Pyrazinamide

Pyrazinamide is an antibiotic that fights bacteria.

Pyrazinamide is used to treat tuberculosis (TB) in adults and children.

Pyrazinamide must be used with other TB medicines. Tuberculosis can become resistant to treatment if pyrazinamide is used alone. Take all your medicines as prescribed by your doctor.

Pyrazinamide may also be used for purposes not listed in this medication guide.

You should not use pyrazinamide if you have active gout or severe liver disease.

You should not use pyrazinamide if you are allergic to it, or if you have:

• active gout; or
• severe liver disease.

To make sure pyrazinamide is safe for you, tell your doctor if you have:

• HIV or AIDS;
• gout;
• liver disease;
• diabetes; or
• if you drink large amounts of alcohol.

Your doctor will check your liver enzymes and uric acid levels before you start treatment, to make sure you can safely take pyrazinamide.

It is not known whether pyrazinamide will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

Pyrazinamide can pass into breast milk and may harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Pyrazinamide is a prescription medication used to treat active tuberculosis. Pyrazinamide belongs to a group of drugs calledantituberculous agents. These work by stopping the growth of bacteria that causes tuberculosis (TB).  

This medication comes in as a tablet form and is taken once a day with or without food. Pyrazinamide can also taken twice a week at a higher dose.

Common side effects of pyrazinamide include upset stomach, joint and muscle pain, nausea, and vomiting.

Pyrazinamide is a prescription medication used with other medications to treat active tuberculosis.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.  

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• fever;

• joint pain or swelling;

• easy bruising or bleeding (nosebleeds, bleeding gums);

• gout flare-up symptoms--joint pain, stiffness, redness, or swelling (especially at night); or

• liver problems--nausea, upper stomach pain, itching, tiredness, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:

• joint or muscle pain;

• nausea, vomiting; or

• loss of appetite.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Antituberculosis agent; synthetic niacinamide derivative.124

Specific Drugs and Laboratory Tests

Drug	Interaction	Comments
Rifampin	Severe liver injuries, including some fatalities, reported in patients receiving a 2-month daily regimen of rifampin and pyrazinamide for treatment of LTBI101 125 127	Use of rifampin and pyrazinamide for treatment of LTBI should be considered only in carefully selected patients with close monitoring and only if potential benefits outweigh the risk of hepatotoxicity and death127
Tests for ketones in urine (Acetest, Ketostix)	Pyrazinamide produces a pink-brown color that may interfere with interpretation of test124

Absorption

Bioavailability

Well absorbed from the GI tract; peak plasma concentrations attained within 2 hours.124

Distribution

Extent

Distributed into body tissues and fluids, including liver and lung.124

CSF concentrations are approximately equal to concurrent plasma concentrations in patients with inflamed meninges.124

Not known whether pyrazinamide crosses the placenta.c

Distributed into milk.124

Plasma Protein Binding

10%.124

Elimination

Metabolism

Hydrolyzed in the liver to major active metabolite, pyrazinoic acid; pyrazinoic acid undergoes further hydrolysis.124

Elimination Route

Excreted in urine (70%), mainly by glomerular filtration.124

Removed by dialysis.124

Half-life

9–10 hours.124

Special Populations

Half-life may be prolonged in patients with renal or hepatic impairment.124

• Bacteriostatic or bactericidal in action.108 110

• The exact mechanism of action has not been fully elucidated.109 110 g Pyrazinoic acid, the active metabolite, appears to disrupt membrane energetics and inhibit membrane transport function in susceptible M. tuberculosis.g

• A highly specific agent; active only against M. tuberculosis.124 Other mycobacteria, including M. kansasii and M. marinum, are resistant.f

• Natural and acquired resistance to pyrazinamide observed in vitro and in vivo in strains of M. tuberculosis.c

Pyrazinamide belongs to the family of medicines called anti-infectives. It is used, along with other medicines, to treat tuberculosis (TB).

To help clear up your tuberculosis (TB) infection completely, you must keep taking pyrazinamide for the full time of treatment, even if you begin to feel better. This is very important. It is also important that you do not miss any doses.

Pyrazinamide is available only with your doctor's prescription.

To help clear up your TB completely, it is important that you keep taking pyrazinamide for the full time of treatment, even if you begin to feel better after a few weeks. It is important that you do not miss any doses.

Dosing

The dose of pyrazinamide will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of pyrazinamide. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (tablets):
  • For tuberculosis (TB):
    • Adults and children—Dose is based on body weight. The usual dose is 15 to 30 milligrams (mg) of pyrazinamide per kilogram (kg) (6.8 to 13.6 mg per pound) of body weight once a day; or 50 to 70 mg per kg (22.7 to 31.8 mg per pound) two times a week or three times a week, depending on the schedule your doctor chooses for you. pyrazinamide must be taken along with other medicines used to treat TB.

Missed Dose

If you miss a dose of pyrazinamide, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

1. Drug Information, American Hospital Formulary Service. American Society of Hospital Pharmacists. Bethesda, Md. 1991. 2. USPDI, Drug Information for the Health Care Professional. United States Pharmacopeial Convention, Inc. Rockville, Md. 1991: 1B : 2226-2227. 3. Goodman-Gilman A, Rall TW, Nies AS, Taylor P. The Pharmacological Basis of Therapeutics, ed 8. New York, Pergamon Press. 1990; 1154. 4. Treatment of tuberculosis and tuberculosis infection in adults and children. Am Rev Respir Dis. 1986; 134: 363-368. 5. Reynolds JEF, Parfitt K, Parsons AV, Sweetman SC. Martindale The Extra Pharmacopoeia, ed 29. London, The Pharmaceutical Press. 1989; 569-570. 6. Bioassay of Pyrazinamide for possible carcinogenicity. National Cancer Institute Carcinogenesis Technical Report Series No. 48, 1978. 7. 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. 8. Roman IC, Georgian L. Cytogenetic effects of some antituberculosis drugs in vitro. Mutation Research. 1977; 48: 215- 224. 9. Holdiness M. Antituberculosis drugs and breast-feeding. Arch Intern Med. 1984; 144: 1888. 10. Turcios N, Evans H. Preventing and managing tuberculosis in children. J Resp Dis. 1989; 10 (6) (Jun): 23. 11. Starke JR. Multidrug therapy for tuberculosis in children. PediatrInfecDis J. 1990; 9: 785-793. 12. Specific requirements on content and format of labeling for human prescription drugs; proposed addition of "geriatric use" subsection in the labeling. Federal Register. 1990; 55 (212) (Nov 1): 46134-46137. 13. 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.

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Generic: 500 mg

Tuberculosis: Adjunctive treatment of tuberculosis (TB) in combination with other antituberculosis agents

Hypersensitivity to pyrazinamide or any component of the formulation; acute gout; severe hepatic damage

There are no dosage adjustments provided in the manufacturer's labeling. Use is contraindicated in cases of severe hepatic impairment.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience muscle pain. Have patient report immediately to prescriber signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), joint pain, or joint edema (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.