Atorvastatin calcium is a lipid-lowering drug that acts by irreversibly inhibiting the key rate-limiting enzyme HMG CO-A reductase inhibitor.

It is used for:

• Dysbetalipoproteinemia:

  • primary dysbetalipoproteinemia (Fredrickson type III).

• Heterozygous familial and nonfamilial hypercholesterolemia and mixed dyslipidemia:

  • To reduce elevated:
    • total cholesterol
    • low-density lipoprotein cholesterol (LDL-C),
    • apolipoprotein B (apo B), and
    • triglyceride levels,
    • and to increase HDL-C in patients with primary hypercholesterolemia (heterozygous familial and nonfamilial) and mixed dyslipidemia (Fredrickson type IIa and IIb).

• Heterozygous familial hypercholesterolemia:

• Total-C, LDL-C, and apo B levels reduction in:
  • pediatric patients 10 to 17 years of age with heterozygous familial hypercholesterolemia with LDL-C ≥190 mg/dL,
  • LDL-C of more than 160 mg/dL with a family history of premature cardiovascular disease (CVD), or
  • LDL-C of more than 160 mg/dL with two or more other CVD risk factors.

• Homozygous familial hypercholesterolemia:

  • To reduce total-C and LDL-C in:
    • Homozygous familial hypercholesterolemia patients as an adjunct to other lipid-lowering treatments (eg, LDL apheresis) or if such treatments are unavailable.

• Hypertriglyceridemia:

  • Treatment of elevated serum triglyceride levels (Fredrickson type IV).
  • Limitations of use: It has not been studied in conditions where the major lipid abnormality is the elevation of chylomicrons (Fredrickson Types I and V).

• Prevention of cardiovascular disease (CVD):

  • Primary prevention of cardiovascular disease (high-risk for CVD):
    • To reduce the risk of MI, stroke, and revascularization procedures and angina in adult patients without clinically evident coronary heart disease who have multiple CHD risk factors (eg, age, smoking, hypertension, low high-density lipoprotein cholesterol [HDL-C], family history of early CHD)
    • to reduce the risk of MI and stroke in patients with type 2 diabetes and without clinically evident CHD but with multiple risk factors for CHD (eg, retinopathy, albuminuria, smoking, hypertension).

  • Secondary prevention of cardiovascular disease:

    • To reduce the risk of nonfatal MI, fatal and nonfatal stroke, revascularization procedures, hospitalization for decompensated heart failure, and angina in patients with clinically evident CHD.

• Off Label Use of Atorvastatin In Adults:

  • Cardiac risk reduction for noncardiac surgery (perioperative therapy);
  • Secondary prevention of non-cardioembolic stroke and TIA.

Atorvastatin Dose in Adults

Note: Doses should be given according to the baseline LDL-cholesterol serum levels and patient response; adjust the doses every 2 to 4 weeks.

Atorvastatin calcium dose in the treatment of Hypercholesterolemia (heterozygous familial and nonfamilial) and mixed hyperlipidemia (Fredrickson types IIa and IIb):

• Start with 10 or 20 mg orally once a day and if patients requiring >45% reduction in LDL-C may be started at 40 mg once a day to a range of 10 to 80 mg once a day.

Atorvastatin calcium dose in the treatment of Homozygous familial hypercholesterolemia:

• 10 to 80 mg orally once a day.

Atorvastatin calcium dose in the Prevention of cardiovascular disease/reduce the risk of atherosclerotic cardiovascular disease:

• ACC/AHA Blood Cholesterol Guideline recommendations (ACC/AHA [Grundy 2018]; ACC/AHA [Stone 2013]):
  • Primary Prevention: 
    • LDL-C of more than 190 mg/dL and age 20 - 75 years: High-intensity therapy:
      • 80 mg once orally a day and if the patient was unable to tolerate the dose, may reduce dose to 40 mg once a day.
    • Diabetes, age 40 - 75 years, and an estimated 10-year ASCVD risk <7.5%: Moderate- intensity therapy:
      • 10 to 20 mg once orally a day.
    • Diabetes, age 40 - 75 years, and an estimated 10-year ASCVD risk ≥7.5%:  High- intensity therapy:
      • 80 mg orally once a day and if the patient was unable to tolerate the dose, may reduce dose to 40 mg once a day.
    • LDL-C 70 - 189 mg/dL, age 40 to 75 years and an estimated 10-year ASCVD risk ≥7.5%: Moderate- to high-intensity therapy:
      • 10 to 80 mg orally once a day.

