Isoniazid 300mg Tablets
WARNING: Severe and sometimes deadly liver problems have happened with this drug. Call your doctor right away if you have signs of liver problems like dark urine, tiredness, decreased appetite, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.The chance of liver problems is higher the older you are. The chance may also be raised by drinking alcohol every day, long-term liver problems, or injection drug use. The chance of liver problems may also be raised in females, mainly females who are Black or Hispanic or who have just had a baby. Most of the time, liver problems caused by this drug happen within the first 3 months of care, but they can happen at any time. Most of the time, liver function has gone back to normal but sometimes it has not. Blood work will need to be done before starting this drug and while taking it. If you have questions, talk with the doctor.If you have liver disease, talk with your doctor. This drug may not be right for you. @ COMMON USES: It is used to treat TB (tuberculosis). It is used to prevent TB (tuberculosis).
Drug Class
Antimycobacterial; Anti-tuberculosis agent
Pharmacologic Class
Mycolic acid synthesis inhibitor
Pregnancy Category
C
FDA Approved
Aug 1952
DEA Schedule
Not Controlled
Overview
What is this medicine?
Isoniazid is an antibiotic used to treat and prevent tuberculosis (TB). It works by stopping the growth of the bacteria that cause TB. It's often used in combination with other medicines for active TB, or by itself to prevent TB in people who have been exposed.
How to Use This Medicine
Taking Your Medication Correctly
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. Take your medication on an empty stomach, either 1 hour before or 2 hours after meals. Continue taking your medication as directed by your doctor or healthcare provider, even if you start to feel well.
Storing and Disposing of Your Medication
Store your medication at room temperature, protected from light and moisture. Keep it in a dry place, away from the bathroom. Make sure to keep all medications in a safe location, out of the reach of children and pets. When disposing of unused or expired medication, do not flush it down the toilet or pour it down the drain unless instructed to do so. Instead, check with your pharmacist for guidance on the best way to dispose of your medication. You may also want to explore drug take-back programs 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. Do not take two doses at the same time or take extra doses to make up for a missed one.
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. Take your medication on an empty stomach, either 1 hour before or 2 hours after meals. Continue taking your medication as directed by your doctor or healthcare provider, even if you start to feel well.
Storing and Disposing of Your Medication
Store your medication at room temperature, protected from light and moisture. Keep it in a dry place, away from the bathroom. Make sure to keep all medications in a safe location, out of the reach of children and pets. When disposing of unused or expired medication, do not flush it down the toilet or pour it down the drain unless instructed to do so. Instead, check with your pharmacist for guidance on the best way to dispose of your medication. You may also want to explore drug take-back programs 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. Do not take two doses at the same time or take extra doses to make up for a missed one.
Lifestyle & Tips
- Take on an empty stomach (1 hour before or 2 hours after meals) for best absorption.
- Avoid or limit alcohol consumption, as it significantly increases the risk of liver damage.
- Take vitamin B6 (pyridoxine) as prescribed by your doctor to prevent nerve damage (peripheral neuropathy), especially if you have diabetes, kidney disease, HIV, or are malnourished or pregnant.
- Complete the full course of medication as prescribed, even if you feel better, to prevent drug resistance and ensure effective treatment.
- Do not share this medication with others.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Active TB: 5 mg/kg orally once daily (max 300 mg/day) or 15 mg/kg (max 900 mg) 2-3 times weekly. Latent TB: 300 mg orally once daily for 6-9 months.
Dose Range:
5 - 15 mg
Condition-Specific Dosing:
Active Tuberculosis:
5 mg/kg (max 300 mg) daily OR 15 mg/kg (max 900 mg) 2-3 times weekly.
Latent Tuberculosis Infection:
300 mg daily for 6-9 months OR 900 mg twice weekly for 9 months (often with rifapentine).
Pediatric Dosing
Neonatal:
Not established (use with caution, consult specialist)
Infant:
Active TB: 10-15 mg/kg orally once daily (max 300 mg/day). Latent TB: 10-15 mg/kg orally once daily (max 300 mg/day) for 6-9 months.
Child:
Active TB: 10-15 mg/kg orally once daily (max 300 mg/day) or 20-40 mg/kg (max 900 mg) 2-3 times weekly. Latent TB: 10-15 mg/kg orally once daily (max 300 mg/day) for 6-9 months.
Adolescent:
Active TB: 10-15 mg/kg orally once daily (max 300 mg/day) or 20-40 mg/kg (max 900 mg) 2-3 times weekly. Latent TB: 10-15 mg/kg orally once daily (max 300 mg/day) for 6-9 months.
Dose Adjustments
Renal Impairment:
Mild:
No adjustment typically needed.
Moderate:
No adjustment typically needed.
Severe:
Reduce dose to 2-3 mg/kg daily or 300 mg 3 times weekly if CrCl < 10 mL/min.
Dialysis:
Administer dose after hemodialysis. Supplemental dose not typically needed after peritoneal dialysis.
Hepatic Impairment:
Mild:
Use with caution; monitor LFTs closely.
Moderate:
Use with caution; monitor LFTs closely. Consider dose reduction or alternative if severe impairment.
Severe:
Contraindicated in acute liver disease or history of isoniazid-associated liver injury. Use with extreme caution in chronic liver disease; benefits must outweigh risks.
Pharmacology
Mechanism of Action
Isoniazid is a prodrug that is activated by the mycobacterial catalase-peroxidase enzyme KatG. The activated form (isonicotinoyl radical) inhibits the synthesis of mycolic acids, which are essential components of the mycobacterial cell wall. Specifically, it targets InhA (enoyl-ACP reductase) and KasA (beta-ketoacyl-ACP synthase), leading to cell wall disruption and bactericidal activity against actively growing Mycobacterium tuberculosis.
Pharmacokinetics
Absorption:
Bioavailability:
90-100%
Tmax:
1-2 hours
FoodEffect:
Food (especially high-fat meals) can decrease the rate and extent of absorption. Should be taken on an empty stomach.
Distribution:
Vd:
0.6-0.8 L/kg
ProteinBinding:
<10%
CnssPenetration:
Yes (readily penetrates CSF, pleural fluid, ascitic fluid, and caseous lesions)
Elimination:
HalfLife:
1-4 hours (fast acetylators); 2-5 hours (slow acetylators)
Clearance:
Varies significantly based on NAT2 phenotype
ExcretionRoute:
Renal (primarily as metabolites)
Unchanged:
10-30% (higher in slow acetylators)
Pharmacodynamics
OnsetOfAction:
Rapid (bactericidal effect begins within hours of exposure)
PeakEffect:
Peak plasma concentrations reached within 1-2 hours, leading to maximal bactericidal activity shortly thereafter.
DurationOfAction:
Plasma half-life dictates dosing frequency (daily or intermittent).
Safety & Warnings
BLACK BOX WARNING
Severe and sometimes fatal hepatitis may occur, usually within the first 3 months of treatment. The risk of hepatitis is age-related and is increased with daily alcohol consumption. Patients should be monitored for symptoms of hepatitis and liver function tests should be performed at baseline and periodically during treatment, especially in patients at higher risk.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
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
+ Difficulty breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of high blood sugar, including:
+ Confusion
+ Drowsiness
+ Increased thirst or hunger
+ Frequent urination
+ Flushing
+ Rapid breathing
+ Fruity-smelling breath
Signs of lupus, such as:
+ Rash on the cheeks or other body parts
+ Easy sunburn
+ Muscle or joint pain
+ Chest pain or shortness of breath
+ Swelling in the arms or legs
Signs of pancreatitis (pancreas problems), including:
+ Severe stomach pain
+ Severe back pain
+ Severe nausea or vomiting
Signs of acidosis (too much acid in the blood), such as:
+ Confusion
+ Rapid breathing
+ Rapid heartbeat
+ Abnormal heartbeat
+ Severe stomach pain
+ Nausea or vomiting
+ Drowsiness
+ Shortness of breath
+ Feeling extremely tired or weak
Abnormal sensations, such as burning, numbness, or tingling
Seizures
Confusion or memory problems
Changes in vision
Mood changes
Fever, chills, or sore throat
Unexplained bruising or bleeding
Feeling extremely tired or weak
Joint pain or swelling
Enlarged breasts
Severe skin reactions, including:
+ Toxic epidermal necrolysis (TEN)
+ Other serious skin reactions
+ Signs may include:
- Red, swollen, blistered, or peeling skin
- Red or irritated eyes
- Sores in the mouth, throat, nose, eyes, genitals, or skin
- Fever
- Chills
- Body aches
- Shortness of breath
- Swollen glands
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you notice any of the following side effects or any other unusual symptoms, contact your doctor or seek medical attention:
