TULIP

Active material: Atorvastatin
When ATH: C10AA05
CCF: Lipid-lowering drugs
ICD-10 codes (testimony): E78.0, E78.2
When CSF: 16.01.01
Manufacturer: LEK d.d. (Slovenia)

DOSAGE FORM, COMPOSITION AND PACKAGING

Pills, coated white or nearly white, round, lenticular, with an inscription “HLA 10” on one side.

Excipients: microcrystalline cellulose, lactose monohydrate, Croscarmellose sodium, hydroksypropyltsellyuloza, polysorbate 80, magnesium oxide, heavy, colloidal silicon dioxide, magnesium stearate.

The composition of the shell: gipromelloza, gidropropilcelljuloza, Titanium dioxide (E171), polyethylene glycol 6000, talc.

10 PC. – blisters (3) – packs cardboard.

Pills, coated light yellow, round, lenticular, with an inscription “HLA 20” on one side.

Excipients: microcrystalline cellulose, lactose monohydrate, Croscarmellose sodium, hydroksypropyltsellyuloza, polysorbate 80, magnesium oxide, heavy, colloidal silicon dioxide, magnesium stearate.

The composition of the shell: gipromelloza, hydroksypropyltsellyuloza, Titanium dioxide (E171), polyethylene glycol 6000, talc, iron oxide yellow (E172).

10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (6) – packs cardboard.
10 PC. – blisters (9) – packs cardboard.

Pharmacological action

Lipid-lowering drugs of the statin. Selective competitive inhibitor of HMG-CoA reductase inhibitors, enzyme, participating in the transformation of 3-Hydroxy-3-metilgljutarilkojenzim and the mevalonat, which is the precursor of steroid, incl. cholesterol. Cholesterol (Hs) and triglycerides (TG) circulates in sossoudistom line comprising lipoprotein molecules. From TG and Xr are synthesized in the liver of VLDL, that of the liver get into blood plasma and delivered to the peripheral tissues. LDL is formed of VLDL, their catabolism is mainly through interaction with receptors, LDL.

Tulip^® impact synthesis and content in plasma LDL-Cholesterol, total Xc, Apolipoprotein in patients with homozygous and heterozygous Familial Hypercholesterolemia, primary hypercholesterolemia and mixed Hyperlipidemia. It was also a decrease in the level of Hs-VLDL and TG and increase levels of HS-HDL and apolipoprotein (a).

Atorvastatin reduces the total cholesterol, LDL-C, Hs-LPONP, apolipoprotein B, TG and non-HDL Cholesterol and increases the level of HDL Cholesterol in patients with isolated hypertriglyceridemia, CHS level-LPSP in patients with disbetalipoproteinemiej.

Tulip^® (dose 10 mg 20 mg) reduces level of overall Hs on 29% and 33%, XC-LDL- 39% and 43%, Apolipoprotein b is on 32% and 35%, triglycerides- 14% and 26%. CHS level this increases-lpvp respectively on 6% and 9%.

Pharmacokinetics

Absorption

Atorvastatin is almost completely absorbed after administration inwards; C_max achieved through 1-2 no. Although food reduces the rate and extent of absorption by approximately 25% and 9% respectively, However, CHS level of LDL cholesterol when taken on an empty stomach and atorvastatin during meals is reduced to the same extent. After administration of atorvastatin in the evening in the plasma levels below (C_max and AUC by approximately 30%), than after taking in the morning. Revealed a linear relationship between the degree of suction and dose of medication.

Bioavailability of atorvastatin is approximately 12%, and system bioavailability inhibiting activity against g-KOA-reduktaza-about 30%. Low system bioavailability due to presistemnym metabolism in GASTROINTESTINAL mucosa and/or “first pass” through the liver.

Distribution

Average V_d Atorvastatin is approximately 381 l. The degree of binding to plasma proteins – 98%.

Metabolism

Biotransformiroetsa mainly in the liver under the influence of izofermenta 3A4 zitohroma P450 with the formation of pharmacologically active metabolites: ortho- and para-hydroxylated derivatives and various products beta oxidation.

