Published: 5 September 2024

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Drug-induced tendinopathy

Published: 5 September 2024
Prescriber Update 45(3): 51–53
September 2024

Key messages

  • Fluoroquinolones, long-term glucocorticoids, statins and aromatase inhibitors are the most common medicine classes associated with tendinopathy.
  • Progressive tendon degeneration without inflammation is a typical sign of drug-induced tendinopathy.
  • Although the Achilles tendon is most commonly affected, drug-induced tendinopathy can occur in any tendon.


Tendonitis and tendon rupture have recently been associated with aromatase inhibitors, along with tenosynovitis. This article reviews tendon disorders with the most common classes of medicines.

Terminology of tendon disorders

Tendon disorders include tendonitis (tendon inflammation), tendon rupture (tendon tears) and tenosynovitis (inflammation of the tendon sheath).1 The term tendonitis is often used to describe a broad range of tendon conditions. However, where inflammation is minimal or absent, tendinopathy may be more accurate.2

Inside a tendon

Tenoblasts and tenocytes make up 90% of cells in the tendon.2 Together, they generate collagen and elastin fibres, as well as extracellular matrix components.2 Chondrocytes make up the remaining 10% of tendon cells and these are found at entheses (tendon-bone junctions).3

Classic drug-induced tendinopathy shows signs of progressive tendon degeneration without inflammation.3

Medicines associated with tendinopathy

Drug-induced tendinopathy is most commonly associated with fluoroquinolones, long-term treatment with glucocorticoids, statins and aromatase inhibitors.3 Table 1 summarises characteristics of drug-induced tendinopathy with these medicine classes.

Fluoroquinolones

Tendinopathy can occur with any fluoroquinolone (eg, ciprofloxacin, moxifloxacin, norfloxacin) and at any dose and route of administration.3 It is usually an acute event occurring as early as within 48 hours but has been reported to occur up to several months after discontinuation of treatment.4–6 Tendinopathy with fluoroquinolones may be prolonged, disabling and irreversible.4–6

Discontinue fluoroquinolone treatment at the first sign of tendonitis (eg, pain, swelling, inflammation) and use alternative treatment.4–6 Advise patients to rest the affected limb and avoid inappropriate physical exercise.5

Long-term glucocorticoids

Tendinopathy usually occurs after at least three months of treatment with an oral or inhaled glucocorticoid.3 Patients with autoimmune connective tissue disorders (eg, rheumatoid arthritis, systemic lupus erythematosus) treated with long-term oral glucocorticoids are particularly at risk.2,3

Statins3

Statin-induced tendinopathy can occur at any dose and about 8 to 10 months after exposure. Discontinue statin treatment if tendinopathy is suspected. Tendinopathy may recur if statin treatment is restarted.

Aromatase inhibitors

Tenosynovitis, particularly of the hands and wrists, has been linked with aromatase inhibitors (eg, anastrozole, letrozole, exemestane).3 The onset time is reported to range from 2 weeks to 19 months.2 More recently, cases of tendonitis and tendon rupture have also been reported in association with aromatase inhibitors.1

Closely monitor patients with tendon disorders and initiate appropriate measures such as immobilisation of the affected limb.7,8

Medsafe has requested the data sheets for aromatase inhibitors be updated to include more information on tendon disorders.

Table 1: Characteristics of drug-induced tendinopathy associated with the four main medicine classes

Medicine class Route and dose Time to onset Type and site
Fluoroquinolonesa,b any within 48 hours Achilles tendon in 90% of cases, of which 40% of cases lead to tendon rupture
Glucocorticoidsb oral, inhaled ≥3 months Achilles tendon and other large lower limb tendons, leading to rupture several years after starting a glucocorticoid
Statinsb any dose 8-10 months Achilles tendon in just over 50% of cases, of which, one-third result in tendon rupture
Aromatase inhibitorsb–d unknown 2 weeks to 19 months Tenosynovitis of the hands and wrists, tendonitis, tendon rupture (rare)


