Clinically Relevant Drug-Drug Interactions in Primary Care

Mary Carpenter, PharmD; Holly Berry, PharmD; Allen L. Pelletier, MD

Disclosures

Am Fam Physician. 2019;99(9):558-564. 

In This Article

Abstract and Introduction

Abstract

Drug interactions are common in the primary care setting and are usually predictable. Identifying the most important and clinically relevant drug interactions in primary care is essential to patient safety. Strategies for reducing the risk of drug-drug interactions include minimizing the number of drugs prescribed, re-evaluating therapy on a regular basis, considering nonpharmacologic options, monitoring for signs and symptoms of toxicity or effectiveness, adjusting dosages of medications when indicated, and adjusting administration times. Inhibition or induction of cytochrome P450 drug metabolizing isoenzymes is the most common mechanism by which clinically important drug interactions occur. The antimicrobials most likely to affect the international normalized ratio significantly in patients receiving warfarin are trimethoprim/sulfamethoxazole, metronidazole, and fluconazole. An empiric warfarin dosage reduction of 30% to 50% upon initiation of amiodarone therapy is recommended. In patients receiving amiodarone, limit dosages of simvastatin to 20 mg per day and lovastatin to 40 mg per day. Beta blockers should be tapered and discontinued several days before clonidine withdrawal to reduce the risk of rebound hypertension. Spironolactone dosages should be limited to 25 mg daily when coadministered with potassium supplements. Avoid prescribing opioid cough medicines for patients receiving benzodiazepines or other central nervous system depressants, including alcohol. Physicians should consider consultation with a clinical pharmacist when clinical circumstances require the use of drugs with interaction potential.

Introduction

Drug interactions are estimated to cause approximately 2.8% of all hospitalizations annually in the United States, representing more than 245,000 hospitalizations, costing the health care system $1.3 billion.[1] Exact figures are unknown because few studies have highlighted the significance of drug interactions in primary care. Many interactions are theoretical or clinically trivial; however, some may have serious or life-threatening consequences. This review focuses on the most common drug interactions likely to be encountered in the primary care setting.

Physicians should be aware of common and serious drug interactions and prescribe to avoid these interactions where possible. Strategies for reducing the risk of drug-drug interactions include minimizing the number of drugs prescribed, re-evaluating therapy on a regular basis, considering nonpharmacologic options, monitoring for signs and symptoms of toxicity and/or effectiveness, adjusting dosages of medications when indicated, and adjusting administration times.[1] Physicians should monitor for early detection of adverse reactions and be aware of patient risk factors that increase the chance of an undesirable outcome.

Communication between primary care physicians and subspecialist physicians is critical to mutually understand the goals of drug therapy and to avoid or modify drug combinations that may put patients at risk. Patients should be educated about possible drug interactions when a reaction or potential adverse effect can be anticipated. Electronic drug information resources, as well as software that detects and alerts to a potential drug interaction (often built into electronic prescribing programs), lower the risk of some drug interactions but can cause alert fatigue.[2] Medication review and reconciliation by a pharmacist (especially during transitions of care) may reduce the risk of clinically significant drug interactions.[3–5] Physicians should consider consultation with a clinical pharmacist when clinical circumstances require the use of drugs with interaction potential.

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