Atorvastatin Alkaloid, 10 mg 30 pcs

How to take, the dosage

Usually the starting dose is 10 mg once a day. The dose varies from 10 to 80 mg/day. The drug can be taken at any time of the day once a day regardless of meals. Doses should be selected individually, taking into account the initial LDL cholesterol level, the purpose of therapy and patient’s response to treatment. At the beginning and/or during increasing of Atorvatatin dose it is necessary to monitor plasma lipid levels every 2-4 weeks and adjust the dose accordingly.

Dose adjustment should be carried out at intervals of at least 4 weeks. The maximum daily dose is 80 mg.

For patients with established coronary heart disease (CHD) and other patients at high risk of cardiovascular complications, the following lipid level adjustment targets are recommended: LDL cholesterol less than 3.0 mmol/L (or less than 115 mg/dL) and total cholesterol less than 5.0 mmol/L (or less than 190 mg/dL).

Primary hypercholesterolemia and combined (mixed) hyperlipidemia

In most patients the necessary control of lipid levels is provided by taking 10 mg of Atorvastatin once daily. Significant therapeutic effect is usually observed after 4 weeks. In long-term treatment this effect remains.
Heterozygous familial hypercholesterolemia.

Treatment of patients should be started with administration of Atorvastatin 10 mg daily. Making individual dose adjustments every 4 weeks, the dose should be brought to 40 mg/day. After this it is possible to increase a dose up to Maximal level equal to 80 mg/day or use combined administration of 40 mg Atorvastatin and bile acids sequestrant.

Homozygous familial hypercholesterolemia
Prescribed in dose of 80 mg once per day. In patients with renal insufficiency.

Renal diseases do not affect atorvastatin plasma concentration or degree of lipid reduction during its use; in this regard, any dose adjustment in patients with renal disease is not required.

In patients with hepatic impairment.
In patients with hepatic impairment a dose reduction or cancellation of the drug may be required (see section “Special Precautions”).

Interaction

The risk of myopathy during treatment with HMG-CoA reductase inhibitors increases when used in combination with cyclosporine, fibrates, macrolide antibiotics (including erythromycin), azole antifungal agents or nicotinic acid.

In some rare cases these combinations cause rhabdoMyolysis, accompanied by renal failure due to myoglobinuria. In this regard, a careful assessment of the risk-benefit ratio of combined treatment is required (see section “Special notes”).
Inhibitors of P450 CYP isoenzyme CYP 3A4

Atorvastatin is metabolized with participation of cytochrome P450 CYP 3A4 isoenzyme. When using atorvastatin in combination with inhibitors of cytochrome P450 CYP 3A4 isoenzyme (for example, cyclosporine, macrolide antibiotics such as erythromycin and clarithromycin, nefazodone, azole antifungal agents such as itraconazole and HIV protease inhibitors) drug interactions may occur. When combined use of drugs, increased plasma concentrations of atorvastatin may be observed. In this regard, special caution should be exercised when using atorvastatin in combination with the above-mentioned drugs (see section “Special indications”).

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).
P-glycoprotein inhibitors

Atorvastatin and its metabolites are substrates for P-glycoprotein. P-glycoprotein inhibitors (e.g., cyclosporine) may increase the bioavailability of atorvastatin.

Erythromycin, clarithromycin

If atorvastatin and erythromycin (500 mg 4 times/day) or clarithromycin (500 mg 2 times/day.), which inhibit cytochrome P450 CA4, an increase of plasma concentration of atorvastatin was observed.

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

Itraconazole
In combined administration of atorvastatin at a dose of 40 mg and itraconazole at a dose of 200 mg once daily the AUC was increased to three times higher than normal.

Protease inhibitors
Concomitant use of atorvastatin with protease inhibitors known as cytochrome P450 WA4 inhibitors was accompanied by an increase in plasma concentration of atorvastatin.

