Skip to Content

Ciprofloxacin (Systemic)

Pronunciation

(sip roe FLOKS a sin)

Index Terms

  • Ciprofloxacin HCl
  • Ciprofloxacin Hydrochloride
  • Proquin XR

Dosage Forms

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

Solution, Intravenous:

Cipro in D5W: 200 mg/100 mL (100 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])

Solution, Intravenous [preservative free]:

Cipro in D5W: 200 mg/100 mL (100 mL [DSC]); 400 mg/200 mL (200 mL) [latex free]

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

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); 500 mg/5 mL (100 mL)

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, 1000 mg

Generic: 500 mg, 1000 mg

Brand Names: U.S.

  • Cipro
  • Cipro in D5W
  • Cipro XR

Pharmacologic Category

  • Antibiotic, Fluoroquinolone

Pharmacology

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

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

Vd: 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 (30% to 50% as unchanged drug); feces (15% to 43%; <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: 3 to 5 hours

Protein Binding

20% to 40%

Special Populations: Renal Function Impairment

The half-life is prolonged.

Special Populations: Elderly

Cmax 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.

Off Label Uses

Anthrax

Based on the Centers for Disease Control and Prevention (CDC) expert panel meetings on prevention and treatment of anthrax in adults and recommendations from the American Academy of Pediatrics (AAP) for pediatric anthrax clinical management, ciprofloxacin is an effective and recommended agent for treatment of cutaneous or systemic anthrax.

Bite wound infection (animal and human bites)

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), 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 (non-disseminated)

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 2017].

Chancroid

Based on the Centers for Disease Control and Prevention (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)

Based on the 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].

Diabetic foot infections

Based on the Infectious Diseases Society of America (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 infections.

Endocarditis, treatment (adults)

Based on the American Heart Association (AHA) Scientific Statement for 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.

Endocarditis, treatment (children/adolescents)

Based on the AHA Scientific Statement for Infective Endocarditis in Childhood, ciprofloxacin, in combination with other antibiotics, is an effective and recommended treatment option for empiric therapy of culture-negative endocarditis.

Granuloma inguinale (Donovanosis)

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.

Hematopoietic cell transplant antibacterial prophylaxis

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 or more.

Meningitis, bacterial

Based on the Infectious Diseases Society of America (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 for 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)

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

Mycobacterium avium complex (MAC), severe or disseminated disease, HIV-exposed/-infected (children)

Based on the US Department of Health and Human Services (HHS) Guidelines for Prevention and Treatment of Opportunistic Infections among HIV-Exposed and HIV-Infected Children, ciprofloxacin is an effective and recommended alternative adjunct for the treatment of severe or disseminated MAC in pediatric HIV-exposed/-infected patients.

Neutropenia (chemotherapy-induced), antibacterial prophylaxis

Based on The Infectious Disease Society of America (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).

Neutropenic fever, low-risk cancer patients (empiric)

Data from 2 randomized, double-blind trials support the use of oral ciprofloxacin (in combination with amoxicillin and clavulanate) for the outpatient empiric management of low-risk neutropenic fever [Kern 1999]. The American Society of Clinical Oncology (ASCO) and Infectious Disease Society of America (IDSA) guidelines for treatment of patients with fever and neutropenia 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 infections

Based on the International Society for Peritoneal Dialysis (ISPD) 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)

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-acquired

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 bacterial

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 infection

Based on the Infectious Diseases Society of America (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 the chronic 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 prophylaxis

Based on the American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (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 infection

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTI), 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).

Tularemia (adults)

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

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

Cutaneous (without systemic involvement), empiric therapy (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 (Hendricks 2014). Note: Patients with cutaneous lesions of the head or neck or extensive edema should be treated for systemic involvement.

Systemic (meningitis excluded) (off-label use): IV: 400 mg every 8 hours in combination with other appropriate agents for 2 weeks until clinically stable (Hendricks 2014)

Meningitis (off-label use): IV: 400 mg every 8 hours in combination with other appropriate agents for 2 to 3 weeks until clinically stable (Hendricks 2014)

Note: 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.

Bite wound infection, prophylaxis or treatment (animal and human bites; alternative agent) (off-label use) (IDSA [Stevens 2014]): 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; duration of treatment for established infection varies based on patient-specific factors

Cat scratch disease, lymphadenitis (non-disseminated; alternative agent) (off-label use): Oral: 500 mg twice daily (Holley 1991). Additional data may be necessary to further define the role of ciprofloxacin in this condition.

