Fluoroquinolones have been associated with disabling and potentially irreversible serious adverse reactions that have occurred together, including: tendinopathy 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.
Fluoroquinolones may exacerbate muscle weakness in patients with myasthenia gravis. Avoid ciprofloxacin in patients with known history of myasthenia gravis.
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 [PEP]):
Oral: 500 mg every 12 hours for 42 to 60 days.
IV: 400 mg every 12 hours for 42 to 60 days.
Note: Anthrax vaccine should also be administered to exposed individuals (CDC [Bower 2019]; CDC [Hendricks 2014]). Duration of therapy: If the PEP anthrax vaccine series is administered on schedule (for all regimens), antibiotics may be discontinued in immunocompetent adults 18 to 65 years of age at 42 days after initiation of vaccine or 2 weeks after the last dose of the vaccine (whichever comes last and not to exceed 60 days); if the vaccination series cannot be completed, antibiotics should continue for 60 days (CDC [Bower 2019]). In addition, adults with immunocompromising conditions or receiving immunosuppressive therapy, patients >65 years of age, and patients who are pregnant or breastfeeding should receive antibiotics for 60 days (CDC [Bower 2019]).
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 2021a; Baddour 2021b).
Cat scratch disease, lymphadenitis (nondisseminated) (alternative agent) (off-label use):
Note: Some experts reserve use for patients who are immunocompetent and are unable to receive other agents (Spach 2022).
Oral: 500 mg twice daily for 7 to 10 days (Holley 1991; Spach 2022).
Chancroid (alternative agent) (off-label use): Oral: 500 mg twice daily for 3 days (CDC [Workowski 2021]; Hicks 2021)
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): Note: Some experts reserve for patients with risk factors for poor outcomes (eg, ≥65 years of age, FEV1 <50% predicted, frequent exacerbations, significant comorbidities) who are at risk of Pseudomonas infection (Sethi 2022).
Oral: 500 to 750 mg twice daily (Nouira 2010; Umut 1999) for 5 to 7 days (GOLD 2021).
Crohn disease, treatment of simple perianal fistulas, adjunctive agent (off-label use): Oral: 500 mg twice daily, with or without metronidazole, for 4 weeks (ACG [Lichtenstein 2018]; AGA [Feuerstein 2021]; 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 2020).
Moderate to severe infection: IV: 400 mg every 12 hours (400 mg every 8 hours if P. aeruginosa is suspected) (IDSA [Lipsky 2012]; Weintrob 2020).
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]).
Intra-abdominal infection, mild to moderate, community-acquired in patients without risk factors for resistance or treatment failure:
Note: 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]).
Cholecystitis, acute:
Note: The addition of anaerobic therapy (eg, metronidazole) is recommended if biliary-enteric anastomosis is present (SIS/IDSA [Solomkin 2010]).
IV: 400 mg every 12 hours.
or
Oral: 500 mg every 12 hours.
Duration: Continue for 1 day after gallbladder removal or until clinical resolution in patients managed nonoperatively (SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]; Vollmer 2021).
Other intra-abdominal infections (eg, perforated appendix, diverticulitis, intra-abdominal abscess):
Note: For acute diverticulitis, some experts suggest deferring antibiotics in otherwise healthy immunocompetent patients with mild disease; however, data on this approach in outpatients are limited (AGA [Stollman 2015]; Desai 2019; Shah 2017; SIS [Mazuski 2017]; van Dijk 2020).
IV: 400 mg every 12 hours in combination with metronidazole.
or
Oral: 500 mg every 12 hours in combination with metronidazole.
Duration: Total duration of therapy (which may include transition to oral antibiotics) is for 4 to 5 days following adequate source control (Sawyer 2015; SIS [Mazuski 2017]); for diverticulitis or uncomplicated appendicitis managed without intervention, duration is 7 to 10 days (Barshak 2021; Pemberton 2021).
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 [Cohn 2013]).
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 2020); some clinicians will provide antibacterial prophylaxis if ANC is anticipated to be <500 cells/mm3 for >7 days (Wingard 2020). 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]).
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, as a component of empiric therapy or pathogen-specific therapy for P. aeruginosa in hospitalized patients : Note: For empiric therapy, use in combination with other appropriate agents (IDSA/ATS [Kalil 2016]).
Oral: 750 mg every 12 hours (West 2003).
IV: 400 mg every 8 hours (IDSA/ATS [Kalil 2016]).
Duration of therapy: Varies based on disease severity and response to therapy; treatment is typically given for 7 days (IDSA/ATS [Kalil 2016]).
Pouchitis (post–ileal pouch-anal anastomosis), acute (off-label use):
Initial therapy: Oral: 500 mg every 12 hours for 14 days (Navaneethan 2009; Nguyen 2019; Shen 2001; Shen 2020; Wall 2011).
Refractory disease: Oral: 500 mg every 12 hours for 28 days as part of an appropriate combination regimen (Benlice 2019; Shen 2020).
Prostatitis:
Acute bacterial prostatitis (off-label use):
Oral: 500 mg every 12 hours (Meyrier 2020a).
IV: 400 mg every 12 hours (Meyrier 2020a).
Duration of therapy: 4 to 6 weeks (Meyrier 2020a; Yoon 2013).
Chronic bacterial prostatitis: Oral: 500 mg every 12 hours for 4 to 6 weeks (Meyrier 2021).
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 14 days (7 to 14 days in patients with HIV with a CD4 count ≥200 cells/mm3). Note: Immunosuppressed patients (eg, patients with HIV and CD4 count <200 cells/mm3) require a longer duration of treatment (eg, weeks to months) and may require a higher dose (eg, 750 mg twice daily) (HHS [OI adult 2020]; Hohmann 2020a).
Nontyphoidal bloodstream infection: IV: 400 mg twice daily for 14 days. Note: Immunosuppressed patients (eg, patients with HIV with CD4 count <200 cells/mm3) and those with an extraintestinal focus of infection require a longer duration of treatment (eg, weeks or months) (HHS [OI adult 2020]; Hohmann 2020b).
Typhoid fever (Salmonella typhi and paratyphi): Severe disease or mild to moderate infection in patients at high risk of developing invasive disease. Note: Use only if MIC ≤0.06 mcg/mL as the incidence of fluoroquinolone-resistant strains is increasing (Humphries 2012).
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): Note: Use only if MIC is < 0.12 mcg/mL (HHS [OI adult 2020]); IDSA [Shane 2017]).
