NDC 0093-7909 Tiopronin

Tiopronin

NDC Product Code 0093-7909

NDC CODE: 0093-7909

Proprietary Name: Tiopronin What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Tiopronin What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • This medication is used to prevent kidney stones in people with a certain inherited disorder (cystinuria). Cystinuria occurs when there is too much of a certain natural substance (the amino acid cystine) in the urine, leading to formation of kidney stones. Tiopronin works by making cystine more dissolvable in the urine. This medication should be used in combination with other methods to prevent kidney stones (such as drinking plenty of water, taking alkali treatment, following a special diet).

Product Characteristics

Color(s):
WHITE (C48325 - WHITE TO OFF-WHITE)
Shape: ROUND (C48348)
Size(s):
9 MM
Imprint(s):
W
Score: 1

NDC Code Structure

  • 0093 - Teva Pharmaceuticals Usa, Inc.

NDC 0093-7909-01

Package Description: 100 TABLET, SUGAR COATED in 1 BOTTLE

NDC Product Information

Tiopronin with NDC 0093-7909 is a a human prescription drug product labeled by Teva Pharmaceuticals Usa, Inc.. The generic name of Tiopronin is tiopronin. The product's dosage form is tablet, sugar coated and is administered via oral form.

Labeler Name: Teva Pharmaceuticals Usa, Inc.

Dosage Form: Tablet, Sugar Coated - A solid dosage form that contains medicinal substances with or without suitable diluents and is coated with a colored or an uncolored water-soluble sugar.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Tiopronin Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • TIOPRONIN 100 mg/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • STARCH, CORN (UNII: O8232NY3SJ)
  • ETHYLCELLULOSE (7 MPA.S) (UNII: H3UP11403C)
  • HYDROXYPROPYL CELLULOSE (90000 WAMW) (UNII: UKE75GEA7F)
  • LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)
  • LOW-SUBSTITUTED HYDROXYPROPYL CELLULOSE (11% HYDROXYPROPYL; 130000 MW) (UNII: 7773C1ROEU)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • MICROCRYSTALLINE CELLULOSE (UNII: OP1R32D61U)
  • STEARIC ACID (UNII: 4ELV7Z65AP)
  • GLYCERYL MONOCAPRYLOCAPRATE (UNII: G7515SW10N)
  • GLYCERYL MONOSTEARATE (UNII: 230OU9XXE4)
  • HYPROMELLOSE 2910 (5 MPA.S) (UNII: R75537T0T4)
  • MEDIUM-CHAIN TRIGLYCERIDES (UNII: C9H2L21V7U)
  • POLYVINYL ALCOHOL, UNSPECIFIED (UNII: 532B59J990)
  • POLYETHYLENE GLYCOL 3350 (UNII: G2M7P15E5P)
  • SODIUM LAURYL SULFATE (UNII: 368GB5141J)
  • SUCROSE (UNII: C151H8M554)
  • TALC (UNII: 7SEV7J4R1U)
  • AMMONIA (UNII: 5138Q19F1X)
  • FERROSOFERRIC OXIDE (UNII: XM0M87F357)
  • PROPYLENE GLYCOL (UNII: 6DC9Q167V3)
  • SHELLAC (UNII: 46N107B71O)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Cystine Disulfide Reduction - [MoA] (Mechanism of Action)
  • N-substituted Glycines - [CS]
  • Reducing and Complexing Thiol - [EPC] (Established Pharmacologic Class)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Teva Pharmaceuticals Usa, Inc.
Labeler Code: 0093
FDA Application Number: ANDA214326 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 05-17-2021 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2022 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

* Please review the disclaimer below.

Tiopronin Product Label Images

Tiopronin Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

Tiopronin 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 9 years of age and older with severe homozygous cystinuria, who are not responsive to these measures alone.Additional pediatric use information is approved for Mission Pharmacal Company’s Thiola (tiopronin) tablets. However, due to Mission Pharmacal Company’s marketing exclusivity rights, this drug product is not labeled with that information.

