Ciprofloxacin(Tablet 250 , 500 mg)

Category

Antibacterial (PDR 2007)

Composition:

Each tablet contains ciprofloxacin (as HCI) 250 or 500mg.

Chemistry:

Ciprofloxacin hydrochloride, a fluoroquinolone, is the monohydrochloride monohydrate salt of 1-cyclopropyl-6-fluoro-1, 4- dihydro-4-oxo-7-(1-piperazinyl) -3-quinolinecarboxylic acid. C17H18FN3O3. HCl. H2O and its chemical structure is as follows: (PDR 2007)

Pharmacokinetics:

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. Maximum serum concentrations are attained 1 to 2 hours after oral dosing. Mean concentrations 12 hours after dosing with 250, 500, or 750mg are 0.1, 0.2 and 0.4 µg/ml, respectively. 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. When ciprofloxacin tablet is given concomitantly with food, there is a delay in the absorption of the drug, resulting in peak concentrations that occur closer to 2 hours after dosing rather than 1 hour. (PDR 2007)

Microbiology:

Ciprofloxacin has in vitro activity against a wide range of gram- positive & gram negative organisms. The bactericidal action of ciprofloxacin results from interference with the enzymes topoisomerase II (DNA gyrase ) and topoisomerase IV DNA gyrase which are needed for the synthesis of bacterial DNA.
Ciprofloxacin does not cross react with other antimicrobial agents such as beta-lactams or aminoglycosides; therefore, organisms resistant to these drugs may be susceptible to ciprofloxacin. Synergy has been reported particularly with the combination of ciprofloxacin and a beta-lactam; antagonism is observed only rarely. (PDR 2007)

Uses and administrations:

• Acute sinusitis caused by Haemophilus influenzae, streptococcus pneumoniae, or moraxella catarrhalis.
• Lower respiratory tract infections: Caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus influenzae, Haemophilus parainfluenzae, or Streptococcus pneumoniae. Also, Moraxella catarrhalis for the treatment of acute exacerbations of chronic bronchitis. Although effective in clinical trials, ciprofloxacin is not a drug of first choice in the treatment of presumed or confirmed pneumonia secondary to Streptococcus pneumoniae.
• Urinary tract infections: Caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcesense, Proteus mirabilis, Providencia rettgeri, Morganella morganii, Citrobacter diversus, Citrobacter freundii, Pseudomonas aeruginosa, Staphylococcus epidermidis, Staphylococcus saprophyticus, or Enterococcus faecalis.
• Acute uncomplicated cystitis in females caused by Escherichia coli or Staphylococcus saprophyticus.
• Chronic bacterial prostatitis caused by Escherichia coli or Proteus mirabilis.
• Complicated intra-Abdominal infections (used in combination with metronidazole) caused by Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, or Bacteroides fragilis.
• Skin and skin structure infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris, Providencia stuartii, Morganella morganii, Citrobacter freundii, Pseudomonas aeruginosa, Staphylococcus aureus (methicillin susceptible), Staphylococcus epidermidis, or Streptococcus pyogenes.
• Bone and joint infections caused by Enterobacter cloacae, Serratia marcescens, or Pseudomonas aeruginosa.
• Infectious diarrhea caused by Escherichia coli (enterotoxigenic strains), Campylobacter jejuni, Shigella boydii, Shigella dysenteriae, Shigella flexneri or Shigella sonnei when antibacterial therapy is indicated.
• Typhoid fever (Enteric fever) caused by salmonella typhi. The efficacy of ciprofloxacin in the eradication of the chronic thyphoid carrier state has not been demonstrated.
• Uncomplicated cervical and urethral gonorrhea due to Neisseria gonorrhoeae.
• Complicated urinary tract infections and pyelonephritis due to E.coli. Although effective in clinical trials, ciprofloxacin is not a drug of first choice in the pediatric population due to an increased incidence of adverse events compared to controls, including events related to joints and surrounding tissues.
• Inhalational anthrax (Post-exposure): To reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis. (PDR 2007)

