Pyrazinamide 500mg Tablets
It is used to treat TB (tuberculosis). This drug is taken with other drugs. Be sure you know about the warnings, benefits, and risks of these other drugs. Talk with the doctor if you have questions or concerns about any of the drugs.
Drug Class
Antitubercular Agent
Pharmacologic Class
Pyrazine Carboxamide Derivative
Pregnancy Category
Category C
FDA Approved
Jan 1972
DEA Schedule
Not Controlled
Overview
What is this medicine?
Pyrazinamide is an antibiotic used to treat tuberculosis (TB). It works by killing the bacteria that cause TB, especially those that are harder to reach within the body. It is usually taken with other TB medications.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, take it exactly as directed by your doctor. Carefully read all the information provided with your prescription, and follow the instructions closely. Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it at room temperature in a dry location, avoiding bathrooms. Keep all medications in a secure place, out of the reach of children and pets. When disposing of unused or expired medications, do not flush them down the toilet or pour them down the drain unless specifically instructed to do so. Instead, consult with your pharmacist for guidance on the proper disposal method. You may also want to inquire about drug take-back programs available in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Avoid taking two doses at the same time or taking extra doses, as this can increase the risk of adverse effects.
To get the most benefit from your medication, take it exactly as directed by your doctor. Carefully read all the information provided with your prescription, and follow the instructions closely. Continue taking your medication as prescribed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
To maintain the quality and safety of your medication, store it at room temperature in a dry location, avoiding bathrooms. Keep all medications in a secure place, out of the reach of children and pets. When disposing of unused or expired medications, do not flush them down the toilet or pour them down the drain unless specifically instructed to do so. Instead, consult with your pharmacist for guidance on the proper disposal method. You may also want to inquire about drug take-back programs available in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it's close to the time for your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Avoid taking two doses at the same time or taking extra doses, as this can increase the risk of adverse effects.
Lifestyle & Tips
- Avoid alcohol consumption during treatment due to increased risk of liver damage.
- Report any new or worsening symptoms to your doctor immediately.
- Take the medication exactly as prescribed, do not skip doses, and complete the full course of treatment, even if you feel better.
Available Forms & Alternatives
Available Strengths:
Dosing & Administration
Adult Dosing
Standard Dose:
15-30 mg/kg orally once daily (max 2 g/day) or 50-70 mg/kg orally 2-3 times weekly (max 4 g/dose)
Dose Range:
1000 - 2000 mg
Condition-Specific Dosing:
Tuberculosis (initial phase):
15-30 mg/kg orally once daily (max 2 g/day) for 2 months, or 50-70 mg/kg orally 2-3 times weekly (max 4 g/dose) for 2 months.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
15-30 mg/kg orally once daily (max 2 g/day) or 50-70 mg/kg orally 2-3 times weekly (max 4 g/dose)
Adolescent:
15-30 mg/kg orally once daily (max 2 g/day) or 50-70 mg/kg orally 2-3 times weekly (max 4 g/dose)
Dose Adjustments
Renal Impairment:
Mild:
No adjustment needed
Moderate:
No adjustment needed
Severe:
Reduce dose to 12-20 mg/kg 3 times weekly or 25-35 mg/kg 2 times weekly. Max 2 g/dose.
Dialysis:
Administer after dialysis. Reduce dose to 12-20 mg/kg 3 times weekly or 25-35 mg/kg 2 times weekly. Max 2 g/dose.
Hepatic Impairment:
Mild:
Use with caution, monitor LFTs closely.
Moderate:
Contraindicated or use with extreme caution; significant risk of hepatotoxicity.
Severe:
Contraindicated
Pharmacology
Mechanism of Action
Pyrazinamide is a prodrug that is converted to pyrazinoic acid (POA) by mycobacterial pyrazinamidase. POA is thought to disrupt mycobacterial membrane potential and transport functions, inhibit fatty acid synthase I (FAS I), and lower intracellular pH, leading to bactericidal activity against Mycobacterium tuberculosis, particularly against organisms residing within acidic phagolysosomes.
