Clinically Relevant Drug-Drug Interactions in Primary Care

 

Am Fam Physician. 2019 May 1;99(9):558-564.

Author disclosure: No relevant financial affiliations.

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.

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.

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

Software programs that identify potentially serious drug interactions may reduce risk of harm.

C

2

Pharmacist-directed anticoagulation clinics can identify drug interactions with warfarin (Coumadin) and improve patient outcomes.

B

3, 5

Medication reconciliation and review by a pharmacist as part of a transition of care process can identify potential drug interactions and may improve patient outcomes.

B

4

An empiric warfarin dosage reduction of 30% to 50% upon initiation of amiodarone therapy is recommended.

C

14, 15

Beta blockers should be tapered and discontinued several days before clonidine withdrawal to reduce the risk of rebound hypertension.

C

39, 40

If the combination is necessary, the spironolactone dosage should be limited to 25 mg per day when coadministered with potassium supplements.

C

4446


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferences

Software programs that identify potentially serious drug interactions may reduce risk of harm.

C

2

Pharmacist-directed anticoagulation clinics can identify drug interactions with warfarin (Coumadin) and improve patient outcomes.

B

3, 5

Medication reconciliation and review by a pharmacist as part of a transition of care process can identify potential drug interactions and may improve patient outcomes.

B

4

An empiric warfarin dosage reduction of 30% to 50% upon initiation of amiodarone therapy is recommended.

C

14, 15

Beta blockers should be tapered and discontinued several days before clonidine withdrawal to reduce the risk of rebound hypertension.

C

39, 40

If the combination is necessary, the spironolactone dosage should be limited to 25 mg per day when coadministered with potassium supplements.

C

4446


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

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BEST PRACTICES IN GERIATRIC MEDICINE

Recommendations from the Choosing Wisely Campaign

RecommendationSponsoring organization

Prescribe a medication only after conducting a drug regimen review.

American Geriatrics Society

Do not

The Authors

show all author info

MARY CARPENTER, PharmD, is a clinical pharmacy specialist and clinical assistant professor in the Department of Family Medicine at the Medical College of Georgia at Augusta University....

HOLLY BERRY, PharmD, is a clinical pharmacy specialist at Duke University Hospital, Durham, N.C.

ALLEN L. PELLETIER, MD, is a professor in the Department of Family Medicine at the Medical College of Georgia at Augusta University.

Address correspondence to Mary Carpenter, PharmD, Augusta University, 1120 15th St., Augusta, GA 30912. Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

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