Mode of action of every drug in akurit 4 with their side effects
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tuberculosis treatment adverse effects
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Akurit-4 composition rifampicin isoniazid pyrazinamide ethambutol prescribing information
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CDC tuberculosis medicines side effects rifampin isoniazid pyrazinamide ethambutol
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Akurit-4 is a fixed-dose combination used for drug-susceptible tuberculosis. A commonly supplied tablet contains:
- Rifampicin 150 mg
- Isoniazid 75 mg
- Pyrazinamide 400 mg
- Ethambutol 275 mg
Confirm the exact strengths on your strip, since formulations can vary.
| Drug | Mode of action | Important side effects |
|---|---|---|
| Rifampicin (R) | Binds the beta subunit of bacterial DNA-dependent RNA polymerase, stopping RNA synthesis and thereby killing M. tuberculosis. | Orange-red discoloration of urine, sweat, saliva and tears is expected and harmless. Nausea, rash, flu-like illness, hepatitis/cholestatic jaundice, low platelets and rarely kidney inflammation. It is a potent enzyme inducer, so it can reduce the effect of oral contraceptives, warfarin, some HIV medicines, antifungals, anticonvulsants, and many others. |
| Isoniazid (H) | A prodrug activated by mycobacterial KatG catalase-peroxidase. It inhibits InhA, blocking mycolic-acid synthesis, an essential component of the mycobacterial cell wall. | Hepatitis, nausea, rash, fever. Peripheral neuropathy: tingling, burning or numbness of hands/feet due to functional vitamin B6 deficiency. Vitamin B6 (pyridoxine) is often prescribed with it. Rarely seizures, psychosis, or lupus-like illness. |
| Pyrazinamide (Z) | A prodrug converted by mycobacterial pyrazinamidase into pyrazinoic acid. It is especially active in acidic environments, such as within macrophages and TB lesions. Its precise downstream mechanism has multiple targets and is not fully settled. | Hepatotoxicity, nausea/vomiting, poor appetite, rash. It reduces uric-acid excretion, causing hyperuricemia, joint pains, and occasionally acute gout. |
| Ethambutol (E) | Inhibits arabinosyl transferase, preventing formation of arabinogalactan and lipoarabinomannan in the mycobacterial cell wall. It is mainly bacteriostatic. | Optic neuritis/optic neuropathy: reduced visual sharpness, blurred vision, and impaired red-green color discrimination. Risk rises with high dose or kidney impairment. It can also raise uric acid, cause rash, and GI upset. |
Why all four are used together: they act at different bacterial targets and reduce the chance that TB becomes drug-resistant. The standard intensive phase for drug-susceptible TB commonly uses HRZE together. CDC TB treatment guidance supports this four-drug approach. Mechanisms are described in Goodman & Gilman’s The Pharmacological Basis of Therapeutics, p. 1288, and Harrison’s Principles of Internal Medicine, p. 1465.
Seek medical advice urgently if any of these occur
- Yellow eyes/skin, dark brown urine, pale stools, severe nausea/vomiting, marked fatigue, or right-upper abdominal pain: possible drug-induced hepatitis
- Blurred vision, reduced vision, or difficulty distinguishing red from green: possible ethambutol eye toxicity
- Severe rash, facial swelling, breathing difficulty
- Easy bruising or bleeding
- Severe tingling/numbness or weakness in hands/feet
- Severe painful swollen joint, especially the big toe, suggesting gout
Rifampicin-related orange urine/tears alone is usually harmless, but dark brown urine plus jaundice or illness is not. The CDC adverse-effect table lists liver toxicity with isoniazid, rifampicin, and pyrazinamide, and vision changes with ethambutol.
Do not stop only one tablet or change the number of tablets yourself, because incomplete therapy can lead to treatment failure and resistance. Contact the TB clinic or prescriber promptly if adverse effects occur.
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