Isoniazid 50mg/5ml Syrup
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
Antitubercular agent
Pharmacologic Class
Mycolic acid synthesis inhibitor
Pregnancy Category
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), a serious bacterial infection that mainly affects the lungs. It works by stopping the growth of the bacteria that cause TB.
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 medication 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.
When taking a liquid dose, measure it carefully using the measuring device that comes with the medication. If no device is provided, ask your pharmacist for a suitable measuring device to ensure accurate dosing.
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. Store all medications in a safe location, out of the reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so by your pharmacist. Check with your pharmacist for guidance on the best way to dispose of medications, and consider participating in local drug take-back programs.
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 dose.
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your medication 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.
When taking a liquid dose, measure it carefully using the measuring device that comes with the medication. If no device is provided, ask your pharmacist for a suitable measuring device to ensure accurate dosing.
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. Store all medications in a safe location, out of the reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so by your pharmacist. Check with your pharmacist for guidance on the best way to dispose of medications, and consider participating in local drug take-back programs.
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 dose.
Lifestyle & Tips
- Take isoniazid on an empty stomach (1 hour before or 2 hours after meals) for best absorption.
- Take pyridoxine (Vitamin B6) daily as prescribed by your doctor to prevent nerve damage (peripheral neuropathy).
- Avoid or limit alcohol consumption during treatment, as it can increase the risk of liver damage.
- Avoid foods high in tyramine (e.g., aged cheese, red wine, tuna, certain processed meats) and histamine (e.g., skipjack, tuna, other tropical fish) as they may cause adverse reactions like headache, flushing, or palpitations.
- Complete the full course of treatment, even if you feel better, to prevent the infection from returning and to reduce the risk of drug resistance.
- Inform your doctor about all other medications, supplements, and herbal products you are taking.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
5 mg/kg orally once daily (max 300 mg/day) or 15 mg/kg (max 900 mg) orally twice weekly or thrice weekly (DOT)
Dose Range:
5 - 15 mg
Condition-Specific Dosing:
Latent Tuberculosis Infection (LTBI):
300 mg orally once daily for 6 or 9 months, or 900 mg orally twice weekly for 9 months (with DOT)
Active Tuberculosis (TB):
5 mg/kg (max 300 mg) orally once daily, or 15 mg/kg (max 900 mg) orally twice or thrice weekly (with DOT), as part of a multi-drug regimen.
Pediatric Dosing
Neonatal:
Not established for routine use; consult specialist. Generally 10-15 mg/kg/day.
Infant:
10-15 mg/kg orally once daily (max 300 mg/day) or 20-40 mg/kg (max 900 mg) twice weekly (DOT)
Child:
10-15 mg/kg orally once daily (max 300 mg/day) or 20-40 mg/kg (max 900 mg) twice weekly (DOT)
Adolescent:
10-15 mg/kg orally once daily (max 300 mg/day) or 20-40 mg/kg (max 900 mg) twice weekly (DOT)
Dose Adjustments
Renal Impairment:
Mild:
No adjustment needed
Moderate:
No adjustment needed
Severe:
CrCl < 10 mL/min: Reduce dose to 2-3 mg/kg/day or administer 3 times weekly.
Dialysis:
Administer after dialysis on dialysis days. For intermittent hemodialysis, 300 mg 3 times weekly. For peritoneal dialysis, 300 mg 3 times weekly.
Hepatic Impairment:
Mild:
Use with caution; monitor liver function closely.
Moderate:
Use with caution; monitor liver function closely. Consider dose reduction or alternative if severe impairment.
Severe:
Contraindicated in acute liver disease or history of isoniazid-associated liver injury. If used, significant dose reduction and close monitoring required; generally avoided.
Pharmacology
Mechanism of Action
Isoniazid is a prodrug that is activated by the mycobacterial catalase-peroxidase enzyme (KatG) to form several reactive species. These reactive species inhibit the synthesis of mycolic acids, which are essential components of the mycobacterial cell wall. Specifically, it inhibits enoyl-ACP reductase (InhA) and beta-ketoacyl-ACP synthase (KasA), enzymes involved in fatty acid elongation, thereby disrupting cell wall integrity.
