Isoniazid

Tell your doctor about all prescription, non-prescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking, especially:

• Antabuse (disulfiram)
• Antacids
• Dilantin (phenytoin)
• Nizoral (ketoconazole)
• Tegretol (carbamazepine)
• Theophylline (Theobid, Theo-Dur)
• Tylenol (acetaminophen)
• Valproic acid (Depakene, Depakote)
• Vitamins

Isoniazid and Alcohol

Don't drink alcohol while taking isoniazid.

Consuming alcohol while using this medicine can increase your risk of liver damage.

Tell your doctor if you drink alcoholic beverages or have a history of alcohol abuse.

Isoniazid and Food

You might have to avoid foods that are high in tyramine or histamine because they could cause high blood pressure.

Some of these include:

• Aged cheese
• Red wine
• Beer
• Meats and sausages
• Liver
• Sour cream
• Soy sauce
• Raisins
• Bananas
• Avocados
• Tropic fish
• Skipjack tuna

Talk to your doctor about what foods to limit or avoid while using isoniazid.

Isoniazid Injection USP is available for intramuscular use in 10 mL vials providing 100 mg isoniazid per mL NDC 0781-3056-70.

Storage

Store at 20°-25°C (68°-77°F) (see USP Controlled Room Temperature). Protect from light.

Isoniazid Injection USP may crystallize at low temperatures. If this occurs, warm the vial to room temperature before use to redissolve the crystals.

REFERENCES

6. American Thoracic Society/Centers for Disease Control: Treatment of Tuberculosis and Tuberculosis Infection in Adults and Children. Amer. J. Respir Crit Care Med. 1994; 149: p1359-1374.

8. Committee on infectious Diseases American Academy of Pediatrics: 1994, Red Book: Report of the Committee on Infectious Diseases; 23 edition; p487.

9. Schraufnagel, DE; Testing for Isoniazid; Chest (United States) 1990, August: 98 (2) p314-316.

Manufactured in Canada by: Sandoz Canada Inc. for: Sandoz Inc., Princeton, NJ 08540

The most frequent reactions are those affecting the nervous system and the liver.

Nervous System Reactions

Peripheral neuropathy is the most common toxic effect. It is dose-related, occurs most often in the malnourished and in those predisposed to neuritis (e.g., alcoholics and diabetics) and is usually preceded by paresthesias of the feet and hands. The incidence is higher in “slow inactivators”.

Other neurotoxic effects, which are uncommon with conventional doses, are convulsions, toxic encephalopathy, optic neuritis and atrophy, memory impairment and toxic psychosis.

Hepatic Reactions

See BOXED WARNING. Elevated serum transaminase (SGOT; SGPT), bilirubinemia, bilirubinuria, jaundice and occasionally severe and sometimes fatal hepatitis. The common prodromal symptoms of hepatitis are anorexia, nausea, vomiting, fatigue, malaise and weakness. Mild hepatic dysfunction, evidenced by mild and transient elevation of serum transaminase levels occurs in 10 to 20 percent of patients taking isoniazid. This abnormality usually appears in the first 1 to 3 months of treatment but can occur at any time during therapy. In most instances, enzyme levels return to normal and generally, there is no necessity to discontinue medication during the period of mild serum transaminase elevation. In occasional instances, progressive liver damage occurs, with accompanying symptoms. If the SGOT value exceeds three to five times the upper limit of normal, discontinuation of the isoniazid should be strongly considered. The frequency of progressive liver damage increases with age. It is rare in persons under 20, but occurs in up to 2.3 percent of those over 50 years of age.

Gastrointestinal Reactions

Nausea, vomiting, epigastric distress, and pancreatitis.

Hematologic Reactions

Agranulocytosis; hemolytic, sideroblastic or aplastic anemia, thrombocytopenia; and eosinophilia.

