Ciprofloxacin

Ciprofloxacin is an Antibiotic agent belonging to Flouroquionoles

Ciprofloxacin is used in the treatment of Skin and Skin Structure Infections, Bone and Joint Infections, Complicated Intra-Abdominal Infections, Infectious Diarrhea, Typhoid Fever (Enteric Fever), Uncomplicated Cervical and Urethral Gonorrhea, Plague, Chronic Bacterial Prostatitis, Lower Respiratory Tract Infections, Urinary Tract Infections. It is also used to treat Anthrax; Bite wound infection (animal and human bites); Cat scratch disease, lymphadenitis (nondisseminated); Chancroid; Cholera (Vibrio cholera); Chronic obstructive pulmonary disease, acute exacerbation; Crohn disease, treatment of simple perianal fistulas; Diabetic foot infection; Endocarditis, treatment; Meningitis, bacterial; Meningococcal disease (prevention and control); Neutropenia (chemotherapy-induced), antibacterial prophylaxis; Neutropenic fever, low-risk cancer patients (empiric therapy); Peritoneal dialysis catheter-related infection; Pouchitis (post–ileal pouch-anal anastomosis), acute; Prostatitis, acute bacterial; Prosthetic joint infection; Spontaneous bacterial peritonitis, prophylaxis; Surgical prophylaxis; Surgical site infection; Tularemia.

Ciprofloxacin is Rapidly and well absorbed from the gastrointestinal tract. Bioavailability: Approx 70-80%. It is Widely distributed in the tissues. Crosses placenta, enters breast milk, bile (high concentrations), and CSF (10% noninflamed meninges; 14-37% inflamed meninges). It is partially metabolized in the liver to desthyleneciprofloxacin (M1), sulphociprofloxacin (M2), oxociprofloxacin (M3), and formylciprofloxacin (M4) in low concentrations and get excreted via urine [approx 40-50% as unchanged drug, approx 15%, as metabolites (oral); 70% as unchanged drug, 10% as metabolites (parenteral)]; feces [20-35% (oral), 15% (IV)] with elimination half-life: Approx 3-5 hours

The Tmax of Ciprofloxacin was achieved within 0.5-2 hours (conventional tab); 1-2.5 hours (extended-release tab). Cmax was about 3.5mg/ml.

Ciprofloxacin shows common side effects like Headache, dizziness, Diarrhea, sore throat, runny nose, sneezing, joint pain, etc.

Ciprofloxacin is available in the form of an Injection solution, Suspension, and Tablets.

Ciprofloxacin is available in India, Germany, Canada, Italy, USA

Ciprofloxacin diffuses into Mycobacterium cells. Once inside the cell, Ciprofloxacin inhibits the arabinosyltransferases (embA, embB, and emcee), preventing the formation of the cell wall components arabinogalactan and lipoarabinomannan, and preventing cell division. Decreased concentrations of arabinogalactan in the cell wall reduce the number of binding sites for mycolic acid, leading to the accumulation of mycolic acid, trehalose monomycolate, and trehalose dimycolate.

Ciprofloxacin is available in the form of Injection solution, Suspension, Tablets

• Oral: May administer with most foods to minimize GI upset; avoid antacid use; maintain proper hydration and urine output. Avoid concomitant administration with dairy products (eg, milk, yogurt) or calcium-fortified juices alone, however, may be taken with meals that contain these products; separate administration of Cipro XR and calcium >800 mg by at least 2 hours. Administer immediate-release ciprofloxacin and Cipro XR at least 2 hours before or 6 hours after antacids or other products containing calcium, iron, or zinc. Separate oral administration from drugs that may impair absorption (see Drug Interactions).

• Oral suspension: Should not be administered through feeding tubes (suspension is oil-based and adheres to the feeding tube). Shake vigorously before use for ~15 seconds; administer using the co-packaged graduated teaspoon. Do not chew the microcapsules in the suspension; swallow whole.

• Nasogastric/orogastric tube: Crush immediate-release tablet and mix with 20 to 60 mL water. Flush feeding tube before and after administration. Do not administer simultaneously with enteral nutrition (Ref). The optimal time frame for dose separation is unknown; one recommendation is to hold tube feedings at least 2 hours before and 4 hours after administration, which may require adjustment of feeding rates to compensate for lost feeding time.

• Tablet, extended release: Do not crush, split, or chew.

• Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Switch to IR formulation (tablet or oral solution).

