Ciprofloxacin Lactate

(BANM, rINNM)
Synonyms: Ciprofloxacine, Lactate de; Ciprofloxacini Lactas; Lactato de ciprofloxacino.
Cyrillic synonym: Ципрофлоксацина Лактат.

💊 Chemical information

Chemical formula: C17H18FN3O3,C3H6O3 = 421.4.
CAS — 97867-33-9.
ATC — S02AA15.
ATC Vet — QS02AA15.

Incompatibility.

Ciprofloxacin infusion is stated in UK licensed product information to have a pH of 3.9 to 4.5 and to be incompatible with injections chemically or physically unstable at this pH range. Incompatibility has been reported between ciprofloxacin and other drugs including some antibacterials. 1-5 1. Lyall D, Blythe J. Ciprofloxacin lactate infusion. Pharm J 1987; 238: 290. 2. Janknegt R, et al. Quinolones and penicillins incompatibility. DICP Ann Pharmacother 1989; 23: 91–2. 3. Goodwin SD, et al. Compatibility of ciprofloxacin injection with selected drugs and solutions. Am J Hosp Pharm 1991; 48: 2166–71. 4. Jim LK. Physical and chemical compatibility of intravenous ciprofloxacin with other drugs. Ann Pharmacother 1993; 27: 704–7. 5. Elmore RL, et al. Stability and compatibility of admixtures of intravenous ciprofloxacin and selected drugs. Clin Ther 1996; 18: 246–55.

Stability.

For mention of loss of activity in ciprofloxacin solutions exposed to ultraviolet light see under Precautions, below.

💊 Adverse Effects

Ciprofloxacin is generally well tolerated. The range of adverse effects associated with ciprofloxacin and the other fluoroquinolones is broadly similar to that of earlier quinolones such as nalidixic acid. They most often involve the gastrointestinal tract, CNS, or skin. Gastrointestinal disturbances include nausea, vomiting, diarrhoea, abdominal pain, and dyspepsia and are the most frequent adverse effects. Pseudomembranous colitis, pancreatitis, and dysphagia have been reported rarely. Headache, dizziness, confusion, insomnia, and restlessness are among the commonest effects on the CNS. Others include tremor, drowsiness, nightmares, visual and other sensory disturbances, hallucinations, psychotic reactions, depression, convulsions, and intracranial hypertension. Paraesthesia and peripheral neuropathy have also been reported. In addition to rash and pruritus, hypersensitivity-type reactions affecting the skin have included, rarely, vasculitis, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Photosensitivity has occurred, although it may be more frequent with some other fluoroquinolones such as lomefloxacin and sparfloxacin. Anaphylaxis has been associated with ciprofloxacin and some other quinolones. As with other quinolones, reversible arthralgia or myalgia has sometimes occurred and joint erosions have been documented in immature animals. Tendon damage has also been reported. Other adverse effects reported with ciprofloxacin include crystalluria, transient increases in serum creatinine or blood urea nitrogen and, rarely, acute renal failure secondary to interstitial nephritis. Elevated liver enzyme values, jaundice, and hepatitis have occurred, as have haematological disturbances including eosinophilia, leucopenia, thrombocytopenia and, very rarely, pancytopenia, haemolytic anaemia or agranulocytosis. Cardiovascular adverse effects include tachycardia, hypotension, oedema, syncope, hot flushes, and sweating. Some fluoroquinolones may rarely cause prolongation of the QT interval and ventricular arrhythmias, including torsade de pointes (see below). As with other antibacterials, superinfection with organisms not very susceptible to ciprofloxacin is possible. Such organisms include Candida, Clostridium difficile, and Streptococcus pneumoniae. There is some evidence that fluoroquinolone use may be associated with an increased risk of colonisation by MRSA. Pain and irritation may occur at the site of infusion accompanied rarely by phlebitis or thrombophlebitis. Adverse effects reported after ocular use of ciprofloxacin include local burning or discomfort, keratopathy, corneal staining, corneal precipitates or infiltrates, and photophobia. Local discomfort, pain, or pruritus have occurred after use of ear drops containing ciprofloxacin.
1. Lipsky BA, Baker CA. Fluoroquinolone toxicity profiles: a review focusing on newer agents. Clin Infect Dis 1999; 28: 352–64
2. Ball P, et al. Comparative tolerability of the newer fluoroquinolone antibacterials. Drug Safety 1999; 21: 407–21
3. Rubinstein E. History of quinolones and their side effects. Chemotherapy 2001; 47 (suppl 3): 3–8
4. Leone R, et al. Adverse drug reactions related to the use of fluoroquinolone antimicrobials: an analysis of spontaneous reports and fluoroquinolone consumption data from three Italian regions. Drug Safety 2003; 26: 109–20
5. Stahlmann R, Lode H. Fluoroquinolones in the elderly: safety considerations. Drugs Aging 2003; 20: 289–302
6. Owens RC, Ambrose PG. Antimicrobial safety: focus on fluoroquinolones. Clin Infect Dis 2005; 41 (suppl 2): S144–S157
7. Mehlhorn AJ, Brown DA. Safety concerns with fluoroquinolones. Ann Pharmacother 2007; 41: 1859–66
8. Segev S, et al. Safety of long-term therapy with ciprofloxacin: data analysis of controlled clinical trials and review. Clin Infect Dis 1999; 28: 299–308
9. Heyd A, Haverstock D. Retrospective analysis of the safety profile of oral and intravenous ciprofloxacin in a geriatric population. Clin Ther 2000; 22: 1239–50.

Effects on the blood.

Haematological disturbances including thrombocytopenia,1 eosinophilia,2 leucopenia, and, very rarely, pancytopenia,3 haemolytic anaemia,4 or agranulocytosis have been reported with ciprofloxacin and some other fluoroquinolones. There has also been a case report5 of haemolytic-uraemic syndrome associated with ciprofloxacin therapy; the patient recovered with routine supportive treatment (haemodialysis and plasma exchange) after the drug was stopped. In addition, transient reductions in factor VIII and von Willebrand’s factor leading to bleeding in 2 patients receiving ciprofloxacin has been reported.6 Neutropenia that developed in an elderly patient a few days after starting treatment with intravenous moxifloxacin resolved on stopping the drug.7
1. Starr JA, Ragucci KR. Thrombocytopenia associated with intravenous ciprofloxacin. Pharmacotherapy 2005; 25: 1030–4
2. Mofredj A, et al. Norfloxacin-induced eosinophilia in a cirrhotic patient. Ann Pharmacother 2002; 36: 1107–8
3. Deng JY, Tovar JM. Pancytopenia with levofloxacin therapy for pelvic inflammatory disease in an otherwise healthy young patient. Ann Pharmacother 2006; 40: 1692–3
4. Oh YR, et al. Levofloxacin-induced autoimmune hemolytic anemia. Ann Pharmacother 2003; 37: 1010–13
5. Allan DS, et al. Ciprofloxacin-associated hemolytic-uremic syndrome. Ann Pharmacother 2002; 36: 1000–1002
6. Castaman G, Rodeghiero F. Acquired transitory von Willebrand syndrome with ciprofloxacin. Lancet 1994; 343: 492
7. Chang C-M, et al. Moxifloxacin-associated neutropenia in a cirrhotic elderly woman with lower extremity cellulitis. Ann Pharmacother 2008; 42: 580–3.

Effects on the cardiovascular system.

