Ciprofloxacin (Systemic)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Generic: 200 mg/100 mL (100 mL [DSC]); 400 mg/200 mL (200 mL [DSC])

Solution, Intravenous [preservative free]:

Cipro in D5W: 400 mg/200 mL (200 mL [DSC]) [latex free]

Generic: 200 mg/100 mL (100 mL); 400 mg/200 mL (200 mL); 200 mg/20 mL (20 mL [DSC]); 400 mg/40 mL (40 mL [DSC])

Suspension Reconstituted, Oral:

Cipro: 250 mg/5 mL (100 mL); 500 mg/5 mL (100 mL) [strawberry flavor]

Generic: 250 mg/5 mL (100 mL [DSC]); 500 mg/5 mL (100 mL [DSC])

Tablet, Oral, as hydrochloride [strength expressed as base]:

Cipro: 250 mg, 500 mg

Generic: 100 mg, 250 mg, 500 mg, 750 mg

Tablet Extended Release 24 Hour, Oral, as base and hydrochloride [strength expressed as base]:

Cipro XR: 500 mg [DSC], 1000 mg [DSC]

Generic: 500 mg [DSC], 1000 mg [DSC]

Pharmacology

Mechanism of Action

Inhibits DNA-gyrase in susceptible organisms; inhibits relaxation of supercoiled DNA and promotes breakage of double-stranded DNA

Pharmacokinetics/Pharmacodynamics

Absorption

Oral: Well-absorbed; 500 mg orally every 12 hours produces an equivalent AUC to that produced by 400 mg IV over 60 minutes every 12 hours

Distribution

V_d: 2.1 to 2.7 L/kg; tissue concentrations often exceed serum concentrations especially in kidneys, gallbladder, liver, lungs, gynecological tissue, and prostatic tissue; CSF concentrations: 10% of serum concentrations (noninflamed meninges), 14% to 37% (inflamed meninges)

Metabolism

Partially hepatic; forms 4 metabolites (limited activity)

Excretion

Urine (35% to 70% as unchanged drug); feces (15% to 35%; <1% as unchanged drug)

Clearance: After IV:

CF children: 0.84 L/hour/kg

Adults: 0.5 to 0.6 L/hour/kg

Time to Peak

Oral:

Immediate release tablet: 0.5 to 2 hours

Extended release tablet: Cipro XR: 1 to 2.5 hours

Half-Life Elimination

Children: 4 to 5 hours; Adults: Normal renal function: 4 to 6 hours

Protein Binding

20% to 40%

Use in Specific Populations

Special Populations: Renal Function Impairment

The half-life is prolonged.

Special Populations: Elderly

C_max increased 16% to 40%, AUC increased approximately 20% to 30%, and half-life increased approximately 20%.

Use: Labeled Indications

Children and Adolescents: Treatment of complicated urinary tract infections and pyelonephritis due to E. coli. Note: Although effective, ciprofloxacin is not the drug of first choice in children.

Infants, Children, Adolescents, and Adults: Prophylaxis to reduce incidence or progression of disease following inhalation exposure to Bacillus anthracis; prophylaxis and treatment of plague (Yersinia pestis).

Adults: Treatment of the following infections when caused by susceptible bacteria: Urinary tract infections; acute uncomplicated cystitis in females, chronic bacterial prostatitis, bone and joint infections, complicated intra-abdominal infections (in combination with metronidazole), infectious diarrhea, typhoid fever (Salmonella typhi), hospital-acquired (nosocomial) pneumonia.

Limitations of use: Because fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions (eg, tendinitis and tendon rupture, peripheral neuropathy, CNS effects), reserve ciprofloxacin for use in patients who have no alternative treatment options for acute uncomplicated cystitis.

Use: Off Label

Anthraxyes

Based on the Centers for Disease Control and Prevention (CDC) expert panel meetings on prevention and treatment of anthrax, ciprofloxacin is an effective and recommended agent for treatment of cutaneous or systemic anthrax.

Bite wound infection (animal and human bites)yes

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTIs), ciprofloxacin, in combination with an appropriate agent for anaerobes, is an effective and recommended alternative option for prophylaxis and treatment of human or animal bite wounds, particularly in patients who are hypersensitive to beta-lactams.

Cat scratch disease, lymphadenitis (nondisseminated)c

Data from a limited number of patients suggest that ciprofloxacin may be beneficial for the treatment of cat scratch disease Holley 1991.

Clinical experience suggests the utility of ciprofloxacin as an alternative agent in the treatment of cat scratch disease Spach 2019.

Chancroidyes

Based on the CDC sexually transmitted diseases treatment guidelines, ciprofloxacin is an effective and recommended alternative agent in the treatment of chancroid due to H. ducreyi. However, intermediate resistance to ciprofloxacin has been reported in several isolates. Potential resistance issues should be considered when initiating therapy for the treatment of chancroid.

Cholera (Vibrio cholerae)yes

Based on the CDC guidelines for cholera treatment with antibiotics, ciprofloxacin is an effective and recommended alternative agent for the treatment of moderate to severe cholera, in combination with aggressive hydration. Potential resistance issues should be considered when initiating therapy Saha 2006.

Chronic obstructive pulmonary disease, acute exacerbationa

Data from a randomized, double-blind study support the use of ciprofloxacin for the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD) Nouira 2010. In addition, data from a smaller randomized study support the use of ciprofloxacin for treatment of acute exacerbations of COPD Umut 1999.

Crohn disease, treatment of simple perianal fistulasyes

Based on the American College of Gastroenterology guidelines for the management of Crohn disease in adults, ciprofloxacin (with or without metronidazole) is an effective and recommended treatment for patients with simple perianal fistulas.

Diabetic foot infectionyes

Based on the IDSA guidelines for diagnosis and treatment of diabetic foot infections, ciprofloxacin, in combination with other appropriate agents, is an effective and recommended treatment option for diabetic foot infection.

Endocarditis, treatmentyes

Based on the American Heart Association (AHA) scientific statement on infective endocarditis in adults, ciprofloxacin is an effective and recommended alternative treatment option for infective endocarditis (native or prosthetic valve) due to HACEK organisms (Haemophilus spp., Aggregatibacter spp., Cardiobacterium hominis, Eikenella corrodens, and Kingella spp.) in patients unable to tolerate beta-lactam therapy.

Granuloma inguinale (donovanosis)yes

Based on the CDC sexually transmitted diseases treatment guidelines, ciprofloxacin is an effective and recommended alternative agent in the treatment of granuloma inguinale (donovanosis) when azithromycin is not appropriate.

Meningitis, bacterialyes

Based on the IDSA guidelines for the management of bacterial meningitis and health care-associated ventriculitis and meningitis, ciprofloxacin is an effective and recommended alternative therapy for susceptible Pseudomonas aeruginosa meningitis; meningitis caused by susceptible multidrug-resistant gram-negative bacilli (in patients who have not responded to or cannot receive standard antimicrobial therapy); and health care-associated meningitis or ventriculitis requiring empiric therapy for gram-negative pathogens in patients with anaphylaxis to beta-lactams (in combination with other appropriate agents).

Meningococcal disease (prevention and control)yes

Based on the CDC guidelines for the prevention and control of meningococcal disease (Neisseria meningitidis), ciprofloxacin is an effective and recommended agent for management of this disease.

