OFLOXIN Film-coated tablet Ref.[50389] Active ingredients: Ofloxacin

Source: Υπουργείο Υγείας (CY)  Revision Year: 2022  Publisher: Codal-Synto Ltd, 21 Constantinoupoleos Street, 3011 Limassol, Cyprus

4.3. Contraindications

  • Hypersensitivity to the active substance, to 4-quinolone antibacterials or to any of the excipients listed in section 6.1.
  • Ofloxacin should not be used in patients with a past history of tendinitis.
  • Ofloxacin, like other 4-quinolones, is contraindicated in patients with a history of epilepsy or with a lowered seizure threshold.
  • Ofloxacin is contraindicated in children or growing adolescents, and in pregnant or breast-feeding women, since animal experiments do not entirely exclude the risk of damage to the cartilage of joints in the growing subject.
  • Patients with latent or actual defects in glucose-6-phosphate dehydrogenese activity may be prone to haemolytic reactions when treated with quinolone antibacterial agents.

4.4. Special warnings and precautions for use

The use of ofloxacin should be avoided in patients who have experienced serious adverse reactions in the past when using quinolone or fluoroquinolone containing products (see section 4.8). Treatment of these patients with ofloxacin should only be initiated in the absence of alternative treatment options and after careful benefit/risk assessment (see also section 4.3).

Aortic aneurysm and dissection, and heart valve regurgitation/incompetence

Epidemiologic studies report an increased risk of aortic aneurysm and dissection, particularly in elderly patients, and of aortic and mitral valve regurgitation after intake of fluoroquinolones. Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal ones), and of regurgitation/incompetence of any of the heart valves have been reported in patients receiving fluoroquinolones (see section 4.8).

Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients with positive family history of aneurysm disease or congenital heart valve disease, or in patients diagnosed with pre-existing aortic aneurysm and/or dissection or heart valve disease, or in presence of other risk factors or conditions predisposing

  • for both aortic aneurysm and dissection and heart valve regurgitation/incompetence (e.g. connective tissue disorders such as Marfan syndrome or Ehlers-Danlos syndrome, Turner syndrome, Behcet’s disease, hypertension, rheumatoid arthritis) or additionally
  • for aortic aneurysm and dissection (e.g. vascular disorders such as Takayasu arteritis or giant cell arteritis, or known atherosclerosis, Sjögren’s syndrome) or additionally
  • for heart valve regurgitation/incompetence (e.g. infective endocarditis).

The risk of aortic aneurysm and dissection, and their rupture may also be increased in patients treated concurrently with systemic corticosteroids.

In case of sudden abdominal, chest or back pain, patients should be advised to immediately consult a physician in an emergency department.

Patients should be advised to seek immediate medical attention in case of acute dyspnoea, new onset of heart palpitations, or development of oedema of the abdomen or lower extremities.

  • Ofloxacin is not the drug of first choice for pneumonia caused by Pneumococci or Mycoplasma, or angina tonsillaris caused by β-haemolytic Streptococci.
  • Hypersensitivity and allergic reactions have been reported for fluoroquinolones after first administration. Anaphylactic and anaphylactoid reactions can progress to life-threatening shock, even after the first administration. In these cases ofloxacin should be discontinued and suitable treatment (e.g treatment for shock) should be initiated.

Prolonged, disabling and potentially irreversible serious adverse drug reactions

Very rare cases of prolonged (continuing months or years), disabling and potentially irreversible serious adverse drug reactions affecting different, sometimes multiple, body systems (musculoskeletal, nervous, psychiatric and senses) have been reported in patients receiving quinolones and fluoroquinolones irrespective of their age and pre-existing risk factors. Ofloxacin should be discontinued immediately at the first signs or symptoms of any serious adverse reaction and patients should be advised to contact their prescriber for advice.

Clostridium difficile-associated disease

Diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment with ofloxacin, may be symptomatic of pseudo-membranous colitis. If pseudo-membranous colitis is suspected, ofloxacin must be stopped immediately. Appropriate specific antibiotic therapy must be started without delay (e.g. oral vancomycin, oral teicoplanin or metronidazole). Products inhibiting the peristalsis are contraindicated in this clinical situation.

