Pirazinid (Pyrazinamide)

Pirazinid (Pyrazinamide) Uses, Dosage, Side Effects, Food Interaction and all others data.

Pirazinid (Pyrazinamide) may be bacteriostatic or bactericidal in action, depending on the concentration of the drug attained at the site of the infection and the susceptibility of the infecting organism. Its activity appears to partly depend on conversion of the drug to pyrazinoic acid (POA), which lowers the pH of the environment below that which is necessary for growth of Mycobacterium tuberculosis. Susceptible strains of M. tuberculosis produce pyrazinamidase, an enzyme that deaminates pyrazinamide to POA, and the in vitro susceptibility of a given strain of the organism appears to correspond to its pyrazinamidase activity.

Pirazinid (Pyrazinamide) kills or stops the growth of certain bacteria that cause tuberculosis (TB). It is used with other drugs to treat tuberculosis. It is a highly specific agent and is active only against Mycobacterium tuberculosis. In vitro and in vivo, the drug is active only at a slightly acid pH. Pyrazinamie gets activated to Pyrazinoic acid in the bacilli where it interferes with fatty acid synthase FAS I. This interferes with the bacteriums ability to synthesize new fatty acids, required for growth and replication.

Trade Name Pirazinid (Pyrazinamide)
Availability Prescription only
Generic Pyrazinamide
Pyrazinamide Other Names 2-carbamylpyrazine, 2-pyrazinecarboxamide, Aldinamide, Pirazinamida, Pirazinamide, Pyrazinamid, Pyrazinamida, Pyrazinamide, Pyrazinamidum, Pyrazine carboxamide, Pyrazineamide, Pyrazinecarboxamide, Pyrazinoic acid amide, Pyrizinamide
Related Drugs ciprofloxacin, levofloxacin, Levaquin, rifampin, isoniazid, rifapentine, Rifadin, Priftin, Nydrazid
Type
Formula C5H5N3O
Weight Average: 123.1127
Monoisotopic: 123.043261797
Protein binding

~10% (bound to plasma proteins)

Groups Approved, Investigational
Therapeutic Class Anti-Tubercular Chemotherapeutics
Manufacturer
Available Country Turkey
Last Updated: September 19, 2023 at 7:00 am
Pirazinid (Pyrazinamide)
Pirazinid (Pyrazinamide)

Uses

Pirazinid (Pyrazinamide) is used 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 Pirazinid (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. Pirazinid (Pyrazinamide) frequently will be an important component of such therapy.
  • In patients with concomitant HIV infection, the physician should be aware of current recommendation of CDC. It is possible these patients may require a longer course of treatment

It is also used after treatment failure with other primary drugs in any form of active tuberculosis.

Pirazinid (Pyrazinamide) should only be used in conjunction with other effective antituberculous agents.

Pirazinid (Pyrazinamide) is also used to associated treatment for these conditions: Active Tuberculosis, Pulmonary Tuberculosis (TB)

How Pirazinid (Pyrazinamide) works

Pirazinid (Pyrazinamide) diffuses into active M. tuberculosis that express pyrazinamidase enzyme that converts pyrazinamide to the active form pyrazinoic acid. Pyrazinoic acid can leak out under acidic conditions to be converted to the protonated conjugate acid, which is readily diffused back into the bacilli and accumulate intracellularly. The net effect is that more pyrazinoic acid accumulates inside the bacillus at acid pH than at neutral pH. Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids. However, this theory was thought to have been discounted. However, further studies reproduced the results of FAS I inhibition as the putative mechanism first in whole cell assay of replicating M. tuberculosis bacilli which have shown that pyrazinoic acid and its ester inhibit the synthesis of fatty acids. This study was followed by in vitro assay of tuberculous FAS I enzyme that tested the activity with pyrazinamide, pyrazinoic acid and several classes of pyrazinamide analogs. Pirazinid (Pyrazinamide) and its analogs inhibited the activity of purified FAS I.

It has also been suggested that the accumulation of pyrazinoic acid disrupts membrane potential and interferes with energy production, necessary for survival of M. tuberculosis at an acidic site of infection. Pyrazinoic acid has also been shown to bind to the ribosomal protein S1 (RpsA) and inhibit trans-translation. This may explain the ability of the drug to kill dormant mycobacteria.

Dosage

Pirazinid (Pyrazinamide) dosage

Usual Adult Dose for Tuberculosis: Active:

15 to 30 mg/kg (up to 2 g) orally once a day in combination with three other antituberculous drugs for the initial 2 months of a 6-month or 9-month treatment regimen, until drug susceptibility tests are known. An alternate dosing regimen of 50 to 75 mg/kg (up to 3 g) orally twice a week may be used after 2 weeks of daily therapy to increase patient compliance.

