A Guide To Drug-Drug Interactions In Podiatry

Robert G. Smith, DPM, MSc, RPh, CPed

   Some NSAIDs also alter the pharmacokinetics of warfarin. One should avoid concurrent warfarin and NSAID therapy, including celecoxib (Celebrex, Pfizer), when possible. Acetaminophen may alter the warfarin response but the effect is relatively small. Antiplatelet therapy with aspirin primarily increases the risk of minor bleeding. Finally, opioid analgesics are not known to interact with warfarin.

   While most interactions between NSAIDs and other drugs are pharmacokinetic, NSAID-related pharmacodynamic interactions may be considerably more important in the clinical context. For a list of selected NSAID-related adverse drug interactions, see “A Guide To Potential Drug Interactions With NSAIDs” at the right. When it comes to NSAIDs, one can reduce the risk of adverse drug interactions by rational prescribing and careful monitoring of drugs and therapy periods, particularly for high-risk patients.22

   Prescribing NSAIDs is relatively contraindicated for patients on oral anticoagulants due to hemorrhage and for patients taking high dose methotrexate (Trexall, Barr Laboratories) due to bone marrow toxicity, renal failure and hepatic dysfunction.23 The podiatric physician should consider the use of either aspirin or sulindac (Clinoril, Merck) in the presence of lithium or antihypertensives. He or she should also monitor the patient’s blood pressure and lithium level for toxicity. Avoid indomethacin (Indocin, Merck) and triamterene (Dyrenium, WellSpring Pharmaceutical) due to the risk of renal failure.

   The concurrent administration of amiodarone (Cordarone, Pfizer) with fluconazole, itraconazole or ketoconazole has caused increased plasma levels of amiodarone and possible toxicity.24 Desethylamiodarone is a major metabolite of amiodarone and has exhibited more potent inhibitory effects on human CYP activities.25

Pertinent Pointers On Drug-Food Interactions

Sometimes when patients take medications with food, they can have less of an effect than if patients took the drugs on an empty stomach. Food can speed up or slow down the action of a drug. Medications may alter how the body uses nutrients.

   As foods are a complex mixture of different constituents, the potential exists to alter the pharmacodynamic, pharmacokinetic and clinical response obtained with a medication.26 The podiatric physician should realize that food can act as a physical barrier and thereby prevent drug access to the absorptive surface of the gastrointestinal mucosa.27 Food and drug interactions can happen with both prescription and over-the-counter medications.

   The acidity of fruit juice may decrease the effectiveness of antibiotics such as penicillin. Dairy products may blunt the infection fighting effects of tetracycline and fluoroquinolones by decreasing the absorption of these drugs. Fluoroquinolones can inhibit the clearance of xanthine derivatives, including theophylline and caffeine, which may result in seizures. Antidepressants, specifically monoamine oxidase inhibitors (MAOIs), are dangerous when mixed with foods or drinks that contain tyramine (i.e., beer, red wine and some cheeses). Linezolid (Zyvox, Pfizer) is a reversible, non-selective inhibitor of monoamine oxidase and has the potential for interacting with adrenergic and serotonergic agents as well as tyramine.

   Grapefruit juice contains various bioflavonoids that have the ability to inhibit CYP450 isoenzymes. Grapefruit juice inhibits cytochrome P-450 3A4 in the wall of the small intestine. This impairs the oxidative metabolism of some drugs. The dose of grapefruit juice will markedly affect the magnitude of the interaction. Eating grapefruit pulp also reportedly inhibits CYP3A4. Grapefruit juice inhibition of CYP3A may last for up to 24 hours after a single dose and up to 72 hours after multiple doses.28 Finally, a number of selected drugs are known to interact with grapefruit juice to cause adverse reactions (see “Which Drugs Are Significantly Affected By Grapefruit Juice?” below.28

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