Isoniazid

Registered South African indications:

• Tuberculosis

Contraindications 

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy
• Breastfeeding
• Severe renal impairment
• Moderate to severe hepatic impairment
• Alcoholism 
• Convulsive disorders
• History of psychosis
• Risk of neuropathy 
• Risk of pyridoxine deficiency
• Diabetes mellitus
• Malnourished patients
• Uraemic patients 

Forms avail. in SA and covered in this monograph: tab

Active pulmonary and extrapulmonary TB

Between 30-37kg

• Oral (tab): 150mg, dly; Treatment duration: 6 months 

Between 38-54kg

• Oral (tab): 225mg, dly; Treatment duration: 6 months 

Between 55-70kg

• Oral (tab): 300mg, dly; Treatment duration: 6 months

Greater than 70kg

• Oral (tab): 375mg, dly; Treatment duration: 6 months 

TB prophylaxis in HIV positive patients

• Oral (tab): 4-6mg/kg, dly; Treatment duration: 6 months (in combination with pyridoxine)

Paed. forms avail. in SA and covered in this monograph: tab

Active pulmonary and extrapulmonary TB 

• Oral (tab): 7-15mg/kg, dly; Max: 300mg/24hrs

Miliary TB
TB meningitis

• Oral (tab): 15-20mg/kg, dly

TB prophylaxis in HIV positive children and children younger than 5 years

• Oral (tab): 10mg/kg, dly; Max: 300mg/24hrs; Treatment duration: 6 months

Decisions related to dose adjustment/discontinuing TB regimen must be discussed in advance with Pulmonologists/Infectious Disease specialists, and cases must be dealt with individually

Pregnancy

• Safe
• Isoniazid crosses the placenta. Therefore, isoniazid should only be used in pregnant women or in women of child-bearing potential if the potential benefit justifies the potential risk to the foetus. It is considered that untreated tuberculosis represents a far greater hazard to a pregnant woman and her foetus than does the treatment of the disease. Pyridoxine supplementation is recommended

Breastfeeding 

• Compatible
• Isoniazid passes into breast milk. When administered to the breastfeeding mother, breastfed infants should be monitored for possible signs of isoniazid toxicity. Administration of pyridoxine to the breastfeeding mother and infant may be considered

Renal Impairment 

• Mild to moderate: No dose adjustment recommended 
• Severe: Caution; No dose adjustment recommended
  Administer with pyridoxine to prevent peripheral neuropathy

Hepatic Impairment 

• Mild (Child-Pugh class A): No dose adjustment recommended
  Recommend treatment with two potentially hepatotoxic agents (rifampicin and isoniazid; in continuation phase); likely to be well tolerated
• Moderate (Child-Pugh class B): Use not recommended
  Recommend a regimen with only one potentially hepatotoxic agent (rifampicin; in continuation phase)
• Severe (Child-Pugh class C): Use not recommended
  Recommend treatment as MDR-TB; Can use streptomycin, ethambutol, fluoroquinolones, amikacin, kanamycin and other second-line oral agents for 18–24 months

Elderly

• No dose adjustment recommended

Porphyria Information

• Possibly porphyrinogenic (PSP)

Drugs in Sport

•  Permitted - No warnings

Central Nervous System Disorders

• Psychotic reactions
• Convulsions
• Optic neuritis
• Peripheral neuropathy

Gastrointestinal Disorders

• Nausea and vomiting
• Pellagra

Genitourinary Disorders

• Urinary retention

Endocrine and Metabolic Disorders

• Hyperglycaemia
• Metabolic acidosis
• Gynaecomastia

Musculoskeletal Disorders

• Rheumatoid syndrome

Skin and Subcutaneous Tissue Disorders

• Skin eruptions
• Pellagra-like dermatitis 

Immune, Blood and Lymphatic System Disorders

• Lymphadenopathy
• Vasculitis associated with positive antinuclear antibodies
• Sideroblastic anaemia
• Haemolytic anaemia
• Aplastic anemia
• Agranulocytosis
• Thrombocytopenia
• Eosinophilia
• Lupus-like syndrome 

Others

• Fever

• Alfentanil
• Warfarin
• Benzodiazepines
• Carbamazepine
• Phenytoin
• Theophylline
• Paracetamol
• Alcohol
• Rifampicin
• Aluminium-containing antacids
• Glucocorticoid corticosteroids
• Cycloserine
• Disulfiram
• Other neurotoxic medicines
• Enflurane
• Ketoconazole
• Miconazole

Hepatic function

Treatment for patients who cannot tolerate one of the first line medicines

• If patient cannot tolerate Isoniazid: Treat with Moxifloxacin/ Rifampicin/ Ethambutol for 12 months (Pyrazinamide may be added during the intensive phase)

Isoniazid is a prodrug and must be activated by bacterial catalase. Activation is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with oxygen to form an oxyferrous enzyme complex. Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. Specifically isoniazid inhibits InhA, the enoyl reductase from Mycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA.

Tablet 100mg

• Be-Tabs Isoniazid (Be-Tabs)
• Norstan-Isoniazid (Sanofi)
• Lennon Isoniazid 100mg (Pharmacare)
• Winthrop Isoniazid (Sanofi)

Tablet 300mg

• Norstan-Isoniazid (Sanofi)
• Winthrop Isoniazid (Sanofi)

COMBINATION PREPARATIONS

Rifampicin/ Isoniazid

Tablet 60mg/30mg

• Rimactazid Paed 60/30 (Sandoz)

Tablet 60mg/60mg

• Rimactazid Paed 60/60 (Sandoz)

Tablet 300mg/150mg

• Ebsar-2 DS (Dezzo Trading)
• Rimactazid 300/150 (Sandoz)

Tablet 150mg/75mg

• Rimactazid 150/75 (Sandoz)

Isoniazid/ Rifampicin/ Pyrazinamide

Tablet 30mg/60mg/150mg

• Rimcure Paed 3-Fdc (Sandoz)

Isoniazid/ Rifampicin/ Pyrazinamide/ Ethambutol Hcl

Tablet 75mg/150mg/400mg/275mg

• Antib-4 (Medicine Dev)
• Rifafour E-275 (Sanofi)
• Rimstar 4-Fdc (Sandoz)