Relative and Absolute Risk of Tendon Rupture with Fluoroquinolone and Concomitant Fluoroquinolone/Corticosteroid Therapy

Population-Based Nested Case-Control Study

Daniel R. Morales (Lead / Corresponding author), Jim Slattery, Alexandra Pacurariu, Luis Pinheiro, Patricia McGettigan, Xavier Kurz

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background and Objective: Tendon rupture can result from fluoroquinolone exposure. The objective of this study was to quantify relative and absolute risk and determine how risk is affected by timing of exposure.

Methods: The UK Health Improvement Network primary care database was used to perform a nested case-control study measuring the association between fluoroquinolone exposure and tendon rupture. Adults with tendon rupture were matched on age, sex, general practice and calendar time to four controls selected from a cohort prescribed systemic fluoroquinolone or co-amoxiclav antibiotics. The relative and absolute risk of tendon rupture with fluoroquinolone exposure was calculated.

Results: Current fluoroquinolone exposure was associated with an increased risk of any tendon rupture (adjusted incidence rate ratio [aIRR] 1.61, 95% CI 1.25-2.09) and Achilles tendon rupture (aIRR 3.14, 95% CI 2.11-4.65) that persisted for 60 days. Risk increased with cumulative exposure and was greatest when co-prescribed with oral corticosteroids (aIRR 19.36, 95% CI 7.78-48.19 for Achilles tendon rupture). The adjusted rate difference (aRD) with fluoroquinolone exposure was 2.9 and 2.1 per 10,000 patients for any and Achilles tendon rupture, respectively, and was greatest in people aged ≥ 60 years prescribed concomitant oral corticosteroid therapy (aDR 19.6 for any tendon and 6.6 Achilles tendon rupture per 10,000). No association was seen with co-amoxiclav or statin exposure, or with biceps or other tendon ruptures.

Conclusions: Risk of tendon rupture with fluoroquinolones depends on timing, cumulative dose and concomitant exposure to oral corticosteroids. Absolute risk significantly varied by age and concomitant corticosteroid exposure, affecting elderly patients the greatest.

Original languageEnglish
Pages (from-to)205-213
Number of pages9
JournalClinical Drug Investigation
Volume39
Issue number2
Early online date21 Nov 2018
DOIs
Publication statusPublished - Feb 2019

Fingerprint

Fluoroquinolones
Tendons
Case-Control Studies
Rupture
Adrenal Cortex Hormones
Population
Achilles Tendon
Therapeutics
Amoxicillin-Potassium Clavulanate Combination
Incidence
Hydroxymethylglutaryl-CoA Reductase Inhibitors
General Practice
Primary Health Care
Databases
Anti-Bacterial Agents

Keywords

  • Achilles Tendon/injuries
  • Adrenal Cortex Hormones/adverse effects
  • Adult
  • Aged
  • Anti-Bacterial Agents/adverse effects
  • Case-Control Studies
  • Female
  • Fluoroquinolones/adverse effects
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Risk
  • Rupture, Spontaneous
  • Tendon Injuries/chemically induced