Pharmacokinetics
Absorption:
Bioavailability:
90-95%
Tmax:
2 hours
FoodEffect:
Food may delay absorption but does not significantly affect bioavailability.
Distribution:
Vd:
0.57-0.74 L/kg
ProteinBinding:
10-20%
CnssPenetration:
Yes
Elimination:
HalfLife:
9-10 hours (normal renal function)
Clearance:
Not available
ExcretionRoute:
Renal (primarily as metabolites, some unchanged drug)
Unchanged:
3-4%
Pharmacodynamics
OnsetOfAction:
Not precisely defined for clinical effect, but bactericidal activity begins rapidly after conversion to POA.
PeakEffect:
Not precisely defined for clinical effect.
DurationOfAction:
Not precisely defined for clinical effect, but allows for once-daily or intermittent dosing due to post-antibiotic effect.
Safety & Warnings
Side Effects
Serious Side Effects: Seek Medical Attention Immediately
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems, including:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Joint pain or swelling
Fever
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other unusual symptoms that bother you or do not go away, contact your doctor:
Muscle pain
Upset stomach or vomiting
* Decreased appetite
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects not mentioned here. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of liver problems, including:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes
Joint pain or swelling
Fever
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other unusual symptoms that bother you or do not go away, contact your doctor:
Muscle pain
Upset stomach or vomiting
* Decreased appetite
Reporting Side Effects
This list is not exhaustive, and you may experience other side effects not mentioned here. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Unusual tiredness or weakness
- Loss of appetite
- Nausea or vomiting
- Dark urine
- Yellowing of the skin or eyes (jaundice)
- Pain in the upper right side of the abdomen
- Joint pain or swelling, especially in the big toe, ankle, or knee (symptoms of gout)
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Gout
+ Liver problems
This list is not exhaustive, and it is crucial to discuss all your health problems and medications with your doctor.
To ensure your safety, provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter (OTC) medications you are taking
Natural products
Vitamins
Health problems
Carefully review your medications and health conditions with your doctor to confirm it is safe to take this medication. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the symptoms you experienced.
Certain health conditions, including:
+ Gout
+ Liver problems
This list is not exhaustive, and it is crucial to discuss all your health problems and medications with your doctor.
To ensure your safety, provide your doctor and pharmacist with a comprehensive list of:
All prescription and over-the-counter (OTC) medications you are taking
Natural products
Vitamins
Health problems
Carefully review your medications and health conditions with your doctor to confirm it is safe to take this medication. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regularly undergo blood work and other laboratory tests as instructed by your doctor to ensure close monitoring of your condition. If you have diabetes (high blood sugar), be aware that certain urine ketone tests may produce inaccurate results; consult your doctor for guidance. Be vigilant for signs of gout attacks, and discuss your alcohol consumption with your doctor before drinking. If you are pregnant, planning to become pregnant, or are breastfeeding, notify your doctor to discuss the potential benefits and risks of this medication to both you and your baby.
Overdose Information
Overdose Symptoms:
- Liver damage (hepatotoxicity)
- Hyperuricemia
- Gouty arthritis
- Gastrointestinal upset (nausea, vomiting, abdominal pain)
What to Do:
Call 1-800-222-1222 (Poison Control). Treatment is supportive and symptomatic. Gastric lavage may be considered if ingestion is recent. Monitor liver function and uric acid levels closely.
Drug Interactions
Contraindicated Interactions
- Drugs that cause severe hepatotoxicity (e.g., high-dose acetaminophen, certain antifungals) in patients with pre-existing liver disease.
Major Interactions
- Other hepatotoxic drugs (e.g., rifampin, isoniazid, ethionamide, alcohol): Increased risk of hepatotoxicity.
- Allopurinol, Probenecid: Pyrazinamide can increase uric acid levels, potentially antagonizing the effects of these uricosuric agents.
Moderate Interactions
- Cyclosporine: Pyrazinamide may decrease cyclosporine levels.
- Phenytoin: Pyrazinamide may increase phenytoin levels.
