Drug Interactions of Lipid Lowering Drugs (Part 1):

Drug Interactions of Statins:

More presentations from Naina Mohamed Pakkir Maideen

©   Statins (HMG CoA Reductase Inhibitors) include Simvastatin, Lovastatin, Atorvastatin, Rosuvastatin, Pravastatin, Fluvastatin and Pitavastatin.

©   Statins are commonly used to reduce LDL cholesterol.

©   Mechanism of Action of Statins:

©   Lipophilic statins like Simvastatin, Lovastatin and Atorvastatin are the substrates for cytochrome P (450) 3A4 enzyme and hence they are involved in many Adverse drug interactions (Myotoxicity). Potent CYP3A4 inhibitors such as Azole Antifungals, Macrolide Antibiotics, Antivirals (Protease Inhibitors), Fibrates, Potent CYP3A4 Inhibitors, CYP3A4 Inducers, Warfarin, Niacin, Colchicine, Daptomycin and Grapefruit Juice can significantly increase the plasma concentrations and toxicity of Simvastatin, Lovastatin and Atorvastatin.
©   Lipophilic Fluvastatin is metabolized by CYP2C9 and is less prone to pharmacokinetic interactions.
©   Hydrophilic statins such as Pravastatin and Rosuvastatin are not significantly metabolized by cytochrome P (450) enzymes. 

©   Concomitant use of Statins (Simvastatin or Lovastatin) and Azole antifungals (Fluconazole, Itraconazole, Ketoconazole, Posaconazole, Voriconazole and Miconazole), Macrolide Antibiotics (Erythromycin, Telithromycin and Clarithromycin), Protease Inhibitors (Lopinavir, Ritonavir, Darunavir, Saquinavir, Indinavir, Fosamprenavir, Nelfinavir, Ritonavir, Atazanavir, etc), Fibrates (Gemfibrozil, Ciprofibrate, Bezafibrate, Clofibrate, etc) or Potent CYP3A4 Inhibitors (Cyclosporine, Nefazodone, Mifepristone, Cobicistat, Idelalisib, Mibefradil) is Contraindicated.

©   Monitor the patients for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness) and creatine kinase (CK) levels, if other statins such as Atorvastatin, Fluvastatin or Cerivastatin used along with Azole antifungals, Macrolide antibiotics, Protease inhibitors, Fibrates or Potent CYP3A4 Inhibitors.

©   Monitoring for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness) and creatine kinase (CK) levels is recommended when Statins and Weak CYP3A4 Inhibitors (Verapamil, Diltiazem, Amiodarone, Ranolazine, Conivaptan, Nilotinib, Ceritinib, Delavirdine), Warfarin, Niacin, Colchicine, Daptomycin or Grapefruit Juice co-administered.

©   The International normalized ratio (INR) should be closely monitored in patients taking statins and Warfarin.

©   Adjust the dose of statins, if statins and CYP3A4 inducers (Carbamazepine, Eslicarbazepine, Dabrafenib) are used concomitantly.

©   Concomitant use of Simvastatin and Ciprofloxacin, Amlodipine, Tadalafil or Cranberry juice warrants the monitoring of signs and symptoms of myopathy or rhabdomyolysis.

©   Statins are contraindicated during Pregnancy.

©   Nursing mothers should avoid using statins.

©   To reduce the rate of interactions, consider substituting CYP3A4-substrate statins (Simvastatin, Lovastatin and Atorvastatin) with other statin such as pravastatin which is not metabolized by CYP 3A4, if possible.

©   The patients with hyperlipidemia should bring a list of all the drugs they are taking including prescription drugs, over the counter (OTC) drugs, and any supplements during their visit to the Doctor or Pharmacist.