Nausea or vomiting
Other side effects not listed here
If you have questions or concerns about side effects, contact 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, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek immediate medical attention:
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
+ Difficulty breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of high blood sugar, including:
+ Confusion
+ Drowsiness
+ Increased thirst or hunger
+ Frequent urination
+ Flushing
+ Rapid breathing
+ Fruity-smelling breath
Signs of lupus, such as:
+ Rash on the cheeks or other body parts
+ Easy sunburn
+ Muscle or joint pain
+ Chest pain or shortness of breath
+ Swelling in the arms or legs
Signs of pancreatitis (pancreas problems), including:
+ Severe stomach pain
+ Severe back pain
+ Severe nausea or vomiting
Signs of acidosis (too much acid in the blood), such as:
+ Confusion
+ Rapid breathing
+ Rapid heartbeat
+ Abnormal heartbeat
+ Severe stomach pain
+ Nausea or vomiting
+ Drowsiness
+ Shortness of breath
+ Feeling extremely tired or weak
Abnormal sensations, such as burning, numbness, or tingling
Seizures
Confusion or memory problems
Changes in vision
Mood changes
Fever, chills, or sore throat
Unexplained bruising or bleeding
Feeling extremely tired or weak
Joint pain or swelling
Enlarged breasts
Severe skin reactions, including:
+ Toxic epidermal necrolysis (TEN)
+ Other serious skin reactions
+ Signs may include:
- Red, swollen, blistered, or peeling skin
- Red or irritated eyes
- Sores in the mouth, throat, nose, eyes, genitals, or skin
- Fever
- Chills
- Body aches
- Shortness of breath
- Swollen glands
Other Possible Side Effects
Like all medications, this drug can cause side effects. Many people experience no side effects or only mild ones. If you notice any of the following side effects or any other unusual symptoms, contact your doctor or seek medical attention:
Nausea or vomiting
Other side effects not listed here
If you have questions or concerns about side effects, contact 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 stomach
- Numbness, tingling, burning, or pain in the hands or feet
- Blurred vision or changes in vision
- Unexplained fever or rash
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 allergic reaction and its symptoms.
If you have experienced severe side effects from taking isoniazid in the past, including liver problems, drug fever, chills, or arthritis.
* If you have a history of liver problems caused by other medications.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your existing treatments and health conditions. Never start, stop, or adjust the dosage of any medication without consulting your doctor first.
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 allergic reaction and its symptoms.
If you have experienced severe side effects from taking isoniazid in the past, including liver problems, drug fever, chills, or arthritis.
* If you have a history of liver problems caused by other medications.
This list is not exhaustive, and it is crucial to discuss all your medications (prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe to take this medication with your existing treatments and health conditions. Never start, stop, or adjust the dosage of any medication without consulting your doctor first.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Before consuming alcohol, discuss the potential risks with your doctor. As directed by your doctor, take vitamin B6 (pyridoxine) to minimize potential side effects. If you have diabetes, it is crucial to closely monitor your blood sugar levels. Adhere to your doctor's recommendations for regular blood tests and eye exams to ensure your overall health.
Be aware that certain foods and beverages, such as cheese and red wine, can cause a sudden and severe increase in blood pressure, which can be life-threatening. Consult your doctor to understand your risk for this reaction and obtain a list of foods and drinks to avoid. It is vital to abstain from these foods and drinks for the duration specified by your doctor, even after you have stopped taking this medication.
If you are pregnant, planning to become pregnant, or are breastfeeding, inform your doctor immediately. You and your doctor will need to discuss the potential benefits and risks of this medication to both you and your baby to make an informed decision.