Neutropenia (chemotherapy-induced), antibacterial prophylaxisyes

Based on IDSA guidelines for the use of antimicrobial agents in neutropenic patients with cancer, oral ciprofloxacin is effective and recommended for antibiotic prophylaxis in high-risk patients with expected durations of prolonged and profound neutropenia (ANC ≤100 cells/mm³ for >7 days). Based on the Center for International Blood and Marrow Transplant Research, the National Marrow Donor Program, the European Blood and Marrow Transplant Group, and multiple other organizations guidelines for preventing infectious complications among hematopoietic cell transplant (HCT) recipients, oral ciprofloxacin may be used in adult HCT recipients to prevent bacterial infections in the first 100 days after transplant when the anticipated period of neutropenia is ≥7 days.

Neutropenic fever, low-risk cancer patients (empiric therapy)ayes

Data from 3 randomized trials (blinding varied) support the use of oral ciprofloxacin (in combination with amoxicillin and clavulanate) for the outpatient empiric management of low-risk neutropenic fever Freifeld 1999, Kern 1999, Kern 2013. The American Society of Clinical Oncology (ASCO) and IDSA guidelines for outpatient management of fever and neutropenia in adults treated for malignancy and the IDSA guidelines for use of antimicrobial agents in neutropenic patients with cancer also support oral ciprofloxacin use (in combination with amoxicillin and clavulanate) in this patient population. Use should be avoided in patients who have received fluoroquinolone prophylaxis.

Peritoneal dialysis catheter-related infectionyes

Based on the International Society for Peritoneal Dialysis catheter-related infection recommendations, ciprofloxacin is an effective and recommended agent for the management of peritoneal dialysis catheter exit-site or tunnel infection.

Peritonitis, spontaneous bacterial (prevention)byes

Limited data from controlled trials support use of ciprofloxacin as an alternative to norfloxacin for primary long-term prophylaxis in cirrhotic patients with low protein ascites, or as secondary long-term prophylaxis in patients who have experienced a prior spontaneous bacterial peritonitis (SBP) episode. Additional trials may be necessary to further define the role of ciprofloxacin in the prevention of SBP.

According to AASLD and EASL guidelines, ciprofloxacin is suggested as an alternative to norfloxacin; however, recommendations regarding the use of daily or weekly dosing vary. The AASLD prefers daily dosing, given the risk of increasing quinolone bacterial resistance rates with weekly dosing. Increasing bacterial resistance rates to antibiotics used in the treatment and prevention of SBP have been documented; therefore, local epidemiological patterns should be considered, and use of antibiotic prophylaxis should be restricted to patients at high risk of SBP.

Pneumonia, community-acquiredyes

Based on the IDSA/American Thoracic Society (ATS) consensus guidelines on the management of community-acquired pneumonia, ciprofloxacin, in combination with an antipneumococcal, antipseudomonal beta-lactam, is effective and recommended as empiric therapy in hospitalized patients with community-acquired pneumonia who require coverage for P. aeruginosa.

Prostatitis, acute bacterialc

Data from a limited number of patients studied suggest that ciprofloxacin may be beneficial for the treatment of acute bacterial prostatitis Ulleryd 2003.

Clinical experience also suggests the utility of ciprofloxacin in the treatment of acute bacterial prostatitis Coker 2016.

Prosthetic joint infectionyes

Based on the IDSA guidelines for the management of prosthetic joint infection, ciprofloxacin is an effective and recommended agent for treatment of prosthetic joint infection with either Pseudomonas aeruginosa, Enterobacter spp, or Enterobacteriaceae. Ciprofloxacin is also an effective and recommended agent for indefinite oral antimicrobial suppression of Pseudomonas aeruginosa. Ciprofloxacin, in combination with rifampin, is also an effective and recommended agent for oral phase treatment of prosthetic joint infection with staphylococci after completion of parenteral therapy.

Surgical prophylaxisyes

Based on the American Society of Health-System Pharmacists (ASHP), the IDSA, the Surgical Infection Society (SIS), and the Society for Healthcare Epidemiology of America (SHEA) guidelines for antimicrobial prophylaxis in surgery, ciprofloxacin is an effective and recommended agent for prophylaxis of certain surgical procedures (eg, gastroduodenal, biliary tract, appendectomy, hysterectomy, and some urologic procedures) when allergy to beta-lactams exist and is a recommended agent for lower urologic tract instrumentation in patients with risk factors for infection (including transrectal prostate biopsy).

Surgical site infectionyes

Based on the IDSA guidelines for the diagnosis and management of SSTIs, ciprofloxacin, in combination with metronidazole, is an effective and recommended option for treatment of surgical site infections occurring after surgery of the intestinal or genitourinary tract, perineum, or axilla. Systemic antibacterials are not routinely indicated for surgical site infections, but may be beneficial (in conjunction with suture removal plus incision and drainage) in patients with significant systemic response (eg, temperature >38.5°C, heart rate >110 beats per minute, erythema/induration extending >5 cm from incision, WBC >12,000/mm³).

Tularemiacyes

Data from retrospective studies and case reports/series demonstrate varied results with the use of ciprofloxacin in the management of tularemia. Guidelines created by the Infectious Diseases Society of America, Working Group on Civilian Biodefense, and the European Commission's Task Force on Biological and Chemical Agent Threats (BICHAT) recommend ciprofloxacin as an alternative in the management of mild tularemia infection. In scenarios of mass casualty management and postexposure prophylaxis, the Working Group on Civilian Biodefense considers oral ciprofloxacin and doxycycline as drugs of choice.

Contraindications

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

Canadian labeling: Additional contraindications (not in the US labeling): Concurrent administration of agomelatine

Dosage and Administration

Dosing: Adult

Note: Extended-release tablets and immediate-release formulations are not interchangeable. Unless otherwise specified, oral dosing reflects the use of immediate-release formulations.

Anthrax: Note: Consult public health officials for event-specific recommendations.

Inhalational exposure (postexposure prophylaxis):

Oral: 500 mg every 12 hours for 60 days

IV: 400 mg every 12 hours for 60 days

Note: Anthrax vaccine should also be administered to exposed individuals (CDC [Hendricks 2014]).

Cutaneous (without systemic involvement), treatment (off-label use): Oral: 500 mg every 12 hours for 7 to 10 days after naturally acquired infection; 60 days following biological weapon-related event. Note: Patients with cutaneous lesions of the head or neck or extensive edema should be treated for systemic involvement (CDC [Hendricks 2014]).

Systemic (meningitis excluded), treatment (off-label use): IV: 400 mg every 8 hours, in combination with other appropriate agents for 2 weeks or until clinically stable, whichever is longer (CDC [Hendricks 2014])

Meningitis, treatment (off-label use): IV: 400 mg every 8 hours, in combination with other appropriate agents for 2 to 3 weeks or until clinically stable, whichever is longer (CDC [Hendricks 2014])

Note: Antitoxin should also be administered for systemic anthrax. Following the course of IV combination therapy for systemic anthrax infection (including meningitis), patients exposed to aerosolized spores require oral monotherapy to complete a total antimicrobial course of 60 days (CDC [Hendricks 2014]).

Bite wound infection, prophylaxis or treatment (animal and human bites) (alternative agent) (off-label use): Note: Use in combination with an appropriate agent for anaerobes.

Oral: 500 to 750 mg twice daily

IV: 400 mg every 12 hours

Duration of therapy: 3 to 5 days for prophylaxis (IDSA [Stevens 2014]); duration of treatment for established infection is typically 5 to 14 days and varies based on patient-specific factors, including clinical response (Baddour 2019a; Baddour 2019b).

