Chapter 27 - Dyslipidemia Flashcards
(123 cards)
1
Q
Primary (familial) hypercholesterolemias (FH)
A
Genetic defects that cause severe cholesterol elevations.
Heterozygous familial hypercholesterolemia (HeFH) and Homozygous familial hypercholesterolemia (HoFH).
Familial dyslipidemias are categorized by the Fredrickson classification.
2
Q
SECONDARY(OR ACQUIRED)
A
poor diet and lack of physical activity –> central adiposity.
Medical conditions that cause dyslipidemia include hypothyroidism and diabetes.
very high risk and must be treated: LDL > 190 and TG > 500 mg/dL
3
Q
Friedewald equation:
A
Lipid panels (i.e.,TC,HDL,TG) are taken after 9- 12hour fast.
Non-HDL and apoB do not require fasting for accurate assessment. If not fasting, the TG level can be falsely elevated, which can cause an incorrect LDLcalculation.
LDL = TC - HDL - (TG/5)
not used when the TGs are > 400 mg/dL.
4
Q
Drug that inc LDL + TG
A
Immunosuppressants (cyclosporine and tacrolimus)
Atypical antipsychotics
steroids
Effavirenz
Diuretics
Protease inhibitors
(Imm A Ste Eff Di Pro)
5
Q
Drugs that inc LDL
A
fish oil (Except Vascepa)
6
Q
Drugs that inc TG
A
Propofol
IV lipids emulsions
bile acid sequestrants (5%)
7
Q
Conditions that inc LDL/ TG …
A
obesity
smoking
alcoholism
diabetes
hypothyroidism
nephrotic syndrome
liver/ kidney disease
poor diet
pregnancy
pcos
8
Q
non HDL
A
non HDL = TC - HDL
desirable < 130 mg/dl
9
Q
LDL levels
A
desirable: <100 mg/dl
high: >= 190
10
Q
HDL
A
desirable:
men: >= 40 mg/dl
women: >= 50 mg/dl
11
Q
TG
A
desirable: < 150
very high: >= 500 (Severe hypertriglyceridemia)
12
Q
Calculating ASCVD risk Input
A
■ Gender, age (20 - 79 years) and race
■ TC and HDL
■ Systolic blood pressure & whether antihypertensive treatment is used
■ The presence of diabetes and smoking status
(9)
13
Q
when should the ASCVD risk assessment be repeated in those with a low 10 yr risk
A
This risk assessment should be repeated every 4 - 6 years in those found to be at a low 10-year risk (<7.5%).
14
Q
Risk score is not needed for patients with:
and why
A
- clinical ASCVD,
- diabetes or
- LDL >= 190 mg/dL
as all patients in these groups should be started on a statin.
15
Q
If a risk-based treatment decision is still uncertain after a quantitative risk assessment
A
Additional risk-enhancing factors should be considered to assist with decision making.
Risk-enhancing factors:
- very high LDL,
- family history of premature ASCVD,
- metabolic syndrome,
- chronic kidney disease,
- history of preeclampsia or premature menopause,
- chronic inflammatory disorders,
- high CRP,
- high coronary artery calcium score (CAC)
- abnormal ankle brachial index.
16
Q
What does CAC indicates?
A
The CAC measurement is helpful in deciding if statins should be initiated in those with 10-year ASCVD risk of
7.5 - 19.9%.
A CAC score >= 100 Agatston units indicates statins should be initiated.
17
Q
What is an ASCVD event?
A
CVA, TIA, ACS, MI, angina, CAD, PAD
18
Q
Lifestyle modification
A
- Diet to maintain a healthy weight (BMI18.5 - 24.9 kg/m 2)
- Rich in vegetables, fruits, whole grains and high-fiber foods, such as in plant-based and Mediterranean diets.
- Fish with high-fat content (rich in omega-3 fatty acids).
- Limit saturated fat, trans fat (partially hydrogenated) & cholesterol by choosing lean meats, non-meat alternatives & low-fat dairy products.
- Aim for 5 - 6%of calories from saturated fat.