Hypers ens itivity Reactions

Fever, skin eruptions (morbilliform, maculopapular, purpuric or exfoliative), lymphadenopathy, vasculitis, toxic epidermal necrolysis, and drug reaction with eosinophilia syndrome (DRESS).

Metabolic And Endocrine Reactions

Pyridoxine deficiency, pellagra, hyperglycemia, metabolic acidosis and gynecomastia.

Miscellaneous Reactions

Rheumatic syndrome and systemic lupus erythematosus-like syndrome.

Isoniazid acts against actively growing tubercle bacilli.

Within one to two hours after oral administration, isoniazid produces peak blood levels which decline to 50 percent or less within six hours. It diffuses readily into all body fluids (cerebrospinal, pleural, and ascitic), tissues, organs, and excreta (saliva, sputum, and feces). The drug also passes through the placental barrier and into milk in concentrations comparable to those in the plasma. From 50 to 70 percent of a dose of isoniazid is excreted in the urine in 24 hours.

Isoniazid is metabolized primarily by acetylation and dehydrazination. The rate of acetylation is genetically determined. Approximately 50 percent of Blacks and Caucasians are slow acetylators and the rest are rapid acetylators; the majority of Eskimos and Orientals are rapid acetylators.

The rate of acetylation does not significantly alter the effectiveness of isoniazid therapy when dosage is administered daily. However, slow acetylation may lead to higher blood levels of the drug and thus an increase in toxic reactions.

Pyridoxine (B6) deficiency is sometimes observed in adults with high doses of isoniazid and is considered probably due to its competition with pyridoxal phosphate for the enzyme apotryptophanase.

Mechanism of Action

Isoniazid inhibits the synthesis of mycolic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms.

Isoniazid resistant Mycobacterium tuberculosis bacilli develop rapidly when isoniazid monotherapy is administered.

Microbiology

Two standardized in vitro susceptibility methods are available for testing isoniazid against Mycobacterium tuberculosis organisms. The agar proportion method (CDC or NCCLS M24-P) utilizes middlebrook 7H10 medium impregnated with isoniazid at two final concentrations, 0.2 and 1.0 mcg/mL. MIC99 values are calculated by comparing the quantity of organisms growing in the medium containing drug to the control cultures. Mycobacterial growth in the presence of drug ≥1% of the control indicates resistance.

The radiometric broth method employs the BACTEC 460 machine to compare the growth index from untreated control cultures to cultures grown in the presence of 0.2 and 1.0 mcg/mL of isoniazid. Strict adherence to the manufacturers instructions for sample processing and data interpretation is required for this assay.

Mycobacterium tuberculosis isolates with an MIC99 ≤0.2 mcg/mL are considered to be susceptible to isoniazid. Susceptibility test results obtained by the two different methods discussed above cannot be compared unless equivalent drug concentrations are evaluated.

The clinical relevance of in vitro susceptibility for mycobacterium species other than M. tuberculosis using either the BACTEC or the proportion method has not been determined.

Isoniazid is a prescription medication used in the prevention and treatment of tuberculosis. Isoniazid belongs to a group of drugs called antitubercular agents. It is believed to work by preventing the bacteria from multiplying in the body.

Tell your doctor if you are breastfeeding or plan to breastfeed. Isoniazid is excreted in human breast milk.

The most frequent reactions are those affecting the nervous system and the liver.

Nervous System Reactions

Peripheral neuropathy is the most common toxic effect. It is dose-related, occurs most often in the malnourished and in those predisposed to neuritis (e.g., alcoholics and diabetics) and is usually preceded by paresthesias of the feet and hands. The incidence is higher in “slow inactivators”.

Other neurotoxic effects, which are uncommon with conventional doses, are convulsions, toxic encephalopathy, optic neuritis and atrophy, memory impairment and toxic psychosis.