Cat scratch disease, lymphadenitis (nondisseminated) (alternative agent) (off-label use): Oral: 500 mg twice daily (Holley 1991).

Chancroid (alternative agent) (off-label use): Oral: 500 mg twice daily for 3 days (CDC [Workowski 2015])

Cholera (Vibrio cholerae) (alternative agent) (off-label use): Oral: 1 g as a single dose (IDSA [Guerrant 2001]; Khan 1996)

Chronic obstructive pulmonary disease, acute exacerbation (off-label use): Oral: 500 to 750 mg twice daily (Nouira 2010; Umut 1999) for 5 to 7 days (GOLD 2018). Note: Some experts reserve ciprofloxacin for patients with complicated chronic obstructive pulmonary disease (eg, age ≥65 years, FEV₁ <50% predicted, frequent exacerbations, major comorbidities) at risk of Pseudomonas infection (Bartlett 2019; Sethi 2008).

Crohn disease, treatment of simple perianal fistulas (off-label use): Oral: 500 mg twice daily, with or without metronidazole, for 4 weeks (ACG [Lichtenstein 2018]; Bitton 2019); some experts recommend treatment duration up to 8 weeks (ACG [Lichtenstein 2018]).

Diabetic foot infection (off-label use): Note: When used as empiric therapy, ciprofloxacin should be used in combination with other appropriate agents.

Mild to moderate infection: Oral: 500 mg every 12 hours (750 mg every 12 hours if Pseudomonas aeruginosa is suspected) (IDSA [Lipsky 2012]; Weintrob 2019).

Moderate to severe infection: IV: 400 mg every 12 hours (400 mg every 8 hours if P. aeruginosa is suspected) (IDSA [Lipsky 2012]; Weintrob 2019).

Endocarditis due to HACEK organisms (alternative agent) (off-label use):

Oral: 500 mg every 12 hours for 4 weeks (native valve) or 6 weeks (prosthetic valve) (AHA [Baddour 2015]).

IV: 400 mg every 12 hours for 4 weeks (native valve) or 6 weeks (prosthetic valve) (AHA [Baddour 2015]).

Granuloma inguinale (donovanosis) (alternative agent) (off-label use): Oral: 750 mg twice daily for at least 3 weeks (and until lesions have healed). Note: If symptoms do not improve within the first few days of therapy, another agent (eg, aminoglycoside) can be added (CDC [Workowski 2015]).

Intra-abdominal infection (including perforated appendix, appendiceal abscess, acute diverticulitis, acute cholecystitis), community-acquired: Note: For empiric therapy, usually administered in combination with metronidazole. The addition of metronidazole may not be necessary for uncomplicated biliary infection of mild to moderate severity (SIS/IDSA [Solomkin 2010]; Vollmer 2019). Empiric oral regimens may be appropriate for patients with mild to moderate infection. Other patients may be switched from IV to oral therapy when clinically improved and able to tolerate an oral diet (SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]).

Oral: 500 mg every 12 hours

IV: 400 mg every 12 hours

Duration: Duration of therapy is for 4 to 7 days following adequate source control (SIS/IDSA [Solomkin 2010]); for uncomplicated appendicitis and diverticulitis managed nonoperatively, a longer duration is necessary (Barshak 2019; Pemberton 2019).

Meningitis, bacterial (community-acquired or health care-associated) (alternative agent) (off-label use): IV: 400 mg every 8 to 12 hours; for empiric therapy, must be used in combination with other appropriate agents (IDSA [Tunkel 2004]; IDSA [Tunkel 2017])

Meningococcal meningitis prophylaxis (off-label use): Oral: 500 mg as a single dose (CDC 2005)

Neutropenia (chemotherapy-induced), antibacterial prophylaxis in high-risk patients anticipated to have an ANC ≤100 cells/mm³ for >7 days (off-label use): Oral: 500 to 750 mg twice daily (IDSA [Freifeld 2011]; Wingard 2019); some clinicians will provide antibacterial prophylaxis if ANC is anticipated to be <500 cells/mm³ for >7 days (Wingard 2019). For hematopoietic cell transplant recipients, begin at the time of stem cell infusion and continue until recovery of neutropenia or until initiation of empiric antibiotic therapy for neutropenic fever (Tomblyn 2009).

Neutropenic fever, low-risk cancer patients (empiric therapy) (off-label use): Oral: 750 mg every 12 hours (Kern 1999; Kern 2013) in combination with amoxicillin and clavulanate; continue until fever and neutropenia have resolved. Note: Avoid in patients who have received fluoroquinolone prophylaxis. Administer first dose in the health care setting (after blood cultures are drawn); observe patient for ≥4 hours before discharge (ASCO/IDSA [Taplitz 2018]; IDSA [Freifeld 2011]).

Osteomyelitis:

Oral:

Treatment: 500 to 750 mg every 12 hours; when treating P. aeruginosa, 750 mg every 12 hours for ≥6 weeks (Calhoun 2005; IDSA [Berbari 2015]; Osmon 2019).

Chronic suppression in presence of retained infected orthopedic hardware: 250 to 500 mg every 12 hours (IDSA [Osmon 2013]).

IV: 400 mg every 12 hours; when treating P. aeruginosa, 400 mg every 8 hours for ≥6 weeks (Calhoun 2005; IDSA [Berbari 2015]; Osmon 2019).

Peritoneal dialysis catheter, exit-site or tunnel infection (off-label use): Oral: 250 mg twice daily. When used for empiric therapy, must be used in combination with other appropriate agents (ISPD [Szeto 2017]).

Peritonitis, spontaneous bacterial (prevention), high-risk patients (eg, hospitalized patients with Child-Pugh class B or C cirrhosis and active GI bleeding) (alternative agent) (off-label use):

Oral: 500 mg every 12 hours; total duration of therapy is 7 days (parenteral and oral) (Runyon 2019).

IV (alternative for nonfunctional GI tract): 400 mg every 12 hours; total duration of therapy is 7 days (parenteral and oral) (Runyon 2019).

Long-term secondary spontaneous bacterial peritonitis prophylaxis: Oral: 500 mg once daily (Runyon 2019).

Plague (Yersinia pestis) infection (alternative agent): Note: Consult public health officials for event-specific recommendations:

Postexposure prophylaxis: Oral: 500 mg twice daily for 7 days (CDC 2015a).

Treatment: Note: Duration of therapy is 10 to 14 days (CDC 2015a).

Oral: 500 to 750 mg every 12 hours (CDC 2015a).

IV: 400 mg every 8 to 12 hours (CDC 2015a).

Pneumonia, community acquired, as a component of empiric therapy for P. aeruginosa coverage (hospitalized patient) (off-label use): Note: For empiric therapy, must be used in combination with other appropriate agents.

Oral: 750 mg every 12 hours (File 2019; IDSA/ATS [Mandell 2007]).

IV: 400 mg every 8 hours (File 2019; IDSA/ATS [Mandell 2007]).

Duration of therapy: Minimum of 5 days and varies based on disease severity and response to therapy; patients should be afebrile for ≥48 hours and clinically stable prior to discontinuation (File 2019; IDSA/ATS [Mandell 2007]).

Pneumonia, hospital acquired (nosocomial) (including ventilator associated), as a component of empiric therapy for P. aeruginosa coverage: Note: For empiric therapy, must be used in combination with other appropriate agents.

