Transcript Slide 1

นสภ.อัจจิมา บัวหลวงงาม
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


lipophilic
 Atorvastatin, Fluvastatin, Lovastatin, Simvastatin
hydrophilic
 Pravastatin, Rosuvastatin
Mechanism
HMG-CoA
HMG-CoA
reductase
Statins
Atrogin-1
mevalonate
ubiquinone
(coenzyme Q10)
mitochondrial adenosine
triphosphate (ATP)
antioxidant and membrane
stabilizer that is utilized by
mitochondria for electron
transport
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 use
 2. Myalgia: muscle complaints without serum CK
elevations
 3. Myositis: muscle symptoms with serum CK
elevations
 4. 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
สารราชวิทยาลัยอายุรแพทย์ ฯ
 myopathy
 มีอาการกล้ามเนื้ออักเสบร่วมกับระดับของ creatine kinase (CK) >10 เท่า
ของ ULN
สารราชวิทยาลัยอายุรแพทย์ฯ ปี ที2่ 3 ฉบับที่ 3 กรกฎาคม–ธันวาคม 2549
The National Lipid Association
 rhabdomyolysis
 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 Association
 Classify 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)
Incidence
 Myalgia 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 weeks
 Follow up every 1-2 time per year
 High dose or more than 2 medication
 3-6 months
Guidelines for Management of Dyslipidemia,สารราชวิทยาลัยอายุรแพทย์ฯ 2545