Atorvastatin (Lipitor)

1. Health Canada Product Monograph — Atorvastatin

• Used as an adjunct to diet to lower elevated total cholesterol, LDL-C, triglycerides, and apolipoprotein B, and to raise HDL-C across several hyperlipidemia and dyslipidemia types, including familial hypercholesterolemia.
• Used to reduce the risk of myocardial infarction and stroke in patients with elevated cardiovascular risk factors or established coronary heart disease.

Contraindicated in pregnancy. Confirm pregnancy status and discuss alternative therapy with the prescriber before dispensing.

• Contraindicated in pregnancy; cholesterol synthesis is important for fetal development, and the drug should be stopped immediately if pregnancy occurs.
• Should only be given to women of childbearing potential when pregnancy is highly unlikely and the patient has been counselled on the risks.

• Contraindicated during breastfeeding because it is not known whether atorvastatin passes into human milk and animal data suggest it may concentrate there.

• Approved for use in older adults; plasma exposure is higher in patients 65 and older, so the lowest effective dose should be used initially.
• Older adults may be more susceptible to muscle-related adverse effects and should be monitored accordingly.

• Authorized for boys and postmenarchal girls aged 10 to under 18 years with heterozygous familial hypercholesterolemia who have not responded adequately to diet alone, at doses up to 20 mg/day.
• Not authorized and not studied in children under 10 years of age.

• Usual starting dose is 10 to 20 mg once daily, up to 80 mg/day for severe dyslipidemia, individualized to baseline lipid levels and treatment goals.
• May be taken at any time of day, with or without food, though evening dosing is preferred; adjust doses no more often than every 2 to 4 weeks.
• Patients with severe renal insufficiency should be started and maintained on the lowest dose.

• Atorvastatin may cause nasopharyngitis (cold-like symptoms).
• Joint pain (arthralgia) may occur.
• Diarrhea may occur.
• Pain in the arms or legs may occur.
• Indigestion (dyspepsia) may occur.
• Nausea may occur.
• Constipation may occur.
• Muscle aches, muscle spasms, or general muscle pain (myalgia) may occur.
• Headache may occur.
• Increased blood sugar (hyperglycemia) may occur.
• Mild elevations in liver enzymes or creatine kinase may be seen on routine blood tests.
• Pain or discomfort in the throat may occur.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Rare myopathy or rhabdomyolysis may occur, with muscle pain, tenderness, or weakness alongside markedly elevated creatine kinase, which can progress to acute kidney injury.
• Rare immune-mediated necrotizing myopathy may occur, with muscle weakness that persists even after stopping the statin.
• Serious liver injury may occur rarely, including reports of hepatic failure.
• The highest dose (80 mg) has been linked to an increased risk of hemorrhagic stroke in patients with a recent stroke or transient ischemic attack.
• Severe hypersensitivity reactions may occur, including angioedema, anaphylaxis, and severe skin reactions such as Stevens-Johnson syndrome or toxic epidermal necrolysis.
• Very rare interstitial lung disease may occur, particularly with long-term use.
• Statins may rarely induce or worsen myasthenia gravis or ocular myasthenia.
• Reversible cognitive effects such as memory loss, forgetfulness, or confusion have been reported rarely.
• Seek immediate medical attention if unexplained muscle pain, tenderness, or weakness occurs (especially with fever or fatigue), or if signs of liver injury (yellowing of the skin or eyes, dark urine, abdominal pain) or a severe allergic reaction (facial swelling, difficulty breathing) develop.

• Use cautiously in patients with risk factors for myopathy, including hypothyroidism, renal or hepatic impairment, advanced age, frailty, or heavy alcohol use.
• Caution is advised in patients with a recent hemorrhagic stroke or transient ischemic attack, as high-dose therapy has been linked to increased hemorrhagic stroke risk.
• Temporary discontinuation may be appropriate during acute conditions that predispose to rhabdomyolysis, such as major surgery, sepsis, or severe metabolic disturbance.

• Contraindicated in patients with known hypersensitivity to atorvastatin or any ingredient in the formulation.
• Contraindicated in active liver disease or unexplained persistent elevation of liver transaminases greater than 3 times the upper limit of normal.
• Contraindicated during pregnancy.
• Contraindicated while breastfeeding.
• Contraindicated with concomitant hepatitis C antiviral therapy.
• Contraindicated with concomitant use of the immunosuppressant cyclosporine.

• Strong CYP3A4 inhibitors, including certain macrolide antibiotics (clarithromycin, erythromycin) and azole antifungals (itraconazole), can raise atorvastatin blood levels and increase muscle toxicity risk.
• HIV protease inhibitors, such as lopinavir/ritonavir, tipranavir/ritonavir, saquinavir/ritonavir, darunavir/ritonavir, fosamprenavir, and nelfinavir, can markedly raise atorvastatin levels and may require dose limits or avoidance.
• Hepatitis C antiviral combinations (such as telaprevir, boceprevir, glecaprevir/pibrentasvir, elbasvir/grazoprevir, simeprevir, and ledipasvir/sofosbuvir or velpatasvir/sofosbuvir) are contraindicated or can substantially raise atorvastatin exposure.
• Cyclosporine markedly increases atorvastatin exposure and concomitant use is contraindicated.
• Fibrates (such as gemfibrozil) and niacin increase the risk of myopathy when combined with atorvastatin and should generally be avoided or used only with careful risk-benefit assessment.
• Colchicine has been associated with reports of myopathy when combined with atorvastatin; caution is advised.
• Fusidic acid should not be combined with atorvastatin, as the combination has been linked to reports of fatal rhabdomyolysis.
• Rifampin can substantially reduce atorvastatin plasma concentrations if not taken at the same time, and separate dosing should be avoided.
• Digoxin levels can rise modestly with high-dose atorvastatin, so patients on digoxin should be monitored.
• Oral contraceptives may have increased hormone levels (norethindone and ethinyl estradiol) when combined with atorvastatin.
• Aluminum- and magnesium-containing antacids can reduce atorvastatin absorption.
• Bile acid sequestrants such as colestipol can reduce atorvastatin absorption if taken together; doses should be separated by at least 2 hours.

• Avoid grapefruit juice, as it can meaningfully raise atorvastatin blood levels and increase the risk of muscle-related side effects.
• May be taken with or without food; food modestly reduces the rate of absorption but does not change the cholesterol-lowering effect.

• May be taken at any time of day, with a slight preference for evening dosing, and should be taken consistently.

• Store at controlled room temperature and keep out of reach and sight of children.

• Atorvastatin is a statin used along with diet and lifestyle changes to lower cholesterol and triglycerides and to reduce the risk of heart attack and stroke.
• It is usually taken once a day, at any time of day, with a slight preference for the evening; keep taking it consistently and continue diet and exercise measures alongside it.
• Common side effects include joint pain, diarrhea, indigestion, nausea, constipation, muscle aches, and headache.
• Serious side effects such as unexplained muscle pain, tenderness, or weakness, or signs of liver problems like yellowing of the skin or eyes and dark urine, warrant contacting the doctor's office or prescriber right away.
• It can be taken with or without food, but grapefruit juice should be avoided since it can raise atorvastatin levels and increase side effect risk.
• Store at controlled room temperature, out of reach and sight of children.