Ciprofloxacin, a faint to light yellow crystalline powder which is soluble in water, is a fluoroquinolone antibacterial.
Empirical Formula: C17H18FN3O3·HCl·H2O.
Molecular Weight: 385.8.
Chemical Name: The monohydrochloride monohydrate salt of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid.
CAS Registry Number: 86393-32-0.
Ciprofloxacin Sterile Eye Drops contain the equivalent of 3 mg/mL ciprofloxacin base. It is compounded as a sterile, multi-dose product, for topical ophthalmic use. The pH of CIPROFLOXACIN Eye Drops is approximately 4.5 and the osmolality is approximately 300 mOsm. CIPROFLOXACIN Eye Drops.
Excipients/Inactive Ingredients: Sodium acetate, acetic acid, mannitol, disodium edetate, hydrochloric acid and/or sodium hydroxide (to adjust pH), purified water and benzalkonium chloride (0.006 mg/mL) as preservative.
Pharmacology: Ciprofloxacin has in vitro activity against a wide range of gram-negative and gram-positive organisms, possessing the greatest antibacterial activity of all quinolones. The bactericidal action of ciprofloxacin results from interference with the enzyme DNA gyrase which is needed for the synthesis of bacterial DNA. Ciprofloxacin has been shown to be active against most strains of the following organisms both in vitro and in clinical infections (see Indications/Uses): Gram-Positive: Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant strains), Staphylococcus epidermidis, Streptococcus pneumoniae, Viridans group of Streptococcus.
Gram-Negative: Pseudomonas aeruginosa, Serratia marcescens, Haemophilus influenzae.
Other Organisms: Most strains of Pseudomonas cepacia and some strains of Pseudomonas maltophilia are resistant to ciprofloxacin as are most anaerobic bacteria, including Bacteroides fragilis and Clostridium difficile.
The minimal bactericidal concentration (MBC) generally does not exceed the minimal inhibitory concentration (MIC) by more than a factor of 2. Resistance to ciprofloxacin in vitro usually develops slowly (multiple-step mutation). A plasmid-mediated bacterial resistance does not appear to occur with the fluoroquinolone class of antibiotics; however, parallel resistance is seen with this group of gyrase inhibitors.
There is no cross-over resistance between ciprofloxacin and other antibacterial compounds with different chemical structures, such as â-lactam antibiotics, aminoglycosides, tetracyclines, macrolide and peptide antibiotics as well as sulfonamides, trimethoprim and nitrofuran derivatives because of its special mode of action.
Pharmacodynamics: Clinical Studies: Following therapy with CIPROFLOXACIN Eye Drops 76% of the patients with corneal ulcers and positive bacterial cultures were clinically cured and complete re-epithelialization occurred in about 92% of the ulcers. In 3 and 7 day multicentre clinical trials, 52% of the patients with conjunctivitis and positive conjunctival cultures were clinically cured and 70-80% had all causative pathogens eradicated by the end of treatment.
Pharmacokinetics: Results of a systemic absorption study of CIPROFLOXACIN Eye Drops administered in each eye every two hours while awake for two days followed by every four hours while awake for an additional 5 days showed: the maximum reported plasma concentration of ciprofloxacin was 4.7 ng/mL (some 450-fold less than levels observed following simple 250 mg oral administration). The mean concentration was usually less than 2.5 ng/mL.
Toxicology: Toxicological Properties: Results of research on Ciprofloxacin and related drugs have shown them to cause arthropathy in immature animals of most species tested following oral administration. However, a one-month topical ocular study using immature Beagle dogs did not demonstrate any articular lesions. Acute topical ocular toxicology studies performed in rabbits employing an exaggerated topical ocular exposure to 0.3%, 0.75%, or 1.5% ciprofloxacin ophthalmic solution showed findings that were minimal and transient in nature, confined to the conjunctiva and generally comparable to those effects observed in the untreated control and vehicle control groups.