Patients predisposed to seizures

In case of convulsive seizures, treatment with ofloxacin should be discontinued (see section 4.5 lowering of the cerebral seizure threshold).

Cardiac disorders

Very rare cases of QT interval prolongation have been reported in patients taking fluoroquinolones. Caution should be taken when using fluoroquinolones, including ofloxacin, in patients with known risk factors for prolongation of the QT interval such as, for example:

  • congenital long QT syndrome
  • concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics)
  • uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia)
  • cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)

Elderly patients and women may be more sensitive to QTc-prolonging medications. Therefore, caution should be taken when using fluoroquinolones, including ofloxacin, in these populations.

(See section 4.2 Elderly, section 4.5, section 4.8, section 4.9).

Patients being treated with ofloxacin should not expose themselves unnecessarily to strong sunlight and should avoid UV rays (sun lamps, solaria).

Patients with history of psychotic disorder

Psychotic reactions have been reported in patients receiving fluoroquinolones. In some cases these have progressed to suicidal thoughts or self-endangering behaviour including suicide attempt, sometimes after a single dose. In the event that a patient develops these reactions, ofloxacin should be discontinued and appropriate measures instituted. Ofloxacin should be used with caution in patients with a history of psychotic disorder or in patients with psychiatric disease.

Patients with impaired liver function

Ofloxacin should be used with caution in patients with impaired liver function, as liver damage may occur. Cases of fulminant hepatitis potentially leading to liver failure (including fatal cases) have been reported with fluoroquinolones. Patients should be advised to stop treatment and contact their doctor if signs and symptoms of hepatic disease develop such as anorexia, jaundice, dark urine, pruritis or tender abdomen. (See section 4.8)

Patients treated with vitamin K antagonists

Due to possible increase in coagulation tests (PT/INR) and/or bleeding in patients treated with fluoroquinolones, including ofloxacin, in combination with a vitamin K antagonist (e.g.warfarin), coagulation tests should be monitored when these drugs are given concomitantly (see section 4.5)

Myasthenia gravis

Ofloxacin should be used with caution in patients with a history of myasthenia gravis.

Administration of antibiotics, especially of prolonged, may lead to proliferation of resistant micro-organisms. The patient’s condition must therefore be checked at regular intervals. If a secondary infection occurs, appropriate measures must be taken.

Tendinitis and tendon rupture

Tendinitis and tendon rupture (especially but not limited to Achilles tendon), sometimes bilateral, may occur as early as within 48 hours of starting treatment with quinolones and fluoroquinolones and have been reported to occur even up to several months after discontinuation of treatment. The risk of tendinitis and tendon rupture is increased in older patients, patients with renal impairment, patients with solid organ transplants, and those treated concurrently with corticosteroids. Therefore, concomitant use of corticosteroids should be avoided.

At the first sign of tendinitis (e.g. painful swelling, inflammation) the treatment with ofloxacin should be discontinued and alternative treatment should be considered. The affected limb(s) should be appropriately treated (e.g. immobilisation). Corticosteroids should not be used if signs of tendinopathy occur.

Peripheral neuropathy

Cases of sensory or sensorimotor polyneuropathy resulting in paraesthesia, hypaesthesia, dysesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones. Patients under treatment with ofloxacin should be advised to inform their doctor prior to continuing treatment if experiences symptoms of neuropathy such as pain, burning, tingling, numbness, or weakness develop in order to prevent the development of potentially irreversible condition (see section 4.8).

Hypoglycaemia

As with all quinolones, hypoglycaemia has been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycaemic agent (e.g. glibenclamide) or with insulin. In these diabetic patients, careful monitoring of blood glucose is recommended.

Patients with glucose-6-phosphate-dehydrogenase deficiency

Patients with latent or diagnosed glucose-6-phosphate-dehydrogenase deficiency may be predisposed to haemolytic reactions if they are treated with quinolones. Ofloxacin should therefore be administered with caution in such patients.

Interaction with laboratory tests

Determination of opiates or porphyrins in urine may give false-positive results during treatment with ofloxacin. It may be necessary to confirm positive opiate or porphyrin screens by more specific methods.

Vitamin K antagonists

Coagulation tests should be monitored in patients treated with vitamin K antagonists because of a possible increase in the effect of coumarin derivatives.

