What is the schedule of anti-tubercular medications for spinal tuberculosis?

Anti-Tubercular Treatment Schedule for Spinal Tuberculosis in India

For drug-susceptible spinal tuberculosis, treat with 2 months of isoniazid, rifampicin, pyrazinamide, and ethambutol (2HRZE), followed by 4 months of isoniazid and rifampicin (4HR), for a total duration of 6 months. 1, 2

Standard Regimen Components

Intensive Phase (First 2 Months)

• Isoniazid (H): 5 mg/kg daily (typically 300 mg) or 15 mg/kg thrice weekly (typically 900 mg) 1, 3
• Rifampicin (R): 10 mg/kg daily (typically 600 mg) or 10 mg/kg thrice weekly (600 mg) 1
• Pyrazinamide (Z): 15-30 mg/kg daily (maximum 2 g/day) or 50-70 mg/kg twice weekly 1, 4
• Ethambutol (E): 15-25 mg/kg daily or 50 mg/kg twice/thrice weekly 1

Continuation Phase (Next 4 Months)

• Isoniazid (H): Same dosing as intensive phase 1
• Rifampicin (R): Same dosing as intensive phase 1

India-Specific Considerations

The Revised National TB Control Programme (RNTCP) in India advocates thrice-weekly intermittent therapy: 2E₃H₃R₃Z₃ followed by 4H₃R₃ (subscript 3 indicates thrice weekly dosing). 5 This higher-dose intermittent regimen has been implemented specifically to improve compliance in resource-limited settings.

Fixed-dose combinations (FDCs) are strongly recommended as they minimize the risk of selective drug intake and improve adherence. 1, 5 Two-drug (HR), three-drug (HRZ), and four-drug (HRZE) combinations are available and provide more convenient administration. 1

Critical Spinal TB-Specific Modifications

When to Consider Extended Duration

If spinal cord compression is present, add adjuvant corticosteroids (dexamethasone or prednisone) during the first 6-8 weeks. 1 This prevents neurological complications and reduces inflammation around the spinal cord.

For children with spinal tuberculosis, extend treatment to 12 months rather than the standard 6 months due to the severity of bone/joint involvement. 1, 6

Surgical Considerations

Surgery may be required for spinal cord compression or spinal instability, but ambulatory chemotherapy alone is highly effective for most thoracic and lumbar spine tuberculosis without neurological complications. 1 The presence of sclerotic bone around vertebral foci significantly blocks drug penetration, with undetectable drug levels found inside sclerotic walls. 7 This pharmacokinetic barrier means that surgical debridement should be considered when extensive sclerotic bone surrounds the focus, as medical therapy alone may be insufficient. 7

Essential Monitoring and Adjuncts

Pyridoxine Supplementation

Add pyridoxine (vitamin B₆) 25-50 mg daily to all patients receiving isoniazid who have diabetes, HIV infection, malnutrition, chronic renal failure, alcoholism, pregnancy, or advanced age to prevent peripheral neuropathy. 1, 2

Hepatotoxicity Monitoring

Monitor liver function tests at baseline and if symptoms develop (fever, malaise, vomiting, jaundice). 1 If AST/ALT rises to 5 times normal or bilirubin rises, stop rifampicin, isoniazid, and pyrazinamide immediately. 1 Routine monitoring is not required in patients with normal baseline liver function. 1

Drug Susceptibility Testing

Ethambutol can be discontinued once drug susceptibility confirms full susceptibility to isoniazid and rifampicin, particularly in previously untreated patients with low risk of drug resistance. 1, 2 However, in India where primary isoniazid resistance in Delhi has been documented at 14%, maintaining all four drugs for the full 2-month intensive phase is prudent. 5

Treatment Delivery

Directly Observed Therapy (DOT) is strongly recommended for all tuberculosis patients to ensure adherence and prevent drug resistance. 1, 5 The thrice-weekly regimen specifically facilitates DOT implementation in outpatient settings. 4, 5

Daily dosing is preferred over intermittent dosing when feasible, though 5-days-a-week DOT is an acceptable alternative to 7-days-a-week administration based on clinical experience. 1

Common Pitfalls to Avoid

• Never use pyrazinamide beyond 2 months in the standard regimen, as prolonged use increases hepatotoxicity risk without additional benefit 1, 4
• Do not omit ethambutol in the initial phase unless drug susceptibility is confirmed and primary isoniazid resistance is less than 4% in your community 1
• Avoid streptomycin in pregnant women due to fetal ototoxicity; use the standard four-drug oral regimen instead 5, 6
• Do not extend treatment duration routinely to 9-12 months for spinal TB in adults without specific indications (such as HIV co-infection with poor response or pediatric cases), as 6 months is effective for most cases 1, 6