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Major Amiodarone prolongs AV nodal refractory period and decreases sinus node automaticity. Because beta-blockers have similar effects, concomitant administration of beta-blockers with amiodarone may cause additive electrophysiologic effects slow sinus rate or worsen AV block , resulting in symptomatic bradycardia, sinus arrest, and atrioventricular block. This is particularly likely in patients with preexisting partial AV block or sinus node dysfunction.
Concomitant administration of amiodarone and carvedilol increased the concentration of the S - enantiomer of carvedilol by at least 2-fold. Caution is advised as metoprolol, another beta-blocker metabolized by CYP2D6, in combination with amiodarone has resulted in severe sinus bradycardia. While the combination should be used cautiously and with close monitoring, it should be noted that post-hoc analysis of amiodarone therapy in patients after acute myocardial infarction in two clinical trials revealed that amiodarone in addition to a beta-blocker significantly lowered the incidence of cardiac and arrhythmic death or resuscitated cardiac arrest when compared with amiodarone or beta-blocker therapy alone.
Patients receiving amiodarone concurrently with carvedilol should be monitored for bradycardia or heart block, especially when one agent is added to pre-existing treatment with the other.
Moderate Concomitant use of carvedilol and atorvastatin may result in increased atorvastatin concentrations. Carvedilol is a P-glycoprotein P-gp inhibitor and atorvastatin is a P-gp substrate. Monitor serum lipid profile and for signs and symptoms of myopathy during coadministration.
Moderate Although concurrent use of amobarbital with antihypertensive agents may lead to hypotension, barbiturates, as a class, can enhance the hepatic metabolism of beta-blockers that are significantly metabolized by the liver. Beta-blockers that may be affected include betaxolol, labetalol, metoprolol, pindolol, propranolol, and timolol. Clinicians should closely monitor patients blood pressure during times of coadministration. Carvedilol and lansoprazole are both substrates and inhibitors of P-glycoprotein P-gp.
Use caution if concomitant use is necessary and monitor for increased side effects. Carvedilol and omeprazole are both substrates and inhibitors of P-glycoprotein P-gp. Moderate Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as antihypertensive agents or other peripheral vasodilators. Patients should be monitored more closely for hypotension if nitroglycerin, including nitroglycerin rectal ointment, is used concurrently with any beta-blockers.
Minor Hyperthyroidism may cause increased clearance of beta blockers that possess a high extraction ratio. A dose reduction of some beta-blockers may be needed when a hyperthyroid patient treated with methimazole becomes euthyroid. Major Concomitant use of carvedilol and apixaban may result in increased apixaban concentrations. Carvedilol is a P-glycoprotein P-gp inhibitor and apixaban is a P-gp substrate. Increased exposure to apixaban may result in increased risk of bleeding.
Monitor for evidence of bleeding during concurrent use. Extreme caution should be exercised if apomorphine is used concurrently with antihypertensive agents. Minor Theoretically, additive blood pressure reductions could occur when apraclonidine is combined with antihypertensive agents. Minor Aripiprazole may enhance the hypotensive effects of antihypertensive agents.
It may be advisable to monitor blood pressure when these medications are coadministered. Moderate Concomitant use of carvedilol and armodafinil may result in increased armodafinil concentrations.
Carvedilol is a P-glycoprotein P-gp inhibitor. An in vitro study indicated that and armodafinil is a P-gp substrate. Observation of the patient for increased effects from armodafinil may be needed. Moderate Lumefantrine is an inhibitor and carvedilol is a substrate of the CYP2D6 isoenzyme; therefore, coadministration may lead to increased carvedilol concentrations. Concomitant use warrants caution due to the potential for increased side effects.
Moderate Local anesthetics may cause additive hypotension in combination with antihypertensive agents. Thus, patients receiving antihypertensive agents may experience additive hypotensive effects. Moderate Secondary to alpha-blockade, asenapine can produce vasodilation that may result in additive effects during concurrent use of carvedilol. The potential reduction in blood pressure can precipitate orthostatic hypotension and associated dizziness, tachycardia, and syncope.
If concurrent use is necessary, patients should be counseled on measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning and rising slowly from a seated position. Close monitoring of blood pressure is recommended until the full effects of the combination therapy are known; the carvedilol dosage may need to be adjusted.