Hepatic Reactions

See BOXED WARNING. Elevated serum transaminase (SGOT; SGPT), bilirubinemia, bilirubinuria, jaundice and occasionally severe and sometimes fatal hepatitis. The common prodromal symptoms of hepatitis are anorexia, nausea, vomiting, fatigue, malaise and weakness. Mild hepatic dysfunction, evidenced by mild and transient elevation of serum transaminase levels occurs in 10 to 20 percent of patients taking isoniazid. This abnormality usually appears in the first 1 to 3 months of treatment but can occur at any time during therapy. In most instances, enzyme levels return to normal and generally, there is no necessity to discontinue medication during the period of mild serum transaminase elevation. In occasional instances, progressive liver damage occurs, with accompanying symptoms. If the SGOT value exceeds three to five times the upper limit of normal, discontinuation of the isoniazid should be strongly considered. The frequency of progressive liver damage increases with age. It is rare in persons under 20, but occurs in up to 2.3 percent of those over 50 years of age.

Gastrointestinal Reactions

Nausea, vomiting, epigastric distress, and pancreatitis.

Hematologic Reactions

Agranulocytosis; hemolytic, sideroblastic or aplastic anemia, thrombocytopenia; and eosinophilia.

Hypers ens itivity Reactions

Fever, skin eruptions (morbilliform, maculopapular, purpuric or exfoliative), lymphadenopathy, vasculitis, toxic epidermal necrolysis, and drug reaction with eosinophilia syndrome (DRESS).

Metabolic And Endocrine Reactions

Pyridoxine deficiency, pellagra, hyperglycemia, metabolic acidosis and gynecomastia.

Miscellaneous Reactions

Rheumatic syndrome and systemic lupus erythematosus-like syndrome.

Read the entire FDA prescribing information for Isoniazid (isoniazid)

Take all of the isoniazid that has been prescribed for you even if you begin to feel better. Your symptoms may begin to improve before the infection is completely treated.

Avoid alcohol while taking isoniazid. Alcohol may increase the risk of damage to the liver during isoniazid treatment.

Contact your doctor immediately if you experience numbness or tingling in the hands or feet, weakness, fatigue, loss of appetite, nausea and vomiting, yellowing of the skin or eyes, or darkening of the urine.

Usual Adult Dose for Tuberculosis -- Active:

Active infection: 5 mg/kg (up to 300 mg) IM or orally once a day, or 15 mg/kg (up to 900 mg) 2 to 3 times a week. Therapy is usually continued for 6 months, or 3 months beyond culture conversion (when given with rifampin and pyrazinamide).

Latent infection: 10-20 mg/kg/day orally once a day, not to exceed 300 mg/day

If isoniazid and pyrazinamide are used alone, isoniazid should be continued for 9 months. If the patient is HIV-positive, therapy should be continued for at least 9 months, or for 6 months beyond culture conversion. Longer duration of therapy should be considered for silico-, bone, and meningeal tuberculosis.

Usual Adult Dose for Tuberculosis -- Prophylaxis:

300 mg orally once a day or 900 mg orally 2 to 3 times a week. Isoniazid should be continued for 6 months to prevent the development of active tuberculosis in patients with no complicating factors. Patients with complicating factors such as HIV infection, diabetes, hematologic malignancy, or scars on chest X-ray should receive prophylaxis for 12 months.

Usual Adult Dose for Mycobacterium kansasii:

600 to 900 mg IM or orally once a day.

Usual Pediatric Dose for Tuberculosis -- Active:

Oral, IM:
Infants, Children 40 kg or less, and Adolescents 14 years or less and less than 40 kg:

Treatment of active infection: CDC Recommendations: 10 to 15 mg/kg/day once daily (maximum dose: 300 mg/day) or 20 to 30 mg/kg/dose (maximum dose: 900 mg/day) 2 times weekly as part of a multidrug regimen.

Treatment of latent infection: 10 to 20 mg/kg/day once daily (maximum dose: 300 mg/day) or 20 to 40 mg/kg/dose (maximum dose: 900 mg/day) 2 times weekly. Treatment duration: 9 months.

