Product Manual: Florocin

PRODUCT BRIEF

NAME OF THE PRODUCTBrand Name:FlorocinGeneric Name:Ciprofloxacin USP.

DOSAGE FORM & STRENGTH OF THE PRODUCT1. Tablet : Ciprofloxacin 500 mg

2. PFS : Ciprofloxacin 250mg/5mlDESCRIPTION OF THE PRODUCT

1. Florocin 500F

Presentation:A caplet of size # 2 with off white colour.

Packing :Alu-Alu Blister of 10 Tablets.

Pack Size :3 ( 10 Tablets in a box.

2. Florocin PFS

Presentation :Dry powder to reconstitute suspension

Packing :Amber glass bottle.

Pack Size :60ml.

PRODUCT MONOGRAPH

CHEMISTRY

Florocin (Ciprofloxacin) Tablets and Florocin (ciprofloxacin) Powder For Suspension are synthetic broad spectrum antimicrobial agents for oral administration. Ciprofloxacin hydrochloride, USP, a fluoroquinolone, is the monohydrochloride monohydrate salt of l-cyclopropyl-6-fluoro-l, 4-dihydro-4-oxo-7-(l-piperazinyl)-3-quinolinecarboxylic acid. It is a faintly yellowish to light yellow crystalline substance with a molecular weight of 385.8. Its empirical formula is C17H18FN3O3HClH2O and its chemical structure is as follows:

PHARMACOKINETICS

Absorption

Ciprofloxacin given as an oral tablet is rapidly and well absorbed from the gastrointestinal tract after oral administration. The absolute bioavailability is approximately 70% with no substantial loss by first pass metabolism. Ciprofloxacin maximum serum concentrations and area under the curve are shown in the chart for the 250 mg to 1000 mg dose range.

Dose (mg)Maximum Serum Concentration (g/mL)Area Under Curve (AUC)

2501.24.8

5002.411.6

7504.320.2

10005.430.8

Maximum serum concentrations are attained 1 to 2 hours after oral dosing. Mean concentrations 12 hours after dosing with 250, 500, or 750 mg are 0.1, 0.2, and 0.4 g/mL, respectively. The serum elimination half-life in subjects with normal renal function is approximately 4 hours. Serum concentrations increase proportionately with doses up to 1000 mg.

A 500 mg oral dose given every 12 hours has been shown to produce an area under the serum concentration time curve (AUC) equivalent to that produced by an intravenous infusion of 400 mg ciprofloxacin given over 60 minutes every 12 hours. A 750 mg oral dose given every 12 hours has been shown to produce an AUC at steady-state equivalent to that produced by an intravenous infusion of 400 mg given over 60 minutes every 8 hours. A 750 mg oral dose results in a Cmax similar to that observed with a 400 mg I.V. dose. A 250 mg oral dose given every 12 hours produces an AUC equivalent to that produced by an infusion of 200 mg ciprofloxacin given every 12 hours.

Distribution

The binding of ciprofloxacin to serum proteins is 20 to 40% which is not likely to be high enough to cause significant protein binding interactions with other drugs. After oral administration, ciprofloxacin is widely distributed throughout the body. Tissue concentrations often exceed serum concentrations in both men and women, particularly in genital tissue including the prostate. Ciprofloxacin is present in active form in the saliva, nasal and bronchial secretions, mucosa of the sinuses, sputum, skin blister fluid, lymph, peritoneal fluid, bile, and prostatic secretions. Ciprofloxacin has also been detected in lung, skin, fat, muscle, cartilage, and bone. The drug diffuses into the cerebrospinal fluid (CSF); however, CSF concentrations are generally less than 10% of peak serum concentrations. Low levels of the drug have been detected in the aqueous and vitreous humors of the eye.

Metabolism

Four metabolites have been identified in human urine which together account for approximately 15% of an oral dose. The metabolites have antimicrobial activity, but are less active than unchanged ciprofloxacin. Ciprofloxacin is an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism. Coadministration of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the coadministered drug

Excretion

The serum elimination half-life in subjects with normal renal function is approximately 4 hours. Approximately 40 to 50% of an orally administered dose is excreted in the urine as unchanged drug. After a 250 mg oral dose, urine concentrations of ciprofloxacin usually exceed 200 g/mL during the first two hours and are approximately 30 g/mL at 8 to 12 hours after dosing. The urinary excretion of ciprofloxacin is virtually complete within 24 hours after dosing. The renal clearance of ciprofloxacin, which is approximately 300 mL/minute, exceeds the normal glomerular filtration rate of 120 mL/minute. Thus, active tubular secretion would seem to play a significant role in its elimination. Co-administration of probenecid with ciprofloxacin results in about a 50% reduction in the ciprofloxacin renal clearance and a 50% increase in its concentration in the systemic circulation. Although bile concentrations of ciprofloxacin are several fold higher than serum concentrations after oral dosing, only a small amount of the dose administered is recovered from the bile as unchanged drug. An additional 1 to 2% of the dose is recovered from the bile in the form of metabolites. Approximately 20 to 35% of an oral dose is recovered from the feces within 5 days after dosing. This may arise from either biliary clearance or transintestinal elimination.