Prolongation of the QT interval,1,2 sometimes progressing to torsade de pointes,3-8has been associated with ciprofloxacin and other fluoroquinolones although a review9 considered that ciprofloxacin was least likely to produce this effect. Licensed product information recommends that gatifloxacin, gemifloxacin, levofloxacin, lomefloxacin, moxifloxacin, ofloxacin, and sparfloxacin should be avoided in patients with predisposing factors or who are also receiving other drugs that are known to cause this effect and that norfloxacin should be used with caution in such situations.
1. Noel GJ, et al. Effects of three fluoroquinolones on QT interval in healthy adults after single doses. Clin Pharmacol Ther 2003; 73: 292–303
2. Nykamp DL, et al. QTc prolongation associated with combination therapy of levofloxacin, imipramine, and fluoxetine. Ann Pharmacother 2005; 39: 543–6
3. Frothingham R. Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin. Pharmacotherapy 2001; 21: 1468–72
4. Owens RC, Ambrose PG. Torsades de pointes associated with fluoroquinolones. Pharmacotherapy 2002; 22: 663–8
5. Bertino JS, et al. Gatifloxacin-associated corrected QT interval prolongation, torsades de pointes, and ventricular fibrillation in patients with known risk factors. Clin Infect Dis 2002; 34: 861–3
6. Amankwa K, et al. Torsades de pointes associated with fluoroquinolones: importance of concomitant risk factors. Clin Pharmacol Ther 2004; 75: 242–7
7. Dale KM, et al. Moxifloxacin and torsade de pointes. Ann Pharmacother 2007; 41: 336–40
8. Knorr JP, et al. Ciprofloxacin-induced Q-T interval prolongation. Am J Health-Syst Pharm 2008; 65: 547–51
9. Owens RC. QT prolongation with antimicrobial agents: understanding the significance. Drugs 2004; 64: 1091–1124.

Effects on the gast

rointestinal tract. There have been case reports and studies of pseudomembranous colitis or superinfection with Clostridium difficile in patients given ciprofloxacin1-6and other fluoroquinolones7-10 although some commentators have questioned this association and pointed out that other circumstances, such as poor infection control, may be significant contributory factors.
1. Cain DB, O’Connor ME. Pseudomembranous colitis associated with ciprofloxacin. Lancet 1990; 336: 946
2. Bates CJ, et al. Ciprofloxacin and Clostridium difficile infection. Lancet 1990; 336: 1193
3. Low N, Harries A. Ciprofloxacin and pseudomembranous colitis. Lancet 1990; 336: 1510
4. Hillman RJ, et al. Ciprofloxacin as a cause of Clostridium difficile-associated diarrhoea in an HIV antibody-positive patient. J Infect 1990; 21: 205–7
5. McFarland LV, et al. Ciprofloxacin-associated Clostridium difficile disease. Lancet 1995; 346: 977–8
6. Angel CA, et al. Severe ciprofloxacin-associated pseudomembranous colitis in an eight-year-old child. J Pediatr Surg 2004; 39: 1590–2
7. Dan M, Samra Z. Clostridium difficile colitis associated with ofloxacin therapy. Am J Med 1989; 87: 479
8. Ortiz-de-Saracho J, et al. Moxifloxacin-induced Clostridium difficile diarrhea. Ann Pharmacother 2003; 37: 452–3
9. Gaynes R, et al. Outbreak of Clostridium difficile infection in a long-term care facility: association with gatifloxacin use. Clin Infect Dis 2004; 38: 640–5
10. Pépin J, et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec. Clin Infect Dis 2005; 41: 1254–60.

Effects on glucose metabolism.

For the effects of fluoroquinolones, and in particular gatifloxacin, on blood glucose see under Gatifloxacin.

Effects on the kidneys.

A review1 of case reports of renal toxicity (including interstitial nephritis, acute renal failure, acute tubular necrosis, and crystalluria) associated with ciprofloxacin and other fluoroquinolones indicated that such toxicity, although potentially serious, was rare. It was also noted that nearly all patients developing acute renal failure were over 50 years of age. Another review,2 confirming that the problem remained rare, noted that risk factors for quinolone-induced nephrotoxicity seemed to include the particular quinolone chosen, with ciprofloxacin the most often involved, as well as the use of high doses, patient age, inadequate hydration, and use of other nephrotoxic drugs or the presence of other processes likely to contribute to renal damage such as diabetes.
1. Lomaestro BM. Fluoroquinolone-induced renal failure. Drug Safety 2000; 22: 479–85
2. Montagnac R, et al. Les insuffisances rénales aiguës aux quinolones: revue générale à propos d’une observation avec cristallisation liée à la ciprofloxacine. Nephrol Ther 2005; 1: 44–51.

Effects on the liver.

Fluoroquinolones, including ciprofloxacin, may cause elevated liver enzyme values. In most patients this effect is transient and reversible without stopping the drug. More serious cases of hepatotoxicity, including fatalities, have been reported both with ciprofloxacin1-5 and with other fluoroquinolones4,6-14 but they are rare. In many cases the patients were elderly and had co-morbid conditions.
1. Grassmick BK, et al. Fulminant hepatic failure possibly related to ciprofloxacin. Ann Pharmacother 1992; 26: 636–9
2. Sherman O, Beizer JL. Possible ciprofloxacin-induced acute cholestatic jaundice. Ann Pharmacother 1994; 28: 1162–4
3. Villeneuve J-P, et al. Suspected ciprofloxacin-induced hepatotoxicity. Ann Pharmacother 1995; 29: 257–9
4. Jones SE, Smith RH. Quinolones may induce hepatitis. BMJ 1997; 314: 869
5. Contreras MÁ, et al. Severe ciprofloxacin-induced acute hepatitis. Eur J Clin Microbiol Infect Dis 2001; 20: 434–5
6. González Carro P, et al. Fatal subfulminant hepatic failure with ofloxacin. Am J Gastroenterol 2000; 95: 1606
7. Björnsson E, et al. Norfloxacin-induced eosinophilic necrotizing granulomatous hepatitis. Am J Gastroenterol 2000; 95: 3662–4
8. Spahr L, et al. Acute fatal hepatitis related to levofloxacin. J Hepatol 2001; 35: 308–9
9. Karim A, et al. Possible levofloxacin-induced acute hepatocellular injury in a patient with chronic obstructive lung disease. Clin Infect Dis 2001; 33: 2088–90
10. Soto S, et al. Moxifloxacin-induced acute liver injury. Am J Gastroenterol 2002; 97: 1853–4
11. Coleman CI, et al. Possible gatifloxacin-induced fulminant hepatic failure. Ann Pharmacother 2002; 36: 1162–7
12. Schwalm J-D, Lee CH. Acute hepatitis associated with oral levofloxacin therapy in a hemodialysis patient. CMAJ 2003; 168: 847–8
13. Cheung O, et al. Gatifloxacin-induced hepatotoxicity and acute pancreatitis. Ann Intern Med 2004; 140: 73–4
14. Çoban Ş, et al. Levofloxacin-induced acute fulminant hepatic failure in a patient with chronic hepatitis B infection. Ann Pharmacother 2005; 39: 1737–40.

Effects on the musculoskeletal system.

