Interaksjoner mellom metoprolol og antidepressive legemidler

Molden, Espen; Spigset, Olav

doi:10.4045/tidsskr.11.0143

Cited by 17 publications

(9 citation statements)

References 12 publications

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“…Metoprolol and mirtazapine is reported to have no interaction; therefore, it may provide a good contrast for the interaction effect of metoprolol-paroxetine/fluoxetine. 9,28 As expected, the results indicated that metoprolol-paroxetine/fluoxetine co-prescriptions had a significant risk of having early discontinuation of metoprolol.…”

Section: Discussionsupporting

confidence: 70%

“…The first limitation is that they did not consider the weak CYP2D6 inhibitory capacity of citalopram as well as fluvoxamine in their analysis. 9,11,26,33,34 Although citalopram is considered to be safely combined with metoprolol, it is still able to increase the AUC of metoprolol approximately 2 to 3 times. 9,33,35 This weak inhibition may be important in the older people because of the age-related physiological changes.…”

Section: Discussionmentioning

confidence: 99%

“…cytochrome P450 2D6 (CYP2D6) mediated pharmacokinetic DDI. [8][9][10] Metoprolol is predominantly metabolized by CYP2D6, while paroxetine and fluoxetine are strong inhibitors of the enzyme. [11][12][13] Consequently, co-prescription of these drugs leads to the substantial increase of the blood concentration of metoprolol and potentially induces metoprolol-related adverse drug reactions.…”

mentioning

confidence: 99%

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Discontinuation and dose adjustment of metoprolol after metoprolol‐paroxetine/fluoxetine co‐prescription in Dutch elderly

Bahar

Wang

Bos

et al. 2018

Pharmacoepidemiology and Drug

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PurposeCo‐prescription of paroxetine/fluoxetine (a strong CYP2D6 inhibitor) in metoprolol (a CYP2D6 substrate) users is common, but data on the clinical consequences of this drug‐drug interaction are limited and inconclusive. Therefore, we assessed the effect of paroxetine/fluoxetine initiation on the existing treatment with metoprolol on the discontinuation and dose adjustment of metoprolol among elderly.MethodsWe performed a cohort study using the University of Groningen IADB.nl prescription database (www.IADB.nl). We selected all elderly (≥60 years) who had ever been prescribed metoprolol and had a first co‐prescription of paroxetine/fluoxetine, citalopram (weak CYP2D6 inhibitor), or mirtazapine (negative control) from 1994 to 2015. The exposure group was metoprolol and paroxetine/fluoxetine co‐prescription, and the other groups acted as controls. The outcomes were early discontinuation and dose adjustment of metoprolol. Logistic regression was applied to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).ResultsCombinations of metoprolol‐paroxetine/fluoxetine, metoprolol‐citalopram, and metoprolol‐mirtazapine were started in 528, 673, and 625 patients, respectively. Compared with metoprolol‐citalopram, metoprolol‐paroxetine/fluoxetine was not significantly associated with the early discontinuation and dose adjustment of metoprolol (OR = 1.07, 95% CI:0.77‐1.48; OR = 0.87, 95% CI:0.57‐1.33, respectively). In comparison with metoprolol‐mirtazapine, metoprolol‐paroxetine/fluoxetine was associated with a significant 43% relative increase in early discontinuation of metoprolol (OR = 1.43, 95% CI:1.01‐2.02) but no difference in the risk of dose adjustment. Stratified analysis by gender showed that women have a significantly high risk of metoprolol early discontinuation (OR = 1.62, 95% CI:1.03‐2.53).ConclusionParoxetine/fluoxetine initiation in metoprolol prescriptions, especially for female older patients, is associated with the risk of early discontinuation of metoprolol.

