Medications> Dyslipidemia>

INDICATIONS

• Hypercholesterolemia (primary prevention of cardiovascular disease)
• Atherosclerosis (primary and secondary prevention)
• Cardiovascular events (secondary prevention)
• Hypercholesterolemia (secondary prevention)

MECHANISM

• By inhibiting the enzyme HMG CoA reductase, which controls the route of cholesterol synthesis, the statins reduce the amount of free cholesterol in the liver. The result is activation of the gene that forms the LDL receptor, especially in the liver.
• Increased membrane levels of the LDL receptor leads to removal of more LDL from the blood which lowers blood levels of total and LDL cholesterol.

USUAL ADULT DOSING

• Atorvastatin: 10 to 80 mg once daily at any time
• Fluvastatin: 20 to 80 mg without regard to meals OR Fluvastatin (Lescol) XL 80 mg daily
• Lovastatin: 20 to 80 mg once daily at bedtime 
• Pitavastatin: 1 to 4 mg daily
• Pravastatin: 10 to 80 mg daily at any time of the day, with or without food.
• Rosuvastatin: 5 to 40 mg once daily at any time
• Simvastatin: 10 to 40 mg once daily at bedtime .
• Ezetimibe + simvastatin is co-formulated as Vytorin 10/10 mg, 10/20 mg, 10/40 mg, and 10/80 mg. Vytorin dose: 1 tab once daily at bedtime
• Niacin + lovastatin is co-formulated as Advicor 500/20 mg, 750/20 mg, 1000/20 mg, and 1000/40 mg. Advicor dose: 1000/20 mg to 2000/40 mg once daily
• Niacin + simvastatin are co-formulated as Simcor 500/20 mg, 750/20 mg, and 1000/20 mg. Simcor dose 1000/20 mg to 2000/20 mg once daily.

FORMS

*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP). AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's information, and the McKesson database.

^Dosage is indicated in mg unless otherwise noted.

DOSING IN SPECIAL POPULATIONS

• No special dosing needed.

• Active liver disease or unexplained persistent elevations of serum transaminases are contraindications for statin use.

• Statins are contraindicated in pregnant women. Category X.
• Statins should be administered to women of child-bearing age only with adequate birth control methods and after being informed of the potential hazards.

• Women should not breastfeed if they are taking a statin.

ADVERSE DRUG REACTIONS

• Muscle pain and/or weakness are the most common symptoms.
• Severe myositis is uncommon but dangerous.

• Myalgia

• Abdominal pain
• Nausea
• Insomnia
• Dizziness
• Abnormal liver transaminases

• SEVERE MYOSITIS, RHABDOMYOLYSIS AND RENAL FAILURE (Joy)

DRUG INTERACTIONS

• Fibrates, especially gemfibrozil, and niacin: may increase risk of myopathy. Co-administer with close monitoring for myopathy. (Joy)
• Antibiotics: erythromycin and clarithromycin may significantly increase simvastatin and lovastatin serum concentrations. Consider alternative statins such as pravastatin and rosuvastatin.
• HIV-protease inhibtors: contraindicated with simvastatin and lovastatin. Consider low dose atorvastatin (10mg), rosuvastatin (5mg) , or pravastatin.
• Itraconazole, ketoconazole, voriconazole, and posaconazole: may significantly increase simvastatin and lovastatin serum concentrations. Consider alternative statins such as pravastatin and rosuvastatin.
• Coumarin anticoagulants: INR may be increased. Monitor INR closely with co-administration.
• Diltiazem: may significantly increase simvastatin and lovastatin serum concentrations. Consider alternative statins such as pravastatin and rosuvastatin.
• Oral contraceptives: rosuvastatin increases ethinyl estradiol and norgestrel by 26% and 34%, respectively. Monitor for potential ADR.

PHARMACOKINETIC

COMMENTS

• The statins are by far the most effective and best-tolerated class of drugs for lowering total and LDL cholesterol levels and also decrease TGs by 10 to 25% and raise HDL-C by about 5 to 10%.
• At recommended dose range the potency of statins is as follows: pitavastatin > rosuvastatin > atorvastatin > lovastatin > simvastatin > pravastatin > fluvastatin, with mean LDL reduction of 55-60%, 48-52%, 48%, 39-41%, 32%, and 23%, respectively. (Jones, 1998; Jones, 2003)
• Due to lack of drug-drug interaction, pravastatin is often recommended in patients on drugs that are potent inhibitors of CYP3A4 (e.g macrolides, HIV-protease inhibitors, azole antifungals) but more potent agents including atorvastatin (use with caution at lowest dose of 10 mg with slow titration up to maximum of 40 mg/d) or rosuvastatin (start with 5 mg/d) may be considered; lovastatin and simvastatin contraindicated in patients taking CYP3A4 inhibitors.
• Patients should be counselled about symptoms of rhabdomyolysis (e.g. muscle ache, weakness) especially with concurrent fibrate therapy. (Joy)
• Statins have beneficial effects other than lowering LDL cholesterol; these pleiotropic effects include lowering blood levels of inflammatory markers such as C-reactive protein and improved function of endothelial cells which likely contribute to its role in cardiovascular disease prevention (see cardiovascular disease management) (Shaw)
• Ingestion of a statin and grapefruit juice (>1 quart/day) can increase blood concentrations of the statins. (Li)
• Statins lower the incidence of cardiovascular events in individuals who do or do not have diabetes. (Pedersen; Heart Protection Study Collaborative Group)
• Statin therapy is associated with a 9% increased risk of development of diabetes, but the risk is low when compared with the reduction in cardiovascular events. (Sattar)

REFERENCES

RELATED MODULES

• Cardiovascular Disease Screening and Management