Atorvastatin Calcium

ATORVASTATIN CALCIUM- atorvastatin tablet
NuCare Pharmaceuticals,Inc.

1 INDICATIONS AND USAGE

Atorvastatin calcium tablets is indicated:

• To reduce the risk of:
  • Myocardial infarction (MI), stroke, revascularization procedures, and angina in adults with multiple risk factors for coronary heart disease (CHD) but without clinically evident CHD
  • MI and stroke in adults with type 2 diabetes mellitus with multiple risk factors for CHD but without clinically evident CHD
  • Non-fatal MI, fatal and non-fatal stroke, revascularization procedures, hospitalization for congestive heart failure, and angina in adults with clinically evident CHD
• As an adjunct to diet to reduce low-density lipoprotein cholesterol (LDL-C) in:
  • Adults with primary hyperlipidemia.
  • Adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH).
• As an adjunct to other LDL-C-lowering therapies, or alone if such treatments are unavailable, to reduce LDL-C in adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH).
• As an adjunct to diet for the treatment of adults with:
  • Primary dysbetalipoproteinemia
  • Hypertriglyceridemia

2 DOSAGE AND ADMINISTRATION

2.1 Important Dosage Information

• Take Atorvastatin calcium tablets orally once daily at any time of the day, with or without food.
• Assess LDL-C when clinically appropriate, as early as 4 weeks after initiating Atorvastatin calcium tablets, and adjust the dosage if necessary.

2.2 Recommended Dosage in Adult Patients

The recommended starting dosage of Atorvastatin calcium tablets is 10 mg to 20 mg once daily. The dosage once daily. Patients who require reduction in LDL-C greater than 45% may be started at 40 mg once daily.

2.3 Recommended Dosage in Pediatric Patients 10 Years of Age and Older with HeFH

The recommended starting dosage of Atorvastatin calcium tablets is 10 mg once daily. The dosage range is 10 mg to 20 mg once daily.

2.4 Recommended Dosage in Pediatric Patients 10 Years of Age and Older with HoFH

The recommended starting dosage of Atorvastatin calcium tablets is 10 mg to 20 mg once daily. The dosage range is 10 mg to 80 mg once daily.

2.5 Dosage Modifications Due to Drug Interactions

Concomitant use of Atorvastatin calcium tablets with the following drugs requires dosage modification of Atorvastatin calcium tablets [see Warnings and Precautions ( 5.1) and Drug Interactions ( 7.1)] .

Anti-Viral Medications

• In patients taking saquinavir plus ritonavir, darunavir plus ritonavir, fosamprenavir, fosamprenavir plus ritonavir, elbasvir plus grazoprevir or letermovir, do not exceed Atorvastatin calcium tablets 20 mg once daily.
• In patients taking nelfinavir, do not exceed Atorvastatin calcium tablets 40 mg once daily .

Select Azole Antifungals or Macrolide Antibiotics

• In patients taking clarithromycin or itraconazole, do not exceed Atorvastatin calcium tablets 20 mg once daily.

For additional recommendations regarding concomitant use of Atorvastatin calcium tablets with other anti-viral medications, azole antifungals or macrolide antibiotics, see Drug Interactions ( 7.1).

3 DOSAGE FORMS AND STRENGTHS

Atorvastatin calcium tablets:

• 10 mg of atorvastatin: White to off-white, film-coated, oval shaped tablets “ATO” debossed on one side and “10” on other side.
• 20 mg of atorvastatin: White to off-white, film-coated, oval shaped tablets “ATO” debossed on one side and “20” on other side.
• 40 mg of atorvastatin: White to off-white, film-coated, oval shaped tablets “ATO” debossed on one side and “40” on other side.
• 80 mg of atorvastatin: White to off-white, film-coated, oval shaped tablets “ATO” debossed on one side and “80” on other side.

4 CONTRAINDICATIONS

• Acute liver failure or decompensated cirrhosis [see Warnings and Precautions ( 5.3)]
• Hypersensitivity to atorvastatin or any excipients in atorvastatin calcium tablets. Hypersensitivity reactions, including anaphylaxis, angioneurotic edema, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported [see Adverse Reactions ( 6.2)].

5 WARNINGS AND PRECAUTIONS

5.1 Myopathy and Rhabdomyolysis

Atorvastatin calcium tablets may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Acute kidney injury secondary to myoglobinuria and rare fatalities have occurred as a result of rhabdomyolysis in patients treated with statins, including atorvastatin calcium tablets.

Risk Factors for Myopathy

Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs (including other lipid-lowering therapies), and higher atorvastatin calcium tablets dosage [see Drug Interactions ( 7.1) and Use in Specific Populations ( 8.5, 8.6)].

Steps to Prevent or Reduce the Risk of Myopathy and Rhabdomyolysis

Atorvastatin calcium tablet sexposure may be increased by drug interactions due to inhibition of cytochrome P450 enzyme 3A4 (CYP3A4) and/or transporters (e.g., breast cancer resistant protein [BCRP], organic anion-transporting polypeptide [OATP1B1/OATP1B3] and P-glycoprotein [P-gp]), resulting in an increased risk of myopathy and rhabdomyolysis. Concomitant use of cyclosporine, gemfibrozil, tipranavir plus ritonavir, or glecaprevir plus pibrentasvir with atorvastatin calcium tablets is not recommended. Atorvastatin calcium tablets dosage modifications are recommended for patients taking certain anti-viral, azole antifungals, or macrolide antibiotic medications [see Dosage and Administration ( 2.5)] . Cases of myopathy/rhabdomyolysis have been reported with atorvastatin coadministered with lipid modifying doses (>1 gram/day) of niacin, fibrates, colchicine, and ledipasvir plus sofosbuvir. Consider if the benefit of use of these products outweighs the increased risk of myopathy and rhabdomyolysis [see Drug Interaction s ( 7.1)] .

Concomitant intake of large quantities, more than 1.2 liters daily, of grapefruit juice is not recommended in patients taking atorvastatin calcium tablets [see Drug Interactions ( 7.1)].

Discontinue atorvastatin calcium tablets if markedly elevated CK levels occur or myopathy is diagnosed or suspected. Muscle symptoms and CK elevations may resolve if atorvastatin calcium tablets is discontinued. Temporarily discontinue atorvastatin calcium tablets in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis (e.g., sepsis; shock; severe hypovolemia; major surgery; trauma; severe metabolic, endocrine, or electrolyte disorders; or uncontrolled epilepsy).

Inform patients of the risk of myopathy and rhabdomyolysis when starting or increasing the atorvastatin calcium tablets dosage. Instruct patients to promptly report any unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever.

5.2 Immune-Mediated Necrotizing Myopathy

There have been rare reports of immune-mediated necrotizing myopathy (IMNM), an autoimmune myopathy, associated with statin use, including reports of recurrence when the same or a different statin was administered. IMNM is characterized by proximal muscle weakness and elevated serum creatine kinase that persists despite discontinuation of statin treatment; positive anti-HMG CoA reductase antibody; muscle biopsy showing necrotizing myopathy; and improvement with immunosuppressive agents. Additional neuromuscular and serologic testing may be necessary. Treatment with immunosuppressive agents may be required. Discontinue atorvastatin calcium tablets if IMNM is suspected.