Atorvastatin - instructions for use, dose, side effects, contraindications

Excipients: calcium carbonate, microcrystalline cellulose, lactose, Tween 80, hydroxypropylcellulose, crosscarmellose, magnesium stearate, hydroxypropylmethylcellulose, titanium dioxide, polyethylene glycol.

Description:

White round biconvex tablets, covered with a film sheath. On broken pills white or almost white.

Pharmacotherapeutic group:Hypolipidemic agent - inhibitor of HMG-CoA reductase

ATX: & nbsp

C.10.A.A Inhibitors of HMG-CoA reductase

C.10.A.A.05 Atorvastatin

Pharmacodynamics:

A hypolipidemic agent from the group of statins. The main mechanism of action of atorvastatin is the inhibition of the activity of 3-hydroxy-3-methylglutarylcoenzyme A- (HMG-CoA) reductase, an enzyme that catalyzes the conversion of HMG-CoA to mevalonic acid. This transformation is one of the early stages in the cholesterol synthesis chain in the body. Atorvastatin suppression of cholesterol synthesis leads to increased reactivity of LDL receptors (low density lipoproteins) in the liver, as well as in extrahepatic tissues. These receptors bind LDL particles and remove them from the blood plasma, which leads to a decrease in LDL cholesterol in the blood.

The antisclerotic effect of atorvastatin is a consequence of the effect of the drug on the walls of blood vessels and blood components. The drug inhibits the synthesis of isoprenoids, which are the growth factors of the cells of the inner shell of the vessels. Under the influence of atorvastatin, the endothelium-dependent dilatation of blood vessels improves. Atorvastatin reduces the content of cholesterol, low-density lipoproteins, apolipoprotein B, triglycerides. Causes an increase in the content of HDL cholesterol (high-density lipoproteins) and apolipoprotein A.

The effect of the drug, as a rule, develops after 2 weeks of taking, and the maximum effect is achieved in four weeks.

Pharmacokinetics:

Absorption is high. Time to reach the maximum concentration - 1-2 hours, the maximum concentration in women is higher by 20%, AUC (the area under the curve) is lower by 10%, the maximum concentration in patients with alcoholic liver cirrhosis is 16 times, AUC - 11 times higher than normal. Food slightly reduces the speed and duration of absorption of the drug (by 25% and 9%, respectively), but the reduction in LDL cholesterol is similar to that with atorvastatin without food. The concentration of atorvastatin when used in the evening is lower than in the morning (about 30%). A linear relationship between the degree of absorption and the dose of the drug has been revealed.

Bioavailability - 14%, systemic bioavailability of inhibitory activity against HMG-CoA reductase - 30%. Low systemic bioavailability is due to presystemic metabolism in the mucous membrane of the gastrointestinal tract and "first pass" through the liver.

The average volume of distribution is 381 liters, the connection with plasma proteins is 98%. Metabolized mainly in the liver under the influence of cytochrome P450 CYP3A4, CYP3A5 and CYP3A7 with the formation of pharmacologically active metabolites (ortho- and para-hydroxylated derivatives, beta-oxidation products). The inhibitory effect of the drug against HMG-CoA reductase is approximately 70% determined by the activity of circulating metabolites.

It is excreted with bile after hepatic and / or extrahepatic metabolism (it does not undergo significant intestinal hepatic recirculation).

The elimination half-life is 14 hours. The inhibitory activity against HMG-CoA reductase is maintained for about 20-30 hours, due to the presence of active metabolites. Less than 2% of the dose taken internally is determined in the urine.

It is not excreted during hemodialysis.

Indications:

Primary hypercholesterolemia, mixed hyperlipidemia, heterozygous and homozygous familial hypercholesterolemia (as a supplement to the diet).

Contraindications:

Hypersensitivity to any of the components of the drug, liver disease in the active stage (including active chronic hepatitis, chronic alcoholic hepatitis),an increase in the activity of "liver" transaminases (more than 3 times in comparison with the upper limit of the norm) of unclear genesis, hepatic insufficiency (A and B severity in the Child-Puga system), cirrhosis of any etiology, pregnancy, lactation, age 18 years (efficacy and safety of use not established).

Carefully:

Liver disease in history, severe electrolyte imbalance, endocrine and metabolic disorders, alcoholism, arterial hypotension, severe acute infections (sepsis), uncontrolled convulsions, extensive surgical interventions, trauma.

Pregnancy and lactation:Contraindicated.