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

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

Diabetic foot infections (off-label use) (IDSA [Lipsky 2012]; Weintrob 2017): Note: When used as empiric therapy, must be used in combination with other appropriate agents.

Mild to moderate: Oral: 750 mg every 12 hours

Moderate to severe: IV: 400 mg every 8 to 12 hours

Endocarditis due to HACEK organisms (alternative agent) (off-label use) (AHA [Baddour 2015]):

Oral: 500 mg every 12 hours for 4 weeks (native valve) or 6 weeks (prosthetic valve)

IV: 400 mg every 12 hours for 4 weeks (native valve) or 6 weeks (prosthetic valve)

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

Hematopoietic cell transplant (HCT) antibacterial prophylaxis (off-label use): Oral: 500 mg twice daily; begin at the time of stem cell infusion and continue until recovery of neutropenia or until initiation of empiric antibiotic therapy for febrile neutropenia (Tomblyn 2009)

Intra-abdominal infections (including perforated appendix, appendiceal abscess, acute diverticulitis, acute cholecystitis), community-acquired: Note: For empiric therapy, use in combination with metronidazole.

Oral: 500 mg every 12 hours

IV: 400 mg every 12 hours

Duration of therapy: Duration depends on whether source of infection has been controlled. Guidelines recommend treatment duration of 4 to 7 days (provided source controlled) (IDSA [Solomkin 2010])

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, 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 mg twice daily (IDSA [Freifeld 2011]; Wingard 2017); some clinicians will provide antibacterial prophylaxis if ANC is anticipated to be <500 cells/mm3 for >7 days (Wingard 2017)

Neutropenic fever, low-risk cancer patients (empiric) (off-label use): Oral: 750 mg every 12 hours until afebrile and neutropenia has resolved; use in combination with amoxicillin and clavulanate. Note: Avoid in patients who have received fluoroquinolone prophylaxis (ASCO [Flowers 2013]; IDSA [Freifeld 2011]; Kern 1999)

Osteomyelitis:

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

Oral:

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

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

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) (Runyon 2017):

Oral: 500 mg every 12 hours for total duration of 7 days (oral and IV)

IV (alternative for nonfunctional GI tract): 400 mg every 12 hours for total duration of 7 days (oral and IV)

Long-term secondary SBP prophylaxis: Oral: 500 mg once daily

Plague (Yersinia pestis) infection (alternative agent) (CDC [plague] 2015): Note: Consult public health officials for event-specific recommendations:

Postexposure prophylaxis: Oral: 500 mg twice daily for 7 days

Treatment: Note: Duration of therapy is 10 to 14 days

Oral: 500 to 750 mg every 12 hours

IV: 400 mg every 8 to 12 hours

Pneumonia, community-acquired, as a component of empiric therapy for P. aeruginosa coverage (hospitalized patient) (off-label use) (File 2017a; IDSA/ATS [Mandell 2007]): Note: For empiric therapy, must be used in combination with other appropriate agents.

IV: 400 mg every 8 hours for 5 to 7 days

Oral: 750 mg every 12 hours for 5 to 7 days

Pneumonia, hospital-acquired (nosocomial) including ventilator-associated, as a component of empiric therapy for P. aeruginosa coverage (File 2017b; IDSA [Kalil 2016]): Note: For empiric therapy, must be used in combination with other appropriate agents.

IV: 400 mg every 8 hours for 7 days

Oral: 750 mg every 12 hours for 7 days

Prostatitis (acute, bacterial) (off-label use): Note: When used for empiric therapy, must be used in combination with other appropriate agents.

Oral: 500 mg every 12 hours (Meyrier 2017a)

IV: 400 mg every 12 hours (Meyrier 2017a)

Duration of therapy: 6 weeks (Meyrier 2017a; Yoon 2013)

Prostatitis (chronic, bacterial) (Meyrier 2017b):

Oral: 500 mg every 12 hours for ≥6 weeks

IV: 400 mg every 12 hours for ≥6 weeks

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

Treatment:

Gram-negative bacilli (IDSA [Osmon 2013]):

Oral: 750 mg twice daily

IV: 400 mg every 12 hours

Staphylococci: Oral: 750 mg twice daily (Zimmerli 1998). Note: For use in combination with rifampin, following pathogen-specific IV therapy in patients undergoing 1-stage exchanges or debridement with retention of prosthesis (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 (non-bacteremic) 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 2017; 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 2017)

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 2017).

