What question did this study set out to answer?

To evaluate the impact of CYP2D6 genetic polymorphisms on plasma drug concentrations and the clinical tolerability of metoprolol in a primary care setting.

September 30, 2005Clinical Pharmacology & TherapeuticsOpen Access

Impact of genotype on adverse effects during treatment with metoprolol: A prospective clinical study

Q: What is the clinical evidence from this study?

Study design: Observational. Population: Hypertension (n=121). Intervention: Metoprolol vs. CYP2D6 genotype-derived phenotype (EMs+UMs vs PMs+IMs). Primary outcome: Cold extremities (RR 3.8, 95% CI 1.03-14.3, p=0.056).

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Key result

CYP2D6 genotype was not significantly associated with overall adverse effects during metoprolol treatment, though cold extremities were more frequent in PMs/IMs vs EMs/UMs (16.0% vs 4.2%; P=0.056).

Why the study?

Does CYP2D6 genotype-derived phenotype impact the tolerability and adverse effects of metoprolol in patients treated in primary care?

Key Points

To evaluate the impact of CYP2D6 genetic polymorphisms on plasma drug concentrations and the clinical tolerability of metoprolol in a primary care setting.
Enrolled N=121 evaluable white patients in a prospective, 6-week multicenter study with individualized metoprolol dosing, primarily for hypertension (~90%).
Genotyped CYP2D6 alleles (*3–*10, *41, and duplications) and measured blood pressure, resting heart rate, and plasma levels of metoprolol and alpha-hydroxymetoprolol.
Monitored central nervous system, cardiovascular, and sexual dysfunction adverse effects over 6 weeks using standardized rating scales and questionnaires.
Median dose-normalized metoprolol concentrations rose significantly across CYP2D6 phenotypes: 0.0088 ng/mL (ultrarapid), 0.047 ng/mL (extensive), 0.34 ng/mL (intermediate), and 1.34 ng/mL (poor metabolizers) (P < .0001).
No statistically significant overall association occurred between CYP2D6 metabolizer status (extensive and ultrarapid vs. intermediate and poor) and reported adverse effects.
Cold extremities occurred more frequently in poor and intermediate metabolizers compared to extensive and ultrarapid metabolizers (16.0% vs. 4.2%, P = .056; RR 3.8, 95% CI 1.03–14.3).

Study Design

Type

Observational (n=121)

Multicenter

Yes

Structured PICO

Does CYP2D6 genotype-derived phenotype impact the tolerability and adverse effects of metoprolol in patients treated in primary care?

Population

121 white patients in a primary care setting in whom treatment with metoprolol was considered (indication for treatment was hypertension in about 90% of cases)

Intervention

Metoprolol treatment with individually determined dosage

Comparator

Comparison between CYP2D6 genotype-derived phenotypes (extensive and ultrarapid metabolizers combined versus poor and intermediate metabolizers combined)

Outcome

Adverse effects related to the central nervous system, cardiovascular effects, and sexual dysfunction assessed by standardized rating scales and questionnairessafety

Main Result

Effect estimate: RR 3.8 (95% CI 1.03-14.3)

Absolute Event Rate: 16% vs 4.2%

p-value: p=0.056

Limitations

Small number of poor metabolizers (PMs) enrolled making tolerability results in this group inconclusive
Small number of poor metabolizers (PMs) enrolled made results concerning tolerability in PMs inconclusive

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

No support for CYP2D6-guided metoprolol dosing in primary care; leaves open possible cold extremities link for prospective confirmation.

Cite This Study

Fux et al. (2005) conducted an observational in Hypertension (n=121). Metoprolol vs. CYP2D6 genotype-derived phenotype (EMs+UMs vs PMs+IMs) was evaluated on Cold extremities (RR 3.8, 95% CI 1.03-14.3, p=0.056). CYP2D6 genotype was not significantly associated with overall adverse effects during metoprolol treatment, though cold extremities were more frequent in PMs/IMs vs EMs/UMs (16.0% vs 4.2%; P=0.056).

synapsesocial.com/papers/6a0ba4d65f2af8d200c20138 https://doi.org/10.1016/j.clpt.2005.07.004

Topics

Hypertension management

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Impact of genotype on adverse effects during treatment with metoprolol: A prospective clinical study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Discussion

Implication

Cite This Study

Topics

Impact of genotype on adverse effects during treatment with metoprolol: A prospective clinical study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Discussion

Implication

Cite This Study

Also Consider

Topics

Also Consider