Reversible arthralgia has sometimes occurred with the fluoroquinolones;1 joint erosions have been documented in immature animals. In a report,2 treatment with pefloxacin may have contributed to the destructive arthropathy that occurred in a 17-year-old youth. For a discussion of the use of fluoroquinolones in children and adolescents, see Administration in Children, under Precautions, below. There have been reports3-7 of tendinitis and tendon rupture associated with fluoroquinolones. By July 1995, the UK CSM5 had received 21 reports of tendon damage, often of the Achilles tendon, associated with these antibacterials—11 with ciprofloxacin and 10 with ofloxacin. In a later case-control study8 of a cohort of 46 776 users of fluoroquinolones between July 1992 to June 1998, 704 had Achilles tendinitis and 38 had Achilles tendon rupture; the adjusted relative risk of Achilles tendon disorders with current use was 1.9. The risk of tendon damage is increased by use with corticosteroids and is more common with increasing age:5 the case-control study8 found that the relative risk for current users rose to 3.2 among those aged 60 and over, and to 6.2 in those in this age group also using corticosteroids. Another case-control study9 using data from 1988 to 1998 held on a different UK general practice database reported similar findings and concluded that ofloxacin was associated with a higher risk of tendon damage than other fluoroquinolones. A review10 of the literature between 1966 and 2001 revealed 98 case reports of fluoroquinolone-associated tendon damage. Of these, 36 were associated with pefloxacin therapy and 25 with ciprofloxacin; ofloxacin was associated with 6 cases. Renal disease or impairment was also considered as a risk factor. Onset may be rapid: rupture has occurred within 48 hours of starting therapy.11 The CSM5 warned that at the first sign of pain or inflammation the fluoroquinolone should be withdrawn and the affected limb rested until the tendon symptoms had resolved. Similar warnings have been issued in other countries, but some cases have continued to be reported.12 In the USA the FDA has required a warning to be added to prescribing information for the fluoroquinolones stating that there is an increased risk in patients over 60, in kidney, heart, and lung transplant recipients, and with use of concomitant corticosteroid therapy.13 There have been reports14,15 of rhabdomyolysis in patients given fluoroquinolones, including one fatality associated with levofloxacin therapy.14
1. Alfaham M, et al. Arthropathy in a patient with cystic fibrosis taking ciprofloxacin. BMJ 1987; 295: 699
2. Chevalier X, et al. A case of destructive polyarthropathy in a 17year-old youth following pefloxacin treatment. Drug Safety 1992; 7: 310–14
3. Huston KA. Achilles tendinitis and tendon rupture due to fluoroquinolone antibiotics. N Engl J Med 1994; 331: 748
4. Szarfman A, et al. More on fluoroquinolone antibiotics and tendon rupture. N Engl J Med 1995; 332: 193
5. Committee on Safety of Medicines/Medicines Control Agency. Tendon damage associated with quinolone antibiotics. Current Problems 1995; 21: 8. Also available at: http://www.mhra.gov.uk/ home/idcplg?IdcService=GET_FILE&dDocName= CON2015619&RevisionSelectionMethod=LatestReleased (accessed 12/07/06
6. Carrasco JM, et al. Tendinitis associated with ciprofloxacin. Ann Pharmacother 1997; 31: 120
7. Mathis AS, et al. Levofloxacin-associated Achilles tendon rupture. Ann Pharmacother 2003; 37: 1014–17
8. van der Linden PD, et al. Fluoroquinolones and risk of Achilles tendon disorders: case-control study. BMJ 2002; 324: 1306–7
9. van der Linden PD, et al. Increased risk of Achilles tendon rupture with quinolone antibacterial use, especially in elderly patients taking oral corticosteroids. Arch Intern Med 2003; 163: 1801–7
10. Khaliq Y, Zhanel GG. Fluoroquinolone-associated tendinopathy: a critical review of the literature. Clin Infect Dis 2003; 36: 1404–10
11. Committee on Safety of Medicines/Medicines Control Agency. Reminder: fluoroquinolone antibiotics and tendon disorders. Current Problems 2002; 28: 3–4. Also available at: http:// www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE& dDocName=CON007454&RevisionSelectionMethod= LatestReleased (accessed 12/07/06
12. Adverse Drug Reactions Advisory Committee (ADRAC). Fluoroquinolone antibiotics: remember tendon disorders. Aust Adverse Drug React Bull 2006; 25: 3. Also available at: http:// www.tga.health.gov.au/adr/aadrb/aadr0602.pdf (accessed 12/07/06
13. FDA. Fluoroquinolone Antimicrobial Drugs [ciprofloxacin (marketed as Cipro and generic ciprofloxacin), ciprofloxacin extended release (marketed as Cipro XR and Proquin XR), gemifloxacin (marketed as Factive), levofloxacin (marketed as Levaquin), moxifloxacin (marketed as Avelox), norfloxacin (marketed as Noroxin), and ofloxacin (marketed as Floxin and generic ofloxacin)] (issued 8th July, 2008). Available at: http://www.fda.gov/cder/drug/ InfoSheets/HCP/fluoroquinolonesHCP.htm (accessed 12/08/08
14. Petitjeans F, et al. A case of rhabdomyolysis with fatal outcome after a treatment with levofloxacin. Eur J Clin Pharmacol 2003; 59: 779–80
15. Hsiao S-H, et al. Acute rhabdomyolysis associated with ofloxacin/levofloxacin therapy. Ann Pharmacother 2005; 39: 146–9.

Effects on the nervous system.

By 1991 the UK CSM1 had received 26 reports of convulsions associated with ciprofloxacin, 1 with norfloxacin, and 1 with ofloxacin. It was noted that convulsions could occur both in patients with epilepsy and in those with no history of convulsions. Generalised seizures have been reported in patients given gatifloxacin2 and levofloxacin.3,4 Seizures have also been associated with the use of ear drops containing ciprofloxacin.5 All 5 case reports2-5 involved patients aged 65 years and over; of these, 1 had a history (although unclear) of seizures,2 3 had chronic renal impairment,3-5 and 1 had neither.3 Other reports of CNS toxicity associated with ciprofloxacin have included eosinophilic meningitis,6 delirium,7 and acute psychoses.8,9 Peripheral neuropathy,10 dysaesthesia,11 catatonia,12 hemiparesis,13 and tinnitus14 have also been reported. Acute psychosis occurred15 in a patient using ciprofloxacin eye drops. A review16of published and spontaneous reports found an association between adverse manic reactions and the use of certain antibacterials including ciprofloxacin and ofloxacin. There have also been reports of sleep disturbances17 and of a Tourette-like syndrome18 associated with ofloxacin. Ataxia19and hallucinations20 have been reported with the use of gatifloxacin.
1. Committee on Safety of Medicines. Convulsions due to quinolone antimicrobial agents. Current Problems 32 1991. Also available at: http://www.mhra.gov.uk/home/idcplg? IdcService=GET_FILE&dDocName=CON2024450& RevisionSelectionMethod=LatestReleased (accessed 02/03/07
2. Quigley CA, Lederman JR. Possible gatifloxacin-induced seizure. Ann Pharmacother 2004; 38: 235–7
3. Kushner JM, et al. Seizures associated with fluoroquinolones. Ann Pharmacother 2001; 35: 1194–8
4. Christie MJ, et al. Generalized seizure and toxic epidermal necrolysis following levofloxacin exposure. Ann Pharmacother 2005; 39: 953–5
5. Orr CF, Rowe DB. Eardrop attacks: seizures triggered by ciprofloxacin eardrops. Med J Aust 2003; 178: 343
6. Asperilla MO, et al. Eosinophilic meningitis associated with ciprofloxacin. Am J Med 1989; 87: 589–90
7. Jay GT, Fitzgerald JM. Ciprofloxacin-induced delirium. Ann Pharmacother 1997; 31: 252
8. McCue JD, Zandt JR. Acute psychoses associated with the use of ciprofloxacin and trimethoprim-sulfamethoxazole. Am J Med 1991; 90: 528–9
9. Reeves RR. Ciprofloxacin-induced psychosis. Ann Pharmacother 1992; 26: 930–1
10. Aoun M, et al. Peripheral neuropathy associated with fluoroquinolones. Lancet 1992; 340: 127
11. Zehnder D, et al. Painful dysaesthesia with ciprofloxacin. BMJ 1995; 311: 1204
12. Akhtar S, Ahmad H. Ciprofloxacin-induced catatonia. J Clin Psychiatry 1993; 54: 115–16
13. Rosolen A, et al. Acute hemiparesis associated with ciprofloxacin. BMJ 1994; 309: 1411
14. Paul J, Brown NM. Tinnitus and ciprofloxacin. BMJ 1995; 311: 232
15. Tripathi A, et al. Acute psychosis following the use of topical ciprofloxacin. Arch Ophthalmol 2002; 120: 665–6
16. Abouesh A, et al. Antimicrobial-induced mania (antibiomania): a review of spontaneous reports. J Clin Psychopharmacol 2002; 22: 71–81
17. Upton C. Sleep disturbance in children treated with ofloxacin. BMJ 1994; 309: 1411
18. Thomas RJ, Reagan DR. Association of a Tourette-like syndrome with ofloxacin. Ann Pharmacother 1996; 30: 138–41
19. Mohan N, et al. Oral gatifloxacin-induced ataxia. Am J HealthSyst Pharm 2002; 59: 1894
20. Adams M, Tavakoli H. Gatifloxacin-induced hallucinations in a 19-year-old man. Psychosomatics 2006; 47: 360.

