Drug-drug interaction of fluoroquinolones
Fluoroquinolones x antacids, calcium carbonate, ferrous sulphate and sucralfate:
The oral absorption of all fluoroquinolones is significantly impaired when co-administered with aluminum- and magnesium-containing antacids and sucralfate, as well as with other metal cations such as calcium and iron. Concomitant use of these agents, even when dosed several hours apart, should be avoided.
Fluoroquinolones, especially enoxacin and ciprofloxacin x theophylline:
Fluoroquinolones, especially enoxacin, and to a lesser extent ciprofloxacin and pefloxacin, inhibit the metabolic clearance of theophyllinc and caffeine. Leading to significantly increased serum concentrations. It is advisable to use non-interacting quinolones such as ofloxacin or norfloxacin or to measure theophylline levels and reduce caffeine intake where appropriate.
Fluoroquinolones x warfarin:
The exact warfarin-quinolone drug interaction is unknown. Reduction of intestinal flora responsible for vitamin K production by antibiotics is probable as well as decreased metabolism and clearance of warfarin.
Pefloxacin x cimetidine:
Cimetidine reduces the metabolic clearance of pefloxacin.
Enoxacin x Fenbrufen:
A high incidence of convulsions has been observed in patients receiving the combination enoxacin and fenbrufen, an NSAID.A synergistic inhibitory effect of fluoroquinolones and several NSAIDs has been observed on the binding of the neurotransmitter GABA. Although the relevance of this interaction is probably not great, except with fenbrufen, a possible epileptogenic effect of the combination cannot be excluded.
Quinolones x penicillins:
Incompatibilities are observed between quinolones and penicillins such as flucloxacillin and amoxicillin and with clindamycin when mixed in an administration set.
Fluoroquinolones x midazolam:
A potential interaction with midazolam needs further study.
Fluoroquinolones x cyclosporine:
Fluoroquinolone antibiotics inhibit cytochrome P450-mediated microsomal drug metabolism so decrease cyclosporine clearance and increase its blood level.
Quinolones x Benzodiazepine:
Administration of quinolone antibiotics to a benzodiazepine dependent individual can precipitate acute benzodiazepine withdrawal symptoms due to quinolones displacing benzodiazepines from their binding site.
Fluoroquinolones xTizanidine:
The proposed mechanism is an inhibition of the liver metabolism of tizanidine. The interaction resulted in a severe decrease in blood pressure and enhanced central nervous system effects. The combination of these is now contraindicated.
Fluoroquinolones x Probenecid:
Probenecid administration increases peak plasma concentrations and prolongs the half-life of quinolones primarily excreted by the renal route, such as ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and gemifloxacin. The mechanism of this effect is inhibition of renal tubular secretion, most likely secondary to inhibition of renal transport proteins by probenecid. Accordingly, trovafloxacin and moxifloxacin are less affected, since they are excreted primarily by hepatic clearance mechanisms.
N.B:
Fluoroquinolones have varying specificity for Cytochrome P450, and so may have interactions with drugs cleared by those enzymes; the order from most P450-inhibitory to least is: enoxacin > ciprofloxacin > norfloxacin > ofloxacin, levofloxacin, trovafloxacin, gatifloxacin, moxifloxacin.
Drug-food interaction
Food does not impair the absorption of most quinolones. However, quinolones chelate with cations such as aluminum, magnesium, calcium, iron, and zinc. This interaction significantly reduces absorption and bioavailability, resulting in lower serum drug concentrations and less target-tissue penetration.
Drug-disease interaction
Quinolones (Includes Ciprofloxacin) ↔ CNS Disorders
Therapy with quinolones should be administered cautiously in patients with or predisposed to seizures or other CNS abnormalities because Quinolones may cause CNS stimulation manifested as tremors, agitation, restlessness, anxiety, confusion, hallucinations, paranoia, insomnia, toxic psychosis, and/or seizures. Benign intracranial hypertension has also been reported.
Quinolones (Includes Ciprofloxacin) ↔ QT Interval Prolongation
Quinolones have been reported to prolong the QT interval of the electrocardiogram in some patients. QT prolongation may potentiate the risk of ventricular arrhythmias including ventricular tachycardia, ventricular fibrillation, and torsade de pointes. The risk appears to be greatest with grepafloxacin and sparfloxacin. Cardiovascular morbidity and mortality attributable to QT prolongation have also been reported rarely with others like gatifloxacin, levofloxacin, ciprofloxacin, and ofloxacin. Therapy with quinolones should be avoided in patients with known QT prolongation and/or uncorrected electrolyte disorders (hypokalemia or hypomagnesemia) and in patients treated concomitantly with class IA or III antiarrhythmic agents.
Quinolones (Includes Ciprofloxacin) ↔ Colitis
Antibiotic therapy can alter the normal flora of the colon and permit overgrowth of Clostridium difficile, whose toxin is believed to be a primary cause of antibiotic-associated colitis. So, it should be administered cautiously in patients with a history of gastrointestinal diseases, particularly colitis.
Quinolones (Includes Ciprofloxacin) ↔ Crystalluria
Crystalluria has been reported rarely during quinolone therapy. Although it is not expected to occur under normal circumstances with usual recommended dosages, patients who are dehydrated (e.g., due to severe diarrhea or vomiting) may be at increased risk and should be encouraged to consume additional amounts of liquid or given intravenous fluid to ensure an adequate urinary output. Alkalinity of the urine should be avoided, since it may also increase the risk of crystalluria.
Quinolones (Includes Ciprofloxacin) ↔ Diabetes
Administration of ciprofloxacin, levofloxacin, norfloxacin, and especially gatifloxacin in patients treated with sulfonylureas or other oral hypoglycemic agents has resulted in severe, refractory hypoglycemia and hypoglycemic coma.
Gatifloxacin has been known to cause hypoglycemic episodes generally within the first 3 days of therapy and sometimes even after the first dose, while hyperglycemia usually occurs 4 to 10 days after initiation of therapy.
Quinolones (Includes Ciprofloxacin) ↔ Hemodialysis
The following quinolones are known to be partially removed by hemodialysis and should be administered after dialysis: ciprofloxacin, enoxacin, gatifloxacin, levofloxacin, lomefloxacin, and ofloxacin.
Quinolones (Includes Ciprofloxacin) ↔ Renal Dysfunction
Quinolones (except trovafloxacin, moxifloxacin, and nalidixic acid) and their metabolites are eliminated by the kidney. Patients with renal impairment may be at greater risk for adverse effects from quinolones, including nephrotoxicity, due to decreased drug clearance. Dosage adjustments may be necessary.