Clinically Relevant Drug-Drug Interactions in Primary Care

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


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

In This Article

Drugs With Chelation Risk

Chelation occurs when insoluble complexes are formed in the gut as a result of coadministration of multivalent cations and tetracycline drugs, fluoroquinolone antibiotics, or thyroid drugs. When these complexes form, the absorption of these drugs is reduced.[18] Managing dosing times for tetracycline antibiotics (administer two hours before or at least four hours after cation[41]), fluoroquinolone antibiotics (administer two hours before or six hours after cation[42]), and thyroid drugs (administer two hours before or six hours after cation[42]) helps to minimize these drug interactions. Many cations are present in over-the-counter products (Table 4[40]). It is important to inquire about the use of over-the-counter medications because patients may not initially report usage.[43]

Potassium supplements coadministered with angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers, direct renin inhibitors, or potassium-sparing diuretics can increase the risk of hyperkalemia. This is considered a pharmacodynamic interaction, and the combination should be used with caution. If the combination is necessary, the spironolactone dosage should be limited to 25 mg daily when coadministered with potassium supplements.[44–46] Monitoring should be performed; if serum potassium levels increase to greater than 5.5 mEq per L (5 mmol per L) or renal function worsens, doses of these antihypertensive drugs should be held until the potassium level is less than 5 mEq per L (5 mmol per L) and the renal function normalizes for at least 72 hours.[45,46]