Dyslipidemia Flashcards
Calculate LDL (using the Friedrickson equation)
LDL = Total CH - HDL — (TG/’5)
This formula can not be used when the TGs are > 400 mg/dL
Calculate LDL (using the Friedewald equation)
LDL = Total CH - HDL — (TG/’5)
This formula can not be used when the TGs are > 400 mg/dL
Identification of 4 Statin Benefit Groups
1- ASCVD including ACS s/p MI, stable or unstable angina ,stroke, TIA, etc.
2- Primary elevations of LDL > 190 mg/dL
3- Diabetes and 40-75 years of age with LDL between 70- 189 mg/dL
4- 40-75 years of age with LDL between 70-189 mg/dL and estimated 10-year ASCVD risk of >, = 7.5%
Identification of 4 Statin Benefit Groups
1- ASCVD including ACS s/p MI, stable or unstable angina ,stroke, TIA, etc.
2- Primary elevations of LDL > 190 mg/dL
3- Diabetes and 40-75 years of age with LDL between 70- 189 mg/dL
4- 40-75 years of age with LDL between 70-189 mg/dL and estimated 10-year ASCVD risk of >, = 7.5%
Additional factors may be considered to assist with quantitative risk assessment
1- LDL >, = 160 mg/dL, or genetic hyperglycemia
2- Family history of premature ASCVD with onset
Additional factors may be considered to assist with quantitative risk assessment
1- LDL >, = 160 mg/dL, or genetic hyperglycemia
2- Family history of premature ASCVD with onset = 300 Agaston units or a 75 percentile for age, sex, and ethnicity
5- Ankle Brachial Index
Additional factors may be considered to assist with quantitative risk assessment
1- LDL >, = 160 mg/dL, or genetic hyperglycemia
2- Family history of premature ASCVD with onset = 300 Agatston units or a 75 percentile for age, sex, and ethnicity
5- Ankle Brachial Index
Statin Treatment~
- High Intensity
- Primary elevation of LDL >, = 190 mgIdL
- Diabetes and 40-75 years with LDL between 70-189 mg/dL with estimated 10-year ASCVD risk >, = 7.5%
- Clinical atherosclerotic cardiovascular disease (ASCVD = ACS, MI, Stroke, TIA, Stable, unstable angina, PAD)
Statin Treatment~
- High Intensity
- Primary elevation of LDL >, = 190 mgIdL
- Diabetes and 40-75 years with LDL between 70-189 mg/dL with estimated 10-year ASCVD risk >, = 7.5%
- Clinical atherosclerotic cardiovascular disease (ASCVD = ACS, MI, Stroke, TIA, Stable, unstable angina, PAD)
Statin Treatment~
- Moderate Intensity
- Diabetes and 40-75 years with LDL between 70-189 mg/dL with estimated 10-year ASCVD risk
Statin Treatment
- High Intensity
- Primary elevation of LDL >, = 190 mgIdL
- Diabetes and 40-75 years with LDL between 70-189 mg/dL with estimated 10-year ASCVD risk >, = 7.5%
- Clinical atherosclerotic cardiovascular disease (ASCVD = ACS, MI, Stroke, TIA, Stable, unstable angina, PAD)
Statin Treatment
- Moderate Intensity
- Diabetes and 40-75 years with LDL between 70-189 mg/dL with estimated 10-year ASCVD risk
Statin Treatment
- Moderate-High Intensity
- 40-75 years with LDL between 70-189 mg/dL with estimated 10-year ASCVD risk >, = 7.5%
Statin Treatment
- High Intensity
- Primary elevation of LDL >, = 190 mgIdL
- Diabetes and 40-75 years with LDL between 70-189 mg/dL with estimated 10-year ASCVD risk >, = 7.5%
- Clinical atherosclerotic cardiovascular disease (ASCVD = ACS, MI, Stroke, TIA, Stable, unstable angina, PAD)
Statin Treatment
- Moderate-High Intensity
- 40-75 years with LDL between 70-189 mg/dL with estimated 10-year ASCVD risk >, = 7.5%
- Clinical atherosclerotic cardiovascular disease (ASCVD = ACS, MI, Stroke, TIA, Stable, unstable angina, PAD) > 75 years
Statin Treatment
- Moderate-High Intensity
- 40-75 years with LDL between 70-189 mg/dL with estimated 10-year ASCVD risk >, = 7.5%
- Clinical atherosclerotic cardiovascular disease (ASCVD = ACS, MI, Stroke, TIA, Stable, unstable angina, PAD) > 75 years
Statin Treatment
- Consider risk benefit
- Ages 40-75 years with LDL between 70-139 mgfdL with estimated 10-year ASCVD risk
Statin Treatment
- Consider risk benefit
- Ages 40-75 years with LDL between 70-139 mg/dL with estimated 10-year ASCVD risk
Statin Treatment
- High Intensity
- Primary elevation of LDL >, = 190 mg/dL
- Diabetes and 40-75 years with LDL between 70-189 mg/dL with estimated 10-year ASCVD risk >, = 7.5%
- Clinical atherosclerotic cardiovascular disease (ASCVD = ACS, MI, Stroke, TIA, Stable, unstable angina, PAD)
Statin Treatment
- Moderate-High Intensity
- 40-75 years with LDL between 70-189 mg/dL with estimated 10-year ASCVD risk >, = 7.5%
- Clinical atherosclerotic cardiovascular disease (ASCVD = ACS, MI, Stroke, TIA, Stable, unstable angina, PAD) > 75 years
Statin Treatment
High Intensity Therapy
DAILY DOSE decrease LDL > 50%
Atorvastatin 40-80 mg daily
Rosuvastatin 20-40 mg daily
Statin Treatment
- Moderate-High Intensity
- 40-75 years with LDL between 70-189 mg/dL with estimated 10-year ASCVD risk >, = 7.5%
- Clinical atherosclerotic cardiovascular disease (ASCVD = ACS, MI, Stroke, TIA, Stable, unstable angina, PAD) > 75 years
Statin Therapy
High Intensity
DAILY DOSE decrease LDL > 50%
Atorvastatin 40-80 mg daily
Rosuvastatin 20-40 mg daily
Statin Therapy
- Moderate Intensity
DAILY DOSE decrease LDL > 30- 49% Rosuvastatin 5-10 mg daily Atorvastatin 10-20 mg daily Simvastatin 20-40 mg daily Pravastatin 40-80 mg daily Lovastatin 40 mg daily Fluvastatin XL 80 mg daily Fluvastatin 40 mg BID Pitavastatin 2-4 rrig daily
Statin Therapy
- Low Intensity
DAILY DOSE decrease LDL
Statin Therapy
High Intensity
DAILY DOSE decrease LDL > 50%
Atorvastatin 40-80 mg daily
Rosuvastatin 20-40 mg daily
Statin Therapy
- Moderate Intensity
DAILY DOSE decrease LDL > 30- 49%
Rosuvastatin 5-10 mg daily Atorvastatin 10-20 mg daily Simvastatin 20-40 mg daily Pravastatin 40-80 mg daily Lovastatin 40 mg daily Fluvastatin XL 80 mg daily Fluvastatin 40 mg BID Pitavastatin 2-4 rrig daily
Statin Therapy
- Low Intensity
DAILY DOSE decrease LDL
Agents for treating homozygous familial hypercholesterolemia (HoFH)
lomitapide and mipomerson
STATINS MOA
inhibit the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase preventing the conversion of HMG-CoA to mevalonate (the rate-limiting step in cholesterol synthesis).
