Basic Information
ID DDInter1791 and DDInter384
Interaction Coadministration with ciprofloxacin may significantly increase the serum concentrations of theophylline and the associated risk of toxicity. The mechanism is ciprofloxacin inhibition of theophylline metabolism via CYP450 1A2.
Management The use of theophylline or its salts in combination with ciprofloxacin should generally be avoided. If coadministration is required, theophylline dosage may need to be reduced. Pharmacologic response and serum levels should be closely monitored following initiation, discontinuation or change of dosage of ciprofloxacin, and the theophylline dosage adjusted accordingly. Patients should be advised to contact their physician if they experience signs and symptoms suggestive of theophylline toxicity such as nausea, vomiting, diarrhea, anorexia, headache, tremor, irritability, confusion, insomnia, seizure, palpitation, and arrhythmia.
References [1] Wijnands WJ, Vree TB "Interaction between the fluoroquinolones and the bronchodilator theophylline." J Antimicrob Chemother 22 (1988): 109-14 [2] Davis RL, Quenzer RW, Kelly HW, Powell JR "Effect of the addition of ciprofloxacin on theophylline pharmacokinetics in subjects inhibited by cimetidine." Ann Pharmacother 26 (1992): 11-3 [3] Bader MB "Role of ciprofloxacin in fatal seizures." Chest 101 (1992): 883-4 [4] Grasela TH, Dreis MW "An evaluation of the quinolone-theophylline interaction using the Food and Drug Administration spontaneous reporting system." Arch Intern Med 152 (1992): 617-21 [5] Semel JD, Allen N "Seizures in patients simultaneously receiving theophylline and imipenem or ciprofloxacin or metronidazole." South Med J 84 (1991): 465-8 [6] Thomson AH, Thomson GD, Hepburn M, Whiting B "A clinically significant interaction between ciprofloxacin and theophylline." Eur J Clin Pharmacol 33 (1987): 435-6 [7] Richardson JP "Theophylline toxicity associated with the administration of ciprofloxacin in a nursing home patient." J Am Geriatr Soc 38 (1990): 236-8 [8] Karki SD, Bentley DW, Raghavan M "Seizure with ciprofloxacin and theophylline combined therapy." DICP 24 (1990): 595-6 [9] Takagi K, Hasegawa T, Ogura Y, et al "Comparative studies on interaction between theophylline and quinolones." J Asthma 25 (1988): 63-71 [10] Rockwood RP, Embardo LS "Theophylline, ciprofloxacin, erythromycin: a potentially harmful regimen." Ann Pharmacother 27 (1993): 651-2 [11] Schwartz J, Jauregui L, Lettieri J, Bachmann K "Impact of ciprofloxacin on theophylline clearance and steady-state concentrations in serum." Antimicrob Agents Chemother 32 (1988): 75-7 [12] Batty KT, Davis TM, Ilett KF, Dusci LJ, Langton SR "The effect of ciprofloxacin on theophylline pharmacokinetics in healthy subjects." Br J Clin Pharmacol 39 (1995): 305-11 [13] Mizuki Y, Fujiwara I, Yamaguchi T "Pharmacokinetic interactions related to the chemical structures of fluoroquinolones." J Antimicrob Chemother 37 ( Suppl (1996): 41-55 [14] Robson RA, Begg EJ, Atkinson HC, et al "Comparative effects of ciprofloxacin and lomefloxacin on the oxidative metabolism of theophylline." Br J Clin Pharmacol 29 (1990): 491-3 [15] Upton RA "Pharmacokinetic interactions between theophylline and other medication (Part I)." Clin Pharmacokinet 20 (1991): 66-80 [16] Segev S. Rehavi M, Rubinstein E "Quinolones, theophylline, and diclofenac interactions with the gamma-aminobutyric acid receptor." Antimicrob Agents Chemother 32 (1988): 1624-6 [17] Holden R "Probable fatal interaction between ciprofloxacin and theophylline." Br Med J 297 (1988): 1339 [18] Bachmann