The Relative Risk of Achilles Tendon Injury in Patients Taking Quinolones

Jupiter, Daniel C.; Fang, Xiao; Ashmore, Zachary; Shibuya, Naohiro; Mehta, Hemalkumar B.

doi:10.1002/phar.2162

Cited by 13 publications

(13 citation statements)

References 29 publications

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“…Fluoroquinolones (FQ) are among the most widely prescribed antibiotics in the outpatient setting 1 2 due to their broad spectrum treatment of bacteria found in respiratory, urinary, joint, and skin infections. Several observational studies have reported the association between the use of FQs and tendinitis and tendon rupture (TR), especially of the Achilles tendon [3][4][5][6][7][8][9][10][11][12] and the US Food and Drug Administration (FDA) issued black box warnings to FQ antibiotics beginning in 2008. 13 The warning was updated in 2016 to recommend using alternative antibiotics when possible.…”

Section: Introductionmentioning

confidence: 99%

Association between tendon ruptures and use of fluoroquinolone, and other oral antibiotics: a 10-year retrospective study of 1 million US senior Medicare beneficiaries

et al. 2020

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ObjectivesTo assess the association of fluoroquinolone use with tendon ruptures compared with no fluoroquinolone and that of the four most commonly prescribed non-fluoroquinolone antibiotics in the USA.DesignRetrospective observational study.SettingUS seniors enrolled in the federal old-age, survivor’s insurance programme.Participants1 009 925 Medicare fee-for-service beneficiaries and their inpatient, outpatient, prescription drug records were used.InterventionsSeven oral antibiotics, fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) and amoxicillin, amoxicillin-clavulanate, azithromycin and cephalexin.Primary and secondary outcome measuresAll tendon ruptures combined, and three types of tendon ruptures by anatomic site, Achilles tendon rupture, rupture of rotator cuff and other tendon ruptures occurred in 2007–2016.ResultsOf three fluoroquinolones, only levofloxacin exhibited a significant increased risk of tendon ruptures—16% (HR=1.16; 95% CI 1.06 to 1.28), and 120% (HR=2.20; 95% CI 1.50 to 3.24) for rotator cuff and Achilles tendon rupture, respectively, in the ≤30 days window. Ciprofloxacin (HR=0.96; 95% CI 0.89 to 1.03) and moxifloxacin (HR=0.59; 95% CI 0.37 to 0.93) exhibited no increased risk of tendon ruptures combined.Among the non-fluoroquinolone antibiotics, cephalexin exhibited increased risk of combined tendon ruptures (HR=1.31; 95% CI 1.22 to 1.41) and modest to large risks across all anatomic rupture sites (HRs 1.19–1.93) at ≤30 days window. Notably, the risk of levofloxacin never exceeded the risk of the non-fluoroquinolone, cephalexin in any comparison.ConclusionsIn our study, fluoroquinolones as a class were not associated with the increased risk of tendon ruptures. Neither ciprofloxacin nor moxifloxacin exhibited any risk for tendon ruptures. Levofloxacin did exhibit significant increased risk. Cephalexin with no reported effect on metalloprotease activity had an equal or greater risk than levofloxacin; so we question whether metalloprotease activity has any relevance to observed associations with tendon rupture. Confounding by indication bias may be more relevant and should be given more consideration as explanation for significant associations in observational studies of tendon rupture.

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Section: Introductionmentioning

confidence: 99%

Association between tendon ruptures and use of fluoroquinolone, and other oral antibiotics: a 10-year retrospective study of 1 million US senior Medicare beneficiaries

et al. 2020

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“…However, the small number of patients with a history of diabetes or renal disease may make it difficult to detect differences in the incidence of AEs between the two groups. Steroid use is often considered to be a risk factor for FQ-induced tendinopathy in adults 19–23 , but it is unclear whether this observation applies to children as well. The non-significant association between steroid use and the occurrence of side effects observed in the current study may be associated with differences in patterns of steroid use and pharmacokinetic/pharmacodynamic characteristics between children and adults.…”

Section: Discussionmentioning

confidence: 99%

“…The results of this study suggest that among the different subtypes of musculoskeletal AEs, soft tissue disorders such as tendinopathy may be a concern in children as well as in adults. Several studies have demonstrated the association between FQ use and soft tissue disorders such as tendinitis and tendon rupture in adults 18,23,24 . Based on prior findings, the US FDA issued a black box warning regarding tendon injuries after FQ use in 2008 and added warning and caution notices on medication labels 25 .…”

