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Lipid modification - primary and secondary CVD prevention - Management
What drug interactions are associated with statins?
- The combination of a fibrate and statin should be used with caution, as there is an increased risk of muscular adverse effects (e.g. myopathy and rhabdomyolysis) [MHRA, 2007].
- Simvastatin and atorvastatin are metabolized by cytochrome P450 isoenzymes and interact with drugs which inhibit these liver enzymes.
- For simvastatin, see Table 1 for prescribing advice.
- For atorvastatin, the manufacturer recommends the following maximum doses [Pfizer Ltd, 2007]:
- With ciclosporin: do not exceed 10 mg atorvastatin.
- With clarithromycin: do not exceed 20 mg atorvastatin (consider temporary cessation of atorvastatin if antibiotic treatment is short term).
- With itraconazole: do not exceed 40 mg atorvastatin.
- Grapefruit juice:
- Avoid grapefruit juice when taking simvastatin.
- Concomitant intake of large quantities of grapefruit juice and atorvastatin is not recommended.
- In contrast, pravastatin is not extensively metabolized by cytochrome P450 isoenzymes and does not share these interactions (except with ciclosporin) [ABPI Medicines Compendium, 2005b]:
- The manufacturer of pravastatin warns that co-administration with ciclosporin can elevate the plasma level of pravastatin and advises closer clinical and biochemical monitoring in these people (no dose adjustment was recommended).
Table 1. Prescribing advice for simvastatin and drugs and food that interfere with cytochrome P450 enzymes.
Interacting drugs | Prescribing advice |
|---|
HIV protease inhibitors | Avoid simvastatin |
Azole antifungal drugs (e.g. itraconazole, ketoconazole) Erythromycin, clarithromycin, and telithromycin | Avoid simvastatin or Temporaily withhold simvastatin for the duration of antibiotic or antifungal treatment (if a short course prescribed) |
Ciclosporin Gemfibrozil (only on specialist advice; otherwise avoid) Nicotinic acid (dose greater than 1 g/day) | Do not exceed a simvastatin dose of 10 mg |
Amiodarone Verapamil | Do not exceed a simvastatin dose of 20 mg |
Diltiazem | Do not exceed a simvastatin dose of 40 mg |
Grapefruit juice | Avoid grapefruit juice when taking simvastatin |
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