Oral: 500 to 750 mg twice daily

IV: 400 mg every 12 hours

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 S. dysenteriae type 1 infection or HIV coinfection (Agha 2017; 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) (IDSA [Stevens 2014]):

Oral: 750 mg every 12 hours, in combination with metronidazole

IV: 400 mg every 12 hours, in combination with metronidazole

Traveler’s diarrhea, uncomplicated (empiric therapy) (off-label dose): Oral: 500 mg twice daily for 1 to 3 days or 750 mg as a single dose (ACG [Riddle 2016]); IDSA [Hill 2006]). If symptoms not resolved after 24 hours following single-dose therapy, continue with a 3-day therapy course. The 3-day therapy course is recommended in patients with fever or dysentery; enteric infection due to Shigella dysenteriae is an exception and a 5-day treatment duration is 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 or postexposure prophylaxis: Oral: 500 or 750 mg twice daily (Bossi [tularemia] 2004; Dennis 2001).

Urinary tract infection:

Cystitis, acute uncomplicated: Note: Use for uncomplicated urinary tract infections is discouraged due to significant E. coli resistance and safety issues; reserve for clinical situations where other appropriate treatment options cannot be used (Bidell 2016; 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

Cystitis, acute complicated (Hooton 2017):

Oral, immediate release: 250 mg every 12 hours for 5 to 7 days

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

Pyelonephritis, uncomplicated (outpatient): Oral: 500 mg every 12 hours for 7days (IDSA [Gupta 2010])

Pyelonephritis, complicated (inpatient): IV: 400 mg every 12 hours for a total of 7 to 14 days (Hooton 2017)

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).

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

Usual dosage range (Red Book [AAP 2015]): Infants, Children, and Adolescents:

Mild to moderate infections: Oral: 10 mg/kg/dose twice daily (maximum dose: 500 mg/dose)

Severe infections:

Oral: 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: Note: Consult public health officials for event-specific recommendations:

Inhalational exposure (postexposure prophylaxis):

Oral: 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; do not exceed 400 mg/dose (800 mg/day)

Cutaneous, treatment (without systemic involvement) (off-label use) (AAP [Bradley 2014]): Oral: 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.

Systemic, treatment (including meningitis) (off-label use) (AAP [Bradley 2014]): IV: Initial: 10 mg/kg/dose every 8 hours (maximum dose: 400 mg/dose) as part of combination therapy; continue until clinical criteria for stability are met, then may switch to oral therapy (15 mg/kg/dose orally twice daily) to complete a 60-day course

Chancroid (off-label use): Adolescents: Oral: 500 mg twice daily for 3 days (Red Book [AAP 2015])

Endocarditis, culture negative, empiric therapy (off-label use): Note: Administer in combination with other antibiotics: Children and Adolescents (AHA [Baltimore 2015]):

Oral: 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

Intra-abdominal infection, complicated (off-label use): 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 (off-label use): Infants, Children, and Adolescents: Oral: 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 (off-label use): Infants and Children: Oral: 10 to 15 mg/kg/dose twice daily in addition to other antibiotics; maximum dose: 750 mg/dose (HHS [pediatric] 2013)

Peritoneal dialysis catheter, exit site or tunnel infection (off-label use): Infants, Children, and Adolescents: 10 to15 mg/kg/dose once daily (maximum dose: 500 mg/dose) (Warady [ISPD 2012])

Plague:

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

Oral: 15 mg/kg/dose every 8 to 12 hours for 10 to 21 days; maximum: 500 mg/dose

IV: 10 mg/kg/dose every 8 to 12 hours for 10 to 21 days; maximum: 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: 20 mg/kg/dose twice daily; maximum dose: 500 mg/dose.

