Clinically Significant Drug Interactions

Acetaminophen plus carbamazepine, phenytoin - increased production of toxic acetaminophen metabolites.

ACE inhibitors plus potassium-sparing diuretic (spironolactone, amiloride, triamterene), potassium supplements, tacrolimus, cyclosporine - risk of hyperkalemia, a potential cardiac emergency [1].

Benzodiazepines plus azole antifungals, selective serotonin reuptake inhibitors, cimetidine, antiepileptic drugs, macrolide antibiotics - increased benzodiazepine effect [2-3].

Digoxin plus calcium channel blockers, amiodarone, quinidine, azole antifungals, certain antibiotics (tetracyclines, erythromycin, clarithromycin), cyclosporine - increased digoxin toxicity, potentially fatal cardiac arrhythmias [4-10].

Carbamazepine plus azole antifungals, calcium channel blockers, cimetidine, erythromycin, clarithromycin, etronidazole, valproic acid, sulphonamides - increased risk of carbamazepine toxicity [11-14].

Fluoroquinolone plus divalent/trivalent cations (aluminum- or magnesium-containing antacids, sucralfate, products containing calcium, iron, or zinc) - marked reduction of absorption of the fluoroquinolone. Studies have shown that the absorption of fluoroquinolones is reduced by 60 to 75 percent when these antibiotics are administered concomitantly with divalent or trivalent cations [15, 16].

Lithium plus NSAID, diuretic - increased lithium levels. Diuretics and NSAIDs alter the sodium balance at the level of the kidney. As a result, serum lithium levels increase due to enhanced reabsorption [17].

MAO inhibitors plus carbamazepine, tricyclic antidepressants, SSRIs, SNRIs - serotonin syndrome, CNS overstimulation, hyperpyrexia, seizures, and even death [18].

Oral contraceptive plus rifampin, carbamazepine, phenobarbital, phenytoin, troglitazone - decreased effectiveness of oral contraception. These agents can reduce the plasma concentrations of oral contraceptives through an P450 isoenzyme-inducing mechanism. The problems are most likely to occur with formulations containing a low dosage of estrogen (less than 35 mg of ethinyl estradiol) [19-20].

Phenytoin plus amiodarone, cimetidine, diltiazem, verapamil, isoniazid, metronidazole, erythromycin, clarithromycin, sulfonamides, fluoxetine - increased risk of phenytoin toxicity [21-22].

Phenytoin plus carbamazepine, doxorubicin, estrogens, oral contraceptives, phenobarbital, rifampin - decreased phenytoin levels and effect.

Phenobarbital plus cimetidine, erythromycin, clarithromycin, sulphonamides, fluconazole - increased phenobarbital levels [22].

Quinidine plus tricyclic antidepressants, codeine - increased level of antidepressants or codeine [6].

Quinidine plus cimetidine, azole antifungals and calcium antagonists - increased quinidine effect [6].

Sildenafil plus nitrates - risk of severe hypotension, which may lead to cardiovascular collapse. Sildenafil therapy is absolutely contraindicated in patients who are taking any form of nitrates [23].

Statins (HMG-CoA reductase inhibitors) plus niacin, gemfibrozil, erythromycin, cyclosporine - can cause toxicity that manifests as elevated serum transaminase levels, myopathy, rhabdomyolysis and acute renal failure [24].

Theophylline plus ciprofloxacin, enoxacin, pefloxacin, ofloxacin, erythromycin, clarithromycin, amiodarone, itraconazole, ketoconazole, fluconazole, cimetidine, quinidine, fluoxetine - theophylline levels can increase to a toxic degree [25-26].

Triazole antifungals (ketoconazole, fluconazole, and itraconazole) plus phenytoin, warfarin, sulfamethoxazole, cyclosporin, tacrolimus, alprazolam, triazolam, midazolam, nifedipine, felodipine, simvastatin, lovastatin, vincristine, terfenadine, astemizole, losartan - antifungal drugs can cause many clinically significant interactions by increasing the concentrations of other drugs [27].

Drug interactions involving WARFARIN are among the most serious, because they are associated with a high risk of fatal bleeding.

Warfarin plus antibiotic (ciprofloxacin, clarithromycin, erythromycin, metronidazole, trimethoprim-sulfamethoxazole) - Increased effects of warfarin, with potential for bleeding. Reduction of intestinal flora responsible for vitamin K production by antibiotics is probable as well as decreased metabolism and clearance of warfarin [28-29].

Warfarin plus itraconazole, ketoconazole, fluconazole, cimetidine, omeprazole, amiodarone, propafenone, quinidine, nefazodone, fluoxetine - increased warfarin effect [30-31].

Warfarin plus acetaminophen, aspirin, NSAIDs - potential for serious gastrointestinal bleeding [32-33].

Warfarin plus phenytoin, carbamazepine, phenobarbital, rifampin - decreased warfarin effect [34].

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By HealthyStock Research Group, October 21, 2012
Medical resources reviewed: August 2018