Oral: 750 mg every 12 hours (IDSA [Kalil 2016]; Klompas 2019).

IV: 400 mg every 8 hours (IDSA [Kalil 2016]; Klompas 2019).

Duration of therapy: 7 days; may be individualized based on patient-specific factors and response to therapy (IDSA [Kalil 2016]; Klompas 2019).

Prostatitis:

Acute bacterial prostatitis (off-label use):

Oral: 500 mg every 12 hours (Meyrier 2019a).

IV: 400 mg every 12 hours (Meyrier 2019a).

Duration of therapy: 4 to 6 weeks (Meyrier 2019a; Yoon 2013).

Chronic bacterial prostatitis: Oral: 500 mg every 12 hours for 4 to 6 weeks (Meyrier 2019b).

Prosthetic joint infection (off-label use): Note: Alternative agent for certain pathogens.

Treatment:

Gram-negative bacilli:

Oral: 750 mg twice daily (IDSA [Osmon 2013]).

IV: 400 mg every 12 hours (IDSA [Osmon 2013]); some experts prefer 400 mg every 8 hours for infections caused by P. aeruginosa (Berbari 2019).

Staphylococcus aureus, oral continuation therapy (following pathogen-specific IV therapy in patients undergoing 1-stage exchange or debridement with retention of prosthesis):

Oral: 500 to 750 mg twice daily (Berdal 2005; Zimmerli 1998) in combination with rifampin; total treatment duration is a minimum of 3 months, depending on patient-specific factors (Berbari 2019; IDSA [Osmon 2013]).

Chronic suppressive therapy for P. aeruginosa: Oral: 250 to 500 mg twice daily (IDSA [Osmon 2013]).

Salmonella species, GI infection:

Nontyphoidal, severe (nonbacteremic) illness or any severity in patients at high risk for invasive disease: Oral: 500 mg twice daily for 3 to 7 days. Note: Immunosuppressed patients require longer duration of treatment (eg, weeks to months) (Hohmann 2019; IDSA [Guerrant 2001]).

Typhoid fever (Salmonella typhi and paratyphi): Severe disease or mild to moderate infection in patients at high risk of developing invasive disease (Ryan 2019)

Oral: 500 mg every 12 hours for 7 to 10 days.

IV: 400 mg every 12 hours for 7 to 10 days.

Septic arthritis (without prosthetic material) (alternative agent): Note: Use in combination with an aminoglycoside for initial treatment if P. aeruginosa suspected (Goldenberg 2019).

Oral: 500 to 750 mg twice daily.

IV: 400 mg every 12 hours.

Duration of therapy: 3 to 4 weeks (in the absence of osteomyelitis), including oral step-down therapy (Goldenberg 2019).

Shigella GI infection (off-label dose): Oral: 500 mg twice daily or 750 mg once daily for 3 days; the duration should be extended to 5 to 7 days for those with Shigella dysenteriae type 1 infection or HIV coinfection (Agha 2019; IDSA [Guerrant 2001]).

Surgical (preoperative) prophylaxis (alternative agent) (off-label use): Note: Use in combination with other appropriate agents may be warranted (procedure-dependent). IV: 400 mg within 120 minutes prior to surgical incision (Bratzler 2013).

Surgical site infection (intestinal or GU tract, perineum, or axilla) (off-label use):

Oral: 750 mg every 12 hours, in combination with metronidazole (IDSA [Stevens 2014]).

IV: 400 mg every 12 hours, in combination with metronidazole (IDSA [Stevens 2014]).

Traveler's diarrhea, uncomplicated (empiric therapy) (off-label dose): Oral: 500 mg twice daily for 3 days or 750 mg as a single dose (ACG [Riddle 2016]; Riddle 2017). If symptoms not resolved after 24 hours following single-dose therapy, continue with 500 mg twice daily for 2 more days. The 3-day therapy course is recommended in patients with fever or dysentery; enteric infection due to S. dysenteriae is an exception as a 5-day treatment duration appears to be superior to single-dose or 3-day regimens (ACG [Riddle 2016]). Note: Fluoroquinolone resistance is increasing; azithromycin may be preferred, particularly in regions such as Southeast Asia or India with a high prevalence of Campylobacter (ACG [Riddle 2016]).

Tularemia (Francisella tularensis) (off-label use): Note: Consult public health officials for event-specific recommendations.

Mild disease: Oral: 500 or 750 mg twice daily for 10 to 14 days (Bossi 2004; Dennis 2001).

Postexposure prophylaxis: Oral: 500 or 750 mg twice daily for 14 days (Bossi 2004; Dennis 2001).

Urinary tract infection: Note: Uncomplicated urinary tract infection (UTI) has traditionally been defined as infection in an otherwise healthy nonpregnant female with a normal urinary tract; UTI in other patient populations has been considered complicated. Some experts instead categorize UTI as either acute simple cystitis (mild infection limited to the bladder with no signs/symptoms of upper tract or systemic infection in a nonpregnant adult) or complicated UTI (pyelonephritis or cystitis symptoms with other signs/symptoms of systemic infection) (Hooton 2019a; Hooton 2019b).

Acute uncomplicated or simple cystitis in females: Note: Use is discouraged due to safety concerns and significant Escherichia coli resistance; reserve for those who have no alternative treatment options (Bidell 2016; FDA Drug Safety Communication 2016; Hooton 2019a; IDSA [Gupta 2011]).

Oral, immediate release: 250 mg every 12 hours for 3 days.

Oral, extended release: 500 mg every 24 hours for 3 days.

Acute pyelonephritis or other complicated UTI: Note: If the prevalence of fluoroquinolone resistance is >10%, an initial dose of a long-acting parenteral antimicrobial, such as ceftriaxone, ertapenem, or a consolidated 24-hour dose of an aminoglycoside is recommended for outpatients (Hooton 2019b; IDSA [Gupta 2011]).

Oral, immediate release: 500 mg every 12 hours for 5 to 7 days.

Oral, extended release: 1,000 mg every 24 hours for 5 to 7 days.

IV (inpatient): 400 mg every 12 hours for a total of 5 to 7 days.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: 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 (Bradley 2011b). 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 (Red Book [AAP 2015]): 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 (AAP [Bradley 2014])

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 (Bradley 2014):

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 (HHS [adult] 2015): 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 (Warady [ISPD 2012])

Chancroid: Adolescents: Oral, immediate release: 500 mg twice daily for 3 days (Red Book [AAP 2015])

Cystic fibrosis: Limited data available: Children and Adolescents:

Oral, immediate release: 20 mg/kg/dose every 12 hours; maximum dose: 1,000 mg/dose (Stockmann 2012)

IV: 10 mg/kg/dose every 8 hours; maximum dose: 400 mg/dose (Stockmann 2012)

Endocarditis, culture negative, empiric therapy: AHA guidelines (Baltimore 2015): 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

Infectious diarrhea: Limited data available:

Cholera: Infants, Children, and Adolescents: Oral, immediate release: 15 mg/kg/dose twice daily for 3 days; maximum dose: 500 mg/dose (Red Book [AAP 2015]; WHO 2012). Alternately, 20 mg/kg/dose as a single dose has been used (Red Book [AAP 2015]).

