Top Things to Know: Cardio-Oncology Drug Interactions
Published: March 07, 2022
Prepared by Paul St. Laurent, DNP, RN, Senior Science and Medicine Advisor, Lead
- Hypertension commonly occurs as a side effect of treatment with vascular endothelial growth factor (VEGF) inhibitors, Bruton’s tyrosine kinase inhibitors and endocrine therapies among others. First and second line therapies include ACEIs/ARBs and CCBs, respectively.
- Combination regimens including anthracyclines, HER2-targeted therapies, and immune checkpoint inhibitors (ICIs) increase the risk of cardiotoxicity, thus routine echocardiogram monitoring throughout therapy is important to monitor heart function, and neurohormonal therapies for heart failure may be warranted.
- Numerous cancer treatments and supportive therapies have been associated with QT prolongation. Key principles to mitigate these effects include early identification of patient-related risk factors, accurate measurement of QT/QTc, correction of reversible causes, increased awareness of pharmacodynamic (PD) and pharmacokinetic (PK) drug-drug interactions affecting arrhythmia risk, and frequent monitoring during treatment.
- Tyrosine kinase inhibitors (TKIs) including dasatinib, ibrutinib and imatinib, are dependent on acid environments for absorption. It is important for clinicians to evaluate the need for acid suppression therapy including the use of OTC medications or select a TKI that is not altered in a basic environment.
- Inhibition of various renal transporters by cardiovascular (CV) agents such as amiodarone and verapamil can lead to increased levels of renally cleared anti-cancer agents like vinblastine, promoting risk of toxicity. Discontinuation of these agents or switching to alternatives may be needed.
- Patients receiving CV therapies that rely heavily on renal clearance, such as digoxin, dofetilide, sotalol, and atenolol, require close monitoring if on concomitant nephrotoxic anti-cancer therapy, such as cisplatin. If renal function declines, reducing the dose or stopping the drug may be required to prevent adverse effects.
- Conventional and liposomal anthracyclines, cyclophosphamide, taxanes, cytarabine, and TKIs can induce P-glycoprotein (P-gp). Clinicians should be aware of CV medications that are P-gp substrates and avoid or monitor for reduced efficacy or assess levels if available (e.g., digoxin).
- Numerous CV and chemotherapeutic agents are substrates for or undergo metabolism through CYP450 or other metabolic pathways and thus are at risk for significant drug-drug interactions (DDIs). In many cases, a dose reduction or alternate therapy may be warranted.
- Several supportive therapies for cancer can contribute to various important DDIs with cardio-oncology agents and should also be evaluated.
- Pharmacists serve as a uniquely trained resource for addressing both PD and PK interactions, specifically identifying clinically relevant DIs and recommending dose adjustment or alternative therapies to assure safe and effective medication use.
Citation
Beavers CJ, Rodgers JE, Bagnola AJ, Beckie TM, Campia U, Di Palo KE, Okwuosa TM, Przespolewski ER, Dent S; on behalf of the American Heart Association Clinical Pharmacology Committee and Cardio-Oncology Committee of the Council on Clinical Cardiology and Council on Genomic and Precision Medicine; and the Council on Peripheral Vascular Disease. Cardio-oncology drug interactions: a scientific statement from the American Heart Association [published online ahead of print March 7, 2022]. Circulation. doi: 10.1161/CIR.0000000000001056