SUMMARY OF PHARMACOKINETICS

FactorFlorocin (Ciprofloxacin)

AbsorptionGastrointestinal Tract, 70%

Tmax 1-2 hr

Half-life4 hr

Distribution20-40% plasma protein-bound; volume of distribution about 2.5 L

MetabolismHepatic, Cytochrome P450 1A2 (CYP1A2)

ExcretionExcreted through feces (20-35%) and urine (40-50%)

MECHANISM OF ACTION

Florocin (Ciprofloxacin) is a synthetic bactericidal antibiotic that inhibits bacterial nuclear DNA synthesis, so that bacteria rapidly die. The target is the enzyme DNA gyrase (topoisomerase II), which is responsible for the supercoiling and uncoiling of the DNA. Supercoiling of the DNA allows the long DNA molecule to fit into the cell. Uncoiling of the structure is the initiative step for replication, transcription, and repair of the DNA. Thus, prolonged inhibition will lead to the death of the cell.FLOW CHART

Florocin (Ciprofloxacin)

Binds with DNA gyrase (topoisomerase II),Interferes with supercoiling and uncoiling of the DNAInterferes with replication, transcription, and repair of the DNAInhibits bacterial nuclear DNA synthesis

Leads to the death of bacterial cell.INDICATIONS

Urinary tract infections: urethritis (infection of the urethra), cystitis (infection of the bladder ), pyelonephritis (infection of the kidneys).

Acute uncomplicated cystitis in women

Chronic bacterial prostatitis

Lower respiratory infections (pneumonia, bronchitis, tracheobronchitis). Ciprofloxacin is not a drug of first choice in the treatment of pneumonia secondary to Streptococcus pneumoniae.

Acute sinusitis (inflammation of the paranasal sinuses).

Skin and skin structure infections: cellulitis (infection of the dermis and subcutaneous tissue), erysipelas (superficial form of cellulitis), folliculitis (inflammation of the hair follicles, if the infection of the follicle is deeper and involves more follicles, it moves into the furuncle and carbuncle), furuncles, carbuncles, abscesses, impetigo (large vessicles or honey-crusted sores), infected ulcers and infected burns and other.

Bone and joint infections: septic (infectious) arthritis (infection in the fluid and tissues of a joint), osteomyelitis (bone infection).

Complicated intra-abdominal infections (used in combination with metronidazole). Complicated intra-abdominal infections are defined by the FDA as those in which an operation would not remove all of the infected tissue. Intra-abdominal infections include: intra-abdominal abscess, peritonitis (infection of the abdominal cavity and its lining), cholecystitis, cholangitis, diverticulitis and some other.

Infectious diarrhea: Escherichia coli infection, Campylobacter infection, and shigellosis.

Typhoid fever (enteric fever) .

STDs: uncomplicated cervical and urethral gonorrhea

Complicated urinary tract iInfections and pyelonephritis in children (1 to 17 years of age)

Inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis (in adults and children)

DOSAGE AND ADMINISTRATION

The determination of dosage for any particular patient must take into consideration the severity and nature of the infection, the susceptibility of the causative organism, the integrity of the patient's host-defense mechanisms, and the status of renal function and hepatic function. The duration of treatment depends upon the severity of infection. The usual duration is 7 to 14 days; however, for severe and complicated infections more prolonged therapy may be required. Ciprofloxacin should be administered at least 2 hours before or 6 hours after magnesium/aluminum antacids, or sucralfate.

ADULT DOSAGE GUIDELINES

InfectionSeverityDoseFrequencyUsual Durations

Urinary TractAcute Uncomplicated 250 mgq12h3 days

Mild/Moderate 250 mgq12h7 to 14 days

Severe/Complicated500 mgq12h7 to 14 days

Chronic Bacterial Mild/Moderate Prostatitis500 mgq12h 28 days

Lower Respiratory Tract Mild/Moderate500 mgq12h7 to 14 days

Severe/Complicated750 mgq12h7 to 14 days

Acute SinusitisMild/Moderate500 mgq12h10 days

Skin and Skin StructureMild/Moderate500 mg q12h7 to 14 days

Severe/Complicated750 mgq12h7 to 14 days

Bone and JointMild/Moderate 500 mgq12h 4 to 6 weeks

Severe/Complicated750 mgq12h 4 to 6 weeks

Intra- Abdominal*Complicated500 mgq12h7 to 14 days

Infectious DiarrheaMild/Moderate/Severe500 mgq12h5 to 7 days

Typhoid FeverMild/Moderate500 mgq12h10 days

Urethral and Cervical Gonococcal InfectionsUncomplicated250 mgsingle dosesingle dose

Inhalational anthrax (post-exposure)** 500 mgq12h60 days

* used in conjunction with metronidazole Generally ciprofloxacin should be continued for at least 2 days after the signs and symptoms of infection have disappeared, except for inhalational anthrax (post-exposure). ** Drug administration should begin as soon as possible after suspected or confirmed exposure.