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 (Agha 2021; IDSA [Guerrant 2001]). Note: Patients with HIV require a longer duration of treatment (eg, 5 to 7 days) and may require a higher dose (eg, 750 mg twice daily) (Agha 2021; HHS [OI adult 2020]).
Spontaneous bacterial peritonitis, prophylaxis (alternative agent) (off-label use):
Note: For secondary prophylaxis in patients with prior spontaneous bacterial peritonitis (SBP) and primary prophylaxis in patients at high risk for SBP (eg, low ascites protein [<1.5 g/dL] with advanced liver failure or impaired kidney function). Some experts also use for prophylaxis during hospitalization in patients with cirrhosis and either acute GI bleeding or ascites protein <1 g/dL (AASLD [Biggins 2021]; Runyon 2021).
Oral: 500 mg once daily (AASLD [Biggins 2021]). For patients with cirrhosis and acute GI bleeding, some experts use 500 mg twice daily following, or as an alternative to parenteral prophylaxis, for a total antibiotic duration of 7 days (Runyon 2021).
Surgical prophylaxis (off-label use): Note: Use in combination with other appropriate agents may be warranted (procedure-dependent) (ASHP [Bratzler 2013]).
IV (alternative agent): 400 mg within 120 minutes prior to surgical incision (ASHP [Bratzler 2013]).
Oral: 500 mg within 120 minutes prior to surgical incision. Note: Reserve use for high-risk cystoscopy (eg, urine culture positive, preoperative catheter, or placement of prosthetic material), cystoscopy with manipulation (eg, transrectal prostate biopsy), or upper GU tract instrumentation. Due to increasing resistance among urinary pathogens, review local sensitivity prior to use (Anderson 2021; ASHP [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]).
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:
Cystitis, acute uncomplicated or acute simple cystitis (infection limited to the bladder without signs/symptoms of upper tract, prostate, or systemic infection) (alternative agent):
Note: Use is discouraged due to safety concerns and increasing resistance; reserve for those who have no alternative treatment options (Bidell 2016; FDA Drug Safety Communication 2016; Hooton 2021a; Hooton 2021b; IDSA/ESCMID [Gupta 2011]). However, for men who have severe symptoms or there is concern for early prostate involvement, some experts prefer fluoroquinolones (Hooton 2021b).
Oral: Immediate release: 250 mg every 12 hours (Hooton 2012; manufacturer’s labeling).
Oral: Extended release: 500 mg every 24 hours.
Duration: 3 days (females) (Hooton 2012; IDSA/ESCMID [Gupta 2011]) or 5 days (males) (Hooton 2021b).
Urinary tract infection, complicated (including pyelonephritis):
Note: If the prevalence of fluoroquinolone resistance is >10%, an initial dose of a long-acting parenteral antimicrobial (eg, ceftriaxone) followed by oral therapy is recommended for outpatients (Hooton 2021c; IDSA/ESCMID [Gupta 2011]).
Oral: Immediate release: 500 mg every 12 hours for 5 to 7 days.
Oral: Extended release: 1 g every 24 hours for 5 to 7 days.
IV (inpatient): 400 mg every 12 hours for a total of 5 to 7 days.
Missed dose:
Oral, immediate release: Administer as soon as possible if ≥6 hours until next scheduled dose, otherwise, wait until next scheduled dose; do not double doses to compensate for missed dose.
Oral, extended release: Administer as soon as possible if ≥8 hours until next scheduled dose, otherwise, wait until next scheduled dose; do not double doses to compensate for missed dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function:
CrCl (mL/minute) |
Oral, immediate release |
Oral, extended release |
IV |
---|---|---|---|
aExpert opinion derived from manufacturer's labeling, Heintz 2009, Mrhar 1990. bFor severe infections, 750 mg may be administered at the intervals noted above. cConsider administering a loading dose of 400 mg × 1 if utilizing 200 mg every 24 hours. dConsider administering a loading dose of 500 mg × 1 if utilizing 250 mg every 24 hours. eMinimally dialyzable (<10%); when scheduled dose falls on a dialysis day, administer post dialysis. | |||
CrCl >50 to <130 |
500 to 750 mg every 12 hours |
1 g every 24 hours |
400 mg every 8 to 12 hours |
CrCl 30 to 50 |
250 to 500 mg every 12 hoursb |
1 g every 24 hours |
400 mg every 8 to 12 hours |
CrCl <30 |
500 mg every 24 hoursb |
500 mg every 24 hours |
200c to 400 mg every 12 to 24 hours |
Hemodialysis, intermittent (thrice weekly)e |
250d to 500 mg every 24 hoursb |
500 mg every 24 hours |
200c to 400 mg every 24 hours |
Peritoneal dialysis |
250d to 500 mg every 24 hoursb |
500 mg every 24 hours |
200c to 400 mg every 24 hours |
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post-trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Bilbao-Meseguer 2018; Udy 2010).
IV: 400 mg every 8 hours when organism minimum inhibitory concentration (MIC) ≤0.125 mg/L. Monte Carlo simulations suggest a dose of 600 mg every 8 hours may be required to achieve pharmacodynamic goals for organisms with MICs >0.125 mg/L (Roberts 2019); monitor closely, especially with prolonged courses, or utilize another agent (expert opinion).
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.
IV: 200 to 400 mg every 8 to 12 hours (Roger 2016; Spooner 2011; Wallis 2001). Note: Utilize 400 mg every 8 hours only in severe infections or when difficult-to-treat organisms (MIC ≥0.5 mg/L) are suspected or confirmed (Roger 2016); monitor closely.
Oral, immediate release: 250 to 750 mg every 12 hours (expert opinion inferred from relative IV clearance).
PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important. Dosing based on Monte Carlo simulations of 8- to 10-hour treatments with 4 to 5 L/hour flow rates.
IV: 400 mg every 12 hours assuming MIC susceptibility breakpoint ≤0.5 mg/L (Lewis 2016; expert opinion).
Oral, immediate release: 500 mg every 12 hours (administer after PIRRT) (expert opinion inferred from relative IV clearance).
There are no dosage adjustments provided in manufacturer's labeling. Use with caution in severe impairment.
(For additional information see "Ciprofloxacin (systemic): Pediatric drug information")
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 2013).
IV: 10 mg/kg/dose every 8 hours; maximum dose: 400 mg/dose (Stockmann 2013).