Hypersensitivity.

Hypersensitivity and skin reactions have been associated with ciprofloxacin and other fluoroquinolones. Reports have included anaphylaxis (which has sometimes been fatal, and may occur after the first dose),1-7 serum sickness,8 Stevens-Johnson syndrome,9 toxic epidermal necrolysis (sometimes fatal),10-17 laryngeal oedema,18 and vasculitis.19-21 Fatal vasculitis has been reported with ofloxacin.22
1. Davis H, et al. Anaphylactoid reactions reported after treatment with ciprofloxacin. Ann Intern Med 1989; 111: 1041–3
2. Peters B, Pinching AJ. Fatal anaphylaxis associated with ciprofloxacin in a patient with AIDS related complex. BMJ 1989; 298: 605
3. Wurtz RM, et al. Anaphylactoid drug reactions to ciprofloxacin and rifampicin in HIV-infected patients. Lancet 1989; i: 955–6
4. Assouad M, et al. Anaphylactoid reactions to ciprofloxacin. Ann Intern Med 1995; 122: 396–7
5. Smythe MA, Cappelletty DM. Anaphylactoid reaction to levofloxacin. Pharmacotherapy 2000; 20: 1520–3
6. Ho DY, et al. Anaphylactoid reaction to ciprofloxacin. Ann Pharmacother 2003; 37: 1018–23
7. Sachs B, et al. Fluoroquinolone-associated anaphylaxis in spontaneous adverse drug reaction reports in Germany: differences in reporting rates between individual fluoroquinolones and occurrence after first-ever use. Drug Safety 2006; 29: 1087–1100
8. Slama TG. Serum sickness-like illness associated with ciprofloxacin. Antimicrob Agents Chemother 1990; 34: 904–5
9. Hällgren J, et al. Stevens-Johnson syndrome associated with ciprofloxacin: a review of adverse cutaneous events reported in Sweden as associated with this drug. J Am Acad Dermatol 2003; 49 (suppl): S267–S269
10. Tham TCK, et al. Possible association between toxic epidermal necrolysis and ciprofloxacin. Lancet 1991; 338: 522
11. Moshfeghi M, Mandler HD. Ciprofloxacin-induced toxic epidermal necrolysis. Ann Pharmacother 1993; 27: 1467–9
12. Yerasi AB, Oertel MD. Ciprofloxacin-induced toxic epidermal necrolysis. Ann Pharmacother 1996; 30: 297
13. Livasy CA, Kaplan AM. Ciprofloxacin-induced toxic epidermal necrolysis: a case report. Dermatology 1997; 195: 173–5
14. Melde SL. Ofloxacin: a probable cause of toxic epidermal necrolysis. Ann Pharmacother 2001; 35: 1388–90
15. Sahin MT, et al. Norfloxacin-induced toxic epidermal necrolysis. Ann Pharmacother 2005; 39: 768–70
16. Christie MJ, et al. Generalized seizure and toxic epidermal necrolysis following levofloxacin exposure. Ann Pharmacother 2005; 39: 953–5
17. Islam AFMS, Rahman MS. Levofloxacin-induced fatal toxic epidermal necrolysis. Ann Pharmacother 2005; 39: 1136–7
18. Baciewicz AM, et al. Laryngeal edema related to ciprofloxacin therapy. Ann Pharmacother 1992; 26: 1456
19. Choe U, et al. Ciprofloxacin-induced vasculitis. N Engl J Med 1989; 320: 257–8
20. Stubbings J, et al. Cutaneous vasculitis due to ciprofloxacin. BMJ 1992; 305: 29
21. Drago F, et al. Henoch-Schönlein purpura induced by fluoroquinolones. Br J Dermatol 1994; 131: 448
22. Pace JL, Gatt P. Fatal vasculitis associated with ofloxacin. BMJ 1989; 299: 658.

Superinfection.

Superinfection with Streptococcus pneumoniae has been reported in patients receiving ciprofloxacin.1-3 For references to superinfection with Clostridium difficile and associated pseudomembranous colitis, see under Effects on the Gastrointestinal Tract, above. Fungal otitis externa is also associated with the use of ear drops containing fluoroquinolones.4
1. Righter J. Pneumococcal meningitis during intravenous ciprofloxacin therapy. Am J Med 1990; 88: 548
2. Gordon JJ, Kauffman CA. Superinfection with Streptococcus pneumoniae during therapy with ciprofloxacin. Am J Med 1990; 89: 383–4
3. Lee BL, et al. Infectious complications with respiratory pathogens despite ciprofloxacin therapy. N Engl J Med 1991; 325: 520–1
4. Schrader N, Isaacson G. Fungal otitis externa: its association with fluoroquinolone eardrops. Pediatrics 2003; 111: 1123.

💊 Precautions

Ciprofloxacin should be used with caution in patients with epilepsy or a history of CNS disorders. Care is also necessary in those with renal impairment, G6PD deficiency, or myasthenia gravis. An adequate fluid intake should be maintained during treatment with ciprofloxacin and excessive alkalinity of the urine avoided because of the risk of crystalluria. Since ciprofloxacin and related fluoroquinolones have, like nalidixic acid, been shown to cause degenerative changes in weight-bearing joints of young animals, it has been suggested that these drugs should not generally be used in patients aged under 18 years (see also below), pregnant women, or breast-feeding mothers (but see also below) unless the benefits outweigh the risks. Tendon damage may occur rarely with fluoroquinolones (see Effects on the Musculoskeletal System, above) and treatment should be stopped if patients experience tendon pain, inflammation, or rupture; subsequent use of fluoroquinolones is contra-indicated in these patients. Exposure to strong sunlight or sunlamps should be avoided during treatment with ciprofloxacin. The ability to drive or operate machinery may be impaired, especially when alcohol is also taken. Some fluoroquinolones have the potential to prolong the QT interval (see Effects on the Cardiovascular System, above) and should be avoided or used with caution in patients with QT prolongation or relevant risk factors such as uncorrected electrolyte disturbances, bradycardia, or pre-existing cardiac disease. Certain drugs may also increase the risk (see Interactions, below). Ciprofloxacin and other fluoroquinolones should be avoided in MRSA infections because of the high level of resistance.

Administration in children.

