Disclaimer:

Medidex is not a provider of medical services and all information is provided for the convenience of the user. No medical decisions should be made based on the information provided on this website without first consulting a licensed healthcare provider.This website is intended for persons 18 years or older. No person under 18 should consult this website without the permission of a parent or guardian.

Pyrazinamide

×

Overview

What is Pyrazinamide?

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:

C H N O              M.W. 123.11

Each Pyrazinamide tablet for oral administration contains 500 mg of pyrazinamide and the following inactive ingredients: Corn Starch, Magnesium Stearate, Pregelatinized Starch and Stearic Acid.



What does Pyrazinamide look like?



What are the available doses of Pyrazinamide?

Sorry No records found.

What should I talk to my health care provider before I take Pyrazinamide?

Sorry No records found

How should I use Pyrazinamide?

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.* )

(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.

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:

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.


What interacts with Pyrazinamide?


  • Pyrazinamide is contraindicated in persons:

    • with severe hepatic damage.
    • who have shown hypersensitivity to it.
    • with acute gout.



What are the warnings of Pyrazinamide?

Withdrawal symptoms of the barbiturate type have occurred after the discontinuation of benzodiazepines (see ).

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.


What are the precautions of Pyrazinamide?

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 to pyrazinamide is uncommon. In cases with known or suspected drug resistance, susceptibility tests with recent cultures of against pyrazinamide and the usual primary drugs should be performed. There are few reliable 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.

Carcinogenicity, Mutagenicity, Impairment of Fertility

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.

Usage in Children

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

Geriatric Use

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.


What are the side effects of Pyrazinamide?

General

Fever, porphyria and dysuria have rarely been reported. Gout (see ).

Gastrointestinal

The principal adverse effect is a hepatic reaction (see ). 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 Lymphatic

Thrombocytopenia 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.

Other

Mild 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.


What should I look out for while using Pyrazinamide?

Pyrazinamide is contraindicated in persons:

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.


What might happen if I take too much Pyrazinamide?

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.


How should I store and handle Pyrazinamide?

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Keep tightly closed (protect from moisture). Protect from light.Pyrazinamide Tablets, USP 500 mg are round, white, scored tablets, debossed S above the score, 660 below the score.   NDC 67253-660-10 - Bottle of 100   NDC 67253-660-50 - Bottle of 500Store 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.Pyrazinamide Tablets, USP 500 mg are round, white, scored tablets, debossed S above the score, 660 below the score.   NDC 67253-660-10 - Bottle of 100   NDC 67253-660-50 - Bottle of 500Store 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.Pyrazinamide Tablets, USP 500 mg are round, white, scored tablets, debossed S above the score, 660 below the score.   NDC 67253-660-10 - Bottle of 100   NDC 67253-660-50 - Bottle of 500Store 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.Pyrazinamide Tablets, USP 500 mg are round, white, scored tablets, debossed S above the score, 660 below the score.   NDC 67253-660-10 - Bottle of 100   NDC 67253-660-50 - Bottle of 500Store 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.Pyrazinamide Tablets, USP 500 mg are round, white, scored tablets, debossed S above the score, 660 below the score.   NDC 67253-660-10 - Bottle of 100   NDC 67253-660-50 - Bottle of 500Store 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.


×

Clinical Information

Chemical Structure

No Image found
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. Pyrazinamide is approximately 10% bound to plasma proteins.

The 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.

Approximately 70% of an oral dose is excreted in urine, mainly by glomerular filtration within 24 hours.

Pyrazinamide may be bacteriostatic or bactericidal against depending on the concentration of the drug attained at the site of infection. The mechanism of action is unknown. and the drug is active only at a slightly acidic pH.

Non-Clinical Toxicology
Pyrazinamide is contraindicated in persons:

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.

Ranitidine has been reported to affect the bioavailability of other drugs through several different mechanisms such as competition for renal tubular secretion, alteration of gastric pH, and inhibition of cytochrome P450 enzymes.

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 to pyrazinamide is uncommon. In cases with known or suspected drug resistance, susceptibility tests with recent cultures of against pyrazinamide and the usual primary drugs should be performed. There are few reliable tests for pyrazinamide resistance. A reference laboratory capable of performing these studies must be employed.

General

Fever, porphyria and dysuria have rarely been reported. Gout (see ).

Gastrointestinal

The principal adverse effect is a hepatic reaction (see ). 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 Lymphatic

Thrombocytopenia 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.

Other

Mild 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.

×

Reference

This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"

While we update our database periodically, we cannot guarantee it is always updated to the latest version.

×

Review

Rate this treatment and share your opinion


Helpful tips to write a good review:

  1. Only share your first hand experience as a consumer or a care giver.
  2. Describe your experience in the Comments area including the benefits, side effects and how it has worked for you. Do not provide personal information like email addresses or telephone numbers.
  3. Fill in the optional information to help other users benefit from your review.

Reason for Taking This Treatment

(required)

Click the stars to rate this treatment

This medication has worked for me.




This medication has been easy for me to use.




Overall, I have been satisfied with my experience.




Write a brief description of your experience with this treatment:

2000 characters remaining

Optional Information

Help others benefit from your review by filling in the information below.
I am a:
Gender:
×

Professional

Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72
×

Tips

Tips

×

Interactions

Interactions

A total of 440 drugs (1549 brand and generic names) are known to interact with Imbruvica (ibrutinib). 228 major drug interactions (854 brand and generic names) 210 moderate drug interactions (691 brand and generic names) 2 minor drug interactions (4 brand and generic names) Show all medications in the database that may interact with Imbruvica (ibrutinib).