Major Beta-blockers should generally be withheld before dipyridamole-stress testing. Monitor the heart rate carefully following the dipyridamole injection. Moderate Atazanavir can prolong the PR interval. Coadministration with other agents that prolong the PR interval, like beta blockers, may result in elevated risk of conduction disturbances and atrioventricular block. Moderate Coadministration of cobicistat a CYP2D6 inhibitor with beta-blockers metabolized by CYP2D6, such as carvedilol, may result in elevated beta-blocker serum concentrations.
If used concurrently, close clinical monitoring with appropriate beta-blocker dose reductions are advise. Moderate Cutaneous vasodilation induced by niacin may become problematic if high-dose niacin is used concomitantly with other antihypertensive agents.
This effect is of particular concern in the setting of acute myocardial infarction, unstable angina, or other acute hemodynamic compromise. Moderate Carvedilol and azithromycin are both substrates and inhibitors of P-glycoprotein PGP ; therefore, increased concentrations of either drug may occur with coadministration.
Monitor patients for increased side effects if these drugs are given together. Moderate Baclofen has been associated with hypotension. Concurrent use with baclofen and antihypertensive agents may result in additive hypotension.
Dosage adjustments of the antihypertensive medication may be required. Belladonna Alkaloids; Ergotamine; Phenobarbital: Moderate Concurrent use of beta-blockers and ergot alkaloids should be approached with caution. Concomitant administration with beta-blockers may enhance the vasoconstrictive action of certain ergot alkaloids including dihydroergotamine, ergotamine, methylergonovine, and methysergide.
The risk of peripheral ischemia, resulting in cold extremities or gangrene, has been reported to be increased when ergotamine or dihydroergotamine is coadministered with selected beta-blockers, including propranolol, a beta-blocker commonly used for migraine prophylaxis.
However, the precise mechanism of these interactions remains elusive. Additionally, because of the potential to cause coronary vasospasm, these ergot alkaloids could antagonize the therapeutic effects of anti-anginal agents including beta-blockers; clinicians should keep in mind that ergot alkaloids are contraindicated for use in patients with coronary heart disease or hypertension.
Moderate Use of a betaselective cardioselective beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used.
Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present. Major Avoid betrixaban use in patients with severe renal impairment receiving carvedilol. Reduce betrixaban dosage to 80 mg PO once followed by 40 mg PO once daily in all other patients receiving carvedilol.
Bleeding risk may be increased; monitor patients closely for signs and symptoms of bleeding. Betrixaban is a substrate of P-gp; carvedilol inhibits P-gp. Moderate Concurrent use of beta-blockers with bismuth subsalicylate and other salicylates may result in loss of antihypertensive activity due to inhibition of renal prostaglandins and thus, salt and water retention and decreased renal blood flow.
Bismuth Subsalicylate; Metronidazole; Tetracycline: Moderate Close clinical monitoring is advised when administering carvedilol with boceprevir due to an increased potential for carvedilol and or boceprevir-related adverse events.
If carvedilol dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of carvedilol.
Carvedilol is an inhibitor and substrate of the drug efflux transporter P-glycoprotein PGP ; boceprevir is an inhibitor and substrate of this efflux protein. Coadministration may result in elevated plasma concentrations of either drug. Moderate Although no specific interactions have been documented, bosentan has vasodilatory effects and may contribute additive hypotensive effects when given with beta-blockers.
Major Because the pharmacologic effects of carvedilol include AV nodal conduction depression, additive effects are possible when used in combination with antiarrhythmics such as bretylium. Moderate Due to brexpiprazole's antagonism at alpha 1-adrenergic receptors, the drug may enhance the hypotensive effects of alpha-blockers and other antihypertensive agents. Minor Bromocriptine has only minimal affinity for adrenergic receptors; however, hypotension can occur during bromocriptine administration.
It is unknown if bromocriptine is the exact cause of this effect. However, the drug should be used cautiously with other medications known to lower blood pressure such as antihypertensive agents. Monitoring of blood pressure should be considered, especially during the initial weeks of concomitant therapy. Minor Increased concentrations of budesonide may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein P-gp inhibitor and budesonide is a P-gp substrate.
Use extreme caution with the concomitant use of bupivacaine and antihypertensive agents. Peripheral vasodilation may occur after use of bupivacaine. Blood concentrations of local anesthetics achieved after therapeutic doses are associated with minimal change in peripheral vascular resistance.
Higher blood concentrations of local anesthetics may occur due to inadvertent intravascular administration or repeated doses.
