Carvedilol interactions to avoid

Key takeaways | Drug interactions | Food interactions | Other interactions | Avoiding interactions | When to see a doctor

Carvedilol (Coreg) is a nonselective beta-adrenergic blocking agent (beta blocker) approved by the U.S. Food and Drug Administration (FDA) to treat congestive heart failure and hypertension. Carvedilol is also used off-label for multiple other indications, like angina or chest pain, atrial fibrillation, early treatment and secondary prevention of heart attacks, left ventricular dysfunction, and ventricular tachycardias. Carvedilol interacts with medications that inhibit or induce the enzymes it metabolizes and with other medications that may act similarly on heart rate or blood pressure levels. It is important to be aware of carvedilol’s interactions, as other drugs can affect carvedilol’s effectiveness or enhance its action, leading to adverse effects.

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Carvedilol drug interactions

Carvedilol typically interacts with medications that impact heart rate or manage high blood pressure but can also interact with medications that rev up or slow down its metabolism. 

Antidiabetic agents

Carvedilol may mask or enhance the blood glucose-lowering effects of certain diabetic agents, resulting in episodes of hypoglycemia. Interacting antidiabetic agents include insulin, canagliflozin, dapagliflozin, exenatide, linagliptin, liraglutide, metformin, pioglitazone, semaglutide, and voglibose, among others. Beta blockers may mask symptoms of low blood sugar in their ability to suppress the adrenergic response to hypoglycemia, and carvedilol may prolong or enhance low blood sugar levels by inhibiting liver glucose mobilization in response to hypoglycemia.

CYP2D6 inhibitors

Many medications are metabolized by a group of enzymes in the liver referred to as the cytochrome P450 enzymes, also known as CYP450. These enzymes can then be even further subclassified. Some medications may also act as inhibitors or inducers of those enzymes. Medications that require metabolism by a category of these CYP450 enzymes, but are also administered with medications that inhibit or induce them, can result in supratherapeutic or subtherapeutic serum concentrations of the medication whose metabolism is being altered. Carvedilol is metabolized by the subclass of CYP450 enzymes known as CYP2D6. When administered with CYP2D6 inhibitors, carvedilol serum concentrations and heart rate and blood pressure effects are increased. Known strong CYP2D6 inhibitors span multiple drug classes. The commonly prescribed serotonergic agents bupropion, fluoxetine, paroxetine, and duloxetine are a few of these medications. Database analysis revealed that patients treated with beta blockers metabolized by CYP2D6 and strong CYP2D6 inhibitor potential antidepressants faced a higher risk of hospitalization or emergency department visits. This increased risk was associated with events related to deteriorating cardiovascular function, presumed to result from excessive beta-receptor blockade when compared to patients not using such antidepressants. Patients receiving carvedilol with any moderate to strong CYP26 inhibiting medication should be monitored for signs and symptoms of increased carvedilol blood levels-including low blood pressure, slowed heart rate, or a drop in heart rate when going from a laying or sitting position to standing. 

Amiodarone

The interaction between amiodarone and carvedilol can be serious, even life-threatening, to the point of cardiac arrest. Amiodarone may enhance the decreased heart rate effect of beta-blockers, partially by increasing the blood levels of carvedilol through inhibition of its metabolism through CYP2D6, but also due to contributory beta-blockade from amiodarone itself. Many individuals are often purposefully placed on the combination of amiodarone and carvedilol by their physicians, but increased education about and monitoring for toxicities should be enforced.

Digoxin

The interaction between carvedilol and digoxin is complicated in that digoxin may enhance the bradycardic effect of carvedilol while carvedilol may increase the serum concentration of digoxin, which in worse-case scenarios, could result in digoxin toxicity. Digoxin toxicity may present as a constellation of symptoms, ranging from nausea and vomiting to visual disturbances and life-threatening arrhythmias. Digoxin serum concentrations must be measured before initiating carvedilol, and the digoxin dose may need to be decreased by up to 30% with further close monitoring. The mechanism of this interaction is likely due to carvedilol inhibition of P-glycoprotein, which plays a role in the digoxin’s disposition. Carvedilol’s prescribing information warns that concomitant use with digoxin can increase the risk of bradycardia. Caution should be exercised when these medications are taken together, with counseling provided by a healthcare professional on increased monitoring. 

Alpha 2 agonists 

Certain alpha-2 agonists, including clonidine, guanfacine, and methyldopa, may enhance the atrioventricular (AV) node-blocking effect of beta blockers like carvedilol. The AV node is a critical component of the heart’s electrical conduction system, connecting the heart’s atria and ventricles to coordinate beating. An AV node block can be a partial or complete interruption of this electrical transmission, making the heart beat more slowly or even resulting in irregular heartbeats. This interaction may be of more significance in individuals taking carvedilol for heart failure versus the management of hypertension. In addition to this interaction, carvedilol use may enhance the rebound hypertensive effect of alpha 2 agonists, such that clonidine prescribing information recommends that beta blockers be discontinued several days before clonidine is disrupted to decrease the risk. An increase follows the withdrawal of clonidine in levels of circulating catecholamines, which in the presence of certain beta blockers, allows the vasoconstrictive properties of these catecholamines on blood vessels to operate unopposed as a counterbalance. This can result in an exaggerated hypertensive response. Even if the beta blocker is discontinued several days before clonidine, blood pressure should be monitored closely. 