Postexposure prophylaxis: Oral: 20 mg/kg/dose twice daily for 7 days; maximum dose: 500 mg/dose)

Pneumonia, community-acquired (H. influenzae) (off-label use): Infants >3 months and Children: IV: 15 mg/kg/dose every 12 hours (IDSA/PIDS [Bradley 2011a])

Surgical (preoperative) prophylaxis (off-label use): Children and Adolescents: IV: 10 mg/kg/dose within 120 minutes prior to surgical incision (maximum dose: 400 mg/dose) (Bratzler 2013)

Urinary tract infection:

Cystitis, acute uncomplicated: Adolescents ≥18 years: Oral, extended release: Refer to adult dosing

Complicated, including pyelonephritis:

Oral, immediate release: Children and Adolescents ≤17 years: 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: Refer to adult dosing

IV: 6 to 10 mg/kg/dose every 8 hours for 10 to 21 days (maximum dose: 400 mg/dose)

Dosing: Renal Impairment

Adults:

Manufacturer's labeling:

Oral, immediate release:

CrCl >50 mL/minute: No dosage adjustment necessary.

CrCl 30 to 50 mL/minute: 250 to 500 mg every 12 hours

CrCl 5 to 29 mL/minute: 250 to 500 mg every 18 hours

ESRD on intermittent hemodialysis (IHD)/peritoneal dialysis (PD) (administer after dialysis on dialysis days): 250 to 500 mg every 24 hours

Oral, extended release:

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: 500 mg every 24 hours

ESRD on intermittent hemodialysis (IHD)/peritoneal dialysis (PD) (administer after dialysis on dialysis days): 500 mg every 24 hours

IV:

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl 5 to 29 mL/minute: 200 to 400 mg every 18 to 24 hours

Alternate recommendations: Oral (immediate release), IV:

CrCl >50 mL/minute: No dosage adjustment necessary (Aronoff 2007).

CrCl 10 to 50 mL/minute: Administer 50% to 75% of usual dose every 12 hours (Aronoff 2007).

CrCl <10 mL/minute: Administer 50% of usual dose every 12 hours (Aronoff 2007).

Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis days): Minimally dialyzable (<10%): Oral: 250 to 500 mg every 24 hours or IV: 200 to 400 mg every 24 hours (Heintz 2009). Note: Dosing dependent on the assumption of 3 times weekly, complete IHD sessions.

Continuous renal replacement therapy (CRRT) (Heintz 2009; Trotman 2005): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment:

CVVH/CVVHD/CVVHDF: IV: 200 to 400 mg every 12 to 24 hours

Dosing: Hepatic Impairment

There are no dosage adjustments provided in manufacturer’s labeling. Use with caution in severe impairment.

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 food 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 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 which 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 approximately 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 water. Flush feeding tube before and after administration. Hold tube feedings at least 1 hour before and 2 hours after administration.

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: Drug may cause GI upset; take without regard to meals (manufacturer prefers that immediate release tablet is taken 2 hours after meals). 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 2 hours.

Oral multivitamins with zinc, magnesium/aluminum antacids, and mineral supplements: Absorption of ciprofloxacin is decreased by divalent and trivalent cations. Immediate release ciprofloxacin and Cipro XR may be taken 2 hours before or 6 hours after any of these products.

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. Avoid combination

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

Angiotensin II Receptor Blockers: May enhance the arrhythmogenic effect of Ciprofloxacin (Systemic). Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: May enhance the arrhythmogenic effect of Ciprofloxacin (Systemic). Monitor therapy

Antacids: May decrease the absorption of Quinolones. Of concern only with oral administration of quinolones. 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

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: Ciprofloxacin (Systemic) may increase the serum concentration of Bendamustine. Concentrations of the active metabolites of bendamustine may be decreased. Monitor therapy

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

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

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

CYP1A2 Substrates (High risk with Inhibitors): CYP1A2 Inhibitors (Moderate) may decrease the metabolism of CYP1A2 Substrates (High risk with Inhibitors). Monitor therapy

Delamanid: Quinolones may enhance the QTc-prolonging effect of Delamanid. Management: Avoid concomitant use of delamanid and quinolone antibiotics if possible. If coadministration is considered to be unavoidable, frequent monitoring of electrocardiograms (ECGs) throughout the full delamanid treatment period should occur. 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

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

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

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

Hydroxychloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Ibrutinib: Ciprofloxacin (Systemic) may increase the serum concentration of Ibrutinib. Management: When treating B-cell malignancies, consider decreasing ibrutinib to 140 mg daily. When treating graft versus host disease, monitor patients closely and reduce the ibrutinib dose as needed based on adverse reactions. Consider therapy modification

Iron Salts: May decrease the serum concentration of Quinolones. Management: Administer 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-, or ofloxacin or nalidixic acid) oral iron salts. Exceptions: Ferric Carboxymaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Isomaltoside; Iron Sucrose. Consider therapy modification

