Ciprophil

Ciprofloxacin HCl.

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.

Ciprofloxacin is a bactericidal agent which inhibits an essential step in the reproduction of bacterial deoxyribonucleic acid (DNA), the A subunit of DNA gyrase (topoisomerase).
Ciprofloxacin is more potent and has a broader spectrum of activity than nalidixic acid, a non-fluorinated quinolone.
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, Gardenerella vaginalis, Helicobacter pylori, Legionella spp, Aeromonas, Plesiomonas, Pasteurella multocida and Vibrio spp. Ciprofloxacin has variable activity against Brucella melitensis.
Gram-positive aerobic staphylococci bacteria including penicillinase-producing and nonproducing 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 (Branhamelia) catarrhalis, Neisseria gonorrhea, N. meningitidis. This is also true to β-lactamase-producing strains of H. influenzae, M. catarrhalis and N. gonorrhea.
Mycobacteria, mycoplasmas, rickettsias, Plasmodium falciparum and Clostridium difficile may be sensitive to ciprofloxacin. Moderate susceptibility to ciprofloxacin is exhibited by Chlamydia trachomatis.
Resistance: Bacteroides fragilis, C. difficile, other anaerobic bacteria, Campylobacter spp, non-typhoid Salmonella spp, multi-resistant Salmonella typhii, S. paratyphi and β-lactamase-producing gonococcus are resistant to ciprofloxacin.
Ciprofloxacin is also inactive against against fungi and the spirochete, Treponema pallidum.
Nocardia asteroides, Ureaplasma urealyticum, are usually considered to be resistant to ciprofloxacin.
During treatment with ciprofloxacin, resistant strains of Staphylococcus aureus (including methicillin-resistant strains), P. aeruginosa, Enterobacteriaceae including E. coli and Serratia marcescens were found.
Monotherapy with ciprofloxacin was reported to have caused the development of mutational resistance in mycobacteria.
Cross-resistance exists between ciprofloxacin and other fluoroquinolones.
Resistance of Staphylococcus epidermidis to ciprofloxacin may have been caused by the presence of the drug in sweat.
Effects when Given with Other Antimicrobial Agents: Enhanced effect is exhibited when ciprofloxacin is given with imipenem against P. aeruginosa. The activity of ciprofloxacin against S. aureus and P. aeruginosa is enhanced if given with aminoglycosides. The same is true against anaerobic bacteria if given concomitantly with clindamycin or cefotaxime.
Pharmacokinetics: Ciprofloxacin, upon ingestion, is readily absorbed in the gastrointestinal tract. Peak plasma concentration of 2.5 mcg/mL is reached 1-2 hrs after 500 mg oral dose. The oral bioavailability 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 (t_½) of ciprofloxacin is 3.5-4.5 hrs and may be delayed in patients with end-stage renal disease (8 hrs) and in the elderly. In patients with severe liver cirrhosis, t_½ is slightly prolonged.
Ciprofloxacin is 20-40% protein bound. It is widely distributed in 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 concentration 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 1 day. Fecal excretion involves 20-35% of ciprofloxacin taken orally.
Few amounts of the drug may be removed by dialysis.

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 externa, peritonitis, Q fever, lower respiratory tract infections to include pseudomonal infections in cystic fibrosis except infections caused by Streptococcus pneumoniae (eg, pneumococcal pneumonia), septicemia, skin and soft tissue infections, spotted fevers, typhoid and paratyphoid fever, typhus, urinary tract infection, tuberculosis and opportunistic mycobacterial infections.
It is also used in the prophylaxis of meningococcal meningitis and surgery.

Adults ≥18 years: 500 mg twice a day every 12 hrs.
Uncomplicated Acute Gonorrhea: Recommended Dose: 250 mg as single dose.
Meningococcal Meningitis Prophylaxis: 500 mg.
Children and Adolescents: Inhalation of Anthrax: 15 mg/kg twice a day, not to exceed 500 mg twice a day for 60 days.
Patients with renal impairment are given reduced doses with regular monitoring of the plasma concentrations of the drug. If CrCl <20 mL/min, 250 mg oral ciprofloxacin is administered.

Caution should be taken when giving ciprofloxacin to epileptic patients and to those with history of central nervous system (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 should be discontinued.
Ciprofloxacin is contraindicated in children, adolescents. It was reported to cause arthralgia and degenerative changes in joints that bear weight in young animals.
Use in pregnancy & lactation: Ciprofloxacin is contraindicated in pregnancy. It is also excreted in breast milk. It should be used in caution when given to breastfeeding mothers as this was found to cause arthropathy in young animals.

The risk of crystalluria is high in patients with alkaline urine.
Renal Impairment: Ciprofloxacin should be use with caution in patients with impaired renal function. Dose should be reduced when giving ciprofloxacin to patients with severe renal impairment. (See Dosage & Administration.)
Hepatic Impairment: Ciprofloxacin should be used with caution in patients with severe hepatic impairment where peak plasma concentration and serum t_½ may be increased.
Effects on the Ability to Drive or Operate Machinery: Patients who drive and operate machines must not take ciprofloxacin with alcohol.
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.

Ciprofloxacin is contraindicated in pregnancy. It is also excreted in breast milk. It should be used in caution when given to breastfeeding mothers as this was found to cause arthropathy in young animals.

Among the usual adverse effects of ciprofloxacin are gastrointestinal disturbances, 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 psychoses, peripheral neuropathy, dysesthesia, catatonia, hemisparesis and tinnitus.
Patients taking ciprofloxacin may also experience hypersensitivity reactions eg, 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, leukopenia, thrombocytopenia, pancytopenia, hemolytic 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 superinfection with Candida, C. difficile and S. pneumoniae associated with the use of ciprofloxacin were reported. The risk of methicillin-resistant S. aureus and vancomycin-resistant enterococci colonization are high in patients taking ciprofloxacin.

Ciprofloxacin may interfere with the clearance of drugs metabolized by the liver eg, theophylline and caffeine on account of the ability of ciprofloxacin to inhibit hepatic metabolism. In 1 study, seizures had developed after concomitant use of ciprofloxacin with theophylline.
Ciprofloxacin is not recommended to be administered orally within 4 hrs 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 antagonist 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 concentration 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 25°C. Protect from direct light including sunlamps.

Quinolones

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

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