Statins Drugs
- Atorvastatin (Lipitor)
- Simvastatin (Zocor) + ezetimibe (Vytorin)
- Rosuvastatin (Crestor)
- Pravastatln (Pravachol)
- Lovastatin (Mevacor, Altoprev) + niacin (Advicor)
- Fluvastatin (Lescol, Lescoi XL)
- Pitavastatin (Livalo)
Dosing: Atorvastatin (Lipitor)
+ amlodipine (Caduet)
+ ezetirnibe {Liptruzet)
10-80 mg daily
Equiv dose = 10 mg
Slmvastatin (Zocor)
+ ezetimibe (Vitoryn)
+ niacin (Simcor)
+ sitaGLlPtin (Juvisync)
10-40 mg daily in the evening
Equiv dose = 20 mg
Dosing: Simvastatin (Zocor)
+ ezetimibe (Vitoryn)
+ niacin (Simcor)
+ sitaGLlPtin (Juvisync)
10-40 mg daily in the evening
Equiv dose = 20 mg
Dosing: Rosuvastatin (Crestor)
5-40 mg daily
Equiv dose = 5 mg
Dosing: Pravastatin (Pravachol)
10-80 mg daily
Equiv dose = 40 mg
Lovastatin (Mlevacor, Altoprev) + niacin (Advicor)
20-80 mg
Mevacor (immediate release) is taken with evening meal Altoprev (extended release) is
taken at bedtime
Equiv dose = 40 mg
Fluvastatin (Lescol, Lescoi XL)
20-80mg at bedtime with immediate release (anytime with XL)
Equiv dose = 80 mg
Dosing: Simvastatin (Zocor)
+ ezetimibe (Vytoryn)
+ niacin (Simcor)
+ sitaGLlPtin (Juvisync)
10-40 mg daily in the evening
Equiv dose = 20 mg
Lovastatin (Mevacor, Altoprev) + niacin (Advicor)
20-80 mg
Mevacor (immediate release) is taken with evening meal Altoprev (extended release) is
taken at bedtime
Equiv dose = 40 mg
Fluvastatin (Lescol, Lescol XL)
20-80mg at bedtime with immediate release (anytime with XL)
Equiv dose = 80 mg
Pitavastatin (Livalo)
1-4 mg daily
Most potent statin
Equiv dose = 2 mg
Statin Contraindications
- Active liver disease (including any unexplained elevations in hepatic transaminases)
- Pregnancy, breastfeeding;
- Cconcurrent use of strong 3A4 inhibitors- with simvastatin and lovastatin
Statin Warnings
Skeletal muscle effects (e.g., myopathy, including risk of rhabdomyolysis)— unexplained and/or persistent muscle pain, tenderness, or weakness
Statin Warnings
- Skeletal muscle effects (e.g., myopathy, including risk of rhabdomyolysis)— unexplained and/or persistent muscle pain, tenderness, or weakness
- Diabetes - can up A1C and fasting blood glucose; benefits of statin therapy far outweigh the risk of hyperglycemia
- Immune-mediated necrotizing myopathy (IMNM): immunosuppressive therapy (e.g., corticosteroids, azathioprine) may be used for treatment
- Liver enzyme abnormalities- persistent elevations in hepatic transaminases can occur (rare)
Statin SIDE EFFECTS
Myalgias Arthralgias Myopathy Diarrhea, Up CPK Rhabdomyolysis (up risk with higher doses) Cognitive impairment (memory loss, confusion - reversible) Up blood glucose, Up A1C Possible up risk of cataracts Up LFTs
Statin MONITORING
LFTs at baseline and as clinically indicated thereafter;
obtain a lipid panel 4-12 weeks after initiation or up titration of therapy; then every 3-12 months thereafter
Statin MONITORING
LFTs at baseline and as clinically indicated thereafter;
obtain a lipid panel 4-12 weeks after initiation or up titration of therapy; then every 3-12 months thereafter
NOTES
- Pregnancy Category X
- Can take Crestor; Lipitor; Livalo, Lescol XL and Pravachol at any time of day
- Use lower doses if CrCi
Statins Drug Interations
- Avoid other lipid-low therapies (esp. gemfibrozil)
- Avoid w/ Niacin > 1 gram (myopathies)
- Avoid w/ colchicine
Statins Drug Interations
- Avoid other lipid-low therapies (esp. gemfibrozil)
- Avoid w/ Niacin > 1 gram (myopathies)
- Avoid w/ colchicine
- Avoid SAL (Simvastatin, lovastatin and atorvastatin) with 3A4 inhibitors; less with atorvastatin
- Avoid simvastation 80mg (myopathy)
- Use Simvastatin 10mg/day with verapamil, diltiazem or dronedarone
- Use Simvastatin 20 mg/day with amiodarone, amlodipine or ranolazine
Statins Drug Interations
- Avoid other lipid-low therapies (esp. gemfibrozil)
- Avoid w/ Niacin > 1 gram (myopathies)
- Avoid w/ colchicine
- Avoid SAL (Simvastatin, lovastatin and atorvastatin) with 3A4 inhibitors; less with atorvastatin
- Avoid simvastation 80mg (myopathy)
- Use Simvastatin 10mg/day with verapamil, diltiazem or dronedarone
- Use Simvastatin 20 mg/day with amiodarone, amlodipine or ranolazine
- Do not exceed lovastatin 20mg/day with danazol, diltiazem, dronedarone or verapamil.