Kola Nut: Ciprofloxacin (Systemic) may increase the serum concentration of Kola Nut. Specifically, ciprofloxacin may increase serum concentrations of caffeine, a major component of kola nut. Monitor therapy

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

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

Magnesium Salts: May decrease the serum concentration of Quinolones. Management: Administer oral quinolones 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-, or ofloxacin or nalidixic acid) oral magnesium salts. Consider therapy modification

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

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

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

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

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

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: Ciprofloxacin (Systemic) 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 daily (ie, 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

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

Probucol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

Promazine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

QTc-Prolonging Agents (Highest Risk): QTc-Prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of QTc-Prolonging Agents (Highest Risk). Avoid combination

QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Monitor therapy

QTc-Prolonging Agents (Moderate Risk): May enhance the QTc-prolonging effect of other QTc-Prolonging Agents (Moderate Risk). Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

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

Rasagiline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Rasagiline. Consider therapy modification

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

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

Ropivacaine: Ciprofloxacin (Systemic) 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: Administer oral quinolones at least 2 hours before or 6 hours after the sucralfate dose. Greater separation of doses may further lessen the risk for a significant interaction. Consider therapy modification

Teriflunomide: May increase the serum concentration of OAT3 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

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

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

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

Vinflunine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Avoid combination

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

Xipamide: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Moderate Risk). Monitor therapy

Zinc Salts: May decrease the serum concentration of Quinolones. Management: Administer 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-, 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

1% to 10%:

Central nervous system: Neurological signs and symptoms (children 2%; includes dizziness, insomnia, nervousness, somnolence), headache (IV administration), restlessness (IV administration)

Dermatologic: Skin rash (children 2%, adults 1%)

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

Hepatic: Increased serum AST (adults 1%), increased serum ALT

Local: Injection site reactions (IV administration)

Respiratory: Rhinitis (children 3%)

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

<1% (Limited to important or life-threatening): Abnormal gait, acute generalized exanthematous pustulosis, acute gout attack, acute renal failure, ageusia, agitation, agranulocytosis, albuminuria, anaphylactic shock, anaphylaxis, anemia, angina pectoris, angioedema, anorexia, anosmia, anxiety, arthralgia, ataxia, atrial flutter, bone marrow depression (life-threatening), bronchospasm, candidiasis, candiduria, cardiorespiratory arrest, casts in urine, cerebral thrombosis, chills, cholestatic jaundice, chromatopsia, Clostridium difficile-associated diarrhea, confusion, constipation, crystalluria (particularly in alkaline urine), decreased hematocrit, decreased hemoglobin, decreased prothrombin time, delirium, depersonalization, depression (including self-injurious behavior), dizziness, drowsiness, dyspepsia (adults), dysphagia, dysphasia, dyspnea, edema, eosinophilia, erythema multiforme, erythema nodosum, exacerbation of myasthenia gravis, exfoliative dermatitis, fixed drug eruption, flatulence, gastrointestinal hemorrhage, hallucination, headache (oral), hematuria, hemolytic anemia, hepatic failure, hepatic necrosis, hepatotoxicity (idiosyncratic) (Chalasani, 2014), hyperesthesia, hyperglycemia, hyperpigmentation, hypersensitivity reaction, hypertension, hypertonia, hypoglycemia, hypotension, increased blood urea nitrogen, increased creatine phosphokinase, increased INR (in patients treated with vitamin K antagonists), increased intracranial pressure, increased lactate dehydrogenase, increased serum alkaline phosphatase, increased serum bilirubin, increased serum cholesterol, increased serum creatinine, increased serum glucose, increased serum lipase, increased serum triglycerides, increased uric acid, insomnia, interstitial nephritis, intestinal perforation, irritability, jaundice, laryngeal edema, lethargy, lymphadenopathy, malaise, manic behavior, mastalgia, methemoglobinemia, migraine, myalgia, myocardial infarction, myoclonus, nephritis, nephrolithiasis, nightmares, nystagmus, orthostatic hypotension, palpitations, pancreatitis, pancytopenia (life-threatening), paranoia, paresthesia, peripheral neuropathy, petechia, phobia, phototoxicity, pneumonitis, polyneuropathy, prolonged prothrombin time (in patients treated with vitamin K antagonists), pseudotumor cerebri, pulmonary edema, rupture of tendon, seizure (including grand mal), serum sickness-like reaction, skin photosensitivity, status epilepticus, Stevens-Johnson syndrome, suicidal ideation, suicidal tendencies, syncope, tachycardia, tendonitis, thrombocythemia, thrombocytopenia, thrombophlebitis, tinnitus, torsades de pointes, toxic epidermal necrolysis, toxic psychosis, tremor, twitching, unresponsive to stimuli, urethral bleeding, vaginitis, vasculitis, ventricular arrhythmia, ventricular ectopy, visual disturbance, vulvovaginal candidiasis, weakness

