Ciprofloxacin Caffeine

Ciprofloxacin (Cipro, Cipro XR, Proquin XR) [Antibiotic/ Fluoroquinolone] Uses Rx lower resp tract, sinuses, skin skin structure, bone/joints, urinary tract Infxns including prostatitis Action Quinolone antibiotic DNA gyrase Dose Adults. 250-750 mg PO ql2h XR 500-1000 mg PO q24h or 200-400 mg IV ql2h in renal impair Caution [C, /-] Children <18 y Contra Component sensitivity Disp Tabs, susp, inj SE Restlessness, N/V/D, rash, ruptured tendons, T LFTs Interactions T Effects Wf probenecid T effects OF diazepam, theophylline, caffeine, metoprolol, propranolol, phenytoin, warfarin effects W/ antacids, didanosine, Fe salts. Mg, sucralfate, Na bicarbonate,... 

Caffeine [P] Ciprofloxacin, enoxacin, pipedemic acid, and to a lesser extent, norfloxacin, inhibit caffeine metabolism. 

CNS, smooth muscle T diuresis X- pit aggregation Available forms Daily t doses w/ max 3 g PO daily Contra Avoid in PRG lactation, CAD, hyperthyroidism, anxiety disorders d/t high, caffeine content Notes/SE Insomnia, tach, anxiety, N/V, HA, HTN, Sz Interactions T Effects OF anticoagulants, anti-pits, BBs, bron-choclilators T risk of hypertensive crisis W/ MAOIs T effects W/ cimetidine, ciprofloxacin, ephedrine, hormonal contraceptives, dieophylline, cola, coffee X-effects OF adenosine, antihypertensives, benzodiazepines, Fe, X- effects W/ smoking EMS Tinctures contain EtOH may exacerbate GI disorders HTN T effects of anticoagulants and BBs... 

The interaction between the quinolone antibacterials and CYP1A2 has been studied in some depth for enoxacin and pefloxacin. Both compounds have been shown to inhibit CYPlA2-mediated metabolism of caffeine in vitro (49). This in vitro inhibition translated into a twofold decrease in caffeine clearance by pefloxacin and a sixfold decrease in clearance by enoxacin (50). Because pefloxacin undergoes N-demethylation to norfloxacin (51) and norfloxacin is much more potent as an inhibitor than pefloxacin (50), the observed in vivo interaction seen for pefloxacin may, in part, be due to norfloxacin. Many other quinolone antibacterial agents have been investigated for their interaction with theophylline, and ciprofloxacin has also been shown to have notable inhibitory effects (52). 

A mixture of four fluoroquinolones (including ciprofloxacin hydrochloride) was determined by high performance capillary electrophoresis using caffeine as an internal standard [58], A portion of the solution was... 

Drug interactions The effect of antacids and cations on the absorption of these agents was considered above. Ciprofloxacin, ofloxacin and enoxacin can increase the serum levels of theophylline by inhibiting its metabolism. They also may raise levels of warfarin, caffeine and cyclosporine. Cimetidine interferes with the... 

In 24 healthy volunteers, 12 men and 12 women, the women had significantly different caffeine pharmacokinetics in the presence of ciprofloxacin and fleroxacin compared with the men (132). There were also significant differences between the sexes in the pharmacokinetics of ciprofloxacin and fleroxacin in the presence of caffeine. The differences were in part due to different body weights. 

Kim MK, Nightingale C, Nicolau D. Influence of sex on the pharmacokinetic interaction of fleroxacin and ciprofloxacin with caffeine. Clin Pharmacokinet 2003 42(ll) 985-96. 

CYP1A2 15 -5 Fluvoxamine Caffeine Cyclobenzaprine Theophylline Thiothixene Olanzapine Ciprofloxacin Fluvoxamine Ticlopidine Halogenated biphenyls Polycyclic aromatic Hydrocarbons Omeprazole Rosiglitazone Phenylisothiocyanate... 

Noninterfering adenosine, albuterol, alphenal, aspirin, caffeine, carbamazepine, cefazo-lin, cephalexin, cephalothin, cimetidine, ciprofloxacin, claforan, desipramine, enoxacin, fleroxacin, furosemide, hydralazine, hydrochlorothiazide, minoxidil, norfloxacin, pheny-toin, propafenone, sulindac, teicoplanin, theophylline, vancomycin Interfering some indocyanine green impurities... 

CYP1A2 caffeine, imipramine, paracetamol, theophylline cigarette smoke, omeprazole cimetidine, ciprofloxacin, enoxacin, fluvoxamine... 

Enoxacin markedly increases caffeine levels. The effects of caffeine derived from drinks such as tea, coffee or cola, would be expected to be increased. Pipemidic acid interacts to a lesser extent, and ciprofloxacin, norfloxacin and pefloxacin interact less still Fleroxacin, lomefloxacin, ofloxacin, rufloxacin, and trovafloxacin appear not to interact. 

The effects of various quinolones on the pharmacokinetics of caffeine " are summarised in Table 33.3 , (p.l 167). In one study ciprofloxacin and fleroxacin increased caffeine levels more in women than men, but this difference in effect was not significant when the results were normalised for body weight. ... 

Established interactions. Based on the results of two studies, on a scale of 100 to 0, the relative potencies of these quinolones as inhibitors of caffeine elimination have been determined as follows enoxacin 100, pipemidic acid 29, ciprofloxacin 11, norfloxacin 9 and ofloxacin 0. From further studies, clinafloxacin appears to be similar to enoxacin (profound effect), pefloxacin to norfloxacin (to which it is metabolised modest effect), and fleroxacin, lomefloxacin, rufloxacin, and trovafloxacin appear to behave like ofloxacin (no effect). Patients taking enoxacin might be expected to experience an increase in the effects of caffeine (such as headache, jitteriness, restlessness, insomnia) if, for example, they continue to drink their usual amounts of caffeine-containing drinks (tea, coffee, cola drinks, etc.). They should be warned to cut out or reduce their intake of caffeine if this occurs. The authors of one report suggest that patients with hepatic disorders, cardiac arrhythmias or latent epilepsy should avoid caffeine if they take enoxacin for one week or more. The effects of pipemidic acid arc less, and those of ciprofloxacin, norfloxacin and pefloxacin arc probably of little or no clinical importance. Fleroxacin, lomefloxacin, ofloxacin, rufloxacin, and trovafloxacin do not interact. 

Healy DP, Polk RE, Kanawati L, Rock DT, Mooney ML. Interaction between oral ciprofloxacin and caffeine in normal volunteers Antimicrob Agents Chemother (1989) 33,474-8... 

Nicolau DP, Nightingale CH, Tessier PR, Fu Q, Xuan D-W, Esguerra EM, Quintiliani R. The effect of fleroxacin and ciprofloxacin on the pharmacokinetics of multiple dose caffeine. Drugs (1995) 49 (Suppl 2), 357-9. 

Caffeine is metabolized by the isoenzyme CYP1A2. Drugs that inhibit this isoenzyme (including fluvoxamine, ciprofloxacin, cimetidine, amiodarone, fluoroquinolones, furafylline, interferon, methoxsalen, and mibefradil) may slow the metabolism of caffeine. In persons drinking multiple cups of coffee daily, high levels of caffeine could accumulate (Carrillo and Benitez 2000). 

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