Deduction

Write mainly jelchew after liver and/or vnepechenochnogo metabolism (Atorvastatin is not subject to pronounced kishechno-pechenocna recycling, not displayed using hemodialysis). T_1/2 is 14 no. Inhibiting activity against g-KOA-reduktaza about 20-30 h thanks to active metabolites. Less 2% from the inside of the dosage is determined in the urine.

Pharmacokinetics in special clinical situations

Concentrations of atorvastatin significantly increases (C_max and AUC approximately 16 and 11 times, respectively,) in patients with alcoholic cirrhosis of the liver.

Testimony

- Primary Hypercholesterolemia (Fredrickson type IIa);

-mixed Hyperlipidemia (Fredrickson type IIb);

— geterozigotnaja and homozygous Familial Hypercholesterolemia (as an adjunct to diet).

Dosage regimen

Before treatment, the patient must be transferred to a diet low in cholesterol.

The drug is taken orally at any time of the day, regardless of the meal.

Therapeutic daily dose ranging from 10 to 80 mg; they picked on the basis of baseline LDL-Cholesterol, the goal of treatment effectiveness. Correction dose should be carried out at intervals of 4 of the week.

At primary hypercholesterolemia and mixed Hyperlipidemia The recommended starting dose is 10 mg 1 time / day. Then dose picked individually (in the range 10-80 mg / day) depending on the clinical situation (target cholesterol levels and the patient's response to therapy). Through 2-4 weeks after the start of therapy or dose adjustment should be carried out monitoring of the level of plasma lipids and adjust dose.

At heterozygous hypercholesterolemia is hereditary starting dose is 10 mg / day, possibly increasing doses up to 80 mg.

At Homozygous Familial Hypercholesterolemia the same doses applied range, the starting dose set depending on the patient's condition. The maximum daily dose – 80 mg.

To elderly patients (senior 70 years) dose adjustment is required.

Patients with impaired hepatic function the drug is prescribed with caution due to the slowdown of its removal from the body. This situation illustrates the control of clinical and laboratory parameters and the detection of significant lesions dose should be reduced or treatment should be discontinued.

Patients with impaired renal function dose adjustment is required.

Side effect

From the digestive system: in more 2% cases – nausea; less 2% cases – heartburn, constipation or diarrhea, flatulence, stomach ache, anorexia, decreased or increased appetite, dry mouth, belching, dysphagia, vomiting, stomatitis, esophagitis, glossitis, erosivno-azwenne defeat of oral cavity, gastroenteritis, hepatitis, želčnaâ how, cheilitis, duodenal ulcer, pancreatitis, cholestatic jaundice, abnormal liver function, ground, krovotochivosty right, tenesmus.

The respiratory system: in more 2% cases – bronchitis, rhinitis; rarely – pneumonia, dyspnoea, bronchial asthma, nosebleeds.

From the central and peripheral nervous system: in more 2% cases – insomnia, dizziness; less 2% cases – drowsiness, headache, asthenia, unusual dreams, malaise, amnesia, paresthesia, perifericheskaya neuropathy, emotional lability, ataxia, hyperkinesis, depression, giperesteziya, loss of consciousness, Bell's paralysis.

From the senses: less 2% cases – amblyopia, tinnitus, dryness of the conjunctiva, ccomodation, bleeding in the eye, deafness, increased intraocular pressure, loss of taste, dysgeusia, parosmija.

On the part of the musculoskeletal system: in more 2% cases – arthritis; less 2% cases – cramping of the leg muscles, ʙursit, tendosynovyt, myositis, myopathy, artralgii, myalgia, joint contractures, stiffness of neck muscles, raʙdomioliz.

Dermatological reactions: less 2% cases – alopecia, Sweating, eczema, seborrhea, ecchymosis, petechiae.

Allergic reactions: less 2% cases – itching, skin rash, contact dermatitis; rarely - urticaria, anaphylaxis, angioedema, erythema multiforme exudative, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), photosensitivity.

With the genitourinary system: in more 2% cases – urogenital infections, peripheral edema; less 2% cases – dizurija (incl. thamuria, nocturia, urinary incontinence or urinary retention, urgent need to urinate), jade, hematuria, vaginal bleeding, uterine bleeding, urolithiasis disease, epididymitis, decreased libido, impotence, abnormal ejaculation.

Cardio-vascular system: in more 2% cases – chest pain; less 2% cases – heartbeat, vasodilation, orthostatic hypotension, increased blood pressure, phlebitis, arrhythmia, angina.

