STATIN DRUG INTERACTION POCKET GUIDE

Fluvastatin Lovastatin Pravastatin Simvastatin Atorvastatin Rosuvastatin

Antidepressants
Nefazodone Max: 40mg 10 Do Not Use 2,7,9 Max: 40mg 7,10 Do Not Use 4,7 Do Not Use 7,9 Max: 20mg 7,10
Antifungal Agents
* Fluconazole Max: 40mg 10 No Change 7 Max: 40mg 10 No Change 7 No Change 7 No Change 7
* Itraconazole No Change 9 Do Not Use 10 Max: 40mg 10 Do Not Use 10 Do Not Use 10 Do Not Use 6
* Ketoconazole(PO) Do Not Use 1 Do Not Use 2,7 Do Not Use 3 Do Not Use 4 Do Not Use 7 Do Not Use 7
* Posaconazole Unknown Do Not Use8c Unknown Do Not Use25 Do Not Use8c Unknown
* Voriconazole Unknown Do Not Use 11 Unknown Do Not Use 11 Do Not Use 11 Unknown
Calcium Channel Blockers
Amlodipine Unknown Unknown Unknown ***Max:80mg27 No Change26 Unknown
Diltiazem Unknown Max: (40mg) 9 Unknown Max: 10mg 24 Max: (20mg) 9 Unknown
Verapamil Unknown Max: 40 mg 2,8 Unknown Max: 10mg 24 Max: 10mg 8 Unknown
Macrolides & Ketolides
Azithromycin Unknown No Change 7,9 Unknown No Change 7,9 No Change 7,9 Unknown
Clarithromycin Unknown Do Not Use 2 Max: 40mg Do Not Use 4 Do Not Use 8,9 Unknown
Erythromycin Unknown Do Not Use 8a,9 Unknown Do Not Use 9 Do Not Use 8,9 Unknown
Telithromycin Unknown Do Not Use 2 Unknown Do Not Use 9 Do Not Use 8,10 Unknown
Protease Inhibitors
* Atazanavir No Change 9 Do Not Use 2,7 Unknown Do Not Use 4,7 Max: (10mg) 7,8 Max: (10mg) 8
* Darunavir/Ritonavir No Change 9 Do Not Use 2,7 Do Not Use7 Do Not Use 4,7 Max: (10mg) 7 Max: 10mg 8
* Fosamprenavir No Change 9 Do Not Use 2,7 Unknown Do Not Use 4,7 Max: (10mg) 7,8 Do Not Use 8
* Indinavir No Change 9 Do Not Use 2,7 Unknown Do Not Use 4,7 Max: (10mg) 7 Do Not Use 8
Pravastatin
* Lopinavir/Ritonavir No Change 9 Do Not Use 2,7 Do Not Use 4,7 Do Not Use 5,7 Max:10mg 7,8
AUC 33%7
* Nelfinavir No Change 9 Do Not Use 2,7 Unknown Do Not Use 4,7 Do Not Use 7 Max:10mg 8
Pravastatin level
* Saquinavir/Ritonavir No Change 9 Do Not Use 2,7 Do Not Use 4,7 Do Not Use7 Max:10mg8
by 50%7
* Tipranavir/Ritonavir No Change 9 Do Not Use 2,7 Unknown Do Not Use 4,7 Do Not Use7 Max:10mg8
Table Key: Max Maximum dose of statin should not exceed dose listed No Change No significant change in statin level (Dose) Estimated dose; no data available,
VAMC recommendation have been derived from pharmacokinetic data. * For questions regarding the use of statins in combination with antifungal agents or any other
infectious disease medication please contact Sharanie Sims, Pharm. D, BCPS ** The PBM-MAP-VPEs discourage the use of any statin-fibrate combination because of the
known risks and yet to be proven incremental benefit of these combinations beyond statin therapy alone. *** Doses of Simvastatin 40mg and 80mg can be used in combination
with Amlodipine as long as the dose is separated 4 hours from Amlodipine. The Lipid Clinic advises AM Amlodipine administration and Evening Simvastatin
Medications highlighted in RED are listed on the VAMC List of TOP 20 DRUG INTERACTIONS
For additional inquiries regarding the use of statins with the medications listed above please contact Toni Swartz, Pharm.D., CLS of the Lipid Clinic Revised 09/27/11
 STATIN DRUG INTERACTION POCKET GUIDE
Fluvastatin Lovastatin Pravastatin Simvastatin Atorvastatin Rosuvastatin
Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
* Delavirdine Unknown Do Not Use 7 Unknown Do Not Use 7 Max: 20mg 7,8 Unknown
Unknown Pravastatin Simvastatin Atorvastatin
* Efavirenz Unknown Unknown
AUC 40% 7 AUC 58% 7 AUC 43% 7,8
* Nevirapine Unknown Unknown Unknown Unknown Unknown Unknown
Atorvastatin
