Drug Interactions between Dutoprol and galantamine
This report displays the potential drug interactions for the following 2 drugs:
- Dutoprol (hydrochlorothiazide/metoprolol)
- galantamine
Interactions between your drugs
metoprolol hydroCHLOROthiazide
Applies to: Dutoprol (hydrochlorothiazide / metoprolol) and Dutoprol (hydrochlorothiazide / metoprolol)
MONITOR: Although they are often combined in clinical practice, diuretics and beta-blockers may increase the risk of hyperglycemia and hypertriglyceridemia in some patients, especially in patients with diabetes or latent diabetes. In addition, the risk of QT interval prolongation and arrhythmias (e.g. torsades de pointes) due to sotalol may be increased by potassium-depleting diuretics.
MANAGEMENT: Monitoring of serum potassium levels, blood pressure, and blood glucose is recommended during coadministration. Patients should be advised to seek medical assistance if they experience dizziness, weakness, fainting, fast or irregular heartbeats, or loss of blood glucose control.
References
- Dornhorst A, Powell SH, Pensky J (1985) "Aggravation by propranolol of hyperglycaemic effect of hydrochlorothiazide in type II diabetics without alteration of insulin secretion." Lancet, 1, p. 123-6
- Roux A, Le Liboux A, Delhotal B, Gaillot J, Flouvat B (1983) "Pharmacokinetics in man of acebutolol and hydrochlorothiazide as single agents and in combination." Eur J Clin Pharmacol, 24, p. 801-6
- Dean S, Kendall MJ, Potter S, Thompson MH, Jackson DA (1985) "Nadolol in combination with indapamide and xipamide in resistant hypertensives." Eur J Clin Pharmacol, 28, p. 29-33
- (2002) "Product Information. Lozol (indapamide)." Rhone Poulenc Rorer
- Marcy TR, Ripley TL (2006) "Aldosterone antagonists in the treatment of heart failure." Am J Health Syst Pharm, 63, p. 49-58
metoprolol galantamine
Applies to: Dutoprol (hydrochlorothiazide / metoprolol) and galantamine
MONITOR: Since acetylcholinesterase inhibitors can cause bradycardia and heart block due to vagotonic effects on the sinoatrial and atrioventricular nodes, additive effects may occur with other agents that also possess bradycardic effects such as beta-blockers, calcium channel blockers, digitalis, some protease inhibitors (atazanavir, lopinavir-ritonavir, saquinavir), amiodarone, dronedarone, moricizine, lacosamide, and mefloquine. A group of French investigators conducted a retrospective analysis of spontaneous reports in the French Pharmacovigilance Database concerning adverse drug reactions (ADRs) associated with use of the acetylcholinesterase inhibitors donepezil, galantamine, and rivastigmine. Two hundred and five cases of potential drug-drug interaction with bradycardic drugs (beta-blockers, calcium channel blockers, amiodarone, digoxin) were identified, 73 of which were associated with serious ADRs including five deaths due to syncope, bradycardia, arrhythmia, or cardiac arrest. However, no details on the individual cases such as patient characteristics or concomitant risk factors were provided, making the contribution of a potential drug interaction difficult to evaluate. The remainder of the cases were of no apparent clinical consequences. In contrast, a phase III trial of donepezil consisting of 1035 patients reported no significant increase in risk ratios for bradycardia during concomitant use of beta-blockers, nondihydropyridine calcium channel blockers, or digoxin.
MANAGEMENT: Caution is advised if acetylcholinesterase inhibitors are used concomitantly with bradycardic drugs. Patients with underlying structural heart disease, preexisting conduction system abnormalities, ischemic heart disease, or cardiomyopathies may be at increased risk for developing cardiac conduction disturbances and atrioventricular block. Patients should be advised to notify their physician if they experience dizziness, lightheadedness, fainting, or irregular heartbeat.
