Pharmacokinetic drug–drug interactions between 1,4-dihydropyridine calcium channel blockers and statins: factors determining interaction strength and relevant clinical risk management

Figures & data

Table 1 DDI potential in combination use of DHP-CCBs and statins

Category	Combination	Pharmacokinetic profile	Potential clinical outcome
“Not recommended” category	Pravastatin–nimodipine	Pravastatin could significantly increase AUC0-∞ and absolute bioavailability of oral nimodipine^Citation10	Enhanced vasodilatory effect of nimodipine
	Lovastatin–nicardipine	Lovastatin significantly increased AUC0-∞ bioavailability of oral nicardipine in rats by 67.4% and 38.5%, respectively^Citation11	Enhanced vasodilatory effect of nicardipine and relevant adverse drug reactions
	Isradipine–lovastatin	Isradipine (5 mg twice daily) could decrease AUC of lovastatin (20 mg once daily) by 40% in male subjects^Citation12	Decreased cholesterol-lowering efficacy
	Lacidipine–simvastatin	Lacidipine (4 mg once daily) could increase Cmax of simvastatin (40 mg once daily) by 70% and AUC0–24h by 35%^Citation13	Increased risk of myopathy
	Amlodipine–simvastatin	Amlodipine (10 mg/day) could increase AUC and Cmax of simvastatin (40 mg) by 1.8-and 1.9-fold, respectively^Citation14	Increased risk of myopathy
	Azelnidipine–simvastatin	Azelnidipine (8 mg) could increase AUC of simvastatin (10 mg) by 90%^Citation15	Increased risk of myopathy
	Lercanidipine–simvastatin	Lercanidipine (20 mg) could increase simvastatin (40 mg) bioavailability by 56%^Citation16	Increased risk of myopathy
	Lercanidipine–fluvastatin	Fluvastatin (40 mg) could decrease AUC of lercanidipine enantiomers by 42%, whereas lercanidipine (20 mg) could increase AUC of (+)-3R,5S-fluvastatin (the more pharmacologically active enantiomer) by 13%^Citation17	Decreased antihypertensive efficacy; increased cholesterol-lowering efficacy as well as risk of myopathy
“Recommended, monitor therapy” category	Benidipine–simvastatin	Benidipine (8 mg) did not alter AUC of simvastatin (10 mg)^Citation15	Limited DDI potential and absence of clinical significance
	Amlodipine–atorvastatin	Amlodipine had no effect on the Cmax of atorvastatin, but increased the AUC of atorvastatin by 18%^Citation18	Absence of clinical significance

Abbreviations: AUC, area under the plasma concentration-time curve; AUC_0-∞, area under the plasma concentration-time curve from time zero to infinity; AUC_0–24h, area under the plasma concentration-time curve from time zero to 24 hours; C_max, maximum concentration; DDI, drug-drug interaction; DHP-CCBs, 1,4-dihydropyridine calcium channel blockers.

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