Grapefruit juice
Grapefruit juice contains at least one ingredient that is a CYP3A4 inhibitor and may cause increased plasma concentrations of those drugs that are metabolized by CYP3A4. Daily consumption of 240 ml of grapefruit juice increased the AUC of atorvastatin by 37% and decreased the AUC of the active orthohydroxy metabolite by 20.4%. Consumption of large amounts of grapefruit juice (more than 1.2 liters per day for 5 days) increased the AUC of atorvastatin by 2.5 times, and the AUC of active HMG-CoA reductase inhibitors (atorvastatin + its metabolites) – by 1.3 times. In this regard it is not recommended to consume large amounts of grapefruit juice during treatment with atorvastatin.

Cytochrome P450 inducers.
Effects of drugs inducing cytochrome P450 isoenzyme CYP WA4. (e.g., rifampicin and phenazone) on atorvastatin is unknown. Interactions with atorvastatin and other substrates of this isoenzyme are unknown; however, the possibility of these interactions should be considered when using drugs with low therapeutic index – in particular, antiarrhythmic drugs of class III, such as amiodarone.

Hemfibrozil/Fibrates
The risk of myopathy caused by atorvastatin may increase with concomitant use of fibrates. In vitro studies suggest that gemfibrozil may also interact with atorvastatin by inhibiting eiro glucuronidation, which may cause increased plasma concentrations of atorvastatin (see

Digoxin
When digoxin and atorvastatin were repeatedly administered at a dose of 10 mg, equilibrium plasma concentrations of digoxin were unchanged. However, when digoxin was used 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 observed.

Oral contraceptives
Administration of atorvastatin in combination with oral contraceptives containing norethisterone and ethinylestradiol caused increased plasma concentrations of norethisterone and ethinylestradiol. These increases in concentrations should be considered when choosing doses of oral contraceptives. When concomitant use of atorvastatin and oral contraceptives containing norethisterone and ethinylestradiol, a significant increase in AUC of norethisterone and ethinylestradiol by approximately 30% and 20%, respectively, was observed. This effect should be considered when choosing an oral contraceptive for a woman receiving atorvastatin.

Colestipol
When administering colestipol in combination with atorvastatin, a decrease in plasma concentration of atorvastatin by about 25% was noted. However, when combining atorvastatin and colestipol the effect on lipids was more pronounced than when using each of these drugs separately.

Antacids
Concomitant oral administration of atorvastatin and suspension containing magnesium and aluminum hydroxide decreased plasma concentration of atorvastatin by approximately 35%; however, the degree of LDL level decrease did not change.

Warfarin
When receiving atorvastatin in combination with warfarin a slight decrease of prothrombin time in the first days of receiving atorvastatin was observed; however in the next 15 days prothrombin time returned to normal. Nevertheless, if atorvastatin and warfarin are used together, patients should be closely monitored.

Phenazone
Atorvastatin does not affect pharmacokinetics of phenazone, so interaction with other drugs metabolized by the same cytochrome isoenzymes is not expected.

Cimetidine
A study of combined administration of cimetidine and atorvastatin showed no significant interaction between these drugs.

Amlodipine
No changes in pharmacokinetic parameters of atorvastatin in equilibrium have been found during combined administration of 80 mg atorvastatin and 10 mg amlodipine.

Other
No clinically significant adverse interactions of atorvastatin and antihypertensive agents were observed. Studies of interaction with all specific drugs were not conducted.

Atorvastatin had no clinically significant effect on plasma concentration of terfenadine, which is metabolized primarily by cytochrome P450 WA4; in this regard, it seems unlikely that atorvastatin can significantly affect pharmacokinetic parameters of other cytochrome P450 WA4 substrates.

Special Instructions

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

Use of HMG-CoA reductase inhibitors to decrease blood lipid levels may lead to changes in biochemical parameters that affect 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, for example, every 6 months. Elevation of serum hepatic enzymes activity may be observed during therapy with atorvastatin. Patients with increased enzyme levels should be monitored until enzyme levels return to normal. In case of persistent increase of alanine aminotransferase (ALT) or aspartate aminotransferase (ACT) values to the level exceeding more than 3 times the upper allowable limit, it is recommended to reduce Atorvastatin dose or stop treatment.