Alternatively, the CDC, The American Thoracic Society, and the Infectious Diseases Society of America suggest the following dosing based on estimated lean body weight:

Daily dosing:

  • 40 to 45 kg: 1000 mg
  • 56 to 75 kg: 1500 mg
  • 76 to 90 kg: 2000 mg

Twice weekly dosing:

  • 40 to 55 kg: 2000 mg
  • 56 to 75 kg: 3000 mg
  • 76 to 90 kg: 4000 mg

Thrice weekly dosing:

  • 40 to 55 kg: 1500 mg
  • 56 to 75 kg: 2500 mg
  • 76 to 90 kg: 3000 mg

Usual Adult Dose for Tuberculosis: Latent:

A public health expert should be consulted prior to the use of the combination regimen with rifampin.

15 to 20 mg/kg, based on actual body weight (lean), orally once daily (maximum 2 g) for 2 months. Alternatively, a dosage of 50 mg/kg may be administered orally twice-weekly (maximum 4 g).

Usual Pediatric Dose for Tuberculosis: Active:

(Used as part of a multidrug regimen. Treatment regimens consist of an initial 2-month phase, followed by a continuation phase of 4 or 7 additional months. Frequency of dosing may differ depending on phase of therapy)

Infants, Children less than 40 kg and Adolescents 14 years and younger and less than 40 kg:Non-HIV patients:

  • Daily therapy: 15 to 30 mg/kg/dose (maximum: 2 g/dose) once daily
  • Directly observed therapy (DOT): 50 mg/kg/dose (maximum: 2 g/dose) twice weekly

HIV-exposed/infected patients:

  • Daily therapy: 20 to 40 mg/kg/dose once daily (maximum: 2 g/day)

Side Effects

General: Fever, porphyria and dysuria have rarely been reported. Gout.

Gastrointestinal: The principal adverse effect is a hepatic reaction. 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 pruritis have been reported. Fever, acne, photosensitivity, porphyria, dysuria and interstitial nephritis have been reported rarely.

Toxicity

Side effects include liver injury, arthralgias, anorexia, nausea and vomiting, dysuria,malaise and fever, sideroblastic anemia, adverse effects on the blood clotting mechanism or vascular integrity, and hypersensitivity reactions such as urticaria, pruritis and skin rashes.

Precaution

Pirazinid (Pyrazinamide) is contraindicated in patients with severe hepatic disease and with acute gout.

Patients started on pyrazinamide should have baseline serum uric acid and liver function test results. Liver function should be monitored closely during therapy. Patients with preexisting liver disease or those at increased risk of drug related hepatitis should be monitored closely.

Pirazinid (Pyrazinamide) should be discontinued and not restarted if signs of hepatocellular damage or hyperuricemia with an acute gouty arthritis appear.

Polyarthralgias have been reported in patients. The pain may respond to aspirin or other nonsteroidal anti-inflammatory agents.

Caution should be used in patients with a history of diabetes mellitus, as management of the disease may be more difficult.

Primary resistance of Mycobacterium tuberculosis to pyrazinamide is not common. In cases with known or suspected drug resistance, in vitro susceptibility tests with recent cultures of Mycobacterium tuberculosis against pyrazinamide and the usual primary drugs should be conducted. There are few reliable in vitro tests for pyrazinamide resistance. A reference laboratory capable of performing these tests must be utilized.

Clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for elderly patients should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased renal or hepatic function, and of concomitant disease or other drug therapy.

Interaction

Antagonises the effect of uricosuric agents (e.g. probenecid, sulfinpyrazone). May reduce the contraceptive effect of oestrogens. May inactivate oral typhoid vaccine. May increase the serum concentration of ciclosporin. May enhance the hepatotoxic effect of rifampicin.

Food Interaction

  • Take with or without food. The absorption is unaffected by food.

Elimination Route

Rapidly and well absorbed from the gastrointestinal tract.

Half Life

9-10 hours (normal conditions)

Elimination Route

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

Pregnancy & Breastfeeding use

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

Nursing Mothers: Pirazinid (Pyrazinamide) has been found in small amounts in breast milk. Therefore, it is advised that Pirazinid (Pyrazinamide) be used with caution in nursing mothers taking into account the risk-benefit of this therapy.

Contraindication

Pirazinid (Pyrazinamide) is contraindicated in persons:

  • With severe hepatic damage.
  • Who have shown hypersensitivity to it.
  • With acute gout.

Special Warning

Usage in Children: Pirazinid (Pyrazinamide) regimens employed in adults are probably equally effective in children. Pirazinid (Pyrazinamide) appears to be well tolerated in children.

Geriatric Use: Clinical studies of Pirazinid (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.

