988
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NDANDA01956908/11/1988
Labeler - Mission Pharmacal Company (008117095)
Registrant - Mission Pharmacal Company (927726893)
Establishment
NameAddressID/FEIBusiness Operations
Mission Pharmacal Company927726893MANUFACTURE(0178-0900)

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