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Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Discontinuation and dose adjustment of metoprolol after metoprolol‐paroxetine/fluoxetine co‐prescription in Dutch elderly

Bahar

Wang

Bos

et al. 2018

Pharmacoepidemiology and Drug

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“…Antidepressiver som er kraftige hemmere av enzymet CYP2D6, vil øke plasmakonsentrasjonen av metoprolol betydelig (18), og paroksetin og fluoksetin kan øke metoprololnivåene med en faktor på 4 -6. Det vil si at en pasient som behandles med en døgndose på 100 mg metoprolol kombinert med 20 mg fluoksetin, vil få like høye plasmanivåer som ved inntak av 400 -600 mg metoprolol per dag.…”

Section: Type Interaksjonunclassified

“…Det vil si at en pasient som behandles med en døgndose på 100 mg metoprolol kombinert med 20 mg fluoksetin, vil få like høye plasmanivåer som ved inntak av 400 -600 mg metoprolol per dag. I kasuistikker er det blant annet beskrevet alvorlige bivirkninger som AV-blokk grad III og uttalt bradykardi når metoprolol er blitt kombinert med fluoksetin eller paroksetin (18).…”

Section: Type Interaksjonunclassified

Legemiddelinteraksjoner hos pasienter i sykehjem

Søraas¹,

Staurset²,

Slørdal³

et al. 2014

Tidsskriftet

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The incidence of serious drug-drug interactions among nursing home patients in Trondheim Municipality is low. Polypharmacy is widespread, and the incidence of drug interactions where precautions should be taken is high. As nursing home patients are a vulnerable group with respect to drug interactions, the risk of interactions should be carefully considered when treatment with a new drug is started.

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Combining Antidepressants with β‐Blockers: Evidence of a Clinically Significant CYP2D6 Drug Interaction

2020

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BACKGROUND The b-blockers and antidepressants are two of the most commonly prescribed drug classes in the United States. Several antidepressants are potent inhibitors of cytochrome P450 2D6 liver enzymes (CYP2D6) and can increase the plasma concentrations of certain b-blockers when administered concomitantly, potentially leading to serious medical consequences such as hypotension, bradycardia, and falls. OBJECTIVE The primary objective of this investigation was to determine whether initiating an antidepressant in patients receiving b-blockers increased the risk of hemodynamic adverse events. Our primary outcome was time to hospital admissions or emergency department (ED) visits for an International Classification of Diseases-9 diagnosis suggestive of excessive b-blockade. METHODS We conducted a survival analysis for adults continuously enrolled in the California Medicaid system (Medi-Cal) between 2004 and 2012. Eligible patients were required to be receiving b-blocker medications that are primarily CYP2D6 substrates (e.g., metoprolol, propranolol, or carvedilol). Univariate and multivariable analyses were performed for patients who concurrently received antidepressants with b-blockers. An additional multivariable analysis analyzed the association of this combination upon hospitalizations or ED visits for all causes. RESULTS A total of 21,292 beneficiaries met the inclusion criteria, and 4.3% of patients required hospitalization or ED visits within 30 days of co-medication. In multivariable analysis, patients receiving antidepressants with moderate to strong CYP2D6 inhibitory potential (fluoxetine, paroxetine, duloxetine, or bupropion) had a greater risk for hospitalization or ED visits for hemodynamic events than those initiated on antidepressants with weak CYP2D6 inhibition for 30 days or less when each was compared with patients receiving no antidepressants (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.03-2.81; p=0.04 vs HR 1.24; 95% CI 0.82-1.88; p=0.30). Other demographic variables associated with increased morbidity included advanced age, male sex, higher b-blocker doses, and African American race or Hispanic ethnicity. CONCLUSIONS Results of this analysis suggest that initiation of certain antidepressants was associated with an increased risk for serious medical sequelae among patients concurrently receiving b-blockers. Greater risk was observed with antidepressants that potently inhibit the CYP2D6 enzyme, implying that increased morbidity may be mediated by a metabolic drug interaction. KEY WORDS b-blockers, antidepressants, drug interactions, cytochrome P450 2D6, pharmacoepidemiology.

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Interaksjoner mellom metoprolol og antidepressive legemidler

Cited by 17 publications

References 12 publications

Discontinuation and dose adjustment of metoprolol after metoprolol‐paroxetine/fluoxetine co‐prescription in Dutch elderly

Discontinuation and dose adjustment of metoprolol after metoprolol‐paroxetine/fluoxetine co‐prescription in Dutch elderly

Legemiddelinteraksjoner hos pasienter i sykehjem

Combining Antidepressants with β‐Blockers: Evidence of a Clinically Significant CYP2D6 Drug Interaction

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