- Limit added sugars & salt
- Limit smoking and alcohol
- Aerobic physical activity 3 - 4 times per week,
lasting 40 minutes/session (decreases LDL3 - 6 mg/dL)
19
Q
NATURAL PRODUCTS that can lower LDL
A
- Red yeast rice (contains naturally occurring HMG-CoAreductase inhibitors in low amounts.)
- Fibrous foods
20
Q
What organ damage can many cholesterol lowering drugs cause? Explain.
A
- Drugs: niacin, fibrates, potentially statins and ezetimibe
- Cause: Liver damage
- Do not use if the AST or ALTis > 3 times the upper limit of normal.
- Statins: nonsignificant inc in liver enzymes but LFTs should still be monitored.
21
Q
MOA of Statins
A
inhibits the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, which prevents the conversion of HMG-CoA to mevalonate.
rate- limiting step in cholesterol synthesis.
22
Q
What statin intensity should be used for Secondary Prevention of ASCVD
A
high intensity
except: (Give mod)
- not a candidate for high-intensity or
- patient > 75 years with LDL 70-189 mg!dL
23
Q
primary elevation of LDL >= 190 mg/dl
A
give high int statin
24
Q
Diabetes + Age 40 - 75 years + LDL between 70 -189 mg/dl
A
Regardless of 10-year ASCVD risk –> Mod
Multiple ASCVD risk factors –> High
25
Age 40-75 years + LDL between 70-189 mg/dl
10-yr ASCVD risk >= 20% --> High
10-yr ASCVD risk 7.5-19.9% + risk-enhancing factor --> Mod
26
high intensity statins
Atorvastatin: 40 - 80 mg (Lipitor)
Rosuvastatin: 20 - 40 mg (Crestor)
27
Mod intensity statins
Pitavastatin: 2 - 4 mg
Rosuvasttain: 5 - 10 mg
Atorvastatin: 10 - 20 mg
Simvastatin: 20 - 40 mg
Lovastatin: 40 mg
Pravastatin: 40 - 80 mg
Fluvastatin: 40 BID or 80 XL mg
28
Low intensity statins
Pitavastatin: 1 mg
Simvasttain: 10 mg
Pravastatin: 10 - 20 mg
Lovastatin: 20 mg
Fluvastatin: 20 - 40
29
Muscle Damage from Statins
- symmetrical pain
- within 6 weeks
- Rhabdomyolysis: muscle symptoms with very high CPK {>10,000) + muscle protein in the urine (myoglobinuria), which can lead to acute renal failure
30
What could provide relief for mild sx of muscle SE from statins?
Coenzyme Q 10
31
How can you reduce the risk of myalgia?
- Avoid drug interactions, including OTC products.
- Do not use simvastatin 80 mg/day.
- Do not use gemfibrozil + statin.
32
How can you manage myalgias?
- Hold statin, check CPK, check other possible causes.
- After 2-4 weeks: re-challenge with same statin at same or lower dose.
- Most patients who did not tolerate a statin will tolerate it when re-challenged, or will tolerate a different statin.
- If myalgias return, discontinue statin.
- Once muscle symptoms resolve, use a low dose of a different statin; gradually inc dose.
33
atorvastatin
Lipitor
34
GF is a 58 year old male who presents to his primary care manager for his annual checkup. His past medical history is significant for hypertension, allergic rhinitis, and GERD. He currently takes diltiazem 240mg daily, hctz 25mg daily, loratadine 10mg daily, and omeprazole 20mg daily. Based on GF's lipid profile and current CV risk, the decision is made to start statin therapy, specifically simvastatin. Which of the following is true regarding dosing of simvastatin with GF's current medication regimen?
A. The dose of simvastatin should not exceed 40mg daily.
B. The dose of simvastatin should not exceed 20mg daily.
C. The dose of simvastatin should not exceed 10mg daily.
D. The dose of simvastatin should not exceed 5mg daily.
Answer with rationale:
The correct answer is C. Close attention is required when administering simvastatin with certain medications due to the potential for decreased simvastatin metabolism and increased risk of toxicity due to CYP 3A4 inhibition. Additionally, grapefruit juice due to its potent CYP 3A4 inhibition should be avoided with simvastatin therapy. There are some medications such as itraconazole or clarithromycin (common with H. pylori regimens) that are contraindicated with simvastatin. Answer C is correct as this patient is receiving dilitiazem which necessitates a dose maximum of 10mg daily. The other medications on GF's profile do not require adjustment of simvastatin making the other answers incorrect.
