Atorvastatin-Teva, 40 mg 30 pcs

Indications

• .In patients with primary hypercholesterolemia, heterozygous familial and non-familial hypercholesterolemia and combined (mixed) hyperlipidemia (Fredrickson types IIa and IIb) in combination with diet to reduce elevated total cholesterol, LDL cholesterol, apolipoprotein B and triglyceride levels and increase HDL cholesterol levels;
• to treat patients with elevated serum triglyceride levels (Fredrickson type IV) and patients with dysbetalipoproteinemia (Fredrickson type III) in whom diet therapy is not having an adequate effect;

Active ingredient

Atorvastatin

Composition

1 tablet contains:

the active ingredient atorvastatin calcium (converted to atorvastatin) 10.36 mg (10 mg) / 20.72 mg (20 mg) / 41.44 mg (40 mg) / 82.88 mg (80 mg); excipients: 94.94/189.88/379.76/759.52 mg lactose monohydrate; 4.00/ 8.00/16.00/32.00 mg povidone K-30; Eudragite E100 (butyl methacrylate, dimethylaminoethyl methacrylate and methyl methacrylate copolymer 1:2:1) 1.50/3.00/6.00/12.00 mg; alpha-tocopherol macrogol succinate 3.00/6.00/12.00/24.00 mg; croscarmellose sodium 5.00/10.00/20.00/40.00 mg; sodium stearyl fumarate 1.20/2.40/4.80/9.60 mg; Opadray YS-1R-7003 (titanium dioxide 0.9375/1.8750/3.7500/7.500 mg; hypromellose-2910 3cP (E464) 0.8963/1.7926/3.5852/7.1704 mg; Hypromelose-2910 5cP (E464) 0.8963/1.7926/3.5852/7.1704 mg; macrogol-400 0.240/0.480/0.960/1.920 mg; polysorbate-80 0.030/0.060/0.120/0.240 mg).

How to take, the dosage

The usual starting dose is 10 mg once daily. 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 dose increase of Atorvastatin-Teva it is necessary to monitor plasma lipid levels every 2-4 weeks and adjust the dose accordingly.

Dose adjustments should be made 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 goals 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-Teva once daily. Significant therapeutic effect is usually observed after 4 weeks. With long-term treatment this effect is maintained.

Heterozygous familial hypercholesterolemia

The treatment of patients should be started with administration of 10 mg of Atorvastatin-Teva daily. Making individual dose adjustments every 4 weeks, the dose should be brought to 40 mg/day. Thereafter, the dose can be increased to a maximum level of 80 mg/day, or a combined prescription of 40 mg Atorvastatin-Teva and bile acid sequestrant can be used.

Homozygous familial hypercholesterolemia

Prescribe in a dose of 80 mg once daily.

In patients with renal impairment

Kidney disease does not affect the plasma concentration of atorvastatin or the degree of lipid reduction with its use; Therefore, no dose adjustment is required in patients with renal disease.

In patients with hepatic impairment

Hepatic impairment may require dose reduction or discontinuation of the drug (see section “Special Precautions”).

Interaction

Drug effects on the effects of atorvastatin

. The risk of myopathy during treatment with HMG-CoA reductase inhibitors increases with concomitant use with cyclosporine, fibrates, macrolides (including erythromycin), azole antifungal agents or nicotinic acid.

In some rare cases, these combinations may cause rhabdomyolysis accompanied by renal failure. In this regard, a careful assessment of the ratio of possible risk to expected benefits of the combined treatment is necessary (see section “Special indications”).

Inhibitors of CYP3A4 isoenzyme

Atorvastatin metabolism is mediated by CYP3A4 isoenzyme. In concurrent use of atorvastatin with CYP3A4 isoenzyme inhibitors (e.g. cyclosporine, macrolide antibiotics such as erythromycin and clarithromycin, nefazodone, azole antifungal agents such as itraconazole and HIV protease inhibitors) there may be drug interactions. In combined use of the drugs increased plasma concentrations of atorvastatin may be observed.

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.

OATP1B1 transport protein inhibitors

Atorvastatin and its metabolites are substrates for the OATP1B1 transport protein. Inhibitors of OATP1B1 transport protein (e.g., cyclosporine) may increase the bioavailability of atorvastatin.

Itraconazole

Concomitant use of atorvastatin and itraconazole showed an increase in AUC to three times greater than normal.

Protease inhibitors

. Concomitant use of atorvastatin with protease inhibitors known as CYP3A4 isoenzyme inhibitors was accompanied by an increase in plasma concentration of atorvastatin.

Grapefruit juice

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

Inductors of CYP3A4 isoenzyme

. Concomitant use of atorvastatin with drugs inducing CYP3A4 isoenzyme (rifampicin, phenazone, efavirenz, preparations of St. John’s Wort) may significantly reduce plasma concentration of atorvastatin. Mechanism of interaction with atorvastatin and other substrates of CYP3A4 isoenzyme is unknown; however, the possibility of these interactions should be considered when using drugs with low therapeutic index – in particular antiarrhythmic agents of class III, such as amiodarone.