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 (WHO 2005)

HIV-exposed-infected (HHS [adult] 2015): 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 (IDSA [Solomkin 2010])

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 (Red Book [AAP 2015])

Mycobacterium avium Complex, severe or disseminated disease, HIV-exposed/-infected (HHS [pediatric] 2013): 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:

Manufacturer's labeling: Infants, Children, and Adolescents:

Oral, immediate release: 15 mg/kg/dose every 8 to 12 hours for 10 to 21 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 (CDC [plague] 2015): Children and Adolescents:

Treatment:

Initial treatment: IV: 15 mg/kg/dose every 12 hours; maximum dose: 400 mg/dose; continue until 2 days after fever subsides, then may change to oral therapy

Oral step-down to complete a 10 to 14 day course: Oral, immediate release: 20 mg/kg/dose twice daily; maximum dose: 500 mg/dose

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

Pneumonia, community acquired (Haemophilus influenza): Infants >3 months and Children: IV: 15 mg/kg/dose every 12 hours (IDSA/PIDS [Bradley 2011a])

Salmonellosis, HIV-exposed/-infected (HHS [adult] 2015): 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 (ASHP [Bratzler 2013])

Tularemia, mild disease: Limited data available: 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 (Dennis 2001; WHO 2007)

Prophylaxis, mass casualty situation: Oral, immediate release: 15 mg/kg/dose twice daily for 14 days; maximum dose: 500 mg/dose (Dennis 2001)

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

Reconstitution

Injection, vial: May be diluted with NS, D5W, SWFI, D10W, D5¹/₄NS, D5¹/₂NS, LR to a final concentration not to exceed 2 mg/mL.

Extemporaneously Prepared

A 50 mg/mL oral suspension may be made using 2 different vehicles (a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of Methylcellulose 1% and Simple Syrup, NF). Crush twenty 500 mg tablets and reduce to a fine powder. Add a small amount of vehicle and mix to a uniform paste; mix while adding the vehicle in geometric proportions to almost 200 mL; transfer to a calibrated bottle, rinse mortar with vehicle, and add quantity of vehicle sufficient to make 200 mL. Label "shake well" and "refrigerate". Stable 91 days refrigerated and 70 days at room temperature. Note: Microcapsules for oral suspension available (50 mg/mL; 100 mg/mL); not for use in feeding tubes.

Nahata MC, Pai VB, and Hipple TF, Pediatric Drug Formulations, 5th ed, Cincinnati, OH: Harvey Whitney Books Co, 2004.

Administration

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 (Beckwith 2004; Healy 1996). 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 (Beckwith 2004).

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

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

Dietary Considerations

Food: May be taken with meals that contain dairy products (eg, milk, yogurt) or calcium-fortified juices, but not with these products alone; separate administration of Cipro XR and calcium >800 mg by at least 2 hours.

Caffeine: Patients consuming regular large quantities of caffeinated beverages may need to restrict caffeine intake if excessive cardiac or CNS stimulation occurs.

Storage

Injection:

Premixed infusion: Store between 5°C to 25°C (41°F to 77°F); avoid freezing. Protect from light.

Vial: Store between 5°C to 30°C (41°F to 86°F); avoid freezing. Protect from light. Diluted solutions of 0.5 to 2 mg/mL in D5¹/₄NS, D5¹/₂NS, D5W, D10W, LR, NS are stable for up to 14 days refrigerated or at room temperature.

Microcapsules for oral suspension: Prior to reconstitution, store below 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from freezing. Following reconstitution, store at 25°C (77°F) for 14 days; excursions permitted to 15°C to 30°C (59°F to 86°F) for up to 14 days. Protect from freezing.

Tablet:

Immediate release: Store between 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Extended release: Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

Drug Interactions

Agomelatine: Ciprofloxacin (Systemic) may increase the serum concentration of Agomelatine. Avoid combination

Alosetron: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Alosetron. Management: Avoid concomitant use of alosetron and moderate CYP1A2 inhibitors whenever possible. If combined use is necessary, monitor for increased alosetron effects/toxicities. Consider therapy modification

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Monitor therapy

Amphetamines: May enhance the cardiotoxic effect of Quinolones. Monitor therapy

Antacids: May decrease the absorption of Quinolones. Of concern only with oral administration of quinolones. Management: Avoid concurrent administration of quinolones and antacids to minimize the impact of this interaction. Recommendations for optimal dose separation vary by specific quinolone. Exceptions: Sodium Bicarbonate. Consider therapy modification

ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy

Asenapine: Ciprofloxacin (Systemic) may increase the serum concentration of Asenapine. Monitor therapy

Ataluren: May increase the serum concentration of Ciprofloxacin (Systemic). Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Bendamustine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Bendamustine. Management: Consider alternatives to moderate CYP1A2 inhibitors during therapy with bendamustine due to the potential for increased bendamustine plasma concentrations and increased bendamustine toxicity. Consider therapy modification

Blood Glucose Lowering Agents: Quinolones may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Bromazepam: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Bromazepam. Monitor therapy

Caffeine and Caffeine Containing Products: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Caffeine and Caffeine Containing Products. Monitor therapy

Calcium Salts: May decrease the absorption of Quinolones. Of concern only with oral administration of both agents. Exceptions: Calcium Chloride. Consider therapy modification

CarBAMazepine: Ciprofloxacin (Systemic) may increase the serum concentration of CarBAMazepine. Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination

ClomiPRAMINE: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ClomiPRAMINE. Monitor therapy

CloZAPine: Ciprofloxacin (Systemic) may enhance the QTc-prolonging effect of CloZAPine. Ciprofloxacin (Systemic) may increase the serum concentration of CloZAPine. Management: Reduce the clozapine dose to one-third of the original dose when adding ciprofloxacin and monitor closely for evidence of excessive QTc prolongation and clozapine toxicity. Resume the previous clozapine dose following ciprofloxacin discontinuation. Consider therapy modification

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Quinolones. Specifically, the risk of tendonitis and tendon rupture may be increased. Monitor therapy

Delamanid: Quinolones may enhance the QTc-prolonging effect of Delamanid. Management: Avoid concomitant use if possible. If coadministration is unavoidable, frequent monitoring of electrocardiograms (ECGs) throughout the full delamanid treatment period should occur. Exceptions are discussed in separate monographs. Consider therapy modification

Didanosine: Quinolones may decrease the serum concentration of Didanosine. Didanosine may decrease the serum concentration of Quinolones. Management: Administer oral quinolones at least 2 hours before or 6 hours after didanosine. Monitor for decreased therapeutic effects of quinolones, particularly if doses cannot be separated as recommended. This does not apply to unbuffered enteric coated didanosine. Consider therapy modification

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy

DULoxetine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of DULoxetine. Monitor therapy

Erlotinib: Ciprofloxacin (Systemic) may increase the serum concentration of Erlotinib. Management: Avoid use of this combination when possible. When the combination must be used, monitor the patient closely for the development of severe adverse reactions, and if such severe reactions occur, reduce the erlotinib dose (in 50 mg decrements). Consider therapy modification

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy

Fosphenytoin: May enhance the QTc-prolonging effect of Ciprofloxacin (Systemic). Ciprofloxacin (Systemic) may diminish the therapeutic effect of Fosphenytoin. Ciprofloxacin (Systemic) may decrease the serum concentration of Fosphenytoin. Monitor therapy

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

Heroin: Quinolones may enhance the adverse/toxic effect of Heroin. Monitor therapy

