Atorvastatin-Vertex, 10 mg 30 pcs

Cholesterol Reduction, Cholesterol, Heart Attack and Stroke Prevention

• In combination with diet to reduce elevated levels of total cholesterol, cholesterol/LDL, apolipoprotein B and triglycerides and increase HDL cholesterol levels in patients with primary hypercholesterolemia, heterozygous familial and non-familial hypercholesterolemia and combined (mixed) hyperlipidemia (Fredrickson types IIa and IIb);
• in combination with diet for treatment of patients with increased serum levels of triglycerides (Fredrickson type IV) and patients with dysbetalipoproteinemia (Fredrickson type III), in which diet therapy is not effective
• For lowering total cholesterol and LDL-cholesterol levels in patients with homozygous familial hypercholesterolemia when diet therapy and other non-pharmacological methods of treatment are not effective enough.

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Active ingredient

Composition

Active ingredient:

Atorvastatin calcium trihydrate (in terms of atorvastatin) – 10.00 mg;

Auxiliary substances:

Microcrystalline cellulose – 49.68 mg,

Lactose monohydrate – 40.00 mg,

Calcium carbonate – 33.00 mg,

Crospovidone – 7.50 mg,

Sodium carboxymethyl starch (sodium starch glycolate) – 4.50 mg,

Hyprolose (hydroxypropyl cellulose) – 3.00 mg,

Magnesium stearate – 1.50 mg;

Film coating:

[hypromellose 2.250 mg, talc 0.882 mg, hyprolose (hydroxypropyl cellulose) 0.873 mg, titanium dioxide 0.495 mg] or [dry film coating mixture containing hypromellose (50.0%), talc (19.6%), hyprolose (hydroxypropyl cellulose) (19.4%), titanium dioxide (11.0%)] – 4,500 mg.

How to take, the dosage

Ingestion.

Before Atorvastatin is prescribed, the patient should be advised on a standard hypolipidemic diet, which he should continue to follow during the entire period of therapy.

The initial dose is on average 10 mg/day. The dose varies from 10 to 80 mg/day.

The drug can be taken at any time of the day with food or regardless of the time of meals. The dose is adjusted with regard to baseline cholesterol/LDL levels, the goal of therapy, and individual effect. At the beginning of treatment and/or during dose increase of Atorvastatin it is necessary to monitor plasma lipid levels every 2-4 weeks and adjust the dose accordingly.

In order to ensure the following dosing regimen of the drug it is possible to use Atorvastatin in other dosage forms: film-coated tablets 10 mg and 20 mg. The maximum daily dose of the drug is 80 mg.

In concomitant use with cyclosporine, the daily dose of Atorvastatin should not exceed 10 mg.

Primary hypercholesterolemia and mixed hyperlipidemia. In most cases, it is sufficient to prescribe a dose of 10 mg of Atorvastatin once daily. Significant therapeutic effect is observed after 2 weeks, and the maximum therapeutic effect is usually observed after 4 weeks. With long-term treatment this effect is maintained.

Special groups of patients

Kidney function disorders. Administration of the drug in patients with renal insufficiency and renal diseases does not affect the plasma levels of Atorvastatin or the degree of reduction of cholesterol/LDL with its use, therefore no change in the dose of the drug is required.

Hepatic disorders. In case of hepatic insufficiency, the dose should be reduced.

Elderly patients. No differences in safety, efficacy or achievement of hypolipidemic therapy goals have been noted when using the drug in elderly patients compared to the general population.

Interaction

The risk of myopathy during treatment with other drugs of this class is increased with concomitant use of cyclosporine, fibrates, erythromycin, azole antifungals and nicotinic acid.

Concomitant oral administration of Atorvastatin and suspension containing magnesium and aluminum hydroxide decreased plasma concentrations of Atorvastatin by approximately 35%, but the degree of decrease in cholesterol/LDL levels was not changed.

In concomitant use Atorvastatin does not affect pharmacokinetics of antipyrine (phenazone), therefore, interaction with other drugs metabolized by the same cytochrome isoenzymes is not expected.

Concomitant use of colestipol decreased plasma concentrations of Atorvastatin by approximately 25%. However, the hypolipidemic effect of combination of Atorvastatin and colestipol was superior to that of each drug separately.

The equilibrium plasma concentrations of digoxin and Atorvastatin at a dose of 10 mg did not change when digoxin and Atorvastatin were repeatedly administered. However, when using digoxin in combination with Atorvastatin at a dose of 80 mg/day, digoxin concentrations increased by approximately 20%. Patients receiving digoxin in combination with Atorvastatin should be monitored.

In concomitant use of Atorvastatin and erythromycin (500 mg 4 times/day) or clarithromycin (500 mg 2 times/day), which inhibit cytochrome Р450 3A4, an increase in plasma concentration of Atorvastatin was observed.

Concomitant administration of Atorvastatin (10 mg once daily) and azithromycin (500 mg once daily) did not change Atorvastatin plasma concentration.

Atorvastatin had no clinically significant effect on plasma concentrations of terfenadine, which is metabolized primarily by cytochrome Р450 3А4; in this regard, it seems unlikely that Atorvastatin can significantly affect pharmacokinetic parameters of other cytochrome Р450 3А4 substrates.

In concomitant use of Atorvastatin and oral contraceptives containing norethindrone and ethinylestradiol, a significant increase in AUC of norethindrone and ethinylestradiol of approximately 30% and 20% respectively was observed. This effect should be considered when choosing an oral contraceptive for a woman receiving Atorvastatin.

Concomitant use with drugs that reduce the concentration of endogenous steroid hormones (including cimetidine, ketoconazole, spironolactone) increases the risk of reduction of endogenous steroid hormones (caution should be exercised).