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 9 years of age and older is 15 mg/kg/day. Avoid dosages greater than 50 mg/kg per day in pediatric patients [see Warnings and Precautions (5.1), Use in Specific Populations (8.4)].Additional pediatric use information is approved for Mission Pharmacal Company’s Thiola (tiopronin) tablets. However, due to Mission Pharmacal Company’s marketing exclusivity rights, this drug product is not labeled with that information.Administer tiopronin tablets in 3 divided doses at the same times each day at least one hour before or 2 hours after meals.Consider starting tiopronin tablets at a lower dosage in patients with history of severe toxicity to d-penicillamine.

2.2 Monitoring

Measure urinary cystine 1 month after starting tiopronin tablets and every 3 months thereafter. Adjust tiopronin 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 [see Warnings and Precautions (5.1)].Discontinue tiopronin tablets in patients who develop proteinuria, and monitor urinary protein and renal function. Consider restarting tiopronin tablets treatment at a lower dosage after resolution of proteinuria.

3 Dosage Forms And Strengths

Tablets for oral use:100 mg tablets: White to off-white round shaped, sugar coated tablets, imprinted with W on one side in black ink.

4 Contraindications

Tiopronin is contraindicated in patients with hypersensitivity to tiopronin or any other components of tiopronin tablets [see Warnings and Precautions (5.2)].

5.1 Proteinuria

Proteinuria, including nephrotic syndrome, and membranous nephropathy, have been reported with tiopronin use. Pediatric patients receiving greater than 50 mg/kg of tiopronin per day may be at increased risk for proteinuria [see Dosage and Administration (2.2), Adverse Reactions (6.1, 6.2), Use in Specific Populations (8.4)]. Monitor patients for the development of proteinuria and discontinue therapy in patients who develop proteinuria [see Dosage and Administration (2.2)].

5.2 Hypersensitivity Reactions

Hypersensitivity reactions (drug fever, rash, fever, arthralgia and lymphadenopathy) have been reported [see Contraindications (4)].

6 Adverse Reactions

  • 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 tiopronin. In those without prior history of d-penicillamine treatment, 6% developed reactions of sufficient severity to require tiopronin withdrawal.Table 1 presents adverse reactions ≥5% in either treatment group occurring in this trial.Table 1: Adverse Reactions Occurring in One or More PatientsSystem Organ ClassAdverse ReactionGroup 1Previously treatedwithd-penicillamine(N=49)Group 2Naïve tod-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 DisturbanceA 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 postapproval use of tiopronin. Because the postapproval 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 exposure.Adverse reactions reported during the postmarketing use of tiopronin are listed by body system in Table 2.Table 2: Adverse Reactions Reported for Tiopronin Pharmacovigilance by System Organ Class and Preferred TermSystem Organ ClassPreferred TermCardiac Disorderscongestive heart failureEar and Labyrinth DisordervertigoGastrointestinal Disordersabdominal discomfort; abdominal distension; abdominal pain; chapped lips; diarrhea; dry mouth; dyspepsia; eructation; flatulence; gastrointestinal disorder; gastroesophageal reflux disease; nausea; vomiting; jaundice; liver transaminitisGeneral Disorders and Administration Site Conditionsasthenia; chest pain; fatigue; malaise; pain; peripheral swelling; pyrexia; swellingInvestigationsglomerular filtration rate decreased; weight increasedMetabolism and Nutrition Disordersdecreased appetite; dehydration; hypophagiaMusculoskeletal and Connective Tissue Disordersarthralgia; back pain; flank pain; joint swelling; limb discomfort; musculoskeletal discomfort; myalgia; neck pain; pain in extremityNervous System Disordersageusia; burning sensation; dizziness; dysgeusia; headache; hypoesthesiaRenal and Urinary Disordersnephrotic syndrome; proteinuria; renal failureSkin and Subcutaneous Tissue Disordersdry skin; hyperhidrosis; pemphigus foliaceus; pruritus; rash; rash pruritic; skin irritation; skin texture abnormal; skin wrinkling; urticaria

8.1 Pregnancy

Risk SummaryAvailable 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 ConsiderationsDisease-associated maternal and/or embryo/fetal riskRenal stones in pregnancy may increase the risk of adverse pregnancy outcomes, such as preterm birth and low birth weight.DataAnimal DataNo 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 SummaryThere 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 tiopronin.

