STATINS Flashcards
MOA
- They competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA)
reductase - This enzyme is involved in cholesterol synthesis
When should statins be taken? i.e. what part of the day
- Atorvastatin can be taken anytime during the day
- Simvastatin, pravastatin, and fluvastatin should be taken in the evening
Cautions
- Elderly
- High alcohol intake
- History of liver disease
- Hypothyroidism (because of higher risk of muscle toxicity)
- Those with increased risk of muscle toxicity (e.g Rhabdomyolosis) due to FHx
Which patients are at high risk of muscle toxicity (rhabdomyolysis)
which requires caution when using a statin?
- Personal or family history of muscular disorders
- previous history of muscular toxicity
- high alcohol intake
- renal impairment
- hypothyroidism
Side effects - common
- Headache
- Gl disturbances
- Myalgia (just muscle pain/ ache)
- Hyperglycaemia
Side effects - rare
- Muscle effects (Myopathy, myositis, rhabdomyolysis)
- Interstitial lung disease: dyspnoea, cough, weight loss
RED FLAG
Pregnancy
AVOID
- congenital abnormalities
- decreased synthesis of cholesterol affects foetal development
Statins and conception
- Statins needs to be discontinued 3 months before attempting to conceive
Statins and women of childbearing potential?
- Contraception required during treatment and 1 month after stopping statins (not necessarily the pill but at least condom)
Breastfeeding
NO
Hepatic impairment
- Caution in Hx of liver disease
- Avoid in active liver disease
- Avoid when there are unexplained persistent elevations in serum transaminases
Why should statins be used with caution in history of liver disease
Statins can cause hepatoxicity
What are the monitoring requirements for statins?
- One full lipid profile (non-fasting)
- Thyroid stimulating hormone (TSH)
- Renal function
- Liver function tests (LFTs)
- Creatinine kinase
- HbA1c (for patient at high risk of diabetes)
Monitoring - full lipid profile
- Total cholesterol, HDL-cholesterol, non-HDL and triglycerides
- Before treatment
- 3 months after in prevention of CVD to assess reduction
Monitoring - Renal function
- renally excreted requiring dose adjustment or avoidance
Thyroid stimulating hormone (TSH)
Before treatment
- Hypothyroidism is a reversible cause of hyperlipidaemia
- By correcting hyperthyroidism, you can get normal cholesterol
- increases the risk of muscle toxicity with statins
How do you interpret the LFT result for statins?
- Before treatment, then within 3 months then 12 months after starting
- Measure before if signs of hepatoxicity
- STOP if more than 3 x UP
Monitoring - creatinine kinase
- Before initiation if patient had persistent, unexplained muscle pain (not necessarily due to lipid-regulating drug)
- If patient complains of muscle pain whilst on statin
- If more than 5 x UL = repeat after 7 days, if still 5 x UL then don’t start statin
If the patient reports muscle symptoms
AND
Creatinine kinase is elevated
STOP
Monitoring - HbA1c
- patients at high risk of diabetes should have HbAc checked before starting statin treatment and then repeated after 3 months
- Statins can cause hyperglycaemia
What symptoms should patients be referred to with regards to muscle effects?
- Unexplained muscle pain
- Tenderness
- Weakness
Drug interactions
- Amiodarone
- Diltiazem
- Itraconazole
- macrolides (e.g. clarithromycin)
- protease inhibitors
-
Amlodipine (With Simvistatin)
This is because statins are metabolised by CYP enzymes
Interactions - CYP450 Enzyme Inducers
Reduces the concentration of statin
Interactions - CYP450 Enzyme Inhibitors
Increases the concentration of statin → increased risk of rhabdomyolysis
* Patients prescribed macrolides should stop taking their statin during treatment
* Avoid drinking grapefruit juice
Interactions Fusidic Acid (oral)
Stop statin during treatment → restart 7 days after last dose
Amlodipine + Simvastatin = 20mg
important interaction
statin may not exceed 20mg
amlodipine increases levels of simvastatin
increased risk of rhabdomyolysis
statin + ezetimibe
increased risk of rhabdomyolysis
Statins + alcohol
- Advise to keep alcohol to a minimum
- As both increase the risk hepatoxicity
Simvastatin and concomitant use of drugs
- Max 10mg it also taking bezafibrate or
Ciprofibrate - Max 20mg daily
Amiodarone, Amlodipine, Ranolazine - Max 20mg with verapamil and diltiazem
- Max 40mg with Ticagrelor
Which statin has a lower initial dose and max dose in patients of Asian origin?
Rosuvastatin
- lower initial dose (5mg) than normal (5-10mg)
- Max 20mg (rather than
40mg)