* Etravirine Fluvastatin level8 Lovastatin level 8 Unknown Simvastatin level8 Unknown
AUC 38%8
Anti-Infective
Unknown Unknown Unknown Unknown Atorvastatin level Unknown
* Metronidazole
2 fold 9
Fluvastatin Unknown Unknown Simvastatin Atorvastatin Unknown
* Rifampin
AUC 51% 1 AUC 87% 9 AUC 80% 8
Hormones
Danazol Unknown Max:20mg 2,8,9a Unknown Do Not Use24 Do Not Use 9 Unknown
Miscellaneous Agents
Amiodarone No Change Max: 40mg 2,8 No Change10 Max: 10mg 24 Max: (20mg) No Change
Cimetidine Max: 40mg 1 Max: 40mg 9 No Change10 Max: 40mg 9 No Change 10 No Change 10
Cyclosporine Max: 40mg 1,7 Max:20mg 2,7 Max:20mg a Do Not Use24 Max:10mg5 Max:5mg 6,7
Tacrolimus Unknown Max: 40mg 12 Max:40mg 12 Max: 20mg 12 Max: 40mg 12,18 Unknown
Digoxin
Digoxin Unknown No Change 3 Unknown Max: 10mg 9 Unknown
level 11% 1
Fenofibrate Unknown Unknown Unknown Unknown Unknown Unknown
**Gemfibrozil Do Not Use24 Do Not Use24 Do Not Use24 Do Not Use 24 Do Not Use24 Do Not Use24
Atorvastatin
Phenytoin Do Not Use 1,8 Unknown Pravastatin level 9 Unknown No Change 9
level 9
Ranolazine Unknown Unknown Unknown Max: 20mg24 Max: 40mg 8 Unknown
Warfarin Monitor INR1 Monitor INR 1 Monitor INR 1 Monitor INR 1 Monitor INR1 Monitor INR1
Zafirlukast Unknown Do Not Use 2 Unknown Do Not Use 4 Unknown Unknown
Table Key: Max Maximum dose of statin should not exceed dose listed No Change No significant change in statin level (Dose) Estimated dose; no data available,
VAMC recommendation have been derived from pharmacokinetic data. * For questions regarding the use of statins in combination with antifungal agents or any other
infectious disease medication please contact Sharanie Sims, Pharm. D, BCPS ** The PBM-MAP-VPEs discourage the use of any statin-fibrate combination because of the
known risks and yet to be proven incremental benefit of these combinations beyond statin therapy alone. *** Doses of Simvastatin 40mg and 80mg can be used in combination
with Amlodipine as long as the dose is separated 4 hours from Amlodipine. The Lipid Clinic advises AM Amlodipine administration and Evening Simvastatin

Medications highlighted in RED are listed on the VAMC List of TOP 20 DRUG INTERACTIONS
For additional inquiries regarding the use of statins with the medications listed above please contact Toni Swartz, Pharm.D., CLS of the Lipid Clinic Revised 09/27/11
 Statin Dosing For Reduced Creatinine Clearance
(Chart adapted from The National Lipid Association's Safety Task Force)
CrCl 60-89ml/min CrCl 30-59ml/min CrCl 15-29ml/min CrCl <15 ml/min or
Dialysis
HMG CoA Reductase Inhibitors
Atorvastatin 10-80 10-80 10-80 10-80
Fluvastatin 10-80 10-80 10-40 10-40
Lovastatin 20-80 20-80 10-10 10-40
Pravastatin 20-40 20-40 20-40 20-40
Rosuvastatin 5-40 5-40 5-10
Simvastatin 20-80 20-80 10-40 10-40
Cholesterol Absorption Inhibitors
Ezetimibe 10 10 10 10
Bile Acid Sequestrant
Colesevalam 2.6-3.8
Cholestyramine 4-16
Colestipol 5-20
Fibric Acid Derivatives
Fenofibrate 160 50-160* 50 Avoid
Gemfibrozil 1200 1200^ 1200^ 1200
Other
Niacin (g) 1-2g 1-2g 1-2g to 50%
Fish Oil 1.5 2.4 1.5 2.4 1.5 2.4 1.5 2.4
Plant Stanols 2g 2g 2g 2g
Table Key:
^ = VHA Pharmacy Benefits Management Services and the Medical Advisory Panel and The National Lipid Associations Safety Task
Force recommend the dose be reduced to 600mg daily.22
= The National Lipid Associations Safety Task Force recommends that it be avoided.
* = Dose of Fenofibrate (Triglide) should be reduced to 50mg/day in patients with a CrCl < 50ml/min
Note: all doses are listed as mg per day unless stated and are based on ATP III, KDOQI Recommendations, and manufacturer package insert.