Ezetemibe, fusidic acid

The risk of musculoskeletal adverse effects, including rhabdomyolysis, increases with concomitant use.

Hemfibrozil/fibrates

The risk of atorvastatin-induced myopathy may increase with concomitant use of fibrates. In vitro studies suggest that gemfibrozil may also interact with atorvastatin by inhibiting its glucuronidation, which may cause increased plasma concentrations of atorvastatin (see section “Cautions”).

Colestipol

When concomitant use with colestipol a decrease in plasma concentrations of atorvastatin by approximately 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 concentrations of atorvastatin by approximately 35%; however, LDL concentrations were not altered.

Phenazone

. When used concomitantly, atorvastatin does not affect the pharmacokinetics of phenazone, so it can be assumed that interactions with other drugs that are metabolized by the same cytochrome P450 isoenzymes are not expected.

Cimetidine

A study of concomitant use of cimetidine and atorvastatin showed no significant interaction between these drugs.

Amlodipine

No changes in equilibrium atorvastatin were detected when 80 mg atorvastatin and 10 mg amlodipine were used concomitantly.

Others

No clinically significant adverse interactions of atorvastatin and hypotensive agents were observed.

Atorvastatin had no clinically significant effect on plasma concentrations of terfenadine, which is metabolized by CYP3A4 isoenzyme. Therefore, it seems unlikely that atorvastatin can significantly affect pharmacokinetic parameters of other drugs that are metabolized by CYP3A4 isoenzyme.

Table 1. The effect of drugs on the pharmacokinetics of atorvastatin .When concomitant use

Effect of atorvastatin on other medications

Digoxin

The equilibrium plasma concentrations of digoxin did not change when digoxin and atorvastatin were repeated at a dose of 10 mg. However, when digoxin was used in combination with atorvastatin at a dose of 80 mg/day, digoxin concentrations increased by approximately 20%.

Internal contraceptives

. Concomitant use of atorvastatin with oral contraceptives containing norethisterone and ethinylestradiol has resulted in 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, there was a significant increase in AUC of norethisterone and ethinylestradiol by 30% and 20%, respectively. This effect should be considered when choosing an oral contraceptive for a woman receiving atorvastatin.

Warfarin

When concomitant use of atorvastatin with warfarin, a slight decrease in prothrombin time was observed in the first days of atorvastatin administration; However, in the next 15 days, prothrombin time returned to normal.

Table 2. Effects of atorvastatin on the pharmacokinetics of other drugs with concomitant use.

Special Instructions

Before using the drug Atorvastatin-Teva, the patient should start a standard hypocholesterol diet, which he should follow during the entire period of treatment.

The use of HMG-CoA reductase inhibitors to decrease blood lipid concentrations may lead to changes in biochemical parameters reflecting the functional state of the liver. Liver function should be monitored before the start of therapy, at 6 weeks, 12 weeks after the start of atorvastatin administration and after each dose increase, as well as periodically, e.g., every 6 months. Elevated serum hepatic transaminases may be observed during therapy with Atorvastatin-Teva. Patients with increased hepatic transaminases should be monitored until their activity decreases. In case of persistent increase of “hepatic” transaminases activity to the level more than 3 times higher than IUF, it is recommended to reduce the dose of Atorvastatin-Teva or discontinue treatment.

The drug Atorvastatin-Teva should be used with caution in patients who abuse alcohol and/or have a history of liver disease. Active liver disease or persistent increase in the activity of “hepatic” transaminases of unknown genesis are contraindications to the use of Atorvastatin-Teva.

Treatment with Atorvastatin-Teva, like other HMG-CoA reductase inhibitors, may cause myopathy. The diagnosis of myopathy should be considered in patients with widespread myalgia or muscle weakness and/or a marked increase in CPK activity (more than 10 times that of HGH). Patients should be warned to inform their physician immediately of unexplained muscle pain or weakness if accompanied by malaise or fever. Atorvastatin-Teva should not be started if baseline CPK level is 5 times higher than IGN (repeat in 5-7 days). In the course of therapy, if CPK level is more than 5 times of IGN or in the presence of confirmed or suspected myopathy, Atorvastatin-Teva should be interrupted with possible resumption of therapy when CPK activity decreases. The risk of myopathy during treatment with other drugs of this class was increased with concomitant use of cyclosporine, clarithromycin, delavirdine, stiripentol, ketoconazole, itraconazole, protease inhibitors, fibrates, erythromycin, nicotinic acid or azole antifungals. If the patient is receiving therapy with these drugs or there is a need for their use, it is required to adjust the dose of Atorvastatin-Teva.

The simultaneous use of Atorvastatin-Teva and fusidic acid is not recommended. If it is necessary to use fusidic acid, therapy with Atorvastatin-Teva should be temporarily stopped.

The CPK activity must be determined before starting therapy with Atorvastatin-Teva in patients with renal insufficiency, hypothyroidism, congenital skeletal muscle disease, toxicity with statins or fibrates, history of liver disease, alcoholism, over 70 years of age.

