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