This document summarizes the interaction between the drugs amiodarone and simvastatin. It explains that amiodarone inhibits the CYP3A4 enzyme in the liver that metabolizes simvastatin, increasing simvastatin levels in the blood and risk of the muscle damage side effect rhabdomyolysis. It warns patients taking both drugs to notify their healthcare provider, as the simvastatin dose may need reducing or an alternative statin prescribed to lower cholesterol safely. Prescribers are advised not to exceed a daily 20mg dose of simvastatin for patients also taking amiodarone.

1. University of Sulaymania
School of Pharmacy
Third Stage
Report for pharmaceutical information
Report about : amiodarone – simvastatin interaction
Prepared by: Muhammad Koksh Sdiq

2. Simvastatin(Rx) : ( Zocor ) lipid- lowering agents (statins) and HMG- CoA Reductase
Inhibitors .
Mechanism of Action of simvastatin :
Simvastatin is a prodrug and is hydrolyzed to its active β-hydroxy acid form, simvastatin acid,
after administration. Simvastatin is a specific inhibitor of 3-hydroxy-3-methylglutaryl-
coenzyme A (HMG-CoA) reductase, the enzyme that catalyzes the conversion of HMG-CoA to
mevalonate, an early and rate limiting step in the biosynthetic pathway for cholesterol. In
addition, simvastatin reduces VLDL and TG and increases HDL-C.
Indication :
For the treatment of hypercholesterolemia and for the reduction in the risk of cardiac heart
disease mortality and cardiovascular events. It can also be used in adolescent patients for the
treatment of heterozygous familial hypercholesterolemia.
Amiodarone (Rx) : ( cordarone) anti arrhythmic agents ( class III ) .
Mechanism of action of amiodarone :
The antiarrhythmic effect of amiodarone may be due to at least two major actions. It prolongs the
myocardial cell-action potential (phase 3) duration and refractory period works by blocking
potassium channels in the heart, which prevents potassium from leaving the cells of the heart
muscle. This causes the heart tissue to resist any premature electrical signals that are trying to tell
the heart to beat before it should , and acts as a noncompetitive a- and b-adrenergic inhibitor.
Indication :
Intravenously, for initiation of treatment and prophylaxis of frequently recurring ventricular
fibrillation and hemodynamically unstable ventricular tachycardia in patients refractory to other
therapy. Orally, for the treatment of life-threatening recurrent ventricular arrhythmias such as
recurrent ventricular fibrillation and recurrent hemodynamically unstable ventricular tachycardia.
Simvastatin – amiodarone interaction : Increased risk of rhabdomyolysis .
How the interaction occurs:
Amiodarone may slow down how quickly liver metabolize cholesterol medicine( simvastatin).
but is related to the fact that amiodarone inhibits the cytochrome P450 3A4 (CYP3A4)
enzyme. This is the same enzyme that metabolizes simvastatin. So by this Amiodarone increase
toxicity of simvastatin by decreasing metabolism .
(1)

3. What might happen:
The amount of cholesterol medicine in your blood may increase and damage your muscles.
Medical warning:
These medicines may interact and cause very harmful effects and are usually not taken together.
Contact your healthcare professional (e.g. doctor or pharmacist) for more information.
What you should do about this interaction:
Let your healthcare professionals (e.g. doctor or pharmacist) know right away that you are
taking these medicines together. Your doctor may want to change the dose of your cholesterol
medicine or you may need to take a different cholesterol medicine.Tell your doctor right away if
you experience muscle pain, tenderness, or weakness; unexplained tiredness; or discolored
urine.Your healthcare professionals may already be aware of this interaction and may be
monitoring you for it. Do not start, stop, or change the dosage of any medicine before checking
with them first.
Prescribers should consider use of another statin for patients taking amiodarone, or initiating
amiodarone therapy, who require simvastatin doses greater than 20 mg daily to meet their lipid
goals.
If you are taking amiodarone and a cholesterol-lowering drug product containing simvastatin,
you should not take more than 20 mg of simvastatin each day because your risk of developing
rhabdomyolysis increases.
(2)