Primary prophylaxis for TB in HIV-exposed positive patients: 10 to 15 mg/kg/day once daily (maximum dose: 300 mg/day) or 20 to 30 mg/kg/dose twice weekly (maximum dose: 900 mg/day). Treatment duration: 9 months.

Usual Pediatric Dose for Tuberculosis -- Latent:

Oral, IM:
Infants, Children 40 kg or less, and Adolescents 14 years or less and less than 40 kg:

Treatment of active infection: CDC Recommendations: 10 to 15 mg/kg/day once daily (maximum dose: 300 mg/day) or 20 to 30 mg/kg/dose (maximum dose: 900 mg/day) 2 times weekly as part of a multidrug regimen.

Treatment of latent infection: 10 to 20 mg/kg/day once daily (maximum dose: 300 mg/day) or 20 to 40 mg/kg/dose (maximum dose: 900 mg/day) 2 times weekly. Treatment duration: 9 months.

Primary prophylaxis for TB in HIV-exposed positive patients: 10 to 15 mg/kg/day once daily (maximum dose: 300 mg/day) or 20 to 30 mg/kg/dose twice weekly (maximum dose: 900 mg/day). Treatment duration: 9 months.

Administration

Administer orally.c d May be given IM when oral therapy is not feasible.b

Used in conjunction with other antimycobacterial agents for treatment of active (clinical) TB.176 b c d e Used alone for treatment of LTBI.166 177 b c d

Fixed-combination preparations (Rifamate containing rifampin and isoniazid; Rifater containing rifampin, isoniazid, and pyrazinamide) can be used for treatment of active TB infection to reduce the pill burden and ensure compliance, especially when directly observed (supervised) therapy (DOT) cannot be used.176 A fixed-combination preparation should be used only when all drugs in the preparation are indicated.176

Oral Administration

Administer orally in the fasting state.c d Do not administer with food.c d (See Food under Pharmacokinetics.)

Rifamate or Rifater: Administer orally with a full glass of water 1 hour before or 2 hours after a meal.141 143

Dosage

Oral and IM dosage is the same.a

Dosage of Rifamate is expressed as number of capsules;143 dosage of Rifater is expressed as number of tablets.141

Concomitant administration of pyridoxine (vitamin B6) is recommended in adults, adolescents, and pediatric patients who are malnourished (including those on meat- or milk-deficient diets) and in those predisposed to neuropathy (e.g., those with alcoholism, diabetes, HIV infection, seizure disorders, or renal failure).141 145 147 166 176 b c d f Administration of pyridoxine also is recommended in pregnant or nursing women;145 176 breast-feeding infants do not require pyridoxine unless they are receiving isoniazid.145 166 176 (See Nervous System Effects under Cautions.)

Pediatric Patients

Children: 10–15 mg/kg (up to 300 mg) once daily or 20–40 mg/kg (up to 900 mg) 2 or 3 times weekly recommended by the manufacturers.c d

Children <15 years of age or weighing ≤40 kg: 10–15 mg/kg (up to 300 mg) once daily or 20–30 mg/kg (up to 900 mg) twice weekly recommended by ATS, CDC, IDSA, AAP, and others.145 176 f j

Adolescents ≥15 years of age: 5 mg/kg (up to 300 mg) once daily or 15 mg/kg (up to 900 mg) 1–3 times weekly recommended by ATS, CDC, and IDSA.176 e

Rifater in adolescents ≥15 years of age: 4 tablets once daily in those weighing ≤44 kg, 5 tablets once daily in those weighing 45–54 kg, or 6 tablets once daily in those weighing ≥55 kg.141 Used only in the initial phase of treatment.141

Children: 10–15 mg/kg (up to 300 mg) once daily or 20–40 mg/kg (up to 900 mg) 2 or 3 times weekly.b