- Do not, exceed lovastatin 40mg/day with amiodarone
Statins Drug Interations in general
- Avoid other lipid-low therapies (esp. gemfibrozil)
- Avoid w/ Niacin > 1 gram (myopathies)
- Avoid w/ colchicine
SAL (Simvastatin, lovastatin and atorvastatin) Drug Interations
- Avoid SAL with 3A4 inhibitors; less with atorvastatin
- Avoid simvastation 80mg (myopathy)
- Use Simvastatin 10mg/day with verapamil, diltiazem or dronedarone
- Use Simvastatin 20 mg/day with amiodarone, amlodipine or ranolazine
- Do not exceed lovastatin 20mg/day with danazol, diltiazem, dronedarone or verapamil.
- Do not, exceed lovastatin 40mg/day with amiodarone
- Atorvastatin: avoid with cyclosporine, tipranavir plus ritonavir or telaprevir.
- Do not exceed atorvastatin 20mg/day with clarithromycin, itraconazole, lopinavir + ritonavir, darunavir + ritonavir, fosamprenavir + ritonavir. Do not exceed atorvastatin 40 mg/day with nelfinavir and boceprevir
- Digoxin levels may go up with these agents; monitor
Rosuvastatin Interactions
- Rosuvastatin is a substrate of 2C9 (minor) and 3A4 (minor): may up INR in patients taking warfarin; monitor.
- Cyclosporine may up rosuvastatin; do not exceed 5 mg/day of rosuvastatin.
- Ritonavir-boosted lopinavir or atazanavir: do not exceed 10 mg/day of rosuvastatin.
Rosuvastatin Interactions
- Rosuvastatin is a substrate of 2C9 (minor) and 3A4 (minor): may up INR in patients taking warfarin; monitor.
- Cyclosporine may up rosuvastatin; do not exceed 5 mg/day of rosuvastatin.
- Ritonavir-boosted lopinavir or atazanavir: do not exceed 10 mg/day of rosuvastatin.
Pravastatin Interactions
- Cyclosporine can up pravastatin; do not exceed pravastatin 20 mg/day.
- Clarithromycin can up pravastatin; do not exceed pravastatin 40 mg/day.
Pravastatin Interactions
- Cyclosporine can up pravastatin; do not exceed pravastatin 20 mg/day.
- Clarithromycin can up pravastatin; do not exceed pravastatin 40 mg/day.
Fluvastatin Interactions
- Fluvastatin inhibits 2C9 (moderate): may up INR in patients taking warfarin; monitor.
- Cyclosporine and fluconazole can up fluvastatin.
- Fluvastatin can enhance the levels of glyburide and phenytoin, monitor.
Pitavastatin Interactions
- Minimal CYP450 metabolism. Contraindicated with cyclosporine.
- Limit dose to 1 mg daily with erythromycin and 2 mg daily with rifampin.
- Monitor PT/INR in patients taking warfarin
Statin Pt Counselling
- Lifestyle changes including a heart healthy food
pattern and exercise - Contact PCP right away if you have
muscle weakness, tenderness, aching, cramps, stiffness or pain that happens without a good reason, especially if you also have a fever or feel more tired than usual. These may be symptoms of muscle damage. - Contact PCP right away if you are passing brown or dark-colored urine, have pale stools, feel more tired than usual or if your skin and/or whites of your eyes become yellow. These may be symptoms of liver damage.
Statin Pt Counselling
- Lifestyle changes including a heart healthy food
pattern and exercise - Contact PCP right away if you have
muscle weakness, tenderness, aching, cramps, stiffness or pain that happens without a good reason, especially if you also have a fever or feel more tired than usual. These may be symptoms of muscle damage. - Contact PCP right away if you are passing brown or dark-colored urine, have pale stools, feel more tired than usual or if your skin and/or whites of your eyes become yellow. These may be symptoms of liver damage.
- Grapefruit and grapefruit juice may interact with this
medicine. This could lead to higher amounts of drugs in
your body. Do not consume grapefruit products without
discussing with your healthcare provider (for lovastatin,
simvastatin, atorvastatin). - Do not use if pregnant or if you think you may be pregnant. This drug may harm your unborn baby. If you get pregnant, stop taking and call healthcare provider right away
Statin Pt Counseling
- Lifestyle changes including a heart healthy food
pattern and exercise - Contact PCP right away if you have
muscle weakness, tenderness, aching, cramps, stiffness or pain that happens without a good reason, especially if you also have a fever or feel more tired than usual. These may be symptoms of muscle damage. - Contact PCP right away if you are passing brown or dark-colored urine, have pale stools, feel more tired than usual or if your skin and/or whites of your eyes become yellow. These may be symptoms of liver damage.
- Grapefruit and grapefruit juice may interact with this
medicine. This could lead to higher amounts of drugs in
your body. Do not consume grapefruit products without
discussing with your healthcare provider (for lovastatin,
simvastatin, atorvastatin). - Do not use if pregnant or if you think you may be pregnant. This drug may harm your unborn baby. If you get pregnant, stop taking and call healthcare provider right away
Strong 3A4 Inhibitors
- ltraconazole
- Ketoconazole
- Posaconazole
- Voriconazole
- Erythromycin
- Clarithromycin
- Telithrornycin
- HIV protease inhibitors
- Boceprevir
- Telaprevir
- Nefazodone
- Cyctosporine
- Gemiibrozil
- Danazol (with simvastatin)
- Grapefruit juice
Strong 3A4 Inhibitors
- ltraconazole
- Ketoconazole
- Posaconazole
- Voriconazole
- Erythromycin
- Clarithromycin
- Telithrornycin
- HIV protease inhibitors
- Boceprevir
- Telaprevir
- Nefazodone
- Cyctosporine
- Gemiibrozil
- Danazol (with simvastatin)
- Grapefruit juice
EZETIMIBE MOA
Inhibits absorption of cholesterol at the brush border of the small intestine
EZETIMIBE MOA
Inhibits absorption of cholesterol at the brush border of the small intestine
EZETIMIBE Dosing
Ezetimibe (Zetia)
+ simvastatin (Vytorin)
+ Atorvastatin (Liptruzet)
Dosing: 10mg daily
EZETIMIBE Dosing
Ezetimibe (Zetia)
+ simvastatin (Vytorin)
+ Atorvastatin (Liptruzet)
Dosing: 10mg daily
EZETIMIBE WARNING .
