Dosing for oral* rechallenges with antituberculosis drugs following nonanaphylactic allergic reactions (adults)

Drug	Dose – Day 1	Dose – Day 2^¶	Dose – Day 3
Isoniazid	50 mg	300 mg	Usual daily dose^Δ
Rifampin	75 mg^◊	300 mg	600 mg
Pyrazinamide	250 mg	1 g	Usual daily dose^Δ
Ethionamide	125 mg	375 mg	500 to 750 mg
Cycloserine	125 mg^§	250 mg	500 to 750 mg
Ethambutol	100 mg	400 mg	Usual daily dose^Δ
Para-aminosalicylic acid	1 g^¥	4 g	6 to 8 g
Streptomycin*	125 mg	500 mg	Usual daily dose^Δ
Doses for the following drugs were not supplied by the Philadelphia program but have been extrapolated (based on the doses above) to the following:
Amikacin*	125 mg	500 mg	Usual daily dose^Δ
Capreomycin*	125 mg	500 mg	Usual daily dose^Δ
Levofloxacin	50 mg^‡	200 to 250 mg	Usual daily dose^Δ

Reintroducing antituberculosis drugs (rechallenge) should only be considered in patients who have experienced a nonanaphylactic reaction, such as isolated hives (urticaria) or rash without systemic symptoms or organ involvement. Reintroduction would not be appropriate for a patient who had symptoms of possible anaphylaxis (ie, the rapid onset of some combination of hives, angioedema, airway compromise, bronchospasm, nausea and vomiting, hypotension) or of a more serious systemic hypersensitivity reaction, such as Stevens-Johnson syndrome or toxic epidermal necrolysis (ie, blistering or peeling of the skin, high fever, flu-like symptoms, or involvement of mucous membranes).
Drugs should be reintroduced one at a time. If the patient was taking several drugs at the time of the reaction and all were stopped, the most important one should be reintroduced first. If the first drug causes no adverse reaction, then it is continued and challenge to the second drug is performed, etc, until the patient is again taking all the required meds and/or the drug causing the reaction is identified.
The patient can be premedicated with oral diphenhydramine 25 mg with or without a small dose of oral glucocorticoid (eg, prednisone 10 to 20 mg) given 30 minutes before the first dose. If the initial dose is well-tolerated, give diphenhydramine 30 minutes before the second dose, without the prednisone. If that is well-tolerated, give the third dose without premedication.
Premedication may not prevent cutaneous symptoms entirely but typically makes the reaction less severe. Patients who develop a mild rash as a result of reintroduction may benefit from a short course of low-dose glucocorticoids, allowing the drug to be continued.

* All rechallenge regimens are based upon oral administration except for streptomycin, amikacin, capreomycin which may be administered intramuscularly.
¶ If the day 2 dose is less than the normal recommended dose based on the patient's weight, increase the day 3 dose to the correct weight-based dose (eg, dose of ethambutol for a 70 kg patient: day 1 = 100 mg, day 2 = 500 mg, and day 3 = 1000 mg).
Δ Usual daily dose means the daily dose that the individual patient in question will require, which may vary by regimen and patient characteristics.
◊ Rifampin is available in 150 mg capsules. Empty capsule contents into a small amount of applesauce or jelly and administer one-half.
§ Cycloserine comes in 250 mg capsules. Empty capsule contents into a small amount of no sugar added chocolate pudding or grape jelly and administer one-half.
¥ Para-aminosalicylic acid comes in 4 gram packets. Suspended in orange juice and administer one-quarter.
‡ Levofloxacin is available in an oral solution of 25 mg/mL.

Adapted from: Curry International Tuberculosis Center and California Department of Public Health, 2016: Drug-Resistant Tuberculosis: A Survival Guide for Clinicians, Third Edition, p. 255.
Additional data from:

Philadelphia Tuberculosis Control Program, Lawrence Flick Memorial Tuberculosis Clinic. Guidelines for the Management of Adverse Drug Effects of Antimycobacterial Agents. Philadelphia: Philadelphia Tuberculosis Control Program, 1998.
Peloquin CA, Durbin D, Childs J, et al. Stability of antituberculosis drugs mixed in food. Clin Infect Dis 2007; 45:521.

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Dosing for oral* rechallenges with antituberculosis drugs following nonanaphylactic allergic reactions (adults)