Summary

Everolimus can significantly increase digoxin blood levels by inhibiting P-glycoprotein transport, potentially leading to digoxin toxicity. This interaction requires careful monitoring of digoxin levels and possible dose adjustments when these medications are used together.

Introduction

Everolimus is an mTOR (mechanistic target of rapamycin) inhibitor used as an immunosuppressant in organ transplant recipients and as an anticancer agent in certain malignancies. It belongs to the class of drugs known as sirolimus analogs. Digoxin is a cardiac glycoside derived from the foxglove plant, primarily used to treat heart failure and certain arrhythmias, particularly atrial fibrillation. It works by inhibiting the sodium-potassium ATPase pump, leading to increased intracellular calcium and improved cardiac contractility.

Mechanism of Interaction

The interaction between everolimus and digoxin occurs through inhibition of P-glycoprotein (P-gp), an efflux transporter protein. Everolimus acts as a P-glycoprotein inhibitor, reducing the active transport of digoxin out of cells, particularly in the intestines and kidneys. This inhibition leads to increased absorption of digoxin from the gastrointestinal tract and decreased renal elimination, resulting in elevated plasma digoxin concentrations. The interaction is pharmacokinetic in nature, affecting digoxin's distribution and elimination rather than its pharmacodynamic effects.

Risks and Symptoms

The primary risk of this interaction is digoxin toxicity due to elevated serum digoxin levels. Signs and symptoms of digoxin toxicity include nausea, vomiting, loss of appetite, visual disturbances (such as yellow-green halos around lights), confusion, and potentially life-threatening cardiac arrhythmias including bradycardia, heart block, and ventricular arrhythmias. The narrow therapeutic index of digoxin makes this interaction clinically significant, as small increases in digoxin levels can lead to toxicity. Elderly patients and those with renal impairment are at particularly high risk for developing digoxin toxicity when these drugs are combined.

Management and Precautions

When everolimus and digoxin must be used concurrently, close monitoring is essential. Obtain baseline digoxin levels before starting everolimus and monitor levels frequently during the first few weeks of combination therapy. Consider reducing the digoxin dose by 25-50% when initiating everolimus, with further adjustments based on serum levels and clinical response. Monitor patients closely for signs and symptoms of digoxin toxicity, including cardiac rhythm monitoring when appropriate. Regular assessment of renal function is also important, as both drugs can affect kidney function. If everolimus is discontinued, digoxin levels may decrease, potentially requiring dose increases to maintain therapeutic efficacy. Always consult with a clinical pharmacist or physician experienced in managing these drug interactions for optimal patient care.

Everolimus interactions with food and lifestyle

Everolimus should be taken consistently either with food or without food, but not alternating between the two, as food can significantly affect absorption and blood levels. Grapefruit and grapefruit juice should be avoided as they can increase everolimus blood levels and potentially lead to increased side effects. St. John's wort should be avoided as it can decrease everolimus effectiveness by reducing blood levels. Live vaccines should be avoided during everolimus treatment due to immunosuppressive effects.

Digoxin interactions with food and lifestyle

Digoxin has several important food and lifestyle interactions that patients should be aware of. High-fiber foods, including bran cereals and fiber supplements, can significantly reduce digoxin absorption and should be taken at least 2 hours apart from digoxin doses. St. John's wort, an herbal supplement, can decrease digoxin levels and reduce its effectiveness, so concurrent use should be avoided. Alcohol consumption can affect digoxin levels and increase the risk of side effects, particularly heart rhythm abnormalities. Patients should limit alcohol intake and discuss any alcohol use with their healthcare provider. Additionally, maintaining consistent dietary habits is important, as sudden changes in fiber intake or meal timing can affect digoxin absorption and blood levels. Patients should also be cautious with salt substitutes containing potassium, as changes in potassium levels can affect digoxin's effectiveness and safety.