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 (Yersinia pestis infection) (alternative agent):
Manufacturer's labeling: Infants, Children, and Adolescents:
Oral, immediate release: 15 mg/kg/dose every 8 to 12 hours for 14 days; maximum dose: 500 mg/dose.
IV: 10 mg/kg/dose every 8 to 12 hours for 10 to 21 days; maximum dose: 400 mg/dose.
Alternate dosing (CDC 2020):
Postexposure prophylaxis: Children and Adolescents: Oral, immediate release: 20 mg/kg/dose twice daily for 7 days; maximum dose: 500 mg/dose.
Treatment: Note: Treat for a total of 10 to 14 days (combined IV and oral) or until 2 days after fever subsides, whichever is longer.
Children and Adolescents:
Initial treatment: IV: 15 mg/kg/dose every 12 hours; maximum dose: 400 mg/dose; once patient improves may switch to oral therapy to complete treatment course.
Oral step-down treatment: Oral, immediate release: 20 mg/kg/dose twice daily; maximum dose: 500 mg/dose; higher maximum doses (up to 750 mg twice daily) are recommended for adults.
Pneumonia, community acquired (Haemophilus influenza): Infants >3 months and Children: IV: 15 mg/kg/dose every 12 hours (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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents:
IV and Oral, immediate release: There are no dosage adjustments provided in the manufacturer's labeling; however, the following guidelines have been used by some clinicians (Aronoff 2007):
GFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary
GFR 10 to 29 mL/minute/1.73 m2: 10 to 15 mg/kg/dose every 18 hours
GFR <10 mL/minute/1.73 m2: 10 to 15 mg/kg/dose every 24 hours
Hemodialysis/peritoneal dialysis (PD) (after dialysis on dialysis days): Minimally dialyzable (<10%): 10 to 15 mg/kg/dose every 24 hours
CRRT: 10 to 15 mg/kg/dose every 12 hours
Oral, extended release: Adolescents ≥18 years:
CrCl ≥30 mL/minute: No dosage adjustment necessary
CrCl <30 mL/minute: 500 mg every 24 hours
Hemodialysis/peritoneal dialysis (PD) (administer after dialysis on dialysis days): 500 mg every 24 hours
There are no dosage adjustments provided in manufacturer's labeling; use with caution in severe impairment.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
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: 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]:
Generic: 500 mg [DSC], 1000 mg [DSC]
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Intravenous:
Generic: 10 mg/mL ([DSC]); 2 mg/mL in D5W (100 mL, 200 mL)
Suspension Reconstituted, Oral:
Cipro: 500 mg/5 mL (100 mL) [contains soybean lecithin]
Tablet, Oral, as hydrochloride [strength expressed as base]:
Cipro: 250 mg [DSC], 500 mg [DSC], 750 mg [DSC] [contains corn starch]
Generic: 100 mg, 250 mg, 500 mg, 750 mg
Tablet Extended Release 24 Hour, Oral, as base and hydrochloride [strength expressed as base]:
Cipro XL: 500 mg, 1000 mg
Generic: 500 mg
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Cipro: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/019537s092lbl.pdf#page=39
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.
Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. Switch to IR formulation (tablet or oral solution).
Parenteral: Administer by slow IV infusion over 60 minutes into a large vein (reduces risk of venous irritation).
Oral: May administer with food to minimize GI upset; divalent and trivalent cations [dairy foods (milk, yogurt) and mineral supplements (eg, iron, zinc, calcium) or calcium-fortified juices] decrease ciprofloxacin absorption; usual dietary calcium intake (including meals which include dairy products) has not been shown to interfere with ciprofloxacin absorption (per manufacturer). Administer immediate release ciprofloxacin and Cipro XR at least 2 hours before or 6 hours after any of these products.
Oral suspension: Shake vigorously prior to each dose. Should not be administered through feeding tubes (suspension is oil-based and adheres to the feeding tube). Patients should avoid chewing on the microcapsules.
Tablets:
Immediate release: Administering 2 hours after meals is preferable.
Extended release: Do not crush, split, or chew. May be administered with meals containing dairy products (calcium content <800 mg), but not with dairy products alone.
Missed dose:
Immediate release (oral suspension, tablet): Administer as soon as possible if ≥6 hours until next scheduled dose; otherwise, wait until next scheduled dose.
Extended release: Administer as soon as possible if ≥8 hours until next scheduled dose; otherwise, wait until next scheduled dose.
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.
Parenteral: Administer by slow IV infusion over 60 minutes to reduce the risk of venous irritation (burning, pain, erythema, and swelling).
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 infection; 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, tendinopathy and tendon rupture, peripheral neuropathy, CNS effects), reserve ciprofloxacin for use in patients who have no alternative treatment options for acute uncomplicated cystitis.
Anthrax; Bite wound infection (animal and human bites); Cat scratch disease, lymphadenitis (nondisseminated); Chancroid; Cholera (Vibrio cholerae); Chronic obstructive pulmonary disease, acute exacerbation; Crohn disease, treatment of simple perianal fistulas; Diabetic foot infection; Endocarditis, treatment; Meningitis, bacterial; Meningococcal disease (prevention and control); Neutropenia (chemotherapy-induced), antibacterial prophylaxis; Neutropenic fever, low-risk cancer patients (empiric therapy); Peritoneal dialysis catheter-related infection; Pouchitis (post–ileal pouch-anal anastomosis), acute; Prostatitis, acute bacterial; Prosthetic joint infection; Spontaneous bacterial peritonitis, prophylaxis; Surgical prophylaxis; Surgical site infection; Tularemia
Ciprofloxacin may be confused with cephalexin
Cipro may be confused with Ceftin
Fluoroquinolones have been associated with aortic aneurysm and aortic dissection with risk of aortic aneurysm higher than aortic dissection. Risk of aortic dissection may be lower with ciprofloxacin and moxifloxacin than with levofloxacin (Ref).
Mechanism: Time-related; up-regulation of matrix metalloproteinase (MMP) enzymes capable of damaging components of the extracellular matrix, including collagen and elastin (Ref). MMP-2 and MMP-9 have been shown to play a role in development of aneurysms via degradation of collagen fibril (Ref). May also have a direct effect on the viability of chondrocytes and tenocytes responsible for collagen synthesis, due to generation of reactive oxygen species, caspase activation, and apoptosis (Ref).
Onset: Delayed in most cases. Studies evaluating risk generally evaluated the time period of 60 days after the initiation of fluoroquinolone therapy (Ref).
