Atorvastatin, 10 mg 30 pcs

Pharmacological group: Hypolipidemic drug.

Pharmacotherapeutic group: Hypolipidemic drug – HMG-CoA reductase inhibitor.

Pharmacological action

Hypolipidemic agent of the statin group. By the principle of competitive antagonism the statin molecule binds to the part of the coenzyme A receptor where HMG-CoA reductase is attached. The other part of the statin molecule inhibits the conversion of hydroxymethylglutarate into mevalonate, an intermediate product in the synthesis of the cholesterol molecule. Inhibition of HMG-CoA reductase activity leads to a series of sequential reactions resulting in a decrease of intracellular cholesterol content and a compensatory increase of LDL-receptor activity and corresponding acceleration of LDL cholesterol (Xc) catabolism.

The hypolipidemic effect of statins is associated with a decrease in total Xc levels at the expense of LDL Xc. The decrease in LDL levels is dose-dependent and has exponential rather than linear character. Atorvastatin inhibitory effect with respect to HMG-CoA reductase is approximately 70% determined by the activity of its circulating metabolites.

Statin does not affect the activity of lipoprotein and hepatase lipases and has no significant effect on the synthesis and catabolism of free fatty acids, so their effect on TG level is secondary and mediated through their main effects on reduction of LDL-C. A moderate decrease in TG levels during treatment with statins seems to be due to the expression of remnant (apo E) receptors on the surface of hepatocytes involved in catabolism of LDL, which includes approximately 30% of TG. Compared with other statins (with the exception of rosuvastatin) atorvastatin causes a more pronounced decrease in TG levels.

In addition to hypolipidemic action, statins have a positive effect in endothelial dysfunction (preclinical sign of early atherosclerosis), on the vascular wall, atheroma condition, improve rheological properties of blood, have antioxidant, antiproliferative properties.

Atorvastatin reduces cholesterol levels in patients with homozygous familial hypercholesterolemia, which usually does not respond to therapy with hypolipidemic agents.

Pharmacokinetics

Atorvastatin is rapidly absorbed from the GI tract. Absolute bioavailability is low – about 12%, which is due to presystemic clearance in the gastrointestinal mucosa and/or due to “first passage” through the liver, mainly at the site of action.

Atorvastatin is metabolized with the participation of CYP3A4 isoenzyme to form a number of substances that are HMG-CoA reductase inhibitors.

The T1/2 from plasma is approximately 14 h, although the T1/2 of HMG-CoA reductase inhibitor activity is approximately 20-30 h, which is due to the participation of active metabolites.

The binding to plasma proteins is 98%.

Atorvastatin is excreted in the form of metabolites mainly in the bile.

Indications

Prevention of heart attacks and strokes, Atherosclerosis

• Primary hypercholesterolemia with ineffective diet therapy;

• Combined hypercholesterolemia and hypertriglyceridemia;

• Heterozygous and homozygous familial hypercholesterolemia with ineffective diet therapy.

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Active ingredient

Atorvastatin

Composition

Active substances:

Atorvastatin 10 mg.

Auxiliary substances:

Cellulose microcrystalline – 52.52 mg;

Corn starch pregelatinized – 52.51 mg;

Colloidal silica – 0.38 mg;

Magnesium carbonate – 33 mg;

Magnesium stearate – 0.75 mg.

How to take, the dosage

The treatment is carried out on a standard diet for patients with hypercholesterolemia. The dose is set individually, depending on the initial level of cholesterol. It is taken orally. The initial dose is usually 10 mg once a day. The effect is manifested within 2 weeks, and the maximum effect – within 4 weeks. If necessary, the dose can be gradually increased at intervals of 4 weeks or more. The maximum daily dose is 80 mg.

Interaction

Concomitant use of atorvastatin with digoxin slightly increases plasma concentrations of digoxin.

Diltiazem, verapamil, izradipine inhibit CYP3A4 isoenzyme, which is involved in metabolism of atorvastatin, therefore concomitant use with these calcium channel blockers may increase plasma concentration of atorvastatin and increase the risk of myopathy.

Concomitant use of itraconazole significantly increases plasma concentrations of atorvastatin, probably due to inhibition of its metabolism in the liver, which occurs with the participation of CYP3A4 isoenzyme; increased risk of myopathy.

Concomitant use of colestipol may decrease the plasma concentration of atorvastatin, and the hypolipidemic effect is enhanced.

When used concomitantly, antacids containing magnesium hydroxide and aluminum hydroxide decrease the concentration of atorvastatin by approximately 35%.

Concomitant use of cyclosporine, fibrates (including gemfibrozil), antifungal drugs azole derivatives, nicotinic acid increases the risk of myopathy.

Concomitant use of erythromycin, clarithromycin moderately increases plasma concentrations of atorvastatin, increases the risk of myopathy.

Concomitant use of ethinylestradiol, norethisterone (norethindrone) slightly increases plasma concentrations of ethinylestradiol, norethisterone and (norethindrone).

Concomitant use of protease inhibitors increases plasma concentration of atorvastatin because protease inhibitors are inhibitors of CYP3A4 isoenzyme.

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Contraindications

• Liver disease in the active stage;

• Elevation of serum transaminase activity by more than 3 times of unclear genesis;

• Pregnancy, lactation (breastfeeding);

• Women of reproductive age who do not use reliable contraception;

• Hypersensitivity to atorvastatin.

Side effects

Nervous system disorders: > 1% – insomnia, dizziness; < 1% – headache, asthenia, malaise, drowsiness, nightmares, paresthesias, peripheral neuropathy, amnesia, emotional lability, ataxia, facial nerve palsy, hyperkinesias, migraine, depression, hypoesthesia, loss of consciousness.

Sensory organs: < 1% – amblyopia, tinnitus, dry conjunctiva, accommodation disorders, retinal hemorrhage, deafness, glaucoma, parosmia, loss of taste sensation, perversion of taste.

Cardiovascular system: > 1% – chest pain; < 1% – palpitations, vasodilation symptoms, orthostatic hypotension, increased BP, phlebitis, arrhythmias, angina pectoris.

Hematopoietic system: < 1% – anemia, lymphoadenopathy, thrombocytopenia.

In the respiratory system: > 1% – bronchitis, rhinitis; < 1% – pneumonia, dyspnea, exacerbation of bronchial asthma, nasal bleeding.

Digestive system disorders: > 1% – nausea; < 1% – heartburn, constipation or diarrhea, flatulence, gastralgia, abdominal pain, decreased or increased appetite, dry mouth, belching, dysphagia, vomiting, stomatitis, esophagitis, glossitis, erosive and ulcerative lesions of the oral mucosa, gastroenteritis, hepatitis, biliary colic, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, impaired liver function, rectal bleeding, melena, bleeding gums, tenesmus.

Muscular system side: > 1% – arthritis; < 1% – leg muscle cramps, bursitis, tenosynovitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, torticollis, muscle hypertonicity, joint contractures, joint swelling, tendopathy (in some cases with tendon rupture).

Urogenital system disorders: > 1% – urogenital infections, peripheral edema; < 1% – dysuria (including pollakiuria, nycturia, urinary incontinence or urinary retention, imperative urge to urinate), leukocyturia, nephritis, hematuria, vaginal bleeding, nephrourolithiasis, metrorrhagia, epididymitis, decreased libido, impotence, ejaculation disorders.

Dermatological reactions: > 1% – alopecia, xeroderma, photosensitization, increased sweating, eczema, seborrhea, ecchymoses, petechiae.

From the endocrine system: < 1% – gynecomastia, mastodynia.

Metabolic side: < 1% – weight gain, aggravation of gout.

Allergic reactions: < 1% – skin itching, skin rash, contact dermatitis, rarely – urticaria, angioedema, facial edema, anaphylaxis, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome).

Laboratory findings: < 1% – hyperglycemia, hypoglycemia, increased serum CPK, albuminuria.