Pharmacokinetics
Absorption:
Bioavailability:
90-100%
Tmax:
1-2 hours
FoodEffect:
Food (especially high-fat meals) may decrease the rate and extent of absorption. Administer on an empty stomach (1 hour before or 2 hours after meals).
Distribution:
Vd:
0.57-0.76 L/kg
ProteinBinding:
<10%
CnssPenetration:
Yes (achieves therapeutic concentrations in CSF)
Elimination:
HalfLife:
0.5-1.6 hours (fast acetylators); 2-5 hours (slow acetylators)
Clearance:
Not available (highly variable due to acetylation polymorphism)
ExcretionRoute:
Renal (primarily as metabolites)
Unchanged:
5-12% (fast acetylators); 10-30% (slow acetylators)
Pharmacodynamics
OnsetOfAction:
Bactericidal effect begins within hours of first dose.
PeakEffect:
Peak plasma concentrations reached within 1-2 hours.
DurationOfAction:
Sustained effect due to intracellular accumulation and slow elimination from mycobacteria.
Safety & Warnings
BLACK BOX WARNING
Severe and sometimes fatal hepatitis associated with isoniazid therapy may occur and may develop even after many months of treatment. The risk of developing hepatitis is age related and increases with concurrent use of other hepatotoxic drugs (e.g., rifampin). Patients should be monitored for symptoms of hepatitis, and liver enzymes should be measured at baseline and periodically during treatment. Discontinue isoniazid if signs or symptoms of hepatic damage develop.
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 medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or tightness in the chest or throat
+ Difficulty breathing, swallowing, or talking
+ Unusual hoarseness or swelling of the mouth, face, lips, tongue, or throat
Signs of high blood sugar, including:
+ Confusion or feeling sleepy
+ Unusual thirst or hunger
+ Frequent urination
+ Flushing or fast breathing
+ Breath that smells like fruit
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 problem), including:
+ Severe stomach pain
+ Severe back pain
+ Severe upset stomach or vomiting
Signs of acidosis (too much acid in the blood), such as:
+ Confusion
+ Fast breathing
+ Fast heartbeat or irregular heartbeat
+ Severe stomach pain, upset stomach, or vomiting
+ Feeling extremely sleepy
+ Shortness of breath
+ Feeling very tired or weak
Abnormal sensations, such as burning, numbness, or tingling
Seizures
Confusion or memory problems
Changes in eyesight
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)
+ 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. 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 symptoms that bother you or do not go away, contact your doctor:
Upset stomach or vomiting
Reporting Side Effects
If you have questions about side effects or want to report any, you can:
Call your doctor for medical advice
Contact the FDA at 1-800-332-1088
Report side effects 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 medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash or hives
+ Itching or red, swollen, blistered, or peeling skin (with or without fever)
+ Wheezing or tightness in the chest or throat
+ Difficulty breathing, swallowing, or talking
+ Unusual hoarseness or swelling of the mouth, face, lips, tongue, or throat
Signs of high blood sugar, including:
+ Confusion or feeling sleepy
+ Unusual thirst or hunger
+ Frequent urination
+ Flushing or fast breathing
+ Breath that smells like fruit
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 problem), including:
+ Severe stomach pain
+ Severe back pain
+ Severe upset stomach or vomiting
Signs of acidosis (too much acid in the blood), such as:
+ Confusion
+ Fast breathing
+ Fast heartbeat or irregular heartbeat
+ Severe stomach pain, upset stomach, or vomiting
+ Feeling extremely sleepy
+ Shortness of breath
+ Feeling very tired or weak
Abnormal sensations, such as burning, numbness, or tingling
Seizures
Confusion or memory problems
Changes in eyesight
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)
+ 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. 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 symptoms that bother you or do not go away, contact your doctor:
Upset stomach or vomiting
Reporting Side Effects
If you have questions about side effects or want to report any, you can:
Call your doctor for medical advice
Contact the FDA at 1-800-332-1088
Report side effects 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, or burning sensation in the hands or feet
- Blurred vision or changes in color 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 safety while taking this medication. 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 and obtain a list of foods and drinks to avoid during and after treatment with this medication, for as long as your doctor advises. Additionally, if you are pregnant, planning to become pregnant, or breastfeeding, discuss the benefits and risks of this medication with your doctor to make an informed decision about your treatment.