PEDIATRIC DOSAGE GUIDELINESInfectionRoute of AdministrationDose(mg/kg)FrequencyTotal Duration

Complicated Urinary Tract or Pyelonephritis(patients from 1 to 17 years of age)10-21 days*

Oral10 mg/kg to 20 mg/kg (maximum 750 mg per dose; not to be exceeded even in patients weighing > 51 kg)Every 12 hours

Inhalational Anthrax (Post-Exposure)**60 days

Oral15 mg/kg (maximum 500 mg per dose)Every 12 hours

* The total duration of therapy for complicated urinary tract infection and pyelonephritis in the clinical trial was determined by the physician. The mean duration of treatment was 11 days (range 10 to 21 days). **Drug administration should begin as soon as possible after suspected or confirmed exposure to Bacillus anthracis spores. This indication is based on a surrogate endpoint, ciprofloxacin serum concentrations achieved in humans, reasonably likely to predict clinical benefit.5 For a discussion of ciprofloxacin serum concentrations in various human populations.

Side Effects

The most frequently reported drug related events, from clinical trials of all formulations, all dosages, all drug-therapy durations, and for all indications of ciprofloxacin therapy were nausea (2.5%), diarrhea (1.6%), liver function tests abnormal (1.3%), vomiting (1%), and rash (1%).

Additional medically important events that occurred in less than 1% of ciprofloxacin patients are listed below.

BODY AS A WHOLE: headache, abdominal pain/discomfort, foot pain, pain, pain in extremities, injection site reaction (ciprofloxacin intravenous)

CARDIOVASCULAR: palpitation, atrial flutter, ventricular ectopy, syncope, hypertension, angina pectoris, myocardial infarction, cardiopulmonary arrest, cerebral thrombosis, phlebitis, tachycardia, migraine, hypotension

CENTRAL NERVOUS SYSTEM: restlessness, dizziness, lightheadedness, insomnia, nightmares, hallucinations, manic reaction, irritability, tremor, ataxia, convulsive seizures, lethargy, drowsiness, weakness, malaise, anorexia, phobia, depersonalization, depression, paresthesia, abnormal gait, grand mal convulsion

GASTROINTESTINAL: painful oral mucosa, oral candidiasis, dysphagia, intestinal perforation, gastrointestinal bleeding, cholestatic jaundice, hepatitis

HEMIC/LYMPHATIC: lymphadenopathy, petechia

METABOLIC/NUTRITIONAL: amylase increase, lipase increase

MUSCULOSKELETAL: arthralgia or back pain, joint stiffness, achiness, neck or chest pain, flare up of gout

RENAL/UROGENITAL: interstitial nephritis, nephritis, renal failure, polyuria, urinary retention, urethral bleeding, vaginitis, acidosis, breast pain

RESPIRATORY: dyspnea, epistaxis, laryngeal or pulmonary edema, hiccough, hemoptysis, bron-chospasm, pulmonary embolism

SKIN/HYPERSENSITIVITY: allergic reaction, pruritus, urticaria, photosensitivity/ phototoxicity reaction, flushing, fever, chills, angioedema, edema of the face, neck, lips, conjunctivae or hands, cutaneous candidiasis, hyperpigmentation, erythema nodosum, sweating

SPECIAL SENSES: blurred vision, disturbed vision (change in color perception, overbrightness of lights), decreased visual acuity, diplopia, eye pain, tinnitus, hearing loss, bad taste, chromatopsia

In several instances nausea, vomiting, tremor, irritability, or palpitation were judged by investigators to be related to elevated serum levels of theophylline possibly as a result of drug interaction with ciprofloxacin.

Drug Interaction

Concurrent administration of ciprofloxacin with theophylline may lead to elevated serum concentrations of theophylline and prolongation of its elimination half-life. This may result in increased risk of theophylline-related adverse reactions.

Ciprofloxacin interferes with the metabolism of caffeine. This may lead to reduced clearance of caffeine and a prolongation of its serum half-life.

Concurrent administration of ciprofloxacin, with multivalent cation-containing products such as magnesium/aluminum antacids, sucralfate, may substantially decrease its absorption, resulting in serum and urine levels considerably lower than desired.

Histamine H2-receptor antagonists appear to have no significant effect on the bioavailability of ciprofloxacin.

Altered serum levels of phenytoin (increased and decreased) have been reported in patients receiving concomitant ciprofloxacin.

The concomitant administration of ciprofloxacin with the sulfonylurea glyburide has, on rare occasions, resulted in severe hypoglycemia.

Ciprofloxacin, have been associated with transient elevations in serum creatinine in patients receiving cyclosporine concomitantly.