Revised 09/27/11
 Dose Limits and Considerations
Drug/Simvastatin Dose Limit PBM-MAP-VPE Recommendations
Amlopidine/Simvastatin 10 mg Ok to use medications concurrently
Amlopidine/Simvastatin 20 mg Ok to use medications concurrently
Amlopidine/Simvastatin 40 mg Separate the administration of meds by a minimum of 4 hours
Alternative: change anti-hypertensive agent; consider recommending
provider optimize BP regimen based on patients comorbid disease states
Amlopidine/Simvastatin 80 mg Use caution, weigh risk vs. benefit. Separate med by ~4 hours
Alternative: change anti-hypertensive agent; consider recommending
provider optimize BP regimen based on patients comorbid disease states
Statin/Fenofibrate Discourages the use of any statin-fibrate combination because of
known risks and yet to be proven incremental benefit of these combos
beyond statin therapy alone.
If triglyceride (TG) lowering therapy is needed, first recommend lifestyle
changes, ensure the lab is fasting, diabetes is well controlled if diabetic
and minimize alcohol.
Fish oil and niacin can also be used for lowering TG.
Fenofibrate may be an option if Fasting TG >500mg/dl (when therapy is
initiated) or h/o TG induced pancreatitis.
PBM-MAP-VPE - VHA Pharmacy Benefits Management Services, Medical Advisory Panel and VISN Pharmacist Executives24
Revised 9/27/2011
References:
1) Lescol [package insert]. East Hanover, NJ: Norvartis Pharmaceuticals Corporation, 2003.
2) Mevacor [package insert]. Whitehouse Station, NJ: Merck & Co. Inc, 2002.
3) Pravachol [package insert]. Princeton, NJ: Bristol-Myers Squibb Company, 2005.
4) Zocor [package insert]. Whitehouse Station, NJ: Merck & Co. Inc, 2005.
5) Lipitor [package insert]. New York, NY: Pfizer, Inc, 2007.
6) Crestor [package insert]. Wilmington, DE: AstraZeneca Pharmaceuticals LP, 2007.
7) Expert Opinion: National Lipid Association Self Study Module. Jacksonville, FL: National Lipid Association; 2007.
8) Micromedex online
a. Wong et. al. Case report. 73 year old man developed rhabdomyolysis after ingesting 9 grams of erythromycin over 2 weeks.
b. Merz T. Case report 73 year old man increased serum transaminase levels amiodarone 200mg with rosuvastatin 5mg.
c. Drug Interactions: Posaconazole Atorvastatin; Posaconazole Lovastatin
i. Although the interaction between Atorvastatin/Lovastatin, both CYP3A4 substrates, and Posaconazole, a CYP3A4 inhibitor, has not been studied, concomitant use of
Posaconazole and another CYP3A4 substrate and statin, Simvastatin, resulted in significant increases in Simvastatin Cmax and AUC. Therefore, it is possible that
concomitant use of Atorvastatin or Lovastatin and Posaconazole may result in increased Atorvastatin/Lovastatin plasma concentrations, which may lead to rhabdomyolysis.
It is recommended that patients be monitored for signs and symptoms of myopathy or rhabdomyolysis (eg, muscle pain, tenderness, or weakness) and that an
Atorvastatin/Lovastatin dose adjustment be considered if these drugs are coadministered (Prod Info NOXAFIL oral suspension, 2010).
9) Lexi-Comp online
a. Case Report. Rhabomyolysis within 2 months after starting danazol 200mg three times daily.
10) Expert Opinion: Use of HMG Reductase Inhibitor in combination with interacting drugs at a Veteran Affairs Hospital.
11) Vfend [package insert]. New York, NY: Pfizer Inc, 2008
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Transpantation 2006;82:771-778.
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21) Jerling. Clinical pharmacokinetics of ranolazine. 2006 45(5):469-491.
22) Washington, DC: Pharmacy Benefits Management Services and the Med ical Advisory Panel, Veterans Health Administration, Department of Veterans Affairs; September 2004.
23) FDA Drug Safety Communication: Ongoing safety review of high-dose Zocor (Simvastatin) and increased risk of muscle injury. March 2010.
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm204882.htm#AdditionalInformationforHealthcareProfessionals2
24) National PBM Bulletin: Simvastatin: Updated Restrictions, Contraindications and Dose Limitations. June 9, 2011. .http://www.pbm.va.gov/vamedsafe/High%20Dose
%20Statins%20and%20Fibrates_National%20PBM%20Bulletin_111009_FINAL.PDF
25) Noxafil [package insert]. Whitehouse Station, NJ: Merck & CO.,INC. 2010.
26) Norvasc [package insert]. New York, NY: Pfizer INC. 2011.
27) Park CG, Lee H, Choi JW, Lee SJ, Kim SH, Lim HE. Non-concurrent dosing attenuates the pharmacokinetic interaction between amlodipine and Simvastatin. Int J Clin
Pharmacol Ther. 2010Aug;48(8):497-503.
28) ACCORD Study Group. Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus. New Engl J Med 2010;362:1563-1574.
29)