APR Oflaone Suspension

INFORMATION FOR THE USER

Ofloxacin 200mg and Ornidazole 500mg Tablets

Read all of this information carefully before you start taking this medicine because it contains important information for you.
Keep this information. You may need to read it again.
If you have any further questions, ask your doctor, pharmacist or nurse.
This medicine is prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this information.

COMPOSITION:
Each tablet contains:
Ofloxacin – 200mg
Ornidazole – 500mg

For oral use only.

DESCRIPTION:
Ofloxacin is an antibacterial that is highly useful for treating infections. It belongs to a class of drugs known as fluoroquinolones.
Metronidazole is an antibacterial and antiprotozoal drug. It belongs to a class of drugs known as nitroimidazoles.

PHARMACOLOGICAL ACTION:
Ofloxacin inhibits bacterial DNA replication by inhibiting bacterial topoisomerases particularly DNA gyrase & topoisomerase IV. It is active after oral administration. Therapeutic doses are devoid of pharmacological effects on the voluntary or autonomic nervous system.
Metronidazole is of the nitroimidazole class. It inhibits nucleic acid synthesis by disrupting the DNA of microbial cells. This function only occurs when it is partially reduced & because this reduction usually happens only in anaerobic bacteria & protozoans it has relatively little effect upon human cells or aerobic bacteria.

CLINICAL PHARMACOKINETICS:
The administration of oral doses was followed by a rapid & almost complete absorption. The peak plasma concentration after a single oral dose averaged 2.6 µg/ml & was reached within 1 hour. The plasma elimination half-life was 5.7-7.0 hours & was not dose related. The apparent distribution volume was 120 litres. The plasma concentration did not materially rise with repeat doses. The plasma protein binding was approx. 25%. The biotransformation was below 5%. The two main metabolites found in urine were N-desmethyl-ofloxacin & ofloxacin-N-oxide. Excretion is primarily renal. Between 80-90% of the dose were recovered from the urine as unchanged substance. It was present in the bile in glucuronidised form. The pharmacokinetics of ofloxacin after IV infusion are very similar to those after oral doses. The plasma half-life is prolonged in renal insufficiency; total & renal clearance decrease in accordance with the creatinine clearance. In renal insufficiency the dose should be reduced.
Following oral administration ornidazole is rapidly absorbed. Mean absorption is 90%. Peak plasma concentrations are reached within 3 hours. The mean volume of distribution is 1 litre per kg. Plasma protein-binding is about 13%. The active ingredient penetrates the cerebrospinal fluid, the body fluids & the tissues very effectively. Plasma concentrations are within the range considered to be optimal for the various indications (6–36 mg/l). After repeated administration an accumulation factor of 1.5–2.5 was calculated. It is mainly metabolised to 2-hydroxymethyl & a-hydroxymethylmetabolites in the liver. Both main metabolites are less active against Trichomonas vaginalis & anaerobic bacteria than the unchanged ornidazole. The half-life is about 13 hours. While 85% of a single dose is eliminated within the first 5 days, 4% of the dose is excreted as unaltered substance in the urine.
INDICATIONS:
Ofloxacin and ornidazole tablets are indicated for:
Diarrhoea of mixed etiology.
Mixed infections
Dental infections

CONTRAINDICATIONS:
Ofloxacin tablets are contraindicated in the following cases:

• Hypersensitivity to the active substance, to any other fluoroquinolone antibacterials, ornidazole, other nitroimidazoles or to any of the excipients.
• History of epilepsy or an existing central nervous system disorder with a lowered seizure threshold.
• History of tendon disorders related to fluoroquinolone administration.
• In children or growing adolescents & in pregnant/breastfeeding women.
• Latent/actual defects in glucose-6-phosphate dehydrogenase activity.

