1. CIPRO HISTORY
How was Cipro discovered?

Cipro is a product of Bayer Pharmaceuticals.

Bayer is a wholly owned subsidiary of Bayer AG, based in Leverkusen, Germany, one of the largest industrial concerns in the world. Comprised of about 350 companies, the Bayer Group has subsidiaries or agents in approximately 150 countries.

Bayer's products are as follows:

Bayer HealthCare

• Animal Health
• Biological Products
• Consumer Care
• Diagnostics
• Pharmaceutical
• Bayer MaterialScience

Coating, Adhesive & Sealant Raw Materials

• Inorganic Basic Chemicals
• Polycarbonates
• Polyurethanes
• Thermoplastic Polyurethanes (TPU)

Note: World-drugs.net sells generic version of Cipro

2. CIPRO FACTS

Cipro is an antibiotic used to treat bladder infections, kidney infections, prostate infections, cervix infections, stomach infections, intestine infections, lung infections, sinus infections, bone infections, and skin infections caused by certain germs called bacteria. Cipro kills many types of bacteria that can infect these areas of the body. Cipro has been shown in a large number of clinical trials to be safe and effective for the treatment of bacterial infections.

Sometimes viruses rather than bacteria may infect the lungs and sinuses (for example the common cold). Cipro, like all other antibiotics, does not kill viruses. You should contact your doctor if your condition is not improving while taking Cipro.

Cipro Tablets are white to slightly yellow in color and are available in 100 mg, 250 mg, 500 mg and 750 mg strengths.

3. ABOUT CIPRO MEDICATION
What are antibiotics?

An antibiotic is a drug that kills or slows the growth of bacteria. Antibiotics are one class of "antimicrobials", a larger group, which also includes anti-viral, anti-fungal, and anti-parasitic drugs. They are relatively harmless to the host, and therefore can be used to treat infections. The term originally described only those formulations derived from living organisms, in contradistinction to "chemotherapeutic agents", which were purely synthetic. Nowadays the term "antibiotic" is also applied also to synthetic antimicrobials, such as the sulfonamides.

Antibiotics are labeled as "magic bullets": drugs, which target disease without harming the host. Antibiotics are not effective in viral, fungal and other nonbacterial infections, and individual Antibiotics vary widely in their effectiveness on various types of bacteria. Some specific Antibiotics target either gram-negative or gram-positive bacteria, and others are more wide-spectrum Antibiotics.

The effectiveness of individual Antibiotics varies with the location of the infection, the ability of the antibiotic to reach the site of infection, and the ability of the bacteria to resist or inactivate the antibiotic. Some Antibiotics actually kill the bacteria (bactericidal), whereas others merely prevent the bacteria from multiplying (bacteriostatic) so that the host's immune system can overcome them.

Classes of Antibiotics?

There are many ways to classify Antibiotics.

One such classification is by chemical structure:

Aminoglycosides

• Amikacin
• Dibekacin
• Gentamicin
• Kanamycin
• Neomycin
• Netilmicin
• Paromomycin
• Sisomycin
• Streptomycin
• Tobramycin

Beta-lactam ring antibiotics

Carbapenems

• Ertapenem
• Imipenem
• Meropenem

Cephalosporins and cephamycins

• Cephalexin
• Cefazolin
• Cefuroxime
• Cefadroxil
• Ceftazidime

Penicillins

• Amoxicillin

Monocyclic beta-lactams

Glycopeptide antibiotics

• Vancomycin
• Teicoplanin
• Ramoplanin
• Decaplanin

Oxazolidinones

• Linezolid
• Quinupristin/dalfopristin

Polyketides

Macrolides

• Erythromycin
• Azithromycin
• Clarithromycin
• Roxithromycin

Ketolides

• Telithromycin

Tetracyclines

• Doxycycline
• Oxytetracycline
• Chlortetracycline

Polymyxins

• Polymyxin B
• Colistin

Quinolones (fluoroquinolones)

• Nalidixic acid
• Ciprofloxacin (Cipro)
• Ofloxacin
• Norfloxacin (Norflox)
• Levofloxacin (Levaquin)
• Trovafloxacin (Trovan)

Streptogramins

Sulfonamides

• Prontosil

Other important antibiotics:

• Chloramphenicol
• Clindamycin
• Fusidic acid
• Trimethoprim

Another such classification is by their mechanism of action

Antibiotics, which interfere with cell-wall synthesis

Beta-lactams, including penicillins like Amoxicillin and cephalosporins; mono-lactams, such as Imipenem; vancomycin, bacitracin

Antibiotics that interfere with bacterial protein synthesis

Antibiotics that bind to the 50S ribosomal unit

Lincosamides/lincosides including clindamycin and lincomycin; chloramphenicol, macrolides

Antibiotics, which interfere the 30S ribosomal unit

Tetracyclines; aminoglycosides including gentamicin

Drugs that inhibit folate synthesis

Sulfonamides and trimethoprim

Drugs that interfere with DNA synthesis

Metronidazole, quinolones, novobiocin

Drugs that interfere with RNA synthesis

Rifampin (rifampicin)

Drugs that interfere with cell membrane function

Polymyxin B, gramicidin

Antibiotics can also be classified by the organisms against which they are effective, and by the type of infection in which they are useful, which depends on the sensitivities of the organisms that most commonly cause the infection and the concentration of antibiotic obtainable in the affected tissue.

How does Cipro work?

Cipro belongs to a group of broad-spectrum antibiotics called the quinolones or fluoroquinolones. Cipro works by entering the bacterial cell and inhibiting a chemical called DNA-gyrase, which is involved in the production of genetic material (DNA). This therefore prevents the bacteria from reproducing and their growth is stopped.

Cipro is effective against several types of bacteria that tend to be resistant to other commonly used Antibiotics.

Uses of Cipro

Cipro is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions listed below.

• Urinary Tract Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, 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.
• 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.
• Acute Sinusitis caused by Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis.
• 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.
• Complicated Intra-Abdominal Infections (used in combination with metronidazole) caused by Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, or Bacteroides fragilis.
• 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.
• Uncomplicated cervical and urethral gonorrhea due to Neisseria gonorrhoeae.
• Inhalational anthrax (post-exposure): To reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis.

4. CIPRO EFFECTIVENESS
When is Cipro best taken?

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 of Cipro. Mean concentrations 12 hours after dosing with 250, 500, or 750 mg 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. Serum concentrations increase proportionately with doses up to 1000 mg.

A 500 mg oral dose of Cipro 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 Cipro given over 60 minutes every 12 hours. A 750 mg oral dose of Cipro 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 of Cipro results in a C max similar to that observed with a 400 mg I.V. dose. A 250 mg oral dose of Cipro given every 12 hours produces an AUC equivalent to that produced by an infusion of 200 mg Cipro given every 12 hours.

Distribution : The binding of Cipro 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, Cipro is widely distributed throughout the body. Tissue concentrations often exceed serum concentrations in both men and women, particularly in genital tissue including the prostate. Cipro 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. Cipro 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 Cipro.

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 Cipro usually exceed 200 µg/mL during the first two hours and are approximately 30 µg/mL at 8 to 12 hours after dosing. The urinary excretion of Cipro is virtually complete within 24 hours after dosing. The renal clearance of Cipro, 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 Cipro results in about a 50% reduction in the Cipro renal clearance and a 50% increase in its concentration in the systemic circulation. Although bile concentrations of Cipro are several folds 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.

5.CIPRO EFFECTS ON SPECIAL POPULATION
How do different people react to Cipro?

Pharmacokinetic studies of the oral (single dose) form of Cipro indicate that plasma concentrations of Cipro are higher in elderly subjects (> 65 years) as compared to young adults. Although the C max is increased 16-40%, the increase in mean AUC is approximately 30%, and can be at least partially attributed to decreased renal clearance in the elderly. Elimination half-life is only slightly (~20%) prolonged in the elderly. These differences are not considered clinically significant.

Nursing Mothers : Cipro is excreted in human milk. The amount of Cipro absorbed by the nursing infant is unknown. Because of the potential for serious adverse reactions in infants nursing from mothers taking Cipro, 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.

Pediatric Use : Safety and effectiveness in pediatric patients and adolescents less than 18 years of age have not been established, except for use in inhalational anthrax (post-exposure). Cipro causes arthropathy in juvenile animals.

For the indication of inhalational anthrax (post-exposure), the risk-benefit assessment indicates that administration of Cipro to pediatric patients is appropriate. For information regarding pediatric dosing in inhalational anthrax (post-exposure).