Contraindications:

Ciprofloxacin 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. (PDR 2007)

Warnings:

The safety and effectiveness of ciprofloxacin in pregnant and lactating women have not been stablished. Ciprofloxacin should be used in pediatric patients (less than 18 years of age) only for infections listed in the usage section.
Convulsions, increased intracranial pressure, and toxic psychosis have been reported in patients receiving quinolones, including ciprofloxacin.
Ciprofloxacin may also cause central nervous system events including: Dizziness, confusion, tremors, hallucinations, depression, and rarely, suicidal thoughts or acts. These reactions may occur following the first dose. If these occur in patients receiving ciprofloxacin the drug should be discontinued and appropriate measures instituted.
As with all quinolones ciprofloxacin should be used with caution in patients with known or suspected CNS disorders that may predispose to seizures or lower the seizure threshold (e.g sever cerebral arteriosclerosis, epilepsy). (PDR 2007)

Precautions:

Serious and fatal reactions have been reported in patients receiving concurrent administration of ciprofloxacin and theophylline. If concomitant use cannot be avoided, serum levels of theophylline should be monitored and dosage adjustments made as appropriate. Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose, have been reported in patients receiving quinolone therapy. Some reactions were accompanied by cardio-vascular collapse, loss of consciousness, tingling pharyngeal or facial edema, dyspnea, urticaria, and itching. Only a few patients had a history of hypersensitivity reactions.
Pseudomembranous colitis has been reported with nearly all antibacterial agents, including ciprofloxacin, and may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhea subsequent to the administration of antibacterial agents.
Ciprofloxacin should be discontinued if the patient experiences pain, inflammation or rupture of a tendon. Alkalinity of the urine should be avoided in patients receiving ciprofloxacin. Patients should be well hydrated to prevent the formation of highly concentrated urine.
Quinolones, including ciprofloxacin, may also cause central nervous system (CNS) events, including: nervousness, agitation, insomnia, anxiety, nightmares or paranoia. Alteration of the dosage regimen is necessary for patients with impairment of renal function.
Excessive sunlight should be avoided. Therapy should be discontinued if phototoxicity occurs.
As with any potent drug, periodic assessment of organ system functions including renal, hepatic, and hematopoietic function, is advisable during prolonged therapy. (PDR 2007)

Pregnancy:

Teratogenic effects. Pregnancy Category C. Ciprofloxacin should not be used during pregnancy unless the potential benefit justifies the potential risk to both fetus and mother. (PDR 2007)

Nursing mothers:

potential for serious adverse reactions in infants nursing from mothers taking ciprofloxacin, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. (PDR 2007)

Drug interactions:

• Concurrent administration of ciprofloxacin with theophylline may lead to elevated serum concentration of theophylline and prolongation of its elimination half life. If concomitant use cannot be avoided serum levels of theophylline should be monitored and dosage adjustments made as appropriate.
• Concurrent administration of a quinolone, including ciprofloxacin with multivalent cation containing products such as magnesium/ aluminium antacids, sucralfate highly buffered drugs, or products containing calcium, iron, or zinc may substantially decrease its absorption, resulting in serum and urine levels considerably lower than desired.
• Altered serum levels of phenytoin (increased or 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. Some quinolones, including ciprofloxacin, have been associated with transient elevations in serum creatinine in patients receiving cyclosporine concomitantly.
• Quinolones 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. (PDR 2007)

Adverse reactions:

The most frequently reported, drug related events, were nausea, diarrhea, liver function tests abnormal, vomiting, and rash. In pediatric patients, the most frequent events were gastrointestinal like: diarrhea, vomiting, nausea, dyspepsia, abdominal pain. Also, rhinitis, dyspepsia, nausea, fever, asthma and rash were reported. (PDR 2007)

Overdosage:

In the event of acute overdosage, the stomach should be emptied by inducing vomiting or by gastric lavage. The patient should be carefully observed and given supportive treatment. Adequate hydration must be maintained. Only a small amount of ciprofloxacin (<10%) is removed from the body after hemodialysis or peritoneal dialysis. (PDR 2007)

Dosage and administrations:

Anthrax, inhalational (treatment): Oral, 500 mg (base) every 12 hours for 60 days.