A subchronic, one-month topical ocular irritation study of 0.3% to 1.5% ciprofloxacin ophthalmic solution did not demonstrate any apparent systemic or ocular toxicity in rabbits.
Treatment of corneal ulcers, conjunctivitis and blepharitis caused by susceptible strains of bacteria in adults and children 12 months of age or older.
Corneal Ulcers: The recommended dosage regimen for the treatment of corneal ulcers is: 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 remainder of the first day. On the second day, instill two drops in the affected eye hourly. On the third through the fourteenth day, place two drops in the affected eye every four hours. Treatment may be continued after 14 days if corneal re-epithelialization has not occurred.
Bacterial Conjunctivitis/Blepharitis: The recommended dosage regimen for the treatment of bacterial conjunctivitis is: One drop instilled into the conjunctival sac(s) every two hours while awake for two days and one drop every four hours while awake for the next five days.
A topical overdose of CIPROFLOXACIN Eye Drops may be flushed from the eye(s) with warm tap water.
A history of hypersensitivity to ciprofloxacin or any other component of the medication. A history of hypersensitivity to other quinolones, including nalidixic acid, may also contraindicate the use of ciprofloxacin.
FOR TOPICAL USE ONLY NOT FOR INJECTION.
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving systemic quinolone therapy. Some reactions were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial oedema, dyspnoea, urticaria, and itching. Only a few patients had a history of hypersensitivity reactions. Serious anaphylactic reactions require immediate emergency treatment with adrenaline and other resuscitation measures, including oxygen, intravenous fluids, intravenous antihistamines, corticosteroids, pressor amines and airway management, as clinically indicated.
Moderate to severe phototoxicity manifested by an exaggerated sunburn reaction has been observed in some patients who were exposed to direct sunlight while receiving some members of the quinolone class of drugs, including oral ciprofloxacin. Excessive sunlight should be avoided.
General: As with other antibacterial preparations, prolonged use of ciprofloxacin may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, appropriate therapy should be initiated. Whenever clinical judgment dictates, the patient's eye(s) should be examined with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein staining. Ciprofloxacin should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity reaction. In clinical studies of patients with bacterial corneal ulcer a white crystalline precipitate located in the superficial portion of the corneal defect was observed in 35 (16.6%) of 210 patients. The onset of the precipitate was within 24 hours to 7 days after starting therapy. In one patient, the precipitate was immediately irrigated out upon its appearance. In 17 patients, resolution of the precipitate was seen in 1 to 8 days (seven within the first 24-72 hours); in five patients, resolution was noted in 10-13 days. In nine patients, exact resolution days were unavailable, however, at follow-up examinations, 18-44 days after onset of the event, complete resolution of the precipitate was noted. In three patients, outcome information was unavailable. The precipitate did not preclude continued use of ciprofloxacin, nor did it adversely affect the clinical course of the ulcer or visual outcome (see Adverse Reactions).
Carcinogenesis, Mutagenesis, Impairment of Fertility: Eight in vitro mutagenicity tests have been conducted with ciprofloxacin and the test results are listed as follows: Salmonella Microsome Test (Negative), E. coli DNA Repair Assay (Negative), Mouse Lymphoma Cell Forward Mutation Assay (Positive), Chinese Hamster V79 Cell HGPRT Test (Negative), Syrian Hamster Embryo Cell Transformation Assay (Negative), Saccharomyces cerevisiae Point Mutation Assay (Negative), Saccharomyces cerevisiae Mitotic Crossover and Gene Conversion Assay (Negative), Rat Hepatocyte DNA Repair Assay (Positive).
Thus, two of the eight tests were positive, but the results of the following three in vivo test systems gave negative results: Rat Hepatocyte DNA Repair Assay, Micronucleus Test (Mice), Dominant Lethal Test (Mice), Carcinogenicity studies in mice (oral doses up to 1090 mg/kg/day and 1455 mg/kg/day in males and females, respectively) and rats (oral doses up to 241 mg/kg/day and 328 mg/kg/day in males and females, respectively) showed no evidence of carcinogenicity.