In studying the interaction of Atorvastatin with warfarin and cimetidine no signs of clinically significant interaction were found.

The pharmacokinetics of Atorvastatin 80 mg and amlodipine 10 mg in equilibrium have not changed.

There were no clinically significant adverse interactions between Atorvastatin and antihypertensive agents.

The concomitant use of Atorvastatin with protease inhibitors known as cytochrome P450 3A4 inhibitors was accompanied by an increase in plasma concentration of Atorvastatin.

Pharmaceutical incompatibility is not known.

Special Instructions

Before starting therapy with Atorvastatin, the patient should be prescribed a standard hypocholesterolemic diet, which should be followed during the entire period of treatment.

The use of HMG-CoA reductase inhibitors to reduce blood lipid levels may lead to changes in biochemical parameters reflecting liver function. Liver function should be monitored before the start of therapy, 6 weeks, 12 weeks after the start of Atorvastatin and after each dose increase, as well as periodically, e.g., every 6 months.

Elevated serum hepatic enzyme activity may be observed during therapy with Atorvastatin. Patients with increased enzyme levels should be monitored until enzyme levels return to normal. In case if values of alanine aminotransferase (ALT) or asparagine aminotransferase (AST) exceed more than 3 times the upper allowable limit, it is recommended to reduce Atorvastatin dose or discontinue treatment.

Atorvastatin should be used with caution in patients who abuse alcohol and/or have liver disease. Active liver disease or persistent increase in aminotransferase activity of unclear genesis are contraindications to Atorvastatin administration.

Treatment with Atorvastatin may cause myopathy. The diagnosis of myopathy (pain and weakness in muscles combined with an increase in creatine phosphokinase (CPK) activity more than 10 times the upper limit of normal) should be discussed in patients with widespread myalgia, muscle soreness or weakness and/or marked increase in CPK activity. Patients should be warned to inform their physician immediately of unexplained muscle pain or weakness if accompanied by malaise or fever.

Atorvastatin therapy should be discontinued if there is a marked increase in CPK activity or if there is confirmed or suspected myopathy. Risk of myopathy during treatment by other drugs of this class was increased with concomitant use of cyclosporine, fibrates, erythromycin, nicotinic acid or azole antifungal agents. Many of these drugs inhibit cytochrome P450 3A4-mediated metabolism and/or drug transport.

Atorvastatin is biotransformed by CYP 3A4. Prescribing Atorvastatin in combination with fibrates, erythromycin, immunosuppressive agents, azole antifungal agents or nicotinic acid in hypolipidemic doses should be carefully weighed the expected benefits and risks of treatment and regularly monitor patients to detect muscle pain or weakness, especially during the first months of treatment and during periods of increasing dose of any drug. In such situations, periodic determination of CPK activity may be recommended, although such monitoring does not prevent the development of severe myopathy.

In Atorvastatin, as well as other drugs of this class, there have been cases of rhabdomyolysis with acute renal failure due to myoglobinuria. Atorvastatin therapy should be temporarily discontinued or completely discontinued in case of signs of possible myopathy or in presence of risk factor of renal failure during rhabdomyolysis (for example, severe acute infection, arterial hypotension, serious surgery, trauma, severe metabolic, endocrine and electrolyte disorders and uncontrolled convulsions).

Before starting therapy with Atorvastatin, an attempt should be made to achieve control of hypercholesterolemia through adequate diet therapy, increasing physical activity, reducing body weight in obese patients and treating other conditions.

Patients should be warned to seek immediate medical attention if they experience unexplained muscle pain or weakness, especially if accompanied by malaise or fever.

Influence on driving and operating machinery

There have been no reports of adverse effects of Atorvastatin on driving and operating machinery.

Contraindications

The drug should be used with caution in patients with chronic alcoholism, history of liver disease, severe electrolyte balance disorders, endocrine and metabolic disorders, arterial hypotension, severe acute infections (sepsis), uncontrolled epilepsy, extensive surgical interventions, trauma, skeletal muscle diseases.

Side effects

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

From the senses: Amblyopia, tinnitus, dry conjunctivae, accommodation disorders, retinal hemorrhage, deafness, glaucoma, parosmia, loss of sense of taste, perversion of taste.

Cardiovascular system:pain in the chest; palpitations, symptoms of vasodilation, orthostatic hypotension, increased BP, phlebitis, arrhythmias, angina pectoris.

Hematopoietic system disorders:anemia, lymphoadenopathy, thrombocytopenia.

In the respiratory system: bronchitis, rhinitis; pneumonia, dyspnea, exacerbation of bronchial asthma, nasal bleeding.

From the digestive system: nausea; 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 disorders: arthritis; 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: 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:alopecia, xeroderma, photosensitization, increased sweating, eczema, seborrhea, ecchymoses, petechiae.

From the endocrine system: gynecomastia, mastodynia.

Metabolic side:increase in body weight, aggravation of gout.

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

Laboratory findings:hyperglycemia, hypoglycemia, increased serum CPK, albuminuria.

Overdose

Treatment: there is no specific antidote, symptomatic therapy is carried out.

Hemodialysis is ineffective.

Pregnancy use

Atorvastatin is contraindicated during pregnancy and lactation (breastfeeding).

It is unknown whether Atorvastatin is excreted with breast milk. Taking into account the possibility of adverse events in breastfed children, if it is necessary to use the drug during lactation, the question of stopping breastfeeding should be considered.

Women of reproductive age should use adequate contraceptive methods during treatment. Atorvastatin can be administered to women of reproductive age only if they are very unlikely to become pregnant and the patient is informed about the possible risk of treatment to the fetus.

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