• Parenteral: Administer by slow IV infusion over 60 minutes into a large vein (reduces risk of venous irritation).

Ciprofloxacin is used in the treatment of Tuberculosis. It is also used to treat Mycobacterium avium complex disease.

Ciprofloxacin , an antimycobacterial, is bacteriostatic against susceptible bacteria. It appears to inhibit the synthesis of bacterial metabolites thereby, inhibiting cellular metabolism and multiplication.

Ciprofloxacin is approved for use in the following clinical indications

• Skin and Skin Structure Infections

Ciprofloxacin is indicated in adult patients for treatment of 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, methicillin- Susceptible Staphylococcus aureus, methicillin-susceptible Staphylococcus epidermidis, or Streptococcus Pyogenes.

• Bone and Joint Infections

Ciprofloxacin is indicated in adult patients for treatment of bone and joint infections caused by Enterobacter Cloacae, Serratia marcescens, or Pseudomonas aeruginosa.

• Complicated Intra-Abdominal Infections

Ciprofloxacin is indicated in adult patients for treatment of complicated intra-abdominal infections (used in Combination with metronidazole) caused by Escherichia coli, Pseudomonas aeruginosa, Proteus Mirabilis, Klebsiella pneumoniae, or Bacteroides fragilis.

• Infectious Diarrhea

Ciprofloxacin is indicated in adult patients for treatment of infectious diarrhea caused by Escherichia coli (enterotoxigenic isolates), Campylobacter jejuni, Shigella boydii, Shigella dysenteriae, Shigella flexneri Or Shigella sonnei when antibacterial therapy is indicated. Although treatment of infections due to this organism in this organ system demonstrated a clinically Significant outcome, efficacy was studied in fewer than 10 patients.

• Typhoid Fever (Enteric Fever)

Ciprofloxacin is indicated in adult patients for the treatment of typhoid fever (enteric fever) caused by Salmonella Typhi. The efficacy of Ciprofloxacin in the eradication of the chronic typhoid carrier state has not been demonstrated.

• Uncomplicated Cervical and Urethral Gonorrhea

Ciprofloxacin is indicated in adult patients for treatment of uncomplicated cervical and urethral gonorrhea due to Neisseria gonorrhoeae . Inhalational Anthrax (Post-Exposure)

Ciprofloxacin is indicated in adults and pediatric patients from birth to 17 years of age for inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis. Ciprofloxacin serum concentrations achieved in humans served as a surrogate endpoint reasonably likely to predict clinical benefit and provided the initial basis for approval of this indication. Supportive clinical Information for Ciprofloxacin for anthrax post-exposure prophylaxis was obtained during the anthrax Bioterror attacks of October 2001.

• Plague

Ciprofloxacin is indicated for the treatment of plague, including pneumonic and septicemic plague, due to Yersinia Pestis (Y. pestis) and prophylaxis for plague in adults and pediatric patients from birth to 17 years of age. Efficacy studies of Ciprofloxacin could not be conducted in humans with plague for feasibility reasons. Therefore this indication is based on an efficacy study conducted in animals only.

• Chronic Bacterial Prostatitis

Ciprofloxacin is indicated in adult patients for treatment of chronic bacterial prostatitis caused by Escherichia Coli or Proteus mirabilis.

• Lower Respiratory Tract Infections

Ciprofloxacin is indicated in adult patients for treatment of lower respiratory tract infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Pseudomonas Aeruginosa, Haemophilus influenzae, Haemophilus parainfluenzae, or Streptococcus pneumoniae. Ciprofloxacin is not a drug of first choice in the treatment of presumed or confirmed pneumonia secondary to Streptococcus pneumoniae.

• Urinary Tract Infections

Urinary Tract Infections in Adults Ciprofloxacin is indicated in adult patients for treatment of urinary tract infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus mirabilis, Providencia rettgeri, Morganella morganii, Citrobacter koseri, Citrobacter freundii, Pseudomonas aeruginosa, Methicillin-susceptible Staphylococcus epidermidis, Staphylococcus saprophyticus, or Enterococcus Faecalis.

• Acute Uncomplicated Cystitis

Ciprofloxacin is indicated in adult female patients for treatment of acute uncomplicated cystitis caused by Escherichia coli or Staphylococcus saprophyticus. Because fluoroquinolones, including Ciprofloxacin , have been associated with serious adverse reactions and for some patients acute uncomplicated cystitis is self-limiting, Reserve CIPROFLOXACIN for treatment of acute uncomplicated cystitis in patients who have no alternative treatment Options.