References
- (2001) "Product Information. Cognex (tacrine)." Parke-Davis
- (2001) "Product Information. Aricept (donepezil)." Pfizer U.S. Pharmaceuticals
- (2001) "Product Information. Exelon (rivastigmine)." Novartis Pharmaceuticals
- (2005) "Product Information. Razadyne (galantamine)." Johnson and Johnson Medical Inc
- Tavassoli N, Sommet A, Lapeyre-Mestre M, Bagheri H, Montrastruc JL (2007) "Drug interactions with cholinesterase inhibitors : an analysis of the French pharmacovigilance database and a comparison of two national drug formularies (vidal, british national formulary)." Drug Saf, 30, p. 1063-71
- Tiseo PJ, Perdomo CA, Friedhoff LT (1998) "Concurrent administration of donepezil HCI and digoxin: assessment of pharmacokinetic changes." Br J Clin Pharmacol, 46(Suppl 1), p. 40-4
Drug and food interactions
metoprolol food
Applies to: Dutoprol (hydrochlorothiazide / 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
- (2001) "Product Information. Lopressor (metoprolol)." Novartis Pharmaceuticals
- Darcy PF (1995) "Nutrient-drug interactions." Adverse Drug React Toxicol Rev, 14, p. 233-54
galantamine food
Applies to: galantamine
ADJUST DOSING INTERVAL: The administration of galantamine with food and adequate fluid intake may reduce the impact of nausea, vomiting, diarrhea, anorexia, and weight loss that are commonly associated with acetylcholinesterase inhibitors (AChEIs). According to product labeling, the administration of food with various galantamine formulations (e.g., liquid, immediate-release tablets, modified/extended-release capsules) has no significant effect on the systemic absorption (AUC) of galantamine. While the presence of food has been shown to delay the rate of absorption (Tmax) and reduce peak concentration (Cmax), these changes are unlikely to be clinically significant. For example, when galantamine modified release was given after food, Tmax increased by approximately 30 minutes. Similarly, in 24 healthy elderly subjects, the presence of food with galantamine immediate release tablets (12 mg twice a day) delayed the Tmax by 1.5 hours and decreased the Cmax by about 25% without affecting the AUC.
MONITOR: Grapefruit and grapefruit juice may increase the plasma concentrations of galantamine, which is partially metabolized by the CYP450 3A4 isoenzyme. 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 with both moderate and potent CYP450 3A4 inhibitors. When study subjects (n=16) received the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice daily for 4 days) with galantamine (4 mg twice daily for 8 days), the systemic exposure (AUC) of galantamine increased by 30%. However, when study subjects (n=16) received the moderate CYP450 3A4 inhibitor erythromycin (500 mg 4 times daily for 4 days) with galantamine (4 mg twice daily for 6 days), the AUC of galantamine only increased by 10%. In general, the effects of grapefruit products are concentration-, dose-, and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit (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. While the clinical significance of this interaction is unknown, increased exposure to galantamine may lead to AChEI related adverse effects such as vagotonic effects on the heart rate (e.g., bradycardia and heart block), neurologic side effects (e.g., seizure activity), respiratory distress, bladder outflow obstruction, dizziness or syncope, nausea, vomiting and/or diarrhea.
MANAGEMENT: According to product labeling, galantamine should be administered with food and adequate fluid intake to reduce the impact of cholinergic-related gastrointestinal adverse effects (e.g., nausea, vomiting, diarrhea, anorexia, and weight loss). Caution and closer monitoring for AChEI related adverse effects may advisable if galantamine is used in combination with grapefruit and/or grapefruit juice. Modified and/or extended-release formulations must also be swallowed whole and not crushed, chewed, or divided.
References
- (2024) "Product Information. Galantamine Hydrobromide ER (galantamine)." Aurobindo Pharma USA Inc
- (2024) "Product Information. Galantamine Hydrobromide (galantamine)." Aurobindo Pharma USA Inc
- (2022) "Product Information. Gaalin (galantamine)." Auro Pharma Inc
- (2023) "Product Information. Galzemic (galantamine)." Zentiva Pharma UK Ltd
- (2023) "Product Information. Galantyl (galantamine)." Viatris UK Healthcare Ltd
- (2020) "Product Information. Auro-Galantamine ER (galantamine)." Auro Pharma Inc
hydroCHLOROthiazide food
Applies to: Dutoprol (hydrochlorothiazide / metoprolol)
MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.
MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.
References
- Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
- Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
- Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
- Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
- Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
- Cerner Multum, Inc. "Australian Product Information."
- Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
- Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
metoprolol food
Applies to: Dutoprol (hydrochlorothiazide / 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
- 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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