(CIPROFLOXACIN 500MG CAPLETS AND CIPROFLOXACIN 0.3% EYE/EAR DROPS)

COMPOSITION

Each caplet of Ciflaxin^® contains 500mg Ciprofloxacin. Ciflaxin^® Eye/Ear Drops contains Ciprofloxacin 3mg/ml ophthalmic sterile solution. Ciprofloxacin is chemically described as 1-Cyclopropyl-6-fluoro-1, 4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline-carboxylic acid.

The chemical formula is C₁₇H₁₈FN₃O₃.HCl.H₂O.

CLINICAL PHARMACOLOGY

Pharmacodynamic properties:

Ciprofloxacin is a synthetic 4-quinolone derivative with bactericidal activity. Ciprofloxacin acts by inhibiting the A subunit of DNAgyrase (Topoisomerase) which is essential in the reproduction of bacterial DNA.

Ciprofloxacin is highly active against a wide range of Gram-positive and Gram-negative organisms and has shown activity against some anaerobes, Chlamydia spp. and Mycoplasma spp.. Killing curves demonstrate the rapid bactericidal effect against sensitive organisms and it is often found that minimum bactericidal concentrations are in the range of minimum inhibitory concentrations.[ The unique chemical structure and mechanism of action peculiar to fluoroquinolones ensures that Ciflaxin^® Eye/Ear Drops is one of the most effective of currently available ophthalmic antibiotics].

Pharmacokinetic properties:

Absorption of oral doses of ciprofloxacin occurs rapidly, mainly from the small intestine, the half-life of absorption being 2-15 minutes. Plasma levels are dose related and peak 0.5-2.0 hours after dosing. The oral bioavailability is approximately 70-80%.

Distribution of Ciprofloxacin within tissues is wide and the volume of distribution high, though slightly lower in the elderly. Protein binding is low (between 19-40%). Only 10-20% of a single oral dose is eliminated as metabolites (which exhibit lower activity than the parent drug).

Elimination of Ciprofloxacin and its metabolites occurs rapidly, primarily by the kidney. Renal elimination takes place mainly during the first 12 hours after dosing and renal clearance levels suggest that active secretion by the renal tubules occurs in addition to normal glomerular filtration.

It is recommended that in patients with severe renal impairment, the total daily dose should be reduced by half, although monitoring of drug serum levels provides the most reliable basis for dose adjustment as necessary.

After topical ocular administration,Ciprofloxacin is also absorbed systemically. Plasma levels in volunteers ranged from non quantifiable to 4.7ng/ml (some 450-fold less than levels observed following 250mg oral administration).

 

INDICATIONS

Ciflaxin^® caplet is indicated for the treatment of the following infections caused by sensitive bacteria:-

• Respiratory tract infections e.g. Lobar and bronchopneumonia, acute and chronic bronchitis, acute exacerbation of cystic fibrosis, bronchiectasis and empyema. Ciprofloxin may be used for treating Gram-negative pneumonia.
• Ear, nose and throat infections e.g. mastoiditis, otitis media and sinusitis, caused by Gram-positive bacteria (including pseudomonas spp.)
• Eye infections e.g. bacterial conjunctivitis.
• Urinary tract infections e.g. uncomplicated and complicated urethritis, cystitis, pyelonephritis, prostatitis and epididymitis.
• Skin and soft tissue infections e.g. infected ulcers, wound infections, abscesses, cellulitis, otitis external, erysipelas and infected burns.
• Bone and joint infections e.g. osteomyelitis, septic arthritis.
• Intra-abdominal infections e.g. peritonitis, intra-abdominal abscesses.
• Infections of the biliary tract: e.g. cholangitis, cholecystitis, empyema of the gall bladder.
• Gastro-intestinal infections e.g. enteric fever, infective diarrhea.
• Pelvic infections: e.g. salpingitis, endometritis, pelvic inflammatory disease.
• Severe systemic infections e.g. septicaemia, bacteraemia, peritonitis infection in immuno-suppressed patients
• Gonorrhoea: including urethral, rectal and pharyngeal gonorrhoea caused by β-lactamase producing organisms or organisms moderately sensitive to penicillin.
• Ciprofloxacin is also indicated for prophylaxis against infection in elective upper gastro-intestinal tract surgery and endoscopic procedures, where there is an increased risk of infection.
• For the treatment of acute pulmonary exacerbation of cystic fibrosis associated with Pseudomonas aeruginosa infection in paediatric patients aged 5-17 years.
• Ciflaxin^® Eye/Ear Drops is effective in the treatment of
• Bacterial conjunctivitis
• Blepharitis
• Bacterial keratitis
• Corneal ulcer
• Otitis external

CONTRAINDICATIONS

Ciflaxin is contraindicated in patients who have shown hypersensitivity to Ciprofloxacin or other quinolone anti-infectives.

Except in cases of exacerbations of cystic fibrosis associated with P. aeruginosa (in patients aged 5-17 years), Ciprofloxacin is contraindicated in child                                                      ren and growing adolescents unless the benefits of treatment are considered to outweigh the risks.

DRUG INTERACTIOS

• Increased plasma levels of theophylline have been observed following concurrent administration with ciprofloxacin.

It is recommended that the dose of theophylline should be reduced

and its plasma levels monitored.

• Phenytoin levels may be altered when Ciprofloxacin is used concomitantly.
• Ciprofloxacin should not be administered within 4 hours of medications containing magnesium, aluminum, calcium or iron salts as interference with absorption may occur.
• Prolongation of bleeding time has been reported during concomitant administration of Ciprofloxacin and oral anticoagulants.
• Transient increase in serum creatinine has been seen following concomitant administration of Ciprofloxacin and Cyclosporine. Therefore, monitoring of serum creatinine levels is advisable.