Dosing and Administration:

Before starting treatment with atorvastatin, the patient should be transferred to a diet that provides a reduction in lipid levels in the blood, which must be observed during treatment with the drug.

Inside, take at any time of the day (but at the same time), regardless of food intake.

The recommended initial dose is 10 mg once a day. Then the dose is selected individually depending on the content of cholesterol - LDL. Change the dose should be at intervals of at least 4 weeks.The maximum daily dose is 80 mg per 1 dose.

Primary (heterozygous hereditary and gender and gene) hypercholesterolemia (type IIa) and mixed hyperlipidemia (type IIb).

Treatment begins with the recommended initial dose, which is increased after 4 weeks of therapy, depending on the patient's reaction. The maximum daily dose is 80 mg.

Dhomozygous hereditary hypercholesterolemia.

The range of doses is the same as for other types of hyperlipidemia. The initial dose is selected individually depending on the severity of the disease. In most patients with homozygous hereditary hypercholesterolemia, the optimal effect is observed when the drug is used in a daily dose of 80 mg (once).

In patients with renal insufficiency and in elderly patients correction of doses of atorvastatin is not required.

Have patients with impaired liver function care should be taken in connection with the delay in removing the drug from the body. Clinical and laboratory indicators should be closely monitored and, if significant pathological changes are detected, the dose should be reduced or treatment should be discontinued.

Side effects:

Co side of the nervous system: in more than 2% of cases - insomnia, dizziness; in less than 2% of cases - headache, asthenic syndrome, malaise, drowsiness, nightmarish dreams, amnesia, paresthesia, peripheral neuropathy, emotional lability, ataxia, facial nerve paralysis, hyperkinesia, depression, hyperesthesia, loss of consciousness.

Co side of the senses: amblyopia, ringing in the ears, dryness of the conjunctiva, disruption of accommodation, eye bleeding, deafness, glaucoma, parosmia, loss of taste sensations, perversion of taste.

Co hand cardiovascular system: in more than 2% of cases - chest pain; in less than 2% of cases - palpitations, vasodilation, migraine, postural hypotension, increased blood pressure, phlebitis, arrhythmia, angina.

Co hematopoiesis side: anemia, lymphadenopathy, thrombocytopenia.

Co the respiratory system: in more than 2% of cases - bronchitis, rhinitis; in less than 2% of cases - pneumonia, dyspnea, bronchial asthma, nosebleeds.

Co side of the digestive system: in more than 2% of cases - nausea; heartburn, constipation or diarrhea, flatulence, gastralgia, abdominal pain,anorexia or increased appetite, dry mouth, belching, dysphagia, vomiting, stomatitis, esophagitis, glossitis, erosive and ulcerative lesions of the oral mucosa, gastroenteritis, hepatitis, hepatic colic, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, dysfunction liver, rectal bleeding, melena, bleeding gums, tenesmus.

Co side of the musculoskeletal system: in more than 2% of cases - arthritis; in less than 2% cases - leg muscle cramps, bursitis, tendosinovitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, torticollis, muscle hypertonia, joint contractures.

Co the side of the genitourinary system: in more than 2% of cases - urogenital infections, peripheral edema; in less than 2% cases - dysuria (including pollakiuria, nocturia, urinary incontinence or urinary retention, mandatory urges to urinate), nephritis, hematuria, vaginal bleeding, nephrourolythiasis, metrorrhagia, epididymitis, decreased libido, impotence, ejaculatory impairment.

Co skin: in less than 2% of cases - alopecia, xeroderma, increased sweating, eczema, seborrhea, ecchymosis, petechiae.

Allergic reactions: in less than 2% of cases - skin itch, skin rash, contact dermatitis, rarely urticaria, angioedema, facial edema, photosensitivity, anaphylaxis, multiforme exudative erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

Laboratory indicators: in less than 2% of cases - hyperglycemia, hypoglycemia, increased serum creatine phosphokinase, alkaline phosphatase, albuminuria, increased alanine aminotransferase (ALT) or asparagine aminotransferase.

Other: in less than 2% of cases - weight gain, gynecomastia, mastodynia, exacerbation of gout.

Overdose:

Treatment. There is no specific antidote. Symptomatic therapy is performed. Take measures to maintain vital body functions and measures to prevent further absorption of the drug: gastric lavage, the reception of activated charcoal. Hemodialysis is not effective.

When there are signs and presence of risk factors for the development of acute liver failure against rhabdomyolysis (a rare but severe side effect), the drug should be immediately withdrawn.

Because the Atorvastatin is largely associated with blood plasma proteins, hemodialysis is an ineffective way of removing this substance from the body.