Iron Preparations: May decrease the serum concentration of Quinolones. Management: Give oral quinolones at least several hours before (4 h for moxi- and sparfloxacin, 2 h for others) or after (8 h for moxi-, 6 h for cipro/dela-, 4 h for lome-, 3 h for gemi-, and 2 h for levo-, nor-, oflox-, pefloxacin, or nalidixic acid) oral iron. Exceptions: Ferric Carboxymaltose; Ferric Derisomaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Sucrose. Consider therapy modification

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Lanthanum: May decrease the serum concentration of Quinolones. Management: Administer oral quinolone antibiotics at least one hour before or four hours after lanthanum. Consider therapy modification

Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Consider therapy modification

Lomitapide: Ciprofloxacin (Systemic) may increase the serum concentration of Lomitapide. Avoid combination

Lumateperone: Ciprofloxacin (Systemic) may increase the serum concentration of Lumateperone. Monitor therapy

Magnesium Salts: May decrease the serum concentration of Quinolones. Management: Administer oral quinolones several hours before (4 h for moxi/pe/spar-, 2 h for others) or after (8 h for moxi-, 6 h for cipro/dela-, 4 h for lome/pe-, 3 h for gemi-, and 2 h for levo-, nor-, or ofloxacin or nalidixic acid) oral magnesium salts. Consider therapy modification

Melatonin: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Melatonin. Monitor therapy

Meptazinol: May decrease the serum concentration of Ciprofloxacin (Systemic). Avoid combination

Methotrexate: Ciprofloxacin (Systemic) may increase the serum concentration of Methotrexate. Monitor therapy

Methylphenidate: May enhance the cardiotoxic effect of Quinolones. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May decrease the serum concentration of Quinolones. Specifically, polyvalent cations in multivitamin products may decrease the absorption of orally administered quinolone antibiotics. Management: Interactions can be minimized by administering the oral quinolone at least 2 hours before, or 6 hours after, the dose of a multivitamin that contains polyvalent cations (i.e., calcium, iron, magnesium, selenium, zinc). Consider therapy modification

Multivitamins/Minerals (with AE, No Iron): May decrease the serum concentration of Quinolones. Specifically, minerals in the multivitamin/mineral product may impair absorption of quinolone antibiotics. Management: Interactions can be minimized by administering the oral quinolone at least 2 hours before, or 6 hours after, the dose of a multivitamin that contains polyvalent cations (i.e., calcium, iron, magnesium, selenium, zinc). Consider therapy modification

Mycophenolate: Quinolones may decrease the serum concentration of Mycophenolate. Specifically, quinolones may decrease concentrations of the active metabolite of mycophenolate. Monitor therapy

Nadifloxacin: May enhance the adverse/toxic effect of Quinolones. Avoid combination

Neratinib: Ciprofloxacin (Systemic) may increase the serum concentration of Neratinib. Management: Avoid concomitant use of neratinib and ciprofloxacin if possible. If combined, monitor for increased neratinib effects/toxicities. Consider therapy modification

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy

Nitisinone: May increase the serum concentration of OAT1/3 Substrates. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the neuroexcitatory and/or seizure-potentiating effect of Quinolones. Nonsteroidal Anti-Inflammatory Agents may increase the serum concentration of Quinolones. Monitor therapy

OLANZapine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of OLANZapine. Monitor therapy

Olaparib: Ciprofloxacin (Systemic) may increase the serum concentration of Olaparib. Monitor therapy

Patiromer: May decrease the serum concentration of Ciprofloxacin (Systemic). Management: Administer oral ciprofloxacin at least 3 hours before or 3 hours after patiromer. Consider therapy modification

Pentoxifylline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pentoxifylline. Monitor therapy

Phenytoin: Ciprofloxacin (Systemic) may diminish the therapeutic effect of Phenytoin. Ciprofloxacin (Systemic) may decrease the serum concentration of Phenytoin. Monitor therapy

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination

Pirfenidone: Ciprofloxacin (Systemic) may increase the serum concentration of Pirfenidone. Management: With ciprofloxacin doses of 1,500 mg/day, the pirfenidone dose should be reduced to 1,602 mg per (534 mg three times a day). With lower daily doses of ciprofloxacin, use pirfenidone with caution. Consider therapy modification

Pomalidomide: Ciprofloxacin (Systemic) may increase the serum concentration of Pomalidomide. Management: Avoid concomitant use of pomalidomide and ciprofloxacin when possible. If coadministration is considered necessary, consider reducing the pomalidomide dose 50% and monitoring patients for increased pomalidomide effects/toxicities. Consider therapy modification

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Monitor therapy

Pretomanid: May increase the serum concentration of OAT1/3 Substrates. Monitor therapy

Probenecid: May decrease the excretion of Quinolones. Specifically, probenecid may decreased the renal excretion of quinolone antibiotics. Probenecid may increase the serum concentration of Quinolones. Monitor therapy

Propranolol: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Propranolol. Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Quinapril: May decrease the serum concentration of Quinolones. Management: Separate doses of quinapril and oral quinolones by at least 2 hours in order to reduce the risk of interaction. Monitor for reduced efficacy of the quinolone if these products are used concomitantly. Consider therapy modification

Ramelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramelteon. Monitor therapy

Ramosetron: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramosetron. Monitor therapy

Rasagiline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Rasagiline. Management: Limit rasagiline dose to 0.5 mg once daily in patients taking moderate CYP1A2 inhibitors. Consider therapy modification

Roflumilast: Ciprofloxacin (Systemic) may increase the serum concentration of Roflumilast. Monitor therapy

ROPINIRole: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ROPINIRole. Monitor therapy

Ropivacaine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ropivacaine. Monitor therapy

Sevelamer: May decrease the absorption of Quinolones. Management: Administer oral quinolones at least 2 hours before or 6 hours after sevelamer. Consider therapy modification

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Spironolactone: May enhance the arrhythmogenic effect of Ciprofloxacin (Systemic). Monitor therapy

Strontium Ranelate: May decrease the serum concentration of Quinolones. Management: In order to minimize any potential impact of strontium ranelate on quinolone antibiotic concentrations, it is recommended that strontium ranelate treatment be interrupted during quinolone therapy. Avoid combination

Sucralfate: May decrease the serum concentration of Quinolones. Management: Avoid concurrent administration of quinolones and sucralfate to minimize the impact of this interaction. Recommendations for optimal dose separation vary by specific quinolone. Consider therapy modification

Tasimelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Tasimelteon. Monitor therapy

Teriflunomide: May increase the serum concentration of OAT1/3 Substrates. Monitor therapy

Theophylline Derivatives: Quinolones may decrease the metabolism of Theophylline Derivatives. Ciprofloxacin and enoxacin are of greatest concern. Theophylline/quinolone therapy might augment the seizure-producing potential of each of the individual agents. Exceptions: Dyphylline. Consider therapy modification

Theophylline Derivatives: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Theophylline Derivatives. Management: Consider avoidance of this combination. If coadministration is necessary, monitor for increased theophylline serum concentrations and toxicities when combined. Theophylline dose reductions will likely be required. Exceptions: Dyphylline. Consider therapy modification

Thyroid Products: Ciprofloxacin (Systemic) may decrease the serum concentration of Thyroid Products. Monitor therapy

TiZANidine: Ciprofloxacin (Systemic) may increase the serum concentration of TiZANidine. Avoid combination

Tolvaptan: May increase the serum concentration of OAT1/3 Substrates. Management: Patients being treated with the Jynarque brand of tolvaptan should avoid concomitant use of OAT1/3 substrates. Concentrations and effects of the OAT1/3 substrate would be expected to increase with any combined use. Consider therapy modification