Infants, children, and adolescents: 10–15 mg/kg (up to 300 mg) once daily or 20–30 mg/kg (up to 900 mg) 2 or 3 times weekly recommended by manufacturers, ATS, CDC, IDSA, AAP, USPHS, and others.145 147 166 b c i j

The usual duration of isoniazid monotherapy for treatment of LTBI in children is 9 months, especially in HIV-infected individuals.145 147 166 i j A 6-month regimen is not recommended for children.145 147 166

ATS and CDC recommend that completion of therapy for LTBI be based on total number of administered doses rather duration of therapy alone.166 When the 9-month once-daily isoniazid regimen is used, at least 270 doses should be administered within 12 months.166 Ideally, patients should receive the drug on a regular dosing schedule until completed; in practice, some doses may be missed requiring the course to be lengthened.166 If the regimen is resumed after an interruption of ≥2 months, a medical examination is indicated to rule out active TB.166

Children: 10 mg/kg (up to 300 mg) once daily or 20–30 mg/kg (up to 900 mg) twice weekly.b

Adults

5 mg/kg (up to 300 mg) once daily176 c d e j or 15 mg/kg (up to 900 mg) 1–3 times weekly176 c d e j recommended by manufacturers, ATS, CDC, IDSA, and others.

Rifamate: 2 capsules once daily.143

Rifater: 4 tablets once daily in adults weighing ≤44 kg, 5 tablets once daily in adults weighing 45–54 kg, or 6 tablets once daily in adults weighing ≥55 kg.141 Used in the initial phase of treatment.141

5 mg/kg (up to 300 mg) once daily or 15 mg/kg (up to 900 mg) 2 or 3 times weekly.b

5 mg/kg (up to 300 mg) once daily or 15 mg/kg (up to 900 mg) twice weekly recommended by ATS, CDC, IDSA, USPHS, and others.124 147 166 j

Adults weighing >30 kg: 300 mg once daily recommended by manufacturers.c

The usual duration of isoniazid monotherapy for treatment of LTBI is 9 months.145 147 163 166 177 j A 6-month regimen may be used in some adults,177 but a 9-month regimen should be used in immunocompromised or HIV-infected individuals or those with fibrotic lesions on chest radiographs.145 147 163 166 177

ATS and CDC recommend that completion of therapy for LTBI be based on total number of administered doses rather duration of therapy alone.166 When the 9-month once-daily isoniazid regimen is used, at least 270 doses should be administered within 12 months.166 When the 6-month once-daily isoniazid regimen is used, at least 180 doses should be administered within 9 months.166 Ideally, patients should receive the drug on a regular dosing schedule until completed; in practice, some doses may be missed requiring the course to be lengthened.166 If the regimen is resumed after an interruption of ≥2 months, a medical examination is indicated to rule out active TB.166

Adults weighing >30 kg: 300 mg once daily or 20–30 mg/kg (up to 900 mg) twice weekly.b

5 mg/kg (up to 300 mg) daily in conjunction with ethambutol (15 mg/kg once daily) and rifampin (10 mg/kg [up to 600 mg] daily), and pyridoxine (50 mg daily) recommended by ATS and IDSA.t

Continue until patient has been culture negative on treatment for 1 year.t A longer duration may be needed in HIV-infected individuals with disseminated infections.t

Prescribing Limits

Pediatric Patients

Maximum 300 mg per dose in once-daily regimens or 900 mg per dose in 2- or 3-times weekly regimens.145 166 176 c f

When used in conjunction with rifampin, isoniazid dosage >10 mg/kg daily may increase the incidence of hepatotoxicity.145 f

Adults

Maximum 300 mg per dose in once-daily regimens or 900 mg per dose in 2- or 3-times weekly regimens.166 176 e

Special Populations

Hepatic Impairment

Risk of drug accumulation may be increased, but no specific dosage recommendations available.176 (See Hepatic Impairment under Cautions.)