Be aware that certain foods and beverages, such as cheese and red wine, can cause a sudden and severe increase in blood pressure, which can be life-threatening. Consult your doctor to understand your risk for this reaction and obtain a list of foods and drinks to avoid. It is vital to abstain from these foods and drinks for the duration specified by your doctor, even after you have stopped taking this medication.
If you are pregnant, planning to become pregnant, or are breastfeeding, inform your doctor immediately. You and your doctor will need to discuss the potential benefits and risks of this medication to both you and your baby to make an informed decision.
Overdose Information
Overdose Symptoms:
- Nausea
- Vomiting
- Dizziness
- Slurred speech
- Blurred vision
- Visual hallucinations
- Hyperreflexia
- Peripheral neuropathy
- Metabolic acidosis (high anion gap)
- Hyperglycemia
- Ketonuria
- Seizures (often refractory to standard anticonvulsants)
- Coma
What to Do:
Seek immediate medical attention. Call 911 or Poison Control (1-800-222-1222). Treatment involves supportive care, gastric lavage, activated charcoal, and importantly, intravenous pyridoxine (Vitamin B6) in doses equal to or greater than the ingested isoniazid dose to counteract neurotoxicity and seizures.
Drug Interactions
Contraindicated Interactions
- Disulfiram (risk of psychotic episodes and ataxia)
Major Interactions
- Alcohol (increased risk of hepatotoxicity)
- Carbamazepine (increased carbamazepine levels, increased risk of hepatotoxicity)
- Phenytoin (increased phenytoin levels, increased risk of toxicity)
- Valproic acid (increased valproate levels, increased risk of hepatotoxicity)
- Acetaminophen (increased risk of hepatotoxicity with chronic use)
- Warfarin (increased anticoagulant effect)
Moderate Interactions
- Antacids (decreased isoniazid absorption; separate administration by at least 1 hour)
- Corticosteroids (may decrease isoniazid levels)
- Ketoconazole (decreased ketoconazole levels)
- Theophylline (increased theophylline levels)
- Cycloserine (increased CNS toxicity)
- Benzodiazepines (e.g., Diazepam, Triazolam - increased levels due to CYP inhibition)
- Levodopa (decreased levodopa effect)
Minor Interactions
- Food (decreased absorption)
Monitoring
Baseline Monitoring
Liver Function Tests (AST, ALT, Bilirubin)
Rationale: To establish baseline liver function and identify pre-existing liver disease, as isoniazid can cause severe hepatotoxicity.
Timing: Prior to initiation of therapy.
Complete Blood Count (CBC)
Rationale: To assess for baseline hematologic abnormalities, though less common, isoniazid can cause blood dyscrasias.
Timing: Prior to initiation of therapy.
Renal Function (BUN, Creatinine)
Rationale: To assess baseline renal function, as dose adjustments may be needed in severe renal impairment.
Timing: Prior to initiation of therapy.
Neurological Assessment
Rationale: To identify pre-existing neuropathy or risk factors (e.g., diabetes, alcoholism, malnutrition) for peripheral neuropathy.
Timing: Prior to initiation of therapy.
Ophthalmic Exam
Rationale: To establish baseline vision, especially if patient reports visual symptoms or has pre-existing ocular conditions, as optic neuritis is a rare side effect.
Timing: Prior to initiation of therapy (if indicated).
Routine Monitoring
Liver Function Tests (AST, ALT)
Frequency: Monthly, or more frequently if risk factors for hepatotoxicity (e.g., age >35, daily alcohol use, pre-existing liver disease, concomitant hepatotoxic drugs) or if symptoms develop.
Target: Within normal limits or stable baseline.
Action Threshold: Discontinue isoniazid if AST/ALT >3-5 times upper limit of normal (ULN) with symptoms, or >5 times ULN without symptoms. Re-evaluate if 3x ULN with symptoms.
Symptoms of Hepatotoxicity
Frequency: Daily patient self-monitoring and at each clinical visit.
Target: Absence of symptoms.
Action Threshold: Prompt evaluation if fatigue, weakness, malaise, anorexia, nausea, vomiting, dark urine, yellow skin/eyes, or abdominal pain occur.
Symptoms of Peripheral Neuropathy
Frequency: At each clinical visit.