Risk factors:
• Older adults with peripheral vascular disease or a history of aneurysms, atherosclerosis, hypertension, or genetic conditions predisposing to aortic aneurysm (eg, Marfan syndrome, Ehlers-Danlos syndrome) (Ref)
• Longer courses of therapy (>14 days) (Ref)
• Severe emotional or physical stress has been correlated to the onset of pain (Ref)
Arthropathy, or joint disease, has been observed in both animal and pediatric human studies following treatment with fluoroquinolone antibiotics, including ciprofloxacin (Ref). In an international, multicenter, randomized trial of ~700 pediatric patients (ciprofloxacin versus comparator), more patients in the ciprofloxacin group experienced musculoskeletal events both within 6 weeks and 1 year of follow-up. Arthropathy and arthralgias appear to resolve after discontinuation of treatment with no long-term sequelae (Ref). Though the true incidence is unknown, arthropathy and arthralgia are considered to be infrequent, but potentially serious adverse reactions.
Mechanism: Unknown; several hypotheses have been proposed including inhibition of mitochondria DNA synthesis in immature chondrocytes, direct toxic effect of fluoride on cartilage, magnesium chelation and subsequent deficiency in cartilage, and defective proteoglycan and procollagen synthesis with decreased incorporation of tritiated thymidine by chondrocytes (Ref).
Onset: Varied; may occur within first day of treatment initiation or months following discontinuation (Ref).
Risk factors:
• Higher doses (Ref)
• Prolonged exposure (Ref)
Fluoroquinolones have been associated with a range of psychiatric and neurologic effects, ranging from dizziness and restlessness to toxic psychosis (Ref). More common reactions include confusion, agitation, insomnia, and drowsiness. More severe reactions, including delusions, hallucinations, suicidal ideation, suicidal tendencies, and toxic psychosis, are less common. Neuroexcitation may include seizure in some patients (Ref).
Mechanism: GABA binding disruption, NMDA binding alterations, and increased excitatory neurotransmitters (Ref). Mitochondrial dysfunction has been hypothesized to contribute (Ref).
Onset: Varied; neuroexcitatory phenomena generally occur in the first week of therapy, often after 2 to 3 days (Ref).
Risk factors:
• Older adults (Ref)
• Kidney impairment with unadjusted or higher doses (Ref)
• Concurrent therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with enhanced neuroexcitation (Ref)
• Concurrent theophylline (Ref)
• History of seizures, seizure disorders, CNS disorders, or concurrent therapy with medications known to lower seizure threshold may increase risk of seizures (Ref)
• History of or risk factor for mental illness (eg, depression)
Clostridioides difficile infection (CDI), including Clostridioides difficile associated diarrhea and Clostridioides difficile colitis, has been reported (Ref).
Onset: Varied; may start on the first day of antibiotic therapy or up to 3 months postantibiotic (Ref).
Risk factors:
• Antibiotic exposure (highest risk factor) (Ref)
• Type of antibiotic (fluoroquinolones among the highest risk) (Ref)
• Long durations in a hospital or other health care setting (recent or current) (Ref)
• Older adults (Ref)
• Immunocompromised conditions (Ref)
• A serious underlying condition (Ref)
• GI surgery/manipulation (Ref)
• Antiulcer medications (eg, proton pump inhibitors and H2 blockers) (Ref)
• Chemotherapy (Ref)
Hyperglycemia and hypoglycemia have been associated with the use of fluoroquinolones, including ciprofloxacin.
Mechanism: Increase in insulin release via blockade of adenosine triphosphate-sensitive potassium channels in the pancreatic beta cells, but the significance at clinical concentrations has been questioned (Ref). Additionally, effects on gluconeogenesis, glucose transport (via expression of GLUT-1), and mitochondrial dysfunction have been implicated (Ref).
Onset: Varied; corresponds to the initiation of therapy but may be delayed by 2 to 3 days. Events requiring emergent care or hospitalization occurred between day 3 and day 10 of therapy (Ref).
Risk factors:
• Patients with diabetes are at highest risk; however, cases in patients without diabetes have been reported (Ref)
• Concurrent therapy with hypoglycemic agents, including insulin (Ref)
Liver injury/drug-induced liver injury: May cause hepatic injury (hepatotoxicity); both cholestatic and hepatocellular patterns are represented in reported clinical presentations (Ref).
Mechanism: Immunologic reactions account for many events; direct toxicity related to mitochondrial dysfunction and increased oxidative stress may also be responsible for some reactions (Ref).
Onset: Varied; acute liver injury may occur in a range of 1 to 39 days.
Risk factors:
• Most fatal events occurred in patients >55 years of age.
Hypersensitivity reactions include anaphylaxis, nonimmune anaphylaxis (previously called anaphylactoid reactions), and delayed cutaneous reactions.
Delayed cutaneous reactions include severe dermatologic reactions, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systems symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis (Ref). Less severe reactions include nonbullous and bullous fixed drug eruption (Ref).
Immunologically mediated organ-specific reactions include pneumonitis, vasculitis, pancreatitis, interstitial nephritis, hemolytic anemia, thrombocytopenia, and some cases of hepatitis (Ref).
Mechanism: Nonimmune anaphylaxis results from binding directly to specific receptors (MGPRX2) on mast cells and basophils, causing direct stimulation of histamine release (and other mediators) (Ref). Importantly, these cases may occur without prior exposure. In other cases, anaphylaxis may be mediated by IgE, formed with prior exposure to the drug (Ref).
Delayed reactions are mediated by activated T-cells. Chemical activation of fluoroquinolones was not required for immune reactions to occur, which implies direct activation (pharmacologic interaction) without covalent binding to host proteins/hapten formation (Ref). Ciprofloxacin forms metabolites, but haptens have not been characterized to date.
Onset: Anaphylaxis (nonimmune and immune): Rapid; may occur within an hour of administration (Ref). Other reactions, particularly various maculopapular cutaneous reactions or organ-specific reactions: Varied; occur after days to weeks of therapy (Ref).
Risk factors:
• Nonimmune anaphylaxis may be dose- and/or infusion rate-related (concentration-related) (Ref)
Fluoroquinolones, including ciprofloxacin, may cause an exacerbation of myasthenia gravis. Disease exacerbations vary in severity from muscular weakness to severe compromise (myasthenic crisis characterized by acute respiratory failure) (Ref).
Mechanism: Neuromuscular blockade is the most frequently cited mechanism, although alterations in mitochondrial energy production has also been suggested as a contributing mechanism (Ref).