  • Secondary prevention:

    • The patient has clinical ASCVD (eg, coronary heart disease, stroke/TIA, or peripheral arterial disease presumed to be of atherosclerotic origin) or is post-CABG.
      • Age ≤75 years: High-intensity therapy:
        • 80 mg once orally once a day and if the patient was unable to tolerate the dose, may reduce dose to 40 mg once a day.
      • Age >75 years: Moderate- to high-intensity therapy:
        • 10 to 80 mg orally once a day (ACC/AHA [Grundy 2018]) and if a moderate-intensity dose of 10 to 20 mg orally once a day is started and tolerated, increase to a high-intensity dose of 40 to 80 mg once a day within 3 months.
      • Not a candidate for high-intensity therapy: Moderate-intensity therapy:
        • 10 to 20 mg orally once a day.

US Preventive Services Task Force Recommendations:

• Age 40 - 75 years, no history of CVD, with 1 or more CVD risk factor (dyslipidemia, diabetes, hypertension, or smoking), and calculated 10-year CVD event risk of 10% or more:
• Primary prevention:
  • Moderate-intensity therapy: 10 to 20 mg orally once a day.

Note: Use clinical judgment in patients with very high CVD risk factors.

Atorvastatin calcium dose in the treatment of Cardiac risk reduction for non-cardiac surgery (off-label):

• 20 mg orally once a day for 45 days; surgical intervention (vascular surgery) was performed during this period but not earlier than 2 weeks after therapy initiation.

Atorvastatin calcium dose in the treatment of Non-cardioembolic stroke/TIA (off-label):

• Initial: 80 mg orally once a day and adjust the dose based on patient tolerability.
• Also, consider the ACC/AHA Blood Cholesterol Guideline recommendations.

Dosage adjustment for atorvastatin with concomitant medications:

• Boceprevir, nelfinavir:
  • Use lowest effective atorvastatin dose (not to exceed 40 mg once a day)
• Clarithromycin, fosamprenavir, itraconazole, ritonavir (plus fosamprenavir, darunavir, or saquinavir):
  • Use lowest effective atorvastatin dose (not to exceed 20 mg once a day)
• Lomitapide:
  • Consider atorvastatin dose reduction (per lomitapide manufacturer).

Atorvastatin Dose in Childrens

 Doses should be given according to the baseline LDL-cholesterol serum levels and patient response; adjust the doses every 2 to 4 weeks.

Dose in the treatment of Heterozygous familial and non-familial hypercholesterolemia: 

Note: Begin treatment if, after adequate trial (6 to 12 months) of intensive lifestyle modification emphasizing body weight normalization and diet, the following are present:

• LDL-C of 190 mg/dL or more, or
• LDL-C remains 160 mg/dL or more and 2 or more cardiovascular risk factors:
  • family history of premature atherosclerotic cardiovascular disease (<55 years of age)
  • overweight
  • obesity or
  • other elements of insulin resistance syndrome or LDL-C ≥130 mg/dL and diabetes mellitus.

• Children 6 to 10 years of age (Tanner stage I):
  • Start with 5 mg orally once a day, may increase the dose by doubling it if target is not achieved i-e, 5 mg to 10 mg to 20 mg (max dose is 80 mg once a day)
• Children and Adolescents 10 to 17 years:
  • Start with 10 mg once daily; may increase the dose by doubling it if target is not achieved i-e, 10 mg to 20 mg to 40 mg (max dose is 80 mg once a day)

Dose in the treatment of Hyperlipidemia: 

• Children and Adolescents 10 to 17 years (males and postmenarchal females):
  • Start with 10 mg orally once a day if the target is not achieved in 1 to 3 months, may increase the dose. (max 80mg/day)

Dose in the Prevention of graft coronary artery disease:

• Children and Adolescents:
  • 0.2 mg/kg/day orally rounded to nearest 2.5 mg increment; not to exceed age-appropriate doses.

