นสภ.อั�จจ�มา บั�วหลวงงาม

Risk of myotoxicity all statins can cause myopathy with a risk of

progressing to rhabdomyolysis. The risk appears to increase with higher

doses.Lipophilicity>>>hydrophillic

lipophilicAtorvastatin, Fluvastatin, Lovastatin,

Simvastatinhydrophilic

Pravastatin, Rosuvastatin

Mechanism

HMG-CoA reductase

StatinsStatins mevalonate

ubiquinone (coenzyme Q10)

HMG-CoA

antioxidant and membrane stabilizer that is utilized by mitochondria for electron transport

mitochondrial adenosine triphosphate (ATP)

Atrogin-1

Classification of Muscular Adverse Events

Br J Cardiol,2005

Classification of Muscular Adverse Events

Br J Cardiol,2005

The American College of Cardiology/American Heart Association/National Heart, Lung, and Blood Institute (ACC/AHA/NHLBI) 1. Statin myopathy: muscle complaints

related to statin drug use2. Myalgia: muscle complaints without serum

CK elevations3. Myositis: muscle symptoms with serum CK

elevations4. Rhabdomyolysis: markedly elevated CK

levels, usually > 10 times ULN, with an elevated creatinine level consistent with pigmentinduced nephropathy

J Am Coll Cardiol. 2002; 40: 567-72

สารราชวิ�ทยาลัยอาย�รแพทย�ฯmyopathy

ม�อัาการกล�ามเน��อัอั�กเสบัร�วมก�บัระดั�บัขอัง creatine kinase (CK) > 10 เท่�า ขอัง ULN

สารราชวิ�ทยาลัยอาย�รแพทย�ฯ ปี�ท��23 ฉบับัท�� 3 กรกฎาคม ธันวิาคม – 2549

The National Lipid Associationrhabdomyolysis

muscle cell destruction or enzyme leakage, regardless of the CK level when measured,

considered to be causally related to a change in renal function

(Thompson et al 2006).

The National Lipid AssociationClassify absolute CK elevation

Mild: CK increases < 10 times ULN Moderate: CK increases ≥ 10 times ULN, and Severe: CK increases ≥ 50 times the ULN

(Thompson et al 2006).

Time to onset Mean duration of thereapy

6.3 months (0.25-48 months)

IncidenceMyalgia without changes in CK levels (Bays 2006).

21 statin-based clinical trials with over 180,000 person years for evidence of muscle toxicity.

The incidence of myopathy was 11 per 100,000 person-years.

The incidence of rhabdomyolysis in 2 cohort studies was 3.4 (1.6–6.5) per 100,000 person-years

10-fold higher when gemfibrozil was used in combination with statins.

For statins metabolized by CYP3A4 such as lovastatin, atorvastatin, and simvastatin), the incidence was 4.2 per 100,000 person-years. In this group, interaction with drugs known to inhibit CYP3A4 (ie, erythromycin and azole antifungals) occurred in 60%

The American Journal of Cardiology. Vol 97 (8A) April 17, 2006

The American Journal of Cardiology. Vol 97 (8A) April 17, 2006

Management

Monitor transaminase level When start Statin or fibrates

After medication 6-12 weeksFollow up every 1-2 time per year

High dose or more than 2 medication3-6 months

Guidelines for Management of Dyslipidemia,สารราชว�ท่ยาล�ยอัาย�รแพท่ย!ฯ 2545