As lawyers in the US move forward with lawsuits against some
manufacturers of quinolone and fluoroquinolone antibiotics following
a worldwide increase in the number of patients reporting serious side-effects
with the drugs, South African healthcare professionals have again been warned
to be extremely cautious in prescribing these antibiotics for non-life-threatening
conditions such as uncomplicated urinary tract infections, bronchitis and
sinusitis.

Following warnings last year by the South African Health Products
Regulatory Authority (SAHPRA), the European Medicines Authority and the FDA, the
investigative TV programme, Carte Blanche, spoke to patients who have and are
still suffering the side-effects of these drugs. Last month, several
pharmaceutical companies in South Africa, including Aspen, Bayer, Sun Pharma,
Ranbaxy, Zentiva South Africa and Fresenius Kabi sent out a letter informing
healthcare professionals that the prescribing information of oral, parenteral
and inhaled quinolones/fluoroquinolones are to be amended in view of new safety
information that has become available.

The letter repeats the warnings sounded by medicine regulatory
authorities of serious adverse reactions that may be disabling, long-lasting
and potentially irreversible. Side-effects include an increased risk of aortic
aneurysm and dissection, psychiatric disorders and other disorders relating to
the nervous system, muscles, tendons and joints.

“As a consequence, the benefits and risks of all oral,
parenteral and inhaled quinolone and fluoroquinolone antibiotics and their
indications are being reviewed,” the letter states. It advises healthcare
professionals that for the indications listed below, only to prescribe
quinolone/fluoroquinolone antibiotics where other antimicrobials are considered
not to be an appropriate treatment option, have failed, are contraindicated or
not tolerated:

• for treating non-severe or self-limiting infections (such
as pharyngitis, tonsillitis and acute bronchitis)

• for preventing travellers’ diarrhoea or recurrent lower
urinary tract infections • for non-bacterial infections, e.g. non-bacterial
(chronic) prostatitis and

• for mild to moderate infections (including uncomplicated
cystitis, acute exacerbation of chronic bronchitis and chronic obstructive
pulmonary disease (COPD), acute bacterial rhinosinusitis and acute otitis
media).

Caution is advised when prescribing for the elderly,
patients with renal impairment, patients with solid organ transplants, and
those concurrently treated with corticosteroids, as the risk of
fluoroquinolone-induced tendinitis and tendon rupture may be exacerbated in
these patients.

Healthcare professionals should advise patients to stop
treatment immediately at the first signs of a serious adverse reaction, such as
tendinitis and tendon rupture, muscle pain, muscle weakness, joint pain, joint
swelling, peripheral neuropathy and central nervous system effects and to
contact their doctor for further advice.

Aortic aneurysm and dissection

There is some evidence of an association of quinolone/fluoroquinolone
use and the risk of aortic aneurysm and dissection particularly in the elderly
population. Therefore, in patients at risk for aortic aneurysm and dissection,
fluoroquinolones should only be used after careful benefit-risk assessment and
after consideration of other therapeutic option. The conditions predisposing to
aortic aneurysm and dissection include a family history of aneurysm disease,
pre-existing aortic aneurysm or aortic dissection, Marfan syndrome, vascular
Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behçet’s
disease, hypertension, and atherosclerosis.

Patients should be advised about risk of aortic aneurysm and
dissection and told to seek immediate medical attention in the emergency
department in case of sudden severe abdominal, chest or back pain. Therefore,
quinolones/ fluoroquinolones should only be prescribed to patients with a
preexisting dilated aorta, aortic aneurysm or dissection, or the presence of
other risk factors predisposing to aortic aneurysm/dissection, where other
antimicrobials have been considered not to be an appropriate treatment option,
have failed, are contraindicated or cannot be tolerated.

Background to safety concern

The European Medicines Agency (EMA) have reviewed systemic
and inhaled quinolone and fluoroquinolone antibiotics to evaluate the risk of
serious and persistent (lasting months or years), disabling and potentially
irreversible adverse reactions mainly affecting the musculoskeletal and nervous
systems. Serious adverse reactions of the musculoskeletal system include
tendinitis, tendon rupture, myalgia, muscle weakness, arthralgia and joint
swelling. Serious peripheral and central nervous system effects include
peripheral neuropathy, psychosis, anxiety, insomnia, depression,
hallucinations, suicidal thoughts, confusion, as well as impairment of vision,
hearing, smell and taste. Due to the seriousness of these reactions in
previously healthy persons, any decision to prescribe quinolones and
fluoroquinolones should be taken after a careful assessment of the benefits and
risk and other appropriate treatment options that are available. The
epidemiological studies [1-3] report an increase in risk of aortic aneurysm and
dissection in patients taking systemic fluoroquinolones compared with patients
taking no antibiotics or other antibiotics (amoxicillin); with older people
being at higher risk. A non-clinical study [4] reported that ciprofloxacin
increases the susceptibility to aortic dissection and rupture in a mouse model.
This finding is likely to be a class effect similar to that of fluoroquinolones
being harmful to tendon tissue.

Reporting adverse effects

Healthcare professionals should report all suspected adverse
effects associated with the use of all quinolones and fluoroquinolones
containing medicines to the applicable company indicated above or to the NADEMC
(National Drug Event Monitoring Centre) – Tel: 021 447 1618 or Fax: 021 448
6181 or SAHPRA Pharmacovigilance Office – Email: adr@health.gov.za