Non-statins Flashcards
Dr. Hess
MOA and dose of Ezetimbie (Zetia)
-10 mg tablet daily
-with or without food (so it doesn’t rely on timing with cholesterol production like statins), can be taken together with statins
-long half-life (it doesn’t matter when it is taken)
-decreases cholesterol absorption in the GI
Effectiveness of Ezetimibe
20-25%
-if taken with statins - LDL reduction is added on top
Combination products of Ezetimibe
EZETIMIBE + Rosuvastatin (Roszet)
EZETIMIBE + Simvastatin (Vytorin)
EZETIMIBE + Bempedoic Acid (Nexletol)
Ezetimibe has been shown to reduce cardiac events
True or False?
False
Only in combination with statins
Adverse effects of Ezetimibe
-Muscle injury
-Liver toxicity -> run a LFT
-diarrhea, steatorrhea
Which labs to run for Ezetimibe?
-CPK for muscle damage
-LFT for liver function
Contraindication: active liver disease 3x ULN
Q: Would you run a LFT anyway or just in case of symptoms
Administration of PCSK-9 inhibitor
SubQ
-every 2 weeks or 1x a month due to long-halflife
-Alirocumab (Praluent) and Evolocumab (Repatha)
MOA of PCSK-9
PCSK-9 breaks down LDL receptors
the drug blocks PCSK-9 -> more LDL receptors taking up LDL from the blood -> lowering LDL plasma level
Effectiveness of PCSK-9 inhibitor
> 50%
Role: 2nd line (2b) ->
EZETIMIBE (2a) -> cheaper, oral
PCSK-9 inhibitors reduce ASCVD events
True
Alone and together with statins
-also used in HoFH and HeFH
Side effects
Well tolerated
injection reaction
Contraindication: Hypersensitivity
PCSK-9 dose
Alirocumab (Praluent):
75 mg SQ every 2 weeks or 150 mg q 2 weeks
300 mg SQ 1x a month
Evolocumab (Repatha):
140 mg SQ q 2 weeks
420 mg 1x a month
if they miss the dose for less than a week, take it and reverse to the original schedule
if more than a week, take it and start a new schedule on the same day OR wait until the next administration day of the old schedule
MOA of Bempedoic Acid
-ATP Citrate Lyase Inhibitor
-Blocks synthesis of cholesterol (1st step block Acetyl-CoA synthesis)
Administration of Bempedoic Acid
Dose: 180 mg daily
with or without food
Effectiveness Bempedoic Acid
20-25%
-3rd line
-has been shown to reduce ASCVD in statin-intolerant!!!
Side Effects of Bempedoic Acid
-Uric acid (gout)
-Tendon rupture
-not much muscle pain (it is a prodrug activated in the liver)
-Drug-Drug Interaction:
Simvastatin 20mg
Pravastatin 40 mg
OATP1B1/B3 (transporters that move statins from blood to the liver -> so higher concentration of statins -> side effects)
MOA Inclisiran (Leqvio)
siRNA -> preventing the gene expression of PCSK-9 (doesnt get produced -> no LDL-receptor removal -> more LDL receptors to clear the blood)
Administration of Inclisiran (Leqvio)
-284 mg SQ
-Day 1 -> day 90 (3 months after day 1) -> day 270 (every 6 months after dose 2)
-if a dose is missed within 3 months take it and stick to the schedule
Effectiveness of Inclisiran (Leqvio)
-40-50%
-4th line
-not known if it reduces ASCVD
Side effects of Inclisiran (Leqvio)
injection site reactions
No contraindications
Bile Acid Sequestrants Administration
-tables, granules/powder (has to be mixed)
Effectiveness of Bile Acid Sequestrants
-20%
-Role: not used -> rather used for diarrhea due to constipating effect
-no evidence in reducing ASCVD
Side effect of Bile Acid Sequestrants
Constipation, bloating, GI upset
Contraindications and DDI of Bile Acid Sequestrants
Contraindications: patients with Pancreatitis (bc it increases TG >400)
obstructive bowel disease (these drugs work by binding bile acids in the intestine)
Drug-Drug-interactions:
reduce drug absorption of warfarin, levothyroxine
-> space 1h before or 4h after
Dose of Bile Acid Sequestrants
Colesevelam (Welchol)
-3.75 g/day - 6 tabs a day (or 3 tabs BID)
Cholestyramine (Questran)
4-24 g/day - 2 doses
Colestipol (Colestid)
2-16g/day once or divided doses
