Lipona (Tablets) Instructions for Use

Marketing Authorization Holder

Sedico South Egypt Drug Industries, Co. (Egypt)

ATC Code

C10AA05 (Atorvastatin)

Active Substance

Atorvastatin (Rec.INN registered by WHO)

Dosage Form

Lipona

Film-coated tablets, 10 mg: 10 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – blisters (1) – cardboard packs.

Clinical-Pharmacological Group

Hypolipidemic agent

Pharmacotherapeutic Group

Hypolipidemic agent – HMG-CoA reductase inhibitor

Pharmacological Action

Hypolipidemic agent from the statin group. By the principle of competitive antagonism, the statin molecule binds to the part of the coenzyme A receptor where HMG-CoA reductase attaches. Another part of the statin molecule inhibits the process of converting hydroxymethylglutarate into mevalonate, an intermediate product in the synthesis of the cholesterol molecule. Inhibition of HMG-CoA reductase activity leads to a series of sequential reactions, resulting in a decrease in intracellular cholesterol content and a compensatory increase in LDL receptor activity and, accordingly, an acceleration of LDL cholesterol (C) catabolism.

The hypolipidemic effect of statins is associated with a decrease in total C levels due to LDL-C. The reduction in LDL levels is dose-dependent and has an exponential, not linear, character. The inhibitory effect of atorvastatin on HMG-CoA reductase is approximately 70% determined by the activity of its circulating metabolites.

Statins do not affect the activity of lipoprotein and hepatic lipases, do not have a significant effect on the synthesis and catabolism of free fatty acids, so their effect on TG levels is secondary and mediated through their main effects of reducing LDL-C levels. The moderate decrease in TG levels during statin treatment is apparently associated with the expression of remnant (apo E) receptors on the surface of hepatocytes involved in the catabolism of IDL, which contain approximately 30% TG. Compared to other statins (except for rosuvastatin), Atorvastatin causes a more pronounced decrease in TG levels.

In addition to the hypolipidemic effect, statins have a positive effect on endothelial dysfunction (a preclinical sign of early atherosclerosis), on the vascular wall, the condition of the atheroma, improve the rheological properties of blood, and have antioxidant and antiproliferative properties.

Atorvastatin reduces cholesterol levels in patients with homozygous familial hypercholesterolemia, which usually does not respond to therapy with hypolipidemic agents.

Pharmacokinetics

Atorvastatin is rapidly absorbed from the gastrointestinal tract. The absolute bioavailability is low – about 12%, which is due to presystemic clearance in the gastrointestinal mucosa and/or due to first-pass metabolism in the liver, mainly at the site of action.

Atorvastatin is metabolized with the participation of the CYP3A4 isoenzyme to form a number of substances that are inhibitors of HMG-CoA reductase.

The plasma T_1/2 is about 14 hours, although the T_1/2 of HMG-CoA reductase inhibitor activity is approximately 20-30 hours, which is due to the participation of active metabolites.

Plasma protein binding is 98%.

Atorvastatin is excreted in the form of metabolites mainly with bile.

Indications

Primary hypercholesterolemia (heterozygous familial and non-familial hypercholesterolemia (Fredrickson type IIa); combined (mixed) hyperlipidemia (Fredrickson types IIa and IIb); dysbetalipoproteinemia (Fredrickson type III) (as an adjunct to diet); familial endogenous hypertriglyceridemia (Fredrickson type IV), resistant to diet; homozygous familial hypercholesterolemia with insufficient effectiveness of diet therapy and other non-pharmacological methods of treatment.

Primary prevention of cardiovascular complications in patients without clinical signs of coronary artery disease, but with several risk factors for its development – age over 55 years, nicotine dependence, arterial hypertension, diabetes mellitus, low plasma HDL-C concentrations, genetic predisposition, including against the background of dyslipidemia.

Secondary prevention of cardiovascular complications in patients with coronary artery disease in order to reduce the overall mortality rate, myocardial infarction, stroke, re-hospitalization for angina pectoris and the need for revascularization.

ICD codes

Dosage Regimen

Treatment is carried out against the background of a standard diet for patients with hypercholesterolemia. The dose is set individually, depending on the initial cholesterol level. It is taken orally. The initial dose is usually 10 mg once a day. The effect appears within 2 weeks, and the maximum effect – within 4 weeks. If necessary, the dose can be gradually increased at intervals of 4 weeks or more. The maximum daily dose is 80 mg.

Adverse Reactions

From the nervous system > 1% – insomnia, dizziness; < 1% - headache, asthenia, malaise, drowsiness, nightmares, paresthesia, peripheral neuropathy, amnesia, emotional lability, ataxia, facial nerve paralysis, hyperkinesis, migraine, depression, hypoesthesia, loss of consciousness.

From the sensory organs:< 1% - amblyopia, tinnitus, dryness of the conjunctiva, accommodation disturbance, retinal hemorrhage, deafness, glaucoma, parosmia, loss of taste sensations, taste perversion; frequency unknown - ocular myasthenia.

From the cardiovascular system: > 1% – chest pain; < 1% - palpitations, vasodilation symptoms, orthostatic hypotension, increased blood pressure, phlebitis, arrhythmia, angina pectoris.

From the hematopoietic system:< 1% - anemia, lymphadenopathy, thrombocytopenia.

From the respiratory system: > 1% – bronchitis, rhinitis; < 1% - pneumonia, dyspnea, exacerbation of bronchial asthma, epistaxis.

