Trade name(s): Lorstat (NZ name), Lipitor. Drug Class: Lipid lowering
Pharmacological action: Effect: Improves LDL-HDL ratios, How: Inhibition of the enzyme HMG-CoA reductase leads to decreased de-novo Cholesterol production. Pleiotropic drug so it has a number of effects.
Pharmacokinetics:
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Absorption: Rapidly absorbed orally, peak plasma conc reached maybe 1-2 hours after administration. Bioavailability is 14%.
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Distribution; mean volume of distribution is approximately 381 litres
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Metabolism: metabolites are as effective in inhibiting HMGCOA reductase as atorvastatin and 70% of the effect can be attributed to metabolites CYP3A4 is an important enzyme in the metabolism of atorvastatin
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Excretion: Half life is 14 hours. However total inhibitory time is around 30 hours due to metabolite effects. Mainly excreted in the bile and little enterohepatic recirculation takes place
Indications: Hypercholesterolaemia, mixed dyslipiaemia familial hypercholesrterol, hypertryglyceridaemia, dysbetalipoproteinaemia when so response to diet is present, prophylaxis against Cardiac ischaemic events when LDL-C is at leadt 3mmol/L and triglyceride levels are no more then 5.6mm\L in parient with CAD. type 2 diabetes, HTN.
Contraindications/precautions: Active liver disease or unexplained persistent elevations of serum transaminases (test for serum transaminase levels)
Concomitant use with fusidic acid can increase risk of rhabdomyolysis.
Pregnancy or lactation Women of child bearing potential should not be put on this drug unless on an effective contraception and unlikely to concieve.
Adverse reactions: GI: dyspepsia, nausea, flatulence, diarrhoea, Infective nasopharyngitis
Investigative for Liver function test abnormal, blood creatine phosphokinase increased
Interactions: Metabolised by CYP3A4 therefore inhibitors of CYP3A4 can increase plasma concentrations of Atorvastatin.
These include: Ciclosporin, macrolide antibiotics including erythromycin and azole antifungals including itraconazole, glecaprevir, leniolisib, paritaprovir, sparsentan, vimseltinib all increase exposure to atvorastatin.
Danger: fusidic acid on the basis of that it increases risk of myopathy and may lead to increased plasma concentration in both through an obscure mechanism.
Dosing/Current guidelines: Dosing dependant on disease:
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Hypercholesterolaemia, mixed dyslipidaemia, Hypertriglyceridaemia, and Dysbetalipoproteinaemia: Adults: 10 mg to 80 mg per day as a single dose as a single daily dose and should be individualised appropriately.
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Primary hypercholesterolaemia and mixed hyperlidipaemia: Adults: one 10mg pill daily.
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Stable coronary artery disease: Adults are to be considered for 80mg/day.
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Homozygous familial hypercholesterolaemia: Adults → study shows 80mg having a beneficial dose. Children → study limited dose up to 80mg over a year
Monitoring: Monitor for raise in serum transaminase levels and rhabdomyolysis.
Overdose: No specific treatment, for symptomatic patients monitor serum creatine, BUN creatinine phosphokinase and urine myoglobin for indications of renal impairment. Additionally liver function tests fro symptomatic patients
Activated charcoal is recommended. Most effective within 1 hour of ingestion.
What to tell patients: Seek medical assistance if you experience muscle pain or weakness (due to rhabdomyolysis)
Comments/Observations/notes: