Fluoroquinolones may induce tendinopathy characterised by tendinitis or tendon rupture.

1. FLUOROQUINOLONES
ASSOCIATED
TENDINOPATHY
Dr. P.Naina Mohamed
Pharmacologist

2. INTRODUCTION
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Fluoroquinolones cause tendinopathies such as tendinitis and tendon
rupture of Achilles tendon and also other tendons like rotator cuff (the
shoulder), the hand, the biceps, and the thumb.
Rupture of the Achilles tendon may require surgical repair.
Tendon rupture can occur during or after completion of fluoroquinolone
use.
There are reports of symptoms and tendon disruptions occurring months
after discontinuation of the medication.
FDA’s recent evaluation of the medical literature and the post-marketing
adverse event reports submitted to the Adverse Events Reporting System
(AERS) confirmed that serious reports of tendinitis and tendon rupture
with the fluoroquinolones continue to be reported in similar or increased
numbers.
The FDA recommends that at the first sign of tendon pain, swelling, or
inflammation, patients should stop taking the fluoroquinolone, avoid
exercise and use of the affected area, and promptly contact their physician
for tendon evaluation and transition to a non-fluoroquinolone antibiotic.
Tendon rupture is a serious adverse event that could potentially be
prevented or reduced in frequency or severity by appropriate use of a
fluoroquinolone, patient selection, and careful monitoring.

3. RISK FACTORS
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Risk factors for the development of fluoroquinolone-induced
tendinopathy are…
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Age (over 60 years)
Renal failure
Long-term dialysis
Kidney, heart, and lung transplantation
Corticosteroid use
Hypercholesterolemia,
Gout
Rheumatoid arthritis
Diabetes mellitus
Hyperparathyroidism
Participation in sports
Previous tendinopathy from fluoroquinolones
Fluoroquinolones dose should be adjusted based on renal
function to avoid possible drug accumulation.
The median duration of fluoroquinolone use before the onset of
tendon injury is eight days.

4. PROPOSED PATHOPHYSIOLOGY
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The exact pathophysiology of FQ-induced tendinopathy
remains elusive; however, some concepts have been
suggested.
Fluoroquinolones
Chelating properties
Form complex with several metal ions (e.g., calcium,
magnesium, aluminum)
Direct toxicity to type 1 collagen synthesis
Promote collagen degradation

5. PROPOSED PATHOPHYSIOLOGY
Fluoroquinolones
Chelating properties
Interact with regulating proteins of tenocytes
Damage at the tendon structure
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In addition, recent study suggests that apoptosis
as the final event in the pathogenetic
mechanism.

6. PROPOSED PATHOPHYSIOLOGY
Fluoroquinolones
Chelation of magnesium in joint cartilage
Radical formation
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Irreversible cartilage lesions
This hypothesis is further substantiated by the fact that
quinolone-induced cartilage lesion can be diminished by
supplementing with magnesium and/or tocopherol.
Narrowed vasculature of the tendon and paratendon
suggest that changes in blood flow may play a role.
The low supply of blood to the tendons, particularly the
Achilles, which is further decreased with age, likely
predisposes to injury.

7. PROPOSED PATHOPHYSIOLOGY
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FQs have a direct cytotoxic effect on enzymes found in
mammalian musculoskeletal tissue.
Because animal studies have shown that FQs may
damage juvenile weight-bearing joints, most FQs are
contraindicated in children and during pregnancy and
lactation.
Experiments on immature laboratory animals (dogs,
rabbits, and rats) have shown that FQs cause
cartilage damage by inducing necrosis of chondrocytes
(36 hours after treatment), disruption of the
extracellular matrix, and formation of vesicles and
fissures at the articular surface.
In-vitro studies in cultured tendon cells have
confirmed the clinical observation that FQs can
increase the risk of tendon rupture.

