Pyrazinamide - Uses, Dosage, Side Effects, Drug Warnings, and Precautions

Overview:

Pyrazinamide is a prescription antibiotic employed against active tuberculosis. It treats the infection with medications like Isoniazid, Ethambutol, Rifampin, and Streptomycin. Pyrazinamide is available as an oral tablet. Pyrazinamide stops the growth of the infection-causing bacteria.

Pyrazinamide is a critical component of tuberculosis treatment, uniquely targeting dormant or semi-dormant bacteria. It is part of a combination therapy that includes other first-line TB drugs and helps shorten the duration of treatment while reducing the risk of developing drug-resistant strains. While pyrazinamide is effective in treating TB, it is not without side effects, and patients must adhere to their prescribed treatment regimen and communicate any adverse reactions to their healthcare provider. The fight against tuberculosis requires a multidisciplinary approach, including proper diagnosis, treatment, and public health interventions, to ensure the effective control and eventual eradication of this global health threat. Pyrazinamide, alongside other TB drugs, plays a vital role in achieving these goals.

Report to the doctor and seek medical treatment immediately if you experience seizures or symptoms of liver damage like yellowing of skin or white of the eye, dark urine, or pale stools while taking this medication.

Drug Group:

Pyrazinamide is an antibiotic from an antitubercular agent class of medications. It is identified as a nicotinamide analog. Pyrazinamide is active against the bacteria Mycobacterium tuberculosis, which causes tuberculosis. The other antitubercular drugs include Rifampin, Streptomycin, Isoniazid, and Ethambutol.

Drug Warnings and Precautions:

Inform the doctor if you have any of the following conditions:

• Drug Allergy: Known history of allergy to the active or inactive components of the drug.

• Diabetes: Disease management may be crucial. Monitoring is required.

• High Uric Acid Levels: Pyrazinamide increases uric acid levels in the blood. Use should be strictly avoided in patients with gout.

• Liver Disease: Can accelerate liver injury. Use with caution.

• Pregnancy and Breastfeeding: Use as directed by the doctor.

For Patients:

What Is Pyrazinamide Used For?

Pyrazinamide is one of the primary drugs in the therapy used to treat active tuberculosis infection. It is generally represented as Z. Tuberculosis is a contagious infection affecting the lungs. It can spread through the cough and sneeze of the infected person. Severe conditions can result in the infection, causing bacteria to affect the other parts of the body like the brain, spinal cord, kidneys, pancreas, etc. Serious medical attention is required to treat and prevent the spread of infection. Untreated infections can be fatal.

Never take Pyrazinamide or other drugs without talking to the doctor first.

How Does Pyrazinamide Work?

The exact mechanism by which Pyrazinamide is not clearly understood. It is converted into pyrazinoic acid, the active form of the drug. This active form inhibits the production of fatty acids in the bacteria, which is required to keep the cell membrane of the infection-causing bacteria intact.

Thus, there is a disruption of the bacterial membrane. Hence, Pyrazinamide acts by both stopping the growth and killing the bacteria.

Onset Of Action:

Pyrazinamide is almost rapidly and completely absorbed after oral administration. It reaches its highest concentration in the blood within 0.75 to 4 hours. About 70 % of the drug is excreted through urine. In short, the onset of action is 2 to 4 hours, and the effect will last up to 9 hours in healthy adults.

Habit-Forming:

Pyrazinamide has not been reported to show any habit-forming tendencies in people taking the medication.

Expiry Date:

Pyrazinamide tablets should not be taken past their expiry date, which will be given on the back of the drug packet.

What Is the Dosage of Pyrazinamide?

Pyrazinamide is typically administered as part of a combination therapy regimen for TB treatment. The exact dose and time period of treatment may vary depending on factors such as the patient's age, weight, overall health, and the drug regimen being used.

For adults, a common dosage of Pyrazinamide is 15 to 30 mg/kg of body weight per day, usually taken as a single daily dose. It is usually taken orally, and the treatment course typically lasts for two months in the initial phase of TB treatment. After the initial phase, Pyrazinamide is often discontinued, and other drugs are continued for the remainder of the treatment.

Patients need to adhere to their prescribed treatment regimen, including the dosage and duration, to ensure the effective treatment of TB and reduce the risk of developing drug-resistant strains.