Since ciprofloxacin and other fluoroquinolones can cause degenerative changes in weightbearing joints of young animals they should only be used in children and adolescents where their use may be justified if the benefits outweigh the risks.1-3 For example, ciprofloxacin is licensed in some countries for use in the prophylaxis and treatment of inhalational anthrax and also in the treatment of certain infections in those under 18 years of age (see under Uses and Administration, below). A comparative cohort study2 involving about 500 children and adolescents found that the incidence of musculoskeletal adverse effects was higher (10 cases out of 264 patients) in those taking fluoroquinolones (ciprofloxacin, ofloxacin, or pefloxacin) than in those taking other antibacterials (1 out of 237). In the former group of patients, these adverse effects, mainly arthralgias, were reversible and were most frequent with pefloxacin therapy.
1. Burstein GR, et al. Ciprofloxacin for the treatment of uncomplicated gonorrhea infection in adolescents: does the benefit outweigh the risk? Clin Infect Dis 2002; 35 (suppl 2): S191–S199
2. Chalumeau M, et al. Fluoroquinolone safety in pediatric patients: a prospective, multicenter, comparative cohort study in France. Abstract: Pediatrics 2003; 111: 1427–8. Full version: http://pediatrics.aappublications.org/cgi/reprint/111/6/e714 (accessed 01/11/06
3. American Academy of Pediatrics Committee on Infectious Diseases. The use of systemic fluoroquinolones. Pediatrics 2006; 118: 1287–92.

Breast feeding.

Ciprofloxacin was found to be undetectable in the serum of a breast-fed infant whose mother took ciprofloxacin 500 mg daily for 10 days.1 In another study2 involving 30 women who underwent termination of pregnancy, 10 each were given ciprofloxacin, ofloxacin, or pefloxacin respectively, and all 3 drugs were found to be highly concentrated in breast milk with ratios exceeding 75% of the simultaneous serum concentrations 2 hours after a dose. It was concluded that, because fluoroquinolones had been shown to cause arthropathy in young animals, their potential benefits should be weighed against the risk to the infant before they were considered for use in breast-feeding women. The American Academy of Pediatrics3 considers that the use of ciprofloxacin is usually compatible with breast feeding.
1. Gardner DK, et al. Simultaneous concentrations of ciprofloxacin in breast milk and in serum in mother and breast-fed infant. Clin Pharm 1992; 11: 352–4
2. Giamarellou H, et al. Pharmacokinetics of three newer quinolones in pregnant and lactating women. Am J Med 1989; 87 (suppl 5A): 49S–51S
3. American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001; 108: 776–89. Correction. ibid.; 1029. Also available at: http://aappolicy.aappublications.org/cgi/content/full/ pediatrics%3b108/3/776 (accessed 25/05/04)

Exposure to UV light.

Loss of antibacterial activity has been reported after irradiation of ciprofloxacin solutions by UV light.1In addition to the possible hazard of photosensitivity reactions, a reduction in both cutaneous and circulating levels of ciprofloxacin was predicted in patients exposed to sunlight through window glass or the longer wavelength UVA radiation from sunbeds.1
1. Phillips G, et al. The loss of antibiotic activity of ciprofloxacin by photodegradation. J Antimicrob Chemother 1990; 26: 783–9.

Interference with diagnostic tests.

Ciprofloxacin did not interfere with determination of urinary-glucose concentrations carried out with Clinitest, Diastix, or Tes-Tape,1 but pseudoglycosuria, a false-positive reaction for glucose in urine, has been reported with BM-Test-7 in elderly patients given ciprofloxacin for urinary-tract infections.2
1. Tartaglione TA, Flint NB. Effect of imipenem-cilastatin and ciprofloxacin on tests for glycosuria. Am J Hosp Pharm 1985; 42: 602–5
2. Drysdale L, et al. Pseudoglycosuria and ciprofloxacin. Lancet 1988; ii: 961.

Myasthenia gravis.

Caution is advised in patients with myasthenia gravis given fluoroquinolones after reports of the possible exacerbation of symptoms in a patient,1 and unmasking of subclinical myasthenia gravis in another,2 by ciprofloxacin. Exacerbation of myasthenia gravis has also been reported with other fluoroquinolones including norfloxacin,3 ofloxacin,4 and pefloxacin.5
1. Moore B, et al. Possible exacerbation of myasthenia gravis by ciprofloxacin. Lancet 1988; i: 882
2. Mumford CJ, Ginsberg L. Ciprofloxacin and myasthenia gravis. BMJ 1990; 301: 818
3. Rauser EH, et al. Exacerbation of myasthenia gravis by norfloxacin. DICP Ann Pharmacother 1990; 24: 207–8
4. Azevedo E, et al. Probable exacerbation of myasthenia gravis by ofloxacin. J Neurol 1993; 240: 508
5. Vial T, et al. Aggravation d’une myasthénie sous péfloxacine. Rev Neurol (Paris) 1995; 151: 286–7.

💊 Interactions

Fluoroquinolones, including ciprofloxacin, are known to inhibit the cytochrome P450 isoenzyme CYP1A2 and may increase plasma concentrations of drugs, such as theophylline and tizanidine, that are metabolised by this isoenzyme. Use of ciprofloxacin with tizanidine is contra-indicated, although theophylline may be used providing its dose is reduced and concentrations monitored. Ciprofloxacin is reported to enhance the effect of oral anticoagulants such as warfarin and the oral antidiabetic glibenclamide. Severe hypoglycaemia, sometimes fatal, has occurred in patients also taking glibenclamide. Renal tubular secretion of methotrexate may be inhibited by ciprofloxacin, potentially increasing its toxicity. The excretion of ciprofloxacin or related drugs is reduced and plasma concentrations may be increased by probenecid. Cations such as aluminium, calcium, magnesium, or iron reduce the absorption of oral ciprofloxacin or related drugs when given together. Changes in the pharmacokinetics of fluoroquinolones have been reported when given with histamine H 2 antagonists, possibly due to changes in gastric pH, but do not seem to be of much clinical significance. Transient increases in serum creatinine have occurred when ciprofloxacin is given with ciclosporin; monitoring of serum creatinine concentrations is recommended. Altered serum concentrations of phenytoin have been reported in patients also receiving ciprofloxacin. Further details concerning some of these interactions, and others, are given below. Some fluoroquinolones have the potential to prolong the QT interval (see Effects on the Cardiovascular System, above) and should be avoided in patients also receiving class Ia antiarrhythmic drugs (such as quinidine and procainamide) or class III antiarrhythmics (such as amiodarone and sotalol). In addition, caution should be exercised when they are used with other drugs known to have this effect (such as the antihistamines astemizole and terfenadine, cisapride, erythromycin, pentamidine, phenothiazines, or tricyclic antidepressants). For physical or chemical incompatibilities with ciprofloxacin, see above.

Analgesics.

Use of fenbufen with fluoroquinolones may increase the incidence of fluoroquinolone CNS adverse effects. Reviews1,2 have noted cases of convulsions associated with the use of fenbufen and enoxacin reported to the Japanese regulatory authorities. The UK CSM3 has recognised that convulsions may occur due to an interaction between the fluoroquinolones and NSAIDs; by 1991, 3 such interactions had been reported to them. Adverse neurological effects have also been reported in a patient receiving naproxen and chloroquine when ciprofloxacin was given, which abated when the antirheumatic drugs were stopped.4 Ciprofloxacin also interacts with opioid analgesics; peak serum concentrations of ciprofloxacin given by mouth pre-operatively were significantly reduced when intramuscular papaveretum was injected.5 In the UK, licensed product information for ciprofloxacin tablets recommends that opioid premedication should not be used if ciprofloxacin is given for surgical infection prophylaxis.
1. Janknegt R. Drug interactions with quinolones. J Antimicrob Chemother 1990; 26 (suppl D): 7–29
2. Christ W. Central nervous system toxicity of quinolones: human and animal findings. J Antimicrob Chemother 1990; 26 (suppl B): 219–25
3. Committee on Safety of Medicines. Convulsions due to quinolone antimicrobial agents. Current Problems 32 1991. Also available at: http://www.mhra.gov.uk/home/idcplg?IdcService=GET_FILE& dDocName=CON2024450&RevisionSelectionMethod= LatestReleased (accessed 02/03/07
4. Rollof J, Vinge E. Neurologic adverse effects during concomitant treatment with ciprofloxacin, NSAIDs, and chloroquine: possible drug interaction. Ann Pharmacother 1993; 27: 1058–9
5. Morran C, et al. Brief report: pharmacokinetics of orally administered ciprofloxacin in abdominal surgery. Am J Med 1989; 87 (suppl 5A): 86S–88S.

