4. Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens, which may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically relevant for oral fluoroquinolones are summarized in Table 5. Only those drug-drug interactions classified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.
| Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level# |
|---|---|---|---|---|
| ciprofloxacin | drugs metabolized by CYP1A2 (e.g., alosetron, caffeine, clozapine, duloxetine, mexiletine, ropinirole, tizanidine) | concurrent administration ciprofloxacin, a known CYP1A2 inhibitor, with drugs metabolized by CYP1A2 may result in increased serum levels of drugs metabolized by CYP1A2 and potentially increased pharmacologic/adverse effects | if combination necessary, monitor for increased adverse effects; alternative FQ that does not affect CYP1A2 enzymes may be considered | contraindicated, major, moderate (DrugReax) 2-major, 3-moderate (CP) |
| ciprofloxacin | methotrexate | co-administration may result in reduced methotrexate renal tubular transport and potential for increased methotrexate levels and increased pharmacologic/adverse effects | measure methotrexate concentrations and observe patients for increased adverse effects | moderate (DrugReax) 3-moderate (CP) |
| ciprofloxacin | mycophenolate | concurrent administration may decrease mycophenolic acid concentrations | monitor response to therapy when ciprofloxacin is started or stopped | moderate (DrugReax) 3-moderate (CP) |
| ciprofloxacin | phenytoin | concurrent use may result in increased or decreased phenytoin concentrations ; mechanism unknown | measure phenytoin concentrations and observe patients for increased or decreased pharmacologic effects | moderate (DrugReax) 3-moderate (CP) |
| ciprofloxacin | phosphodiesterase type 5 (PDE5) inhibitors | concurrent administration may increase PDE5 inhibitor plasma levels and risk of adverse reactions | during coadministration, consider lower dose of PDE5 inhibitor or withholding PDE5 inhibitor in patients at high risk of developing PDE5 inhibitor adverse reactions | moderate (DrugReax) |
| ciprofloxacin | probenecid | co-administration may result in increased serum ciprofloxacin levels due to probenecid inhibition of renal tubular secretion | monitor patients for increased ciprofloxacin adverse effects | moderate (DrugReax) 4-minor (CP) |
| ciprofloxacin | theophyllines | adjuvant administration may result in decreased theophylline clearance and potential for increased serum theophylline levels and enhanced pharmacologic/toxic effects as ciprofloxacin interferes with theophylline clearance | if adjunctive therapy necessary, closely monitor theophylline levels and observe for increased adverse effects; may consider alternative FQ that does not interfere with theophylline clearance | major (DrugReax) 3-moderate (CP) |
| ciprofloxacin | tizanidine (Ziaflex®) | combined administration may result in enhanced tizanidine pharmacologic effects and/or adverse effects (e.g., sedation, hypotension) due to ciprofloxacin inhibition of CYP1A2-mediated tizanidine metabolism | avoid concurrent administration; use alternative spasticity medication | contraindicated (DrugReax) 1-severe (CP) |
| fluoroquinolones (FQ) | antacids | simultaneous administration may result in reduced absorption/bioavailability and clinical effectiveness of the FQ due to chelation of the antacid cations with the quinolone molecule | avoid concurrent administration; give FQ 2 hours before or 6 hours after giving antacids; may consider H2 receptor antagonist as alternative to antacids (e.g., ranitidine) in some clinical situations | moderate (DrugReax) 2-major (CP) |
| FQ | antidiabetic agents | adjunctive administration may result in altered blood glucose levels and increased risk for hypo- or hyperglycemia | monitor serum glucose levels closely with concurrent administration | major (DrugReax) 3-moderate (CP) |
| FQ | corticosteroids | concurrent therapy may increase risk for tendon rupture, especially in patients over 60 years of age | discontinue FQ therapy with any signs of tendon inflammation or pain | moderate (DrugReax) 3-moderate (CP) |
| FQ | didanosine (Videx®) oral solution | didanosine buffers consist of magnesium-aluminum cations; concomitant administration with FQ may result in reduced FQ absorption/ bioavailability and clinical effectiveness due to chelation of the antacid cations with the quinolone molecule | avoid concurrent administration; give FQ 2 hours before or 6 hours after giving didanosine | moderate (DrugReax) 2-major (CP) |
| FQ | iron salts (including iron in multivitamins) | iron salts may bind FQ in GI tract forming insoluble, unabsorbable complexes with resultant reduced FQ serum concentrations/pharmacologic effects | avoid concurrent administration; give FQ 2 hours before or 6 hours after giving drugs containing iron | moderate (DrugReax) 2-major (CP) |
| FQ | nonsteroidal anti-inflammatory drugs (NSAIDs) | concurrent administration may increase risk of central nervous system (CNS) stimulation and convulsive seizures | administer cautiously together and monitor patients closely for increased CNS adverse effects | moderate (DrugReax) 3-moderate (CP) |
| FQ | QTc interval-prolonging medications (e.g., class IA, III anti-arrhythmics, tricyclic antidepressants, clozapine, cyclobenzaprine, macrolide antibiotics, cisapride, ziprasidone) | concurrent administration may increase risk of significant cardiotoxicity (e.g., life-threatening arrhythmias, cardiac arrest) as FQ may cause QTc interval prolongation and, rarely, torsades de pointes | adjunctive administration should be avoided | contraindicated, major (DrugReax) 1-severe, 2-major (CP) |
| FQ | sevelamer (Renagel®) | concurrent administration may cause decreased FQ bioavailability and potential for reduced pharmacologic effects | avoid concurrent administration; administer FQ 1 hour before or 3 hours after sevelamer | moderate (DrugReax) 2-major (CP) |
| FQ | sucralfate | concurrent administration may result in decreased FQ efficacy due to FQ chelation by sucralfate in GI tract | avoid concurrent administration; give FQ 2 hours before or 6 hours after giving sucralfate | moderate (DrugReax) 2-major (CP) |
| FQ | warfarin | concomitant administration may result in enhanced hypoprothrombinemic effects and increased bleeding risk; mechanism of this interaction not identified; changes in PT/INR may occur 2-16 days after addition of FQ to warfarin therapy | if combination cannot be avoided, monitor PT/INR closely and observe for increased adverse effects | major (DrugReax) 2-major (CP) |
| FQ | zinc salts, calcium | zinc salts or calcium may bind FQ in GI tract forming insoluble, unabsorbable complexes with resultant reduced FQ serum concentrations/ pharmacologic effects | avoid concurrent administration; give FQ 2 hours before or 6 hours after giving drugs containing zinc | moderate (DrugReax) |
| select FQ (ciprofloxacin, levofloxacin) | cyclosporine | adjunctive administration has resulted in transiently increased serum creatinine levels and/or increased cyclosporine levels | monitor serum creatinine and cyclosporine levels; observe patients for cyclosporine adverse effects | moderate (DrugReax) |