STATINS

Question 1

MOA

Answer 1

• They competitively inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA)
  reductase
• This enzyme is involved in cholesterol synthesis

Question 2

When should statins be taken? i.e. what part of the day

Answer 2

• Atorvastatin can be taken anytime during the day
• Simvastatin, pravastatin, and fluvastatin should be taken in the evening

Question 3

Cautions

Answer 3

• 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

Question 4

Which patients are at high risk of muscle toxicity (rhabdomyolysis)
which requires caution when using a statin?

Answer 4

• Personal or family history of muscular disorders
• previous history of muscular toxicity
• high alcohol intake
• renal impairment
• hypothyroidism

Question 5

Side effects - common

Answer 5

• Headache
• Gl disturbances
• Myalgia (just muscle pain/ ache)
• Hyperglycaemia

Question 6

Side effects - rare

Answer 6

• Muscle effects (Myopathy, myositis, rhabdomyolysis)
• Interstitial lung disease: dyspnoea, cough, weight loss

RED FLAG

Question 7

Pregnancy

Answer 7

AVOID
- congenital abnormalities
- decreased synthesis of cholesterol affects foetal development

Question 8

Statins and conception

Answer 8

• Statins needs to be discontinued 3 months before attempting to conceive

Question 9

Statins and women of childbearing potential?

Answer 9

• Contraception required during treatment and 1 month after stopping statins (not necessarily the pill but at least condom)

Question 10

Breastfeeding

Answer 10

NO

Question 11

Hepatic impairment

Answer 11

• Caution in Hx of liver disease
• Avoid in active liver disease
• Avoid when there are unexplained persistent elevations in serum transaminases

Question 12

Why should statins be used with caution in history of liver disease

Answer 12

Statins can cause hepatoxicity

Question 13

What are the monitoring requirements for statins?

Answer 13

1. One full lipid profile (non-fasting)
2. Thyroid stimulating hormone (TSH)
3. Renal function
4. Liver function tests (LFTs)
5. Creatinine kinase
6. HbA1c (for patient at high risk of diabetes)

Question 14

Monitoring - full lipid profile

Answer 14

• Total cholesterol, HDL-cholesterol, non-HDL and triglycerides
• Before treatment
• 3 months after in prevention of CVD to assess reduction

Question 15

Monitoring - Renal function

Answer 15

• renally excreted requiring dose adjustment or avoidance

Question 16

Thyroid stimulating hormone (TSH)

Answer 16

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

Question 17

How do you interpret the LFT result for statins?

Answer 17

• Before treatment, then within 3 months then 12 months after starting
• Measure before if signs of hepatoxicity
• STOP if more than 3 x UP

Question 18

Monitoring - creatinine kinase

Answer 18

• 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

Question 19

If the patient reports muscle symptoms
AND
Creatinine kinase is elevated

Answer 19

STOP

Question 20

Monitoring - HbA1c

Answer 20

• patients at high risk of diabetes should have HbAc checked before starting statin treatment and then repeated after 3 months
• Statins can cause hyperglycaemia

Question 21

What symptoms should patients be referred to with regards to muscle effects?

Answer 21

• Unexplained muscle pain
• Tenderness
• Weakness

Question 22

Drug interactions

Answer 22

• Amiodarone
• Diltiazem
• Itraconazole
• macrolides (e.g. clarithromycin)
• protease inhibitors
• Amlodipine (With Simvistatin)
  This is because statins are metabolised by CYP enzymes

Question 23

Interactions - CYP450 Enzyme Inducers

Answer 23

Reduces the concentration of statin

Question 24

Interactions - CYP450 Enzyme Inhibitors

Answer 24

Increases the concentration of statin → increased risk of rhabdomyolysis
* Patients prescribed macrolides should stop taking their statin during treatment
* Avoid drinking grapefruit juice

Question 25

Interactions Fusidic Acid (oral)

Answer 25

Stop statin during treatment → restart 7 days after last dose

Question 26

Amlodipine + Simvastatin = 20mg

Answer 26

important interaction statin may not exceed 20mg amlodipine increases levels of simvastatin increased risk of rhabdomyolysis

Question 27

statin + ezetimibe

Answer 27

increased risk of rhabdomyolysis

Question 28

Statins + alcohol

Answer 28

- Advise to keep alcohol to a minimum - As both increase the risk hepatoxicity

Question 29

Simvastatin and concomitant use of drugs

Answer 29

- Max 10mg it also taking bezafibrate or Ciprofibrate - Max 20mg daily Amiodarone, Amlodipine, Ranolazine - Max 20mg with verapamil and diltiazem - Max 40mg with Ticagrelor

Question 30

Which statin has a lower initial dose and max dose in patients of Asian origin?

Answer 30

Rosuvastatin - lower initial dose (5mg) than normal (5-10mg) - Max 20mg (rather than 40mg)