Onset: Rapid; within hours of the initiation of therapy with a fluoroquinolone (Ref)
Risk factors:
• Patients with myasthenia gravis (diagnosed and undiagnosed) (Ref)
Fluoroquinolones have been associated with peripheral neuropathy and other effects, including axonal neuropathy and Guillain-Barré syndrome (GBS) (Ref). Associated with many types of disturbances of special senses, including several case reports indicating a very slow recovery and/or permanent state of disability (Ref).
Mechanism: Mitochondrial effects related to reactive oxygen species and apoptotic changes (Ref).
Onset: Varied; may present as early as the first day of therapy (Ref).
Risk factors:
• Males (Ref)
• Older adults (>60 years of age) (Ref)
• Duration of therapy (Ref)
• Type 1 diabetes may also be a risk factor (data are limited) (Ref)
• History of peripheral neuropathy
Phototoxicity/skin photosensitivity account for a proportion of the overall cutaneous adverse reactions (Ref). May be more common with other fluoroquinolones (Ref). Published reports with ciprofloxacin are limited (Ref).
Mechanism: Non-dose-related; immunologic. Reactive intermediates are generated by ultraviolet exposure and attach to proteins of Langerhans cells, triggering immune reactions (Ref).
Onset: Rapid; in a study with ofloxacin, occurred within 24 hours of initiation and sun exposure (Ref).
Risk factors:
• Duration and intensity of sun exposure
• Cystic fibrosis (Ref)
• Prior phototoxic reaction to another fluoroquinolone (Ref).
Fluoroquinolones may be associated with prolonged QT interval on ECG and ventricular arrhythmias, such as torsades de pointes (TdP). Ciprofloxacin may have a lower risk than other fluoroquinolones, particularly moxifloxacin (Ref). Change in QTc from baseline for moxifloxacin was found to be +16.34 to 17.83 ms, while the change with ciprofloxacin was +2.27 to 4.93 ms (Ref).
Mechanism: May alter the rapid delayed rectifier potassium current, resulting in prolonged repolarization (Ref). Prolonged repolarization can alter action potentials in cardiac cells and promote arrhythmogenic activity (Ref).
Onset: Varied; effect is concentration-dependent, initially observed at supra-therapeutic doses (Ref). High dose or accumulation may influence concentrations.
Risk factors:
Drug-induced QTc prolongation/TdP (in general):
• Females (Ref)
• Age >65 years (Ref)
• Structural heart disease (eg, history of myocardial infarction or heart failure with reduced ejection fraction) (Ref)
• History of drug-induced TdP (Ref)
• Genetic defects of cardiac ion channels (Ref)
• Congenital long QT syndrome (Ref)
• History of drug-induced TdP (Ref)
• Baseline QT interval prolongation (eg, >500 msec) or lengthening of the QTc by ≥60 msec (Ref)
• Electrolyte disturbances (eg, hypocalcemia, hypokalemia, hypomagnesemia) (Ref)
• Bradycardia (Ref)
• Hepatic impairment (Ref)
• Kidney impairment (Ref)
• Loop diuretic use (Ref)
• Sepsis (Ref)
• Concurrent administration of multiple medications (≥2) that prolong the QT interval or increase drug interactions that increase serum drug concentrations of QT prolonging medications (Ref)
May cause tendinopathy or rupture of tendon; Achilles is most commonly cited, but inflammation/rupture of many other tendons (including hand, rotator cuff, biceps, and thumb) has been reported (Ref).
Mechanism: Dose- and time-related; upregulation of matrix metalloproteinase (MMP) enzymes capable of damaging components of the extracellular matrix, including collagen and elastin (Ref). Direct effect on the viability of chondrocytes and tenocytes responsible for collagen synthesis, due to generation of reactive oxygen species, caspase activation and apoptosis (Ref).
Onset: Varied; per the manufacturer's labeling, tendinopathy or tendon rupture may occur within hours or days of initiation or may be delayed for several months after discontinuation.
Risk factors:
• Age >60 years (Ref)
• Corticosteroid therapy (Ref)
• Kidney failure (Ref)
• Diabetes mellitus (Ref)
• Previous tendon disorders (eg, rheumatoid arthritis) (Ref)
• Solid organ transplant recipients (Ref)
• Strenuous physical activity (Ref)
• Longer duration of therapy and higher dosages (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Neuromuscular & skeletal: Musculoskeletal signs and symptoms (children: 9% to 22%)
1% to 10%:
Dermatologic: Skin rash (1% to 2%)
Gastrointestinal: Abdominal pain (children: 3%; adults: <1%), diarrhea (2% to 5%), dyspepsia (1% to 3%), nausea (3% to 4%), vomiting (1% to 5%)
Genitourinary: Vulvovaginal candidiasis (2%)
Local: Injection site reactions (IV: >1%)
Nervous system: Dizziness (oral: 2%; IV: <1%), drowsiness, headache (oral: 1% to 3%; IV: >1%), insomnia, nervousness, neurological signs and symptoms (IV: children: 3%), restlessness (IV: >1%; oral: <1%)
Respiratory: Asthma (children: 2%)
Miscellaneous: Fever (children: 2%; adults: <1%)
<1%:
Cardiovascular: Acute myocardial infarction, angina pectoris, bradycardia, flushing, hypertension, hypotension, syncope, tachycardia, thrombophlebitis, vasculitis, vasodilation
Dermatologic: Diaphoresis, erythema multiforme, erythema nodosum, exfoliative dermatitis, maculopapular rash, phototoxicity, pruritus, skin photosensitivity, Stevens-Johnson syndrome (Hallgren 2003), toxic epidermal necrolysis, urticaria, vesicobullous dermatitis, xeroderma
Endocrine & metabolic: Albuminuria, gynecomastia, hyperglycemia (Chou 2013), hypoglycemia (Berhe 2019; Chou 2013), increased thirst
Gastrointestinal: Abdominal distress, anorexia, Clostridioides difficile colitis (Cain 1990), constipation, dysgeusia, flatulence, gastrointestinal hemorrhage, intestinal obstruction, intestinal perforation, oral mucosa ulcer, pancreatitis, xerostomia
Genitourinary: Casts in urine, crystalluria, dysmenorrhea, hematuria, hemorrhagic cystitis, urinary frequency, vaginitis
Hematologic & oncologic: Agranulocytosis, petechia, prolonged prothrombin time, purpuric disease
Hepatic: Cholestatic jaundice, hepatic necrosis
Hypersensitivity: Anaphylactic shock, anaphylaxis, angioedema
Nervous system: Abnormal dreams, abnormal gait, anosmia, ataxia, burning sensation, confusion, depersonalization, depression, hallucination, hypertonia, irritability, malaise, manic reaction, migraine, myasthenia, nightmares, pain, paranoid ideation, paresthesia, phobia, seizure, status epilepticus, suicidal ideation, suicidal tendencies, taste disorder, toxic psychosis, unresponsive to stimuli, vertigo
Neuromuscular & skeletal: Arthralgia, asthenia, joint stiffness, tremor
Ophthalmic: Blurred vision, chromatopsia, decreased visual acuity, diplopia, nystagmus disorder, photopsia
Otic: Hearing loss, tinnitus
Renal: Acute kidney injury, interstitial nephritis (Farid 2018; Lim 2003), nephrolithiasis
Respiratory: Bronchospasm, dyspnea, hemoptysis, laryngeal edema
Postmarketing:
Cardiovascular: Aortic aneurysm (rare: <1%) (Meng 2018; Pasternak 2018), aortic dissection (rare: <1%) (Meng 2018; Pasternak 2018), prolonged QT interval on ECG (rare: <1%) (Teng 2019), torsades de pointes (rare: <1%) (Teng 2019)
