Adverse drug reactions (ADRs) are among the leading causes of morbidity and mortality in the United States and worldwide.More than 400,000 preventable ADRs occur annually, with drug-drug interactions (DDIs) accounting for more than 30%.2 Incorrectly prescribed cardiovascular medications are responsible for almost 25% of all preventable ADRs.3 Older adults are particularly affected. It is estimated that close to 1/3 of older adults are taking six or more drugs.2 As the population ages, this number is rising. One study found that 54% of elderly patients were taking more than five medications in 1998, vs. 67% in 2003, and 19% were taking more than 10 medications in 1998, vs. 28% in 2003.4 Since so many elderly patients are taking cardiovascular medications, the vulnerability of this population to DDIs is enormous.

A study of 812 patients in a cardiology department found a 30% incidence of potential DDIs.5 Another study of 400 patients with heart failure found 863 potential DDIs.6 Zhou et al reported that a cardiologist wrote a prescription containing both simvastatin (40 mg) and amlodipine (5 mg). This event inspired the authors’ review of DDIs between 4-dihydropyridine calcium channel blockers (DHP-CCBs) and statin drugs (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors).7 Two additional articles examine potential DDIs between clopidogrel and morphine8 and between novel anticoagulant drugs and other agents.9

Dihydropyridine Calcium Channel Blockers (DHP-CCB) and Statins

Coadministration of DHP-CCBs with statins is common in treating patients with comorbid hypercholesterolemia and hypertension.7 Statins are metabolized by cytochrome P450 (CYP3A4) in the liver. DHB-CCBs have an inhibitory effect on CYP3A4, thereby increasing statin blood levels and increasing risk of myopathies (a potential side effect of statins).7 Zhou et al reviewed 19 pharmacokinetic studies of DDIs between DHB-CCBs and statins. Their findings are summarized in Table 1.

Table 1

Combination

Potential Clinical Outcome

Recommendation

Pravastatin-nimodipine 

Enhanced vasodilatory effect of nimodipine

Not recommended

Lovastatin-nicardipine

Enhanced vasodilatory effect of nicardipine 

Not recommended

Isradipine-lovastatin 

Decreased cholesterol-lowering efficacy

Not recommended

 Amlodipinesimvastatin 

Increased myopathy risk

Not recommended

Amlodipine-atorvastatin

Absence of clinical significance

Recommended, monitor therapy