Renal Impairment

No dosage adjustment needed in patients with renal impairment, including end-stage renal disease; supplemental doses not necessary in hemodialysis patients.176 (See Renal Impairment under Cautions.)

Specific Drugs, Food, and Laboratory Tests

• Bactericidal in action.b c d

• Interferes with metabolism of bacterial proteins, nucleic acids, carbohydrates, and lipids.a Appears to inhibit mycolic acid synthesis in susceptible bacteria which results in loss of acid-fastness and disruption of the bacterial cell wall.a b c d

• A highly specific antibacterial agent; active only against Mycobacterium.a Active in vitro and in vivo against M. tuberculosis,a M. bovis,a and some strains of M. kansasii.a t M. marinum is resistant.t u

• Natural and acquired resistance to isoniazid observed in vitro and in vivo in M. tuberculosis.a

• M. tuberculosis resistant to both isoniazid and rifampin (MDR TB) occurs.k l m n There also have been recent reports of extensively drug-resistant (XDR) TB in various parts of the world, including the US.k l n XDR TB is caused by M. tuberculosis resistant to rifampin and isoniazid (multiple-drug resistant strains) that also are resistant to a fluoroquinolone and at least one parenteral second-line antimycobacterial (capreomycin, kanamycin, amikacin).k l n

• Antitubercular Agent

Hypersensitivity to isoniazid or any component of the formulation, including drug-induced hepatitis; acute liver disease; previous history of hepatic injury during isoniazid therapy; previous severe adverse reaction (drug fever, chills, arthritis) to isoniazid

Do not take with food; avoid tyramine- and/or histamine-containing foods. Increase dietary intake of folate, niacin, magnesium.

Adverse events were observed in some animal reproduction studies. Isoniazid crosses the human placenta. Due to the risk of tuberculosis to the fetus, treatment is recommended when the probability of maternal disease is moderate to high. Drug-susceptible TB guidelines recommend isoniazid as part of the initial treatment regimen. Isoniazid is also recommended for the treatment of TB in pregnant women with HIV-coinfection. Pyridoxine supplementation is recommended (Nahid 2016). Due to biologic changes during pregnancy and early postpartum, pregnant women may have increased susceptibility to tuberculosis infection or reactivation of latent disease (Mathad 2012).

Applies to isoniazid: solution, syrup, tablet

Along with its needed effects, isoniazid may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking isoniazid:

• Clumsiness or unsteadiness
• dark urine
• loss of appetite
• nausea or vomiting
• numbness, tingling, burning, or pain in hands and feet
• unusual tiredness or weakness
• yellow eyes or skin

• Blurred vision or loss of vision, with or without eye pain
• convulsions (seizures)
• fever and sore throat
• joint pain
• mental depression
• mood or other mental changes
• skin rash
• unusual bleeding or bruising

Some side effects of isoniazid may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Diarrhea
• stomach pain

• Irritation at the place of injection

Dark urine and yellowing of the eyes or skin (signs of liver problems) are more likely to occur in patients over 50 years of age.

Applies to isoniazid: intramuscular solution, oral syrup, oral tablet

Nervous system

Overdose of isoniazid has been associated with uncontrollable seizures. Dialysis may be required to decrease isoniazid blood levels, thereby controlling seizures. Seizures, lethargy, and confusion have also been reported in patients with chronic renal failure. Other patients at risk for neurotoxicity include the malnourished and alcoholics. Optic neuritis has also been reported in patients on hemodialysis.[Ref]

Peripheral neuropathy has been observed and occurs frequently, especially at doses greater than 300 mg daily. Neuropathy may be prevented or attenuated by coadministration of pyridoxine 50 to 100 mg daily. Other neurologic reactions, although rare, have included visual disturbances, ataxia, and seizures.[Ref]