• Complicated Urinary Tract Infection and Pyelonephritis in Pediatric Patients

Ciprofloxacin is indicated in pediatric patients aged one to 17 years of age for treatment of complicated urinary tract infections (cUTI) and pyelonephritis due to Escherichia 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 reactions compared to controls, including reactions related to joints and/or surrounding tissues. Ciprofloxacin , like other fluoroquinolones, is associated with arthropathy and histopathological changes in weight-bearing joints of juvenile animals.

• Acute Sinusitis

Ciprofloxacin is indicated in adult patients for treatment of acute sinusitis caused by Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis.

Although not approved there have been certain off label use documented for Ciprofloxacin which includes:

Anthrax; Bite wound infection (animal and human bites); Cat scratch disease, lymphadenitis (nondisseminated); Chancroid; Cholera (Vibrio cholerae); Chronic obstructive pulmonary disease, acute exacerbation; Crohn disease, treatment of simple perianal fistulas; Diabetic foot infection; Endocarditis, treatment; Meningitis, bacterial; Meningococcal disease (prevention and control); Neutropenia (chemotherapy-induced), antibacterial prophylaxis; Neutropenic fever, low-risk cancer patients (empiric therapy); Peritoneal dialysis catheter-related infection; Pouchitis (post–ileal pouch-anal anastomosis), acute; Prostatitis, acute bacterial; Prosthetic joint infection; Spontaneous bacterial peritonitis, prophylaxis; Surgical prophylaxis; Surgical site infection; Tularemia.

Ciprofloxacin is available in various strengths as 200mg/100mL, 200mg/20mL, 400mg/40mL, 400mg/200mL, 250mg/5mL, 500mg/5mL, 100mg, 250mg, 500mg, 750mg, 1000mg

Ciprofloxacin is available in the form of Injection solution, Suspension, Tablets

• Dosage Adjustment in Kidney Patient

Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m²): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post-trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients.

IV: 400 mg every 8 hours when organism minimum inhibitory concentration (MIC) ≤0.125 mg/L. Monte Carlo simulations suggest a dose of 600 mg every 8 hours may be required to achieve pharmacodynamic goals for organisms with MICs >0.125 mg/L ; monitor closely, especially with prolonged courses, or utilize another agent .

CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.

IV: 200 to 400 mg every 8 to 12 hours. Note: Utilize 400 mg every 8 hours only in severe infections or when difficult-to-treat organisms (MIC ≥0.5 mg/L) are suspected or confirmed; monitor closely.

Oral, immediate release: 250 to 750 mg every 12 hours (expert opinion inferred from relative IV clearance).

PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important. Dosing based on Monte Carlo simulations of 8- to 10-hour treatments with 4 to 5 L/hour flow rates.

IV: 400 mg every 12 hours assuming MIC susceptibility breakpoint ≤0.5 mg/L.

Oral, immediate release: 500 mg every 12 hours (administer after PIRRT) (expert opinion inferred from relative IV clearance).

• Dosage Adjustment in Hepatic impairment Patient

No Dose Adjustment is necessary.

· Dosage Adjustment for Pediatric Patients:-

In pediatric patients, ciprofloxacin is not routinely first-line therapy, but after assessment of risks and benefits, can be considered a reasonable alternative for some situations [eg, anthrax, resistance (cystic fibrosis)] or in situations where the only alternative is parenteral therapy and ciprofloxacin offers an oral therapy option Oral liquid products are available in two concentrations (ie, 50 mg/mL and 100 mg/mL); precautions should be taken to verify product selection and avoid confusion between the different concentrations. Extended release tablets and immediate release formulations are not interchangeable.

General dosing, susceptible infection : Infants, Children, and Adolescents:

Mild to moderate infections: Oral, immediate release: 10 mg/kg/dose twice daily; maximum dose: 500 mg/dose.

Severe infections:

Oral, immediate release: 15 to 20 mg/kg/dose twice daily; maximum dose: 750 mg/dose.

IV: 10 mg/kg/dose every 8 to 12 hours; maximum dose: 400 mg/dose.

Anthrax: Infants, Children, and Adolescents:Cutaneous, without systemic involvement: AAP recommendations: Oral, immediate release: 15 mg/kg/dose every 12 hours; maximum dose: 500 mg/dose. Duration: 7 to 10 days for naturally acquired infection, up to 60 days for biological weapon-related event .

