Atorvastatin calcium tablets for lowering cholesterol and reducing cardiovascular risk

Atorvastatin calcium tablets are oral statin medications used primarily to lower LDL cholesterol levels and reduce the risk of cardiovascular events such as heart attack and stroke in adults with or at risk for coronary heart disease (CHD). They are also approved for treatment of certain inherited cholesterol disorders in adults and children aged 10 years and older.

Atorvastatin calcium tablets are indicated for adults to reduce the risk of myocardial infarction (MI), stroke, revascularization procedures, angina, and hospitalization for congestive heart failure in patients with clinically evident coronary heart disease (CHD) or multiple risk factors but without clinically evident CHD. Specifically, they are used:

• In adults with multiple risk factors for CHD but no clinical CHD to reduce risk of MI, stroke, revascularization, and angina.
• In adults with type 2 diabetes mellitus and multiple risk factors but no clinical CHD to reduce risk of MI and stroke.
• In adults with clinically evident CHD to reduce risk of non-fatal or fatal MI, stroke, angina, revascularization procedures, and hospitalization for congestive heart failure.

They are also indicated as an adjunct to diet to lower LDL cholesterol in:

• Adults with primary hyperlipidemia.
• Adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH).
• Adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH), as adjunct to other LDL-C-lowering therapies or alone if others unavailable.

Additionally, atorvastatin calcium tablets treat adults with primary dysbetalipoproteinemia and hypertriglyceridemia as an adjunct to diet.

Atorvastatin calcium

Atorvastatin calcium is an HMG-CoA reductase inhibitor (statin), a class of medicines that work by blocking the enzyme HMG-CoA reductase in the liver. This enzyme plays a key role in cholesterol production. By inhibiting it, atorvastatin lowers the production of cholesterol, particularly low-density lipoprotein cholesterol (LDL-C), which is often called 'bad cholesterol'. Lowering LDL-C helps reduce the risk of plaque buildup in arteries and pathways that lead to heart disease and stroke.

General Administration

Take atorvastatin calcium tablets orally once daily at any time of day, with or without food.

Assess LDL cholesterol levels as early as 4 weeks after starting therapy and adjust dose if needed.

Adults

• Start with 10 or 20 mg once daily.
• Dose range: 10 to 80 mg once daily.
• For patients needing LDL-C reduction greater than 45%, starting dose may be 40 mg once daily.

Pediatric Patients (10 years and older) with Heterozygous Familial Hypercholesterolemia (HeFH)

• Start with 10 mg once daily.
• Dose range: 10 to 20 mg once daily.

Pediatric Patients (10 years and older) with Homozygous Familial Hypercholesterolemia (HoFH)

• Start with 10 to 20 mg once daily.
• Dose range: 10 to 80 mg once daily.

Dosage Modifications Due to Drug Interactions

• With certain antiviral medications (e.g., saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir with or without ritonavir, elbasvir plus grazoprevir, letermovir): do not exceed 20 mg once daily.
• With nelfinavir: do not exceed 40 mg once daily.
• With clarithromycin or itraconazole: do not exceed 20 mg once daily.

Missed Dose

If a dose is missed, do not take the missed dose and resume the usual dosing schedule at the next dose time.

• Acute liver failure or decompensated cirrhosis.
• Hypersensitivity to atorvastatin calcium or any excipients in the tablet.

Myopathy and Rhabdomyolysis

Atorvastatin can cause muscle pain, tenderness, or weakness (myopathy) and a more severe muscle breakdown condition called rhabdomyolysis, which can lead to acute kidney injury. Risk factors for these include age over 65, uncontrolled hypothyroidism, kidney problems, certain drug interactions, and higher doses.

Discontinue atorvastatin if muscle symptoms are accompanied by markedly elevated creatine kinase (CK) levels or if myopathy is suspected or diagnosed. Temporarily stop atorvastatin during any serious acute condition that increases risk of kidney failure due to rhabdomyolysis.

Inform patients to promptly report unexplained muscle symptoms, especially with malaise or fever.

Immune-Mediated Necrotizing Myopathy (IMNM)

Rare autoimmune muscle disease associated with statins; characterized by persistent muscle weakness and elevated CK despite stopping therapy, requiring immunosuppressive treatment. Discontinue atorvastatin if IMNM is suspected.

Hepatic Dysfunction

Serum liver enzyme elevations can occur, with rare cases of fatal and non-fatal liver failure reported. Patients with acute liver failure or decompensated cirrhosis must not take atorvastatin. Liver tests should be done before starting therapy and as clinically indicated. Stop atorvastatin if serious liver injury or jaundice develops.

Increases in Blood Sugar

Statins including atorvastatin may increase HbA1c and fasting blood glucose. Lifestyle optimization is advised.

Hemorrhagic Stroke Risk

In patients with recent hemorrhagic stroke, atorvastatin 80 mg increased the incidence of hemorrhagic stroke compared to placebo. The risk-benefit of high-dose atorvastatin in these patients should be carefully considered.

Common Adverse Reactions (≥5%)

• Nasopharyngitis (common cold symptoms)
• Arthralgia (joint pain)
• Diarrhea
• Pain in extremities
• Urinary tract infections

Other Noted Adverse Reactions

• Dyspepsia (indigestion)
• Nausea
• Musculoskeletal pain and spasms
• Myalgia (muscle pain)
• Insomnia
• Pharyngolaryngeal pain (throat discomfort)
• Transient increases in liver enzymes

Serious Reactions

• Myopathy and rhabdomyolysis
• Immune-mediated necrotizing myopathy
• Hepatic dysfunction, including rare fatal liver failure

Major Drug Interactions

• Certain antiviral drugs (e.g., saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir ± ritonavir, elbasvir plus grazoprevir, letermovir): limit atorvastatin dose to 20 mg daily.
• Nelfinavir: do not exceed 40 mg atorvastatin daily.
• Azole antifungals (e.g., itraconazole) and macrolide antibiotics (e.g., clarithromycin): do not exceed 20 mg atorvastatin daily.
• Concomitant use with cyclosporine, gemfibrozil, tipranavir plus ritonavir, or glecaprevir plus pibrentasvir is not recommended.
• Grapefruit juice: consuming more than 1.2 liters daily may increase risk of myopathy.
• Concurrent use with lipid-modifying doses (>1 g/day) of niacin, fibrates, colchicine, and ledipasvir plus sofosbuvir may increase myopathy risk.

Pregnancy

Safety and efficacy in pregnancy are not provided in this labeling. Use in pregnancy is generally avoided due to potential risks.

Breastfeeding

Information on lactation risk is not specified in the label.