Ciprofloxacin, have been reported to enhance the effects of the oral anticoagulant warfarin or its derivatives. When these products are administered concomitantly, prothrombin time or other suitable coagulation tests should be closely monitored.

Probenecid interferes with renal tubular secretion of ciprofloxacin and produces an increase in the level of ciprofloxacin in the serum. This should be considered if patients are receiving both drugs concomitantly.

Renal tubular transport of methotrexate may be inhibited by concomitant administration of ciprofloxacin potentially leading to increased plasma levels of methotrexate. This might increase the risk of methotrexate associated toxic reactions. Therefore, patients under methotrexate therapy should be carefully monitored when concomitant ciprofloxacin therapy is indicated.

Metoclopramide significantly accelerates the absorption of oral ciprofloxacin resulting in shorter time to reach maximum plasma concentrations. No significant effect was observed on the bioavailability of ciprofloxacin.

Non-steroidal anti-inflammatory drugs (but not acetyl salicylic acid) in combination of very high doses of quinolones have been shown to provoke convulsions in pre-clinical studies.

ContraindicationCiprofloxacin is contraindicated in persons with a history of hypersensitivity to ciprofloxacin, any member of the quinolone class of antimicrobial agents, or any of the product components.

History of tendon disorders caused by previous treatment with a quinolone-type antibiotic.

Allergy to other quinolone-type antibiotics, eg norfloxacin, ofloxacin.

Concomitant administration with tizanidine is contraindicated.

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

SPECIAL POPULATIONS

Pregnancy or breastfeeding

Pregnancy category C. Ciprofloxacin should not be used during pregnancy or breastfeeding. However, Ciprofloxacin may be used in pregnancy or breastfeeding if the benefits to the mother outweigh the risks to the unborn baby.

This medicine is not recommended for use in pregnancy. This is because ciprofloxacin has been shown to cause joint disease in immature animals and may therefore have this effect in humans. There are usually safer alternative antibiotics available.

Ciprofloxacin passes into breast milk. It is not recommended for use during breastfeeding, as there are usually safer alternative antibiotics available.

Pediatric Use

Ciprofloxacin should be used in pediatric patients (less than 18 years of age). An increased incidence of adverse events compared to controls, including events related to joints and/or surrounding tissues, has been observed.In pre-clinical studies, oral administration of ciprofloxacin caused lameness in immature dogs. Histopathological examination of the weight-bearing joints of these dogs revealed permanent lesions of the cartilage. Related quinolone-class drugs also produce erosions of cartilage of weight-bearing joints and other signs of arthropathy in immature animals of various species.

Geriatric Use

Geriatric patients are at increased risk for developing severe tendon disorders including tendon rupture when being treated with Ciprofloxacin. This risk is further increased in patients receiving concomitant corticosteroid therapy. Tendinitis or tendon rupture can involve the Achilles, hand, shoulder, or other tendon sites and can occur during or after completion of therapy; cases occurring up to several months after fluoroquinolone treatment have been reported.

Renal Impairment

Ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and partially cleared through the biliary system of the liver and through the intestine. These alternative pathways of drug elimination appear to compensate for the reduced renal excretion in patients with renal impairment. Nonetheless, some modification of dosage is recommended, particularly for patients with severe renal dysfunction. The following table provides dosage guidelines for use in patients with renal impairment:

Creatinine Clearance (mL/min)Dose

> 50See Usual Dosage.

30-50250 - 500 mg q 12 h

5-29250-500mgql8h

Patients on hemodialysis or Peritoneal dialysis250 - 500 mg q 24 h (after dialysis)

Over Dose In the event of acute overdosage, reversible renal toxicity has been reported in some cases. The stomach should be emptied by inducing vomiting or by gastric lavage. The patient should be carefully observed and given supportive treatment, including monitoring of renal function and administration of magnesium, aluminum, or calcium containing antacids which can reduce the absorption of ciprofloxacin. Adequate hydration must be maintained. Only a small amount of ciprofloxacin ( < 10%) is removed from the body after hemodialysis or peritoneal dialysis.Warnings and Precautions

Ciprofloxacin tablets should be swallowed whole and not chewed.

You should not take milk, yoghurt, antacids for indigestion or heartburn, or medicines containing calcium, iron, zinc, magnesium or aluminium at the same time as ciprofloxacin. (See end of factsheet for more information.)

You should make sure you drink plenty of fluid while taking this medicine.

Avoid exposing your skin to excessive sunlight, sunlamps or sunbeds while taking ciprofloxacin, as it may increase the sensitivity of your skin to UV light. If you get a rash or other skin reaction on exposure to sunlight you should stop taking this medicine and consult your doctor.

This medicine may reduce your ability to drive or operate machinery safely. This effect may be enhanced by drinking alcohol. Do not drive or operate machinery until you know how this medicine affects you and you are sure it won't affect your performance.

Quinolone antibiotics may rarely cause tendon inflammation (tendinitis) and tendon rupture. People aged over 60, people who have had a kidney, heart, or lung transplant and those taking corticosteroid medication are most at risk of this. You should stop taking this medicine immediately if you experience any pain or inflammation in your joints during treatment. Rest the affected limb(s) and consult a doctor immediately.