Antacids and metal ions.

The absorption of ciprofloxacin and other fluoroquinolones is reduced by antacids containing aluminium or magnesium and also by calcium, iron, and zinc salts.1 Sucralfate releases aluminium ions in the stomach and thereby reduces the absorption of ciprofloxacin2,3 and other fluoroquinolones, including norfloxacin,4 ofloxacin, and sparfloxacin.5 In addition, antacids or oral iron preparations might antagonise the antibacterial activity of fluoroquinolones within the gut lumen.6 Dairy products with a high calcium content may also interfere with the absorption of some fluoroquinolones.7-9Enteral feeds, which contain cations, have also been found to reduce absorption of ciprofloxacin.10 A reduction in ciprofloxacin bioavailability has also been reported after chewable tablets of didanosine which contain aluminium and magnesium ion buffering agents.11 It is recommended that oral ciprofloxacin should be given at least 2 hours before or 6 hours after such products; similar advice also applies to other fluoroquinolones.
1. Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones: 1995 update. Drug Safety 1995; 12: 314–33
2. Garrelts JC, et al. Sucralfate significantly reduces ciprofloxacin concentrations in serum. Antimicrob Agents Chemother 1990; 34: 931–3
3. Van Slooten AD, et al. Combined use of ciprofloxacin and sucralfate. DICP Ann Pharmacother 1991; 25: 578–82
4. Parpia SH, et al. Sucralfate reduces the gastrointestinal absorption of norfloxacin. Antimicrob Agents Chemother 1989; 33: 99–102
5. Kamberi M, et al. The effect of staggered dosing of sucralfate on oral bioavailability of sparfloxacin. Br J Clin Pharmacol 2000; 49: 98–103
6. Lewin CS, Smith JT. 4-Quinolones and multivalent ions. J Antimicrob Chemother 1990; 26: 149
7. Neuvonen PJ, et al. Interference of dairy products with the absorption of ciprofloxacin. Clin Pharmacol Ther 1991; 50: 498–502
8. Kivistö KT, et al. Inhibition of norfloxacin absorption by dairy products. Antimicrob Agents Chemother 1992; 36: 489–91
9. Neuvonen PJ, Kivistö KT. Milk and yoghurt do not impair the absorption of ofloxacin. Br J Clin Pharmacol 1992; 33: 346–8
10. Healy DP, et al. Ciprofloxacin absorption is impaired in patients given enteral feedings orally and via gastrostomy and jejunostomy tubes. Antimicrob Agents Chemother 1996; 40: 6–10
11. Sahai J, et al. Cations in the didanosine tablet reduce ciprofloxacin bioavailability. Clin Pharmacol Ther 1993; 53: 292–7.

Antibacterials.

The simultaneous use of parenteral ciprofloxacin and azlocillin has resulted in higher and more prolonged serum concentrations of ciprofloxacin.1 Steady-state plasma concentrations of moxifloxacin are significantly reduced when given with rifampicin and isoniazid for the treatment of tuberculosis.2
1. Barriere SL, et al. Alteration in the pharmacokinetic disposition of ciprofloxacin by simultaneous administration of azlocillin. Antimicrob Agents Chemother 1990; 34: 823–6
2. Nijland HMJ, et al. Rifampicin reduces plasma concentrations of moxifloxacin in patients with tuberculosis. Clin Infect Dis 2007; 45: 1001–7.

Anticoagulants.

For reports of ciprofloxacin and other fluoroquinolones enhancing the effect of oral anticoagulants, see under Warfarin.

Antidiabetics.

For reference to elevated glibenclamide concentrations in patients who were also given ciprofloxacin.

Antiepileptics.

For conflicting reports of the effect of ciprofloxacin on serum-phenytoin concentrations.

Antifungals.

Both fluconazole and levofloxacin can prolong the QT interval. The simultaneous use of intravenous levofloxacin and fluconazole resulted in an episode of torsade de pointes in a patient on haemodialysis.1
1. Gandhi PJ, et al. Fluconazole- and levofloxacin-induced torsades de pointes in an intensive care unit patient. Am J HealthSyst Pharm 2003; 60: 2479–83.

Antimigraine drugs.

For a recommendation to reduce the dosage of zolmitriptan when given with ciprofloxacin.

Antineoplastics.

Absorption of oral ciprofloxacin appears to be reduced after cytotoxic chemotherapy.1 For reference to the effect of ciprofloxacin on the pharmacokinetics of cyclophosphamide.
1. Johnson EJ, et al. Reduced absorption of oral ciprofloxacin after chemotherapy for haematological malignancy. J Antimicrob Chemother 1990; 25: 837–42.

Antivirals.

Both ciprofloxacin and foscarnet can cause convulsions and 2 patients developed generalised tonic-clonic seizures while receiving the drugs together.1 For reference to reduction of ciprofloxacin bioavailability due to the antacid content of chewable didanosine tablets, see under Antacids and Metal Ions, above.
1. Fan-Havard P, et al. Concurrent use of foscarnet and ciprofloxacin may increase the propensity for seizures. Ann Pharmacother 1994; 28: 869–72.

Anxiolytics.

For reference to the effect of ciprofloxacin on the pharmacokinetics of diazepam, midazolam, and temazepam, see under Diazepam.

Immunosuppressants.

For reference to possible interaction between fluoroquinolones and ciclosporin, see Quinolones. For a pharmacokinetic study reporting reduced exposure to mycophenolate mofetil when given with norfloxacin or norfloxacin plus metronidazole.

Muscle relaxants.

For a report of ciprofloxacin increasing the plasma concentrations of tizanidine.

Xanthines.

Ciprofloxacin and other fluoroquinolones (to a greater or lesser extent) decrease the clearance of theophylline and caffeine from the body. Seizures have occurred in patients given ciprofloxacin and theophylline and in one such report1 serum-theophylline concentrations were normal.
1. Bader MB. Role of ciprofloxacin in fatal seizures. Chest 1992; 101: 883–4.

💊 Antimicrobial Action

Ciprofloxacin is bactericidal and acts by inhibiting DNA gyrase and topoisomerase IV, which are essential enzymes in the reproduction of bacterial DNA. It has a broader spectrum of activity and is more potent in vitro than the non-fluorinated quinolone nalidixic acid although resistance to many species or strains previously sensitive is emerging. Activity may be reduced in acid media and in the presence of urine but not of serum. Spectrum of activity. Among Gram-negative aerobic bacteria, ciprofloxacin may be active in vitro against Enterobacteriaceae, including Escherichia coli and Citrobacter, Enterobacter, Klebsiella, Proteus, Providencia, Salmonella, Serratia, Shigella, and Yersinia spp. It may also exhibit activity against Pseudomonas aeruginosa and Neisseria gonorrhoeae. H. influenzae, Moraxella catarrhalis (Branhamella catarrhalis), and N. meningitidis are all sensitive. Other Gram-negative aerobic bacteria reported to be sensitive to ciprofloxacin have included Gardnerella vaginalis, Helicobacter pylori, Legionella spp., Pasteurella multocida, and Vibrio spp. Variable activity has been reported against Acinetobacter spp., Brucella melitensis, and Campylobacter spp. Among Gram-positive aerobic bacteria, ciprofloxacin is active against staphylococci, including penicillinaseproducing and penicillinase-nonproducing strains, and against some MRSA. Streptococci, in particular Streptococcus pneumoniae and enterococci, are less susceptible. Other Gram-positive bacteria sensitive to ciprofloxacin in vitro are Bacillus spp.; variable activity has been noted for Corynebacterium spp. Most anaerobic bacteria, including Bacteroides fragilis and Clostridium difficile, are resistant to ciprofloxacin, although some other Clostridium spp. may be susceptible. Ciprofloxacin has some activity against mycobacteria, mycoplasmas, rickettsias, Chlamydia trachomatis, and Ureaplasma urealyticum. Acquired resistance. Resistant strains, particularly of MRSA, Ps. aeruginosa, E. coli, Klebsiella pneumoniae, C. jejuni, N. gonorrhoeae, and Str. pneumoniae have emerged during treatment with ciprofloxacin although there are widely differing patterns of resistance geographically. Resistance to ciprofloxacin has usually been chromosomally mediated although plasma-mediated resistance has recently been noted.

