Statins and NonStatins

Question 1

STATINS and CYP450

Answer 1

CYP3A4 (have most drug interactions)
- atorvastatin, lovastatin, simvastatin

CYP2C9
- fluvastatin

Not Significantly Metabolized by CYP450 (fewest interactions)
- pitavastatin, pravastatin, rosuvastatin

All need varying degrees of renal dosing except atorvastatin
- Statins with short half life
»> simvastatin, lovastatin, fluvastatin
»> advise to be taken in the evening bc most of cholesterol production occurs at night

Question 2

Statin Adverse Effects

Answer 2

Most common

• GI disturbances
• Headache

Most Serious
- Muscle Pain
»> RHABDO (risk increased with co-administration that inhibit their elimination)
- Diabetes (inhibits enzyme HMG CoAs reductase and other elements including COQ10, an enzyme that plays role in glucose regulation)
- Elevated Liver Enzymes

Question 3

Statin Indications

Answer 3

Primary Prevention
Secondary Prevention
- Of those with CV disease
- Of those with Hyperlipidemia

Question 4

Statins: What to do when muscle symptoms appear?

Answer 4

• Evaluate other causes (activity, hypothyroidism, VitD deficiency)
  »> leg cramps due to other causes??
• Try to avoid interacting meds (fibrates, macrolides, steroids, bisphosphonates)
• Consider statin holiday (2-4weeks) if symptoms persist you can rule out symptoms (or restart after symptoms resolve to establish causal relationship)
• Switch to different low dose statin then titrate
  »> rosuvastatin, pravastatin, fluvastatin (fewer interactions)
• Alternate date or twice weekly dosing if other options fail
• Consider adding ezetimibe for some patients
  » like those with prior CV event who cant tolerate high statin
• Dont count on CoQ10 to help

Question 5

Statin Drug Interactions

Answer 5

Azoles (fluconazole less risky)
Macrolides (usually okay to use azithromycin)
Fenofibrate or gemfibrozil
Grapefruit Juice
- advise with simvastatin or lovastatin to avoid
- keep to less than 4cups a day with atorvastatin
- little to no effect with pitavastatin, pravastatin, fluvastatin, rosuvastatin

Question 6

Cholesterol Absorption Inhibitors

Answer 6

Ezetimibe

• MOA: blocks the dietary and biliary cholesterol absorption in the small intestine without affecting absorption of triglycerides or fat-soluble vits
• use as add on for high risk patients who do not tolerate high intensity statin
• therapeutic effect: Potential LDL education is 13-20%
• adverse reactions: fatigue, diarrhea, elevated serum transaminases, sinusitis, and arthralgia

Question 7

Fibric Acid Derivatives (Fibrates)

Answer 7

gemfibrozil
fenofibrate
desfibrate

MOA: activates lipase that breaks down cholesterol

Indication:

> TG 500

high risk of CV event despite statin

• gemfibrozil CANNOT be given with statin (increases risk of rhabdo) ****
• fenofibrate preferred over gemfibrozil for use with statin safety

Therapeutic Effect:
- decreases serum triglycerides

Adverse Reactions:

• Abd pain
• nausea
• fatigue
• vertigo
• elevated LFTs
• anemia
• leukopenia
• thrombocytopenia
• Possible Cholelithiasis

Requires Renal Dosing

Question 8

Testing before statins

Answer 8

Check liver function test at baseline then when clinically indications

Question 9

Statins in pregnancy

Answer 9

NO - contraindicated