Minor Interactions
- Not available
Monitoring
Baseline Monitoring
Liver Function Tests (ALT, AST, bilirubin)
Rationale: To establish baseline liver function due to risk of hepatotoxicity.
Timing: Before starting therapy
Serum Uric Acid
Rationale: To establish baseline due to risk of hyperuricemia and gout.
Timing: Before starting therapy
Renal Function (BUN, Creatinine)
Rationale: To assess renal clearance and guide dosing in renal impairment.
Timing: Before starting therapy
Routine Monitoring
Liver Function Tests (ALT, AST, bilirubin)
Frequency: Monthly or more frequently if clinically indicated (e.g., symptoms of liver injury)
Target: Within normal limits or stable baseline
Action Threshold: Discontinue if ALT/AST >3-5x ULN with symptoms, or >5x ULN without symptoms. Re-evaluate if >3x ULN.
Serum Uric Acid
Frequency: Periodically, especially if symptoms of gout develop
Target: Within normal limits or acceptable for patient
Action Threshold: Consider allopurinol or NSAIDs if symptomatic hyperuricemia/gout develops.
Clinical symptoms (e.g., nausea, vomiting, abdominal pain, fatigue, dark urine, jaundice, arthralgia)
Frequency: Ongoing
Target: Absence of symptoms
Action Threshold: Investigate immediately if symptoms of hepatotoxicity or severe arthralgia occur.
Symptom Monitoring
- Nausea
- Vomiting
- Anorexia
- Abdominal pain
- Fatigue
- Malaise
- Dark urine
- Yellowing of skin or eyes (jaundice)
- Arthralgia (joint pain)
- Gouty arthritis symptoms (sudden, severe joint pain, swelling, redness, tenderness)
Special Patient Groups
Pregnancy
Pyrazinamide is generally considered acceptable for use in pregnancy for the treatment of tuberculosis, especially in multi-drug regimens, as the benefits of treating active TB outweigh potential risks. However, it is classified as Category C.
Trimester-Specific Risks:
First Trimester:
Limited data, but generally considered acceptable when needed for effective TB treatment.
Second Trimester:
Generally considered acceptable.
Third Trimester:
Generally considered acceptable.
Lactation
Pyrazinamide is excreted into breast milk. While the amount is small, monitoring the infant for adverse effects (e.g., jaundice, poor feeding) is recommended. Generally considered compatible with breastfeeding when the mother is receiving appropriate TB treatment.
Infant Risk:
Low; potential for mild gastrointestinal upset or liver enzyme elevation, but serious adverse effects are rare. Monitor infant for jaundice or other signs of toxicity.
Pediatric Use
Pyrazinamide is an essential component of first-line TB treatment in children. Dosing is weight-based. Close monitoring for hepatotoxicity is crucial, as in adults.
Geriatric Use
Use with caution in elderly patients due to potential for decreased renal function and increased susceptibility to adverse effects, particularly hepatotoxicity and hyperuricemia. Monitor liver and renal function closely.
Clinical Information
Clinical Pearls
- Pyrazinamide is a critical component of the initial intensive phase of tuberculosis treatment due to its unique activity against semi-dormant bacilli within acidic environments (e.g., macrophages, caseous lesions).
- Hepatotoxicity is the most significant adverse effect; regular monitoring of liver function tests is essential.
- Hyperuricemia is common and can lead to gouty arthritis; monitor uric acid levels and manage symptoms if they occur.
- Administer with food to minimize gastrointestinal upset.
- Ensure patient adherence to the full treatment regimen to prevent drug resistance and treatment failure.
Alternative Therapies
- Other antitubercular drugs (e.g., streptomycin, ethionamide, cycloserine, para-aminosalicylic acid, fluoroquinolones, bedaquiline, delamanid) used in specific situations like drug-resistant TB or intolerance to first-line agents.
Cost & Coverage
Average Cost:
Not available per 30 tablets
Generic Available:
Yes
Insurance Coverage:
Tier 1 or 2 (Generic)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide detailed information about the overdose, including the medication taken, the amount, and the time it occurred.