Ciprophil

Ciprofloxacin 500 mg is an oval white or slightly yellowish film-coated tablet.
Each film-coated tablet contains: Ciprofloxacin (as Hydrochloride), USP 500 mg.
Ciprofloxacin is a fluorinated quinolone antibacterial with a wide spectrum of activity against virtually all Gram-negative pathogens Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus, Neisseria spp., Staphylococci and other Gram-positive organism. Anaerobes are generally less susceptible.

Pharmacology: Pharmacodynamics: As a fluoroquinolones antibacterial agent, the bactericidal action of ciprofloxacin results from the inhibition of both type II topoisomerase (DNA-gyrase) and topoisomerase IV, required for bacterial DNA replication, transcription, repair and recombination.
Efficacy mainly depends on the relation between the maximum concentration in serum (C_max) and the minimum inhibitory concentration (MIC) of ciprofloxacin for a bacterial pathogen and the relations between the area under the curve (AUC) and the MIC.
Pharmacokinetics: Ciprofloxacin, upon ingestion, is readily absorbed in the gastrointestinal tract. Peak Plasma concentration of 2.5 mcg/mL is reached 1 to 2 hours after 500 mg oral dose. The Oral bioavailability of the drug is about of the drug is about 70%.
Absorption of the drug may be delayed by food but it does not give significant clinical effects. The Plasma half-life of ciprofloxacin is 3.5 to 4.5 hours and may be delayed in patients with end-stage renal disease (8 hours) and in the elderly. In patients with severe liver cirrhosis, half-life is slightly prolonged.
Ciprofloxacin is 20-40% protein bound. It is widely distributed in the body and tissues. It may be seen in the cerebrospinal fluid. 10% in normal meninges, and is able to cross the placenta,
Ciprofloxacin is found to be excreted in breast milk but is mainly excreted in the urine by active tubular secretion and glomerular filtration which may be reduced by Probenecid. Other means of elimination include hepatic metabolism, excretion in the bile where high concentrations are achieved, and transluminal excretion in the intestinal mucosa.
The urinary metabolite of ciprofloxacin is oxociprofloxacin and primary fecal metabolite is suphociprofloxacin. Oral Ciprofloxacin is 40-50% and 15% is excreted in the urine as unchanged drug and metabolite, respectively, within a period of one day. Fecal excretion involves 20-35% of ciprofloxacin taken orally.
Few amounts of the drug may be removed by dialysis.
Microbiology: Spectrum: Ciprofloxacin is active against (Gram-negative Aerobic bacteria) Enterobacteriaceae including Escherichia coli and Citrobacter, Enterobacter, Klebsiella, Proteus, Providencia, Salmonella, Serratia, Shigella, Yersinia spp., Pseudomonas aeruginosa, Hapnia, Edwardsiella, Morganella, Acinetobacter spp., Campylobacter spp., Gardnerella vaginalis, Helicobacter pylori, Legionella spp., Aeromonas, Plesiomonas, Pasterurella multocida and Vibrio spp. Ciprofloxacin has variable activity against Brucella melitensis.
Gram-positive aerobic staphylococci bacteria including penicillinase-producing and non-producing strains as well as some methicillin-resistant strains are susceptible to ciprofloxacin. Streptococcus pneumoniae and enterococci are less susceptible to the drug.
Ciprofloxacin is also active against Corynebacterium spp. and Listeria monocytogenes.
It exerts bactericidal effect against Pseudomonas spp., Haemophilus ducreyi, H. Influenzae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrheae, N. meningitides. This is also true to beta-lactamase producing strains of H. influenzae, M. catarrhalis, and N. gonorrheae. Mycobacteria, mycoplasma, rickettsias, Plasmodium falciparum and Clostridium difficile may be sensitive to ciprofloxacin. Moderate susceptibility to ciprofloxacin is exhibited to Chlamydia trachomatis.
Resistance: Bacteroides fragilis, Clostridium difficile, other anaerobic bacteria, Campylobacter spp., non-typhoid Salmonella spp., multi-resistant Salmonella typhii, S. paratyphi, and beta-lactamase-producing gonococcus are resistant to ciprofloxacin.
Ciprofloxacin is also inactive against fungi and spirochete, Treponema pallidum.
Nocardia asteroids, Ureaplasma urealyticum, are usually considered to be resistant to ciprofloxacin.
During treatment with ciprofloxacin, resistant strains of Staphylococcus aureus (including methicillin-resistant strains), Pseudomonas aeruginosa, Enterobacteriaceae including Escherichia coli and Serratia marcescens were found.
Monotherapy with ciprofloxacin was reported to have caused the development of mutational resistance in mycobacterial.
Cross resistance exists between ciprofloxacin and other fluoroquinolones.
Resistance of Staphylococcus epidermis to ciprofloxacin may have been caused by the presence of drug in sweat.
Effect when Given with Other Antimicrobial Agents: Enhanced effect is exhibited when are ciprofloxacin is given with imipenem against Pseudomonas aeruginosa. The activity of ciprofloxacin against Staphylococcus aureus and P. aeruginosa is enhanced if given with amino glycosides. The same is true against anaerobic bacteria if given concomitantly with clindamycin or cefotaxime.
Ciprofloxacin is 20-40% protein bound. It is widely distributed in the body and tissues. It may be seen in the cerebrospinal fluid 10% in normal meninges, and is able to cross the placenta.
Ciprofloxacin is found to be excreted in breast milk but is mainly excreted in the urine by active tubular secretion and glomerular filtration which may be reduced by Probenecid. Other means of elimination include hepatic.

Ciprofloxacin is indicated for the treatment of a wide scope of infections which includes anthrax, infected bites and stings, infections of the biliary tract, bone and joints, brucellosis, cat scratch disease, chancroid, exacerbations of cystic fibrosis, gastroenteritis which includes traveler’s diarrhea and campylobacter enteritis, salmonella enteritis, cholera and shigellosis, gonorrhea, neutropenia in immunocompromised patients with infections, Legionnaire’s disease, otitis media and otitis externa, peritonitis, Q fever, lower respiratory tract infections to include pseudomonal infections in cystic fibrosis except infections caused by Streptococcus pneumonia (e.g. pneumococcal pneumonia), septicemia, skin and soft tissue infections, spotted fevers, typhoid and paratyphoid fever, typhus, infections of the urinary tract, tuberculosis and opportunistic mycobacterial infections.
It is also used in the prophylaxis of meningococcal meningitis and surgery.

Ciprofloxacin hydrochloride is given orally to adults 18 years of age and older in doses 500 mg twice per day every 12 hours.
For the treatment of uncomplicated acute gonorrhea, oral ciprofloxacin 250 mg as single dose is recommended.
For meningococcal meningitis prophylaxis, 500 mg oral ciprofloxacin is given.
Ciprofloxacin 15 mg/kg twice per day, not to exceed 500 mg twice per day, may be given for children and adolescents for inhalation of anthrax for 60 days.
Or as prescribed by the physician.
Patients with renal impairment are given reduced doses with regular monitoring of the plasma concentrations of the drug. If creatinine clearance is <20 mL per minute, 250 mg oral ciprofloxacin is administered.

There is limited experience on ciprofloxacin overdose and in events of acute overdosage, reversible renal toxicity has been reported. The patient should be carefully observed and given supportive treatment. The symptoms include dizziness, tremor, headache, tiredness, seizures, hallucinations, and confusion. It also include gastrointestinal upset liver, and kidney abnormalities, crystalluria and hematuria as well.
Treatment includes gastric lavage or induced vomiting. Activated charcoal, Magnesium of Calcium containing antacids can be administered to reduce the absorption of ciprofloxacin. Adequate hydration must be maintained as well. Only a small amount of ciprofloxacin (<10%) is eliminated through hemodialysis or peritoneal dialysis.

Caution should be taken when giving ciprofloxacin to epileptic patients and to those with history of CNS disorders, myasthenia gravis, and glucose-6-phosphate dehydrogenase deficiency. Ciprofloxacin may exacerbate or unmask symptoms of myasthenia gravis. If tendon pain, inflammation or rupture occurs, treatment with ciprofloxacin is contraindicated in children, adolescents, pregnant women and lactating mothers. Ciprofloxacin was reported to cause arthralgia and degenerative changes in joints that bear weight in young animals.

Patients who drive and operate machines musts not take ciprofloxacin with alcohol.
The risk of crystalluria is high in patients with alkaline urine.
Use in Patients with renal impairment: Ciprofloxacin should be used with caution in patients with severe renal impairment (see Dosage & Administration).
Use in Patients with hepatic impairment: Ciprofloxacin should be used with caution in patients with severe hepatic impairment where peak plasma concentration and serum half-life may be increased.
Use in Pregnancy & Lactation: See USE IN PREGNANCY & LACTATION section for further information.
Use in the Elderly: Dose of ciprofloxacin should be reduced in the elderly as increased bioavailability and reduced renal clearance were seen probably due to absorption or first pass elimination.

Use in Pregnant women: The data that are available on administration of ciprofloxacin to pregnant women indicates no malformative or feto/neonatal toxicity of ciprofloxacin. Animal studies do not indicate direct or indirect harmful effects with respect to the reproductive toxicity. In juvenile and prenatal animal exposed to quinolones, effects on immature cartilage have been observed, thus, it cannot be excluded that the drug could cause damage to articular cartilage in human immature organism/fetus.
As precautionary measure, it is preferable to avoid the use of ciprofloxacin during pregnancy.
Use in Lactating mothers: Ciprofloxacin is excreted in breast milk. It should be used in caution when given to breast feeding mothers as this was found to cause arthropathy in young animals. (See Contraindications.)

Among the usual adverse effects of ciprofloxacin are gastrointestinal disturbances, central nervous system (CNS) toxicity and hypersensitivity reactions.
Nausea, vomiting, diarrhea, abdominal pain, and dyspepsia are experienced as common gastrointestinal disturbances. Reports of pseudomembranous colitis are seldom received. Headache, anorexia, flatulence, bilirubinemia, dizziness, and restlessness are the most common CNS effects. Other CNS toxicity associated with the use of ciprofloxacin are tremor, drowsiness, insomnia, agitation, confusion, unpleasant dreams, visual disturbances and other sensory disturbances, hallucinations, depression and convulsions, eosinophilic meningitis, acute pyschoses, peripheral neuropathy, dysaethesia, catatonia, hemisparesis and tinnitus.
Patients taking ciprofloxacin may also experience hypersensitivity reactions such as rash, pruritus, photosensitivity, vasculitis, erythema multiforme; Stevens-Johnson syndrome, toxic epidermal necrolysis, laryngeal edema and anaphylaxis (may be fatal). Reversible arthralgia and joint erosions were seen in animals. A case of tendon damage was also reported. Reports of transient elevation of serum creatinine, blood urea nitrogen and liver enzyme values, acute renal failure secondary to interstitial nephritis, crystalluria, jaundice, moniliasis, asthenia, hepatitis, eosinophilia, leucopenia, thrombocytopenia, pancytopenia, haemolytic anemia or agranulocytosis, myalgia and gynecomastia were received. Tachycardia, edema, syncope, hot flushes and sweating are among the cardiovascular effects of the use of ciprofloxacin.
Pseudomembranous colitis and super infection with Candida, Clostridium difficile, and Streptococcus pneumoniae associated with the use of ciprofloxacin were reported. The risk of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci colonization are high in patients taking ciprofloxacin.

Ciprofloxacin may interfere with the clearance of the drugs metabolized by the liver such as theophylline and caffeine on account of the ability of ciprofloxacin to inhibit hepatic metabolism. In one study, seizures had developed after concomitant use of ciprofloxacin with theophylline.
Ciprofloxacin is not recommended to be administered orally within 4 hours of taking magnesium, aluminum or iron and zinc salts-containing antacids to prevent the reduction of absorption of ciprofloxacin as well as other fluoroquinolones. Sucralfate, which releases aluminum ions in the stomach, may reduce absorption of ciprofloxacin and other quinolones.
The possibility of interfering with the absorption of fluoroquinolones may be present in dairy products having high calcium content.
Although histamine H₂ antagonists affect the pharmacokinetics of ciprofloxacin, clinical effect is found insignificant.
Naproxen and chloroquine were found to cause adverse neurological effect with the addition of ciprofloxacin. Effect was reduced when the antirheumatic drugs were discontinued.
In surgical infection prophylaxis, concomitant administration of ciprofloxacin with opioid analgesics is not recommended as the peak serum concentrations of ciprofloxacin is reduced significantly.
Cytotoxic chemotherapy was reported to reduce the absorption of ciprofloxacin. Enhanced nephrotoxicity was developed after concomitant use of the ciprofloxacin with cyclosporine.
Plasma concentration of midazolam increases when administered with ciprofloxacin.
Probenecid was found to reduce the urinary excretion of ciprofloxacin without increasing plasma concentration of the latter.
Interference with Laboratory Results: In elderly patients treated with ciprofloxacin for urinary tract infections, a false positive reaction for urinary glucose (pseudoglycosuria) has been reported.

Store at temperatures not exceeding 30°C.

Quinolones

J01MA02 - ciprofloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.

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