• Mild to severe: Oral, 500 mg (base) every twelve hours for five to seven days.

Diarrhea, infectious:

• Bone and joint infections:
• Mild or moderate: Oral, 500 mg (base) every twelve hours for at least four to six weeks.
• Severe or complicated: Oral, 750 mg (base) every twelve hours for at least four to six weeks.

Gonorrhea, endocervical and urethral:

Oral, 250 mg (base) as a single dose.

Intra-abdominal infections:

Oral, 500 mg (base) every twelve hours for seven to fourteen days in combination with oral metronidazole.

Lower respiratory tract infections:

• Mild to moderate: Oral, 500 mg (base) every twelve hours for seven to fourteen days.
• Severe or complicated: Oral, 750 mg (base) every twelve hours for seven to fourteen days.

Meningococcal carriers:

Oral, 750 mg (base) as a single dose.

Prostatitis, chronic:

- Mild or moderate: Oral, 500 mg (base) every twelve hours for twenty eight days.

Sinusitis, mild or moderate or typhoid fever:

Oral, 500 mg (base) every twelve hours for ten days.

Skin and soft tissue infections.

• - Mild or moderate: Oral, 500 mg (base) every twelve hours for seven to fourteen days.
• - Severe or complicated: Oral, 750 mg (base) every twelve hours for seven to fourteen days.

Urinary tract infections:

Acute uncomplicated: Oral, 100 mg (base) every twelve hours for three days.

• Mild or moderate: Oral, 250 mg (base) every twelve hours for seven to fourteen days.
• Severe or complicated: Oral, 500 mg (base) every twelve hours for seven to fourteen days.
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Note:

Adults with impaired renal function may require a reduction in dose as follows:
Creatinine Clearance Dose (ml/min)/(ml/sec):
>50/0.83 See usual adult dose
30-50/0.5-0.83 250-500 mg every 12 hours
5-29/0.08 0.48 250-500 mg every 18 hours
Hemodialysis or 250-500 mg every 24 hours
Peritoneal dialysis After dialysis
In patients with severe infection and severe renal function impairment, a unit dose of 750 mg may be administered at the intervals noted above; however these patients should be monitored carefully and serum concentrations of ciprofloxacin should be measured periodically. (USPDI 2007)

Usual adult prescribing limits:

1.5 grams (base) daily.

Usual pediatric dose:

Use is not recommended in infants, children or adolescents. However, ciprofloxacin has been given to pediatric patients, as indicated below, when alternative therapy could not be used.

Anthrax, inhalational(treatment):

Oral,15 mg/kg of body weight per dose (base), not to exceed 500mg per dose, every 12 hours for 60 days.

Cystic fibrosis, pulmonary exacerbations:

For children 14 to 28 kg of body weight: oral, 28 to 20 mg (base) per kg of body weight every 12 hours, up to 2 grams per day.
For children 28 to 42 kg of body weight: oral, 20 to 15 mg ( base) per kg of body weight every 12 hours, up to 2 grams per day.

For other infections:

Oral, 10 to 15 mg (base) per kg of body weight twice a day, up to 1.5 grams per day. (USPDI 2007)

Storage:

Store below 30º C, in a well-closed container. (USP DI 2007)

How supplied:

Ciprofloxacin 250 mg is available as a round white, scored film coated tablet. There are blisters of 10’s boxes of 20’s.
Ciplofloxacin 500mg is available as an oblong, white, scored film coated tablet. There are blisters of 10’s boxes of 20’s.

RAZAK LABORATORIES

Km. 10, Karaj Makhsus Rd., Tehran 13185, Iran__