Target: Absence of symptoms.
Action Threshold: Prompt evaluation if numbness, tingling, burning, or pain in hands/feet occur. Consider pyridoxine dose adjustment or isoniazid discontinuation.
Symptom Monitoring
- Fatigue
- Weakness
- Malaise
- Anorexia
- Nausea
- Vomiting
- Dark urine
- Yellow skin or eyes (jaundice)
- Abdominal pain (especially right upper quadrant)
- Numbness or tingling in hands or feet (paresthesias)
- Burning pain in hands or feet
- Muscle weakness
- Blurred vision or vision changes
- Fever
- Rash
Special Patient Groups
Pregnancy
Isoniazid is generally considered acceptable for use during pregnancy for the treatment of active tuberculosis due to the high risk of untreated TB to both mother and fetus. For latent TB, treatment is often delayed until after delivery, but may be considered in high-risk situations. Pyridoxine supplementation (25-50 mg/day) is strongly recommended to prevent maternal and fetal peripheral neuropathy.
Trimester-Specific Risks:
First Trimester:
Risk of congenital malformations is not significantly increased. Pyridoxine supplementation is important.
Second Trimester:
Generally considered safe for continued use. Pyridoxine supplementation continues.
Third Trimester:
Generally considered safe for continued use. Pyridoxine supplementation continues.
Lactation
Isoniazid is excreted into breast milk. It is generally considered compatible with breastfeeding by most expert guidelines (e.g., CDC, WHO, AAP) when used at therapeutic doses. Monitor breastfed infants for signs of adverse effects, particularly jaundice or unusual drowsiness. Pyridoxine supplementation for the infant (10-25 mg/day) may be considered, especially if the mother is a slow acetylator or if the infant is exclusively breastfed.
Infant Risk:
Low risk of adverse effects in breastfed infants. Potential for mild gastrointestinal upset or, rarely, hepatotoxicity. Pyridoxine supplementation can mitigate potential neurotoxicity.
Pediatric Use
Dosing is weight-based. Children, especially adolescents, may be at increased risk for hepatotoxicity, similar to adults. Pyridoxine supplementation is recommended, particularly in infants and children with risk factors for neuropathy (e.g., poor nutrition). Close monitoring for adverse effects is crucial.
Geriatric Use
Increased risk of hepatotoxicity and peripheral neuropathy due to age-related decline in liver function, polypharmacy, and comorbidities. Close monitoring of liver function and neurological symptoms is essential. Pyridoxine supplementation is highly recommended. Consider lower doses or extended intervals in severe renal impairment.
Clinical Information
Clinical Pearls
- Always co-administer with pyridoxine (Vitamin B6) 25-50 mg daily to prevent peripheral neuropathy, especially in patients with risk factors (e.g., diabetes, alcoholism, malnutrition, HIV, renal failure, pregnancy).
- Counsel patients extensively on the signs and symptoms of hepatotoxicity and the importance of avoiding alcohol during treatment.
- Take isoniazid on an empty stomach for optimal absorption.
- Monitor liver function tests (AST, ALT) at baseline and monthly, or more frequently if symptoms develop or risk factors are present.
- Be aware of drug-drug interactions, particularly with phenytoin, carbamazepine, and warfarin, due to isoniazid's CYP inhibition.
- Genetic polymorphism in NAT2 (N-acetyltransferase 2) affects isoniazid metabolism, leading to 'fast' and 'slow' acetylators, which impacts half-life and risk of toxicity. While not routinely tested, clinical response and adverse effects may provide clues.
Alternative Therapies
- Rifampin (for latent TB, or as part of multi-drug regimens for active TB)
- Rifapentine (for latent TB)
- Pyrazinamide (for active TB)
- Ethambutol (for active TB)
- Streptomycin (for active TB, less common now)
- Newer agents for drug-resistant TB (e.g., Bedaquiline, Delamanid, Pretomanid)
Cost & Coverage
Average Cost:
$10 - $50 per 30 tablets (300mg)
Generic Available:
Yes
Insurance Coverage:
Tier 1 (Generic)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, 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 for more information. 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 reporting the overdose, be prepared to provide details about the medication taken, the amount, and the time it occurred.