Dosage adjustment for atorvastatin calcium with concomitant medications:

• No recommendations are given for individuals less than 18 years of age.
• In adolescents ≥18 years, the following have been suggested:
• Boceprevir, nelfinavir:
  • Use lowest effective atorvastatin dose; maximum daily dose: 40 mg/day
• Clarithromycin, fosamprenavir, itraconazole, ritonavir (plus fosamprenavir, darunavir, or saquinavir):
  • Use lowest effective atorvastatin dose; maximum daily dose: 20 mg/day

Dosing adjustment for toxicity:

• Muscle symptoms (potential myopathy):
  • Children ≥10 years and Adolescents:
    • Discontinue use until symptoms can be evaluated.
    • Check the CPK level.
    • Evaluate patients for conditions that may increase the risk for muscle symptoms (eg, hypothyroidism, reduced renal or hepatic function, rheumatologic disorders such as polymyalgia rheumatica, steroid myopathy, vitamin D deficiency, or primary muscle diseases).
    • Upon resolution (symptoms and any associated CPK abnormalities), resume the original or consider a lower dose of atorvastatin and retitrate.
    • If muscle symptoms recur, discontinue atorvastatin use.
    • After muscle symptom resolution, may then reinitiate a different statin at an initial low dose.
    • Gradually increase the dose if tolerated.
    • Based on experience in adult patients, if muscle symptoms or elevated CPK persists for 2 months in the absence of continued statin use, consider other causes of muscle symptoms.
    • If determined to be due to another condition aside from statin use, may resume statin therapy at the original dose.

Pregnancy Risk Factor: X​​​​​​​

• Pregnant women and those at risk of becoming pregnant should not take Atorvastatin Calcium.
• Congenital anomalies have been reported in some cases following the maternal use of HMG–CoA reductase inhibitors during pregnancy. However, there are not many data.
• The role of cholesterol biosynthesis in fetal development may be significant; serum cholesterol and total triglycerides rise normally during pregnancy.
• It is unlikely that the temporary discontinuation of lipid-lowering medication during pregnancy will have an impact on long-term outcomes for primary hypercholesterolemia treatment.
• If an unplanned pregnancy occurs during treatment, the medication will be discontinued immediately.
• Recommend appropriate contraception for females who are taking statins.
• Stop using the plan pregnancy 1 to 2 months before you are due.

Atorvastatin calcium use during Breast-Feeding:​​​​​​​

• Breastfeeding women should not use this product.
• It is unknown if atorvastatin can be found in breast milk.

Atorvastatin Dose in Renal Disease:

• No dosage adjustment necessary.

Dialysis:

• Due to the high protein binding, atorvastatin calcium is not expected to be cleared by dialysis.

Atorvastatin Dose in Liver Disease:

Contraindicated in active liver disease or in patients with unexplained persistent elevations of serum transaminases.

Common Side Effects of Atorvastatin calcium Include:

• Gastrointestinal:
  • Diarrhea
• Neuromuscular & skeletal:
  • Arthralgia
• Respiratory:
  • Nasopharyngitis

Less Common Side Effects of Atorvastatin calcium Include:

• Cardiovascular:
  • Hemorrhagic Stroke
• Central Nervous System:
  • Insomnia
  • Malaise
  • Nightmares
• Dermatologic:
  • Urticaria
• Endocrine & Metabolic:
  • Diabetes Mellitus
  • Hyperglycemia
• Gastrointestinal:
  • Nausea
  • Dyspepsia
  • Abdominal Distress
  • Cholestasis
  • Eructation
  • Flatulence
• Genitourinary:
  • Urinary Tract Infection
  • Urine Abnormality
• Hepatic:
  • Increased Serum Transaminases
  • Abnormal Hepatic Function Tests
  • Hepatitis
  • Increased Serum Alkaline Phosphatase
• Neuromuscular & Skeletal:
  • Limb Pain
  • Myalgia
  • Musculoskeletal Pain
  • Muscle Spasm
  • Increased Creatine Phosphokinase
  • Joint Swelling
  • Muscle Fatigue
  • Neck Pain
• Ophthalmic:
  • Blurred Vision
• Otic:
  • Tinnitus
• Respiratory:
  • Pharyngolaryngeal Pain
  • Epistaxis
• Miscellaneous:
  • Fever

Frequency not defined:

• Central nervous system:
  • Myasthenia

Contraindication to Atorvastatin calcium Include:

• Allergy reactions to atorvastatin and any component of the formulation
• Active liver disease
• Unexplained persistent increases in serum transaminases
• pregnancy;
• Breastfeeding
• Concurrent therapy with glecaprevir/pibrentasvir

Warnings and precautions

• Diabetes mellitus:
  • Reports have indicated an increase in fasting blood glucose and glycated hemoglobin.
• Hepatotoxicity:
  • It has been associated with persistent transaminitis (elevation of liver function tests)
  • Usually, the liver functions return to normal after a reduction in dose, discontinuation or interruption of drug therapy.
  • Both fatal and nonfatal liver diseases have been reported, but they are rare.
  • If serious hepatotoxicity occurs (with symptoms, hyperbilirubinemia, or jaundice), interrupt therapy immediately.
  • Do not restart atorvastatin if an alternative cause is not found.
  • At baseline, and as indicated by the physician, liver enzyme tests should be performed. If there are signs or symptoms of liver injury, they should also be taken.
  • Ethanol could increase the risk of adverse hepatic reactions.
  • Encourage patients to limit their ethanol intake.
• Myopathy and rhabdomyolysis
  • It has been reported that muscle necrosis (rhabdomyolysis), secondary to myoglobinuria or myopathy, can be caused by its use. If myopathy is diagnosed, patients should be closely monitored.
  • This is a dose-dependent risk and can be increased by concurrent use of strong CYP3A4 inhibitors (eg clarithromycin. Itraconazole. protease inhibitors), cyclosporine. Fibromic acid derivatives (eg gemfibrozil) or niacin (doses >=1 g/day).
  • If concurrent use is necessary, consider lowering the starting and maintenance doses.
  • Patients with hypothyroidism that has not been properly treated and patients who are taking colchicine (eg, for myopathy) should be cautious. These patients are more likely to develop myopathy.
  • HMG-CoA reductase inhibits have been linked to immune-mediated necrotizing myopathy.
  • Patients should be taught to report any unexplained pain, tenderness, weakness or brown urine, especially if it is accompanied by malaise, fever, or other symptoms.
  • If CPK levels are elevated or myopathy is suspected or diagnosed, therapy should be stopped.
• Hepatic impairment, ethanol and/or ethanol abuse:
  • Patients who have had liver disease, or who have consumed large amounts of alcohol in the past should be cautious. It is not recommended for patients with active liver disease or persistent elevated serum transaminases.
• Renal impairment
  • Patients with kidney impairment should be cautious; they are more likely to develop myopathy.
• Stroke
  • Patients who have had a stroke or TIA in the past may be at greater risk of hemorhagic stroke if they are receiving long-term treatment with high-dose (80 mg/day) atorvastatin.
  • The post-hoc analysis revealed that patients suffering from hemorhagic stroke or lacunar may be at greater risk. However, this finding was deemed hypothesis generating.
  • If a hemorhagic stroke is a real possibility, the overall benefits of treatment with atorvastatin (ie. reduced risk of strokes and cardiovascular events) seem to outweigh any increased risk.

Atorvastatin: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitor:

• Lipid panel (total cholesterol, HDL, LDL, triglycerides):
  • Lipid profile (fasting or nonfasting) before initiating treatment.
  • Fasting lipid profile should be rechecked 4 to 12 weeks after starting therapy and every 3 to 12 months thereafter.
  • If 2 consecutive LDL levels are <40 mg/dL, consider decreasing the dose.
• Hepatic transaminase levels:
  • Baseline measurement of hepatic transaminase levels (AST and ALT)
  • measure AST, ALT, total bilirubin, and alkaline phosphatase if symptoms suggest hepatotoxicity (eg, unusual fatigue or weakness, loss of appetite, abdominal pain, dark-colored urine or yellowing of skin or sclera) during therapy.
• CPK:
  • CPK should not be routinely measured.
  • Baseline CPK measurement is reasonable for some individuals (eg, family history of statin intolerance or muscle disease, clinical presentation, concomitant drug therapy that may increase risk of myopathy).
  • Measure CPK in any patient with symptoms suggestive of myopathy (pain, tenderness, stiffness, cramping, weakness, or generalized fatigue).
• Evaluate for new-onset diabetes mellitus during therapy:
  • if diabetes develops, continue statin therapy and encourage adherence to a heart-healthy diet, physical activity, a healthy body weight, and tobacco cessation.
• If patient develops a confusional state or memory impairment, may evaluate patient for nonstatin causes (eg, exposure to other drugs), systemic and neuropsychiatric causes, and the possibility of adverse effects associated with statin therapy.

