title: Flu-like and Other Systemic Drug Reactions Among Persons Receiving Weekly Rifapentine Plus Isoniazid or Daily Isoniazid for Treatment of Latent Tuberculosis Infection in the PREVENT Tuberculosis Study.
abstract: BACKGROUND
  Weekly rifapentine plus isoniazid for 3 months (3HP) is as effective as daily isoniazid for 9 months (9H) for latent tuberculosis infection in high-risk persons, but there have been reports of possible flu-like syndrome.
  
  
  METHODS
  We identified clinically significant systemic drug reactions (SDR) and evaluated risk factors in patients who did not complete treatment in the PREVENT Tuberculosis study.
  
  
  RESULTS
  Among 7552 persons who received ≥ 1 dose of study drug, 153 had a SDR: 138/3893 (3.5%) with 3HP vs 15/3659 (0.4%) with 9H (P < .001). In the 3HP arm, 87 (63%) had flu-like syndrome and 23 (17%) had cutaneous reactions; 13/3893 (0.3%) had severe reactions (6 were hypotensive) and 6 reported syncope. Symptoms occurred after a median of 3 doses, and 4 hours after the dose; median time to resolution was 24 hours. There were no deaths. In multivariate logistic regression analysis, factors independently associated with SDR included receipt of 3HP (adjusted odds ratio [aOR] 9.4; 95% confidence interval [CI], 5.5, 16.2), white non-Hispanic race/ethnicity (aOR 3.3; 95% CI, 2.3, 4.7), female sex (aOR 2.0; 95% CI, 1.4, 2.9), age ≥ 35 years (aOR 2.0; 95% CI, 1.4, 2.9), and lower body mass index (body mass index [BMI]; P = .009). In a separate multivariate analysis among persons who received 3HP, severe SDR were associated with white non-Hispanic race/ethnicity (aOR 5.4; 95% CI, 1.8, 16.3), and receipt of concomitant non-study medications (aOR 5.9; 95% CI, 1.3, 27.1).
  
  
  CONCLUSIONS
  SDR were more common with 3HP, and mostly flu-like. Persons of white race, female sex, older age, and lower BMI were at increased risk. Severe reactions were rare and associated with 3HP, concomitant medication, and white race. The underlying mechanism is unclear.
  
  
  BACKGROUND
  NCT00023452.
authors.affiliation: Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Sterling
authors.affiliation: Centers for Disease Control and Prevention CDC Foundation, Research Collaboration, Atlanta, Georgia.
authors.forename: Ruth N
authors.initials: RN
authors.lastname: Moro
authors.affiliation: Centers for Disease Control and Prevention.
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Borisov
authors.affiliation: Vanderbilt University School of Medicine, Nashville, Tennessee Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Australia.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Phillips
authors.affiliation: New York-Presbyterian Hospital/Weill Cornell Medical Center, New York.
authors.forename: Gillian
authors.initials: G
authors.lastname: Shepherd
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Newton Franklin
authors.initials: NF
authors.lastname: Adkinson
authors.affiliation: University of North Texas Health Science Center at Ft. Worth.
authors.forename: Stephen
authors.initials: S
authors.lastname: Weis
authors.affiliation: Centers for Disease Control and Prevention.
authors.forename: Christine
authors.initials: C
authors.lastname: Ho
authors.affiliation: Centers for Disease Control and Prevention.
authors.forename: Margarita Elsa
authors.initials: ME
authors.lastname: Villarino
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology / Q000473:pathology*; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000008:administration & dosage / Q000009:adverse effects*; D055985:Latent Tuberculosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012140:Respiratory Tract Diseases / Q000139:chemically induced* / Q000453:epidemiology / Q000473:pathology*; D012293:Rifampin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
chemical_list: D000995:Antitubercular Agents; D007538:Isoniazid; D012293:Rifampin; C018421:rifapentine
keywords: adverse drug reaction; flu-like syndrome; isoniazid; rifapentine; treatment of latent M. tuberculosis infection