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Diphenhist

Interactions

Metoprolol/Selected CYP2D6 Inhibitors

This information is generalized and not intended as specific medical advice. Consult your healthcare professional before taking or discontinuing any drug or commencing any course of treatment.

Medical warning:

Moderate. These medicines may cause some risk when taken together. Contact your healthcare professional (e.g. doctor or pharmacist) for more information.

How the interaction occurs:

Some medicines may slow down how quickly your body processes metoprolol.

What might happen:

The amount of metoprolol in your blood may increase and cause more side effects than normal.

What you should do about this interaction:

Let your healthcare professionals (e.g doctor or pharmacist) know that you are taking these medicines together. Let your doctor know if you experience a slow heartbeat, weakness, fatigue, or dizziness. Your medicine may need to be adjusted.Your healthcare professionals may already be aware of this interaction and may be monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking with them first.

References:

1.Lopressor (metoprolol tartrate) US prescribing information. Validus Pharmaceuticals. LLC March, 2013.

2.Toprol-XL (metoprolol succinate) US prescribing information. AstraZeneca LP March, 2011.

3.McCollum DL, Greene JL, McGuire DK. Severe sinus bradycardia after initiation of bupropion therapy: a probable drug-drug interaction with metoprolol. Cardiovasc Drugs Ther 2004 Jul;18(4):329-30.

4.Werner U, Werner D, Rau T, Fromm MF, Hinz B, Brune K. Celecoxib inhibits metabolism of cytochrome P450 2D6 substrate metoprolol in humans. Clin Pharmacol Ther 2003 Aug;74(2):130-7.

5.Celexa (citalopram hydrobromide) US prescribing information. Forest Laboratories Inc. December, 2012.

6.Sharma A, Pibarot P, Pilote S, Dumesnil JG, Arsenault M, Belanger PM, Meibohm B, Hamelin BA. Modulation of metoprolol pharmacokinetics and hemodynamics by diphenhydramine coadministration during exercise testing in healthy premenopausal women. J Pharmacol Exp Ther 2005 Jun; 313(3):1172-81.

7.Hamelin BA, Bouayad A, Methot J, Jobin J, Desgagnes P, Poirier P, Allaire J, Dumesnil J, Turgeon J. Significant interaction between the nonprescription antihistamine diphenhydramine and the CYP2D6 substrate metoprolol in healthy men with high or low CYP2D6 activity. Clin Pharmacol Ther 2000 May;67(5):466-77.

8.Preskorn SH, Greenblatt DJ, Flockhart D, Luo Y, Perloff ES, Harmatz JS, Baker B, Klick-Davis A, Desta Z, Burt T. Comparison of duloxetine, escitalopram, and sertraline effects on cytochrome P450 2D6 function in healthy volunteers. J Clin Psychopharmacol 2007 Feb;27(1):28-34.

9.Belpaire FM, Wijnant P, Temmerman A, Rasmussen BB, Brosen K. The oxidative metabolism of metoprolol in human liver microsomes: inhibition by the selective serotonin reuptake inhibitors. Eur J Clin Pharmacol 1998 May; 54(3):261-4.

10.Walley T, Pirmohamed M, Proudlove C, Maxwell D. Interaction of metoprolol and fluoxetine. Lancet 1993 Apr 10;341(8850):967-8.

11.Somer M, Kallio J, Pesonen U, Pyykko K, Huupponen R, Scheinin M. Influence of hydroxychloroquine on the bioavailability of oral metoprolol. Br J Clin Pharmacol 2000 Jun;49(6):549-54.

12.Wang Y, Zhou L, Dutreix C, Leroy E, Yin Q, Sethuraman V, Riviere GJ, Yin OQ, Schran H, Shen ZX. Effects of imatinib (Glivec) on the pharmacokinetics of metoprolol, a CYP2D6 substrate, in Chinese patients with chronic myelogenous leukaemia. Br J Clin Pharmacol 2008 Jun; 65(6):885-92.

13.Kendall MJ, Jack DB, Quarterman CP, Smith SR, Zaman R. Beta-adrenoceptor blocker pharmacokinetics and the oral contraceptive pill. Br J Clin Pharmacol 1984;17 Suppl 1:87S-89S.

14.Parker RB, Soberman JE. Effects of paroxetine on the pharmacokinetics and pharmacodynamics of immediate-release and extended-release metoprolol. Pharmacotherapy 2011 Jul;31(7):630-41.

15.Stout SM, Nielsen J, Welage LS, Shea M, Brook R, Kerber K, Bleske BE. Influence of metoprolol dosage release formulation on the pharmacokinetic drug interaction with paroxetine. J Clin Pharmacol 2011 Mar;51(3):389-96.

16.Goryachkina K, Burbello A, Boldueva S, Babak S, Bergman U, Bertilsson L. Inhibition of metoprolol metabolism and potentiation of its effects by paroxetine in routinely treated patients with acute myocardial infarction (AMI). Eur J Clin Pharmacol 2008 Mar;64(3):275-82.

17.Hemeryck A, Lefebvre RA, De Vriendt C, Belpaire FM. Paroxetine affects metoprolol pharmacokinetics and pharmacodynamics in healthy volunteers. Clin Pharmacol Ther 2000 Mar;67(3):283-91.

18.Onalan O, Cumurcu BE, Bekar L. Complete atrioventricular block associated with concomitant use of metoprolol and paroxetine. Mayo Clin Proc 2008 May;83(5):595-9.

19.Konig F, Hafele M, Hauger B, Loble M, Wossner S, Wolfersdorf M. Bradycardia after beginning therapy with metoprolol and paroxetine. Psychiatr Prax 1996 Sep;23(5):244-5.

20.Spahn H, Mutschler E, Kirch W, Ohnhaus EE, Janisch HD. Influence of ranitidine on plasma metoprolol and atenolol concentrations. Br Med J (Clin Res Ed) 1983 May 14;286(6377):1546-7.

21.Ranexa (ranolazine) US prescribing information. CV Therapeutics, Inc. December, 2013.

22.Phansalkar S, van der Sijs H, Tucker AD, Desai AA, Bell DS, Teich JM, Middleton B, Bates DW. Drug-drug interactions that should be non-interruptive in order to reduce alert fatigue in electronic health records. J Am Med Inform Assoc 2012 Sep 25.

Selected from data included with permission and copyrighted by First Databank, Inc. This copyrighted material has been downloaded from a licensed data provider and is not for distribution, expect as may be authorized by the applicable terms of use.

CONDITIONS OF USE: The information in this database is intended to supplement, not substitute for, the expertise and judgment of healthcare professionals. The information is not intended to cover all possible uses, directions, precautions, drug interactions or adverse effects, nor should it be construed to indicate that use of a particular drug is safe, appropriate or effective for you or anyone else. A healthcare professional should be consulted before taking any drug, changing any diet or commencing or discontinuing any course of treatment.

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