Overdose Information
Overdose Symptoms:
- Nausea
- Vomiting
- Dizziness
- Slurred speech
- Blurred vision
- Visual hallucinations
- Hyperreflexia
- Peripheral neuropathy
- Metabolic acidosis
- Hyperglycemia
- Ketonuria
- Seizures (often severe and refractory)
- Coma
What to Do:
Seek immediate medical attention or call a poison control center (1-800-222-1222). Treatment involves supportive care, gastric lavage, activated charcoal, and administration of pyridoxine (Vitamin B6) intravenously in doses equal to the amount of isoniazid ingested (or 5g if unknown) to counteract neurotoxicity and seizures.
Drug Interactions
Contraindicated Interactions
- Not explicitly contraindicated with specific drugs, but caution with other hepatotoxic agents.
Major Interactions
- Alcohol (increased risk of hepatotoxicity)
- Carbamazepine (increased carbamazepine levels, neurotoxicity)
- Phenytoin (increased phenytoin levels, toxicity)
- Valproic acid (increased valproic acid levels, hepatotoxicity)
- Warfarin (increased anticoagulant effect, bleeding risk)
- Acetaminophen (increased risk of hepatotoxicity with chronic use)
- Disulfiram (psychotic episodes, ataxia)
Moderate Interactions
- Aluminum-containing antacids (decreased isoniazid absorption; separate administration by at least 1-2 hours)
- Benzodiazepines (e.g., diazepam, triazolam; increased benzodiazepine levels)
- Corticosteroids (decreased isoniazid levels)
- Ketoconazole, Itraconazole (decreased antifungal levels)
- Theophylline (increased theophylline levels)
- Cycloserine (increased CNS toxicity)
- Stavudine (increased risk of peripheral neuropathy)
Minor Interactions
- Food (decreased absorption, administer on empty stomach)
- Tyramine-containing foods (e.g., aged cheese, red wine, tuna; may cause palpitations, flushing, headache due to MAO inhibition)
Monitoring
Baseline Monitoring
Liver function tests (ALT, AST, bilirubin)
Rationale: To establish baseline and identify pre-existing liver disease, as isoniazid can cause severe hepatotoxicity.
Timing: Before initiating therapy.
Renal function (BUN, creatinine)
Rationale: To assess kidney function, as dose adjustment may be needed in severe renal impairment.
Timing: Before initiating therapy.
Complete Blood Count (CBC)
Rationale: To establish baseline and monitor for potential hematologic abnormalities (e.g., agranulocytosis, hemolytic anemia) though rare.
Timing: Before initiating therapy.
Neurological assessment (peripheral neuropathy symptoms)
Rationale: To establish baseline and monitor for symptoms of peripheral neuropathy, especially in patients at risk (e.g., malnourished, diabetic, alcoholic).
Timing: Before initiating therapy.
Ophthalmologic exam (visual acuity, color vision)
Rationale: To establish baseline and monitor for optic neuritis, especially in patients with pre-existing visual impairment.
Timing: Before initiating therapy.
Routine Monitoring
Liver function tests (ALT, AST)
Frequency: Monthly, or more frequently if clinically indicated (e.g., symptoms of hepatitis, risk factors).
Target: Within normal limits or stable baseline.
Action Threshold: Discontinue isoniazid if ALT/AST > 3-5 times upper limit of normal (ULN) with symptoms, or > 5 times ULN without symptoms. Re-evaluate if > 3 times ULN with symptoms.
Symptoms of peripheral neuropathy (numbness, tingling, burning in extremities)
Frequency: At each clinical visit.
Target: Absence of new or worsening symptoms.
Action Threshold: If symptoms develop, ensure pyridoxine supplementation is adequate (10-50 mg/day). Consider dose reduction or discontinuation if severe.
Symptoms of hepatitis (fatigue, weakness, nausea, vomiting, dark urine, jaundice, abdominal pain)
Frequency: At each clinical visit.