Other Animal Studies: Special studies included a cataractogenic potential study of systemic ciprofloxacin in rats. The results indicated that ciprofloxacin was not co-cataractogenic. An intravenous study of ciprofloxacin at dose levels up to 20 mg/kg over a 6-month period in Rhesus monkeys indicated there were no signs of changes in lens transparency due to the administration of ciprofloxacin.
The arthropathogenic potential of some quinolones in immature animals after oral administration is recognised. Topical ocular administration of ciprofloxacin to immature animals did not cause any arthropathy and there is no evidence that the ophthalmic dosage form has any effect on the weight-bearing joints.
Use in Pregnancy: Category B3 - Reproduction studies have been performed in rats and mice at doses up to six times the usual daily human oral dose and have revealed no evidence of impaired fertility or harm to the foetus due to ciprofloxacin. In rabbits, as with most antimicrobial agents, ciprofloxacin (30 and 100 mg/kg orally) produced gastrointestinal disturbances resulting in maternal weight loss and an increased incidence of abortion. No teratogenicity was observed at either dose. After intravenous administration at doses up to 20 mg/kg, no maternal toxicity was produced and no embryotoxicity or teratogenicity was observed. There are no adequate and well controlled studies in pregnant women. Ciprofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Use in Lactation: We do not know whether topically applied ciprofloxacin is excreted in human milk, however, it is known that systemically administered ciprofloxacin is excreted in the milk of lactating rats, and oral ciprofloxacin has been reported in human breast milk after a single 500 mg dose. Caution should be exercised when ciprofloxacin is administered to a nursing mother.
Use in Children: Safety and effectiveness in children below the age of 1 year have not been established. Although ciprofloxacin and other quinolones cause arthropathy in immature animals after oral administration, topical ocular administration of ciprofloxacin to immature animals did not cause any arthropathy, and there is no evidence that the ophthalmic dosage form has any effect on the weight-bearing joints.
Use in Pregnancy: Category B3 - Reproduction studies have been performed in rats and mice at doses up to six times the usual daily human oral dose and have revealed no evidence of impaired fertility or harm to the foetus due to ciprofloxacin. In rabbits, as with most antimicrobial agents, ciprofloxacin (30 and 100 mg/kg orally) produced gastrointestinal disturbances resulting in maternal weight loss and an increased incidence of abortion. No teratogenicity was observed at either dose. After intravenous administration at doses up to 20 mg/kg, no maternal toxicity was produced and no embryotoxicity or teratogenicity was observed. There are no adequate and well controlled studies in pregnant women. Ciprofloxacin should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Use in Lactation: We do not know whether topically applied ciprofloxacin is excreted in human milk, however, it is known that systemically administered ciprofloxacin is excreted in the milk of lactating rats, and oral ciprofloxacin has been reported in human breast milk after a single 500 mg dose. Caution should be exercised when ciprofloxacin is administered to a nursing mother.
The most frequently reported drug related adverse reaction was local burning or discomfort.
Specific drug interaction studies have not been conducted with ophthalmic ciprofloxacin. However, the systemic administration of some quinolones has been shown to elevate plasma concentrations of theophylline, interfere with the metabolism of caffeine, enhance the effects of the oral anticoagulant warfarin and its derivatives and have been associated with transient elevations in serum creatinine in patients receiving cyclosporin concomitantly.
Incompatibilities: Alkaline solutions.
Pharmaceutical Precautions: Store below 30°C. Do not freeze. Protect from light.
Discard container 4 weeks after opening.
S01AE03 - ciprofloxacin ; Belongs to the class of quinolone antiinfectives. Used in the treatment of eye infections.
Celsus Ciprofloxacin Eye Drops eye drops 0.3 %
5 mL x 1's (P185/container)
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