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant weak CYP3A4 inhibitors. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Consider therapy modification

Ubrogepant: Ciprofloxacin (Systemic) may increase the serum concentration of Ubrogepant. Management: Use an initial ubrogepant dose of 50 mg and consider avoiding a second dose for 24 hours when used with ciprofloxacin. Consider therapy modification

Varenicline: Quinolones may increase the serum concentration of Varenicline. Management: Monitor for increased varenicline adverse effects with concurrent use of levofloxacin or other quinolone antibiotics, particularly in patients with severe renal impairment. International product labeling recommendations vary. Consult appropriate labeling. Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Quinolones may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Zinc Salts: May decrease the serum concentration of Quinolones. Management: Give oral quinolones at least several hours before (4 h for moxi- and sparfloxacin, 2 h for others) or after (8 h for moxi-, 6 h for cipro/dela-, 4 h for lome-, 3 h for gemi-, and 2 h for levo-, nor-, pe- or ofloxacin or nalidixic acid) oral zinc salts. Exceptions: Zinc Chloride. Consider therapy modification

Zolpidem: Ciprofloxacin (Systemic) may increase the serum concentration of Zolpidem. Management: Consider avoiding the combination of ciprofloxacin and zolpidem if possible. If combined, monitor for signs of zolpidem toxicity (eg, somnolence, dizziness, lethargy). Consider therapy modification

Test Interactions

Some quinolones may produce a false-positive urine screening result for opioids using commercially-available immunoassay kits. This has been demonstrated most consistently for levofloxacin and ofloxacin, but other quinolones have shown cross-reactivity in certain assay kits. Confirmation of positive opioid screens by more specific methods should be considered.

Adverse Reactions

>10%: Neuromuscular & skeletal: Musculoskeletal signs and symptoms (children: 9% to 22%)

1% to 10%:

Central nervous system: Dizziness (oral: 2%; IV: <1%), neurological signs and symptoms (IV: children: 3%), headache (oral: 1% to 3%; IV: >1%), restlessness (IV: >1%; oral: <1%), insomnia, nervousness, somnolence

Dermatologic: Skin rash (1% to 2%)

Gastrointestinal: Diarrhea (2% to 5%), vomiting (1% to 5%), nausea (3% to 4%), abdominal pain (children: 3%; adults: <1%), dyspepsia (1% to 3%)

Genitourinary: Vulvovaginal candidiasis (2%)

Hepatic: Abnormal hepatic function tests (1%), increased serum aspartate aminotransferase (1%), increased serum alanine aminotransferase

Local: Injection site reactions (IV: >1%)

Respiratory: Asthma (children: 2%)

Miscellaneous: Fever (children: 2%; adults: <1%)

<1%: Abdominal distress, abnormal dreams, abnormal gait, acute myocardial infarction, acute renal failure, agranulocytosis, albuminuria, anaphylactic shock, anaphylaxis, angina pectoris, angioedema, anorexia, anosmia, arthralgia, asthenia, ataxia, blurred vision, bradycardia, bronchospasm, burning sensation, casts in urine, cholestatic jaundice, chromatopsia, Clostridioides difficile colitis, confusion, constipation, crystalluria, decreased prothrombin time, decreased visual acuity, depersonalization, depression, dermatologic disorders, diaphoresis, diplopia, drowsiness, dysgeusia, dysmenorrhea, dyspnea, erythema multiforme, erythema nodosum, exfoliative dermatitis, flatulence, flushing, gastrointestinal hemorrhage, gynecomastia, hallucination, hearing loss, hematuria, hemoptysis, hemorrhagic cystitis, hepatic necrosis, hepatitis, hyperglycemia, hypersensitivity reaction, hypertension, hypertonia, hypoglycemia, hypotension, increased thirst, interstitial nephritis, intestinal obstruction, intestinal perforation, irritability, joint stiffness, laryngeal edema, maculopapular rash, malaise, manic reaction, migraine, myasthenia, nephrolithiasis, nightmares, nystagmus disorder, oral mucosa ulcer, pain, pancreatitis, paranoid ideation, paresthesia, petechia, phobia, photopsia, phototoxicity, prolonged prothrombin time, pruritus, purpuric disease, renal insufficiency, seizure, skin photosensitivity, status epilepticus, Stevens-Johnson syndrome, suicidal ideation, suicidal tendencies, syncope, tachycardia, taste disorder, thrombophlebitis, tinnitus, toxic epidermal necrolysis, toxic psychosis, tremor, unresponsive to stimuli, urinary frequency, urticaria, vaginitis, vasculitis, vasodilation, vertigo, vesicobullous dermatitis, visual disturbance, xeroderma, xerostomia

Postmarketing: Acute generalized exanthematous pustulosis, ageusia, agitation, anemia, anxiety, bleeding tendency disorder, candidiasis, Clostridioides difficile associated diarrhea, decreased serum albumin, decreased serum potassium, decreased serum total protein, delirium, disturbance in attention, eosinophilia, exacerbation of myasthenia gravis, fixed drug eruption, hemolytic anemia, hepatic failure, hepatotoxicity, hyperesthesia, hypoesthesia, hypouricemia, idiopathic intracranial hypertension, increased blood urea nitrogen, increased creatine phosphokinase in blood specimen, increased erythrocyte sedimentation rate, increased gamma-glutamyl transferase, increased intracranial pressure, increased lactate dehydrogenase, increased serum alkaline phosphatase, increased serum amylase, increased serum bilirubin, increased serum calcium, increased serum cholesterol, increased serum creatinine, increased serum potassium, increased serum triglycerides, increased uric acid, jaundice, leukocytosis, leukopenia, lymphocytosis, memory impairment, methemoglobinemia, monocytosis, myalgia, myoclonus, pancytopenia, peripheral neuropathy, pneumonitis, polyneuropathy, prolonged QT interval on ECG, rupture of tendon, serum sickness-like reaction, tendonitis, thrombocythemia, thrombocytopenia, torsades de pointes, twitching, ventricular arrhythmia

Warnings/Precautions

Concerns related to adverse effects:

• Altered cardiac conduction: Fluoroquinolones may prolong QT_c interval; avoid use in patients with a history of or at risk for QT_c prolongation, torsades de pointes, uncorrected electrolyte disorders (hypokalemia or hypomagnesemia), cardiac disease (heart failure, myocardial infarction, bradycardia) or concurrent administration of other medications known to prolong the QT interval (including Class Ia and Class III antiarrhythmics, cisapride, erythromycin, antipsychotics, and tricyclic antidepressants).
• Aortic aneurysm and dissection: Fluoroquinolones have been associated with aortic aneurysm ruptures or dissection within 2 months following use, particularly in elderly patients. Fluoroquinolones should not be used in patients with a known history of aortic aneurysm or those at increased risk, including patients with peripheral atherosclerotic vascular diseases, hypertension, genetic disorders involving blood vessel changes (eg, Marfan syndrome, Ehlers-Danlos syndrome), and elderly patients, unless no other treatment options are available. Longer treatment duration (eg, >14 days) may increase risk (Lee 2018).
• Crystalluria: Rarely, crystalluria has occurred; urine alkalinity may increase the risk. Ensure adequate hydration during therapy.
• Glucose regulation: Fluoroquinolones have been associated with disturbances in glucose regulation, including hyperglycemia and hypoglycemia. These events have occurred most often in patients receiving concomitant oral hypoglycemic agents or insulin. Severe cases of hypoglycemia, including coma and death, have been reported. Diabetic patients should be monitored closely for signs/symptoms of disordered glucose regulation. Discontinue if a hypoglycemic reaction occurs and immediately initiate appropriate therapy.
• Hepatotoxicity: Hepatocellular, cholestatic, or mixed liver injury has been reported, including hepatic necrosis, life-threatening hepatic events, and fatalities. Acute liver injury can be rapid onset (range: 1 to 39 days) and is often associated with hypersensitivity. The pattern of injury can be hepatocellular, cholestatic, or mixed. Most fatalities occurred in patients >55 years of age. Discontinue immediately if signs/symptoms of hepatitis (abdominal tenderness, dark urine, jaundice, pruritus) occur. Additionally, temporary increases in transaminases or alkaline phosphatase, or cholestatic jaundice may occur (highest risk in patients with previous liver damage).
• Hypersensitivity reactions: Severe hypersensitivity reactions, including anaphylaxis, have occurred with fluoroquinolone therapy. The spectrum of these reactions can vary widely; reactions may present as typical allergic symptoms (eg, itching, urticaria, rash, edema) after a single dose, or may manifest as severe idiosyncratic dermatologic (eg, Stevens-Johnson, toxic epidermal necrolysis), vascular (eg, vasculitis), pulmonary (eg, pneumonitis), renal (eg, nephritis), hepatic (eg, hepatitis, jaundice, hepatic failure or necrosis), and/or hematologic (eg, anemia, cytopenias) events, usually after multiple doses. Prompt discontinuation of drug should occur if skin rash or other symptoms arise.
• Photosensitivity/phototoxicity: Avoid excessive sunlight and take precautions to limit exposure (eg, loose fitting clothing, sunscreen); may cause moderate-to-severe phototoxicity reactions which may appear as exaggerated sunburn reactions. Discontinue use if phototoxicity occurs.
• Serious adverse reactions: [US Boxed Warning]: Fluoroquinolones are associated with disabling and potentially irreversible serious adverse reactions that may occur together, including tendinitis and tendon rupture, peripheral neuropathy, and CNS effects. Discontinue ciprofloxacin immediately and avoid use of fluoroquinolones in patients who experience any of these serious adverse reactions. Patients of any age or without preexisting risk factors have experienced these reactions; may occur within hours to weeks after initiation.

- CNS effects: Fluoroquinolones have been associated with an increased risk of CNS effects, including seizures, increased intracranial pressure (including pseudotumor cerebri), dizziness, and tremors. Status epilepticus cases have been reported. Use with caution in patients with a history of seizures, with known or suspected CNS disorder (severe cerebral arteriosclerosis, previous history of convulsion, reduced cerebral blood flow, altered brain structure, or stroke), or with other risk factors that may predispose to seizures or lower the seizure threshold (eg, certain drug therapy, renal dysfunction). Discontinue if seizures occur and institute appropriate therapy.

- Peripheral neuropathy: Fluoroquinolones have been associated with an increased risk of peripheral neuropathy; may occur soon after initiation of therapy and may be irreversible; discontinue immediately if symptoms of sensory or sensorimotor neuropathy occur. Avoid use in patients who have previously experienced peripheral neuropathy.

- Psychiatric reactions: Fluoroquinolones have been associated with an increased risk of psychiatric reactions, including toxic psychosis, hallucinations, or paranoia; may also cause nervousness, agitation, delirium, attention disturbances, insomnia, anxiety, nightmares, memory impairment, confusion, depression, and suicidal thoughts or actions. Use with caution in patients with a history of or risk factor for mental illness. Reactions may appear following the first dose; discontinue if reaction occurs and institute appropriate therapy.

- Tendinitis/tendon rupture: Fluoroquinolones have been associated with an increased risk of tendonitis and tendon rupture in all ages; risk may be increased with concurrent corticosteroids, solid organ transplant recipients, and in patients >60 years of age, but has also occurred in patients without these risk factors. Rupture of the Achilles tendon has been reported most frequently; but other tendon sites (eg, rotator cuff, biceps, hand) have also been reported. Inflammation and rupture may occur bilaterally. Cases have been reported within hours or days of initiation, and up to several months after discontinuation of therapy. Strenuous physical activity, renal failure, and previous tendon disorders may be independent risk factor for tendon rupture. Discontinue at first sign of tendon pain, swelling, inflammation or rupture. Avoid use in patients with a history of tendon disorders or who have experienced tendinitis or tendon rupture.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Myasthenia gravis: [US Boxed Warning]: May exacerbate muscle weakness related to myasthenia gravis; avoid use in patients with a known history of myasthenia gravis. Cases of severe exacerbations, including the need for ventilatory support and deaths have been reported.
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required. May increase risk of tendon rupture.
• Rheumatoid arthritis: Use with caution in patients with rheumatoid arthritis; may increase risk of tendon rupture.
• 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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

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

Other warnings/precautions:

• Appropriate use: [US Boxed Warning]: Reserve use of ciprofloxacin for treatment of acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, or acute uncomplicated cystitis for patients who have no alternative treatment options because of the risk of disabling and potentially serious adverse reactions (eg, tendinitis and tendon rupture, peripheral neuropathy, CNS effects).

Monitoring Parameters

CBC, renal and hepatic function during prolonged therapy, altered mental status, signs and symptoms of tendonitis; signs and symptoms of disordered glucose regulation

Pregnancy

Pregnancy Risk Factor

C

Pregnancy Considerations

Ciprofloxacin crosses the placenta and produces measurable concentrations in the amniotic fluid and cord serum (Ludlam 1997). Based on available data, an increased risk of teratogenic effects has not been observed following ciprofloxacin use during pregnancy (Bar-Oz 2009; Padberg 2014). Ciprofloxacin is recommended for prophylaxis and treatment of pregnant women exposed to anthrax (Meaney-Delman 2014). Serum concentrations of ciprofloxacin may be lower during pregnancy than in nonpregnant patients (Giamarellou 1989).

Patient Education

What is this drug used for?

• It is used to treat or prevent bacterial infections.

Frequently reported side effects of this drug

• Diarrhea
• Vomiting
• Nausea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Tendon inflammation or rupture like pain, bruising, or swelling in the back of the ankle, shoulder, hand, or other joints
• Depression like thoughts of suicide, anxiety, emotional instability, agitation, irritability, panic attacks, mood changes, behavioral changes, or confusion
• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain
• Nerve problems like sensitivity to heat or cold; decreased sense of touch; burning, numbness, or tingling; pain, or weakness in the arms, hands, legs, or feet
• Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating
• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit
• Fast heartbeat
• Abnormal heartbeat
• Passing out
• Chest pain
• Thrush
• Severe loss of strength and energy
• Vision changes
• Sensing things that seem real but are not
• Seizures
• Severe headache
• Trouble sleeping
• Nightmares
• Dizziness
• Restlessness
• Shortness of breath
• Bruising
• Bleeding
• Tremors
• Abnormal gait
• Sunburn
• Chills
• Sore throat
• Vaginal pain, itching, and discharge
• Muscle pain
• Muscle weakness
• Difficulty focusing
• Trouble with memory
• Injection site irritation
• Severe or persistent pain in abdomen
• Severe or persistent chest pain
• Severe or persistent back pain
• Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools
• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.