Inhalational (postexposure prophylaxis):Oral, immediate release: 15 mg/kg/dose every 12 hours for 60 days; maximum dose: 500 mg/dose.

IV: 10 mg/kg/dose every 12 hours for 60 days; maximum dose: 400 mg/dose; may substitute oral antibiotics for IV antibiotics as soon as clinical condition improves.

Systemic (including meningitis): AAP recommendations:

Initial treatment as part of combination therapy: IV: 10 mg/kg/dose every 8 hours; maximum dose: 400 mg/dose; continue until clinical criteria for stability are met.

Oral step-down to complete a 60 day total course: Oral, immediate release: 15 mg/kg/dose twice daily.

Campylobacteriosis, HIV-exposed/-infected : Duration of therapy: 7 to 10 days for gastroenteritis, at least 14 days for bacteremia, 2 to 6 weeks for recurrent bacteremic disease.

Oral, immediate release: Adolescents: 500 to 750 mg every 12 hours.

IV: Adolescents: 400 mg every 12 hours.

Catheter (peritoneal dialysis); exit-site or tunnel infection: Infant, Children, and Adolescents: Oral, immediate release: 10 to 15 mg/kg/dose once daily; maximum dose: 500 mg/dose

Chancroid: Adolescents: Oral, immediate release: 500 mg twice daily for 3 days

Cystic fibrosis: Children and Adolescents:

Oral, immediate release: 20 mg/kg/dose every 12 hours; maximum dose: 1,000 mg/dose .

Endocarditis, culture-negative, empiric therapy: AHA guidelines (Ref): Administer in combination with other antibiotics: Children and Adolescents:

Oral, immediate release: 10 to 15 mg/kg/dose twice daily for 4 to 6 weeks; maximum dose: 750 mg/dose.

IV: 10 to 15 mg/kg/dose twice daily for 4 to 6 weeks; maximum dose: 400 mg/dose.

IV: 10 mg/kg/dose every 8 hours; maximum dose: 400 mg/dose

Infectious diarrhea:

Cholera: Infants, Children, and Adolescents: Oral, immediate release: 15 mg/kg/dose twice daily for 3 days; maximum dose: 500 mg/dose . Alternately, 20 mg/kg/dose as a single dose has been used.

Shigellosis dysentery:

Non-HIV-exposed/-infected: Infants, Children, and Adolescents: Oral, immediate release: 15 mg/kg/dose twice daily for 3 days; maximum dose: 500 mg/dose (Ref).

HIV-exposed-infected : Adolescents: Duration of therapy: 7 to 10 days for gastroenteritis, at least 14 days for bacteremia, up to 6 weeks for recurrent infection.

Oral, immediate release: Adolescents: 500 to 750 mg every 12 hours.

IV: Adolescents: 400 mg every 12 hours.

Intra-abdominal infection, complicated: Infants, Children, and Adolescents: IV: 10 to 15 mg/kg/dose every 12 hours; maximum dose: 400 mg/dose

Meningococcal invasive disease prophylaxis, high-risk contacts: Infants, Children, and Adolescents: Oral: Immediate release: 20 mg/kg as a single dose, maximum dose 500 mg/dose

Mycobacterium avium Complex, severe or disseminated disease, HIV-exposed/-infected: Infants and Children: Oral, immediate release: 10 to 15 mg/kg/dose twice daily in addition to other antibiotics; maximum dose: 750 mg/dose.

Plague (Yersinia pestis infection) (alternative agent):

Infants, Children, and Adolescents:

Oral, immediate release: 15 mg/kg/dose every 8 to 12 hours for 14 days; maximum dose: 500 mg/dose.

IV: 10 mg/kg/dose every 8 to 12 hours for 10 to 21 days; maximum dose: 400 mg/dose.

Alternate dosing :Postexposure prophylaxis: Children and Adolescents: Oral, immediate release: 20 mg/kg/dose twice daily for 7 days; maximum dose: 500 mg/dose.

Treatment: Note: Treat for a total of 10 to 14 days (combined IV and oral) or until 2 days after the fever subsides, whichever is longer.

Children and Adolescents:

Initial treatment: IV: 15 mg/kg/dose every 12 hours; maximum dose: 400 mg/dose; once patient improves may switch to oral therapy to complete treatment course.