Major Drugs such as beta-blockers that decrease cardiac output reduce hepatic blood flow and thereby decrease lidocaine hepatic clearance. Also, opposing effects on conduction exist between lidocaine and beta-blockers while their effects to decrease automaticity may be additive. Propranolol has been shown to decrease lidocaine clearance and symptoms of lidocaine toxicity have been seen as a result of this interaction.
This interaction is possible with other beta-blocking agents since most decrease hepatic blood flow. Monitoring of lidocaine concentrations is recommended during concomitant therapy with beta-blockers.
Minor Monitor for an increased incidence of carvedilol-related adverse effects if bupropion and carvedilol are used concomitantly. Coadministration of bupropion and carvedilol may result in increased plasma concentrations of carvedilol. Bupropion and hydroxybupropion, the major active metabolite, are inhibitors of CYP2D6 in vitro.
Carvedilol is a CYP2D6 substrate. Major Because of its potential to cause coronary vasospasm, ergot alkaloids could theoretically antagonize the therapeutic effects of beta-blockers. Moderate Monitor for an increase in carvedilol-related adverse events if concomitant use with cabozantinib is necessary, as plasma concentrations of carvedilol may be increased. Cabozantinib is a P-glycoprotein P-gp inhibitor and carvedilol is a substrate of P-gp; the clinical relevance of this finding is unknown.
Canagliflozin is a substrate of drug transporter P-glycoprotein P-gp. Carvedilol is a P-gp inhibitor and may theoretically increase concentrations of canagliflozin. Moderate Use caution if coadministration of capecitabine with carvedilol is necessary, and monitor for an increase in carvedilol-related adverse reactions, including bradycardia or heart block.
Moderate Concomitant use of beta-blockers with levodopa can result in additive hypotensive effects. Moderate Orthostatic vital signs should be monitored in patients who are at risk for hypotension, such as those receiving cariprazine in combination with antihypertensive agents.
Atypical antipsychotics may cause orthostatic hypotension and syncope, most commonly during treatment initiation and dosage increases. Patients should be informed about measures to prevent orthostatic hypotension, such as sitting on the edge of the bed for several minutes prior to standing in the morning, or rising slowly from a seated position. Consider a cariprazine dose reduction if hypotension occurs.
Major Avoid coadministration of ceritinib with carvedilol due to the risk of additive bradycardia. If coadministration is unavoidable, monitor heart rate and blood pressure regularly and watch for carvedilol-related adverse reactions. An interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary. Conduction disturbances are possible with concurrent use of beta-blockers and cevimeline.
Major Monitor heart rate in patients receiving concomitant clonidine and agents known to affect sinus node function or AV nodal conduction e. Severe bradycardia resulting in hospitalization and pacemaker insertion has been reported during combination therapy with clonidine and other sympatholytic agents.
Concomitant use of clonidine with beta-blockers can also cause additive hypotension. Beta-blockers should not be substituted for clonidine when modifications are made in a patient's antihypertensive regimen because beta-blocker administration during clonidine withdrawal can augment clonidine withdrawal, which may lead to a hypertensive crisis.
If a beta-blocker is to be substituted for clonidine, clonidine should be gradually tapered and the beta-blocker should be gradually increased over several days to avoid the possibility of rebound hypertension; administration of beta-blockers during withdrawal of clonidine can precipitate severe increases in blood pressure as a result of unopposed alpha stimulation.
Choline Salicylate; Magnesium Salicylate: Moderate Monitor for an increased incidence of carvedilol-related adverse effects if cimetidine and carvedilol are used concomitantly. Maximum serum concentrations of carvedilol are not increased. Minor Cinacalcet, a strong in vitro inhibitor of the CYP2D6 cytochrome P enzyme, may theoretically increase concentrations of other drugs metabolized by this enzyme, including carvedilol. This can result in increased concentrations of drugs metabolized via the same pathway, including carvedilol.
Moderate Calcium-channel blockers, like clevidipine, and beta-blockers frequently are used together with no adverse reactions. Patients should be monitored carefully, however, for excessive bradycardia, cardiac conduction abnormalities, or hypotension if these drugs are given together. Moderate Coadministration of clobazam and carvedilol may result in increased concentrations of either drug. Adverse effects, such as bradycardia, hypotension, sedation, lethargy, ataxia, or insomnia may be potentiated.