Section: Discussionmentioning

confidence: 99%

“…The study also included demographic characteristics such as age and sex. Medical characteristics known to be confounders, such as comorbidities and prescription drug use, were selected according to previous studies 18,19,23,24 . Comorbidities were based on diagnostic codes prior to the index date and included asthma, diabetes mellitus, renal disease, liver disease, and inflammatory bowel disease.…”

Section: Methodsmentioning

confidence: 99%

“…Prescription drugs used in in- and outpatient settings within one year prior to the index date were identified using the first four digits of the Korean national drug codes. Prescription drugs were selected according to criteria established by previous studies 18,23 and by a list of drugs with a substantial number of musculoskeletal AE reports 35 . Drugs such as systemic corticosteroids, retinoids, aminoglycosides, proton pump inhibitors, and tetracyclines were included.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Real-world safety evaluation of musculoskeletal adverse events associated with Korean pediatric fluoroquinolone use: a nationwide longitudinal retrospective cohort study

Kim

Paik

Khan

et al. 2019

Sci Rep

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Though the pediatric use of fluoroquinolones (FQs) is limited for musculoskeletal safety concerns, the clinical usefulness still exists. This study examined the association between FQs and musculoskeletal adverse events (AEs) as well as the possible risk factors associated with the pediatric FQs uses. This population-based, longitudinal, retrospective study was conducted using Korean National Sample Cohort database originating between 2002 and 2015. An FQ-treated pediatric cohort (<18 years old) was compared to a control treated with amoxicillin. Propensity score matching (PSM) and a Cox proportional hazard model was used to estimate the hazard ratio (HR) for a diagnosis of musculoskeletal AEs within 60 days of the first prescription. Among one million participants, total of 15,706 and 147,840 children were eligible for the FQ and amoxicillin cohorts, respectively. The PSM cohorts showed a slightly increased risk of musculoskeletal AEs after FQ treatment (HR, 1.19; 95% confidence interval, 1.01–1.40; p = 0.042). This association was stronger in males, older patients, and some FQs users. This study indicates that pediatric FQ use is associated with a risk of musculoskeletal AEs and that FQ use should be carefully monitored in groups with certain risk factors. Well-designed pragmatic trials could be expected to clarify these issues.

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Common Painful Foot and Ankle Conditions

Cooper

2023

JAMA

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ImportanceMorton neuroma, plantar fasciitis, and Achilles tendinopathy are foot and ankle conditions that are associated with pain and disability, but they can respond to nonoperative treatment.ObservationsMorton neuroma, consisting of interdigital neuronal thickening and fibrosis, is characterized by burning pain in the ball of the foot and numbness or burning pain that may radiate to the affected toes (commonly the third and fourth toes). First-line nonoperative therapy consists of reducing activities that cause pain, orthotics, and interdigital corticosteroid injection; however, approximately 30% of patients may not respond to conservative treatment. Plantar fasciitis accounts for more than 1 million patient visits per year in the US and typically presents with plantar heel pain. Fifteen years after diagnosis, approximately 44% of patients continue to have pain. First-line nonoperative therapy includes stretching of the plantar fascia and foot orthotics, followed by extracorporeal shockwave therapy, corticosteroid injection, or platelet-rich plasma injection. Midportion Achilles tendinopathy presents with pain approximately 2 to 6 cm proximal to the Achilles insertion on the heel. The primary nonoperative treatment involves eccentric strengthening exercises, but extracorporeal shockwave therapy may be used.Conclusions and RelevanceMorton neuroma, plantar fasciitis, and Achilles tendinopathy are painful foot and ankle conditions. First-line therapies are activity restriction, orthotics, and corticosteroid injection for Morton neuroma; stretching and foot orthotics for plantar fasciitis; and eccentric strengthening exercises for Achilles tendinopathy.

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The Relative Risk of Achilles Tendon Injury in Patients Taking Quinolones

Cited by 13 publications

References 29 publications

Association between tendon ruptures and use of fluoroquinolone, and other oral antibiotics: a 10-year retrospective study of 1 million US senior Medicare beneficiaries

Association between tendon ruptures and use of fluoroquinolone, and other oral antibiotics: a 10-year retrospective study of 1 million US senior Medicare beneficiaries

Real-world safety evaluation of musculoskeletal adverse events associated with Korean pediatric fluoroquinolone use: a nationwide longitudinal retrospective cohort study

Common Painful Foot and Ankle Conditions

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