Nondihydropyridine calcium channel blockers 

The nondihydropyridine calcium channel blockers, diltiazem, and verapamil decrease heart rate such that when co-administered with carvedilol, it may enhance its bradycardic effects. Concurrent use of multiple agents that slow the heart rate increases the risk for symptomatic bradycardia. Caution should be exercised when combined with multiple medications capable of causing similar effects. Individuals should be counseled on the potential for the development of bradycardia and related symptoms, such as syncope and hypotension. 

Epinephrine

Epinephrine is a life-saving medication reserved for administration in life-threatening conditions, like a severe allergic reaction. Epinephrine is an alpha- and beta-receptor agonist, so in the setting of beta-blockade with carvedilol, the epinephrine is unable to saturate its site of action. Ultimately, epinephrine should be given in an anaphylaxis episode regardless of concomitant carvedilol use, and patients should be monitored for reduced responses to epinephrine effects.

Carvedilol food interactions

In some circumstances, carvedilol may increase serum potassium levels. Individuals with underlying conditions such as chronic kidney disease, who consume potassium-rich foods like bananas or orange juice, or who already need potassium replacement may reach dangerous levels requiring reversal to prevent heart arrhythmias. Always discuss any questions or concerns with a healthcare provider. 

Carvedilol and grapefruit 

To a minimal extent, grapefruit juice may inhibit the metabolism of carvedilol, increasing its blood concentrations. The best advice is to be consistent with your grapefruit juice intake. Drinking one glass daily can reliably adjust the carvedilol dose to the desired effect. However, if grapefruit juice is only consumed occasionally or occasionally consumed in great volumes, it may be best to find an alternative drink. 

Other carvedilol interactions

Carvedilol should be used cautiously with certain substances and in many medical conditions, especially those with impact circulating catecholamines or heart conditions. 

Carvedilol and heart conditions

Those with underlying heart conditions, including heart rhythm problems like sick sinus syndrome, can worsen their condition by taking carvedilol. Initiation of carvedilol should occur under direct supervision by a healthcare provider familiar with all underlying medical conditions.

Carvedilol and pheochromocytomas

Pheochromocytomas are catecholamine-secreting tumors of the adrenal gland. Management of the tumor is surgery, but pre-operatively a patient must be stabilized with alpha blockage followed by beta blockade. Beta blockage prior to alpha blockage can precipitate a pheochromocytoma crisis with even one dose of carvedilol, characterized by hemodynamic instability and kidney and liver dysfunction. 

Carvedilol and hyperthyroidism

Carvedilol may mask signs of an overactive thyroid, such as tachycardia. If hyperthyroidism is suspected in an individual taking carvedilol, the dose should be tapered conservatively as abrupt discontinuation may exacerbate the thyroid symptoms or precipitate a thyroid storm-which is considered a life-threatening medical emergency.

Carvedilol and reactive airway diseases

Individuals who will benefit from beta blockers, like those with coronary heart disease or severe heart failure, should receive them, given the reduction in mortality observed. There remains some hesitation to initiate beta-blocker therapy in patients with airway diseases since non-cardioselective beta blockers may increase airway reactivity and cause bronchospasm, which may present as shortness of breath. In addition, beta blockers may decrease the response to inhaled beta-receptor agonists, causing trouble breathing. Research has suggested that carvedilol may be less tolerated in asthma patients than in chronic obstructive pulmonary disease (COPD). A risk-to-benefit assessment should be performed between a healthcare professional and a patient to determine the appropriateness of beta-blocker therapy in those with these underlying medical conditions. Another consideration may be implementing cardioselective beta-blocker therapy, like metoprolol or atenolol, over carvedilol.

Carvedilol and alcohol 

Since alcohol can raise blood pressure, avoiding alcohol may be wise. This is particularly true when initiating carvedilol and not knowing how it might impact blood pressure or heart rate. 

Carvedilol and caffeine 

It is best to avoid caffeine when taking beta blockers, as it may decrease the effectiveness of the prescription drugs. In addition, the caffeine jolt increases blood pressure and heart rate, which is likely at least one of the conditions managed with carvedilol. Caffeine intake should be limited to no more than 200 mg per day. 

How to minimize carvedilol interactions

Always carry a complete list of medications, including supplements, on your person. When receiving medical advice with new therapy recommendations, provide this list to a healthcare professional so that a thorough review and drug information assessment can be performed. This will help minimize the risk of drug interactions. Anytime a new medication is started, and new signs or symptoms arise, however mild they might be, it’s best to review them with a healthcare professional. 

When to talk to a healthcare provider about carvedilol interactions

This article is not a complete list of carvedilol interactions. Be mindful of the risk of additive side effects and direct drug interactions, which may occur when carvedilol is used in combination with prescription and over-the-counter medications or supplements. Coordinate directly with a healthcare professional when using carvedilol to thoroughly assess medication interactions, dietary considerations, and existing health conditions. This will help establish an effective monitoring plan.