💊 Pharmacokinetics

Ciprofloxacin is rapidly and well absorbed from the gastrointestinal tract. Oral bioavailability is about 70 to 80% and a peak serum concentration of about 2.4 micrograms/mL occurs 1 to 2 hours after a 500-mg oral dose. Absorption of ciprofloxacin tablets may be delayed by the presence of food, but is not substantially affected overall. Plasma protein binding ranges from 20 to 40%. Ciprofloxacin is widely distributed in the body and tissue penetration is generally good. It appears in the CSF, but concentrations are only about 10% of those in serum when the meninges are not inflamed. Ciprofloxacin crosses the placenta and is also distributed into breast milk. High concentrations are achieved in bile. The elimination half-life is about 3 to 5 hours and there is evidence of modest accumulation. Half-life may be prolonged in renal impairment (a value of 8 hours has been reported in end-stage renal disease) and to some extent in the elderly. However, no dose adjustment is usually necessary in patients with renal impairment unless it is severe; similarly, usual doses can be given to the elderly except in those with severe renal impairment. There is limited information on the effect of hepatic impairment; the half-life of ciprofloxacin has been reported to be slightly prolonged in patients with severe cirrhosis of the liver. With one or two exceptions, most studies have shown that the pharmacokinetics of ciprofloxacin are not markedly affected by cystic fibrosis. Ciprofloxacin is eliminated principally by urinary excretion, but non-renal clearance may account for about one-third of elimination and includes hepatic metabolism, biliary excretion, and possibly transluminal secretion across the intestinal mucosa. At least 4 active metabolites have been identified. Oxociprofloxacin appears to be the major urinary metabolite and sulfociprofloxacin the primary faecal metabolite. Urinary excretion is by active tubular secretion as well as glomerular filtration and is reduced by probenecid; it is virtually complete within 24 hours. About 40 to 50% of an oral dose is excreted unchanged in the urine and about 15% as metabolites. Up to 70% of a parenteral dose may be excreted unchanged within 24 hours and 10% as metabolites. Faecal excretion over 5 days has accounted for 20 to 35% of an oral dose and 15% of an intravenous dose. Only small amounts of ciprofloxacin are removed by haemodialysis or peritoneal dialysis.

General pharmacokinetics.

Reviews of the pharmacokinetics of ciprofloxacin1 and the fluoroquinolones in general.2,3
1. Vance-Bryan K, et al. Clinical pharmacokinetics of ciprofloxacin. Clin Pharmacokinet 1990; 19: 434–61
2. Aminimanizani A, et al. Comparative pharmacokinetics and pharmacodynamics of the newer fluoroquinolone antibacterials. Clin Pharmacokinet 2001; 40: 169–187
3. Wispelwey B. Clinical implications of pharmacokinetics and pharmacodynamics of fluoroquinolones. Clin Infect Dis 2005; 41 (suppl 2): S127–S135.

💊 Uses and Administration

Ciprofloxacin is a fluorinated 4-quinolone or fluoroquinolone antibacterial with a wider spectrum of activity than nalidixic acid (see Antimicrobial Action, above) and more favourable pharmacokinetics allowing its use in systemic infections. It has been used in the treatment of infections including anthrax, biliary-tract infections, infected bites and stings, bone and joint infections, cat scratch disease, chancroid, exacerbations of cystic fibrosis, ear, nose, and throat infections (including otitis externa, otitis media, and sinusitis), HACEK endocarditis, gastro-enteritis (including travellers’ diarrhoea and campylobacter enteritis, cholera, salmonella enteritis, shigellosis, and yersinia enteritis), gonorrhoea, granuloma inguinale, infections in immunocompromised patients (neutropenia), legionnaires’ disease, pelvic inflammatory disease, peritonitis, plague, lower respiratory-tract infections (including pseudomonal infections in cystic fibrosis, but excluding infections due to Streptococcus pneumoniae such as pneumococcal pneumonia), rickettsial infections (including Q fever, spotted fevers, and typhus), septicaemia, skin infections, a 7- to 10-day course of treatment with an oral dose of 500 to 750 mg twice daily is similarly recommended; treatment may need to be extended to 60 days if infection is due to aerosol exposure. Doses should be reduced in patients with severe renal impairment (see below). Single oral doses of 250 or 500 mg or single intravenous doses of 100 mg are used for the treatment of gonorrhoea, depending upon patterns of resistance. A single oral dose of 750 mg is used for surgical infection prophylaxis, given 60 to 90 minutes before the procedure. Although unlicensed in the UK, the BNF suggests a single oral dose of 500 mg for meningococcal meningitis prophylaxis. For details of doses in children, including infants and adolescents, see below. For corneal ulcers and superficial ocular infections caused by susceptible strains of bacteria ciprofloxacin is given as the hydrochloride in eye drops and eye ointment containing the equivalent of 0.3% of ciprofloxacin. Ciprofloxacin is also used topically as the hydrochloride in ear drops containing the equivalent of 0.2 or 0.3% of ciprofloxacin, usually with a corticosteroid such as dexamethasone or hydrocortisone, for the treatment of otitis externa and chronic suppurative otitis media caused by susceptible strains of bacteria.
1. von Rosenstiel N, Adam D. Quinolone antibacterials: an update of their pharmacology and therapeutic use. Drugs 1994; 47: 872–901
2. Balfour JA, Goa KL, eds. Proceedings of the 5th International symposium on new quinolones. Drugs 1995; 49 (suppl 2): 1–505
3. Walker RC. The fluoroquinolones. Mayo Clin Proc 1999; 74: 1030–7
4. Smith A, et al. Fluoroquinolones: place in ocular therapy. Drugs 2001; 61: 747–61
5. Schaeffer AJ. The expanding role of fluoroquinolones. Am J Med 2002; 113 (suppl 1A): 45S–54S
6. Zhanel GG, et al. A critical review of the fluoroquinolones: focus on respiratory infections. Drugs 2002; 62: 13–59
7. Carson C, Naber KG. Role of fluoroquinolones in the treatment of serious bacterial urinary tract infections. Drugs 2004; 64: 1359–73
8. Shams WE, Evans ME. Guide to selection of fluoroquinolones in patients with lower respiratory tract infections. Drugs 2005; 65: 949–91
9. Andriole VT. The quinolones: past, present, and future. Clin Infect Dis 2005; 41 (suppl 2): S113–S119
10. Davis R, et al. Ciprofloxacin: an updated review of its pharmacology, therapeutic efficacy and tolerability. Drugs 1996; 51: 1019–74
11. Campoli-Richards DM, et al. Ciprofloxacin: a review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 1998; 35: 373–447
12. Gould FK, et al., eds. Ten years of ciprofloxacin: the past, present and future. J Antimicrob Chemother 1999; 43 (suppl A): 1–134
13. Blondeau JM. Current issues in the management of urinary tract infections: extended-release ciprofloxacin as a novel treatment option. Drugs 2004; 64: 611–28.

Administration in children.

