Ethambutol + Isoniazid + Pyrazinamide + Rifampicin

Ethambutol + Isoniazid + Pyrazinamide + Rifampicin is a combination medicine used in the treatment of tuberculosis. It prevents the growth of the microorganisms that cause the infection.

This combination contains four medicines: Isoniazid, rifampicin, ethambutol and pyrazinamide which treat tuberculosis. Isoniazid works by preventing the TB bacteria from forming their own protective covering, while rifampicin inactivates a bacterial enzyme (RNA-polymerase) which is required by TB bacteria to make essential proteins and to reproduce.

• Pulmonary and Extrapulmonary Tuberculosis: Used in the intensive initial phase of treatment for pulmonary and extrapulmonary tuberculosis.

Anti-tubercular antibiotics

Anti-tuberculosis Combination

Rifampicin: It is a semisynthetic derivative of rifamycin, suppresses bacterial RNA synthesis by binding to the beta-subunit of DNA-dependent RNA polymerase. Isoniazid: Kills actively growing tubercle bacilli by inhibiting the biosynthesis of mycolic acids. Pyrazinamide: An antituberculous drug, the pyrazine analog of nicotinamide. Ethambutol: Inhibits the synthesis of 1 or more metabolites, causing impaired cell metabolism, arrest cell multiplication and induce cell death.

Rifampicin, isoniazid and pyrazinamide are all active bactericidal antituberculosis drugs. Ethambutol interferes with RNA synthesis, causing suppression of Mycobacteria multiplication. Combination covers activity against 3 different bacterial populations.

Adult Dose (FDC Tablets):

• New patient (Initial 2 months): 2-5 tablets of 4-FDC (Rifampicin 150mg + Isoniazid 75mg + Pyrazinamide 400mg + Ethambutol 275mg) daily based on body weight.
• New patient (Continuation 4 months): 2-5 tablets of 2-FDC (Rifampicin 600mg + Isoniazid 300mg) daily based on body weight.
• Retreatment patient (Initial 3 months): 4-FDC tablets + Streptomycin (500mg-1g) daily; next 5 months: 2-FDC + Ethambutol 400mg.

Average body weight (50 kg): 3 tablets/day.

Take this medicine in the dose and duration as advised by your doctor. Check the label before use. This combination is to be taken on an empty stomach. Avoid tyramine-rich food such as cheese, smoked fish, meats and some types of beer.

If you miss a dose, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular schedule.

Common Side Effects:

• Nausea
• Vomiting
• Rash
• Fever
• Dark colored urine
• Sweating
• Salivation
• Watery eyes
• Peripheral neuropathy
• Increased liver enzymes
• Jaundice
• Increased uric acid level in blood
• Visual impairment

Precautions:

• This combination may cause sight problems and tingling or numbness in hand or feet; do not drive until you know how it affects you.
• Take on an empty stomach and preferably at the same time every day.
• Try not to forget a dose (increases risk of bacterial resistance and side effects).
• It may discolor urine, sweat, saliva and tears reddish/orange (normal and harmless).
• Your doctor may check liver function before and regularly after starting treatment.
• Inform doctor if yellowing of eyes or skin, dark urine, or stomach pain occurs.
• Avoid alcohol (increases risk of side effects on the liver).
• May cause vitamin B6 deficiency; doctor may prescribe supplements.
• Hormonal contraceptives may be less effective; use other methods.
• Do not take antacids within at least two hours of taking this medicine.

Contraindications:

• Hypersensitivity
• History of drug-induced hepatitis
• Acute liver disease
• Peripheral or optic neuritis
• Renal dysfunction
• Epilepsy
• Chronic alcoholism

Drug Interactions:

• Rifampicin: Induces microsomal enzymes (accelerates clearance of methadone, oral anticoagulants, glucocorticoids, oestrogen, oral hypoglycaemic agents, digitoxin, antiarrhythmics, theophylline, anticonvulsants, azole antifungal, cyclosporin).
• Isoniazid: Inhibits metabolism of antiepileptics, benzodiazepines, warfarin, theophylline.
• Pyrazinamide: Decreases efficacy of gout therapy agents.
• Ethambutol: Neurotoxic agents.

Food Interactions: Consuming alcohol may cause flushing, increased heart beat, nausea, thirst, chest pain and low blood pressure (Disulfiram reaction).

Use in Pregnancy: This combination may be unsafe to use during pregnancy. Animal studies have shown harmful effects on the developing baby.

Use in Lactation: This combination is probably safe to use during breastfeeding. Limited human data suggests the drug does not represent significant risk to the baby.

Pediatric Use: Ethambutol is not recommended for use in children under 13 years.

Geriatric Use: Use with caution in elderly patients.

Renal Impairment: Use with caution; dose adjustment may be needed. Kidney function tests advisable before start.

Hepatic Impairment: Use with caution; dose adjustment may be needed; regular monitoring of liver function tests advised.

Overdose: In case of overdose, symptomatic treatment should be given and seek immediate medical attention.

Storage: Store at temperatures not exceeding 30 degree C.

Ethambutol + Isoniazid + Pyrazinamide + Rifampicin