Adult: Dose is individualised according to baseline LDL-C levels, the goal of therapy, and patient response. Usual initial dose: 10 or 20 mg once daily. May be adjusted according to response at 2-4 weeks interval. Usual range: 10-80 mg once daily. Max: 80 mg daily. Patients who require >45% reduction in LDL-cholesterol: May initiate at 40 mg once daily. Child: Heterozygous familial hypercholesterolaemia: 10-17 years Initially, 10 mg once daily. May adjust according to response at 4 weeks interval. Usual dose range: 10-20 mg once daily.
Oral Prophylaxis of cardiovascular events in high-risk patients
Adult: Primary prevention: Initially, 10 mg daily. May be given at higher doses as necessary to attain LDL-cholesterol levels according to current guidelines.
May be taken with or without food. Avoid excessive consumption (>1 L/day) of grapefruit juice.
Contraindications
Active liver disease, unexplained persistent serum transaminase elevation. Pregnancy and lactation. Concomitant use with ciclosporin, systemic fusidic acid, telaprevir, glecaprevir/pibrentasvir and tipranavir/ritonavir combinations.
Special Precautions
Patients with diabetes mellitus, hypothyroidism, hereditary muscular disorders, recent stroke, transient ischaemic attack, severe acute infection, hypotension, major surgery, predisposing factors for rhabdomyolysis, severe metabolic disorder and uncontrolled seizures. Not indicated for elevated chylomicrons as the primary lipid abnormality. Patients who consume large quantities of alcoholic beverages. Renal impairment. Children. Patients taking concomitant CYP3A4 inhibitors [e.g. clarithromycin, itraconazole, fosamprenavir, ritonavir (plus darunavir, fosamprenavir, or saquinavir), elbasvir/grazoprevir, boceprevir and nelfinavir].
Adverse Reactions
Significant: Myopathy, myalgia, diabetes mellitus, persistent serum transaminase elevations. Rarely, immune-mediated necrotising myopathy (IMNM), interstitial lung disease. Blood and lymphatic system disorders: Thrombocytopenia. Ear and labyrinth disorders: Tinnitus, hearing loss. Eye disorders: Blurred vision. Gastrointestinal disorders: Diarrhoea, constipation, nausea, dyspepsia, dysgeusia, flatulence. General disorders and admin site conditions: Malaise, asthenia, fatigue, pyrexia. Hepatobiliary disorders: Cholestasis. Investigations: Abnormal LFT, elevated serum creatine kinase, WBC urine positive. Metabolism and nutrition disorders: Hyperglycaemia. Musculoskeletal and connective tissue disorders: Muscle spasms, joint swelling, musculoskeletal and extremity pain. Nervous system disorders: Headache, dizziness, paraesthesia, amnesia. Psychiatric disorders: Insomnia, nightmares. Renal and urinary disorders: UTI. Reproductive system and breast disorders: Rarely, gynaecomastia. Respiratory, thoracic and mediastinal disorders: Nasopharyngitis, pharyngolaryngeal pain. Skin and subcutaneous tissue disorders: Alopecia, skin rash, pruritus, urticaria. Vascular disorders: Epistaxis. Potentially Fatal: Severe rhabdomyolysis with acute renal failure, hepatitis, hepatic failure. Rarely, Stevens-Johnson syndrome, anaphylaxis, toxic epidermal necrolysis.
Monitor lipid panel (e.g. total cholesterol, HDL, LDL, triglycerides) at baseline, 2-12 weeks after initiation, and 12-48 weeks thereafter. Monitor serum creatine kinase (CK) and LFT at baseline and periodically thereafter. Check for signs and symptoms of increased CK suggestive of myopathy (e.g. fever, muscle pain, weakness, stiffness, cramping, generalized fatigue).
Drug Interactions
May increase risk of myopathy and rhabdomyolysis with moderate to potent CYP3A4 inhibitors (e.g. HIV and HCV protease inhibitors, itraconazole, ketoconazole, clarithromycin, eryhthromycin, verapamil, diltiazem), fenofibrate, gemfibrozil, ezetimibe, niacin, colchicine, fixed combination of lopinavir/ritonavir. Concomitant use with CYP3A4 inducers (e.g. rifampicin, efavirenz, phenytoin), Al or Mg antacids, and colestipol may reduce plasma concentrations of atorvastatin. May increase serum levels of digoxin and oral contraceptives (e.g. norethindrone, ethinyl estradiol). Potentially Fatal: Concomitant use with ciclosporin, telaprevir, glecaprevir/pibrentasvir and tipranavir/ritonavir combinations may potentiate risk of myopathy or rhabdomyolysis. Coadministration with or within 7 days of stopping systemic fusidic acid may increase risk of fatal rhabdomyolysis.
Food Interaction
Grapefruit or grapefruit juice intake may elevate serum concentrations of atorvastatin. Red yeast rice may increase risk for toxic effects. Large consumption of alcoholic beverages may potentiate risk for hepatic impairment. Decreased plasma concentrations with St. John’s wort.
Action
Description: Atorvastatin selectively and competitively inhibits HMG-CoA reductase, the enzyme that catalyses the conversion of HMG-CoA to produce mevalonate. The reduction of mevalonate production results to a compensatory increase in the expression of LDL receptors and stimulation of LDL catabolism, consequently lowering LDL-cholesterol levels. Onset: Initial effect: 3-5 days. Pharmacokinetics: Absorption: Rapidly absorbed from the gastrointestinal tract. Bioavailability: Approx 12-14%. Time to peak plasma concentration: 1-2 hours. Distribution: Volume of distribution: Approx 381 L. Plasma protein binding: ≥98%. Metabolism: Metabolised in the liver by CYP3A4 isoenzyme to active ortho- and parahydroxylated derivatives, and inactive β-oxidation metabolites. Undergoes extensive first-pass metabolism in the gastrointestinal mucosa and liver. Excretion: Mainly via bile; via urine (<2% as unchanged drug). Elimination half-life: Approx 14 hours.
Chemical Structure
Atorvastatin Source: National Center for Biotechnology Information. PubChem Database. Atorvastatin, CID=60823, https://pubchem.ncbi.nlm.nih.gov/compound/Atorvastatin (accessed on Jan. 21, 2020)
C10AA05 - atorvastatin ; Belongs to the class of HMG CoA reductase inhibitors. Used in the treatment of hyperlipidemia.
References
Anon. Atorvastatin Calcium. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 06/03/2019.Anon. Atorvastatin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/03/2019.Atorvastain Calcium Tablet (Zydus Pharmaceuticals (USA) Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 06/03/2019.Atorvastatin Winthrop Tablet (Winthrop Pharmaceuticals Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my/. Accessed 03/04/3019.Buckingham R (ed). Atorvastatin Calcium. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/03/2019.Joint Formulary Committee. Atorvastatin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 03/04/3019.
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