Interaction:

With the simultaneous administration of cyclosporine, fibrates, erythromycin, clarithromycin, immunosuppressive, antifungal drugs (relating to azoles) and nicotinamide, the concentration of atorvastatin in plasma (and the risk of myopathy) is increasing.

Antacids reduce the concentration by 35% (the effect on the content of LDL cholesterol does not change).

The simultaneous use of atorvastatin with protease inhibitors, known as cytochrome P450 inhibitors CYP3A4, is accompanied by an increase in the concentration of atorvastatin in plasma.

When digoxin is used in combination with atorvastatin at a dose of 80 mg / day, the digoxin concentration increases by about 20%.

Increases the concentration by 20% (when administered with atorvastatin at a dose of 80 mg / day) of oral contraceptives containing norethindrone and ethinyl estradiol. The hypolipidemic effect of the combination with colestipol exceeds that for each drug alone.

With simultaneous administration with warfarin in the early days, prothrombin time decreases,but after 15 days this indicator is normalized. In this regard, patients receiving atorvastatin with warfarin should be more often than usual to monitor prothrombin time.

The consumption of grapefruit juice during treatment with atorvastatin may lead to an increase in the concentration of the drug in the blood plasma. In this regard, patients taking the drug should avoid the use of this juice.

Special instructions:

Impaired liver function

The use of HMG-CoA reductase inhibitors to reduce lipid levels in the blood can lead to a change in biochemical indicators that reflect liver function.

The liver function should be monitored before treatment, 6 weeks, 12 weeks after the start of Atorvastatin and after each dose increase, and periodically, for example, every 6 months. The change in the activity of liver enzymes is usually observed during the first three months after the initiation of Atorvastatin. Patients with elevated transaminase levels should be monitored until the enzyme level returns to normal. If the values of alanine aminotransferase (ALT) or asparagine aminotransferase (ACT) more than 3 times higher than the upper limit, it is recommended to reduce the dose of atorvastatin or stop treatment.

Skeletal musculature

Patients with diffuse myalgia, lethargy or muscle weakness and / or a significant increase in CK are a risk group for the development of myopathy (defined as muscle pain with concomitant increase in the level of CK more than 10 times the upper limit of the norm).

When prescribing combined therapy with atorvastatin with cyclosporine, fibrolic acid derivatives, erythromycin, clarithromycin, immunosuppressants, and antifungal azole preparations, and also causing a decrease in lipid levels by doses of niacin, it is necessary to compare the potential benefit and the degree of risk with this treatment and monitor patients with which show signs or symptoms of muscle pain, lethargy or weakness, especially during the first months of treatment and with an increase in the dose of some of drugs.

Treatment with atorvastatin should be temporarily suspended or discontinued with the development of a severe condition that may be a consequence of myopathy,and also in the presence of risk factors for the development of acute renal failure due to rhabdomyolysis (for example, acute severe infection, arterial hypotension, extensive surgery, trauma, severe metabolic and endocrine disorders, and electrolyte imbalance).

In women of reproductive age who do not use reliable contraception, the use of Atorvastatin is not recommended. If the patient is planning a pregnancy, she should stop taking atorvastatin at least a month before the planned pregnancy.

The patient should immediately consult a doctor if unexplained pain or weakness in the muscles occurs, especially if accompanied by malaise and fever.

Effect on the ability to drive transp. cf. and fur:

Atorvastatin's adverse effect on the ability to drive and work with mechanisms requiring increased attention has not been reported.

Form release / dosage:

Tablets coated with 10 mg and 20 mg.

Packaging:

For 7, 10 or 14 tablets in Al / PVC blisters.

For 1,2, 3, 4 blisters in a cardboard pack together with instructions for use.

Storage conditions:

List B.In a dry, protected place at a temperature below 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Obsolete name of the trade product: & nbspLiptonorm®

Registration number:П N016155 / 01

Date of registration:03.12.2009 / 26.01.2017

Expiration Date:Unlimited

The owner of the registration certificate:M. J. Biofarm Pvt. Ltd.M. J. Biofarm Pvt. Ltd. India

Manufacturer: & nbsp

M.J. BIOPHARM, Pvt. Ltd. India

Representation: & nbspM.J. BIOFARM Pvt. Ltd. division of the corporation MJ Group M.J. BIOFARM Pvt. Ltd. division of the corporation MJ Group India

Information update date: & nbsp11.04.2018

Illustrated instructions

Instructions

Atorvastatin (Atorvastatin)