How to Use Pyrazinamide?

• Take with or without food.

• Swallow as a whole with a glass of water.

• Follow the instructions on the label that your pharmacist gives carefully.

Missed Dose:

It is essential to take this medication exactly when prescribed. If you take this medication daily and forget to dose, do so immediately. However, if it is almost time for the next dose, skip the missed dose and administer the next dose as scheduled. To make up for the missed dose, do not take double doses.

If you take this medication weekly and forget to take a dosage, take it immediately if it falls on the same day. If you remember the next day or later, ask your doctor or pharmacist for a different dose plan.

Overdose:

If an overdose happens and unusual symptoms occur, contact emergency help or the nearest poison control center immediately.

What Are the Contraindications of Pyrazinamide?

Do not take Pyrazinamide under the following conditions:

• Known history of allergy to the drug or its components.

• Severe liver damage.

• Gout (a form of joint inflammation).

What Are the Side Effects of Pyrazinamide?

The common side effects include:

• Nausea.

• Vomiting.

• Joint pain.

• Muscle pain.

• Increase in liver enzymes.

These side effects will go away on their own. But if it becomes severe or more persistent, contact your doctor.

The more serious side effects include

• Drug Allergy: Symptoms include rashes, itching, hives, breathlessness, etc.

• Liver Damage: Symptoms such as yellowing of skin or white of the eyes, weakness, and severe abdominal pain are seen.

• Kidney Damage: Symptoms include easy bruising and decreased urine output.

If these symptoms arise, seek medical help immediately.

What Are the Interactions of Pyrazinamide?

Almost all medications interact with other drugs, beverages, food, or supplements. These interactions can result in certain unwanted side effects. The common interactions of Pyrazinamide are

• With Other Drugs:

  • Cyclosporine.

  • Ethionamide.

  • Rifampin.

  • Zidovudine.

• With Alcohol: Avoid consuming alcohol while taking Pyrazinamide as it may cause liver damage.

• With Food: Foods containing tyramine or histamine may interact with Pyrazinamide (such as red wine, cheese, and certain types of fish). Increased blood pressure, skin flushing, headaches, wooziness, or a rapid, hammering heartbeat could all be side effects of this combination. If you experience any of these symptoms, contact your doctor immediately. If you're taking this drug, your doctor might advise you to adhere to a specific diet.

For Doctors:

Indications:

Effective treatment of TB requires a multi-drug approach to prevent the development of drug-resistant strains of Mycobacterium tuberculosis. Pyrazinamide plays a crucial role in this combination therapy as it helps shorten the duration of treatment and reduces the risk of developing resistance to other TB drugs.

Tuberculosis (TB) is a global health concern caused by Mycobacterium tuberculosis. It majorly affects the lungs; however, it can also involve other parts of the body. The treatment of TB is a complex process that typically involves a combination of antibiotics to ensure the complete eradication of the bacteria. Pyrazinamide is one of the essential drugs used in the treatment of TB.

Mechanism of Action:

Pyrazinamide works uniquely compared to other TB drugs. While the exact mechanism of action is not completely understood, Pyrazinamide is thought to be converted into its active form, pyrazinoic acid, by the bacterium inside the host's macrophages. This acidic environment within the macrophage is essential for Pyrazinamide's activity.

Pyrazinoic acid disrupts the bacterium's cell membrane and energy production, which leads to a decrease in bacterial viability. It is particularly effective against dormant or semi-dormant bacteria, which are often not susceptible to other TB drugs. This makes Pyrazinamide an essential component of the treatment regimen, as it targets a different stage of the bacterium's life cycle.

Dosages and Administration:

The drug's dosing is based on the disease's age, weight, severity, and extent. It is often combined with other antitubercular drugs. The therapy may last for months. It is very important to stick to the regimen, and taking the medicines at the instructed frequency is very important. Follow-ups are required to assess the response to the drug. Inform the doctor if you experience any side effects and how well the drug works.

Pyrazinamide is available in 500 mg, 750 mg, 1000 mg, and 1500 mg oral tablets.

The general dosing information of Pyrazinamide tablets for Tuberculosis is as follows:

• Adult Dosing (18 - 64 years):

  • 40 to 55 kg: 1000 mg orally once daily for eight weeks (56 doses) or five days per week for eight weeks (40 doses), given in combination with Isoniazid, Rifampin, and Ethambutol.