Target: Absence of symptoms.
Action Threshold: Promptly evaluate LFTs and discontinue isoniazid if symptoms present.
Pyridoxine (Vitamin B6) supplementation
Frequency: Daily, throughout therapy.
Target: Adequate supplementation (10-50 mg/day) to prevent neuropathy.
Action Threshold: Ensure compliance, especially in patients at high risk for neuropathy.
Symptom Monitoring
- Fatigue
- Weakness
- Nausea
- Vomiting
- Loss of appetite
- Dark urine
- Yellowing of skin or eyes (jaundice)
- Abdominal pain (especially right upper quadrant)
- Numbness or tingling in hands or feet (peripheral neuropathy)
- Burning sensation in hands or feet
- Blurred vision or changes in color perception (optic neuritis)
- Fever
- Rash
- Joint pain
Special Patient Groups
Pregnancy
Isoniazid is generally considered acceptable for use during pregnancy for the treatment of active TB, as the benefits of treating TB outweigh the potential risks. However, it is classified as Category C. Pyridoxine supplementation is strongly recommended.
Trimester-Specific Risks:
First Trimester:
No clear evidence of teratogenicity in humans. Risk of congenital malformations is not increased.
Second Trimester:
Generally considered safe for continued use.
Third Trimester:
Generally considered safe for continued use. Monitor for maternal hepatotoxicity.
Lactation
Isoniazid is excreted into breast milk. However, the amount is generally considered too low to be harmful to the infant. Breastfeeding is generally considered compatible with isoniazid therapy, but the infant should be monitored for signs of adverse effects (e.g., jaundice, lethargy). Pyridoxine supplementation for the infant is not routinely recommended unless the infant is symptomatic.
Infant Risk:
Low risk (L3). Monitor for jaundice, lethargy, or poor feeding. Theoretical risk of peripheral neuropathy in infant, but rare.
Pediatric Use
Isoniazid is a cornerstone of TB treatment and prevention in children. Dosing is weight-based. Children are generally less prone to isoniazid-induced hepatotoxicity than adults, but monitoring is still important. Pyridoxine supplementation is recommended, especially in infants and those with risk factors for neuropathy.
Geriatric Use
Elderly patients are at increased risk for isoniazid-induced hepatotoxicity and peripheral neuropathy. Close monitoring of liver function and neurological status is essential. Pyridoxine supplementation is highly recommended. Dose adjustments may be necessary based on renal function.
Clinical Information
Clinical Pearls
- Always co-administer pyridoxine (Vitamin B6) with isoniazid to prevent peripheral neuropathy, especially in patients with risk factors (e.g., diabetes, alcoholism, malnutrition, HIV, renal failure, pregnancy).
- Isoniazid is a potent inhibitor of several CYP enzymes, leading to significant drug interactions (e.g., phenytoin, carbamazepine, warfarin). Monitor drug levels and clinical effects of co-administered medications.
- Educate patients thoroughly about the signs and symptoms of hepatotoxicity and the importance of reporting them immediately.
- Compliance is critical for successful TB treatment and prevention of resistance. Directly Observed Therapy (DOT) is often recommended, especially for intermittent regimens.
- The 50mg/5ml syrup formulation is particularly useful for pediatric patients or those who have difficulty swallowing tablets.
Alternative Therapies
- Rifampin (for LTBI or active TB as part of multi-drug regimen)
- Rifapentine (for LTBI, often with isoniazid)
- Pyrazinamide (for active TB as part of multi-drug regimen)
- Ethambutol (for active TB as part of multi-drug regimen)
- Streptomycin (for active TB as part of multi-drug regimen)
- Newer agents for drug-resistant TB (e.g., Bedaquiline, Delamanid, Pretomanid)
Cost & Coverage
Average Cost:
Check current market price per 50mg/5ml (e.g., 473ml bottle)
Generic Available:
Yes
Insurance Coverage:
Tier 1 or 2 (Generic)
General Drug Facts
If your symptoms or health issues persist or worsen, it's 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 be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to 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 details about the medication taken, the amount, and the time it happened.