Broad-spectrum antibiotics can sometimes cause inflammation of the bowel (colitis). For this reason, if you get diarrhoea either during or after taking this medicine, particularly if it becomes severe or persistent, or contains blood or mucus, you should consult your doctor immediately.

Unless your doctor tells you otherwise, it is important that you finish the prescribed course of this antibiotic medicine, even if you feel better or it seems the infection has cleared up. Stopping the course early increases the chance that the infection will come back and that the bacteria will grow resistant to the antibiotic.

Use with caution in

Children and adolescents.

People over 60 years of age.

People using corticosteroid medicines.

People who have had a kidney, heart, or lung transplant.

Decreased kidney function.

History of convulsions (fits), eg epilepsy.

History of disorders of the brain and nervous system.

People who a lack an enzyme called G6PD in their blood, or who have a family history of this disorder (G6PD deficiency).

Abnormal muscle weakness (myasthenia gravis).

Storage

Store at room temperature between 59-86 degrees F (15-30 degrees C) in a tightly closed container away from light and moisture. Do not store in the bathroom. Keep all medicines away from children. Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. SUPPLY

Florocin 500 Tablet : Box containing 30 Tablets in 3 x 10's in Alu-Alu blister strips. Florocin PFS : Bottle containing dry powder to reconstitute 60 ml suspension.Advantages and Disadvantages

Advantages: Ease of use - twice daily dosing.

Broad spectrum of antibacterial activity.

Ciprofloxacin is the only fluoroquinolone currently approved for post-exposure prophylaxis of anthrax.

Excellent bioavailability both orally and intravenously. Oral ciprofloxacin is 70-80% bioavailable, meaning that a 500 mg oral dose gives plasma concentrations in the same range as a 400 mg IV dose.

Good tissue penetration (especially in kidneys, gallbladder, liver, lungs, gynecological tissue, and prostatic tissue).

Inexpensive and is available in generic version.

Does not cause a significant prolongation in the QT interval

Most effective antibiotic against P. aeruginosa (bacteria that causes infections of the pulmonary tract, external ear, urinary tract, burns, and wounds and is the most frequent colonizer of medical devices (e.g.catheters)), which is becoming increasingly resistant.

Experience is favorable and extensive for nosocomial pneumonia, osteomyelitis, neutropenic fever, travelers diarrhea, chronic prostatitis and UTIs.

Disadvantages: Poor activity against Streptococcus pneumoniae (major cause of pneumonia and meningitis).

Several serious drug interactions (e.g. theophylline, propranolol). Ciprofloxacin can inhibit (prevent the activity) one of the pathways that is used to eliminate medications from the body. This pathway, called CYP1A2, works through an enzyme in the liver known as cytochrome P450 1A2. If CYP1A2 is inhibited, and the dose is not reduced, the medicine could accumulate in the body to levels that could cause serious adverse reactions.

Widespread use of Ciprofloxacin, often inappropriate, resulted in increasing rates of microbal resistance (development of resistance in P. aeruginosa, Salmonella, Neisseria gonorrhoeae).

Tendon damage. Achilles tendon is the most susceptible, however other tendons also may be affected. Usually, spontaneous tendon rupture occurs during or shortly after a course of antibiotic, but symptoms may occur months after taking the medication. Risk factors for tendon damage include use of corticosteroids, hypercholesterolemia, gout, rheumatoid arthritis, advanced age, long-term dialysis, and renal transplantation.

Peripheral neuropathy (peripheral nervous system side effects). The symptoms of neuropathy include pain, burning, tingling, numbness, and/or weakness, or is found to have deficits in light touch, pain, temperature, position sense, vibratory sensation, and/or motor strength. Ciprofloxacin should be stopped if person experiences these symptoms in order to prevent the development of an irreversible condition.

Phototoxicity.

Severe allergic reactions.

Crystalluria (crystals in the urine). Ciprofloxacin may induce calculi (kidney stones) via urinary supersaturation. The risk is higher when urinary pH is greater than 7.3 and antibiotic doses are greater than 1000 mg.

Absorption may be significantly reduced by dairy products. Ciprofloxacin should not be taken with dairy or calcium-fortified juices alone. However, it may be taken with a meal that contains these products (eg. cereal with milk).

Decrease the metabolism of caffeine ( the half-life of caffeine significantly increases)

Rare cases of vision disturbance

Ciprofloxacin may delay the fracture healing. The research data suggest that use of ciprofloxacin during early fracture repair may compromise the clinical course of fracture-healing.

Comperison with Other drugsCiprofloxacin vs. Levofloxacin Skin and Skin Structure InfectionsCiprofloxacin and Levofloxacin are equally effective for the treatment of skin infections

In clinical study among 253 patients (129 levofloxacin, 124 ciprofloxacin), cure and improvement were observed in 96.1% of levofloxacin-treated patients and in 93.5% of ciprofloxacin-treated patients. Bacteriological eradication rates by pathogen were 93.2% and 91.7%, respectively. Levofloxacin eradicated 94% (66/70) of Staphylococcus aureus and 94% (17/18) of Streptococcus pyogenes isolates, compared with 93% (70/75) and 92% (12/13) for ciprofloxacin. Microbiological eradication rates by subject were approximately 93% and 90% for the levofloxacin and ciprofloxacin groups, respectively. Adverse events were reported by 8.9% of those receiving levofloxacin and 8.2% of those administered ciprofloxacin.

Acute Pyelonephritis, Urinary tract infections (UTI)Levofloxacin is at least as effective as ciprofloxacin in the treatment of pyelonephritis .

In the modified intent-to-treat (mITT) population (levofloxacin 94, ciprofloxacin 98), 83% of levofloxacin-treated and 79.6% of ciprofloxacin-treated persons achieved microbiological eradication. In the microbiologically evaluable (ME) population (levofloxacin 80, ciprofloxacin 76), 92.5% of levofloxacin-treated vs. 93.4% of ciprofloxacin-treated persons achieved microbiologic eradication. Clinical success was achieved in 86.2% vs. 80.6% (mITT) and in 92.5% vs. 89.5% (ME) of levofloxacin-treated and ciprofloxacin-treated patients, respectively. Side effects were similar to those seen previously with both agents.

Chronic bacterial prostatitisLevofloxacin 500 mg once daily for 28 days is as effective as ciprofloxacin 500 mg twice daily for 28 days for the treatment of chronic bacterial prostatitis. Both provide similar clinical success rates, including cured plus improved patients (75% for levofloxacin and 72.8% for ciprofloxacin) and icrobiologic eradication rates (75% for levofloxacin and 76.8% for ciprofloxacin).

Ciprofloxacin vs. NorfloxacinUrinary tract infections in womenBoth agents are equally effective. In a double-blind, randomized controlled study 114 patients receiving ciprofloxacin and 112 receiving norfloxacin were evaluated. Bacteriologic cure was 91.2% in the ciprofloxacin group and 91.9% in the norfloxacin group. Clinical resolution was 91.2 and 93.8%, respectively.

Ciprofloxacin vs. Ofloxacin Complicated urinary tract infections in womenCiprofloxacin 250 mg 2 times per day is at least as effective as ofloxacin 200 mg 2 times per day in women with complicated lower urinary tract infection 11. In the study 90.1% of the ciprofloxacin group and 87.2% of the ofloxacin group had sterile urine 5-9 days after the end of therapy; 77.1% and 76.1% had sterile cultures, respectively. Clinical cure was achieved in 97.2% of both groups 5-9 days after cessation of therapy and a month later in 87.7% and 87.3%, respectively. Adverse events were mild and similar in both groups.

Ciprofloxacin vs. Co-TrimoxazolePyelonephritisCiprofloxacin is more effective than co-trimoxazole (Trimethoprim-Sulfamethoxazole) for pyelonephritis.

In randomized, double-blind comparative study at 4 to 11 days posttherapy, bacteriologic cure rates were 99% with ciprofloxacin and 89% with trimethoprim-sulfamethoxazole therapy. Clinical cure rates were 96% for the ciprofloxacin and 83% for the trimethoprim-sulfamethoxazole regimen. Escherichia coli, which caused more than 90% of infections, was more frequently resistant to co-trimoxazole (18%) than to ciprofloxacin (0%). Among trimethoprim-sulfamethoxazole-treated patients, resistance was associated with greater bacteriologic and clinical failure rates. Adverse events occurred in 24% of ciprofloxacin-treated patients and in 33% of trimethoprim-sulfamethoxazole-treated patients.

Ciprofloxacin vs. AmoxicillinChronic obstructive airways disease (acute exacerbations)

Ciprofloxacin is much more effective than amoxicillin in the treatment of acute exacerbations of chronic obstructive airways disease. In a comparative study ciprofloxacin produced a 91.8% success rate (complete success 21.9%; partial success 69.9%) while amoxicillin produced only 73.1% rate (complete success 10.4%; partial success 62.7%).

Ciprofloxacin vs. AugmentinChronic suppurative otitis mediaCiprofloxacin seems to be an effective treatment of chronic otitis media, and superior to Augmentin.

Ciprofloxacin (500 mg twice daily) was compared with amoxicillin/clavulanic acid (500 mg three times daily) in 76 persons with chronic suppurative otitis media. At the end of treatment, otorrhoea disappeared in 57.5% of the ciprofloxacin group and 37.1% of the amoxicillin/clavulanic acid group. Bacterial eradication rate was also significantly greater with ciprofloxacin (69.7%) than with amoxicillin/clavulanic acid (27.3%).

SinusitisCiprofloxacin appears to be at least as effective as Augmentin in the treatment of chronic sinusitis.