35
Fluvastatin
Lescol
Lescol XL
36
Lovastatin
Altoprev
Mevacor
37
Pitavastatin
Livalo
Zypitamag
38
Pravastatin
Pravachol
39
Rosuvastatin
Crestor
Ezallor
Sprinkle
40
Simvastatin
Zocor
FloLipid
41
What are some contraindications of statin therapy
Do not use in pregnancy, breastfeeding
Do not use strong CYP3A4 inhibitors with simvastatin and lovastatin
Do not use with liver disease, including any unexplained inc LFTs
Do not use cyclosporine with pitavastatin
42
what are some warnings for statin therapy?
Muscle damage
Diabetes: inc AlC/FBG; benefit of statin outweighs risk
Inc Hepatotoxicity, with inc LFTs(rare),
immune-mediated necrotizing myopathy (IMNM) (rare)
Rosuvastatin: proteinuria, hematuria - usually transient
Atorvastatin: hemorrhagic stroke (if recent stroke or TIAs); benefit of statin outweighs risk
43
What increases the risk of muscle damage with statin (Warning)
Muscle damage:
- Myopathy/rhabdomyolysis with inc CPK ± acute renal failure,
- Higher risk with higher dose (e.g.. simvastatin 80 mg),
- advanced age (~ 65 years),
- niacin,
- fibrates (e.g.,gemfibrozil),
- CYP3A4 inhibitors,
- hypothyroidism (uncontrolled),
- renal impairment
44
What should you monitor baseline/routine with statin therapy?
Lipid panel (TC, LDL, HDL, TGs) 4-12 weeks after starting treatment and then every 3-12 months (usually annually), LFTs
45
What should you monitor with statin therapy if pt is symptomatic?
- Myalgia/myopathy: check CPK
- Little/no urine: check SCr/BUN for acute renal failure due to rhabdomyolysis
- Abdominal pain or jaundice: check LFTs for possible hepatotoxicity
46
When can you take:
Crestor, Lipitor, Livalo, Lesco/XL, Pravachol, and FloLipid?
Can take Crestor,Lipitor, Livalo, Lesco/XL and Pravachol at any time of day
FloLipid is taken on an empty stomach
47
What should you do:
For CrCI < 30 ml/min
For eGFR < 60 ml/min
For CrCI < 30 ml/min, use lower starting doses of lovastatin, simvastatin and rosuvastatin
For eGFR < 60 ml/min, use lower starting dose of pitavastatin
48
Rosuvastatin exposures are --- times --- in --- patients - consider ---.
Rosuvastatin exposures are 2 times higher in Asian patients - consider 5 mg starting dose
49
What are the lipid effects of statin?
Dec LDL ~20-55%
Inc HDL ~5-15%
Dec TG ~10-30%
High intensity: dec >= 50% LDL;
Mod intensity: dec 30 - 49 % LDL;
High intensity: dec < 30 %
50
Statins that are cyp substrates:
Statins with the least ddi:
Atorvastatin, lovastatin and simvastatin are CYP3A4substrates.
Rosuvastatin and pravastatin have less drug interactions.
51
what drugs can inc risk of myopathy & rhabdomyolysis with statin?
do not use statin with ...
Fibrates (especially gemfibrozil) and niacin can inc the risk of myopathies and rhabdomyolysis.
Do not use statins with gemfibrozil.
52
amlodipine and statin ddi?
Amlodipine can inc the concentration of atorvastatin, lovastatin and simvastatin (max daily dose 20 mg/day).