When using Atorvastatin-Teva in combination with fibrates, erythromycin, immunosuppressive agents, azole antifungal agents or nicotinic acid in lipid-lowering doses (more than 1 g per day), the possible risk and expected benefits of treatment should be carefully evaluated. During therapy with Atorvastatin-Teva it is necessary to monitor the appearance of complaints in patients about muscle pain or weakness, especially during the first months of treatment and during periods of increasing the dose of any drug. In such situations, periodic determination of CPK activity is recommended.

In Atorvastatin-Teva, as well as other drugs of this class, there have been cases of rhabdomyolysis with acute renal failure due to myoglobinuria. Therapy with Atorvastatin-Teva should be temporarily discontinued or completely stopped if there are signs of myopathy or there are risk factors for renal failure with rhabdomyolysis (for example, severe acute infection, arterial hypotension, extensive surgery and trauma, severe metabolic, endocrine and electrolyte disorders, uncontrolled convulsions).

There have been reports of interstitial lung disease (ILD) in patients treated with statins for a long time, manifested by cough, dyspnea and deterioration of general condition. If CHD develops, therapy with Atorvastatin-Teva should be discontinued.

Influence on driving and operating ability

No adverse effects of atorvastatin on driving and operating machinery have been reported.

Contraindications

• Hepatic hypersensitivity to the components of the drug;
• active liver disease or increased “liver” enzymes activity of unclear origin (more than 3 times the upper limit of normal);
• hepatic failure (degree of severity according to Child-Pugh classification A and B);
• pregnancy;
• breastfeeding period;
• age below 18 years (efficacy and safety not established);
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

With caution

. Alcohol abuse, history of liver disease, severe electrolyte balance disorders, endocrine and metabolic disorders, arterial hypotension, severe acute infections (sepsis), uncontrolled epilepsy, extensive surgery, trauma, skeletal muscle diseases.

Side effects

The frequency of side effects is classified according to the recommendations of the World Health Organization: very common – at least 10%; common – at least 1%, but less than 10%; infrequent – at least 0.1%, but less than 1%; rare – at least 0.01%, but less than 0.1%; very rare (including isolated cases) – less than 0.01%; frequency unknown – adverse reactions with unknown frequency.

With the blood and lymphatic system: rare – thrombocytopenia.

In the immune system: often – allergic reactions; very rare – angioedema; anaphylactic shock.

Nervous system: frequent – headache; infrequent – dizziness, paresthesia, hypoesthesia, amnesia, taste disturbance, insomnia, “nightmares” dreams; rare – peripheral neuropathy; frequency unknown – depression, memory loss or decline, depression, sleep disturbance.

Overlooking organ: infrequent – decreased clarity of vision; rarely – impairment of visual perception.

Hearing organ and labyrinth disorders: infrequent – “noise” in the ears, very rare – hearing loss.

As to the respiratory system, chest and mediastinum organs: frequent – nasopharyngitis, nasal bleeding, pain in the pharyngeal-larynx area; frequency unknown – interstitial lung disease.

Gastrointestinal disorders: frequently – nausea, flatulence, constipation, dyspepsia, diarrhea; infrequently – belching, vomiting, abdominal pain, pancreatitis.

Hepatic and biliary tract disorders: infrequent – hepatitis; rarely – cholestasis; very rare – liver failure.

Skin and subcutaneous tissue disorders: infrequent alopecia, skin rash, pruritus, urticaria; rarely – bullous dermatitis, erythema multiforme; very rare – Stevens-Johnson syndrome, toxic epidermal necrolysis.

Skeletal-muscular system and connective tissue: Frequent – myalgia, arthralgia, pain in the extremities, muscle spasm, back pain, joint swelling; infrequent – neck pain, muscle weakness; rare – myopathy, myositis, rhabdomyolysis, tendinopathy complicated by tendon rupture; frequency unknown – immune-mediated necrotizing myopathy.

Reproductive system: very rare – gynecomastia; frequency unknown – sexual dysfunction.

General disorders: infrequent – asthenia, weakness, chest pain, peripheral edema, increased body temperature, lethargy, weight gain, anorexia.

Laboratory parameters: frequently – hyperglycemia, increased serum creatine kinase activity; infrequently – leukocyturia, hypoglycemia, increased activity of “hepatic” transaminases; frequency unknown – increased concentration of glycolized hemoglobin.

Overdose

There is no specific antidote. In case of overdose, the necessary symptomatic and supportive therapy should be carried out. Control of liver function and serum CPK level is necessary. Hemodialysis is ineffective.

Pregnancy use

Atorvastatin is contraindicated in pregnancy and during breastfeeding. It is unknown whether atorvastatin is excreted with breast milk. Taking into account the possibility of adverse effects in breastfed children, if it is necessary to use the drug during lactation, breastfeeding should be discontinued. Women of reproductive age should use adequate contraception during treatment. Atorvastatin may be administered to women of reproductive age only if the probability of pregnancy in them is very low and the patient is informed about the possible risk of treatment for the fetus.

Similarities

Liprimar, Atoris, Tulip, Atorvastatin, Torvacard, Atorvastatin NW , Atorvastatin-Teva