Oral step-down treatment: Oral, immediate release: 20 mg/kg/dose twice daily; maximum dose: 500 mg/dose; higher maximum doses (up to 750 mg twice daily) are recommended for adults.

Pneumonia, community-acquired (Haemophilus influenza): Infants >3 months and Children: IV: 15 mg/kg/dose every 12 hours.

Salmonellosis, HIV-exposed/-infected : Duration of therapy: At least 7 to 14 days if CD4 > 200 cells/mm2, 2 to 6 weeks if CD4 <200 cells/mm2.

Oral, immediate release: Adolescents: 500 to 750 mg every 12 hours.

IV: Adolescents: 400 mg every 12 hours.

Surgical prophylaxis: Children and Adolescents: IV: 10 mg/kg within 120 minutes prior to surgical incision; maximum dose: 400 mg/dose

Tularemia, mild disease: Infants, Children, and Adolescents:

Treatment or contained casualty situation: IV: 15 mg/kg/dose twice daily for at least 10 days; maximum dose: 400 mg/dose.

Prophylaxis, mass casualty situation: Oral, immediate release: 15 mg/kg/dose twice daily for 14 days; maximum dose: 500 mg/dose.

Urinary tract infection:

Cystitis, acute uncomplicated: Adolescents ≥ 18 years: Oral, extended release: 500 mg every 24 hours for 3 days.

Complicated (including pyelonephritis):

Oral, immediate release: Children and Adolescents: 10 to 20 mg/kg/dose every 12 hours for 10 to 21 days; maximum dose: 750 mg/dose.

Oral, extended-release: Adolescents ≥18 years: 1,000 mg every 24 hours for 7 to 14 days.

IV: Children and Adolescents: 6 to 10 mg/kg/dose every 8 hours for 10 to 21 days; maximum dose: 400 mg/dose.

Do not take with food; avoid tyramine- and/or histamine-containing foods. Increase dietary intake of folate, niacin, magnesium

Hypersensitivity to ciprofloxacin, any component of the formulation, or other quinolones; concurrent administration of tizanidine

Concerns related to adverse effects:

• Crystalluria: Rarely, crystalluria has occurred; urine alkalinity may increase the risk. Ensure adequate hydration during therapy.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required.

• Syphilis: Since ciprofloxacin is ineffective in the treatment of syphilis and may mask symptoms, all patients should be tested for syphilis at the time of gonorrheal diagnosis and 3 months later.

Special populations:

• Older adult: Adverse effects (eg, tendon rupture, QT changes) may be increased in elderly patients.

• G6PD deficiency: Hemolytic reactions may (rarely) occur with fluoroquinolone use in patients with G6PD deficiency .

• Pediatric: Adverse effects, including those related to joints and/or surrounding tissues, are increased in pediatric patients, and therefore, ciprofloxacin should not be considered as drug of choice in children (exception is anthrax treatment).

Ciprofloxacin may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

Ciprofloxacin is present in breast milk.

Information related to the presence of ciprofloxacin in breast milk is available from 10 lactating women given oral ciprofloxacin 750 mg every 12 hours for 3 doses. Average milk concentrations were highest 2 hours after the dose (3.79 mcg/mL) and decreased to 0.02 mcg/mL 24 hours after the last dose (Giamarellou 1989). Using the milk concentration of 3.79 mcg/mL, another author has estimated the potential infant dosage via breastfeeding would be ≤0.569 mg/kg/day

Pregnancy Category C.

Risk Summary

Prolonged experience with ciprofloxacin in pregnant women over several decades, based on available published information from case reports, case-control studies and observational studies on ciprofloxacin administered during pregnancy, have not identified any drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes . Oral administration of ciprofloxacin during organogenesis at doses up to 100 mg/kg to pregnant mice and rats, and up to 30 mg/kg to pregnant rabbits did not cause fetal malformations These doses were up to 0.3, 0.6, and 0.4 times the maximum recommended clinical oral dose in mice, rats, and rabbits, respectively, based on body surface area.