From the digestive system: > 1% – nausea; < 1% - 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, gum bleeding, tenesmus.

From the musculoskeletal system: > 1% – arthritis; < 1% - leg muscle cramps, bursitis, tenosynovitis, myositis, myopathy, arthralgia, myalgia, rhabdomyolysis, torticollis, muscle hypertonia, joint contractures, joint swelling, tendinopathy (in some cases with tendon rupture); frequency unknown - occurrence or exacerbation of myasthenia.

From the genitourinary system: > 1% – urogenital infections, peripheral edema; < 1% - dysuria (including pollakiuria, nocturia, urinary incontinence or retention, imperative urge to urinate), leukocyturia, nephritis, hematuria, vaginal bleeding, nephrourolithiasis, metrorrhagia, epididymitis, decreased libido, impotence, ejaculation disorder.

Dermatological reactions: > 1% – alopecia, xeroderma, photosensitivity, increased sweating, eczema, seborrhea, ecchymosis, petechiae.

From the endocrine system< 1% - gynecomastia, mastodynia.

From metabolism< 1% - weight gain, exacerbation of gout.

Allergic reactions:< 1% - skin itching, skin rash, contact dermatitis, rarely - urticaria, angioedema, facial edema, anaphylaxis, multiform exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).

Laboratory parameters:< 1% - hyperglycemia, hypoglycemia, increased serum CPK, albuminuria.

Contraindications

Active liver disease, unexplained increase in serum transaminase activity (more than 3 times the upper limit of normal), pregnancy, lactation (breastfeeding), women of reproductive age not using reliable contraception; children and adolescents under 18 years of age; hypersensitivity to atorvastatin.

Use in Pregnancy and Lactation

Atorvastatin is contraindicated for use during pregnancy and during lactation (breastfeeding).

It is not known whether Atorvastatin is excreted in breast milk. Given the possibility of adverse events in infants, if it is necessary to use the drug during lactation, the issue of stopping breastfeeding should be decided.

Women of reproductive age during treatment should use adequate methods of contraception. Atorvastatin can be used in women of reproductive age only if the probability of pregnancy is very low and the patient is informed about the possible risk of treatment for the fetus.

Use in Hepatic Impairment

Contraindication: active liver disease.

Before starting and during treatment with atorvastatin, especially when symptoms of liver damage appear, it is necessary to monitor liver function parameters. If transaminase levels increase, their activity should be monitored until normalization. If the activity of AST or ALT, more than 3 times the upper limit of normal, persists, a dose reduction or discontinuation of atorvastatin is recommended.

Pediatric Use

In children, experience with the use of atorvastatin at doses up to 80 mg/day is limited.

Special Precautions

Use with caution in patients who abuse alcohol; with a history of liver disease.

Before starting and during treatment with atorvastatin, especially when symptoms of liver damage appear, it is necessary to monitor liver function parameters. If transaminase levels increase, their activity should be monitored until normalization. If the activity of AST or ALT, more than 3 times the upper limit of normal, persists, a dose reduction or discontinuation of atorvastatin is recommended.

If symptoms of myopathy appear during treatment, CPK activity should be determined. If a significant increase in CPK levels persists, it is recommended to reduce the dose or discontinue Atorvastatin.

The risk of myopathy during treatment with atorvastatin increases with simultaneous use of cyclosporine, fibrates, erythromycin, antifungal drugs belonging to azoles, and niacin.

There is a possibility of developing the following adverse reactions, however, a clear connection with atorvastatin intake has not been established in all cases: muscle cramps, myositis, myopathy, paresthesia, peripheral neuropathy, pancreatitis, hepatitis, cholestatic jaundice, anorexia, vomiting, alopecia, itching, rash, impotence, hyperglycemia and hypoglycemia.

In children, experience with the use of atorvastatin at doses up to 80 mg/day is limited.

Atorvastatin is used with caution in patients with chronic alcoholism.

Drug Interactions

With simultaneous use of atorvastatin with digoxin, the plasma concentration of digoxin slightly increases.

Diltiazem, verapamil, isradipine inhibit the CYP3A4 isoenzyme, which is involved in the metabolism of atorvastatin, therefore, with simultaneous use with these calcium channel blockers, an increase in the plasma concentration of atorvastatin and an increased risk of myopathy are possible.

With simultaneous use of itraconazole, the plasma concentration of atorvastatin significantly increases, apparently due to inhibition of its metabolism in the liver by itraconazole, which occurs with the participation of the CYP3A4 isoenzyme; increased risk of myopathy.

With simultaneous use of colestipol, a decrease in the plasma concentration of atorvastatin is possible, while the hypolipidemic effect is enhanced.

With simultaneous use of antacids containing magnesium hydroxide and aluminum hydroxide, the concentration of atorvastatin is reduced by approximately 35%.

With simultaneous use of cyclosporine, fibrates (including gemfibrozil), antifungal drugs of the azole derivatives, nicotinic acid, the risk of myopathy increases.

With simultaneous use of erythromycin, clarithromycin, the plasma concentration of atorvastatin moderately increases, the risk of myopathy increases.

With simultaneous use of ethinyl estradiol, norethisterone (norethindrone), the plasma concentration of ethinyl estradiol, norethisterone and (norethindrone) slightly increases.

With simultaneous use of protease inhibitors, the plasma concentration of atorvastatin increases, because protease inhibitors are inhibitors of the CYP3A4 isoenzyme.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.