Renal Dose Adjustments: The manufacturer recommends to start therapy at low end of dosage range and monitor patient closely.For the treatment of active tuberculosis, the CDC, ATS, and IDSA recommend against daily dosing. For patients with CrCl less than 30 mL/min or patients receiving hemodialysis the recommended dose is 25 to 35 mg/kg per dose three times per week.

Liver Dose Adjustments: Monitor patients closely.

Dose Adjustments: 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.

If organism is susceptible to isoniazid and rifampin, pyrazinamide is continued for the first 2 months of a 6-month course of therapy (9-months if HIV positive). If primary drug resistance is shown, drug regimens should be adjusted as needed and continued for at least 6 months, or 3 months beyond culture conversion (9 months, or 6 months beyond culture conversion if HIV positive). If multiple-drug resistance is demonstrated, therapy should be continued for 12 to 24 months following culture conversion.

Acute Overdose

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. Pirazinid (Pyrazinamide) is dialyzable.

Storage Condition

Store between 15-30° C.

Innovators Monograph

You find simplified version here Pirazinid (Pyrazinamide)

Pirazinid (Pyrazinamide) contains Pyrazinamide see full prescribing information from innovator Pirazinid (Pyrazinamide) Monograph, Pirazinid (Pyrazinamide) MSDS, Pirazinid (Pyrazinamide) FDA label

FAQ

What is Pirazinid (Pyrazinamide) used for?

Pirazinid (Pyrazinamide) is a prescription medicine used to treat the symptoms of Tuberculosis. Pirazinid (Pyrazinamide) may be used alone or with other medications.

How does Pirazinid (Pyrazinamide) work?

Pirazinid (Pyrazinamide) works by stopping the growth of bacteria. This antibiotic treats only bacterial infections. It will not work for viral infections.

What are the common side effects of Pirazinid (Pyrazinamide)?

Common side effects of Pirazinid (Pyrazinamide) are include:

  • 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);

Is Pirazinid (Pyrazinamide) safe during pregnancy?

Pirazinid (Pyrazinamide) is recommended for use in pregnancy. No reports of fetal malformations are attributable to Pirazinid (Pyrazinamide), although no animal or epidemiological studies have been reported.

Is Pirazinid (Pyrazinamide) safe during breastfeeding?

breastfeeding should not be discouraged in women taking Pirazinid (Pyrazinamide).

Can I drink alcohol with Pirazinid (Pyrazinamide)?

It is best to avoid alcohol-containing beverages while taking Pirazinid (Pyrazinamide).

When should be taken of Pirazinid (Pyrazinamide)?

Pirazinid (Pyrazinamide) is usually taken once per day. However, some people take the medicine only 2 times per week. Use Pirazinid (Pyrazinamide) for the full prescribed length of time.

How should I take Pirazinid (Pyrazinamide)?

You may need to take Pirazinid (Pyrazinamide) for only the first 2 months of your full course of treatment.Pirazinid (Pyrazinamide) is usually taken once per day. However, some people take the medicine only 2 times per week.

How long does Pirazinid (Pyrazinamide) work?

Pirazinid (Pyrazinamide) is administered for the initial 2 months of a 6-month or longer treatment regimen for drug-susceptible patients.

Can I take Pirazinid (Pyrazinamide) for a long time?

Take Pirazinid (Pyrazinamide) only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

What happens if I miss a dose of Pirazinid (Pyrazinamide)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Who should not take Pirazinid (Pyrazinamide)?

You should not use Pirazinid (Pyrazinamide) if you have active gout or severe liver disease.

What happens if I overdose of Pirazinid (Pyrazinamide)?

Seek emergency medical attention.

Is Pirazinid (Pyrazinamide) hepatotoxic?

While Pirazinid (Pyrazinamide) are known to cause hepatotoxicity, ethambutol and streptomycin are considered not to be hepatotoxic.

What should I avoid while taking Pirazinid (Pyrazinamide)?

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

Why does Pirazinid (Pyrazinamide) cause hyperuricemia?

The metabolite Pirazinid (Pyrazinamide) is oxidized by xanthine oxidase and is likely responsible for the hyperuricemic effect.

Does Pirazinid (Pyrazinamide) cause joint pain?

Mild muscle/joint pain may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Can Pirazinid (Pyrazinamide) cause gout?

Pirazinid (Pyrazinamide) an anti-mycobacterial drug, not only induces hyperuricaemia, but may also lead to acute gouty attacks.

Does Pirazinid (Pyrazinamide) cause hepatitis?

Pirazinid (Pyrazinamide) has not been linked to chronic hepatitis or vanishing bile duct syndrome. There is no cross reactivity of the hepatic injury with other currently available antituberculosis agents.

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*** Taking medicines without doctor's advice can cause long-term problems.
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