Drug Interactions between mavacamten and metoprolol
This report displays the potential drug interactions for the following 2 drugs:
- mavacamten
- metoprolol
Interactions between your drugs
metoprolol mavacamten
Applies to: metoprolol and mavacamten
MONITOR CLOSELY: Concomitant use of other drugs that reduce cardiac contractility may potentiate the negative inotropic effects of mavacamten and increase the risk of heart failure.
MANAGEMENT: Close medical supervision and monitoring of left ventricular ejection fraction (LVEF) are recommended if a negative inotrope is initiated or the dose increased during treatment with mavacamten. The prescribing information suggests that use of mavacamten in patients on beta blocker therapy and either diltiazem or verapamil should be avoided. New or worsening arrhythmia, dyspnea, chest pain, fatigue, palpitations, leg edema, or elevations in N-terminal pro-B-type natriuretic peptide (NT-proBNP) may be signs and symptoms of heart failure and should also prompt an echocardiographic evaluation of cardiac function. Asymptomatic LVEF reduction, intercurrent illnesses (e.g., serious infections), and arrhythmias (e.g., atrial fibrillation or other uncontrolled tachyarrhythmia) require additional dosing considerations.
References (2)
- (2022) "Product Information. Camzyos (mavacamten)." MyoKardia Inc
- (2023) "Product Information. Camzyos (mavacamten)." Bristol-Myers Squibb Australia Pty Ltd, 2
Drug and food interactions
mavacamten food
Applies to: mavacamten
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of mavacamten. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. According to the prescribing information, mavacamten is primarily metabolized by CYP450 2C19 (74%) and to a lesser extent by CYP450 3A4 (18%) and 2C9 (8%). When mavacamten (25 mg) was coadministered with the moderate CYP450 3A4 inhibitor verapamil (sustained-release 240 mg) in intermediate and normal metabolizers of CYP450 2C19, mavacamten systemic exposure (AUC) increased by 15% and peak plasma concentration (Cmax) increased by 52%. Concomitant use of mavacamten with diltiazem, another moderate CYP450 3A4 inhibitor, in CYP450 2C19 poor metabolizers is predicted to increase mavacamten AUC and Cmax by up to 55% and 42%, respectively. Concomitant use of mavacamten (15 mg) with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily) is predicted to increase mavacamten AUC and Cmax by up to 130% and 90%, respectively. Because mavacamten reduces systolic contraction and left ventricular ejection fraction, increased exposure may potentiate the risk of heart failure. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.
Food does not affect the extent of absorption of mavacamten. No clinically significant difference in mavacamten exposure was observed following administration with a high-fat meal. However, the time to reach peak plasma concentration (Tmax) was increased by 4 hours.
MANAGEMENT: Mavacamten may be administered with or without food. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with mavacamten.
References (2)
- (2022) "Product Information. Camzyos (mavacamten)." MyoKardia Inc
- (2023) "Product Information. Camzyos (mavacamten)." Bristol-Myers Squibb Australia Pty Ltd, 2
metoprolol food
Applies to: metoprolol
ADJUST DOSING INTERVAL: The bioavailability of metoprolol may be enhanced by food.
MANAGEMENT: Patients may be instructed to take metoprolol at the same time each day, preferably with or immediately following meals.
References (2)
- (2001) "Product Information. Lopressor (metoprolol)." Novartis Pharmaceuticals
- Darcy PF (1995) "Nutrient-drug interactions." Adverse Drug React Toxicol Rev, 14, p. 233-54
metoprolol food
Applies to: metoprolol
ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.
MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.
References (1)
- Kirch W, Schafer-Korting M, Axthelm T, Kohler H, Mutschler E (1981) "Interaction of atenolol with furosemide and calcium and aluminum salts." Clin Pharmacol Ther, 30, p. 429-35
Therapeutic duplication warnings
No warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
No interaction information available. |
Further information
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