Geriatric Use : In a retrospective analysis of 23 multiple-dose controlled clinical trials of Cipro encompassing over 3500 Cipro treated patients, 25% of patients were greater than or equal to 65 years of age and 10% were greater than or equal to 75 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals on any drug therapy cannot be ruled out. Cipro is known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with impaired renal function. No alteration of Cipro dosage is necessary for patients greater than 65 years of age with normal renal function. However, since some older individuals experience reduced renal function by virtue of their advanced age, care should be taken in dose selection for elderly patients, and renal function monitoring may be useful in these patients.

6. CIPRO EFFECTS ON MEDICAL CONDITIONS
How does Cipro affect your existing condition/ailment?

In patients with reduced renal function, the half-life of Cipro is slightly prolonged. Dosage adjustments may be required.

In preliminary studies in patients with stable chronic liver cirrhosis, no significant changes in ciprofloxacin pharmacokinetics have been observed. The kinetics of Cipro in patients with acute hepatic insufficiency, however, has not been fully elucidated.

7. OTHER/ALTERNATE USES OF CIPRO
What else does Cipro treat?

Cipro may be used to treat other infections if prescribed by your physician.

8. ADVERSE/SIDE EFFECTS of CIPRO
What are the side effects of Cipro?

During clinical investigation with Cipro Tablets, 2,799 patients received 2,868 courses of the drug. Most of the adverse events reported were described as only mild or moderate in severity, abated soon after the drug was discontinued, and required no treatment. Cipro was discontinued because of an adverse event in 3.5% of patients treated.

The most frequently reported events, drug related or not, were nausea (5.2%), diarrhea (2.3%), vomiting (2.0%), abdominal pain/discomfort (1.7%), headache (1.2%), restlessness (1.1%), and rash (1.1%).

Additional events that occurred in less than 1% of Cipro patients are listed below.

BODY AS A WHOLE : foot pain

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

CENTRAL NERVOUS SYSTEM : dizziness, lightheadedness, insomnia, nightmares, hallucinations, manic reaction, irritability, tremor, ataxia, convulsive seizures, lethargy, drowsiness, weakness, malaise, anorexia, phobia, depersonalization, depression, paresthesia.

GASTROINTESTINAL : painful oral mucosa, oral candidiasis, dysphagia, intestinal perforation, gastrointestinal bleeding. Cholestatic jaundice has been reported.

HEMIC/LYMPHATIC : lymphadenopathy

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, bronchospasm, pulmonary embolism

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

Allergic reactions ranging from urticaria to anaphylactic reactions have been reported.

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

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.

In randomized, double-blind controlled clinical trials comparing Cipro tablets (500 mg BID) to cefuroxime axetil (250 mg - 500 mg BID) and to clarithromycin (500 mg BID) in patients with respiratory tract infections, Cipro demonstrated a CNS adverse event profile comparable to the control drugs.

Post-Marketing Adverse Events : Additional adverse events, regardless of relationship to drug, reported from worldwide marketing experience with quinolones, including Cipro, are:

Agitation, agranulocytosis, albuminuria, anaphylactic reactions, anosmia, candiduria, cholesterol elevation (serum), confusion, constipation, delirium, dyspepsia, dysphagia, erythema multiforme, exfoliative dermatitis, flatulence, glucose (blood), hemolytic anemia, hepatic necrosis, hypotension (postural), jaundice, methemoglobinemia, myalgia, myasthenia gravis (possible exacerbation), myoclonus, nystagmus, pancreatitis, phenytoin alteration (serum), potassium elevation (serum), prothrombin time prolongation, pseudomembranous colitis (The onset of pseudomembranous colitis symptoms may occur during or after antimicrobial treatment.), psychosis (toxic), renal calculi, Stevens-Johnson syndrome, taste loss, tendinitis, tendon rupture, toxic epidermal necrolysis, triglyceride elevation (serum), vaginal candidiasis, and vasculitis.

Other changes occurring in less than 0.1% of courses were: elevation of serum gammaglutamyl transferase, elevation of serum amylase, reduction in blood glucose, elevated uric acid, decrease in hemoglobin, anemia, bleeding diathesis, increase in blood monocytes, leukocytosis.