DÄ internationalArchive5/2019Potential Drug Interactions Forgotten

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Potential Drug Interactions Forgotten

Dtsch Arztebl Int 2019; 116(5): 71-2; DOI: 10.3238/arztebl.2019.0071c

Regenthal, R

LNSLNS

The authors are to be thanked for the successful, very practice-oriented, and balanced evidence-based presentation (1). In the Pharmacotherapy section, they note that dihydropyridine-type calcium channel blockers can, in principle, be combined with all other first-line antihypertensive agents. This can be agreed upon unconditionally, although the development of peripheral edema is a frequent but dose-dependent side effect (2). After mentioning constipation as a potential side effect in elderly and immobile patients, the authors point out—although with too little differentiation, in our opinion—possible drug interactions with calcium channel blockers. To counter any possible confusion on the part of the readers, it should be emphasized that, from a clinical-pharmacological viewpoint, drug interactions for the dihydropyridine type of drugs due to inhibition of cytochrome P450 3A4 are almost irrelevant clinically but instead are only known for the verapamil/diltiazem type of calcium channel blockers. This type of drug in turn is not very significant for standard hypertension care. However, for the antihypertensives of the dihydropyridine-type listed in Table 2, it should be noted that amlodipine has a clinically relevant interaction with simvastatin, which plays a role in the frequent multiple therapies used for treating comorbid dyslipidemia. Both drugs are metabolized in the intestine and liver, mainly by cytochrome P450 3A4/5. This leads to dose-dependent competition with this isoenzyme, with the result that amlodipine reduces the first pass metabolism of simvastatin (which is normally very pronounced), leading to an increased plasma concentration of statins (3). This in turn is associated with a higher risk of myopathy (4), which is why most specialist information sets a maximum simvastatin dose of 20 mg per day when amlodipine is taken concomitantly

DOI: 10.3238/arztebl.2019.0071c

PD Dr. med. Ralf Regenthal

Selbstständige Abteilung Klinische Pharmakologie, Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, Medizinische Fakultät der Universität Leipzig, Leipzig, Germany

ralf.regenthal@medizin.uni-leipzig.de

Conflict of interest statement

The author declares that no conflict of interest exists.

1.
Jordan J, Kurschat C, Reuter H: Arterial hypertension – diagnosis and treatment. Dtsch Arztebl Int 2018; 115: 557–68 VOLLTEXT
2.
Law MR, Wald NJ, Morris JK, et al.: Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ 2003; 326: 1427–34 CrossRef MEDLINE PubMed Central
3.
Son H, Lee D, Lin LA, et al.: Development of a pharmacokinetic interaction model for co-administration of simvastatin and amlodipine. Drug Metab Pharmacokinet 2014; 29: 120–8 CrossRef MEDLINE
4.
Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA 2003; 289: 1681–90 CrossRef MEDLINE
1.Jordan J, Kurschat C, Reuter H: Arterial hypertension – diagnosis and treatment. Dtsch Arztebl Int 2018; 115: 557–68 VOLLTEXT
2.Law MR, Wald NJ, Morris JK, et al.: Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials. BMJ 2003; 326: 1427–34 CrossRef MEDLINE PubMed Central
3.Son H, Lee D, Lin LA, et al.: Development of a pharmacokinetic interaction model for co-administration of simvastatin and amlodipine. Drug Metab Pharmacokinet 2014; 29: 120–8 CrossRef MEDLINE
4.Thompson PD, Clarkson P, Karas RH. Statin-associated myopathy. JAMA 2003; 289: 1681–90 CrossRef MEDLINE

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