Exponeringen för simvastatin kan öka vid samtidig administrering av amlodipin. Risken för myopati kan öka.Exponeringen för simvastatin kan öka vid samtidig administrering av amlodipin. Risken för myopati kan öka.
Interaktionens kliniska betydelse är inte fastställd. Monitorering för biverkningnar av simvastatin rekommenderas. Enligt tillverkaren bör simvastatindoser över 20 mg undvikas.Interaktionens kliniska betydelse är inte fastställd. Monitorering för biverkningnar av simvastatin rekommenderas. Enligt tillverkaren bör simvastatindoser över 20 mg undvikas.
Possibly competetive inhibition of CYP3A4 by amlodipine.Possibly competetive inhibition of CYP3A4 by amlodipine.
In a clinical trial with eight patients with hypercholeste......In a clinical trial with eight patients with hypercholesterolemia and hypertension subjects were given 4 weeks of oral simvastatin (5 mg/day), followed by 4 weeks of oral amlodipine (5 mg/day) co-administered with simvastatin (5 mg/day). Combined treatment with simvastatin and amlodipine increased the peak concentration of HMG-CoA reductase inhibitors by 43% (from 9.6 +/- 3.7 ng/ml to 13.7 +/- 4.7 ng/ml) and the area under the concentration-time curve by 28% (from 34.3 +/- 16.5 ng h/ml to 43.9 +/- 16.6 ng h/ml) without affecting the cholesterol-lowering effect of simvastatin (1). No adverse effects were seen during co-treatment. Earlier an in vitro study showed that amlodipine is a weak inhibitor of CYP3A4 (2), which was thought to be the mechanism of the present interaction (1). Increased exposure to simvastatin (AUC 1,6-fold) and its metabolite was observed in a pharmacokinetic study when subjects received 10 mg amlodipine every day for 10 days and a single dose 80 mg dose of simvastatin on day 10 (3). The manufacturer states that it is recommended that 20 mg dose of simvastatin daily should not be exceeded due to the increased risk of musculoskeletal advese effects associated with concomitant use (4). Seventeen patients randomly recieved daily doses of 20 mg simvastatin and 5 mg amlodipine for 6 weeks. The drugs were given either at the same time (current, n=8) or separated by four hours (non-concurrent, n=7). In the current group Cmax and AUC of simvastatin acid were 1.9 ± 0.9 ng/ml and 15.6 ± 7.5 h ng/ml, respectively. In the non-concurrent group Cmax and AUC of simvastatin acid were 63.2% and 66.0%, (1.2 ± 1.0 ng/ml and 10.3 ± 8.3 h ng/ml) respectively, of the values in the current group. The authors conclude that non-concurrent dosing may be safe and useful for patients who require both simvastatin and amlodipine (5). However, this study did not have any placebo group and none of the variables were statistically significant when compared between the current and non-current amlodipine dosing groups. A case report describes a 41-year old African woman hospitalized for diffuse myalgia and intense weakness developing over the last 3 days. Her previous medical history included: SLE, glomerulonephritis, and terminal renal failure requiring peritoneal dialysis. She was currently treated with simvastatin 20 mg once daily and amlodipine 10 mg once daily, together with: furosemide, bisoprolol, irbesartan, mycophenolate mofetil, hydroxychloroquine, calcium carbonate, colecalciferol, sevelamer, and calcitriol. Nine days before admission she had been diagnosed with a peritoneal dialysis-related peritonitis and was therefore given ciprofloxacin 500 mg twive daily, vacomycin 2g/3d and a single dose gentamicin 80 mg. Four days later ciprofloxacin was withdrawn. The following day the patient developed severe rhabdomyolysis and was thereafter admitted to the intensive care unit where she stayed for 3 days and recovered. The authors suggest that the myotoxicity in this patient could be a result of a drug-drug interaction between simvastatin and amlodipine together with the introduction of ciprofloxacin (a weak CYP3A4 inhibitor) (6). A Polish case report (according to abstract) describes a 65-year old athletic male with hypertension and hyperlipidemia treated with amlodipine and simvastatin who developed muscle pain, muscle weakness, dizziness, and confusion during physical activity. After amlodipine and simvastatin were discontinued, all his symptoms resolved rapidly. The authors conclude that the combination of a drug-drug interaction and drug-physical activity interaction could have been the reason for the patient's symptoms (7).
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- Katoh M, Nakajima M, Shimada N, Yamazaki H, Yokoi T. Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55:843-52.
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- Park CG, Lee H, Choi JW, Lee SJ, Kim SH, Lim HE. Non-concurrent dosing attenuates the pharmacokinetic interaction between amlodipine and simvastatin. Int J Clin Pharmacol Ther. 2010;48:497-503.
- De Schryver N, Wittebole X, Van den Bergh P, Haufroid V, Goffin E, Hantson P. Severe rhabdomyolysis associated with simvastatin and role of ciprofloxacin and amlodipine coadministration. Case Rep Nephrol. 2015;2015:761393.
- Schetz D, Foerster J, Sein Anand J. [Drug interaction in 63-year-old male sportsman--a case report]. Przegl Lek. 2015;72:488-90.