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DRUG INTERACTIONS CORNER Daniel S.
Streetman, Section Advisor
Clinically relevant vitamin D and atorvastatin interaction
Key point: Vitamin D supplementation may enhance
lipid effects of atorvastatin despite a reduction in atorvastatin
concentrations.
Finer points: A prospective, three-arm, crossover
trial was conducted in 16 patients (age 62.8 ± 11 years) to assess
the effect of vitamin D supplementation on atorvastatin
(Lipitor—Pfizer) and cholesterol concentrations. Patients received
atorvastatin daily as prescribed by a primary care physician and either
6 weeks of vitamin D 800 IU plus calcium 1,000 mg daily by mouth or no
vitamin D supplementation. Vitamin D was supplied as ergocalciferol (D2)
400 IU (multivitamin) and cholecalciferol (D3) 400 IU (vitamin D and
calcium formulation). Dose and formulations of atorvastatin were not
changed during the study. Patients continued taking previously
prescribed medications; none of these medications was a recognized
cytochrome (CYP) 3A4 inhibitor.
Compared with no supplementation, vitamin D supplementation decreased
concentrations of atorvastatin and its active metabolites (P < 0.05).
Despite this, LDL cholesterol and total cholesterol levels also
decreased with vitamin D supplementation (83 ± 30 mg/dL and 157
± 37 mg/dL, respectively) compared with no supplementation (97
± 28 mg/dL and 169 ± 35 mg/dL, respectively; P < 0.005). No
significant difference was found in HDL concentrations between groups.
The ratios of atorvastatin metabolites to parent compounds did not
change between groups. Mean daily intake of vitamin D in the
nonsupplemented and supplemented groups was 25 to 407 IU and 825 to
1,207 IU, respectively.
What you need to know: Taking vitamin D and
atorvastatin concomitantly produces a clinically relevant drug
interaction. According to the author, it is likely that vitamin D
decreases atorvastatin concentrations via increased CYP3A4 metabolism in
the gut or liver and increases cholesterol metabolism or transport. In
addition, a recent study suggests that vitamin D also induces
P-glycoprotein (Pgp), an efflux transporter. Atorvastatin is considered
a Pgp substrate. Considering that atorvastatin metabolite concentrations
were not increased, Pgp induction represents a plausible alternative
mechanism to explain the observed interaction.
The mean difference in LDL concentrations between vitamin D groups was
substantial at 14.4%; this difference can also be observed with
lifestyle modification or the addition of another cholesterol-lowering
medication.
The recommended daily adequate intake of vitamin D for persons age 51 to
70 years is 400 IU; adequate intake is 600 IU daily for persons older
than 71 years. Many study patients had vitamin D deficiency, defined as
serum 25-hydroxyvitamin D concentrations less than 10 to 15 ng/mL, at
baseline and after 6 weeks of supplementation. Vitamin D deficiency is
associated with increased cardiovascular risk and reduced bone density.
It is unclear if vitamin D supplementation reduces cardiovascular risk;
however, when taken consistently, calcium plus vitamin D reduces
fracture risk and bone loss in elderly patients.
What your patients need to know: Explain to patients
that even seemingly benign therapies or nutritional changes such as
vitamin D supplementation can affect concurrent drugs. While the
interaction may not necessarily be a negative one, as in this case, it
could be for other drugs. Always ask your patients what OTC supplements
and vitamins they are taking.
Sources:
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