  • 56 to 75 kg: 1500 mg orally once daily for eight weeks (56 doses) or five days per week for eight weeks (40 doses), given in combination with Isoniazid, Rifampin, and Ethambutol.

  • 76 to 90 kg: 2000 mg orally once daily for eight weeks (56 doses) or five days per week for eight weeks (40 doses); given in combination with Isoniazid, Rifampin, and Ethambutol.

  • Doses will be adjusted for the elderly and people with liver or kidney diseases.

• Child Dosing:

  • Younger Than 15 Years and 40 kg or Less: 30 to 40 mg/kg orally once daily for eight weeks (56 doses) or five days per week for eight weeks (40 doses), given in combination with Isoniazid, Rifampin, and Ethambutol.

  • 15 Years or Older or 40 to 55 kg: 1000 mg orally once daily for eight weeks (56 doses) or five days per week for eight weeks (40 doses), given in combination with Isoniazid, Rifampin, and Ethambutol.

  • 15 Years or Older or 56 to 75 kg: 1500 mg orally once daily for eight weeks (56 doses) or five days per week for eight weeks (40 doses), given in combination with Isoniazid, Rifampin, and Ethambutol.

  • 15 Years or Older or 76 to 90 kg: 2000 mg orally once daily for eight weeks (56 doses) or five days per week for eight weeks (40 doses), given in combination with Isoniazid, Rifampin, and Ethambutol.

Side Effects:

While Pyrazinamide is a crucial component of TB treatment, it is not without side effects. Some common side effects include:

• Gastrointestinal Issues: Pyrazinamide can cause gastrointestinal discomfort, including nausea, vomiting, and abdominal pain. Administering the medication with food can help alleviate these symptoms.

• Hepatotoxicity: Pyrazinamide has the potential to cause liver toxicity, leading to elevated liver enzyme levels. Monitoring of liver function regularly is essential during treatment to detect any abnormalities promptly.

• Hyperuricemia and Gout: Pyrazinamide can increase uric acid levels in the blood, which may lead to gouty arthritis in some individuals. Patients with a history of gout must be monitored closely.

• Hypersensitivity Reactions: While rare, some individuals may experience allergic reactions, such as rash, itching, or fever.

• Photosensitivity: Pyrazinamide may increase sensitivity to sunlight, so patients should take precautions when exposed to sunlight or ultraviolet (UV) light.

Patients must promptly communicate any side effects or adverse reactions to their healthcare provider. Sometimes, the healthcare provider may need to adjust the treatment regimen or switch to alternative medications.

Pyrazinamide and Drug Resistance:

One of the significant advantages of Pyrazinamide in TB treatment is its ability to target dormant or semi-dormant bacteria. This is particularly important because these dormant bacteria are often less susceptible to other TB drugs, making them a potential source of drug-resistant TB strains. However, the emergence of resistance to Pyrazinamide has been reported in some cases, highlighting the importance of proper treatment adherence and the need for ongoing research into TB drug resistance.

Combination Therapy and the Fight Against TB:

The treatment of tuberculosis includes a combination of drugs called Directly Observed Treatment, Short-Course (DOTS). This approach aims to ensure that patients receive the right combination of drugs, adhere to the treatment regimen, and complete the entire course of treatment. Pyrazinamide is typically used in combination with other first-line TB drugs, such as isoniazid, rifampicin, and ethambutol, during the initial phase of treatment. This combination therapy helps to achieve several essential goals in TB treatment:

• Bactericidal Activity: The combination of drugs targets different aspects of the bacterium's life cycle, increasing the overall bactericidal activity.

• Shortening Treatment Duration: Pyrazinamide, in particular, helps shorten the duration of the initial phase of TB treatment, which can improve patient adherence and reduce the risk of developing drug resistance.

• Preventing Resistance: Using multiple drugs simultaneously minimizes the risk of the bacterium developing resistance to any one drug.

• Reducing Relapse: Completing the full course of combination therapy reduces the risk of TB relapse after initial treatment.

• Preventing Transmission: Effective treatment reduces the number of viable bacteria, decreasing the risk of transmission to others.