- Avoid use in moderate-or-severe hepatic impairment
- Skeletal muscle effects (e.g. myopathy, including risk of rhabdomyolysis) when combined with statin
EZETIMIBE SIDE EFFECTS
URTls, diarrhea, arthralgias, myalgias, pain in extremities, sinusitis
EZETIMIBE SIDE EFFECTS
URTls, diarrhea, arthralgias, myalgias, pain in extremities, sinusitis
EZETIMIBE MONITORING
When used with a statin and/or fibrate, obtain liver function tests at baseline and as clinically indicated thereafter
EZETIMIBE MONITORING
When used with a statin and/or fibrate, obtain liver function tests at baseline and as clinically indicated thereafter
NOTES
Pregnancy Category C
Clinical trial results showed a down in LDL, but no reduction in clinical outcomes If CrCl
Ezetimibe Drug Interactions
- When ezetimibe and cyclosporine are given together, the concentration of both can go up; monitor levels of cyclosporine.
- Concomitant bile acid resins decrease ezetimibe; give ezetimibe 2 hours before or 4 hours after
bile acid resin. - Can up risk of cholelithiasis when used with fenofibrate; avoid use with gemfibrozil.
- If using warfarin, monitor INR/bleeding.
Ezetimibe Patient Counseling
- Especially if taken with statin: Contact your healthcare provider right away if you are passing brown or dark-colored urine, have pale stools, feel more tired than usual or if your skin and/or whites of your eyes become yellow. These may be symptoms of liver damage.
- Contact your healthcare provider right away if you have muscle weakness, tenderness, aching, cramps, stiffness or pain that happens without a good reason, especially
if you also have a fever or feel more tired than usual. These may be symptoms of muscle damage. - Take this medicine once daily, with or without food.
Ezetimibe Patient Counseling
- Especially if taken with statin: Contact your healthcare provider right away if you are passing brown or dark-colored urine, have pale stools, feel more tired than usual or if your skin and/or whites of your eyes become yellow. These may be symptoms of liver damage.
- Contact your healthcare provider right away if you have muscle weakness, tenderness, aching, cramps, stiffness or pain that happens without a good reason, especially
if you also have a fever or feel more tired than usual. These may be symptoms of muscle damage. - Take this medicine once daily, with or without food.
BILE ACID SEQUESTRANTS/BILE ACID BINDING RESINS
MOA
Binds bile acids in the intestine forming a complex that is excreted in the feces. This nonsystemic action results in a partial removal of the bile acids from the enterohepatic circulation, preventing their reabsorption.
Cholestyramine
Questran, Questran Light, Prevalite
Also approved for pruritus due to increased levels of bile acids
Cholestyramine
Questran, Questran Light, Prevalite
Also approved for pruritus due to increased levels of bile acids
- 4 grams initially (max 24 grams), divided BID with meals — mix the powder with water or other non-carbonated liquid (2- 6 oz.)
Colesevelam (Welchoi)
625 mg tablet, 3.75 g packet (Also approved for DM Type 2 (A1c ~0.5%)
Dosing: 3.75 grams (6 tabs or 1 packet daily or 3 tabs BID) with a meal and liquid
Colestipol (Colestid)
Tablets: 2 g daily or BID (max 16 g/day)
Granules: 5 g daily or BID (max 30 g/day)
BILE ACID SEQUESTRANTS/BILE ACID BINDING RESINS
MOA
Binds bile acids in the intestine forming a complex that is excreted in the feces. This nonsystemic action results in a partial removal of the bile acids from the enterohepatic circulation, preventing their reabsorption.
Cholestyramine; Colesevelam; Colestipol
BILE ACID SEQUESTRANTS/BILE ACID BINDING RESINS
CONTRAINDICATIONS
Cholestyramine — Complete biliary obstruction
Colesevelam — Bowel obstruction, TG > 500 mg/dL, history of hypertriglyceridemla-induced pancreatitis
BILE ACID SEQUESTRANTS/BILE ACID BINDING RESINS
SIDE EFFECTS
- Constipation (may need dose reduction or laxative),
- dyspepsia
- nausea
- abdominal
- pain
- cramping
- gas,
- bloating
- hypertriglyceyridemia
- esophageal obstruction
- up LFTs
BILE ACID SEQUESTRANTS/BILE ACID BINDING RESINS
SIDE EFFECTS
- Constipation (may need dose reduction or laxative),
- dyspepsia
- nausea
- abdominal pain
- cramping
- gas,
- bloating
- hypertriglyceyridemia
- esophageal obstruction
- up LFTs
BILE ACID SEQUESTRANTS/BILE ACID BINDING RESINS
SIDE EFFECTS
- Constipation (may need dose reduction or laxative),
- dyspepsia
- nausea
- abdominal pain
- cramping
- gas,
- bloating
- hypertriglyceyridemia
- esophageal obstruction
- up LFTs
BILE ACID SEQUESTRANTS/BILE ACID BINDING RESINS
NOTES
- Pregnancy Category B (Welchol) /C (others)
- ATP IV guidelines do not recommend using these agents when TGs are > 300 mg/dL
- Cholestyramine — 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
1/2-1 cup (4-8 ounces) of water, fruit juice, or a diet soft drink and mix well. - Colestipol: Add granules to at least 90 mL of liquid and stir until completely mixed.
Lipid Effects
down LDL ~10-30%
Up HDL ~3-5%
No change or up TG (~5%)
Bile Acid Sequestrants Drug Interactions
- Colesevelam has less drug interactions than the other 2 bile acid sequestrants and is more commonly used. For cholestyramine or colestipol, separate all other drugs by 1-4 hours before or 4-6 hours after the bile acid sequestrants.
- The following medications should be taken 4 hours prior to colesevelam:
- cyclosporine,
- oral contraceptives
- levothyroxine
- olmesartan
- phenytoin
- sulfonylureas
- and tetracyclines.
