How to reintroduce tuberculosis (TB) treatment after recovery from skin side effects?

Reintroduction of TB Treatment After Recovery from Skin Side Effects

After recovery from skin side effects, tuberculosis treatment should be reintroduced using a sequential drug reintroduction protocol, starting with one drug at a time at low doses and gradually increasing to therapeutic doses while monitoring for recurrence of reactions. 1

Sequential Drug Reintroduction Protocol

• Stop all TB medications during an active skin reaction and wait for complete resolution of symptoms before attempting reintroduction 1
• Begin reintroduction only after skin lesions have completely healed and any abnormal laboratory values have normalized 1, 2
• Reintroduce drugs one at a time with a 2-3 day observation period between each new drug to clearly identify the offending agent if reactions recur 1

Specific Reintroduction Schedule

• Isoniazid reintroduction: Start at 50 mg/day, increase to 300 mg/day after 2-3 days if no reaction occurs, then continue for 2-3 more days before adding the next drug 1
• Rifampicin reintroduction: Start at 75 mg/day, increase to 300 mg after 2-3 days, then increase to weight-appropriate dose after 2-3 more days 1
• Pyrazinamide reintroduction: Start at 250 mg/day, increase to 1.0 g after 2-3 days, then increase to weight-appropriate dose 1
• Ethambutol reintroduction: Follow similar gradual dose escalation pattern as other medications 1

Monitoring During Reintroduction

• Perform daily clinical monitoring during the reintroduction phase, watching for recurrence of rash, pruritus, fever, or other symptoms 1, 2
• If reactions recur, immediately stop the most recently added drug and identify it as the offending agent 1
• Consider more intensive monitoring for patients with HIV, as they have higher risk of adverse drug reactions (up to 92% of TB-associated cutaneous adverse drug reactions occur in HIV-infected patients) 3

Alternative Regimens When a Drug Must Be Excluded

If a drug is confirmed as the cause of the reaction and must be permanently excluded:

• If isoniazid cannot be used: Continue treatment for at least 12 months with rifampicin and ethambutol, supplemented with pyrazinamide for the initial two months 1
• If pyrazinamide cannot be used: Treat with rifampicin and isoniazid for nine months, supplemented with ethambutol for the initial two months 1
• If ethambutol cannot be used: The six-month regimen of rifampicin and isoniazid supplemented by two months' initial pyrazinamide is satisfactory 1
• If rifampicin cannot be used: Consider consultation with a TB specialist as rifampicin is a cornerstone of treatment 1, 2

Risk Factors to Consider

• Be especially vigilant in patients with HIV infection, who have significantly higher risk of cutaneous adverse drug reactions 4, 3
• Other risk factors include polypharmacy (21.3%), advanced age (19.1%), autoimmune disorders (6.4%), and pre-existing renal or liver disorders (4.3%) 4
• Rifampicin is implicated in 57% of reintroduction reactions, followed by isoniazid (22%) and pyrazinamide (13%) 3

Special Considerations

• For severe reactions like Stevens-Johnson syndrome or toxic epidermal necrolysis, consider permanent avoidance of the offending drug 1, 5
• For multidrug-resistant TB, treatment should be conducted by physicians with substantial experience in managing complex resistant cases 1
• In cases where drug options are extremely limited due to resistance patterns, desensitization protocols may be considered under the cover of two other anti-tuberculosis drugs 1, 6

Patient Education

• Counsel patients about potential adverse effects before and during treatment 2
• Educate patients to report any symptoms immediately, including rash, itching, fever, or malaise 2
• Ensure patients understand the importance of completing TB treatment despite prior adverse reactions 2