What are the doses and side effects of all anti-tubercular (anti-tuberculosis) drugs?

Anti-Tubercular Drugs: Doses and Side Effects

First-Line Anti-Tubercular Drugs

Isoniazid (INH)

Dosing:

• Adults: 5 mg/kg daily (maximum 300 mg) or 15 mg/kg (maximum 900 mg) 2-3 times weekly 1, 2
• Children: 10-15 mg/kg daily (maximum 300 mg) or 20-40 mg/kg (maximum 900 mg) 2-3 times weekly 1, 2

Side Effects:

• Hepatitis (most significant toxicity, age-dependent with 0.5-1% incidence, higher in females) 1
• Peripheral neuritis (preventable with pyridoxine 25-50 mg daily) 1, 3
• Lupus erythematosus syndrome 1
• Drowsiness and mood changes 1

Critical Monitoring: Pyridoxine supplementation is mandatory for pregnant women, HIV-infected persons, alcoholics, malnourished patients, and those with chronic renal failure 3

---

Rifampicin (RIF)

Dosing:

• Adults: 10 mg/kg daily; <50 kg: 450 mg, >50 kg: 600 mg 1, 4
• Children: 10-20 mg/kg daily (maximum 600 mg) 1, 4
• Intermittent: 600-900 mg three times weekly 1

Side Effects:

• Drug interactions (major hepatic enzyme inducer affecting oral contraceptives, methadone, anticoagulants) 1
• Hepatitis (3-4% when combined with isoniazid) 1
• Thrombocytopenia 1
• Abdominal distress and diarrhea 1
• Immunologic febrile reactions (more common with intermittent regimens) 1

Critical Warning: Women using oral contraceptives must be advised of reduced effectiveness and need alternative contraception 1

---

Pyrazinamide (PZA)

Dosing:

• Adults: 15-30 mg/kg daily; <50 kg: 1.5 g, >50 kg: 2.0 g (maximum 2 g daily per CDC) 1, 5
• Children: 15-30 mg/kg daily (maximum 2 g) 1, 5
• Intermittent: 50-70 mg/kg three times weekly (<50 kg: 2.0 g, >50 kg: 2.5 g) or 75 mg/kg twice weekly (<50 kg: 3.0 g, >50 kg: 3.5 g) 1

Side Effects:

• Hepatitis (rare but potentially lethal) 1, 6
• Hyperuricemia (common, risk increased in renal insufficiency) 1
• Arthralgia or arthritis 1
• Rash and abdominal distress 1

---

Ethambutol (EMB)

Dosing:

• Adults: 15-25 mg/kg daily; low dose 15 mg/kg as companion drug, high dose 25 mg/kg as bacteriostatic drug 1
• Children: 15-25 mg/kg daily (maximum 2.5 g) 1
• Intermittent: 30 mg/kg three times weekly or 45 mg/kg twice weekly 1

Side Effects:

• Optic neuritis (dose-related; minimal risk at 15 mg/kg daily, 18% at >30 mg/kg daily) 1
• Decreased visual acuity or red-green color discrimination 1
• Abdominal distress 1

Critical Monitoring: Baseline and monthly visual acuity testing (Snellen chart) and color discrimination (Ishihara tests) required, especially for doses >15-25 mg/kg, treatment >2 months, or renal insufficiency 1. Discontinue immediately and permanently if visual toxicity occurs 1.

Caution: Generally not recommended in children <5 years whose visual acuity cannot be monitored, unless drug-resistant disease is suspected 1

---

Streptomycin (SM)

Dosing:

• Adults: 15 mg/kg daily or 25 mg/kg three times weekly (maximum 1 g) 1, 5
• Children: 20-40 mg/kg daily (maximum 1 g) or 25-40 mg/kg twice weekly (maximum 1.5 g) 1

Side Effects:

• Hearing loss (cochlear toxicity) 1
• Ataxia and nystagmus (vestibular toxicity) 1
• Nephrotoxicity (azotemia, proteinuria) 1, 7
• Eosinophilia and serum electrolyte abnormalities 1

Renal Adjustment: Dose or interval adjustment required when creatinine clearance <70 mL/min; 15-20 mg/kg three times weekly after dialysis in end-stage renal disease 1

---

Second-Line Anti-Tubercular Drugs (for Drug-Resistant TB)

Fluoroquinolones

Levofloxacin:

• Adults: 750-1,000 mg daily 1
• Children: 15-20 mg/kg daily 1

Moxifloxacin:

• Adults: 400 mg daily (600-800 mg for severe disease) 1
• Children: 10-15 mg/kg daily 1

Side Effects:

• Cardiotoxicity (QT prolongation) 7
• Abdominal distress, nausea, bloating, diarrhea 1
• Rash and edema 1