53
cyp inhibitors?
do not use these statins with cyp inhibitors:
G* PACMAN*
Grapefruit juice
Protease inhibitors
azoles antifungals
cyclosporin, Cobicistat
Macrolide except azoles
Amiodarone
non dhp ccb
Do not use with simvastatin or lovastatin
54
--- --- mg/day max with cyclosporine only
--- --- mg/day max with cobicistat only
--- --- mg/day max & --- --- mg/day max with amiodarone
--- --- mg/day max & --- --- mg/day max with non dhp ccb
Rosuvastatin 5 mg/day max with cyclosporine only
Atorvastatin 20 mg/day max with cobicistat only
Simvastatin 20 mg/day max Lovastatin 40 mg/day max with amiodarone
Simvastatin 10 mg/day max Lovastatin 20 mg/day max with non dhp ccb
55
Non statin Add on therapy
In most cases, ezetimibe is used because PCSK9 inhibitors are much more expensive.
Fish oils and fibrates are used to target high triglycerides.
Bile acid sequestrants are rarely used, except when statins cannot be tolerated.
56
1) Very high risk pts?
What add on therapy should you add?
Patient Criteria:
2) Very high-risk pt + statin at max dose & LDL remains >= 70 mg/dl
3) Primary hypercholesterolemia (LDL>= 190 mg/dl), statin at max dose & LDL remains >= 100 mg/dl
1) Very high risk:
- History of multiple ASCVD events or
- One ASCVD event in a high-risk patient (eg diabetes)
2) Ezetimibe (preferred) or PCSK9 inhibitors
3) Ezetimibe (preferred) or PCSK9 inhibitors
57
MOA of ezetimibe
Ezetimibe inhibits absorption of cholesterol in the small intestine.
58
zetia
ezetimibe
59
vytorin
warning: if eGFR < 60, ...
ezetimibe + simvastatin
If eGFR < 60 ml/ min, do not exceed simvastatin 20 mg/ day when using combination product (Vytorin)
60
Vytorin CI?
Vytorin:
- Statin contraindications apply;
- Active liver disease (including any unexplained i in LFTs),
- Pregnancy/breastfeeding
61
some warnings with ezetimibe
- Avoid use in moderate or severe hepatic impairment
- Skeletal muscle effects (e.g.,myopathy, rhabdomyolysis), risk inc when combined with a statin
62
SE of ezetimibe
- Myalgias,
- diarrhea,
- URTls,
- arthralgias,
- pain in extremities,
- sinusitis
63
what should you monitor when you use ezetimibe with statin and/or fibrate
When used with a statin and/or fibrate, obtain LFTsat baseline and as clinically indicated thereafter
64
Lipid effects with ezetimibe monotherapy
Lipid effects with ezetimibe monotherapy
- dec LDL 18-23%,
- inc HDL 1-3%,
- dec TG 5-10%
65
Ezetimibe Drug Interactions
■ When ezetimibe and cyclosporine are given together, the concentration of both can inc; monitor levels of cyclosporine.
■ Concurrent bile acid sequestrants dec ezetimibe; give ezetimibe two hours before or four hours after bile acid sequestrants.
■ Can inc risk of cholelithiasis when used with fenofibrate and gemfibrozil. Do not use with gemfibrozil.
66
MOA pcsk9i
The LDL receptor clears circulating LDL.
Proprotein convertase subtilisin kexin type 9 (PCSK9) is an enzyme that increases LDL receptor degradation.
The PCSK9inhibitors, alirocumab and evolocumab, are monoclonal antibodies (MAb) that block the ability of PCSK9to bind to the LDL receptor.
They dramatically dec LDL cholesterol and reduce the risk of cardiac events.
They are costly and given by SC injection.
67
praluent
Alirocumab
68
Evolocumab
Repatha,
Repatha SureC/ick,
Pushtronex
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se of pcsk9 i
- Injection site reactions,
- nasopharyngitis,
- influenza,
- URTls,
- UTI,
- back pain (evolocumab},
- inc lFTs (alirocumab)
- allergic reaction
70
what should you monitor with pcsk9i
lDl at baseline and at 4-8 weeks to assess response
71
storage of pcsk9i
- Store in the refrigerator in the original carton to protect from light
- Can be kept at room temperature for up to 30 days; discard after 30 days if stored at room temperature
- Prior to administration, allow prefilled pen to warm to room temperature (30 - 45 minutes for Pushtronex) and inspect for particulate matter and discoloration
- Expensive: -$14,000/yr
72
lipid effects of pcsk9i
- dec lDl 60%
- dec non-HDl 35%
- dec apoB 50%
- dec TC 36%
73
MOA of bile acid sequ
These drugs bind bile acids in the intestine, forming a complex that is excreted in the feces.