How to take Atorvastatin calcium?

• Oral: with or without food, at any time of the day, do not break the tablet. 

Mechanism of action of Atorvastatin calcium:

• Inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol synthesis (reduces the production of mevalonic acid from HMG-CoA);
• This results in an increase in stimulation of LDL catabolism, and in expression of LDL receptors at hepatocyte membranes.
• HMG-CoA inhibitors are able to lower high-sensitivity CRP (hsCRP) levels.
• They also have pleiotropic effects such as improved endothelial function and reduced inflammation at the site where the coronary plaque is formed.

The onset of action:

• Initial changes: 3 - 5 days;
• Maximal reduction in plasma cholesterol and triglycerides takes 2 to 4 weeks.
• LDL reduction: 10 mg/day: 39% (for each doubling of this dose, LDL is lowered approximately 6%)

Absorption after oral administration is rapid. Extensive first-pass metabolism in Gastrointestinal mucosa and liver occurs.

Distribution: V : ~381 L

Protein binding: ≥98%

Metabolism: Hepatic

Bioavailability is about 14% (parent drug) and about 30% of the parent drug and equipotent metabolites.

Half-life elimination of the Parent drug is about fourteen hours and 20 to 30 hours of the Equipotent metabolites.

Time to peak, serum: 1 to 2 hours

Excretion: Bile  

International Brands of Atorvastatin calcium:

• Acrovastin
• Actalipid
• Aditor
• Aforsatin
• AG-Atorvastatin
• APO-Atorvastatin
• Atorvastatin-10
• Atorvastatin-20
• Atorvastatin-40
• Atorvastatin-80
• Auro-Atorvastatin
• DOM-Atorvastatin
• GD-Atorvastatin
• JAMP-Atorvastatin
• Lipitor
• M-Atorvastatin
• Mar-Atorvastatin
• MYLAN-Atorvastatin
• NOVO-Atorvastatin
• PMS-Atorvastatin
• RAN-Atorvastatin
• RATIO-Atorvastatin
• REDDY-Atorvastatin
• RIVA-Atorvastatin
• SANDOZ Atorvastatin
• TEVA-AtorvastatinAle
• Alipid
• Amicor
• Anxolipo
• Aspavor
• Astatin
• Astator
• Atacor
• Atarva
• Atasin
• Ateroz
• Atocor
• Atofar
• Atolow
• Atopitar
• Atorasat
• Atorcad
• Atorcal
• Atoris
• Atorlip
• Atorphil
• Atorsan
• Atorvaright
• Atorvas
• Atorvast
• Atorwin
• Atoty
• Atrofit
• Atstat
• Atswift
• Atvas
• Avamax
• Axo
• Bestatin
• Carditor
• Cardyl
• Carvastin
• Cheklip
• Chlovas
• Citalor
• Colestop
• Covetor
• Debostin
• Divator
• Enturion
• Fastor
• Hipolixan
• Lipicon
• Lipiduce
• Lipigo
• Lipikhan
• Lipilou
• Lipinon
• Lipitas
• Lipiterol
• Lipitin
• Lipitor
• Lipiwon
• Lipoactin
• Lipodar
• Lipofix
• Lipomax
• Lipomet
• Liponorm
• Lipox
• Litorva
• Lopamol
• Lorstat
• Lowlipen
• Neustatin-A
• Newvast
• Olpit
• Orvast
• Pelearto
• Plan
• Rotaqor
• Saatin
• Safena
• Simtor
• Sortis
• Statol
• Stator
• Storvas
• Tahor
• TG-Tor
• Tolevas
• Torid
• Torolac
• Torvalipin
• Torvast
• Torvatec
• Torvazin
• Tovast
• Trovas
• Truvaz
• Tulip
• Vastor
• Vaztor
• X-Tor
• Xantor
• Xelpid
• Xentor
• Xerova
• You Jia
• Zapitor
• Zarator

Atorvastatin Brands in Pakistan: