CIPROFLOXACIN.

It is a potent fluoroquinolone antimicrobial agent. It has a broad spectrum against gram-negative and gram-negative organisms.

COMPOSITION.

Each tablet contains 500mg of ciprofloxacin hydrochloride USP.
Ciprofloxacin infusion: Each 100ml contains ciprofloxacin USB 200mg, sodium chloride USP 0.9% w/v.

PHARMACOLOGY:

MECHANISM OF ACTION:

Ciprofloxacin is a bactericidal agent. the rapid bactericidal action of ciprofloxacin is attributed to its unique mode of action.
It interacts with both theta and beta subunits of DNA gyrase and disrupts the DNA function leading to death of bacteria.
Bacterial resistance with ciprofloxacin is extremely low. Ciprofloxacin eliminates plasmid-mediated resistance.

ANTIMICROBIAL ACTIVITY.

Ciprofloxacin is active against a wide range of Gram-positive and Gram-negative pathogens including strains resistant to penicillins,
cephalosporins and/or aminoglycosides. Ciprofloxacin is active against both replicating strains and intracellular bacteria.
It is a significant post-antibiotic effect and thus prevents the regrowth of bacteria.
Ciprofloxacin does not disturb normal anaerobic interstinal flora.

Gram-negative bacteria:
  • Enterobacteriaceae: E.coli, Klebsiella species, Proteus species, Enterobacter species, Morganella morgani, Citrobacter species, Sseratia species and providencia species.
  • Pseudomonadaceae: Ps aeruginosa and Ps. cepacia.
  • Enteropathogenic: Salmonella species, Shigella species, enteropathogenic E. coli, Y. enteroclitica, A. hydrophilia, V. cholerae, Campylobacter jejuni and Arizona species.
  • Miscellaneous: N. gonorrhoea, N. meningitidid, H.influenza, Acinetobacter anitratus, Branhamella catarrhalis, Pasteurella, Moraxella and Gardnerella vaginalis.
Gram-positive bacteria:

Staph. aureus including penicillinase-producing and methicillin-resistant strains, Staph. epidermidis, Strep. pyogenes, Strep. pyogenes, Strep. agalactiae, Strep viridans, and Listeria monocytogenes.

Intra-cellular bacteria:

Chlamydia trachomatis, Mycoplasma hominis, Legionella species and Brucella species.

Cprofloxacin is also active against anaerobes including most species of bacteriodes, Clostridium and fusobacteruim.

PHARMACOKINETICS.

Tablets:

Ciprofloxacin is readily absorbed after oral ingestion. It enters most of the body compartments in which infections occur.
The serum half-life ranges from 3.0-3.4 hours after oral administration and the volume of distribution is more than 100 liters.

Infusion:

Ciprofloxacin has favourable pharmacokinetics for systemic use. The mean peak serum concentration following single doses of 100, 150 and 200mg I>V are 1.4, 2.0, 3.2mg/litre respectively. The terminal half life averages between 4.2 and 4.6. The distribution and tissue penetration of Ciprofloxacin is extremely good and the drug reaches theurapeutic concentrations in most body tissues and fluids including sputum, bone, peritoneal fluid, prostate, and pelvic tissues. Average urinary recovery ranges between 45.8 and 48.1%. The protein binding of ciprofloxacin is low. Significant amounts are also excreted in bile and faeces.

INDICATIONS.

Ciprofloxacin is indicated for the treatment of a wide variety of infections caused by susceptible Gram-negative and Gram-positive organisms including mixed infections caused by multi-drug resistant bacteria. Ciprofloxacin is indicated for the treatment of the following infections caused by susceptible bacteria.

  • Respiratory tract infections: Acute bronchitis, infected bronchiectasis, lung abscess, exacerbation of chronic obstructive airways disease, empyema, cystic fibrosis, and pneumonia.
  • Urinary tract infections: Acute and chronic polynephritis, prostatitis, cystitis, epididymitis and chronic complicated or recurrent UTI caused by multi-resistant organisms and/or Pseudomonas aeruginosa.
  • Skin and soft tissue infections: In surgical and postoperative wound infections due to Gram-negative organisms such as Enterobacteriaceae and Pseudomonas aeruginosa. Also useful in infections caused by resistant Staphylococci eg infected ulcer, cellulitis, otitis externa, infected burns, etc.
  • Bone and joint infections: Since ciprofloxacin achieves adequate tissue concentrations in the bone. It is useful in the management of acute and chronic osteomyelitis and septic arthritis.
  • Gynaecological infections: Severe pelvic infections caused by susceptible bacteria, salpingitis, and endometritis.
  • Gastrointestinal infections: Effective in the treatment of typhoid and may also eradicate the carrier stage. Useful in resistant Salmonella typhi infections and infective diarrhoea.
  • Severe systemic infections: Septicemia, bacteria, and infections in immunocompromised patients.
  • Surgical infections: Peritonitis , intra-abdominal abscess, cholangitis, cholecystitis and empyema of the gall bladder.
  • Sexually transmitted disease: Gonorrhoea ib=ncluding that caused by beta-lactamase producing strains and chancroid caused by H.ducreyi.
  • Eye, ear nose and throat infections: eg otitis media, sinusitis, mastoditis, and tonsilitis.

DOSAGE AND ADMINISTRATION.

TABLETS:

The dosage for ciprofloxacin is determined on the basis of severity of infection, type of infecting organism and age, weight and renal function of the patient.

The recommended dosage schedule of oral Ciprofloxacin is as follows:

  1. Uncomplicated UTI: 250mg mg every 12 hours’
  2. Prostatitis and complicated UTI in patients with severe underlying structural abnormalities: 500 mg every 12 hrs.
  3. Lower respiratory tract infection: Mild – 250 mg: Moderate to severe – 500mg; all every 12 hours: Dosage of 750mg every 12 hours should be preferably used in cases of infections of resistant Gram-positive bacteria.
  4. Gynaecological infection and diarrhoea of bacterial origin: 500mg every 12 hours.
  5. Septicaemia, bacteremia and surgical infections: Initial I.V ciprofloxacin therapy may be followed by oral ciprofloxacin 500mg to 750mg every 12 hours.
  6. Skin and soft tissue and bone and joint infections: Mild to moderate- 500mg every 12 hours; severe -750mg every 12 hours.
  7. In the majority of other infections: 500-7750mg twice daily should be administered. In enteric fever dose, once a day ciprofloxacin is 500-750 mg twice a day for 10 to 14 days. The total daily dosage should be halved in patients with severe renal impairment. (Creatine clearance <= 20mg/min.

Infusion:

The recommended dosage schedule for ciprofloxacin infusion is as follows:

  1. Gonorrhoea: A single dose of 100mg by slow I.V infusion.
  2. Upper and Lower respiratory tract infections: !00mg twice daily by slow I.V infusion.
  3. Respiratory tract infection: 200 mg twice daily by slow I.V infusion.
  4. In the majority of other infections: 200 mg should be administered by slow I.V infusion every 12 hours daily.
    The total daily dosage should be halved in patients with severe renal impairment. (creatinine clearance <= 20ml/min)
  5. Children: Ciprofloxacin is usually not recommended for use in children. However, if the benefits of ciprofloxacin therapy are considered to outweigh the potential risks, the dosage should be 5-10mg/kg/day (intravenous) or 7.5 to 15 mg/kg/day (oral) in two divided doses depending on the severity of the infection.

TECHNIQUE OD ADMINISTRATION:

Ciprofloxacin infusion of 100 ml (200mg) infusion bottle may be infused directly and should be administered over a period of 30-60 minutes.

NOTE:

Ciprofloxacin infusion contains 0.9% w/v Sodium Choride. It is compatible with all intravenous fluids.

Ciprofloxacin infusion should not be used if it is found discolored or if it contains any suspended particles.

DURATION OF TREATMENT

The usual duration of therapy for acute infections is 5 – 7 days. Generally, therapy should be continued for at least 3 days after the signd=s and symptoms of the infection have disappeared. in some infections, long term therapy may have to be given.

CONTRAINDICATIONS:

Ciprofloxacin is contraindicated in patients hypersensitive to quinolones. Its use is not recommended in children below 12 years of age.

PRECAUTIONS:

As ciprofloxacin as cause CNS stimulation. It should be used with caution in patients with CNS disorders such as epilepsy. Patients receiving this drug should be well hydrated to prevent crystalluria. Excessive alkalinity of the urine should be avoided. The dosage should be reduced in patients with renal impairment.

Antacids containing magnesium hydroxide and/or aluminium hydroxide may interfere with absorption of ciprofloxacin resulting in lower serum and urine levels; concurrent administration of antacids with ciprofloxacin should be avoided.

Reproduction studies in animals at doses up to to 6 times the usual daily human doses have not revealed any evidence of impaired fertility or teratogenicity due to ciprofloxacin. However, information from well-controlled studies in pregnant women is not available. Since Ciprofloxacin causes arthropathy in immature animals, it should not be used in pregnant and breastfeeding women.

DRUG INTERACTIONS:

Serum concentration and elimination half-life of theophylline may be increased when it is used concurrently with ciprofloxacin. It is recommended that patients be monitored for the signs of theophylline toxicity during concurrent and dosage adjustments made appropriate. Probenecid delays the excretion of ciprofloxacin.

ADVERSE REACTIONS:

Ciprofloxacin is generally well tolerated. During clinical trials in a large number of patients, adverse effects related to drug occurred infrequently and were commonly reported as
Diarrhoea, vomiting, abdominal pain, headache, restlessness, pain. Other side effects that have been reported infrequently are; Arthralgia and ib=ncrease in serum transaminases levels.

OVERDOSAGE:

In the case of overdosage, adequate hydration, hemodialysis or peritoneal dialysis is recommended.