Atorvastatin

Atorvastatin Pharmacokinetics please do not publish yet! Atorvastatin: fully synthetic statin; belongs to the group of highly effective statins with max. possible LDL reduction of 50 to 55 %.HWZ 14 hours; statin with long duration of action and slow eliminationlipophilic statin; penetrates the cell membrane via free diffusion and has a widespread effect in various tissues, in contrast to hydrophilic statins, which attach to polar cell surfaces, are only absorbed into the cells via active transport and may have a more liver-specific effect.Atorvastatin is mainly metabolized via CYP3A4; it is also eliminated by OATPB1 (organic anion-transporting polyprotein). Atorvastatin is both a substrate and an inhibitor of P-gp (permeability glycoprotein) and therefore has a very high potential for WW with other substances.Due to the strong first pass effect (very strong metabolization by Cyp P450 enzyme system), it can lead to an 11-fold increase in Cmax and a 16-fold increase in AUC (bioavailability) in cases of impaired liver function! therefore not applicable in cases of chronic liver disease or impaired liver function!Only very low excretion via the kidneys, therefore the drug of choice for CKD or impaired kidney function.High potential for AD with other substances and therefore high risk of occurrence and extent of myotoxic and other ADs due to amplification of effect. Particularly important in older multimorbid patients and other patients with polypharmacotherapy! Indication Treatment on the basis of and in combination with lifestyle changes (dietary changes, exercise, smoking cessation if necessary) in accordance with guidelines (Mach et al 2020).Hypercholesterolemia, dyslipidemia Primary prevention: in case of increased risk of cardiovascular disease (≥10% SCORE2/SCORE2-OP).Secondary prevention: if cardiovascular disease is already present or there is a history of a serious event.homozygous and heterozygous FH (from 10 years of age).In children, observe age-dependent maximum doses, treatment and monitoring only by a specialist (guideline). Pregnancy/nursing period Cholesterol and other intermediate products of cholesterol biosynthesis are essential in embryonic and fetal development and necessary for the synthesis of steroids and cell membranes!Statins are therefore contraindicated during pregnancy and breastfeeding.The potential risk of damage justifies a break in therapy Women and young girls of childbearing age need effective contraception (note interactions!)In case of unexpected pregnancy during treatment, see Embryotox Charité Dosage and method of use Dose according to guidelines according to target value with lowest necessary dose, if necessary dose increases at 4 week intervals; avoid high doses if necessary early combination therapy (ezetimibe), take individual patient factors into account ( ). Doubling the dose brings only approx. 6% additional LDL-C reduction, but higher risk of side effects as side effects are dose-dependent!Dosage: orally as a tablet, once daily, independent of food. Preferably taken in the evening, improved efficacy, as cholesterol synthesis depends on the time of day with the highest cholesterol synthesis at night or early in the morning. Atorvastatin can be taken at any other time of day due to its long half-lifeImportant: daily intake time should always be maintained in order to avoid fluctuations in potency.Adherence to therapy is important and should be discussed with the patient! Undesirable effects Mild side effects are common: headache, dizziness, myalgia, gastrointestinal complaints.frequent: deterioration of blood glucose levels, first manifestation of diabetes, especially in predisposed cases (prediabetes, obesity, metabolic syndrome)Severe NW are rare: myositis, myopathy, rhabdomyolysis (risk of kidney failure), hepatotoxic damage, liver values ≥3 times normal; jaundice, weakness, feeling sick and fever. Individual cases: IMNM; interstitial lung disease, hypersensitivity reaction, angioedema.For further information and details see technical info! Interactions Enzymesystems/carriers and selection of substances with interaction potential(inhibition), risk of concentration increase and risk of adverse effects during treatment with atorvastatin.CYP3A4Amiodarone, amlodipine (CYP3A5), aprepitant, cilostazol, cimetidine, clarithromycin, conivaptan, ciclosporin, cobicistat, diltiazem, erythromycin, fluconazole (higher doses), fluvoxamine, grapefruit, idelalisib, imatinib, isavuconazole, itraconazole, netupitant, posaconazole, ritonavir, voriconazoleP-gp (ABCB1)Amiodarone, azithromycin, captopril, carvedilol, quinidine, cimetidine, clarithromycin, colchicine, conivaptan, ciclosporin, diltiazem, dronedarone (potent), erythromycin, itraconazole, nicardipine, protease inhibitors (HIV), ranolazine, ticagrelor, verapamilOATP1B1Carbamazepine, clarithromycin, ciclosporin, erythromycin, gemfibrozil, protease inhibitors (HIV), roxithromycin, sacubitrilCyp3A4 (Cyt P450 3A4) interactions can greatly increase the concentration of atorvastatin. Risk of severe myopathy with rhabdomyolysis and renal failure! In addition, interaction by hepatic transport proteins (OATP1B1, OATP1B3), MRP1, BCRP and p glycoprotein possible! WW are therefore generally possible with many substances! Glecaprevir/Pibrentasvir: simultaneous use with atorvastatin is contraindicatedGemfibrozil: avoid atorvastatin;Fusidic acid (systemic use): Pause therapy plus 7 days for the duration of use.Ciclosporin, HIV protease inhibitors (tipranavir/ritonavir), hepatitis C protease inhibitors (telaprevir): no more than 10 mg daily!Letermovir: no more than 20 mg!Only use with caution under very strict risk-benefit assessment and use the lowest dose necessary for:HIV protease inhibitors (lopinavir/ritonavir, saquinavir/ritonavir, darunavir/ritonavir, fosamprenavir, fosamprenavir/ritonavir, nelfinavir),Hepatitis C protease inhibitors (boceprevir, elbasvir/grazoprevir, simeprevir*),erythromycin, clarithromycin,itraconazole,Fibrates (except gemfibrozil),colchicine,niacin,Antimycotics of the azole typeHCV NS5A/NS5B inhibitorsThis information is only a selection! Further interactions must be clarified individually in each case! For further information, see Fachinfo! or databases on drug interactions.It should also be noted that statins can alter the effect of concomitant medication and this can also result in additional incompatibilities!Interaction studies have only been carried out in adults. Contraindication Hypersensitivity to the active substance or one of the excipients according to the composition.Patients with active liver disease or unclear permanent elevation of serum transaminases to more than 3 times the normal value.Pregnancy and lactation.In combination with the antivirals glecaprevir/pibrentasvir for the treatment of hepatitis C infection.Cyclosporine For further information, see specialist information! Preparations Atorvastatin (Sortis® , generics) 10 mg, 20 mg, 40 mg, 80 mg (from 10 years) Literature Specialist information atorvastatin

Atorvastatin

Recommended articles

Articlecontent