NDC 0904-6696 Pyrazinamide

Pyrazinamide

NDC Product Code 0904-6696

NDC Code: 0904-6696

Proprietary Name: Pyrazinamide 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: Pyrazinamide 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.

Product Characteristics

Color(s):
WHITE (C48325)
Shape: ROUND (C48348)
Size(s):
13 MM
Imprint(s):
S;660
Score: 2

NDC Code Structure

NDC 0904-6696-60

Package Description: 100 TABLET in 1 BOTTLE

NDC 0904-6696-61

Package Description: 100 BLISTER PACK in 1 CARTON > 1 TABLET in 1 BLISTER PACK

NDC 0904-6696-89

Package Description: 90 TABLET in 1 BOTTLE

NDC Product Information

Pyrazinamide with NDC 0904-6696 is a a human prescription drug product labeled by Major Pharmaceuticals. The generic name of Pyrazinamide is pyrazinamide. The product's dosage form is tablet and is administered via oral form.

Labeler Name: Major Pharmaceuticals

Dosage Form: Tablet - A solid dosage form containing medicinal substances with or without suitable diluents.

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.

Pyrazinamide 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.

  • PYRAZINAMIDE 500 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.

  • STARCH, CORN (UNII: O8232NY3SJ)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • STEARIC ACID (UNII: 4ELV7Z65AP)

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.

  • Antimycobacterial - [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: Major Pharmaceuticals
Labeler Code: 0904
FDA Application Number: ANDA080157 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: 06-03-1971 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: 12-31-2020 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 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. Values = ‘Y’ or ‘N’.

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Information for Patients

Pyrazinamide

Pyrazinamide is pronounced as (peer a zin' a mide)

Why is pyrazinamide medication prescribed?
Pyrazinamide kills or stops the growth of certain bacteria that cause tuberculosis (TB). It is used with other drugs to treat tuberculosis.This medication is sometimes pr...
[Read More]

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Pyrazinamide 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

Description

Pyrazinamide, the pyrazine analogue of nicotinamide, is an antituberculous agent. It is a white crystalline powder, stable at room temperature, and sparingly soluble in water. Pyrazinamide has the following structural formula:C5H5N3O              M.W. 123.11Each Pyrazinamide tablet for oral administration contains 500 mg of pyrazinamide and the following inactive ingredients: Corn Starch, Magnesium Stearate, Pregelatinized Starch and Stearic Acid.

Clinical Pharmacology

Pyrazinamide is well absorbed from the GI tract and attains peak plasma concentrations within 2 hours. Plasma concentrations generally range from 30 to 50 mcg/mL with doses of 20 to 25 mg/kg. It is widely distributed in body tissues and fluids including the liver, lungs and cerebrospinal fluid (CSF). The CSF concentration is approximately equal to concurrent steady-state plasma concentrations in patients with inflamed meninges.1 Pyrazinamide is approximately 10% bound to plasma proteins.2The half-life (t1/2) of pyrazinamide is 9 to 10 hours in patients with normal renal and hepatic function. The plasma half-life may be prolonged in patients with impaired renal or hepatic function. Pyrazinamide is hydrolyzed in the liver to its major active metabolite, pyrazinoic acid. Pyrazinoic acid is hydroxylated to the main excretory product, 5-hydroxypyrazinoic acid. 3Approximately 70% of an oral dose is excreted in urine, mainly by glomerular filtration within 24 hours. 3Pyrazinamide may be bacteriostatic or bactericidal against Mycobacterium tuberculosis depending on the concentration of the drug attained at the site of infection. The mechanism of action is unknown. In vitro and in vivo the drug is active only at a slightly acidic pH.

Indications And Usage

Pyrazinamide is indicated for the initial treatment of active tuberculosis in adults and children when combined with other antituberculous agents. (The current recommendation of the CDC for drug-susceptible disease is to use a six-month regimen for initial treatment of active tuberculosis, consisting of isoniazid, rifampin and pyrazinamide given for 2 months, followed by isoniazid and rifampin for 4 months.* 4) (Patients with drug-resistant disease should be treated with regimens individualized to their situation. Pyrazinamide frequently will be an important component of such therapy.)(In patients with concomitant HIV infection, the physician should be aware of current recommendations of CDC. It is possible these patients may require a longer course of treatment.)It is also indicated after treatment failure with other primary drugs in any form of active tuberculosis.Pyrazinamide should only be used in conjunction with other effective antituberculous agents.*See recommendations of Center for Disease Control (CDC) and American Thoracic Society for complete regimen and dosage recommendations. 4

Contraindications

  • Pyrazinamide is contraindicated in persons: •with severe hepatic damage. •who have shown hypersensitivity to it. •with acute gout.

Warnings

Patients started on pyrazinamide should have baseline serum uric acid and liver function determinations. Those patients with preexisting liver disease or those at increased risk for drug related hepatitis (e.g., alcohol abusers) should be followed closely.Pyrazinamide should be discontinued and not be resumed if signs of hepatocellular damage or hyperuricemia accompanied by an acute gouty arthritis appear.

General

Pyrazinamide inhibits renal excretion of urates, frequently resulting in hyperuricemia which is usually asymptomatic. If hyperuricemia is accompanied by acute gouty arthritis, pyrazinamide should be discontinued.Pyrazinamide should be used with caution in patients with a history of diabetes mellitus, as management may be more difficult.Primary resistance of M. tuberculosis to pyrazinamide is uncommon. In cases with known or suspected drug resistance, in vitro susceptibility tests with recent cultures of M. tuberculosis against pyrazinamide and the usual primary drugs should be performed. There are few reliable in vitro tests for pyrazinamide resistance. A reference laboratory capable of performing these studies must be employed.

Information For Patients

Patients should be instructed to notify their physicians promptly if they experience any of the following: fever, loss of appetite, malaise, nausea and vomiting, darkened urine, yellowish discoloration of the skin and eyes, pain or swelling of the joints.Compliance with the full course of therapy must be emphasized, and the importance of not missing any doses must be stressed.

Laboratory Tests

Baseline liver function studies [especially ALT (SGPT), AST (SGOT) determinations] and uric acid levels should be determined prior to therapy. Appropriate laboratory testing should be performed at periodic intervals and if any clinical signs or symptoms occur during therapy.

Drug/Laboratory Test Interactions

Pyrazinamide has been reported to interfere with ACETEST® and KETOSTIX® urine tests to produce a pink-brown color. 5

Carcinogenicity, Mutagenicity, Impairment Of Fertility 6,7,8

In lifetime bioassays in rats and mice, pyrazinamide was administered in the diet at concentrations of up to 10,000 ppm. This resulted in estimated daily doses for the mouse of 2 g/kg, or 40 times the maximum human dose, and for the rat of 0.5 g/kg, or 10 times the maximum human dose. Pyrazinamide was not carcinogenic in rats or male mice and no conclusion was possible for female mice due to insufficient numbers of surviving control mice.Pyrazinamide was not mutagenic in the Ames bacterial test, but induced chromosomal aberrations in human lymphocyte cell cultures.

Pregnancy: Teratogenic Effects – Pregnancy Category C

Animal reproduction studies have not been conducted with pyrazinamide. It is also not known whether pyrazinamide can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Pyrazinamide should be given to a pregnant woman only if clearly needed.

Nursing Mothers

Pyrazinamide has been found in small amounts in breast milk. Therefore, it is advised the pyrazinamide be used with caution in nursing mothers taking into account the risk-benefit of this therapy.9

Usage In Children

Pyrazinamide regimens employed in adults are probably equally effective in children.4, 10, 11 Pyrazinamide appears to be well tolerated in children.

Geriatric Use12

Clinical studies of pyrazinamide did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic or renal function, and of concomitant disease or other drug therapy.It does not appear that patients with impaired renal function require a reduction in dose. It may be prudent to select doses at the low end of the dosing range, however.13

Adverse Reactions

GeneralFever, porphyria and dysuria have rarely been reported. Gout (see PRECAUTIONS).GastrointestinalThe principal adverse effect is a hepatic reaction (see WARNINGS). Hepatotoxicity appears to be dose related, and may appear at any time during therapy. GI disturbances including nausea, vomiting and anorexia have also been reported.Hematologic and LymphaticThrombocytopenia and sideroblastic anemia with erythroid hyperplasia, vacuolation of erythrocytes and increased serum iron concentration have occurred rarely with this drug. Adverse effects on blood clotting mechanisms have also been rarely reported.OtherMild arthralgia and myalgia have been reported frequently. Hypersensitivity reactions including rashes, urticaria, and pruritus have been reported. Fever, acne, photosensitivity, porphyria, dysuria and interstitial nephritis have been reported rarely.

Overdosage

Overdosage experience is limited. In one case report of overdose, abnormal liver function tests developed. These spontaneously reverted to normal when the drug was stopped. Clinical monitoring and supportive therapy should be employed. Pyrazinamide is dialyzable.13

Dosage And Administration

Pyrazinamide should always be administered with other effective antituberculous drugs. It is administered for the initial 2 months of a 6-month or longer treatment regimen for drug-susceptible patients. Patients who are known or suspected to have drug-resistant disease should be treated with regimens individualized to their situation. Pyrazinamide frequently will be an important component of such therapy.Patients with concomitant HIV infection may require longer courses of therapy. Physicians treating such patients should be alert to any revised recommendations from CDC for this group of patients.Usual dose: Pyrazinamide is administered orally, 15 to 30 mg/kg once daily. Older regimens employed 3 to 4 divided doses daily, but most current recommendations are for once a day. Three grams per day should not be exceeded. The CDC recommendations do not exceed 2 g per day when given as a daily regimen (see table).Alternatively, a twice weekly dosing regimen (50 to 70 mg/kg twice weekly based on lean body weight) has been developed to promote patient compliance with a regimen on an outpatient basis. In studies evaluating the twice weekly regimen, doses of pyrazinamide in excess of 3 g twice weekly have been administered. This exceeds the recommended maximum 3 g/daily dose. However, an increased incidence of adverse reactions has not been reported.The table is taken from the CDC-American Thoracic Society joint recommendations:4Recommended Drugs for the Initial Treatment of Tuberculosis in Children and AdultsDaily Dose*Maximal DailyDose inChildrenand AdultsTwice Weekly DoseDrugChildrenAdultsChildrenAdultsIsoniazid10 to 20 mg/kgPO or IM5 mg/kgPO or IM300 mg20 to 40 mg/kgMax. 900 mg15 mg/kgMax. 900 mg Rifampin10 to 20 mg/kgPO10 mg/kgPO600 mg10 to 20 mg/kgMax. 600 mg10 mg/kgMax. 600 mg Pyrazinamide15 to 30 mg/kgPO15 to 30 mg/kgPO2 g50 to 70 mg/kg50 to 70 mg/kg Streptomycin20 to 40 mg/kgIM15 mg/kg**IM1 g**25 to 30 mg/kgIM25 to 30 mg/kgIM Ethambutol15 to 25 mg/kgPO15 to 25 mg/kgPO2.5 g50 mg/kg50 mg/kg Definition of abbreviations: PO = perorally; IM = intramuscularly.* Doses based on weight should be adjusted as weight changes.**In persons older than 60 yrs of age the daily dose of streptomycin should be limited to 10 mg/kg with a maximal dose of 750 mg.

How Supplied

Pyrazinamide Tablets, USP 500 mg are round, white, scored tablets, debossed S above the score, 660 below the score.Carton of 100 tablets (10 tablets each blister pack x 10) NDC 0904-6696-61Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

References

  • •Drug Information, American Hospital Formulary Service. American Society of Hospital Pharmacists. Bethesda, MD 1991. •USPDI, Drug Information for the Health Care Professional. United States Pharmacopeial Convention, Inc. Rockville, MD 1991:1B:2226-2227. •Goodman-Gilman A, Rall TW, Nies AS, Taylor P. The Pharmacological Basis of Therapeutics, ed 8. New York, Pergamon Press. 1990;1154. •Treatment of tuberculosis and tuberculosis infection in adults and children. Am Rev Respir Dis. 1986;134:363-368. •Reynolds JEF, Parfitt K, Parsons AV, Sweetman-SC. Martindale The Extra Pharmacopoeia, ed 29. London, The Pharmaceutical Press. 1989;569-570. •Bioassay of pyrazinamide for possible carcinogenicity. National Cancer Institute Carcinogenesis Technical Report Series No. 48, 1978. •Zerger E, Anderson B, Haworth S, Lawlor T, Mortelmans K, Speck W. Salmonella mutagenicity tests: III. Results from the testing of 255 chemicals. Environ Mutagen. 1987;9 (Suppl 9):1-109. •Roman IC, Georgian L. Cytogenetic effects of some antituberculosis drugs in vitro. Mutation Research. 1977;48:215-224. •Holdiness M. Antituberculosis drugs and breast-feeding. Arch Intern Med. 1984;144:1888. •Turcios N, Evans H. Preventing and managing tuberculosis in children. J Resp Dis. 1989;10(6)(Jun):23. •Starke JR. Multidrug therapy for tuberculosis in children. Pediatr  Infec Dis J. 1990;9:785-793. •Specific requirements on content and format of labeling for human prescription drugs; proposed addi-tion of “geriatric use” subsection in the labeling. Federal Register. 1990;55(212)(Nov 1):46134-46137. •Stamathakis G, Montes C, Trouvin JH, et al. Pyrazinamide and pyrazinoic acid pharmacokinetics in patients with chronic renal failure. Clinical Nephrology. 1988;30:230-234.Manufactured For:DAVA Pharmaceuticals, Inc.Fort Lee, NJ 07024 USABy:ULTRAtab Laboratories, Inc.Highland, NY 12528 USADistributed By:MAJOR® PHARMACEUTICALS17177 N Laurel Park Dr., Suite 233Livonia, MI 48152Refer to package label for Distributor's NDC Number Revised: 04/13

Package/Label Display Panel

Pyrazinamide Tablets, USP500 mg100 Tablets

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