KA, Schwartz JI, Jauregui L "Predicting the ciprofloxacin-theophylline interaction from single plasma theophylline measurements." Br J Clin Pharmacol 26 (1988): 191-4 [19] Loi CM, Parker BM, Cusack BJ, Vestal RE "Aging and drug interactions .3. individual and combined effects of cimetidine and ciprofloxacin on theophylline metabolism in healthy male and female nonsmokers." J Pharmacol Exp Ther 280 (1997): 627-37 [20] Borcherding SM, Stevens R, Nicholas RA, Corley CR, Self T "Quinolones: a practical review of clinical uses, dosing considerations, and drug interactions." J Fam Pract 42 (1996): 69-78 [21] Prince RA, Casabar E, Adair CG, et al "Effect of quinolone antimicrobials on theophylline pharmacokinetics." J Clin Pharmacol 29 (1989): 650-4 [22] Spivey JM, Laughlin PH, Goss TF, et al "Theophylline toxicity secondary to ciprofloxacin administration." Ann Emerg Med 20 (1991): 1131-4 [23] Duraski RM "Ciprofloxacin-induced theophylline toxicity." South Med J 81 (1988): 1206 [24] Bem JL, Mann RD "Danger of interaction between ciprofloxacin and theophylline." Br Med J (Clin Res Ed) 296 (1988): 1131 [25] Edwards DJ, Bowles SK, Svensson CK, Rybak MJ "Inhibition of drug metabolism by quinolone antibiotics." Clin Pharmacokinet 15 (1988): 194-204 [26] Wijnands GJ, Vree TB, Janssen TJ, Guelen PJ "Drug-drug interactions affecting fluoroquinolones." Am J Med 87 (1989): s47-51 [27] Polk RE "Drug-drug interactions with ciprofloxacin and other fluoroquinolones." Am J Med 87 (1989): s76-81 [28] Wijnands WJ, Vree TB, Baars AM, van Herwaarden CL "Steady-state kinetics of the quinolone derivatives ofloxacin, enoxacin, ciprofloxacin and pefloxacin during maintneance treatment with theophylline." Drugs 34 (1987): 159-69 [29] Raoof S, Wollschlager C, Khan FA "Ciprofloxacin increases serum levels of theophylline." Am J Med 82 (1987): 115-8 [30] Yuk JH, Nightingale CH, Sweeney KR, Quintiliani R, Lettieri JT, Forst RW "Relative bioavailability in healthy volunteers of ciprofloxacin administered through a nasogastric tube with and without enteral feeding." Antimicrob Agents Chemother 33 (1989): 1118-20 [31] Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67 [32] Neuhofel AL, Wilton JH, Victory JM, Hejmanowsk LG, Amsden GW "Lack of bioequivalence of ciprofloxacin when administered with calcium-fortified orange juice: a new twist on an old interaction." J Clin Pharmacol 42 (2002): 461-6 [33] "Product Information. Cipro (ciprofloxacin)." Bayer, West Haven, CT. [34] Yuk JH, Nightingale CH, Quintiliani R "Absorption of ciprofloxacin administered through a nasogastric or a nasoduodenal tube in volunteers and patients receiving enteral nutrition." Diagn Microbiol Infect Dis 13 (1990): 99-102 [35] Noer BL, Angaran DW "The effect of enteral feedings on ciprofloxacin pharmacokinetics." Pharmacotherapy 10 (1990): 254 [36] Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K "Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects." Eur J Clin Pharmacol 44 (1993): 295-8 [37] Jonkman JH, Sollie FA, Sauter R, Steinijans VW "The influence of caffeine on the steady-state pharmacokinetics of theophylline." Clin Pharmacol Ther 49 (1991): 248-55 [38] Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67
Alternative for Theophylline R03D
Omalizumab Tezepelumab Benralizumab Reslizumab Dyphylline Mepolizumab
Bromotheophylline
Alternative for Ciprofloxacin J01R
Tinidazole Cefepime Secnidazole Cefixime Levofloxacin

S03A
Polymyxin B Chloramphenicol Gentamicin Chlorhexidine Neomycin

J01M
Gatifloxacin
More
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.