This non-systemic action results in a partial removal of the bile acids from the enterohepatic circulation, preventing their reabsorption.
74
Cholestyramine brand names
Prevalite
Questran
Questran Light
75
Colesevelam
what is it approved for?
Welchol
Also approved for glycemic control in type 2 DM (dec A1C ~0.5%)
76
Colestipol
Colestid
77
contraindications of bile acid sequestrants
Cholestyramine:
- complete biliary obstruction
Colesevelam:
- bowel obstruction,
- TG > 500 mg/dl,
- history of hypertriglyceridemia-induced pancreatitis
78
Warnings of bile acid sequestrants
Cholestyramine "light" formulations and colesevelam granules contain phenylalanine and should not be used in patients with PKU
inc bleeding tendency due to vitamin K deficiency
79
SE of bile acid sequestrants
Constipation (may need dose reduction or laxative), abdominal pain, cramping, bloating, gas, inc TG, dyspepsia, nausea, esophageal obstruction
80
Bile acid sequestrants are not recommended when TG are --- --- mg/dl
>= 300
81
How do you take Cholestyramine & Colesevelam & Colestipol?
What's a risk with taking it?
Cholestyramine packet:
mix powder with 2-6 oz. water or non-carbonated liquid;
sipping or holding the resin suspension in the mouth for prolonged periods may lead to changes in the surface of the teeth resulting in discoloration, erosion of enamel or decay; good oral hygiene should be maintained
Colesevelam packet: empty 1 packet into a glass; add 8 oz. of water, fruit juice or a diet soft drink and mix well
Colestipol packet: empty 1 packet into at least 3 oz. of liquid and stir until completely mixed
82
Colesevelam is --- in a pregnant patient
an option
83
whats the lipid effect of bile acid sequestrants?
- dec LDL ~10-30%,
- inc HDL -3-5%,
- no change or INC TG ~5%
! Not recommended when TG are >= 300 mg/dl
84
1) which bile acid sequ has fewer DDI?
2) How much should you space from all other drugs with the other 2 bile acid sequ?
3)
1) Colesevelam (Welchol) has fewer drug interactions than the other two bile acid sequestrants and is more commonly used.
2) For cholestyramine or colestipol, take all other drugs ~ least 1 - 4 hours before or 4 - 6 hours after the bile acid sequestrants.
85
DDI between warfarin and bile acid sequ
With warfarin, monitor INR frequently during initiation and after a dose change.
86
1) The following medications should be taken --- hours prior to colesevelam:
2) Colesevelam --- levels of metformin ER.
1) four hours prior to colesevelam:
- cyclosporine,
- glimepiride,
- glipizide,
- glyburide,
- levothyroxine,
- olmesartan,
- phenytoin, and
- oral contraceptives containing ethinyl estradiol and norethindrone.
2) Colesevelam inc levels of metformin ER.
87
Bile acid sequestrants can --- absorption of ---
intervention?
Bile acid sequestrants can dec absorption of fat-soluble vitamins (A, D, E, K), folate and iron.
A multivitamin may be needed, but separate administration time from the bile acid sequestrant.
88
MOA of fibrates
Fibrates are peroxisome proliferator receptor alpha (PPARa) activators, which upregulate the expression of apolipoprotein C2 (apoC-II) and apolipoprotein Al (apoA-I).
ApoC-II increases lipoprotein lipase activity leading to increased catabolism of VLDL particles.
This will decrease TG significantly, but in the setting of high TG (increased VLDL particles), fibrate therapy can lead to an increase of LDL particles and subsequently increase LDL cholesterol.
The decreased TG can lead to an increase in HDL cholesterol.