---

Aminoglycosides (Second-Line)

Amikacin:

• Adults: 15 mg/kg daily or 25 mg/kg three times weekly 1
• Children: 15-20 mg/kg daily 1

Kanamycin:

• Similar dosing to amikacin 1

Side Effects:

• Nephrotoxicity (life-threatening) 7
• Abdominal distress, headache, anxiety, tremulousness 1
• Thrush 1
• Drug interactions 1

Renal Adjustment: May require 2-3 times weekly dosing to allow drug clearance 1

---

Bedaquiline

Dosing:

• Adults: 400 mg daily for 14 days, then 200 mg three times weekly 1
• Children >12 years and >30 kg: Adult dose 1
• Children 6-12 years, 15-30 kg: 200 mg daily for 2 weeks, then 100 mg Monday/Wednesday/Friday for 22-24 weeks 1

Side Effects:

• QT prolongation (cardiotoxicity monitoring essential) 1

---

Linezolid

Dosing:

• Adults: 600 mg daily 1
• Children >12 years: 10 mg/kg once daily (300 or 600 mg) 1
• **Children <12 years:** Weight-based: 5-9 kg: 15 mg/kg; 10-23 kg: 12 mg/kg; >23 kg: 10 mg/kg 1

Side Effects:

• Bone marrow suppression (anemia, thrombocytopenia) 7
• Peripheral neuropathy 7
• Optic neuropathy 7

---

Clofazimine

Dosing:

• Adults: 100 mg daily 1
• Children: 2-5 mg/kg daily 1

Side Effects:

• Skin discoloration (red-brown to black) 7
• Gastrointestinal disturbances 7

---

Cycloserine/Terizidone

Dosing:

• Adults: 250-750 mg daily (15-20 mg/kg) 1
• Children: 15-20 mg/kg daily 1

Side Effects:

• CNS toxicity (mood and cognitive deterioration, psychosis, seizures) 1, 7
• Peripheral neuropathy 7

Renal Adjustment: Start with 250 mg daily and verify with therapeutic drug monitoring 1

---

Ethionamide/Prothionamide

Dosing:

• Adults: 15-20 mg/kg total (usually 250-500 mg once or twice daily) 1
• Children: 15-20 mg/kg daily (divided 1-2 times daily) 1

Side Effects:

• Severe gastrointestinal toxicity (nausea, vomiting, abdominal distress) 7, 6
• Hepatitis 1
• Metallic taste 7

---

Capreomycin

Dosing:

• Similar to aminoglycosides 1

Side Effects:

• Abdominal distress, dysgeusia, diarrhea 1
• Hepatitis and arthralgia 1
• Nephrotoxicity and ototoxicity 7

---

Delamanid

Dosing:

• Adults: 100 mg twice daily 1
• Children >35 kg: Adult dose 1
• Children 6+ years, 20-34 kg: 50 mg twice daily 1
• Children 3-5 years, 10-20 kg: 25 mg twice daily 1

Side Effects:

• QT prolongation 1

---

Para-Aminosalicylic Acid (PAS)

Side Effects:

• Severe gastrointestinal toxicity 7
• Hepatitis 7
• Hypothyroidism 7

---

Standard Treatment Regimen

For drug-susceptible pulmonary tuberculosis, the recommended regimen is:

• Initial phase (2 months): Rifampicin + Isoniazid + Pyrazinamide + Ethambutol daily 1
• Continuation phase (4 months): Rifampicin + Isoniazid daily 1

The fourth drug (ethambutol) can be omitted if isoniazid resistance is <4% in the community and the patient has fully sensitive organisms 1

---

Critical Monitoring Requirements

Baseline evaluation before treatment:

• Liver function tests for HIV-infected patients, pregnant women, and those with chronic liver disease history 8
• Visual acuity and color discrimination testing for ethambutol 1
• Renal function for aminoglycosides and ethambutol 1

During treatment:

• Monthly clinical monitoring for all patients 8
• Liver function monitoring when clinical signs appear (fever, malaise, vomiting, jaundice, weight loss) 1
• Monthly visual testing for ethambutol at doses >15-25 mg/kg or treatment >2 months 1

---

Common Pitfalls

Hepatotoxicity risk is highest when isoniazid and rifampicin are combined (3-4% incidence), particularly in the first 2 weeks of treatment 1. Active hepatitis and end-stage liver disease are relative contraindications 8.

Rifampicin significantly reduces effectiveness of oral contraceptives, requiring alternative contraception methods 1.

Ethambutol-induced optic neuritis can be irreversible; immediate and permanent discontinuation is mandatory if visual changes occur 1, 6.

Pyridoxine supplementation must continue throughout the entire duration of isoniazid therapy, not just the intensive phase, and should not exceed 100 mg daily for routine supplementation 3.