Initiation of Therapy for Active TB

We have discussed the initiation of TB therapy on a few occasions already this year, including a case where a patient developed toxicity to the medications.  Downtown Toronto we are very fortunate to have fast access to input from our infectious disease colleagues as well as specialized TB clinics, but in other locations starting a patient on TB therapy may fall into the scope of practice of a general internist.  This week's blog post will outline a basic approach to treating a patient for TB based on the Canadian guidelines.   

What do I need to do before starting therapy?

·         Counseling:

o   Importance of adherence to therapy

§  Many patients participate in Directly Observed Therapy (DOT) through the Department of Public Health.

o   Avoidance of alcohol and hepatotoxic medications (ie. acetaminophen, herbal remedies)

o   Need to seek immediate medical attention if the following develop:

§  Symptoms of acute hepatitis such as nausea, vomiting, right upper quadrant pain, jaundice

§  Changes in vision

§  Rash

·         Baseline Testing

o   CBC, lytes, creatinine

o   Liver panel

o   Hepatitis A/B/C and HIV

o   Uric acid

o   Visual acuity, red-green color discrimination

What regimen should I start empirically in most patients?

Drug	Daily Dose	Side Effects	Duration
Rifampin (RMP)	10mg/kg Max 600mg	Drug interactions, hepatitis, rash, cytopenias	6 months
Isoniazid (INH)	5mg/kg Max 300mg	Hepatitis, rash, neuropathy, CNS toxicity, anemia	6 months
Pyrazinamide (PZA)	20-25mg/kg Max 2000mg	Hepatitis, arthralgias, rash, gout	2 months
Ethambutol (EMB)	15-20mg/kg 1600mg	Ocular toxicity, rash	2 months*
Pyridoxine	25mg	Prevention of peripheral neuropathy from INH	While on INH

* Can be stopped as soon as sensitivities back if pan-sensitive

How do I monitor patients once they have been started on therapy?

·         Monitoring Disease Activity:

o   Patients who are AFB smear positive require weekly smears until negative

o   Once smears are negative, cultures should be done at 2 months, and 6 months prior to completion of therapy

·         Monitoring for Complications:

o   Patients on active therapy should be seen at least monthly and should be assessed at each visit for adverse reactions

o   There are no clear guidelines regarding how frequently to repeat liver enzymes

§  This is currently based on clinical judgment and baseline risk for toxicity

What happens if my patient develops drug-induced hepatitis?

·         Risk of hepatitis:

o   Pyrazinamide > Isoniazid > Rifampin

·         Immediate action is required if the transaminases are > 5x ULN or the patient becomes jaundiced

o   Stop all three of the above drugs

o   Start alternative regimen with a fluoroquinolone + one other agent

·         Once transaminases normalize, reintroduce rifampin, followed by isoniazid, followed by pyrazinamide

Special Circumstances:

·         Treatment considerations are different in the following scenarios, and expert consultation should be sought:

o   HIV-associated TB

o   Extrapulmonary TB

o   Multi-drug resistant TB

The information in this blog post was adapted from the Canadian Tuberculosis Standards, 7^th Edition, Chapter 5: Treatment of Tuberculosis Disease.  It can be accessed at www.respiratoryguidelines.ca/sites/all/files/CTB_Standards_EN_Chapter%205.pdf. 

For additional reading check out:

Horsburgh CR, Barry CE, Lange C. Treatment of tuberculosis. NEJM. 2015; 373:2149-2160.