Adults with chronic sinusitis were enrolled into prospective double-blind, double-placebo comparison of ciprofloxacin (500 mg twice daily) with amoxicillin/clavulanic acid (500 mg three times daily). Treatment lasted 9 days, at the end of which nasal discharge disappeared in 71/118 (60.2%) patients of the ciprofloxacin group and 69/123 (56.1%) of those in the amoxicillin/clavulanic acid group. The clinical cure and bacteriological eradication rates were 58.6% versus 51.2% and 88.9% versus 90.5% for ciprofloxacin and amoxicillin/clavulanic acid, respectively. These differences were not significant, however, among patients who had a positive initial culture and who were evaluated 40 days later. Ciprofloxacin recipients had a significantly higher cure rate than those treated with amoxicillin/clavulanic acid (83.3% vs. 67.6%). Tolerance was significantly better with ciprofloxacin, essentially due to a large number of gastro-intestinal side-effects in the amoxicillin/clavulanic acid group.

Urinary tract infectionsCiprofloxacin is significantly more effective than Augmentin in the treatment of uncomplicated urinary tract infections.

Cystitis in womenAmoxicillin-clavulanate is not as effective as ciprofloxacin for acute uncomplicated cystitis, even in women infected with susceptible bacteria.

In randomized trial clinical cure was achieved in 93 (58%) of 160 women treated with amoxicillin-clavulanate compared with 124 (77%) of 162 women treated with ciprofloxacin. Amoxicillin-clavulanate was not as effective as ciprofloxacin even against susceptible strains. The difference in clinical cure rates occurred almost entirely within the first 2 weeks after therapy. Microbiological cure at 2 weeks was observed in 118 (76%) of 156 women treated with amoxicillin-clavulanate compared with 153 (95%) of 161 women treated with ciprofloxacin. At this visit, 45% of women in the amoxicillin-clavulanate group compared with 10% in the ciprofloxacin group had vaginal colonization with E. coli.

Ciprofloxacin vs. AzithromycinChronic prostatitisAzithromycin is significantly more effective than ciprofloxacin in the treatment of chronic prostatitis caused by Chlamydia trachomatis. According to the comparative analysis azithromycin has significantly higher eradication and a significantly higher clinical cure rates than ciprofloxacin.

ShigellosisCiprofloxacin is somewhat more effective than azithromycin in the treatment of Shigellosis (a type of infective diarrhea).

In a double-blind, randomized, controlled study azithromycin therapy was clinically successful in 28 (82%) patients and ciprofloxacin therapy in 32 (89%) patients. Therapy was bacteriologically successful in 32 (94%) patients receiving azithromycin and 36 (100%) those receiving ciprofloxacin.

GonorrheaAzithromycin is at least as effective and well tolerated as ciprofloxacin in the treatment of gonococcal infections. Azithromycin is particularly useful for sailors and people constantly on the move.

In the clinical study patients with gonorrhea were treated with azithromycin (n=50) and ciprofloxacin (n=51). After 2 weeks clinical and microbiological cure rates were 96.0% (48 out of 50) in azithromycin group and 92.15% (47 out of 51) in ciprofloxacin group. Side effects were reported in 5 patients treated with azithromycin and 6 with ciprofloxacin.

Ciprofloxacin vs. ClarithromycinChronic bronchitis (acute bacterial exacerbations)

Ciprofloxacin provides longer infection-free interval and higher bacteriologic cure rate than clarithromycin.

In double-blind study, ciprofloxacin was compared with clarithromycin for treatment of acute bacterial exacerbations of chronic bronchitis (ABECB). Patients randomly received either ciprofloxacin or clarithromycin (500 mg twice a day for 14 days). 376 patients with acute exacerbations of chronic bronchitis were enrolled in the study of whom 234 had an ABECB. Clinical resolution was achieved in 90% (89 of 99) of ciprofloxacin treated patients and 82% (75 of 91) of clarithromycin treated patients. The median infection-free interval was 142 days for ciprofloxacin and 51 days for clarithromycin therapy. Bacteriologic eradication rates were 91% (86 of 95) for ciprofloxacin and 77% (67 of 87) for clarithromycin.

SinusitisCure rates immediately after antibiotic therapy are higher with clarithromycin. However relapses rates are twice as higher with clarithromycin.

The clinical study compared the efficacy and safety of ciprofloxacin (500 mg twice daily for 10 days) and clarithromycin (500 mg twice daily for 14 days) in adults with acute sinusitis. Of 457 adults (236 ciprofloxacin, 221 clarithromycin), clinical resolution plus improvement at the end of therapy was 84% for ciprofloxacin-treated patients compared to 91% of those treated with clarithromycin. At the 1-month follow-up, more than twice as many clarithromycin-treated patients, 18 (10%), experienced a relapse, compared to 7 (4%) ciprofloxaci-treated patients. The combined clinical response analyses (end of therapy and 1-month follow-up) demonstrated that both treatments were statistically equivalent. Diarrhea, nausea, headache, and dizziness were the most frequently reported adverse events in both groups. Diarrhea and taste perversion were reported more frequently with clarithromycin.