ALERT: U.S. Boxed Warning

Serious adverse reactions:

Fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together, including: tendinitis and tendon rupture, peripheral neuropathy, and CNS effects. Discontinue ciprofloxacin immediately and avoid the use of fluoroquinolones in patients who experience any of these serious adverse reactions. Because fluoroquinolones have been associated with serious adverse reactions, reserve ciprofloxacin for use in patients who have no alternative treatment options for the following indications: acute exacerbation of chronic bronchitis, acute sinusitis, and acute uncomplicated cystitis.

Exacerbation of myasthenia gravis:

Fluoroquinolones may exacerbate muscle weakness in patients with myasthenia gravis. Avoid ciprofloxacin in patients with known history of myasthenia gravis.

Warnings/Precautions

Concerns related to adverse effects:

• Altered cardiac conduction: Fluoroquinolones may prolong QTc interval; avoid use in patients with a history of or at risk for QTc prolongation, torsade de pointes, uncorrected hypokalemia, 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).

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

• Glucose regulation: Fluoroquinolones have been associated with the development of serious, and sometimes fatal, hypoglycemia. These events have occurred most often in elderly patients with diabetes, but have also been reported in patients without a prior history of diabetes. Prompt identification and treatment of hypoglycemia is essential. Individual quinolones may differ in their potential to cause this effect. It was most evident with gatifloxacin (no longer marketed as a systemic formulation). Hyperglycemia has also been associated with the use of fluoroquinolones. Patients should be monitored closely for signs/symptoms of disordered glucose regulation.

• 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: 1-39 days), often associated with hypersensitivity. 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 quinolone 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), and toxic psychosis; may also cause nervousness, agitation, insomnia, anxiety, nightmares, paranoia, dizziness, confusion, tremors, hallucinations, depression, and suicidal thoughts or actions. May occur following the first dose; discontinue immediately and avoid further use of fluoroquinolones in patients who experience these reactions. Use with caution in patients with known or suspected CNS disorder, or risk factors that may predispose to seizures or lower the seizure threshold.

- 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 if symptoms of sensory or sensorimotor neuropathy occur. Avoid use in patients who have previously experienced peripheral neuropathy.

- 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.

• Theophylline: Serious and fatal reactions including seizures, status epilepticus, cardiac arrest, and respiratory failure have been reported with concomitant administration of theophylline. If concurrent use is unavoidable, monitor serum theophylline levels and adjust theophylline dose as warranted.

Special populations:

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

• Glucose-6-phosphate dehydrogenase (G6PD) deficiency: Hemolytic reactions may (rarely) occur with quinolone use in patients with latent or actual 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).

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

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in some animal reproduction studies. 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

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience headache, diarrhea, vomiting, or nausea. Have patient report immediately to prescriber signs of tendon inflammation or rupture (pain, bruising, or swelling in the back of the ankle, shoulder, hand, or other joints), signs of depression (suicidal ideation, anxiety, emotional instability, or confusion), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of nerve problems (sensitivity to heat or cold; decreased sense of touch; burning, numbness, or tingling; pain, or weakness in the arms, hands, legs, or feet), signs of high blood sugar (confusion, fatigue, increased thirst, increased hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, tachycardia, confusion, increased hunger, or sweating), angina, thrush, severe loss of strength and energy, vision changes, hallucinations, seizures, insomnia, nightmares, dizziness, agitation, behavioral changes, mood changes, shortness of breath, bruising, bleeding, tremors, abnormal gait, sunburn, chills, pharyngitis, vaginitis, tinnitus, muscle pain, muscle weakness, injection site irritation, signs of Clostridium difficile (C. diff)-associated diarrhea (abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools), or signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes) (HCAHPS).

• Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Hide