Moderate Clozapine used concomitantly with the antihypertensive agents can increase the risk and severity of hypotension by potentiating the effect of the antihypertensive drug. Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: Moderate Increased concentrations of tenofovir, pmpa may occur if it is coadministered with carvedilol; exercise caution.
Carvedilol is a P-glycoprotein P-gp inhibitor and tenofovir is a P-gp substrate. Minor If concurrent use of cobimetinib and carvedilol is necessary, use caution and monitor for a possible increase in cobimetinib-related adverse effects.
Cobimetinib is a P-glycoprotein P-gp substrate, and carvedilol is a weak P-gp inhibitor; coadministration may result in increased cobimetinib exposure. However, coadministration of cobimetinib with another P-gp inhibitor, vemurafenib mg twice daily , did not result in clinically relevant pharmacokinetic drug interactions. Moderate Fish oil supplements may cause mild, dose-dependent reductions in systolic or diastolic blood pressure in untreated hypertensive patients.
Relatively high doses of fish oil are required to produce any blood pressure lowering effect. Additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. Moderate High doses of fish oil supplements may produce a blood pressure lowering effect.
It is possible that additive reductions in blood pressure may be seen when fish oils are used in a patient already taking antihypertensive agents. Moderate Co-enzyme Q10, ubiquinone CoQ10 may lower blood pressure. CoQ10 use in combination with antihypertensive agents may lead to additional reductions in blood pressure in some individuals. Patients who choose to take CoQ10 concurrently with antihypertensive medications should receive periodic blood pressure monitoring.
Patients should be advised to inform their prescriber of their use of CoQ Major Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and carvedilol in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations.
Carvedilol can inhibit colchicine's metabolism via P-glycoprotein P-gp , resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity.
Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a P-gp inhibitor like carvedilol in the past 14 days or require concurrent use: Moderate There is potential for additive hypotensive effects when conivaptan is coadministered with antihypertensive agents.
Major Bradycardia has been reported in patients treated with crizotinib, which may be exacerbated when crizotinib is administered concomitantly with agents known to cause bradycardia, such as beta-blockers. This combination should be avoided if possible.
In addition, concomitant use of crizotinib and carvedilol may result in altered concentrations of either drug. Moderate Modest increases in mean trough cyclosporine concentrations may occur following initiation of carvedilol treatment. It is recommended that cyclosporine serum concentrations be monitored to individualize dosage. Moderate Increased serum concentrations of dabigatran are possible when dabigatran, a P-glycoprotein P-gp substrate, is coadministered with carvedilol, a P-gp inhibitor.
Patients should be monitored for increased adverse effects of dabigatran. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran. Moderate Systemic exposure of carvedilol, a P-glycoprotein P-gp substrate, may be increased when administered concurrently with daclatasvir, a P-gp inhibitor. Taking these drugs together could increase or prolong the therapeutic effects of carvedilol; monitor patients for potential adverse effects.
Moderate Beta-blockers can prolong hypoglycemia by interfering with glycogenolysis or can promote hyperglycemia. In addition, beta-blockers may mask the signs and symptoms of hypoglycemia and exaggerate the hypertensive response to hypoglycemia. Patients receiving beta-blockers and antidiabetic agents concomitantly should be closely monitored for an inappropriate response to the antidiabetic agent.
Moderate Coadministration of darunavir with carvedilol may result in elevated carvedilol concentrations. If used concurrently, close clinical monitoring with appropriate dose reductions are advised. Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: Moderate Concurrent administration of carvedilol with dasabuvir; ombitasvir; paritaprevir; ritonavir may result in elevated plasma concentrations of carvedilol and all 4 antiviral drugs. Carvedilol is a substrate of the hepatic isoenzyme CYP2D6 and a substrate and inhibitor of the drug transporter P-glycoprotein P-gp.
In addition, dasabuvir, ombitasvir, paritaprevir, and ritonavir are all P-gp substrates. Caution and close monitoring are advised if these drugs are administered together.
Moderate Concurrent administration of carvedilol with dasabuvir; ombitasvir; paritaprevir; ritonavir or ombitasvir; paritaprevir; ritonavir may result in elevated plasma concentrations of carvedilol and the components of the hepatitis C regimen. In addition, both drugs are inhibitors and subtrates for P-glycoprotein P-gp. Moderate Increased concentrations of daunorubicin may occur if it is coadministered with carvedilol; exercise caution.
