I have new onset dizziness since beginning the continuation phase of tuberculosis therapy with isoniazid and rifampicin; what are the possible causes and how should I initially evaluate and manage it?

New Onset Dizziness During TB Continuation Phase

Most Likely Cause: Isoniazid-Induced Peripheral Neuropathy with Vestibular Involvement

Dizziness during the continuation phase of TB treatment with isoniazid and rifampicin is most commonly caused by isoniazid neurotoxicity, particularly if pyridoxine (vitamin B6) supplementation was not initiated or is inadequate. 1

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Pathophysiology and Risk Factors

• Isoniazid causes neurotoxicity by interfering with pyridoxine metabolism, leading to peripheral neuropathy that can manifest as dizziness, ataxia, or cerebellar dysfunction 2
• The risk is substantially elevated in patients with renal insufficiency, diabetes, alcoholism, malnutrition, HIV infection, or advanced age 1
• Cerebellar syndrome specifically has been documented with isoniazid, presenting as acute cerebellar dysfunction that resolves with dose reduction and pyridoxine supplementation 2

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Initial Evaluation Steps

Immediate Clinical Assessment

• Neurologic examination: Assess for peripheral neuropathy (decreased sensation in stocking-glove distribution, absent ankle reflexes), ataxia, nystagmus, and cerebellar signs (finger-to-nose testing, heel-to-shin testing, Romberg test) 2
• Medication review: Verify whether pyridoxine 25-50 mg daily was prescribed with isoniazid, as this is mandatory for all at-risk patients 1
• Vestibular assessment: Distinguish true vertigo from lightheadedness; check for positional components and associated symptoms (hearing loss, tinnitus)

Laboratory Investigations

• Liver function tests: Rule out hepatotoxicity from isoniazid or rifampicin, as hepatic encephalopathy can present with dizziness 3
• Renal function: Assess creatinine clearance, as renal impairment increases isoniazid accumulation and neurotoxicity risk 2
• Serum glucose: Exclude hypoglycemia, particularly in diabetic patients on rifampicin (which can alter oral hypoglycemic drug levels) 4

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Management Algorithm

Step 1: Immediate Intervention

• Do not discontinue TB therapy unless severe hepatotoxicity or life-threatening reaction is present 1
• Initiate or increase pyridoxine immediately: If not already prescribed, start pyridoxine 50 mg daily; if already on 25-50 mg, increase to 100 mg daily 1, 2
• Continue rifampicin and ethambutol (if part of regimen), as these are not neurotoxic 5

Step 2: If Symptoms Persist After 1 Week of High-Dose Pyridoxine

• Reduce isoniazid dose temporarily: Consider dose reduction while maintaining pyridoxine 100 mg daily 2
• Monitor for improvement: Isoniazid-induced cerebellar dysfunction typically resolves rapidly with dose adjustment and pyridoxine 2

Step 3: If Symptoms Do Not Improve or Worsen

• Discontinue isoniazid temporarily and perform sequential rechallenge after symptom resolution 5
• Alternative regimen if isoniazid cannot be reintroduced: Extend treatment to 9 months total using rifampicin and ethambutol (without pyrazinamide in continuation phase) 1

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Alternative Differential Diagnoses to Consider

Rifampicin-Related Causes

• Drug fever or flu-like syndrome: Rifampicin can cause constitutional symptoms including malaise and dizziness, particularly with twice-weekly dosing 3
• Drug interactions: Rifampicin induces hepatic enzymes and can reduce efficacy of concurrent medications (e.g., oral contraceptives, anticoagulants, antihypertensives), potentially causing secondary symptoms 6

Non-Drug Causes

• Vestibular neuritis or labyrinthitis: Consider if dizziness is true vertigo with sudden onset and no other neurologic findings
• Orthostatic hypotension: Assess blood pressure in supine and standing positions, particularly in patients on antihypertensives
• Anemia or electrolyte disturbances: Check complete blood count and electrolytes if constitutional symptoms are present

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Critical Pitfalls to Avoid

• Never assume dizziness is benign without neurologic examination: Isoniazid cerebellar syndrome can progress rapidly if not recognized 2
• Never discontinue all TB drugs simultaneously for non-life-threatening side effects: This promotes drug resistance and treatment failure 5
• Never omit pyridoxine in at-risk patients: Prophylactic pyridoxine 25-50 mg daily is mandatory for patients with diabetes, renal failure, HIV, malnutrition, alcoholism, pregnancy, or advanced age 1, 4
• Never extend continuation phase beyond 4 months for drug-susceptible TB without specific indication: Only patients with cavitary disease and positive 2-month cultures require 7-month continuation phase 1

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Monitoring During Continuation Phase

• Monthly clinical follow-up is recommended for all patients on isoniazid-rifampicin continuation therapy 6
• Baseline and periodic liver function tests are essential, especially during the first 2 months, but monthly monitoring is adequate during continuation phase if stable 5
• Visual acuity monitoring monthly if ethambutol is part of the regimen 1