Atorvastatin-Vertex, 40 mg 30 pcs

Atorvastatin is a hypolipidemic drug of the III generation from the group of statins.

Indications

– in combination with diet to decrease elevated levels of total chs, chs-LDL, apolipoprotein B and TG and increase HDL chs 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 the treatment of patients with elevated serum levels of TG (Fredrickson type IV) and patients with dysbetalipoproteinemia (Fredrickson type III) in which diet therapy does not give the adequate effect;

– for decrease of total chs and chs-LDL levels in patients with homozygous familial hypercholesterolemia when diet therapy and other non-pharmacological methods of treatment are not effective enough.

Active ingredient

Composition

Active substance:

Atorvastatin calcium trihydrate;

Auxiliary substances:

calcium carbonate;

MCC;

StarCap1500 (corn starch and pregelatinized starch);

silica colloidal dioxide (aerosil);

talk; magnesium stearate;

Opadry II (series 85) (polyvinyl alcohol, macrogol, talc, titanium dioxide, iron oxide yellow dye, iron oxide red dye).

How to take, the dosage

Ingestion. Before administration of Atorvastatin, a standard hypolipidemic diet should be recommended to the patient, 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. When concomitant use with cyclosporine, the daily dose of Atorvastatin should not exceed 10 mg.

Primary hypercholesterolemia and mixed hyperlipidemia. In most cases a dose of 10 mg of Atorvastatin once daily is sufficient.

Significant therapeutic effect is observed after 2 weeks, and the maximum therapeutic effect is usually observed after 4 weeks. This effect persists with long-term treatment.

Special patient groups Renal dysfunction.

Patients with renal insufficiency and renal diseases do not influence on Atorvastatin level in plasma or degree of cholesterol/LDL decrease during the use of the drug, therefore it is not required to change drug dose. Liver function abnormalities.

In case of hepatic impairment, 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 statins is increased when used in combination with cyclosporine, fibrates, erythromycin, nicotinic acid in lipid-lowering doses, strong CYP3A4 inhibitors (including clarithromycin, HIV protease inhibitors, itraconazole).

When using atorvastatin in combination with CYP3A4 isoenzyme inhibitors (e.g. cyclosporine, macrolide antibiotics – erythromycin and clarithromycin; itraconazole, HIV protease inhibitors) may increase plasma concentrations of atorvastatin (atorvastatin is metabolized with the participation of CYP3A4); special caution should be exercised when using atorvastatin in combination with the above-mentioned drugs (see “Cautionary notes. See “Special Indications”).

In combined administration of atorvastatin in dose of 40 mg and itraconazole in dose of 200 mg once a day it was stated 3 times increased AUC of atorvastatin in comparison with AUC in monotherapy. Concomitant use of atorvastatin with protease inhibitors (lopinavir/ritonavir, ritonavir/saquinavir) was accompanied by increased plasma concentration of atorvastatin.

In concomitant administration of atorvastatin in dose of 40 mg and combination lopinavir+ritonavir (in dose 400/100 mg 2 times per day) it was revealed the increase of AUC of atorvastatin 5.9 times in comparison with AUC during monotherapy. When administering atorvastatin at a dose of 40 mg with a combination of ritonavir + saquinavir (in a dose of 400/400 mg 2 times a day) its AUC was increased by 3.9 times.

Antacids decrease the concentration of atorvastatin by 35% (effect on LDL cholesterol is not changed). If digoxin and atorvastatin are taken repeatedly, the Css of digoxin increases by about 20% (patients should be monitored).

When co-administration of atorvastatin and oral contraceptives the AUC of norethindrone and ethinylestradiol is increased by approximately 30 and 20% (this effect should be considered when choosing oral contraceptives for women receiving atorvastatin).

In concomitant administration with erythromycin (CYP3A4 inhibitor) plasma concentration of atorvastatin is increased by about 40%.

Hypolipidemic effect of combination of atorvastatin and colestipol is superior to that of each drug separately.

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

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 of cholesterol/LDL level was not changed.

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 for administration of Atorvastatin. 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 cautioned to inform their physician immediately of unexplained muscle pain or weakness if accompanied by malaise or fever. Atorvastatin therapy should be discontinued in case of marked increase in CPK activity or in the presence of confirmed or suspected myopathy.

The risk of myopathy during treatment with other drugs of this class was increased with concomitant use of cyclosporine, fibrates, erythromycin, nicotinic acid or azole antifungals. Many of these drugs inhibit cytochrome P450 3A4-mediated metabolism and/or drug transport.

Atorvastatin is biotransformed by CYP 3A4. When prescribing Atorvastatin in combination with fibrates, erythromycin, immunosuppressive agents, azole antifungal agents or nicotinic acid in hypolipidemic doses, the expected benefits and risks of treatment should be carefully weighed and patients should be regularly observed for 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.

Contraindications

– active liver disease;

– increased liver enzyme activity of unclear genesis (more than 3 times compared to CHF);

– hepatic failure (grades A and B according to the Child-Pugh scale);

– pregnancy;

– lactation period;

– age under 18 years (efficacy and safety not established);

– hypersensitivity to the drug components.

With caution the drug should be used in patients with chronic alcoholism, history of liver diseases, 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

In controlled clinical trials (n=2502) less than 2% of patients discontinued treatment due to atorvastatin-induced adverse effects. The most frequent adverse effects associated with taking atorvastatin were constipation, flatulence, dyspepsia, and abdominal pain.

Nervous system and sense organs: ≥2% – headache, asthenic syndrome, insomnia, dizziness;

Cardiovascular system disorders: ≥2% – chest pain;BP, phlebitis, arrhythmia, angina pectoris, anemia, lymphadenopathy, thrombocytopenia.

Respiratory system: ≥2% – sinusitis, pharyngitis, bronchitis, rhinitis;

Gastrointestinal organs: ≥2% – abdominal pain, constipation or diarrhea, dyspepsia, flatulence, nausea;

Musculoskeletal disorders: ≥2% – arthralgia, myalgia, arthritis;

Urinary system disorders: ≥2% – urogenital infections, peripheral edema;

Skin disorders: Allergic reactions: ≥2% – skin rash;

Other: ≥2% – infections, accidental trauma, flu-like syndrome, back pain; ALT, elevated ALT or AST, gout exacerbation.

Side effects noted in post-marketing studies with atorvastatin therapy: anaphylaxis, angioneurotic edema, bullous rash (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis), rhabdomyolysis, tendon rupture.

Overdose

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

Hemodialysis is ineffective.

Similarities