Carvedilol is a P-glycoprotein P-gp inhibitor and daunorubicin is a P-gp substrate. Minor Delavirdine inhibits CYP2D6 and may increase concentrations of other drugs metabolized by this enzyme, including carvedilol. Moderate Concurrent use of beta-blockers with desflurane may result in exaggerated cardiovascular effects e. Beta-blockers may be continued during general anesthesia as long as the patient is monitored for cardiac depressant and hypotensive effects. Withdrawal of a beta-blocker perioperatively may be detrimental to the patient's clinical status and is not recommended.
Caution is advised if these drugs are administered together. Minor Because thyroid hormones cause cardiac stimulation including increased heart rate and increased contractility, the effects of beta-blockers may be reduced by thyroid hormones. The reduction of effects may be especially evident when a patient goes from a hypothyroid to a euthyroid state or when excessive amounts of thyroid hormone is given to the patient. Minor Increased concentrations of desloratadine may occur if it is coadministered with carvedilol; exercise caution.
Carvedilol is a P-glycoprotein P-gp inhibitor and desloratadine is a P-gp substrate. Minor Increased concentrations of dexamethasone may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein P-gp inhibitor and dexamethasone is a P-gp substrate. Major In general, the concomitant administration of dexmedetomidine with antihypertensive agents could lead to additive hypotensive effects. Dexmedetomidine can produce bradycardia or AV block and should be used cautiously in patients who are receiving antihypertensive drugs that lower the heart rate such as beta-blockers.
Major Quinidine may have additive effects e. Patients should be monitored for excess beta-blockade. Reduce the beta-blocker dosage if necessary. Moderate Additive hypotensive effects can occur with the concomitant administration of diazoxide with other antihypertensive agent. This interaction can be therapeutically advantageous, but dosages must be adjusted accordingly. The manufacturer advises that IV diazoxide should not be administered to patients within 6 hours of receiving beta-blockers.
No significant changes in digoxin exposure were reported when digoxin was administered intravenously IV. Digoxin and carvedilol are both substrates for P-glycoprotein P-gp. Measure serum digoxin concentrations before initiating carvedilol. No dosage adjustment is required when digoxin is administered IV. In addition, coadministration of digoxin with beta-blockers may produce additive effects on AV node conduction resulting in bradycardia and advanced or complete heart block.
Despite potential for interactions, digoxin sometimes is intentionally used in combination with a beta-blocker to further reduce conduction through the AV node. Nevertheless, these combinations should be used cautiously, and therapy dosages may need adjustment in some patients. Moderate The combination of diltiazem and a beta-blocker, like carvedilol, is usually well tolerated; the combination is often used for their combined therapeutic benefits to reduce angina and improve exercise tolerance.
However, because beta-blockers and diltiazem are negative inotropes and chronotropes, the combination of beta-blockers and diltiazem may cause heart failure, excessive bradycardia, hypotension, cardiac conduction abnormalities, or heart block. Major Disopyramide and beta-blockers, like carvedilol, have been used together for the treatment of ventricular arrhythmias; however, this combination should be used with caution due to the potential for additive AV blocking effects.
Major Increased concentrations of docetaxel may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein P-gp inhibitor and docetaxel is a P-gp substrate. Moderate Increased concentrations of doxorubicin may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein P-gp inhibitor and doxorubicin is a P-gp substrate. Major In dronedarone clinical trials, bradycardia was seen more frequently in patients also receiving beta blockers.
If coadministration of dronedarone and a beta blocker is unavoidable, administer a low dose of the beta blocker initially and increase the dosage only after ECG verification of tolerability. Concomitant administration may decreased AV and sinus node conduction. Coadministration of dronedarone with a single dose of propranolol and multiple doses of metoprolol increased propranolol and metoprolol exposure by 1.
Moderate Increased concentrations of ethinyl estradiol may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein P-gp inhibitor and ethinyl estradiol is a P-gp substrate. Drospirenone; Ethinyl Estradiol; Levomefolate: Moderate Orthostatic hypotension and syncope have been reported during duloxetine administration. The concurrent administration of carvedilol and duloxetine may increase the risk of hypotension. It is advisable to monitor blood pressure if the combination is necessary.
Minor Tamsulosin did not potentiate the hypotensive effects of atenolol. However, since the symptoms of orthostasis are reported more frequently in tamsulosin-treated vs.
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