Usage
This combination drug is primarily prescribed for the treatment of active tuberculosis (TB). It is a first-line treatment for both pulmonary and extrapulmonary TB. It is classified as an antimycobacterial agent or antituberculosis drug. The combination targets different aspects of mycobacterial metabolism, inhibiting cell wall synthesis (Ethambutol), mycolic acid synthesis (Isoniazid), and RNA synthesis (Rifampicin). This multi-pronged approach prevents the development of drug resistance, a crucial factor in TB treatment.
Alternate Names
This specific combination doesn’t have a widely recognized single name. It’s commonly referred to by the constituent drugs. Brand names vary by region and manufacturer but may include combinations of the individual drug brand names such as Rifadin, Rimactane (rifampin), and Myambutol (ethambutol).
How It Works
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Ethambutol: Inhibits arabinosyl transferases, disrupting mycobacterial cell wall synthesis. It’s orally absorbed and well-distributed, primarily excreted renally, with dose adjustments needed in renal impairment.
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Isoniazid: A prodrug activated by mycobacterial catalase-peroxidase, inhibiting mycolic acid synthesis essential for the mycobacterial cell wall. It’s metabolized by acetylation in the liver with significant interindividual variability in metabolism rates. It is primarily eliminated through the kidneys.
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Rifampicin: Inhibits bacterial DNA-dependent RNA polymerase, suppressing RNA synthesis. It’s lipophilic, well-absorbed orally, and undergoes enterohepatic circulation. It induces CYP450 enzymes and is primarily eliminated through the biliary system with some renal excretion.
Dosage
Standard Dosage
Adults:
- Ethambutol: 15 mg/kg orally once daily. For retreatment cases: 25 mg/kg orally once daily initially, then reduced to 15 mg/kg after a few weeks.
- Isoniazid: 5 mg/kg (max 300 mg) orally once daily. Alternatively, 15 mg/kg (max 900 mg) two or three times a week.
- Rifampicin: 10 mg/kg (max 600 mg) orally once daily.
Children:
- Ethambutol: 15-25 mg/kg orally once daily.
- Isoniazid: 10-15 mg/kg (max 300 mg) orally once daily or 20-40 mg/kg (max 900 mg) two to three times a week.
- Rifampicin: 10-20 mg/kg (max 600 mg) orally once daily.
Special Cases:
- Elderly Patients: Standard doses are usually appropriate, but close monitoring for adverse effects is essential.
- Patients with Renal Impairment: Ethambutol dose reduction is required based on creatinine clearance. Isoniazid requires careful monitoring.
- Patients with Hepatic Dysfunction: Isoniazid and rifampicin dosage adjustments are usually needed. Close monitoring for liver function tests is important.
- Patients with Comorbid Conditions: Individualized dosing may be needed.
Clinical Use Cases
The use of this combination in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU, and emergencies is not relevant. This combination is specifically for tuberculosis treatment.
Dosage Adjustments
Dose adjustments are based on renal and hepatic function, drug interactions, and other patient-specific factors. Therapeutic drug monitoring may be beneficial for isoniazid and rifampicin, particularly in special populations.
Side Effects
Common Side Effects
- Nausea, vomiting, abdominal pain
- Loss of appetite
- Peripheral neuropathy (Isoniazid)
- Orange discoloration of body fluids (Rifampicin)
- Visual disturbances (Ethambutol)
Rare but Serious Side Effects
- Hepatotoxicity (Isoniazid, Rifampicin)
- Optic neuritis (Ethambutol)
- Drug-induced lupus (Isoniazid)
- Thrombocytopenia
Long-Term Effects
- Peripheral neuropathy (Isoniazid)
- Visual impairment (Ethambutol)
- Hepatic damage
Adverse Drug Reactions (ADR)
Hepatotoxicity and optic neuritis are serious ADRs needing prompt discontinuation of the offending agent.
Contraindications
- Hypersensitivity to any of the components.
- Acute liver disease.
- Optic neuritis (Ethambutol).
Drug Interactions
Rifampicin is a potent inducer of CYP450 enzymes, leading to reduced concentrations of numerous drugs. Isoniazid can inhibit the metabolism of other drugs. Interactions with antacids (reduced Isoniazid absorption), anticonvulsants, anticoagulants, and many other medications are possible. Alcohol should be avoided during therapy due to the risk of hepatotoxicity.
Pregnancy and Breastfeeding
This combination can be used during pregnancy if the benefits outweigh the risks. Isoniazid can cause pyridoxine deficiency in the neonate. Rifampicin may cause bleeding complications in the newborn. All three drugs are present in breast milk, but breastfeeding is generally considered safe.
Drug Profile Summary
- Mechanism of Action: Inhibits cell wall synthesis (Ethambutol), mycolic acid synthesis (Isoniazid), and RNA synthesis (Rifampicin).
- Side Effects: Nausea, vomiting, peripheral neuropathy, hepatotoxicity, optic neuritis, orange discoloration of body fluids, visual disturbances.
- Contraindications: Hypersensitivity, acute liver disease, optic neuritis.
- Drug Interactions: Numerous, mainly due to Rifampicin’s CYP450 induction.
- Pregnancy & Breastfeeding: Generally safe if benefits outweigh risks. Monitor neonates for pyridoxine deficiency and bleeding issues.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: Liver function tests, visual acuity, complete blood counts.
Popular Combinations
This combination itself is a popular and standard first-line treatment for tuberculosis. Pyrazinamide may be added for the first two months of treatment in some regimens.
Precautions
Assess baseline liver function and visual acuity. Monitor for hepatotoxicity and optic neuritis. Provide pyridoxine supplementation to prevent Isoniazid-induced neuropathy. Caution in patients with renal or hepatic impairment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ethambutol + Isoniazid + Rifampicin?
A: See detailed dosage section above.
Q2: What are the most serious side effects of this combination?
A: Hepatotoxicity and optic neuritis are the most concerning side effects.
Q3: Can this combination be used in pregnant patients?
A: Yes, if the benefits outweigh the risks. Monitor the neonate for potential side effects.
Q4: What are the key drug interactions to consider?
A: Rifampicin induces CYP450 enzymes, affecting many drugs. Isoniazid can inhibit drug metabolism.
Q5: How should the dosage be adjusted in patients with renal impairment?
A: Ethambutol requires dose reduction based on creatinine clearance.
Q6: What are the monitoring parameters for patients on this combination?
A: Liver function tests, visual acuity, and complete blood counts should be monitored regularly.
Q7: What is the role of pyridoxine in this combination therapy?
A: Pyridoxine (Vitamin B6) is given prophylactically to prevent Isoniazid-induced peripheral neuropathy.
Q8: Can patients consume alcohol while on this medication?
A: No, alcohol should be avoided due to the increased risk of hepatotoxicity.
Q9: How is drug resistance prevented with this combination?
A: The drugs have different mechanisms of action, making it harder for the bacteria to develop resistance to all three simultaneously.
