Pyrazinamide (Oral Route)

Pyrazinamide is an essential part of any treatment for tuberculosis.

Overview

Pyrazinamide is one of several different antibacterial drugs used to combat tuberculosis. It is taken orally and absorbed into the body from the GI tract. To this day, the exact mechanism of action for pyrazinamide’s anti tuberculosis qualities is unknown.

Pyrazinamide was first developed in 1936, but was not widely used until 1972. It has since been added to the World Health Organization’s list of essential medicines. Pyrazinamide is available in generic form, manufactured by Akorn Inc. and VersaPharm Incorporated. In the United States, monthly treatments of pyrazinamide can cost as much as 200 USD.

Conditions Treated

  • Tuberculosis

Type of Medicine

  • Antibacterial

Side Effects

In addition to its desired effects, pyrazinamide can have a wide variety of different side effects on different patients. Some of these effects can be serious and require medication, while others are only as debilitating as the discomfort they cause to the patient. Patients who begin to experience any of the following side effects should contact their doctor immediately, as they may require medical attention.

  • Appetite loss
  • Joint pain
  • Swelling of the joints, particularly in the big toe, ankle, or knee
  • Unusual tiredness
  • Unusual weakness
  • Yellow discoloration of the eyes or skin

The most serious conditions that pyrazinamide can bring on (as a side effect) include gout, liver toxicity, and sensitivity to sunlight. Patients should remain vigilant for any signs of the aforementioned conditions.

Not all side effects of pyrazinamide necessarily demand medical attention. Some side effects may simply be the product of the patient’s body adapting to the new medicine. Patients who experience any of the following side effects should consult with their doctor to find out how best to mitigate or lessen any of the most unpleasant side effects.

  • Itching
  • Skin rash

This is not necessarily a complete list of side effects. Patients who begin to experience new or worsening effects/symptoms should contact their doctor immediately. Patients can report new or worsening side effects to the FDA at 1 800 FDA 1088 or on the web at www.fda.gov/medwatch.

Dosage

Pyrazinamide is available in tablet form. The dosage strengths described below call for patients to take X amount of pyrazinamide, not a set number of tablets.

Pyrazinamide is usually taken in conjunction with other drugs to combat tuberculosis. Dosage may vary based on a patient's weight, age, and the strength of the other drugs being taken.

In most cases, patients are directed to take between 15 and 30 mg or pyrazinamide per kilogram of body weight once daily. Tuberculosis treatments can last as long as 9 months, so a patient should rely on their doctor’s advice to determine how long they need to take pyrazinamide.

Alternatively, patients may be directed to take between 50 and 75 mg of pyrazinamide per kilogram of body weight twice a week.

The CDC, The American Thoracic Society, and the Infectious Disease Society of America all agree on an alternative dosing schedule based on lean body weight. Their recommendations are as follows:

For daily dosing:

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

For dosing twice weekly:

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

For dosing three times weekly:

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

Elderly patients are usually recommended to start near the bottom of the dosing range and work up from there. This is because elderly patients are more likely to have renal or hepatic impairments.

Patients who miss a dose should take their dose as soon as they remember to. However, if it is nearly time for the patient to take their next dose (the next day, for example), patients should simply skip the dose they forgot about and resume dosing as usual when it is time for their next dose. Patients should never double their dose in an attempt to retroactively make up for passed doses.

The dosing regimes described above are taken from established guidelines and typical dosing procedures. The dosages described above may not necessarily be ideal for all patients.

Interactions

Different drugs can interact in a variety of different, unique ways in a patient’s body. These interactions may heighten or limit the effects of each drug, or produce an entirely new effect.

Patients who are taking any of the following drugs should exercise extreme caution when considering taking pyrazinamide, as they may react in a serious, possibly deadly way.

  • BCG
  • Cholera vaccine (live)
  • Leflunomide
  • Lomitapide
  • Mipomersen
  • Rifampin
  • Teriflunomide
  • Zidovudine
  • Ethionamide

Additionally, due to the potentially serious effects of pyrazinamide on the liver, patients should avoid combining pyrazinamide with any other drug which puts strain on their liver. Patients should make sure to disclose a complete list of all drugs, medications, and supplements they are taking to their doctor prior to deciding to take pyrazinamide.

The following drugs will interact negatively with pyrazinamide, but not as often or with as much severity as the drugs listed above. Patients who are taking any of the following drugs should still exercise caution when considering taking pyrazinamide. Patients who must take pyrazinamide and any of the following drugs concurrently should consult with their doctor to determine whether or not it is safe to do so and potential alternative treatments.