- Consider separation with other drugs as well. Colesevelam up levels of metformin extended release.
- With warfarin, monitor INR frequently during initiation.
- Bile acid sequestrants may l absorption of fat-soluble vitamins (A, D, E, K), folic acid and iron. Separate administration times with concurrent multivitamin use as noted above.
Bile Acid Sequestrants Drug Interactions
- Colesevelam has less drug interactions than the other 2 bile acid sequestrants and is more commonly used. For cholestyramine or colestipol, separate all other drugs by 1-4 hours before or 4-6 hours after the bile acid sequestrants.
- The following medications should be taken 4 hours prior to colesevelam:
- cyclosporine,
- oral contraceptives
- levothyroxine
- olmesartan
- phenytoin
- sulfonylureas
- and tetracyclines.
- Consider separation with other drugs as well. Colesevelam up levels of metformin extended release.
- With warfarin, monitor INR frequently during initiation.
- Bile acid sequestrants may l absorption of fat-soluble vitamins (A, D, E, K), folic acid and iron. Separate administration times with concurrent multivitamin use as noted above.
Bile Acid Sequestrants Drug Interactions
- Colesevelam has less drug interactions than the other 2 bile acid sequestrants and is more commonly used. For cholestyramine or colestipol, separate all other drugs by 1-4 hours before or 4-6 hours after the bile acid sequestrants.
- The following medications should be taken 4 hours prior to colesevelam:
- cyclosporine,
- oral contraceptives
- levothyroxine
- olmesartan
- phenytoin
- sulfonylureas
- and tetracyclines.
- Consider separation with other drugs as well. Colesevelam up levels of metformin extended release.
- With warfarin, monitor INR frequently during initiation.
- Bile acid sequestrants may l absorption of fat-soluble vitamins (A, D, E, K), folic acid and iron. Separate administration times with concurrent multivitamin use as noted above.
Bile Acid Sequestrants Drug Interactions
- Colesevelam has less drug interactions than the other 2 bile acid sequestrants and is more commonly used. For cholestyramine or colestipol, separate all other drugs by 1-4 hours before or 4-6 hours after the bile acid sequestrants.
- The following medications should be taken 4 hours prior to colesevelam:
- cyclosporine,
- oral contraceptives
- levothyroxine
- olmesartan
- phenytoin
- sulfonylureas
- and tetracyclines.
- Consider separation with other drugs as well. Colesevelam up levels of metformin extended release.
- With warfarin, monitor INR frequently during initiation.
- Bile acid sequestrants may l absorption of fat-soluble vitamins (A, D, E, K), folic acid and iron. Separate administration times with concurrent multivitamin use as noted above.
Fibrates MOA
are peroxisome proliferator receptor alpha (BPARa) activators. By activating PPARa, there is enhanced elimination and decrease synthesis of VLDL [causing decrease in TGs] and an increase in HDL — this causes an increase in apolip oprotein lipase, which may decrease LDL — however, when TGs are high, reducing TGs can increase LDL -be careful to monitor LDL when reducing TGs.
Fenofibrate, Fencfibric Acid
Antara, Fenogiide, Fibricor; Lipofen, Lofibra, TriCor, Trigfide, Triiipix, generics
Antara: 30, 43, 90, 130 mg Fenoglide (with meals]: 40, 120 mg Fibricor: 35, 105 mg Lofibra (micronized capsules - with meals; tablets with or without food): 67, 134, 200 mg Lipofen (with meals): 50, 150 mg TriCor: 48, 145 mg Triglide: 50, 160 mg Trilipix: 45, 135 mg
Fenofibrate, Fencfibric Acid
Antara, Fenogiide, Fibricor; Lipofen, Lofibra, TriCor, Triglide, Triiipix, generics
Antara: 30, 43, 90, 130 mg Fenoglide (with meals]: 40, 120 mg Fibricor: 35, 105 mg Lofibra (micronized capsules - with meals; tablets with or without food): 67, 134, 200 mg Lipofen (with meals): 50, 150 mg TriCor: 48, 145 mg Triglide: 50, 160 mg Trilipix: 45, 135 mg
Gemfibrozil
Lopid
600 mg BID, 30 minutes before breakfast and dinner
Fibrates MOA
Fenofibrate, Fenofibric Acid
Gemfibrozil
are peroxisome proliferator receptor alpha (BPARa) activators. By activating PPARa, there is enhanced elimination and decrease synthesis of VLDL [causing decrease in TGs] and an increase in HDL — this causes an increase in apolip oprotein lipase, which may decrease LDL — however, when TGs are high, reducing TGs can increase LDL -be careful to monitor LDL when reducing TGs.
Fenofibrate, Fenofibric Acid
Antara, Fenogiide, Fibricor; Lipofen, Lofibra, TriCor, Triglide, Triiipix, generics
Antara: 30, 43, 90, 130 mg Fenoglide (with meals]: 40, 120 mg Fibricor: 35, 105 mg Lofibra (micronized capsules - with meals; tablets with or without food): 67, 134, 200 mg Lipofen (with meals): 50, 150 mg TriCor: 48, 145 mg Triglide: 50, 160 mg Trilipix: 45, 135 mg
Gemfibrozil
Lopid
600 mg BID, 30 minutes before breakfast and dinner
Fibrates CONTRAINDICATIONS
Severe liver disease including primary biliary cirrhosis
Severe renal disease (CrCl
Fibrates CONTRAINDICATIONS
Severe liver disease including primary biliary cirrhosis
Severe renal disease (CrCl
Fibrates WARNINGS
Myopathy, including the risk of rhabdomyolysis, has been reported in patients taking fibrates; the risk is higher when fibrates are co-administered with a statin particuiarly in elderly patients and patients with diabetes, renal failure, or hypothyroidism
Fenofibrates increase cholesterol excretion into the bile, leading to risk of cholelithiasis ,
Reversible up SCr (> 2 mg/dL) has been observed with use; clinical significance unknown
Fibrates WARNINGS
Myopathy, including the risk of rhabdomyolysis, has been reported in patients taking fibrates; the risk is higher when fibrates are co-administered with a statin particuiarly in elderly patients and patients with diabetes, renal failure, or hypothyroidism
Fenofibrates increase cholesterol excretion into the bile, leading to risk of cholelithiasis ,
Reversible up SCr (> 2 mg/dL) has been observed with use; clinical significance unknown
Fibrates SIDE EFFECTS, MONITORING, NOTES
SIDE EFFECTS up LFTs (dose related), abdominal pain, up CPK, dyspepsia, URTls
MONITORING
LFTs, renal function
NOTES
Pregnancy Category C
Reduce dose if CrCl 30-80 m/min with fenofibrates (max dose 54 mg/day).