Dermatologic: Acute generalized exanthematous pustulosis (Foti 2017; Hauserman 2005)
Gastrointestinal: Ageusia, Clostridioides difficile associated diarrhea (Bates 1990; Hillman 1990)
Hematologic & oncologic: Anemia (Dutta 1999), eosinophilia (Dutta 1999; Hootkins 1989), hemolytic anemia (Lim 2003), leukopenia (Dutta 1999), lymphocytosis (Dutta 1999), methemoglobinemia, monocytosis (Dutta 1999), pancytopenia (Dutta 1999), thrombocythemia, thrombocytopenia (Dutta 1999; Sim 2018)
Hepatic: Hepatic failure, hepatotoxicity (rare: <1%) (Alshammari 2014; Orman 2011; Radovanovic 2018)
Hypersensitivity: Fixed drug eruption (Illiyas 2019; Mollica 2019; Nair 2015), nonimmune anaphylaxis (Ouni 2019)
Immunologic: Drug reaction with eosinophilia and systemic symptoms (Alkhateeb 2013), serum sickness-like reaction (Slama 1990)
Infection: Candidiasis
Nervous system: Agitation, anxiety, delirium, disturbance in attention, exacerbation of myasthenia gravis (Jones 2011), Guillain-Barré syndrome (rare: <1%) (Ali 2014), hyperesthesia, hypoesthesia, increased intracranial pressure, intracranial hypertension (Tan 2019), memory impairment, myoclonus, peripheral neuropathy (rare: <1%; may be irreversible) (Ali 2014; Francis 2014; Popescu 2018), polyneuropathy, twitching
Neuromuscular & skeletal: Myalgia, rupture of tendon (less frequent: ≥1% to <4%) (Arabyat 2015; van der Linden 2002; Yu 2019), tendinopathy (less frequent: ≥1% to <4%) (van der Linden 2002)
Ophthalmic: Retinal detachment (inconsistent data) (Shin 2018)
Respiratory: Pneumonitis
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
Concerns related to adverse effects:
• Crystalluria: Rarely, crystalluria has occurred; urine alkalinity may increase the risk. Ensure adequate hydration during therapy.
• Superinfection: Prolonged use may result in fungal or bacterial superinfection.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment required.
• Syphilis: Since ciprofloxacin is ineffective in the treatment of syphilis and may mask symptoms, all patients should be tested for syphilis at the time of gonorrheal diagnosis and 3 months later.
Special populations:
• Elderly: Adverse effects (eg, tendon rupture, QT changes) may be increased in elderly patients.
• G6PD deficiency: Hemolytic reactions may (rarely) occur with fluoroquinolone use in patients with G6PD deficiency (Luzzatto 2020).
• 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).
In pediatric patients, fluoroquinolones are not routinely first-line therapy, but after assessment of risks and benefits, can be considered a reasonable alternative for situations where no safe and effective substitute is available (eg, resistance [anthrax, common CF pathogens, multidrug resistant tuberculosis]) or in situations where the only alternative is parenteral therapy and ciprofloxacin offers an oral therapy option (Bradley 2011b).
Substrate of OAT1/3, P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (moderate), CYP3A4 (weak)
Agents with Blood Glucose Lowering Effects: Quinolones may enhance the hypoglycemic effect of Agents with Blood Glucose Lowering Effects. Quinolones may diminish the therapeutic effect of Agents with Blood Glucose Lowering Effects. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Risk C: Monitor therapy
Agomelatine: Ciprofloxacin (Systemic) may increase the serum concentration of Agomelatine. Risk X: 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. Risk D: Consider therapy modification
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy
Amphetamines: May enhance the cardiotoxic effect of Quinolones. Risk C: 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. Risk D: Consider therapy modification
Asenapine: Ciprofloxacin (Systemic) may increase the serum concentration of Asenapine. Risk C: Monitor therapy
Ataluren: May increase the serum concentration of Ciprofloxacin (Systemic). Risk C: Monitor therapy
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: 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. Risk D: Consider therapy modification
Bromazepam: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Bromazepam. Risk C: Monitor therapy
Caffeine and Caffeine Containing Products: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor therapy
Calcium Salts: May decrease the absorption of Quinolones. Of concern only with oral administration of both agents. Management: Consider administering an oral quinolone at least 2 hours before or 6 hours after the dose of an oral calcium supplement to minimize this interaction. Monitor for decrease therapeutic effects of quinolones during coadministration. Risk D: Consider therapy modification
CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
Chloroquine: May enhance the hyperglycemic effect of Ciprofloxacin (Systemic). Chloroquine may enhance the hypoglycemic effect of Ciprofloxacin (Systemic). Chloroquine may enhance the QTc-prolonging effect of Ciprofloxacin (Systemic). Risk C: 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. Risk X: Avoid combination
ClomiPRAMINE: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ClomiPRAMINE. Risk C: 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. Risk D: Consider therapy modification
Corticosteroids (Systemic): May enhance the adverse/toxic effect of Quinolones. Specifically, the risk of tendonitis and tendon rupture may be increased. Risk C: 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. Risk D: 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. Risk D: Consider therapy modification
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy
DULoxetine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of DULoxetine. Risk C: 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). Risk D: Consider therapy modification
Fexinidazole: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Management: Avoid use of fexinidazole with OAT1/3 substrates when possible. If combined, monitor for increased OAT1/3 substrate toxicities. Risk D: Consider therapy modification
Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: 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. Risk C: Monitor therapy
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Heroin: Quinolones may enhance the adverse/toxic effect of Heroin. Risk C: Monitor therapy
Hydroxychloroquine: May enhance the hyperglycemic effect of Ciprofloxacin (Systemic). Hydroxychloroquine may enhance the hypoglycemic effect of Ciprofloxacin (Systemic). Hydroxychloroquine may enhance the QTc-prolonging effect of Ciprofloxacin (Systemic). Risk C: Monitor therapy
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: 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 enox-, levo-, nor-, oflox-, peflox, or nalidixic acid) oral iron. Risk D: Consider therapy modification
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: 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. Risk D: 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. Risk D: Consider therapy modification
Levoketoconazole: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Levoketoconazole. 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. Risk C: Monitor therapy
