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# ATT Drugs (Antitubercular Therapy)
## Overview
Antitubercular therapy typically follows a multi-drug regimen to prevent the emergence of resistant strains. The standard first-line regimen (RIPE therapy) consists of Rifampin (R), Isoniazid (I), Pyrazinamide (P), and Ethambutol (E).
## Primary Indications
Treatment of active *Mycobacterium tuberculosis* (TB) infection and Latent TB Infection (LTBI).
## Adult Dosing
* **Isoniazid (INH):** 5 mg/kg/day (max 300 mg) OR 15 mg/kg (max 900 mg) 2-3 times/week. *Always supplement with Pyridoxine (B6) 25-50 mg/day to prevent peripheral neuropathy.*
* **Rifampin (RIF):** 10 mg/kg/day (max 600 mg).
* **Pyrazinamide (PZA):** 15-30 mg/kg/day (max 2 g/day).
* **Ethambutol (EMB):** 15-25 mg/kg/day (max 2.5 g/day).
## Pediatric Dosing
* **Isoniazid:** 10-20 mg/kg/day (max 300 mg).
* **Rifampin:** 10-20 mg/kg/day (max 600 mg).
* **Pyrazinamide:** 30-40 mg/kg/day (max 2 g).
* **Ethambutol:** 15-25 mg/kg/day (max 2.5 g).
## Dose Adjustments
* **Renal Impairment:** Ethambutol and Pyrazinamide require interval extension or dose reduction (CrCl <30 mL/min).
* **Hepatic Impairment:** Use with extreme caution. Discontinue PZA and possibly INH/RIF if transaminases exceed 3-5x the upper limit of normal with symptoms.
## Contraindications
* **INH:** Acute liver disease; previous history of severe adverse reactions (e.g., drug-induced hepatitis).
* **RIF:** Concomitant use with certain protease inhibitors or other CYP450 inducers/substrates.
* **PZA:** Severe hepatic damage or acute gout.
* **EMB:** Optic neuritis.
## Adverse Effects
* **INH:** Peripheral neuropathy, hepatotoxicity, lupus-like syndrome.
* **RIF:** Red-orange discoloration of body fluids (benign), hepatotoxicity, strong CYP450 induction.
* **PZA:** Hyperuricemia (counsel on gout), hepatotoxicity.
* **EMB:** Optic neuritis (dose-dependent, monitor visual acuity and color discrimination).
## Key Drug Interactions
* **RIF:** Potent inducer of CYP450 (3A4, 2C9, 2C19), P-glycoprotein, and UGT. Significantly decreases levels of oral contraceptives, warfarin, HIV protease inhibitors, and immunosuppressants.
* **INH:** Inhibitor of CYP2C19 and 2E1; may increase levels of phenytoin and carbamazepine.
## Monitoring
* Baseline and periodic LFTs (AST/ALT/Bilirubin).
* Baseline vision exam (Snellen chart and color vision) for Ethambutol; monthly visual follow-up.
* Baseline serum uric acid (if PZA is used).
* Baseline renal function (SCr).
## Clinical Pearls
* **Treatment Phases:** Standard active TB treatment consists of a 2-month Intensive Phase (RIPE) followed by a 4-month Continuation Phase (RI and usually RIF).
* **Adherence:** Directly Observed Therapy (DOT) is the gold standard to prevent MDR-TB.
* **Local Protocols:** Dosing frequency and duration depend heavily on resistance patterns and regional public health guidelines (e.g., CDC/WHO).
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**Educational Disclaimer:** This information is for educational purposes only. Always verify current prescribing information, institutional protocols, and patient-specific factors with the most recent clinical guidelines or a clinical pharmacist before prescribing or administering medication.