Vision disorders

If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately.

Ofloxin contains lactose. Patients with rare hereditary disorders of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5. Interaction with other medicinal products and other forms of interaction

Drugs known to prolong QT interval

Ofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs known to prolong the QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (See section 4.4).

Antacids, Sucralfate, Metal Cations

Co-administered magnesium/aluminium antacids, sucralfate, zinc or iron preparations can reduce absorption. Therefore, ofloxacin should be taken 2 hours before such preparations.

Prolongation of bleeding time has been reported during concomitant administration of Ofloxin and anticoagulants.

There may be a further lowering of the cerebral seizure threshold when quinolones are given concurrently with other drugs which lower the seizure threshold, e.g. theophylline. However ofloxacin is not thought to cause a pharmacokinetic interaction with theophylline, unlike some other fluoroquinolones.

Further lowering of the cerebral seizure threshold may also occur with certain nonsteroidal anti-inflammatory drugs.

In case of convulsive seizures, treatment with ofloxacin should be discontinued.

Ofloxacin may cause a slight increase in serum concentrations of glibenclamide administered concurrently; patients treated with this combination should be closely monitored.

With high doses of quinolones, impairment of excretion and an increase in serum levels may occur when co-administered with other drugs that undergo renal tubular secretion (e.g. probenecid, cimetidine, frusemide and methotrexate).

Probenecid, cimetidine, furosemide and methotrexate

Probenecid decreased the total clearance of ofloxacin by 24%, and increased AUC by 16%.

The proposed mechanism is a competition or inhibition for active transport at the renal tubular excretion. Caution should be exercised when ofloxacin is coadministered with drugs that affect the tubular renal secretion such as probenecid, cimetidine, furosemide and methotrexate.

Vitamin K antagonists

Increased coagulation tests (PT/INR) and/or bleeding, which may be severe, have been reported in patients treated with levofloxacin in combination with a vitamin K antagonists (e.g. warfarin). Coagulation tests, therefore, should be monitored in patients treated with vitamin K antagonists (see section 4.4).

4.6. Pregnancy and lactation

Pregnancy

Based on a limited amount of human data, the use of fluoroquinolones in the first trimester of pregnancy has not been associated with an increased risk of major malformations or other adverse effects on pregnancy outcome. Animal studies have shown damage to the joint cartilage in immature animals but no teratogenic effects. Therefore ofloxacin should not be used during pregnancy (See section 4.3).

Breast-feeding

Ofloxacin is excreted into human breast milk in small amounts. Because of the potential for arthropathy and other serious toxicity in the nursing infant, breast feeding should be discontinued during treatment with ofloxacin (See section 4.3).

4.7. Effects on ability to drive and use machines

Since there have been occasional reports of somnolence, impairment of skills, dizziness and visual disturbances, patients should know how they react to ofloxacin before they drive or operate machinery. These effects may be enhanced by alcohol.

4.8. Undesirable effects

The following adverse reactions are presented by MedDRA frequency and system organ class database convention: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).

System organ
class
Common
(≥1/100 to
<1/10)
Uncommon
(≥1/1,000 to
<1/100)
Rare
(≥1/10,000 to
<1/1,000)
Very rare
(<1/10,000)
Not known (cannot
be estimated from
available data)*
Infections and
infestations
 Fungal infection,
Pathogen resistance
   
Blood and the
lymphatic
system disorders
   Anaemia
Haemolytic
anaemia,
Leukopenia,
Eosinophilia,
Thrombocytopenia
Agranulocytosis
Bone marrow failure
Immune system
disorders
  Anaphylactic
reaction*,
Anaphylactoid
reaction*,
Angioedema*
Anaphylactic
shock*,
Anaphylactoid
shock*
 