Cite this

Morales, Daniel R. ; Slattery, Jim ; Pacurariu, Alexandra ; Pinheiro, Luis ; McGettigan, Patricia ; Kurz, Xavier. / Relative and Absolute Risk of Tendon Rupture with Fluoroquinolone and Concomitant Fluoroquinolone/Corticosteroid Therapy : Population-Based Nested Case-Control Study. In: Clinical Drug Investigation. 2019 ; Vol. 39, No. 2. pp. 205-213.
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abstract = "Background and Objective: Tendon rupture can result from fluoroquinolone exposure. The objective of this study was to quantify relative and absolute risk and determine how risk is affected by timing of exposure.Methods: The UK Health Improvement Network primary care database was used to perform a nested case-control study measuring the association between fluoroquinolone exposure and tendon rupture. Adults with tendon rupture were matched on age, sex, general practice and calendar time to four controls selected from a cohort prescribed systemic fluoroquinolone or co-amoxiclav antibiotics. The relative and absolute risk of tendon rupture with fluoroquinolone exposure was calculated.Results: Current fluoroquinolone exposure was associated with an increased risk of any tendon rupture (adjusted incidence rate ratio [aIRR] 1.61, 95{\%} CI 1.25-2.09) and Achilles tendon rupture (aIRR 3.14, 95{\%} CI 2.11-4.65) that persisted for 60 days. Risk increased with cumulative exposure and was greatest when co-prescribed with oral corticosteroids (aIRR 19.36, 95{\%} CI 7.78-48.19 for Achilles tendon rupture). The adjusted rate difference (aRD) with fluoroquinolone exposure was 2.9 and 2.1 per 10,000 patients for any and Achilles tendon rupture, respectively, and was greatest in people aged ≥ 60 years prescribed concomitant oral corticosteroid therapy (aDR 19.6 for any tendon and 6.6 Achilles tendon rupture per 10,000). No association was seen with co-amoxiclav or statin exposure, or with biceps or other tendon ruptures.Conclusions: Risk of tendon rupture with fluoroquinolones depends on timing, cumulative dose and concomitant exposure to oral corticosteroids. Absolute risk significantly varied by age and concomitant corticosteroid exposure, affecting elderly patients the greatest.",
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Relative and Absolute Risk of Tendon Rupture with Fluoroquinolone and Concomitant Fluoroquinolone/Corticosteroid Therapy : Population-Based Nested Case-Control Study. / Morales, Daniel R. (Lead / Corresponding author); Slattery, Jim; Pacurariu, Alexandra; Pinheiro, Luis; McGettigan, Patricia; Kurz, Xavier.

In: Clinical Drug Investigation, Vol. 39, No. 2, 02.2019, p. 205-213.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Relative and Absolute Risk of Tendon Rupture with Fluoroquinolone and Concomitant Fluoroquinolone/Corticosteroid Therapy

T2 - Population-Based Nested Case-Control Study

AU - Morales, Daniel R.

AU - Slattery, Jim

AU - Pacurariu, Alexandra

AU - Pinheiro, Luis

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AU - Kurz, Xavier

N1 - No source of funding was used for this study

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AB - Background and Objective: Tendon rupture can result from fluoroquinolone exposure. The objective of this study was to quantify relative and absolute risk and determine how risk is affected by timing of exposure.Methods: The UK Health Improvement Network primary care database was used to perform a nested case-control study measuring the association between fluoroquinolone exposure and tendon rupture. Adults with tendon rupture were matched on age, sex, general practice and calendar time to four controls selected from a cohort prescribed systemic fluoroquinolone or co-amoxiclav antibiotics. The relative and absolute risk of tendon rupture with fluoroquinolone exposure was calculated.Results: Current fluoroquinolone exposure was associated with an increased risk of any tendon rupture (adjusted incidence rate ratio [aIRR] 1.61, 95% CI 1.25-2.09) and Achilles tendon rupture (aIRR 3.14, 95% CI 2.11-4.65) that persisted for 60 days. Risk increased with cumulative exposure and was greatest when co-prescribed with oral corticosteroids (aIRR 19.36, 95% CI 7.78-48.19 for Achilles tendon rupture). The adjusted rate difference (aRD) with fluoroquinolone exposure was 2.9 and 2.1 per 10,000 patients for any and Achilles tendon rupture, respectively, and was greatest in people aged ≥ 60 years prescribed concomitant oral corticosteroid therapy (aDR 19.6 for any tendon and 6.6 Achilles tendon rupture per 10,000). No association was seen with co-amoxiclav or statin exposure, or with biceps or other tendon ruptures.Conclusions: Risk of tendon rupture with fluoroquinolones depends on timing, cumulative dose and concomitant exposure to oral corticosteroids. Absolute risk significantly varied by age and concomitant corticosteroid exposure, affecting elderly patients the greatest.

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KW - Adrenal Cortex Hormones/adverse effects

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KW - Fluoroquinolones/adverse effects

KW - Humans

KW - Incidence

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KW - Middle Aged

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KW - Tendon Injuries/chemically induced

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