8.4 Pediatric Use

Tiopronin is indicated in pediatric patients 9 years of age and older 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), Adverse Reactions (6.1)].Tiopronin 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)].Additional pediatric use information is approved for Mission Pharmacal Company’s Thiola (tiopronin) tablets. However, due to Mission Pharmacal Company’s marketing exclusivity rights, this drug product is not labeled with that information.

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.

10 Overdosage

There is no information on overdosage with tiopronin.

11 Description

Tiopronin immediate-release tablets are a reducing and cystine-binding thiol drug (CBTD) for oral use. Tiopronin is N-(2-Mercaptopropionyl) glycine and has the following structure:Tiopronin has the empirical formula C5H9NO3S and a molecular weight of 163.20. In this drug product tiopronin exists as a dl racemic mixture.Tiopronin is a white to off-white crystalline powder, which is freely soluble in water.Each tiopronin tablet contains 100 mg of tiopronin. The inactive ingredients in tiopronin tablets include colloidal silicon dioxide, corn starch, ethylcellulose, hydroxypropyl cellulose, lactose monohydrate, low substituted hydroxypropyl cellulose, magnesium stearate, silicified microcrystalline cellulose, and stearic acid. The tablets contain a coating that consists of glyceryl monocaprylocaprate, glyceryl monostearate, hypromellose 2910, medium chain triglycerides, polyvinyl alcohol-part hydrolyzed, polyethylene glycol 3350, sodium lauryl sulfate, sucrose, and talc. In addition, the imprinting ink contains ammonium hydroxide, black iron oxide, propylene glycol, and shellac.

12.1 Mechanism Of Action

The goal of therapy is to reduce urinary cystine concentration below its solubility limit. 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.

12.2 Pharmacodynamics

The decrement in urinary cystine produced by tiopronin is generally proportional to the dose. A reduction in urinary cystine of 250 to 350 mg/day at tiopronin dosage of 1 g/day, and a decline of approximately 500 mg/day at a dosage of 2 g/day, might be expected. Tiopronin has a rapid onset and offset of action, showing a fall in cystine excretion on the first day of administration and a rise on the first day of drug withdrawal.

12.3 Pharmacokinetics

AbsorptionTiopronin TabletsWhen tiopronin single doses were given to fasted healthy subjects (n=39), the median time to peak plasma level (Tmax) was 1 (range: 0.5 to 2.1) hours.EliminationExcretionWhen tiopronin is given orally, up to 48% of dose appears in urine during the first 4 hours and up to 78% by 72 hours.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

CarcinogenesisLong-term carcinogenicity studies in animals have not been performed.MutagenesisTiopronin was not genotoxic in the chromosomal aberration, sister chromatid exchange, and in vivo micronucleus assays.Impairment of FertilityHigh doses of tiopronin in experimental animals have been shown to interfere with maintenance of pregnancy and viability of the fetus. In 2 published male fertility studies in rats, tiopronin at 20 mg/kg/day intramuscular (IM) for 60 days induced reductions in testis, epididymis, vas deferens, and accessory sex glands weights and in the count and motility of cauda epididymal sperm.

16 How Supplied/Storage And Handling

100 mg: Each white to off-white round shaped, sugar coated tablet, imprinted with W on one side in black ink contains 100 mg of tiopronin. Tablets are available in bottles of 100 (NDC 0093-7909-01).Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

17 Patient Counseling Information

LactationAdvise women that breastfeeding is not recommended during treatment with tiopronin tablets [see Use in Specific Populations (8.2)].Manufactured in India By:Watson Pharma Private LimitedVerna, Salcette Goa 403 722 IndiaManufactured For:Teva Pharmaceuticals USA, Inc.Parsippany, NJ 07054Iss. 2/2021

* Please review the disclaimer below.