Ciprofloxacin is not recommended for general use in children and adolescents (see under Precautions, above) but, if considered essential, UK licensed product information recommends oral doses of 5 to 15 mg/kg twice daily or intravenous doses of 4 to 8 mg/kg twice daily. The BNFC suggests that similar doses may be given to those as young as 1 month of age and that neonates may be given 7.5 mg/kg by mouth twice daily or 5 mg/kg by intravenous infusion twice daily. It is also licensed in different doses for specific indications as outlined below. Ciprofloxacin is licensed in the UK and the USA for the treatment and postexposure prophylaxis of inhalation anthrax in children and adolescents. A 60-day course of treatment with initial intravenous doses of 10 mg/kg (to a maximum of 400 mg) twice daily followed by oral doses of 15 mg/kg (to a maximum of 500 mg) twice daily is recommended; the BNFC suggests that similar doses may be given to those as young as 1 month of age. Although unlicensed, the same regimen is recommended by UK and US public health agencies for the treatment of gastrointestinal anthrax. In the treatment of cutaneous anthrax (also unlicensed), a 7- to 10-day course of treatment with an oral dose of up to 15 mg/kg twice daily is similarly recommended; treatment may need to be extended to 60 days if infection is due to aerosol exposure. It is also licensed in the UK for acute exacerbations of cystic fibrosis associated with Pseudomonas aeruginosa infection in those aged 5 to 17 years. An oral dose of 20 mg/kg (to a maximum of 750 mg) twice daily or an intravenous dose of 10 mg/kg (to a maximum of 400 mg) three times daily is recommended. Although not licensed for younger children, the BNFC suggests giving those aged 1 month to 5 years an oral dose of 5 to 15 mg/kg twice daily or an intravenous dose of 4 to 8 mg/kg twice daily. In the USA, ciprofloxacin is also licensed for complicated urinary-tract infections or pyelonephritis caused by Escherichia coli in those aged 1 to 17 years. An oral dose of 10 to 20 mg/kg (to a maximum of 750 mg) twice daily or an intravenous dose of 6 to 10 mg/kg (to a maximum of 400 mg) three times daily is recommended. Although unlicensed in the UK, the BNFC suggests a single oral dose of 125 mg for meningococcal meningitis prophylaxis in children aged 2 to 5 years; children aged 5 to 12 years may be given a single oral dose of 250 mg, and those aged over 12 years a single oral dose of 500 mg. Single oral doses of 500 mg have also been suggested for the treatment of gonorrhoea in those over 12 years of age.

Administration in renal impairment.

The dose of ciprofloxacin should be reduced in adult patients with renal impairment by either reducing the total daily dose and/or by increasing the dosage interval in accordance with their creatinine clearance (CC); ideally plasma concentrations of ciprofloxacin should be monitored. In the UK, halving the usual daily oral or intravenous dose in those with a CC of less than 20 mL/minute is recommended. In the USA, the following doses are recommended:
CC 30 to 50 mL/minute: up to 500 mg by mouth every 12 hours or the usual dose by intravenous infusion
CC 5 to 29 mL/minute: up to 500 mg by mouth every 18 hours or up to 400 mg by intravenous infusion every 18 to 24 hours
haemodialysis or peritoneal dialysis patients: up to 500 mg by mouth every 24 hours after dialysis A pharmacokinetic study in 10 critically ill patients undergoing continuous renal replacement therapy with either venovenous haemofiltration or haemodiafiltration suggested that a dose of ciprofloxacin 400 mg every 24 hours would be suitable in such situations.1 There appears to be little guidance on the use of ciprofloxacin in paediatric patients with renal impairment but the BNFC states that half the usual dose should be used for those with a CC of less than 20 mL/minute per 1.73 m2.
1. Malone RS, et al. Pharmacokinetics of levofloxacin and ciprofloxacin during continuous renal replacement therapy in critically ill patients. Antimicrob Agents Chemother 2001; 45: 2949–54.

Inflammatory bowel disease.

Ciprofloxacin has been given, sometimes with metronidazole, to treat active Crohn’s disease1,2.
1. Prantera C, et al. An antibiotic regimen for the treatment of active Crohn’s disease: a randomized, controlled clinical trial of metronidazole plus ciprofloxacin. Am J Gastroenterol 1996; 91: 328–32
2. Ishikawa T, et al. Metronidazole plus ciprofloxacin therapy for active Crohn’s disease. Intern Med 2003; 42: 318–21.

Tu b e r c u l o s i s .

Reviews1,2 of data obtained from controlled studies, cohorts, and case series, published up to March 2006, evaluating the clinical efficacy of fluoroquinolones for the treatment of tuberculosis concluded that substituting or adding fluoroquinolones (in particular the older fluoroquinolones such as ciprofloxacin or ofloxacin) to established first-line treatment regimens did not confer additional benefits, although the newer fluoroquinolones are reported to have good in-vitro (levofloxacin, gatifloxacin, moxifloxacin) and in-vivo (gatifloxacin and moxifloxacin) bactericidal activity against Mycobacterium tuberculosis.2 There are very few controlled studies evaluating the use of fluoroquinolones in multi-drug resistant tuberculosis, but 2 retrospective studies support their effectiveness.2 WHO guidelines3,4recommend that patients with multi-drug resistant tuberculosis and those who relapse after completing standard treatment regimens should receive second-line antituberculous drugs as part of a DOTS-plus regimen; such drugs do include ciprofloxacin and ofloxacin, as well as gatifloxacin, levofloxacin, and moxifloxacin. The usual recommended oral doses during the initial phase are as follows:
ciprofloxacin: 1 to 1.5 g daily
gatifloxacin: 400 mg daily
moxifloxacin: 400 mg daily
levofloxacin: 750 mg daily
ofloxacin: 400 mg twice daily
1. Ziganshina LE, Squire SB. Fluoroquinolones for treating tuberculosis. Available in The Cochrane Database of Systematic Reviews; Issu
1. Chichester: John Wiley; 2008 (accessed 07/07/08)
2. Moadebi S, et al. Fluoroquinolones for the treatment of pulmonary tuberculosis. Drugs 2007; 67: 2077–99
3. WHO. Treatment of tuberculosis: guidelines for national programmes. 3rd ed. Geneva: WHO, 2003 (and 2004 revision). Available at: http://whqlibdoc.who.int/hq/2003/ WHO_CDS_TB_2003.313_eng.pdf (accessed 24/01/07
4. WHO. Guidelines for the programmatic management of drugresistant tuberculosis. Geneva: WHO, 2006. Available at: http:// whqlibdoc.who.int/publications/2006/9241546956_eng.pdf (accessed 03/03/08)

💊 Preparations

BP 2008: Ciprofloxacin Intravenous Infusion; Ciprofloxacin Tablets; USP 31: Ciprofloxacin and Dexamethasone Otic Suspension; Ciprofloxacin Injection; Ciprofloxacin Ophthalmic Ointment; Ciprofloxacin Ophthalmic Solution; Ciprofloxacin Tablets.

Proprietary Preparations

Arg.: Argeflox; Atibax C; Biotic; Blader†; Ciloxan; Cipro; Cipro-Otico; Ciprotenk; Cirflox-G; Ciriax; Crisacide; Exertial; Floraxina; Gino Ciriax; Golysine; Lorbifloxacina; Medaflox; Microsulf; Neflox; Novidat; Ocefax; Omaflaxina†; Plusgin†; Quisegen; Rexner; Septicide; Ultramicina; Austral.: CFlox; Ciloquin; Ciloxan; Ciprol; Ciproxin; Profloxin; Proquin; Austria: Agyr†; Ciflox; Ciloxan; Cipromed; Ciprostad; Ciproxin; Belg.: Ciloxan; Ciprobel; Ciproxine; Docciproflo; Braz.:Published January 23, 2019.