Ciprofloxacin vs. Erythromycin Legionella pneumoniaCiprofloxacin is as effective as Erythromycin for Legionella pneumonia. The treatment effects may appear earlier and the duration of treatment is significantly shorter with ciprofloxacin than with Erythromycin.

In clinical study all of the petients with Legionella pneumonia, who were treated with Ciprofloxacin, were cured. In the Erythromycin group 16 out of the 18 patients were cured. Although there were no significant differences, the time to apyrexia, normalization of leukocytosis and a 50% decrease in C-reactive protein (CRP) occurred within a relatively shorter time frame in the Ciprofloxacin group than in the Erythromycin group (3.5 versus 4 days, 4 versus 5.2 days, and 2.9 versus 10.3 days, respectively). And, the duration of treatment with Ciprofloxacin was significantly shorter than with Erythromycin.

Ciprofloxacin (Cipro) vs. Cefuroxime (Ceftin)SinusitisCiprofloxacin is as effective as cefuroxime axetil in the treatment of acute sinusitis.

In randomized, double-blind clinical study of 453 adults valid for clinical efficacy (228 ciprofloxacin, 225 cefuroxime axetil), ciprofloxacin was statistically equivalent to cefuroxime at the end of treatment (87% vs. 83%) and at follow-up (91% vs. 88%). The clinical response was similar for subgroups of patients with positive cultures, including the subset with target organisms. Bacteriologic eradication at the end of therapy was similar between the two groups (97% ciprofloxacin, 95% cefuroxime axetil). Both treatments were equally well tolerated.

RhinosinusitisCiprofloxacin and cefuroxime are equally effective in acute rhinosinusitis.

In comparative study clinical resolution was observed in 559 of 613 (91.2%) ciprofloxacin-treated patients and 546 of 606 (90.1%) cefuroxime treated patients. The two regimens were statistically equivalent. There were 80 adverse events reported in the ciprofloxacin group and 81 adverse events reported in the cefuroxime group. The main adverse events were nausea (n = 18) and diarrhea (n = 7) in patients treated with ciprofloxacin and diarrhea (n = 14), nausea (n = 12), headache (n = 7), and vaginitis (n = 7) in those treated with cefuroxime.

GonorrheaSingle dose cefuroxime axetil is as effective as a single dose of ciprofloxacin in the treatment of uncomplicated gonorrhea caused by penicillinase-producing Neisseria gonorrhoeae (PPNG). However cefuroxime appears to be less effective than ciprofloxacin in treating urethral gonococcal infections in men, although both are highly effective in treating cervical gonococcal infections in women.

In a randomized, multicenter, investigator-blind trial a total of 832 patients (434 females and 398 males) received a single oral dose of cefuroxime axetil 1,000 mg (417 patients) or ciprofloxacin 500 mg (415 patients). Neisseria gonorrhoeae was eradicated from the cervix in 114 of 118 (97%) and 118 of 119 (99%) females treated with cefuroxime axetil and ciprofloxacin, respectively, and from the urethra in 154 of 166 (93%) and 171 of 171 (100%) males treated with cefuroxime axetil and ciprofloxacin, respectively. Both medications were effective in eradicating N. gonorrhoeae in females with rectal infections (cefuroxime axetil, 29 of 30 [97%]; ciprofloxacin, 25 of 25 [100%]). In small numbers of patients, cefuroxime axetil was less effective than ciprofloxacin in treating males with pharyngeal infections (eradication in 4 of 10 and in 8 of 8 patients).

Penicillinase-producing Neisseria gonorrhoeae was eradicated from the cervix in 22 of 23 (96%) and 32 of 32 (100%) females treated with cefuroxime axetil and ciprofloxacin, respectively, and from the urethra in 35 of 36 (97%) and 34 of 34 (100%) males treated with cefuroxime axetil and ciprofloxacin, respectively. The incidences of adverse events were similar for the two study gropes.

Ciprofloxacin vs. CefotaximeSkin infectionsOral ciprofloxacin may be more effective than parenteral cefotaxime in the treatment of infections of the skin and skin structure. Cefotaxime is associated with higher incidence of bacteriologic failure in patients with polymicrobial infected ulcers.

In the double-blind, randomized study of hospitalized patients with skin and skin structure infections clinical response per infected site in the ciprofloxacin group was as follows: resolution in 88%, improvement in 8%, and failure in 4%. In the cefotaxime group, there was resolution in 69%, improvement in 25% and failure in 6%. Bacteriologic response per site in the ciprofloxacin group was eradication in 88% and persistence in 12%. With cefotaxime there was 69% eradication, 3% marked reduction, 6% recurrence, and 22% persistence. Clinical and bacteriologic responses were combined using an algorithm to derive a cure rate, which was 91% for ciprofloxacin and 61% for cefotaxime.

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