Food decreases rate, but not the extent, of absorption. Ciprofloxacin may increase serum caffeine levels if taken concurrently. Rarely, crystalluria may occur. Enteral feedings may decrease plasma concentrations of ciprofloxacin probably by >30% inhibition of absorption. Management: May administer with most foods to minimize GI upset. If unable to avoid the following foods, administer ciprofloxacin at least 2 hours before or 6 hours after dairy products or calcium-fortified juices alone or in a meal containing >800 mg calcium. Restrict caffeine intake if excessive cardiac or CNS stimulation occurs. Ensure adequate hydration during therapy. Ciprofloxacin should not be administered with enteral feedings. The feeding would need to be discontinued for 1 to 2 hours prior to and after ciprofloxacin administration. Nasogastric administration produces a greater loss of ciprofloxacin bioavailability than does nasoduodenal administration

• Common Adverse effects

Irreversible tendinitis, tendon rupture, peripheral neuropathy, CNS effects (e.g. seizures, increased intracranial pressure), QT interval prolongation, torsades de pointes, psychiatric reactions (e.g. depression, psychosis, suicidal ideation), aortic aneurysm ruptures or dissection (long-term use), photosensitivity reactions.

• Less Common Adverse effects:

Nausea, vomiting, diarrhoea, abdominal pain, dyspepsia. General disorders and administration site conditions: Fever, irritability.

• Rare Adverse effects

Crystalluria, Increased intracranial pressure, dizziness, headache, restlessness, tremor.

Increased risk of prolonged QT interval with Class IA (e.g. quinidine, procainamide) and Class III (e.g. amiodarone, sotalol) antiarrhythmics, TCA, macrolides (e.g. erythromycin), cisapride, antipsychotics. Increased serum concentration with probenecid. May increase serum concentration and toxicity of methotrexate; CYP1A2 substrates (e.g. clozapine, ropinirole, theophylline); xanthine derivatives (e.g. caffeine, pentoxifylline). Increased risk of tendon disorders with corticosteroids. Increased serum creatinine with cyclosporin. Increased risk of convulsions with NSAIDs. May alter serum concentrations of phenytoin. Reduced oral absorption with products containing multivalent cations (e.g., Al, Ca, Mg, Fe). May increase the anticoagulant effect of vitamin K, warfarin.

Potentially Fatal: May increase serum concentration and potentiate hypotensive and sedative effects of tizanidine. Rarely, serious and fatal seizures, status epilepticus, cardiac arrest, respiratory failure with theophylline.

The common side effects of Ciprofloxacin include the following Bloody or black, tarry stools · burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings.

Symptoms:

Dizziness, tremor, headache, tiredness, seizures, hallucinations, confusion, abdominal discomfort, crystalluria, haematuria, acute renal and hepatic impairment.

Management:

Symptomatic treatment. Empty stomach by inducing emesis or by gastric lavage. Maintain adequate hydration. May administer antacids containing Mg, Al, or Ca to reduce oral absorption. Monitor ECG, renal function, urinary pH, and acidify urine if required to prevent crystalluria.

Pharmacodynamic

Ciprofloxacin is a second generation fluoroquinolone that is active against many Gram negative and Gram positive bacteria. It produces its action through inhibition of bacterial DNA gyrase and topoisomerase IV. Ciprofloxacin binds to bacterial DNA gyrase with 100 times the affinity of mammalian DNA gyrase. There is no cross resistance between fluoroquinolones and other classes of antibiotics, so it may be of clinical value when other antibiotics are no longer effective. Ciprofloxacin and its derivatives are also being investigated for its action against malaria, cancers, and AIDS.

Pharmacokinetics

• Absorption: Rapid and well absorbed from the gastrointestinal tract. Bioavailability: Approx 70-80%. Time to peak plasma concentration: 0.5-2 hours (conventional tab); 1-2.5 hours (extended-release tab).
• Distribution: Widely distributed in the tissues. Crosses placenta, enters breast milk, bile (high concentrations), and CSF (10% noninflamed meninges; 14-37% inflamed meninges). Volume of distribution: 2.1-2.7 L/kg. Plasma protein binding: 20-40%.
• Metabolism: Partially metabolised in the liver to desthyleneciprofloxacin (M1), sulphociprofloxacin (M2), oxociprofloxacin (M3), and formylciprofloxacin (M4) in low concentrations.
• Excretion: Via urine [approx 40-50% as unchanged drug, approx 15%, as metabolites (oral); 70% as unchanged drug, 10% as metabolites (parenteral)]; faeces [20-35% (oral), 15% (IV)]. Elimination half-life: Approx 3-5 hours

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
• https://reference.medscape.com/drug/colestid-Ciprofloxacin -342452
• https://go.drugbank.com/drugs/DB00375
• https://www.sciencedirect.com/topics/medicine-and-dentistry/Ciprofloxacin
• https://europepmc.org/article/med/6988203