89
Fenofibrate, Fenofibric Acid
- Antara
- Tricor
- Trilipix
- Fenoglide
- Fibricor
- Lipofen
- Triglide
have different dosing regimens
90
Gemfibrozil
dose? before or after food?
Lopid
600 mg BID, 30 minutes before breakfast and dinner
91
CI of fibrates
- Severe liver disease, including primary biliary cirrhosis
- Severe renal disease (CrCI <= 30 ml/min)
- Gallbladder disease
- Breastfeeding (fenofibrate derivatives only)
- Concurrent use with repaglinide or simvastatin (gemfibrozil only)
92
se of fibrates
- Myopathy, inc risk when coadministered with a statin, particularly in the elderly, diabetes, renal failure or hypothyroidism
- Cholelithiasis
- Reversible inc SCr (> 2 mg/dl);
- Dyspepsia (gemfibrozil),
- inc LFTs(dose-related),
- abdominal pain,
- inc CPK,
- URTls
93
monitoring for fibrates
- LFTs,
- renal function
- Reduce dose if CrCI 31-80 ml/min (fenofibrates)
94
lipid effects of fibrates
- dec TG 20-50%,
- inc HDL 15%,
- dec LDL 5-20% (can inc LDL when TG are high)
95
DDI with fibrates
1) Fibrates (especially gemfibrozil) can inc the risk of myopathies and rhabdomyolysis.
Gemfibrozil should not be given with ezetimibe or statins.
2) Colchicine can i the risk of myopathy when coadministered with fenofibrate.
3) Gemfibrozil is contraindicated with repaglinide as it can inc hypoglycemic effects.
4) Fibrates can inc the effects of sulfonylureas and warfarin.
96
MOA of niacin
Niacin decreases the rate of hepatic synthesis of VLDL (decreases TG) and LDL and can also increase the rate of chylomicron TG removal from plasma.
It alters the binding of HDL particles to scavenger receptor B-1 in the liver, which removes the cholesterol inside, but does not take up the HDL particle, which leaves it free to return to the circulation for reverse cholesterol transport.
Niacin is also known as nicotinic acid or vitamin B3, although doses for cholesterol reduction are much higher than doses found in multivitamin products.
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Niacin
1) Immediate-release (IR) (crystalline): Niacor
2) Extended-release (ER): Niaspan
3) Controlled-release (CR)/sustained- release (SR): Sia-Niacin
98
CI of niacin
Do not use with
- active liver disease
- active PUD
- arterial bleeding
99
Warning of niacin
- Rhabdomyolysis with niacin doses >= 1 g/day combined with statins
- Hepatotoxicity
- Lab abnormalities: inc BG, inc uric acid, dec phosphate
- Use with caution in patients with unstable angina or the acute phase of an Ml
100
SE of niacin
Flushing, pruritus (itching), vomiting, diarrhea, inc BG, hyperuricemia (or gout), nausea, cough, orthostatic hypotension, hypophosphatemia, dec platelets
101
monitoring of niacin
- Check LFTs at the start (baseline); every 6-12 weeks for the first year and then about every 6 months,
- blood glucose (if diabetic),
- uric acid (if gout history),
- INR (if on warfarin),
- lipid profile
102
notes on dosing of niacin
- IR niacin has poor tolerability due to flushing/itching
- CR/SR have less (but still significant) flushing but more hepatotoxicity
- The best clinical choice is ER Niaspan, with less flushing and less hepatotoxicity (compared to CR/SR formulations), but it is the most expensive
- To reduce flushing:
Take aspirin 325 mg (or ibuprofen 200 mg) 30-60 minutes before the first dose; take with food, but avoid spicy food, alcohol and hot beverages (which can worsen flushing)
- Formulations of niacin (IR vs. ER) are not interchangeable
- Flush-free niacins (inositol hexaniacinate or hexanicotinate), niacinamide or nicotinamide are
not effective
- Titrate dose slowly
take with food
103
lipid effect of niacin
dec LDL 5-25%,
inc HDL 15-35%,
dec TG 20-50%
104
DDI with niacin
- Monitor for other concurrent drugs that are potentially hepatotoxic.
- Take niacin 4 - 6 hours after bile acid seguestrants.