Lomitapide: Ciprofloxacin (Systemic) may increase the serum concentration of Lomitapide. Risk X: Avoid combination
Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification
Lumateperone: Ciprofloxacin (Systemic) may increase the serum concentration of Lumateperone. Risk C: Monitor therapy
Magnesium Salts: May decrease the serum concentration of Quinolones. Management: Administer oral quinolones several hours before (4 h for moxi/pe/spar/enox-, 2 h for others) or after (8 h for moxi-, 6 h for cipro/dela-, 4 h for lome/pe/enox-, 3 h for gemi-, and 2 h for levo-, nor-, or ofloxacin or nalidixic acid) oral magnesium salts. Risk D: Consider therapy modification
Melatonin: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Melatonin. Risk C: Monitor therapy
Meptazinol: May decrease the serum concentration of Ciprofloxacin (Systemic). Risk X: Avoid combination
Methotrexate: Ciprofloxacin (Systemic) may increase the serum concentration of Methotrexate. Risk C: Monitor therapy
Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy
Methylphenidate: May enhance the cardiotoxic effect of Quinolones. Risk C: Monitor therapy
Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: 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: Administer oral quinolones at least 2 hours before, or 6 hours after, the dose of a multivitamin that contains polyvalent cations (ie, calcium, iron, magnesium, selenium, zinc). Monitor for decreased quinolone efficacy. Risk D: 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: Administer oral quinolones at least 2 hours before, or 6 hours after, the dose of a multivitamin that contains polyvalent cations (ie, calcium, iron, magnesium, selenium, zinc). Monitor for decreased therapeutic effects of quinolones. Risk D: Consider therapy modification
Mycophenolate: Quinolones may decrease the serum concentration of Mycophenolate. Specifically, quinolones may decrease concentrations of the active metabolite of mycophenolate. Risk C: Monitor therapy
Nadifloxacin: May enhance the adverse/toxic effect of Quinolones. Risk X: Avoid combination
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Nitisinone: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: 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. Risk C: Monitor therapy
OLANZapine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of OLANZapine. Risk C: 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. Risk D: Consider therapy modification
Pentoxifylline: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Pentoxifylline. Risk C: Monitor therapy
Phenytoin: Ciprofloxacin (Systemic) may diminish the therapeutic effect of Phenytoin. Ciprofloxacin (Systemic) may decrease the serum concentration of Phenytoin. Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Pirfenidone: Ciprofloxacin (Systemic) may increase the serum concentration of Pirfenidone. Management: Avoid this combination if possible. 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. Risk D: 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 to 2 mg and monitoring patients for increased pomalidomide effects/toxicities. Risk D: Consider therapy modification
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Pretomanid: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: 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. Risk C: Monitor therapy
Propranolol: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Propranolol. Risk C: 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. Risk C: Monitor therapy
Ramelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramelteon. Risk C: Monitor therapy
Ramosetron: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ramosetron. Risk C: 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. Risk D: Consider therapy modification
Roflumilast: Ciprofloxacin (Systemic) may increase the serum concentration of Roflumilast. Risk C: Monitor therapy
ROPINIRole: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of ROPINIRole. Risk C: Monitor therapy
Ropivacaine: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Ropivacaine. Risk C: Monitor therapy
Sevelamer: May decrease the absorption of Quinolones. Management: Administer oral quinolones at least 2 hours before or 6 hours after sevelamer. Risk D: Consider therapy modification
Sildenafil: Ciprofloxacin (Systemic) may increase the serum concentration of Sildenafil. Risk C: Monitor therapy
Simvastatin: Ciprofloxacin (Systemic) may enhance the myopathic (rhabdomyolysis) effect of Simvastatin. Ciprofloxacin (Systemic) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: 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. Risk D: Consider therapy modification
Spironolactone: May enhance the arrhythmogenic effect of Ciprofloxacin (Systemic). Risk C: 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. Risk X: 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. Risk D: Consider therapy modification
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tasimelteon: CYP1A2 Inhibitors (Moderate) may increase the serum concentration of Tasimelteon. Risk C: Monitor therapy
Teriflunomide: May increase the serum concentration of OAT1/3 Substrates (Clinically Relevant). Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Thyroid Products: Ciprofloxacin (Systemic) may decrease the serum concentration of Thyroid Products. Risk C: Monitor therapy
TiZANidine: Ciprofloxacin (Systemic) may increase the serum concentration of TiZANidine. Risk X: Avoid combination
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: 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. Risk D: Consider therapy modification
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Quinolones may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Zinc Salts: May decrease the serum concentration of Quinolones. Management: Give oral quinolones at 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 enox-, levo-, nor-, pe- or ofloxacin or nalidixic acid) oral zinc salts. Risk D: 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). Risk D: Consider therapy modification
Food decreases rate, but not extent, of absorption. Ciprofloxacin may increase serum caffeine levels if taken concurrently. Rarely, crystalluria may occur. Enteral feedings may decrease plasma concentrations of ciprofloxacin probably by >30% inhibition of absorption. Management: May administer with most foods to minimize GI upset. If unable to avoid the following foods, administer ciprofloxacin at least 2 hours before or 6 hours after dairy products or calcium-fortified juices alone or in a meal containing >800 mg calcium. Restrict caffeine intake if excessive cardiac or CNS stimulation occurs. Ensure adequate hydration during therapy. Ciprofloxacin should not be administered with enteral feedings. The feeding would need to be discontinued for 1 to 2 hours prior to and after ciprofloxacin administration. Nasogastric administration produces a greater loss of ciprofloxacin bioavailability than does nasoduodenal administration.
