Can Isoniazid Be Given for Latent TB in This Patient?
Yes, isoniazid can be safely administered to this patient with latent TB who is taking methotrexate for psoriatic arthritis, along with aspirin and amlodipine for heart failure, given that all baseline laboratory tests are normal. However, close monthly monitoring for hepatotoxicity is essential due to the combination of two potentially hepatotoxic medications.
Evidence Supporting Combined Use
The combination of methotrexate and isoniazid is well-tolerated in patients with inflammatory arthritis. A retrospective study of 44 patients with rheumatoid arthritis treated concomitantly with both drugs showed that transient increases in liver function tests occurred in only 11% of patients, and none exceeded twice the upper limit of normal, with all abnormalities resolving spontaneously without intervention 1. This provides reassuring real-world evidence for this specific drug combination.
Treatment Regimen Options
The CDC strongly recommends several options for latent TB treatment 2:
- 9 months of daily isoniazid - the traditional regimen with >90% efficacy if completed, though it has lower completion rates 3, 4
- 4 months of daily rifampin - strongly recommended with better completion rates and less hepatotoxicity than isoniazid 2, 4
- 3 months of once-weekly isoniazid plus rifapentine - strongly recommended if daily medication is challenging 2
For this patient on methotrexate, isoniazid remains an appropriate choice, but rifampin-based regimens may offer advantages with shorter duration and potentially less hepatotoxicity 2, 4.
Baseline Testing Requirements
Before initiating treatment, the following is required 3:
- Baseline liver function tests (AST/ALT and bilirubin) - already completed and normal in this patient
- Rule out active TB through history, physical examination, and chest radiography 2
- Baseline testing is specifically indicated for patients taking other medications for chronic medical conditions 3
Monitoring Protocol During Treatment
Monthly clinical monitoring is essential and effective for preventing severe hepatotoxicity 3, 5:
- Monthly visits to assess for symptoms of hepatotoxicity (nausea, vomiting, abdominal pain, jaundice, dark urine, fatigue) 5, 2
- Educate the patient to stop treatment immediately if symptoms of hepatotoxicity develop 5
- Periodic liver function testing should be considered given the patient is on methotrexate and other chronic medications 3
- Withhold isoniazid if transaminase levels exceed 3 times the upper limit of normal with symptoms, or 5 times the upper limit if asymptomatic 3
Drug Interaction Considerations
There are no significant drug interactions between isoniazid and the patient's current medications 5:
- Aspirin and amlodipine do not interact significantly with isoniazid
- Methotrexate and isoniazid share hepatotoxicity risk but can be safely combined with monitoring 1
- Heart failure itself is not a contraindication to isoniazid treatment
Important Caveats and Pitfalls
Active hepatitis and end-stage liver disease are relative contraindications to isoniazid 3, but this patient has normal baseline liver function tests.
Monitor complete blood count in addition to liver function tests, especially during the first month, as rare cases of neutropenia have been reported with anti-tuberculosis treatment in patients on methotrexate 6.
Ensure active TB is definitively ruled out before starting treatment - adding a single drug to unrecognized active TB can lead to drug resistance 3, 2.
Consider rifampin-based regimens as alternatives if concerns about dual hepatotoxicity arise, though the evidence supports safe use of isoniazid with methotrexate 2, 1.
Treatment Algorithm
- Confirm latent TB diagnosis and rule out active disease with chest X-ray 2
- Review baseline labs (already normal in this patient) 3
- Initiate isoniazid 300 mg daily (or 5 mg/kg) for 9 months 3, 7
- Schedule monthly follow-up visits for clinical assessment 5, 2
- Check liver function tests if any symptoms develop or periodically given methotrexate use 3
- Continue methotrexate, aspirin, and amlodipine without interruption 1