Sources:

  1. Medicine data sheets, available at: www.medsafe.govt.nz/Medicines/infoSearch.asp
  2. Bolon B. 2017. Mini-review: Toxic tendinopathy. Toxicology Pathology 45(7): 834-7. DOI: 10.1177/0192623317711614 (accessed 18 June 2024).
  3. Health Canada. 2023. Summary Safety Review – Third Generation Aromatase Inhibitors (anastrozole, exemestane, letrozole) – Assessing the Potential Risk of Tendon Disorders 17 January 2023. URL: dhpp.hpfb-dgpsa.ca/review-documents/resource/SSR00289 (accessed 18 June 2024).
  4. Kirchgesner T, et al. 2014. Drug-induced tendinopathy: From physiology to clinical applications. Joint Bone Spine 81(6): 485-92. DOI: https://doi.org/10.1016/j.jbspin.2014.03.022 (accessed 18 June 2024).

Other

Drug-induced tendinopathy has also been reported after exposure to several other medicines, but the evidence is less consistent.2 These include anabolic steroids, isotretinoin and antiretroviral agents (especially protease inhibitors).3

Risk factors

Risk factors for drug-induced tendinopathy include:3

  • advanced age (because of deterioration in tenocytes)
  • obesity and physical exertion (because of high loads and sudden shifts in axial stress)
  • pre-existing disease such as autoimmune connective tissue disorders and renal failure
  • treatment with two or more medicines known to induce tendinopathy.

New Zealand case reports

From 1 January 2014 to 30 June 2024, Medsafe and the Centre for Adverse Reactions Monitoring (CARM) received 103 case reports of tendon disorders with medicines (excluding vaccines). The top four suspect medicines in these reports were ciprofloxacin (n=73), norfloxacin (n=9), zoledronic acid (n=5) and prednisone (n=3).

In these 103 cases, the median age was 65 years and the median time to onset was nine days (range 1 day to 561 days).

Further information

References

  1. Health Canada. 2023. Summary Safety Review – Third Generation Aromatase Inhibitors (anastrozole, exemestane, letrozole) – Assessing the Potential Risk of Tendon Disorders 17 January 2023. URL: dhpp.hpfb-dgpsa.ca/review-documents/resource/SSR00289 (accessed 18 June 2024).
  2. Kirchgesner T, et al. 2014. Drug-induced tendinopathy: From physiology to clinical applications. Joint Bone Spine 81(6): 485-92. DOI: https://doi.org/10.1016/j.jbspin.2014.03.022 (accessed 18 June 2024).
  3. Bolon B. 2017. Mini-review: Toxic tendinopathy. Toxicology Pathology 45(7): 834-7. DOI: 10.1177/0192623317711614 (accessed 18 June 2024).
  4. Viatris Ltd. 2022. Cipflox New Zealand Data Sheet 16 June 2022. URL: www.medsafe.govt.nz/profs/Datasheet/c/Cipfloxtabinf.pdf (accessed 10 July 2024).
  5. Bayer New Zealand Limited. 2021. Avelox New Zealand Data Sheet 14 October 2021. URL: www.medsafe.govt.nz/profs/Datasheet/a/AveloxtabIVinf.pdf (accessed 10 July 2024).
  6. Teva Pharma (New Zealand) Limited. 2020. Arrow – Norfloxacin New Zealand Data Sheet 9 November 2020. URL: www.medsafe.govt.nz/profs/Datasheet/a/ArrowNorfloxacintab.pdf (accessed 10 July 2024).
  7. Douglas Pharmaceutical Ltd. 2024. Letara New Zealand Data Sheet 19 February 2024. URL: www.medsafe.govt.nz/profs/Datasheet/l/Letaratab.pdf (accessed 16 July 2024).
  8. Viatris Ltd. 2024. Letrole New Zealand Data Sheet 15 January 2024. URL: www.medsafe.govt.nz/profs/Datasheet/l/letroletab.pdf (accessed 16 July 2024).
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