Hepatic

Hepatitis has been reported in less than 5% of patients receiving isoniazid alone. Jaundice is usually preceded by a prodromal illness with fatigue, nausea, malaise, abdominal pain, and anorexia. Asymptomatic increases in liver function tests may occur. Isoniazid should be discontinued if hepatotoxicity occurs, usually defined as SGOT greater than four times normal.[Ref]

The mechanism of hepatic injury is unknown but may be related to the acetyl metabolite of isoniazid. Patients exhibiting hepatotoxicity are more likely to be fast acetylators of isoniazid. Eight cases of severe hepatitis resulting in death or transplantation have been evaluated by the Department of Health of New York. Duration of isoniazid use before onset of hepatitis ranged from 21 to 142 days, and seven patients continued use of isoniazid at least 10 days after onset of symptoms. Massive hepatic necrosis was a common finding and cholestasis was present in two of five cases.

The risk is age related with a greater occurrence reported in patients who are 35 years or older. The risk of hepatitis is also increased in patients who consume alcohol daily, in women, and in minorities. In a study of 2651 women beginning isoniazid preventive therapy during pregnancy or postpartum, 5 cases of isoniazid-induced hepatitis were identified, including two fatalities. In another review of deaths due to isoniazid, eight of 21 women between 15 and 44 years old were within one year postpartum. In general, death due to isoniazid hepatotoxicity occurs more frequently in women than men.

Fulminate hepatitis, characterized by jaundice, disorders of consciousness and elevated serum transaminases up to 80 times the upper limit of normal, has occasionally occurred in patients receiving isoniazid with rifampin. Rifampin, by virtue of its enzyme-inducing activity, likely increases the reactive metabolite of isoniazid thought to be responsible for the hepatotoxicity associated with isoniazid.

Monthly monitoring and interviewing of patients should take place. Patients should be fully informed regarding the risk of hepatotoxicity associated with isoniazid, educated about the signs and symptoms of liver damage, and instructed to contact their physician immediately if they develop signs or symptoms.[Ref]

Hematologic

Hematologic abnormalities such as anemia have been reported. Anemia is generally reversible following discontinuation of isoniazid. Agranulocytosis, thrombocytopenia, and eosinophilia have rarely been reported.[Ref]

Several cases have been reported of pure red cell aplasia attributable to isoniazid. Abnormalities resolved following drug discontinuation.[Ref]

Hypersensitivity

Hypersensitivity reactions including drug fever, rash, lymphadenopathy, vasculitis, and urticaria have been reported but are rare. These reactions generally subside following drug discontinuation.[Ref]

Immunologic

Isoniazid-induced lupus-like reactions have been reported with an incidence of approximately 1%. However, as many as 22% of patients on this drug may develop positive antinuclear antibodies. Drug discontinuation is recommended if a lupus-like reaction occurs.[Ref]

Psychiatric

Psychosis, depression, and aggression have been rarely reported with isoniazid therapy. Some patients with preexisting schizophrenia have experienced exacerbations when isoniazid was started.[Ref]

Gastrointestinal

Gastrointestinal adverse effects have included nausea, vomiting, and epigastric distress. A few cases of pancreatitis have been reported.[Ref]

Metabolic

Metabolic side effects such as pyridoxine deficiency and pellagra have been reported. Isoniazid induced hypocalcemia and hypophosphatemia has been observed and may be due to altered vitamin D metabolism.[Ref]

Local

Local irritation has been observed at the site of intramuscular injection of isoniazid.[Ref]

Some side effects of isoniazid may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

If liver function tests exceed 3 to 5 times the upper limit of baseline, discontinue use of isoniazid therapy and monitor until liver function tests return to baseline. Symptoms of liver toxicity include anorexia, nausea, vomiting, dark urine, icterus, rash, persistent paresthesias of the hands and feet, persistent fatigue, weakness or fever greater than 3 days duration, and right upper quadrant abdominal tenderness.

Isoniazid therapy may be reinstituted when liver function tests return to baseline and symptoms of toxicity resolve.