Metabolism and
Nutrition
disorders
  Anorexia Hypoglycaemia in
diabetics treated
with hypoglycaemic
agents (see
Section 4.4)
Hyperglycaemia,
Hypoglycaemic
coma
Psychiatric
disorders**
 Agitation,
Sleep disorder,
Insomnia
Psychotic
disorder (for
e.g. hallucination),
Anxiety,
Confusional
state,
Nightmares,
Depression,
Delirium
 Psychotic disorder
and depression with
self-endangering
behaviour including
suicidal ideation
or suicide
attempt (see
Section 4.4)
Nervousness
Nervous system
disorders**
 Dizziness,
Headache
Somnolence,
Paraesthesia,
Dysgeusia,
Parosmia
Peripheral sensory
neuropathy*
Peripheral sensory
motor neuropathy*
Convulsion*,
Extra-pyramidal
symptoms or
other disorders
of muscular
coordination
Tremor
Dyskinesia
Ageusia
Syncope
Eye disorders**  Eye
irritation
Visual
disturbance
 Uveitis
Ear and
labyrinth
disorders**
 Vertigo Tinnitus,
Hearing loss
Hearing Impaired
Cardiac
disorders***
  Tachycardia Ventricular
arrhythmias,
torsades de pointes
(reported
predominantly
in patients
with risk
factors for
QT prolongation),
ECG QT
prolonged (see
section 4.4
and 4.9)
Vascular
disorders***
applies only
to the solution
for infusion:

Phlebitis
 Hypotension applies only
to the solution
for infusion:

During infusion
of ofloxacin,
tachycardia and
hypotension may
occur. Such a
decrease in
blood pressure may,
in very rare
cases, be severe.
Respiratory,
thoracic and
mediastinal
disorders
 Cough,
Naso-pharyngitis
Dyspnoea,
Bronchospasm
 Allergic
pneumonitis, Severe
dyspnoea
Gastrointestinal
disorders
 Abdominal
pain,
Diarrhoea,
Nausea,
Vomiting
Enterocolitis,
sometimes
haemorrhagic
Pseudo-membranous
colitis*
Dyspepsia
Flatulence
Constipation
Pancreatitis
Hepatobilary
disorders
  Hepatic
enzymes
increased
(ALAT, ASAT,
LDH, gamma-GT
and/or alkaline
phosphatase)
Blood bilirubin
increased
Jaundice cholestaticHepatitis, which
may be severe*
Severe liver injury,
including cases with
acute liver failure,
sometimes fatal,
have been reported
with ofloxacin,
primarily in patients
with underlying
liver disorders
(see section 4.4)
Skin and
subcutaneous
tissue disorders
 Pruritus,
Rash
Urticaria, Hot
flushes,
Hyperhidrosis
Pustular rash
Erythema
multiforme, Toxic
epidermal
necrolysis,
Photo-sensitivity
reaction*, Drug
eruption
Vascular purpura,
Vasculitis,
which can lead
in exceptional
cases to skin
necrosis
Stevens-Johnson
syndrome;
Acute generalized
exanthemous
pustulosis; drug rash
Stomatitis
Exfoliative
dermatitis
Musculoskeletal
and Connective
tissue
disorders**
  TendonitisArthralgia,
Myalgia, Tendon
rupture (e.g.
Achilles tendon)
which may occur
within 48 hours of
treatment start and
may be bilateral.
Rhabdomyolysis
and/or Myopathy,
Muscular weakness
Muscle tear, muscle
rupture
Ligament rupture
Arthritis
Renal and
Urinary
disorders
  Serum creatinine
increased
Acute renal failureAcute interstitial
nephritis
Congenital and
familial/genetic
disorders
    Attacks of
porphyria in
patients with
porphyria
General
disorders and
administration
site conditions**
applies only
to the solution
for infusion:

Infusion site
reaction
(pain,
reddening)
   Asthenia
Pyrexia
Pain (including
pain in the back,
chest, and extremities)
Pancytopenia

* Postmarketing experience
** Very rare cases of prolonged (up to months or years), disabling and potentially irreversible serious drug reactions affecting several, sometimes multiple, system organ classes and senses (including reactions such as tendonitis, tendon rupture, arthralgia, pain in extremities, gait disturbance, neuropathies associated with paraesthesia, depression, fatigue, memory impairment, sleep disorders, and impairment of hearing, vision, taste and smell) have been reported in association with the use of quinolones and fluoroquinolones in some cases irrespective of pre-existing risk factors (see Section 4.4).
*** Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal ones), and of regurgitation/incompetence of any of the heart valves have been reported in patients receiving fluoroquinolones (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continuous monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs, Fax: +357 22608649.

6.2. Incompatibilities

None known.

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