PREGNANCY AND LACTATION

Reproductive studies performed in Mice, Rats and Rabbits using parenteral and oral administration did not reveal any evidence of teratogenicity, impairment of fertility or impairment of peri/postnatal development. However, as with other quinolones, Ciprofloxacin has been shown to cause arthropathy in immature animals and therefore its use during pregnancy is not recommended. Studies have indicated that Ciprofloxacin is secreted in breast milk. Administration to nursing mothers is thus not recommended. Excretion of Ciprofloxacin into human milk following topical ophthalmic administration has not been investigated. Therefore, caution should be exercised when Ciflaxin^® Eye/Ear drops is administered to nursing mothers.

WARNINGS/PRECAUTIONS

Ciprofloxacin caplets should be used with caution in patients with epilepsy or history of Central Nervous Systems (CNS) disorders.

• Tendon damage may occur rarely with fluoroquinolones and treatment should be discontinued if patients experience tendon pain, inflammation or rupture.
• An adequate fluid intake should be maintained during treatment with Ciprofloxacin caplets and excessive alkalinity of the urine avoided because of the risk of crystalluria.
• Ciprofloxacin and other quinolones should be avoided in methicillin-resistant Staphylococcus aureus infections because of the high level of resistant.
• Ciflaxin^® Eye/Ear Drops should be used in pregnancy only if the potential benefit outweighs the possible risk to the foetus. However caution should be exercised when Ciflaxin^® Eye/Ear Drops is being administered to nursing mother.
• Ciflaxin^® Eye/Ear Drops is not recommended in children below the age of 12 years.

 

KEEP OUT OF THE REACH OF CHILDREN

SIDE/ADVERSE EFFECTS

Ciprofloxacin caplet is generally well tolerated.

• Gastrointestinal disturbance include nausea, vomiting, diarrhea, abdominal pain and dyspepsia.
• Headache, dizziness and restlessness are among the commonest effects on the central nervous system.
• Hypersensitivity reactions affecting the skin includes rarely vasculitis, erythema multiforme, Steven-Johnson syndrome and toxic epidermal necrolysis.
• Reversible arthralgia has sometimes occurred and joint erosions have been documented in immature animals. Tendon damage has also been reported.

The side effects of Ciprofloxacin Eye/Ear drops include local burning or discomfort. Others occurring in few patients are lid margin crusting, itching, conjunctiva hyperemia and a bad taste following instillation.

SYMTOMS OF OVERDOSE AND ANTIDOTE

Symptoms include acute renal failure and seizures. Treatment includes GI decontamination and supportive care. It is recommended to monitor renal function, including urinary pH and acidify, if required, to prevent crystalluria.

Patients must be kept well hydrated and, in the case of renal damage resulting in oliguria, dialysis should be initiated.

Calcium or magnesium antacids may be administered as soon as possible after ingestion of Ciflaxin^® in order to reduce the absorption of Ciprofloxacin. Serum level of Ciprofloxacin is reduced by dialysis.

A topical overdose of Ciprofloxacin Eye drops may be flushed from the eye(s) with warm tap water.

DOSGE AND ADMINISTRATION

     The usual adult dose of Ciprofloxacin ranges from 250mg to 750mg

twice daily depending on the severity and nature of the infection.

• Urinary tract infection:

250mg-500mg every 12hours for 7-10 days depending on

severity of infection and susceptibility.

• Uncomplicated cystitis(in females):

250mg every 12 hours for 3 days.

• Lower respiratory tract, skin/skin structure infection:

500mg-750mg twice daily for 7-14 days depending on severity of infection and susceptibility.

• Bone/joint infections:

500mg-750mg twice daily for 4-6 weeks, depending on severity of infection and susceptibility.

• Infectious diarrhea:

500mg every 12 hours (twice daily) for 5-7 days.

• Typhoid fever:

500mg every 12 hours (twice daily) for 10 days.

• Urethral/cervical gonococcal infections:

500mg as a single dose.

• Disseminated gonococcal infection:

500mg twice daily to complete 7 days of therapy (initial treatment

with ceftriaxone 1g i.m./i.v daily for 24-48 hours after

improvement begins).

• Chancroid:

500mg twice daily for 3 days

 

• Mild to moderate sinusitis

500mg twice daily for 10 days

• Chronic bacterial prostratitis

500mg twice daily for 28 days

• Instill one or two drops Ciflaxin^® Eye/Ear into the conjunctival sac(s) every two hours for two days and one or two drops every four hours for 5days in case of bacterial conjunctivitis.
• In case of corneal ulcers, instill two drops into the affected eye every 15 minutes for the first six hours and then two drops into the affected eye every 30 minutes for the rest of the day. Two drops every hour on second day and two drops should be placed into the affected eye every four hours from the third to the fourteenth day.
• Two drops to be placed in the affected ear every four hours.

PRESENTATION

Ciflaxin^® is available as caplets containing500mg Ciprofloxacin in a blister of 10’s per pack.

Ciflaxin^® Eye/Ear Drops is supplied as 0.3% solution in sterile lupolen bottle containing 5ml of the ophthalmic solution.

STORAGE

Store Ciflaxin^® Caplets below 30⁰C

Store Ciflaxin^® Eye/Ear Drops between 2⁰C to 30⁰C. Protect from light