WARNINGS AND PRECAUTIONS:
Not the drug of first choice in pneumonia caused by Streptococcus pneumoniae or Chlamydia pneumoniae.
Methicillin-resistant S. aureus: Are very likely to possess co-resistance to fluoroquinolones including ofloxacin. Not recommended for the treatment of known/suspected MRSA infection unless laboratory results have confirmed susceptibility.
Resistance to fluoroquinolones of E. coli: Prescribers are advised to take into account the local prevalence of resistance.
Severe bullous reactions: Severe bullous skin reactions such as Stevens-Johnson syndrome has been reported.
Tendonitis: May occasionally lead to rupture involving Achilles tendon in particular. Tendinitis & tendon rupture sometimes bilateral may occur within 48 hrs of starting treatment.
Hypersensitivity: Hypersensitivity & allergic reactions have been reported after first administration.
Diseases caused by Clostridium difficile: Diarrhoea especially if severe, persistent and/or bloody occurring during/after treatment may indicate a condition caused by C. difficile the most severe form of which is pseudomembranous colitis. Appropriate specific antibiotic therapy must be started without delay (e.g. oral vancomycin). Medicinal products that inhibit peristalsis are contraindicated in such cases.
Patients predisposed to seizures: May lower the seizure threshold & may trigger seizures. Contraindicated in patients with a history epilepsy/with a known predisposition to seizures.
Patients with impaired renal function: Dose should be adjusted in patients with impaired renal function.
Patients with impaired liver function: Should be used with caution in patients with impaired liver function as liver damage may occur.
Patients treated with vitamin K antagonists: Due to possible increase in coagulation tests and/or bleeding in combination with a vitamin K antagonist (e.g. warfarin) coagulation tests should be monitored when these drugs are given concomitantly.
Myasthenia gravis: May exacerbate muscle weakness in patients with myasthenia gravis.
Superinfection: May result in overgrowth of non-susceptible organisms especially Enteracci, resistant strains of some organisms or Candida. If secondary infection occurs during therapy, appropriate measures should be taken.
Prevention of photosensitisation: Photosensitisation has been reported. It is recommended not to expose themselves unnecessarily to strong sunlight/artificial UV rays during treatment & for 48 hours following treatment discontinuation.
QT interval prolongation: Very rare cases of QT interval proplongation have been reported. Caution should be taken when using fluoroquinolones in patients with known risk factors for prolongation of QT interval such as, for example:
– Elderly patients & women
– Uncorrected electrolyte imbalance (e.g. hypokalemia, hypomagnesemia)
– Congenital long QT syndrome
– Concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics)
– Cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)
Dysglycaemia: Disturbances in blood glucose including both hypoglycaemia & hyperglycaemia have been reported.
Peripheral neuropathy: Sensory/sensorimotor peripheral neuropathy has been reported.
Patients with glucose-6-phosphate-dehydrogenase deficiency: Patients with latent/diagnosed glucose-6-phosphate-dehydrogenase deficiency may be predisposed to haemolytic reactions.
Interference with laboratory tests: Determination of opiates or porphyrin levels in urine may give false-positive results.
Vision disorders: If vision becomes impaired/any effects on the eyes are experienced an eye specialist should be consulted immediately.
Caution should be exercised in patients with diseases of the CNS, e.g. epilepsy/multiple sclerosis. The effect of other medicines can be intensified or impaired.

ADVERSE EFFECTS:
Common side effects include:
Agitation, sleep disturbance, insomnia
Dizziness, headache
Eye irritation
Vertigo
Abdominal pain, diarrhoea, nausea vomiting
Pruritis, rash
Tendonitis
DRUG INTERACTIONS:
Antacids, Sucralfate, Metal Cations: Co-administered magnesium/aluminum antacids, sucralfate, zinc or iron preparations & didanosine chewable/buffered tablets can reduce absorption of ofloxacin tablets.
Theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs
No pharmacokinetic interactions were found. However a pronounced lowering of the cerebral seizure threshold may occur when quinolones are given concurrently with theophylline, nonsteroidal antiinflammatory drugs, or other agents, which lower the seizure threshold.
Probenecid, cimetidine, furosemide, and methotrexate: Probenecid decreased the total clearance by 24%, and increased AUC by 16%.
Drugs known to prolong QT interval: Should be used with caution in patients receiving drugs known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants, macrolides & antipsychotics)
Vitamin K antagonists: Increased coagulation tests (PT/INR) and/or bleeding which may be severe,have been reported in patients treated with ofloxacin in combination with a vitamin K antagonist (e.g. warfarin).
Glibenclamide: May cause a slight increase in plasma glibenclamide levels when administered concurrently.
Alcohol must not be ingested when taking ornidazole or for at least 3 days after discontinuing the medicine.

It potentiates the effect of coumarin type oral anticoagulants. The dosage of the anticoagulant has to be adjusted accordingly.

Caution must be exercised when taking ornidazole together with lithium, cimetidine & antiepileptic medicines such as phenytoin & phenobarbital.

Ornidazole prolongs the muscle relaxant effect of vecuronium bromide.

DOSAGE:
The usual dose is 1 as twice-daily therapy.

ADMINISTRATION:
Ofloxacin and ornidazole tablets are supplied for oral administration & should be swallowed whole with a sufficient quantity of liquid. Do not crush or chew the tablets. Never change the dose of your medicine without talking to your doctor first. Continue to take your tablets for as long as your doctor recommends.
PRESENTATION:
STORAGE:
Store below 25°C in a cool & dry pace. Protect from direct sunlight. Keep away from the reach of children.

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This leaflet was last revised on May 2019.