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 major birth defects, miscarriage, or other adverse fetal and maternal outcomes have not been observed following ciprofloxacin use during pregnancy.
Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of ciprofloxacin may be altered. Serum concentrations of ciprofloxacin may be lower during pregnancy than in nonpregnant patients (Giamarellou 1989).
Ciprofloxacin is recommended for prophylaxis and treatment of pregnant patients exposed to anthrax (Meaney-Delman 2014). Alternative antibiotics are recommended in pregnant patients for indications such as chancroid (CDC [Workowski 2021]), meningococcal disease (CDC [Cohn 2013]), or perianal disease and pouchitis in pregnant patients with inflammatory bowel disease (AGA [Mahadevan 2019]).
Ciprofloxacin is present in breast milk.
Information related to the presence of ciprofloxacin in breast milk is available from 10 lactating women given oral ciprofloxacin 750 mg every 12 hours for 3 doses. Average milk concentrations were highest 2 hours after the dose (3.79 mcg/mL) and decreased to 0.02 mcg/mL 24 hours after the last dose (Giamarellou 1989). Using the milk concentration of 3.79 mcg/mL, another author has estimated the potential infant dosage via breastfeeding would be ≤0.569 mg/kg/day (Chung 2002), providing a relative infant dose (RID) of 2.8%, based on an infant therapeutic dose of 20 mg/kg/day. In general, breastfeeding is considered acceptable when the RID is <10% (Anderson 2016; Ito 2000).
There is a case report of perforated pseudomembranous colitis in a breastfeeding infant whose mother was taking ciprofloxacin (Harmon 1992). In general, antibiotics that are present in breast milk may cause non-dose-related modification of bowel flora. Monitor infants for GI disturbances, such as thrush or diarrhea (WHO 2002).
Ciprofloxacin is recommended for the prophylaxis and treatment of Bacillus anthracis in breastfeeding patients (Meaney-Delman 2014). Alternative antibiotics are recommended in breastfeeding patients for the treatment of chancroid (CDC [Workowski 2021]) or meningococcal disease (CDC [Cohn 2013]). In general, quinolone antibiotics should be avoided in breastfeeding women if alternative agents are available (WHO 2002). Based on adverse outcomes observed in animal studies, the manufacturer recommends that breastfeeding be discontinued during therapy and for 2 days after the last ciprofloxacin dose if used for indications other than treating maternal B. anthracis. Mothers may express and discard milk during this time.
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.
CBC, renal and hepatic function during prolonged therapy, altered mental status, signs and symptoms of tendinopathy (tendon pain, swelling, inflammation, or rupture) or peripheral neuropathy; signs and symptoms of disordered glucose regulation (especially in patients with diabetes mellitus); rash; signs and symptoms of hypersensitivity reaction.
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).
Protein binding: 20% to 40%.
Metabolism: Partially hepatic; forms 4 metabolites (limited activity).
Bioavailability: Oral: Children: ~60%; Adults: 70%; younger CF patients have a lower bioavailability of 68% vs CF patients >13 years of age with bioavailability of 95%.
Half-life elimination: Children: 4 to 5 hours; Adults: Normal renal function: 4 to 6 hours.
Time to peak: Oral:
IR tablet: 0.5 to 2 hours.
ER tablet: Cipro XR: 1 to 2.5 hours.
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.
Renal function impairment: The half-life is prolonged.
Geriatric: Cmax increased 16% to 40%, AUC increased approximately 20% to 30%, and half-life increased approximately 20%.
Anti-infective considerations:
Parameters associated with efficacy:
Concentration dependent, associated with AUC24/minimum inhibitory concentration (MIC), goal: ≥125 (>80% clinical and microbiologic cures) (Forrest 1993); and Cmax(peak)/MIC ≥10 (bactericidal, resistance prevention) (Blaser 1987; Drusano 1993). Note: In critically ill patients, some experts recommend AUC24/MIC goal >125 to 250 and Cmax/MIC ≥12 (Abdul-Aziz 2020).
Expected drug exposure in patients with normal renal function:
AUC24:
Pediatric patients: 10 mg/kg/dose 3 times daily (multiple dose): IV:
Neonates and infants: 30.9 mg•hour/L.
Children <2 years of age: 27.8 mg•hour/L.
Children 2 to <6 years of age: 28.9 mg•hour/L.
Children 6 to <12 years of age: 20.4 mg•hour/L.
Adults (multiple dose):
500 mg twice daily: Oral: 27.4 mg•hour/L.
750 mg twice daily: Oral: 31.6 mg•hour/L.
400 mg every 12 hours: IV: 25.4 mg•hour/L.
400 mg every 8 hours: IV: 32.9 mg•hour/L.
Cmax (peak):
Pediatric patients: 10 mg/kg/dose 3 times daily (multiple dose): IV:
Neonates and infants: 2.8 mg/L.
Children <2 years of age: 3.6 mg/L.
Children 2 to <6 years of age: 2.7 mg/L.
Children 6 to <12 years of age: 2 mg/L.
Adults (multiple dose):
500 mg twice daily: Oral: 2.97 mg/L.
750 mg twice daily: Oral: 3.59 mg/L.
400 mg every 12 hours: IV: 4.56 mg/L.
400 mg every 8 hours: IV: 4.07 mg/L.
Postantibiotic effect: Bacterial killing continues after ciprofloxacin concentration falls below the MIC of targeted pathogen and varies based on the organism; generally, 1.5 to 3 hours (Craig 1991; Fuursted 1987; Kumar 1992).
Solution (Ciprofloxacin in D5W Intravenous)
200 mg/100 mL (per mL): $0.02 - $0.03
400 mg/200 mL (per mL): $0.01 - $0.04
Suspension (reconstituted) (Cipro Oral)
250 MG/5ML (5%) (per mL): $1.56
500 MG/5ML (10%) (per mL): $1.83
Tablets (Cipro Oral)
250 mg (per each): $5.88
500 mg (per each): $6.88
Tablets (Ciprofloxacin HCl Oral)
100 mg (per each): $15.22
250 mg (per each): $2.24 - $4.59
500 mg (per each): $0.35 - $5.59
750 mg (per each): $5.45 - $6.19
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.