Pharmacokinetic interaction
Because the carvedilol is both a substrate and an inhibitor of glycoprotein P, when it is simultaneously administered with preparations transported with glycoprotein P, the bioavailability of the latter can increase. In addition, the bioavailability of carvedilol can be altered by the action of inducers or inhibitors of the glycoprotein P.
Inhibitors and inducers CYP2D6 and CYP2C9 can stereoselectively alter the systemic and / or presystemic metabolism of carvedilol, leading to an increase or decrease in concentrations R and S stereoisomers of carvedilol in blood plasma. Some examples of similar interactions observed in patients or in healthy volunteers are listed below, but this list is not complete.
Digoxin
With simultaneous administration of carvedilol and digoxin, digoxin concentrations increase by about 15%. At the beginning of therapy with carvedilol, when selecting its dose or canceling the drug, regular monitoring of the concentration of digoxin in the blood plasma is recommended.
Cyclosporin
In two studies on carvedilol administration, patients who underwent kidney and heart transplant and received ciclosporin orally, there was an increase in the concentration of cyclosporine. It turned out that due to inhibition of the activity of glycoprotein P in the intestine, carvedilol increases the absorption of cyclosporine when taken orally. To maintain concentrations of cyclosporine in the therapeutic range, it was required to reduce the dose of cyclosporine by an average of 10-20%. In connection with the expressed individual fluctuations in the concentration of cyclosporin, careful monitoring of its concentration after the initiation of carvedilol therapy and, if necessary, appropriate correction of the daily dose of cyclosporine is recommended. In the case of intravenous administration of cyclosporine, no interaction with carvedilol is expected.
Rifampicin
In a study involving healthy volunteers rifampicin reduced plasma concentrations of carvedilol, most likely by induction of glycoprotein P, leading to a decrease in carvedilol absorption in the intestine and a decrease in its antihypertensive effect.
Amiodarone
In patients with heart failure amiodarone reduced ground clearance S-steroisomer of carvedilol, suppressing CYP2C9. Average concentration RThe stereoisomer of carvedilol did not change. Consequently, in connection with the increase in concentration Scarbodilol stereoisomer, a risk of an increase in beta-adrenergic blocking effect is possible.
Fluoxetine
In a randomized, cross-design study in patients with heart failure, simultaneous administration of fluoxetine (an inhibitor CYP2D6) led to stereoselective suppression of carvedilol metabolism - an increase in the average AUC for R (+) by 77%. However, there were no differences in side effects, blood pressure or heart rate between the two groups.
Pharmacodynamic interaction
Insulin or hypoglycemic agents for oral administration
Drugs with beta-adrenoblocking properties may increase the hypoglycemic effect of insulin or hypoglycemic agents for oral administration. Symptoms of hypoglycemia, especially tachycardia, can be masked or weakened. Patients receiving insulin or hypoglycemic agents for oral administration are encouraged to regularly monitor blood glucose.
Drugs that reduce the content of catecholamines
Patients taking concomitantly with beta-adrenergic blocking properties and catecholamine-lowering agents (for example, reserpine and monoamine oxidase inhibitors) should be carefully monitored for the risk of arterial hypotension and / or severe bradycardia.
Digoxin
Combination therapy of agents with beta-adrenergic blocking properties and digoxin can lead to an additional delay in atrioventricular conduction.
Verapamil, diltiazem, amiodarone or other antiarrhythmic agents
Simultaneous administration with carvedilol may increase the risk of atrioventricular conduction.
Clonidine
Simultaneous administration of clonidine with drugs with beta-adrenoblocking properties may potentiate an antihypertensive and bradycardic effect.
If you plan to stop combination therapy with a drug with beta-adrenergic blocking properties and clonidine, you should first cancel the beta-blocker, and in a few days you can cancel clonidine, gradually reducing its dose.
Blocks of "slow" calcium channels (BCCI)
With the simultaneous administration of carvedilol and diltiazem, there were isolated cases of conduction disorders (rarely - with disturbances in hemodynamic parameters). As with other drugs with beta-adrenergic blocking properties, the appointment of carvedilol along with BMPC like verapamil or diltiazem is recommended to be performed under the control of ECG and AD.
Antihypertensive drugs
Like other drugs with beta-adrenergic blocking activity, carvedilol may enhance the effect of other concurrently taken antihypertensive agents (eg, alpha 1-blockers) or drugs that cause arterial hypotension as a side effect.
Means for general anesthesia
It should be carefully monitored for the main indicators of life of the body during general anesthesia in connection with the possibility of a synergistic negative inotropic action of carvedilol and funds for general anesthesia.
Non-steroidal anti-inflammatory drugs (NSAIDs)
Joint reception of NSAIDs and beta-blockers can lead to an increase in blood pressure and a decrease in blood pressure control.
Bronchodilators (beta-adrenergic agonists)
Since noncardioselective beta-blockers interfere with the bronchodilating effect of bronchodilators, which are beta-adrenergic receptor stimulants, careful monitoring of patients receiving these drugs is necessary.