105
MOA of fish oil
- The mechanism is not completely understood; it may reduce hepatic synthesis of TG.
- These are indicated as an adjunct to diet when TG >= 500 mg/dL.
- Fish oil is also known as omega-3 fatty acids.
- Icosapent ethyl (Vascepa) is recommended for ASCVD risk reduction in select patients (age > 45 years and clinical ASCVDor age > 50 years with type 2 diabetes and additional risk factors) with triglycerides that are 135- 499 mg/dL despite maximally tolerated statin.
106
Omega-3 Acid Ethyl Esters
lovaza
1 gram capsule contains 465 mg eicosapentaenoic (EPA) acid and 375 mg docosahexaenoic acid (DHA)
107
Icosapent ethyl
Vascepa
Contains 0.5 or 1 gram of icosapent ethyl, an ethyl ester of omega-3 fatty acid EPA
with food
108
warnings with fish oils
- Use with caution in patients with known hypersensitivity to fish and/or shellfish Lovazacan i levels of LDL; monitor
- Monitor LFTs (in patients with hepatic impairment) and LDL periodically during therapy
- There is a possible association between Lovaza and more frequent recurrences of symptomatic atrial fibrillation or flutter in patients with paroxysmal or persistent atrial fibrillation, particularly within the first months of initiating therapy
109
SE with fish oil
- Eructation (burping),
- dyspepsia,
- taste perversions (Lovaza),
- arthralgias (Vascepa)
110
surgeries and fish oil intervention
- Many OTC omega-3 fatty acid products are marketed as dietary supplements; only prescription medications Lovaza and Vascepa are FDA-approved for TG lowering, in addition to diet, when TG >= 500 mg/dl
- Stop prior to elective surgeries due to increased risk of bleeding
111
Lipid effects with fish oil
- dec TG up to 45%,
- inc HDL 9%,
- inc LDL (up to 44% with Lovaza, not seen with Vascepa
112
ddi with fish oil
- Omega-3-fatty acids can prolong bleeding time; use with caution with other medications that can t bleeding risk
(e.g., anti platelets, anticoagulants).
- Monitor INR if patients are taking warfarin at dose initiation or dose change.
113
Lomitapide
- Lomitapide is a specialty drug that decreases apoB, the main component of LDL and VLDL (the precursor to LDL).
- Lomitapide binds to and inhibits microsomal triglyceride transfer protein (MTP), which prevents the assembly of apoB containing lipoproteins. It is approved for use in homozygous familial hypercholesterolemia (HoFH).
Evinacumab-dgnb (Evkeeza)is a novel treatment approved for HoFH.
It blocks the function of angiopoietin-like 3 (ANGPTL3), a protein involved in lipid metabolism.
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Lumitapide
Juxtapide
115
Bempedoic acid
Nexletol
116
Bempedoic acid (Nexletol)
inhibits cholesterol synthesis in the liver by inhibiting adenosine triphosphate-citrate lyase (ACL).
It is approved for use in HeFH and ASCVD requiring additional LDL lowering.
117
warning with juxtapid
Due to the risk of hepatotoxicity, this agent is only available through the Juxtapid Risk Evaluation and Mitigation Strategy (REMS) program
118
dosing of juxtapid
5-60 mg daily
Hepatic impairment or ESRD:dosage adjustment required
Take whole, with water, but without food, at least two hours after the evening meal
119
BBW with juxtapid
Hepatotoxicity (inc LFTs,steatosis)
120
CI with justapid
- Active liver disease (including unexplained inc LFTs),
- moderate or severe hepatic impairment
- Pregnancy
- Do not use with moderate or strong CYP3A4 inhibitors
121
se with juxtapid
N/V/D, dyspepsia, abdominal pain, constipation, flatulence, inc LFTs, chest pain, back pain, fatigue, weight loss, influenza, nasopharyngitis
122
monitoring with juxtapid
LFTs (including total bilirubin), alkaline phosphatase, lipids, pregnancy test in females of reproductive potential at baseline
123
DDI with juxtapid
Drug interactions involving CYP3A4 and P-glycoprotein