  • Allopurinol
  • Bedaquiline
  • Black cohosh
  • Brentuximab
  • Clofarabine
  • Cyclosporine
  • Efavirenz
  • Epirubicin
  • Idelalisib
  • Interferon beta-1a
  • Interferon beta-1b
  • Methotrexate
  • Naltrexone
  • Peginterferon beta-1a
  • Probenecid
  • Sulfinpyrazone
  • Thioguanine
  • Trabectedin
  • Typhoid vaccine (live)

This is not necessarily a complete list of potential drug interactions. Patients should rely on their doctor to identify any potential interactions between pyrazinamide and any other drugs they are taking. Patients should disclose a complete list of any and all drugs, medications, or supplements they are taking to their doctor prior to deciding to take pyrazinamide.

Warnings

When used alone, tuberculosis may develop a resistance to pyrazinamide. For this reason, tuberculosis should never be solely treated with pyrazinamide. As many as four drugs should be used to fight tuberculosis, typically including rifampin and isoniazid.

Patients have been known to suffer severe allergic reactions to pyrazinamide while taking it. Patients who have had an allergic reaction to pyrazinamide before should not take pyrazinamide. Patients taking pyrazinamide should remain vigilant for signs of an allergic reaction, which can include:

  • Rash
  • Hives
  • Swelling of the neck or throat

Pyrazinamide is considered a category C drug in terms of pregnancy. This means that there have been insufficient studies done on human fetuses to determine whether or not pyrazinamide is safe for use in pregnant women. Patients who are pregnant or who may become pregnant should consult with their doctor prior to deciding to take pyrazinamide.

Additionally, it is not known whether or not pyrazinamide can pass into breast milk or whether it is harmful to breastfeeding infants. Generally, patients are cautioned against taking pyrazinamide while pregnant, although taking pyrazinamide while breastfeeding is thought to be more safe.

As with all drugs, patients should weigh the possible risks against the potential benefits before they decide to take the drug.

Pyrazinamide is metabolized by the liver. Patients who suffer from renal impairment or liver disease require close monitoring and may need to seek alternative treatment. Patients should receive serum uric acid and liver function tests prior to taking pyrazinamide as a way to assess risk. Serious hepatic injury is possible in liver damaged patients who take pyrazinamide. Patients should stop taking pyrazinamide immediately and contact their doctor if they begin to experience symptoms of hepatic injury, which can include:

  • Fever
  • Rash
  • Anorexia
  • Nausea
  • Vomiting
  • Fatigue
  • Jaundice
  • Bloody or darkened urine

Patients taking pyrazinamide should see improvement within 2 to 3 weeks of their treatment. If no improvement is noticed, or it the patient’s symptoms become worse, patients should consult with their doctor. Dosage adjustment may be necessary and potential alternative treatments may need to be explored.

Patients who have liver disease or other renal impairment should make sure their doctor is aware of their condition prior to deciding to take pyrazinamide. Additionally, patients should make sure their doctor is fully apprised of all medical conditions they suffer from prior to deciding to take pyrazinamide.

Patients with gout or with a history of gout should be aware that pyrazinamide can intensify the effects of gout. Pyrazinamide can impede the renal excretion of uric acid, exacerbating the effects of gout and possibly precipitating gout in an otherwise gout free patient.

Patients who undergo dialysis should receive treatment after dialysis. Hemodialysis may remove pyrazinamide from the patient, rendering the treatment impotent.

The half life of pyrazinamide is extended in patients who have renal impairment. Pyrazinamide can build up in the systems of renally impaired patients, putting them at increased risk of side effects, liver troubles, and other adverse effects. Dosage adjustments or alternative treatments may be necessary. Patients who suffer from renal impairment or any other condition should make sure that their doctor is fully apprised of any and all medical conditions they suffer from prior to deciding to take pyrazinamide.

Patients with Diabetes Mellitus should be aware that pyrazinamide may exacerbate their condition. Patients with diabetes mellitus or any other condition should make sure their doctor is fully apprised of any and all medical conditions they have prior to deciding to take pyrazinamide.

This is not necessarily a complete list of all the risks associated with pyrazinamide. Patients should rely on their doctor to describe all the potential risks of taking pyrazinamide and instruct the patient on how to minimize those risks.

Storage

Pyrazinamide should be stored in a closed container at room temperature. Patients should keep their pyrazinamide away from extreme temperatures. Patients should never freeze pyrazinamide.

Summary

Pyrazinamide is an integral part of the standard treatment for tuberculosis. When used correctly, in conjunction with other drugs, pyrazinamide is an effective way to treat tuberculosis. Patients who suffer from renal or hepatic impairment, especially hepatic impairment, and contract tuberculosis may be put in a tough bind. There are no robust alternatives to pyrazinamide available, and it can be extremely dangerous to let tuberculosis go untreated. When given the respect it demands, including the potential need to closely monitor liver function, pyrazinamide can be a relatively safe way to treat tuberculosis. Certainly safer than not treating tuberculosis, at least.

 

Resources
Last Reviewed:
January 31, 2018
Last Updated:
January 27, 2018