Lipid Effects
down TGs ~20-50%
Up HDL ~15%
down LDL ~5-20% (but can up LDL when TG are high)
Fibrate Drug Interactions
When used in combination with statins, fibrates can up the risk of myopathies and rhabdomyolysis, especially with gemfibrozil. Only,Trilipix has the indication for use with a statin although others [except gemfibrozil — avoid if on a statin) may have a similar safety profile. Monitor liver enzymes with all fibrates, statins, and when the 2 drug classes are used in combination.
Fibrates may up cholesterol excretion into the bile, leading to cholelithiasis.
Colchicine can up the risk of myopathy when coadministered with fenofibrate.
Gemfibrozil is contraindicated with repaglinide as it may increase hypoglycemic effects.
Fibrates may increase the effects of sulfonylureas and warfarin.
NIACIN MOA
Decreases the rate of hepatic synthesis of VLDL (decr. TGs) and LDL; may also up rate of chylomicron TG removal from plasma. Also known as nicotinic acid or vitamin B3
Immediate-Release (crystalline) niacin (Niacor) — OTC
250 mg with dinner; can T every 4-7 days to max dose 6g daily, divided in 2-3 doses
Extended-Release Niacin (Niaspan) 150, 1,000 mg \+ lovastatin (Adviser) \+ simvastatin (Simcor)
500 mg QHS x 4 weeks
Can up every 4 weeks to a max dose of 6g daily , divided in 2-3 doses
Extended-Release Niacin (Niaspan) 150, 1,000 mg \+ lovastatin (Adviser) \+ simvastatin (Simcor)
500 mg QHS x 4 weeks
Can up every 4 weeks to a max dose of 6g daily, divided in 2-3 doses
Controlled-(or sustained) Release Niacin (Sic-Niacin, OTC) 250, 500, 750 mg
500 mg QHS x 4 weeks
Can up every 4 weeks to a max dose of 2g daily
Niacin CONTRAINDICATIONS
Active liver disease, active PUD, arterial bleeding
Niacin WARNINGS
Use with caution in patients with unstable angina or in the acute phase of an MI
Hepatotoxicity
Niacin SIDE EFFECTS
Flushing, pruritus (itching), nausea, vomiting, diarrhea, Gl distress, hyperglycemia, hyperuricemia (or gout), increased cough, hepatotoxiciiy, orthostatic hypotension, hypophosphatemia
Niacin MONITORING, NOTES
MONITORING
Check LFTs at the start (baseline), every 6 to 12 weeks for the first year, and periodically thereafter (e.g., at approximately 6-month intervals); blood glucose (if have diabetes); uric acid (if have gout); INR (if on warfarin)
NOTES
Pregnancy Category C
Immediate-release niacin has poor tolerability due to flushing, itching. Extended-release forms (CR and SR) have less (but still significant) flushing but more hepatotoxicity. Therefore, the best clinical choice is Niaspan with less flushing and less hepatotoxyicity - but it is the most expensive.
Fovrmulations of niacin (regular release versus extended release) are not interchangeable.
Flush-free niacins (inositol hexaniacinate or hexanicotinate), niacinamide or nicotinamide are not effective.
Take with food, avoid hot beverages and spicy food.
Lipid Effects
down LDL 5-25%
Up HDL 15-35%
down TG 20-50%
Niacin Drug Interactions
Watch for other drugs that are potentially hepatotoxic being used concurrently.
This includes use with statins -stick to lower statin doses. The combination drug lovastatin/niaspan (Advicor) has a max dose of 2,000/40 mg and simvastatin/niaspan (Simcor) has a max dose of 2,000/40 mg.
Take niacin 6 hours after bile acid sequestrants.
FISH OILS MOA
Not completely understood; may be due to reduction of hepatic synthesis of TGs. These are indicated as an adjunct to diet” in patients with TGs > 500 mg/dL. Also known as omega-3 fatty acids.
Omega-3 Acid Ethyl Esters (Lovaza)
Start 2 capsules daily, can up to 4 caps daily
Omega-3 Acid Ethyl Esters (Lovaza)
1 g capsule contains 465 mg EPA (eicosapentaenoic acid) and 375 mg DHA (docosahexaenoic acid)
Start 2 capsules daily, can up to 4 caps daily
lcosapent ethyl (Vascepa) contains 1 gram of icosapent ethyl, an ethyl ester of omega-3 fatty acid eicosapentanoic acid (EPA)
2 capsules twice daily with or following meals
Omega-3 Acid Ethyl Esters (Lovaza)
1 g capsule contains 465 mg EPA (eicosapentaenoic acid) and 375 mg DHA (docosahexaenoic acid)
Start 2 capsules daily, can up to 4 caps daily
lcosapent ethyl (Vascepa) contains 1 gram of icosapent ethyl, an ethyl ester of omega-3 fatty acid eicosapentanoic acid (EPA)
2 capsules twice daily with or following meals
Omega-3-carboxylic acid (Epanova)
1 gram capsule contains omega-3-carboxylic acids with 850mg of polyunsaturated fatty acids (mostly EPA+DHA)
2 capsules or 4 capsules daily
Omega-3 Acid Ethyl Esters (Lovaza)
1 g capsule contains 465 mg EPA (eicosapentaenoic acid) and 375 mg DHA (docosahexaenoic acid)
Start 2 capsules daily, can up to 4 caps daily
Omega-3-carboxylic acid (Epanova)
1 gram capsule contains omega-3-carboxylic acids with 850mg of polyunsaturated fatty acids (mostly EPA+DHA)
2 capsules or 4 capsules daily
Omega-3 Acid Ethyl Esters A (Omtryg)
4 capsules daily or 2 caps BID with meals
Fatty acids WARNINGS
Use with caution in patients with known hypersensitivity to fish and/or shellfish.
Lovaza may up levels of LDL; monitor.
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.