8. CLINICAL MANIFESTATIONS
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The Achilles tendon is most commonly affected in FQ-induced
tendinopathy, occurring in 89.8 percent of cases.
Other tendons, such as biceps brachii, supraspinatus, and extensor
pollicis longus, can also be affected.
Other sites included the triceps epicondyle, flexor tendon sheath,
patellar tendon, quadriceps muscle, rotator cuff, and subscapularis
terrea.
Up to 50 percent of cases may present with bilateral involvement.
Depending on the degree of involvement of the joint, patients may
experience pain, swelling, or inflammation in the tendon area for up
to two weeks before rupture occurs.
Signs of tendon rupture can include a “snap” or “pop“ in the area,
bruising, or immobility of the joint.
Tendon rupture is almost always preceded by spontaneous pain at the
bony insertion 2 to 3cm above the insertion point, believed to be
correlated with diminished vascularization at this anatomic site.
FQ-induced tendinitis is distinguished from other forms of
tendinopathy by both the abrupt onset and sharp pain that occur
spontaneously upon walking or palpation.

9. MANAGEMENT
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Treatment should include rest and decreasing the physical load on
the tendon.
Treatment with a FQ should be discontinued and physical therapy
initiated.
During the first month of rehabilitation of an Achilles tendinopathy,
the affected tendon should be protected with a heel lift, counterforce
bracing, and crutches to decrease the tensile load transmitted to the
Achilles tendon during walking for six weeks to six months.
Approximately 50 percent of patients will recover within 30 days,
with 25 percent of patients having symptoms persistent for longer
than two months.
Patients receiving a FQ should be counseled to seek medical attention
immediately if symptoms, such as redness, pain, swelling, and
stiffness, develop.
Tendinosis usually recovers over a time course of weeks, usually
within two months, after cessation of FQ therapy.
In cases of FQ-induced tendon rupture, orthopedic treatment should
proceed, as in other cases of tendon disruption, with consideration
given to operative therapy after assessing the potential risks versus
anticipated benefits of surgical intervention

10. FDA’S INFORMATION TO HEALTHCARE
PROFESSIONALS
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Pain, swelling, inflammation, and tears of tendons including the Achilles,
shoulder, hand, or other tendons can happen in patients taking
fluoroquinolone antibiotics.
Patients receiving a FQ should be counseled to call healthcare provider
right away at the first signs or symptoms of pain, swelling or
inflammation in a tendon area. These could be symptoms of tendinitis or
tendon rupture.
Some medicines may interact with a fluoroquinolone and cause serious
side effects. Also, some medical conditions may aggravate side effects of
fluoroquinolones.
Fluoroquinolones, like any drug, have possible side effects include
seizures, hallucinations, depression, heart rhythm changes (QTc
prolongation and torsade de points), and intestine infection with diarrhea.
Rarely, damage to the liver, kidneys or bone marrow, and changes to
blood sugar may occur.
Fluoroquinolones are antimicrobials that are effective in treating
infections caused by certain bacteria but not viruses (common cold or the
flu).

11. CONCLUSION
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Pefloxacin, fleroxacin, levofloxacin, and ofloxacin were found to
induce the greatest number of lesions.
Administration of enoxacin, norfloxacin, and ciprofloxacin had
little or no effect.
A research suggested that the substituent at the seventh position
of the fluoroquinolone molecule may increase toxicity.
Pefloxacin, fleroxacin, levofloxacin, and ofloxacin have a
methylpiperadinyl moiety at 7th position, whereas enoxacin,
norfloxacin, and ciprofloxacin have a piperadinyl substituent.
The fluoroquinolone should be discontinued if the patient
experiences pain or inflammation in a tendon (symptoms that
may precede rupture of the tendon), or tendon rupture.
Avoid exercise and use of the affected area.
Healthcare professionals should consider the potential benefit and
risks to each individual patient before prescribing a
fluoroquinolone antimicrobial.
Fluoroquinolones should only be used for the treatment or
prevention of bacterial infections but not viral infections such as
the common cold or influenza.

12. REFERENCES
http://www.fda.gov/drugs/drugsafety/postmarketd
rugsafetyinformationforpatientsandproviders/uc
m126085.htm
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ull
 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC29
21747/
 http://www.ncbi.nlm.nih.gov/pubmed/10832946
 http://www.jwatch.org/id201212120000004/2012/
12/12/achilles-tendinitis-tendon-rupture-and
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