Fatty acids SIDE EFFECTS
SIDE EFFECTS
Eructation (burping), dyspepsia, taste perversions (Lovaza); arthalgias (Vascepa)
Fatty acids MONITORING, NOTES
MONITORING
LFTs (in patients with hepatic impairment) periodically during therapy
NOTES
Pregnancy Category C
There are many OTC omega-8 fatty acid products marketed as dietary supplements. Only Lovaza, Epanova, Omtryg Vascepa (both Rx) are FDA approved for TG lowering when TG > 500 mg/dL in addition to diet.
Stop prior to elective surgeries due to increased risk of bleeding.
Lipid Effects
down TGs up to 45%
Up HDL ~9%
Can up LDL up to 44% (only with Lovaza; no up seen with Vascepa)
Fish Oil Drug Interactions
Omega-3-acids may (prolong bleeding time. Monitor INR if patients are taking warfarin.
Caution with other medications that can T bleeding risk.
Fish Oil Drug Interactions
Omega-3-acids may (prolong bleeding time. Monitor INR if patients are taking warfarin. Caution with other medications that can up bleeding risk.
Fish Oil Patient Counseling
This medication is taken in addition to a healthy diet.
Can take once daily, or split BID.
Take with or without food, but you may find it more comfortable to take with food.
This medicine does not usually cause side effects, but may cause indigestion (stomach upset), burping, or a distorted sense of taste (Lovaza) or joint pain (Vascepa)
NEW AGENTS FOR HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA (HoFH)
Lomitapide MOA
Lomitapide binds to and inhibits microsomal triglyceride transfer protein (MTP) in the endoplasmic reticulum. MTP inhibition prevents the assembly of apo-B containing lipoproteins in enterocytes and hepatocytes resulting in reduced production of chylomicrons and VLDL and subsequently reduced plasma LDL concentrations.
Lomitapide (Juxtapid) Dosing
5-60 mg daily
Initiate at 5 mg daily. If tolerated, increase after 2 weeks to 10 mg and increase at 4 week intervals to a max of 60mg
Take whole with water and without food, at least two hours after the evening mea|
Lomitapide (Juxtapid) Dosing
5-60 mg daily
Initiate at 5 mg daily. If tolerated, increase after 2 weeks to 10 mg and increase at 4 week intervals to a max of 60mg
Take whole with water and without food, at least two hours after the evening mea|
Lomitapide (Juxtapid) BLACK BOX WARNING, Contraindications, Side effects, monitoring, notes
Blackbox: Hepatotoxicity
CI: Pregnancy; concomitant use with moderate or strong CYP3A4 inhibitors; moderate or severe hepatic impairment; active liver disease including unexplained persistent elevations of serum transaminases
Warnings: GI side effects occur in majority of patients and may affect absorption of concomitant oral medications
Side Effects
Diarrhea, nausea, vomiting, dyspepsia, abdominal pain, constipation, flatulence, up LFTs, chest pain, back pain
MONITORING
ALT, AST, alkaline phosphatase, total bilirubin and pregnancy test in females of reproductive potential at baseline; measure transaminases prior to any increase in dose or monthly (whichever occurs first) during the first year, and then every 3 months and prior to dosage increases
NOTES
Pregnancy Category X
Due to the risk of hepatotoxicity, this agent is only available through a Juxtapild Risky Evaluation and Mitigation Strategy (REMS) program
Lomitapide Drug Interactions
Strong and moderate CYP3A4 inhibitors are contraindicated with lomitapide.
If using weak CYP3A4 inhibitors concomitantly, do not exceed 30 mg/day of lomitapide. These include amiodarone, atorvastatin, cyclosporine, fluoxetine, fluvoxamine, isoniazid, oral contraceptives, ranitidine, ranolazine and others.
Warfarin: up INR; monitor.
Simvastatin, lovastatin; concomitant use may increase risk of myopathy. Do not exceed simvastatin 20 mg/day (may use 40 rngfday if patients have previously tolerated simvastatin 80 mg/day for 12 months or more without evidence of muscle toxicity). Lovastatin dose should also be reduced when starting lomitapide concomitantly.
Lomitapide is an inhibitor of P-glycoprotein. Dose reduction of P-glycoprotein substrates should be considered when used concomitantly
Monitor with other hepatotoxic drugs
Reduces reabsorption of fat soluble vits
Separate dosing from bile acid sequestrants by 4 hours
Lomitapide Drug Interactions
Strong and moderate CYP3A4 inhibitors are contraindicated with lomitapide.
If using weak CYP3A4 inhibitors concomitantly, do not exceed 30 mg/day of lomitapide. These include amiodarone, atorvastatin, cyclosporine, fluoxetine, fluvoxamine, isoniazid, oral contraceptives, ranitidine, ranolazine and others.
Warfarin: up INR; monitor.
Simvastatin, lovastatin; concomitant use may increase risk of myopathy. Do not exceed simvastatin 20 mg/day (may use 40 rngfday if patients have previously tolerated simvastatin 80 mg/day for 12 months or more without evidence of muscle toxicity). Lovastatin dose should also be reduced when starting lomitapide concomitantly.
Lomitapide is an inhibitor of P-glycoprotein. Dose reduction of P-glycoprotein substrates should be considered when used concomitantly
Monitor with other hepatotoxic drugs. This includes isotretinoin, amiodarone, high dose acetaminophen, methotrexate, tetracyclines, and tamoxifen
Reduces reabsorption of fat soluble vits
Separate dosing from bile acid sequestrants by 4 hours
P-glycoprotein substrates
Aliskiren, ambrisentan, colchicine, dabigatran, digoxin, everolimus, fexofenadine, imatinib, lapatinib, maraviroc, nilotinib, posaconazole, ranolazine, saxagliptin, sirolimus, sitagliptin, tolvaptan and topotecan.
Mipomersen MOA
Mipomersen is an oligonucleotide inhibitor of apo B-100 synthesis. ApoB is the main component of LDL and very low density lipoprotein (VLDL), which is the precursor to LDL.
Mipomersen (Kyriamrc)
200 mg SC once weekly
Maximal LDL reduction seen after 6 months
Mipomersen (Kynamro)
200 mg SC once weekly
Maximal LDL reduction seen after ~6 months
Lomitapide (Juxtapid) BLACK BOX WARNING, Contraindications, Side effects, monitoring, notes
Blackbox: Hepatotoxicity
CI: Pregnancy; concomitant use with moderate or strong CYP3A4 inhibitors; moderate or severe hepatic impairment; active liver disease including unexplained persistent elevations of serum transaminases
Warnings: GI side effects occur in majority of patients and may affect absorption of concomitant oral medications
Side Effects
Diarrhea, nausea, vomiting, dyspepsia, abdominal pain, constipation, flatulence, up LFTs, chest pain, back pain
MONITORING
ALT, AST, alkaline phosphatase, total bilirubin and pregnancy test in females of reproductive potential at baseline; measure transaminases prior to any increase in dose or monthly (whichever occurs first) during the first year, and then every 3 months and prior to dosage increases
NOTES
Pregnancy Category X
Due to the risk of hepatotoxicity, this agent is only available through a Juxtapild Risky Evaluation and Mitigation Strategy (REMS) program
Mipomersen (Kynamro) Dosing
200 mg SC once weekly
Maximal LDL reduction seen after ~6 months
Mipomersen (Kynamro) Blackbox Warning
Blackbox: Hepatotoxicity
Lomitapide (Juxtapid) BLACK BOX WARNING, Contraindications, Side effects, monitoring, notes
Blackbox: Hepatotoxicity
CI: Pregnancy; concomitant use with moderate or strong CYP3A4 inhibitors; moderate or severe hepatic impairment; active liver disease including unexplained persistent elevations of serum transaminases
Warnings: GI side effects occur in majority of patients and may affect absorption of concomitant oral medications
Side Effects
Diarrhea, nausea, vomiting, dyspepsia, abdominal pain, constipation, flatulence, up LFTs, chest pain, back pain
MONITORING
ALT, AST, alkaline phosphatase, total bilirubin and pregnancy test in females of reproductive potential at baseline; measure transaminases prior to any increase in dose or monthly (whichever occurs first) during the first year, and then every 3 months and prior to dosage increases
NOTES
Pregnancy Category X
Due to the risk of hepatotoxicity, this agent is only available through a Juxtapild Risky Evaluation and Mitigation Strategy (REMS) program
Mipomersen (Kynamro) Blackbox Warning
Blackbox: Hepatotoxicity
Mipomersen (Kynamro) Contraindications, Side effects, monitoring, notes
CONTRAINDICATIONS Liver disease (including unexplained elevations in hepatic transaminases)
WARNINGS
Can cause hepatotoxicity, with elevations in transaminases and/or hepatic steatosis
SIDE EFFECTS
Injection site reactions, flu-like symptoms, nausea, headache, up ALT
MONITORING
ALT, AST, total bilirubin, alkaline phosphatase at baseline; then monthly for the first year of treatment, then every 3 months thereafter
NOTES
Pregnancy Category B
Due to the risk of hepatoxicity, this agent is only available through a Kynamro Risk Evaluation and Mitigation Strategy (REMS) program.
Mipomersen Drug Interactions
Watch for other drugs that are potentially hepatotoxic being used concurrently. This includes isotretinoin, amiodarone, high dose acetaminophen, methotrexate, tetracyclines, and tamoxifen.
Fish Oil Patient Counseling
This medication is taken in addition to a healthy diet.
Can take :ovaza and Omtryg once daily, or split BID. Epanova is taken once daily
Take Omtryg and Vascepa with food. Take Epanova and Lovaza with or without food
Take whole; do not break, crush, dissolve, or chew
This medicine does not usually cause side effects, but may cause indigestion (stomach upset), burping, or a distorted sense of taste (Lovaza) or joint pain (Vascepa)
Niacin Patient Counseling
Niaspan: Take at bedtime after a low-fat snack. Other niacins: Take with food.
Do not crush or chew with long-acting formulations.
Contact your healthcare provider right away if you are passing brown or dark-colored urine, feel more tired than usual or if your skin and/or whites of your eyes become yellow. These may be symptoms of liver damage.
Flushing (warmth, redness, itching and/or tingling of the skin) is a common side effect that may subside after several weeks of consistent use. Pretreatment with 325 mg aspirin (or 200 mg of ibuprofen) 30-60 minutes before the dose (for a few weeks) may help to decrease flushing. With Niaspan, flushing will occur mostly at night; use caution if awakened due to possible dizziness.
Avoid using alcohol or hot beverages or eating spicy foods around the time of taking this medicine to help reduce flushing.
If you have diabetes, check your blood sugar when starting this medicine because there may be a mild increase.
Bile Acid Sequestrant Patient Counseling
See notes section in chart for instructions regarding food/fluid intake for specific agents.
Take this medication at mealtime with plenty of water or other liquid. Never take dry.
Check for other constipating drugs or constipation itself and counsel appropriately (laxative, such as senna, or the stool softener docusate, if appropriate). Maintain adequate fluid and fiber intake.
Separate the dose of this medication from multivitamin dosing due to i absorption of vitamins A, D, E and K (mostly K], folic acid and iron. Supplementation with a multivitamin (esp. in women and children) may be needed while taking this medication.
Bile Acid Sequestrant Patient Counseling
See notes section in chart for instructions regarding food/fluid intake for specific agents.
Take this medication at mealtime with plenty of water or other liquid. Never take dry.
Check for other constipating drugs or constipation itself and counsel appropriately (laxative, such as senna, or the stool softener docusate, if appropriate). Maintain adequate fluid and fiber intake.
Separate the dose of this medication from multivitamin dosing due to i absorption of vitamins A, D, E and K (mostly K), folic acid and iron. Supplementation with a multivitamin (esp. in women and children) may be needed while taking this medication.
Fibrate Patient Counseling
Antara, Fibricor; TriCor, Triglide and Trilipix: Take once daily, with or without food.
Fenoglide, Lofibra (micronized capsules) and Lipofen: Take once daily, with food.
Lopid: Take twice daily, 30 minutes before breakfast and dinner.
Do not crush or chew. Contact your healthcare provider if you experience muscle aches.
Contact your healthcare provider right away if you experience abdominal pain, nausea or vomiting. These may be signs of inflammation of the gallbladder or pancreas.
Contact your healthcare provider right away if you are passing brown or dark-colored urine, feel more tired than usual or if your skin and/or whites of your eyes become yellow. These may be signs of liver damage.