From the hematopoietic system: less 2% cases – anemia, lymphadenopathy, thrombocytopenia.

From the laboratory parameters: less 2% cases – giperglikemiâ, gipoglikemiâ, increasing the level of CPK, albuminuria.

Other: less 2% cases – weight gain, gynecomastia, worsening of gout, mastodinija.

Contraindications

- Liver disease in active phase (incl. chronic active hepatitis, chronic alcoholic hepatitis);

- Liver failure (Classes A and B on the Child-Pugh);

- Increase in liver transaminases of unknown origin (more than 3 fold compared with CAH);

- Pregnancy;

- Lactation (breast-feeding);

- Hypersensitivity to the drug.

The drug is not prescribed to women of reproductive age, not using adequate contraception methods.

FROM caution You should assign Tulip^® when alcohol abuse, a history of liver disease, heavy violations elektrolitnogo balance, endocrine and metabolic irregularities, hypotension, severe acute infections (incl. sepsis), uncontrolled epilepsy, diseases of skeletal muscle, extensive surgery, injuries, as well as children.

Pregnancy and lactation

The use of drugs in pregnancy and lactation is contraindicated.

Cautions

In applying the drug control indicators of liver function should be carried out before starting therapy, through 6 weeks 12 weeks after the start of the reception and after each dose increase, and periodically (1 once every 6 Months). Usually, change in liver enzymes is celebrated during the first 3 months of therapy. Patients with increased activity transaminaz liver must be controlled before normalization of indicators. If ALT or AST exceed more than VGN 3 times, Atorvastatin dose should be reduced or the drug temporarily cancel.

Patients with diffuse myalgia, sluggishness or weakness of muscles and/or with a significant increase in CPK represent a risk group with respect to the Myo (Myalgia and concomitant increase in CPK in more than 10 times compared with FHG).

When it is necessary to carry out concomitant therapy ziklosporinom and atorvastatin is appropriate, fiʙratami, Erythromycin, clarithromycin, immunodepressantami and antifungal azoles drugs from the Group, as well as NICOTINAMIDE in lipid lowering doses should carefully correlate the anticipated benefits and potential risks of this treatment. When applying such combinations should carefully monitor patients for early detection of signs or symptoms of myalgia, half-heartedly, weakness (especially in the first months of treatment or when doses of drugs used together increase).

Treatment Tulipom^® should be suspended or fully lifted health development due to myopathy, and in the presence of risk factors for the development of acute renal failure due to rhabdomyolysis (in acute severe infectious diseases, hypotension, extensive surgery, severe endocrine or metabolic irregularities and violations elektrolitnogo balance).

The patient should be warned of the need to consult a doctor when you see unexplained pain, weakness in muscles, especially involving general malaise and fever.

Overdose

Treatment: There is no specific therapy; symptomatic therapy, activities for the maintenance of the vital functions of the organism and prevent further suction (gastric lavage, administration of activated charcoal). As atorvastatin significantly associated with blood plasma proteins, hemodialysis is ineffective.

Drug Interactions

In a joint application with antatidami, in the form of magnesium and aluminum hydroxide suspension atorvastatin concentration in plasma is reduced by approximately 35%, the degree of lowering the level of LDL-Cholesterol remains unchanged.

At the same time taking atorvastatin with colestipol concentration of atorvastatin in plasma is reduced by 25%, but the therapeutic effect of the combination of the above, than the effect of one drug.

When multiple simultaneous application of atorvastatin and digoxin concentration of plasma of blood is increased by 20% (This combination requires medical supervision).

While admission of atorvastatin with erythromycin (CYP3A4 inhibitor) Atorvastatin concentration in plasma is increased by approx. 40%.

Together with the use of oral contraceptives increased AUC of approximately 30% for norethisterone and 20% for ethinyl estradiol (It should be borne in mind when selecting contraceptives in women, receiving atorvastatin).

The use of atorvastatin patients, long-term receiving warfarin, in the early days may lead to an additional reduction of prothrombin time. This effect disappears after 15 days of simultaneously receiving these drugs (This combination requires more frequent control blood coagulability).

With simultaneous use of atorvastatin with cyclosporine, fiʙratami, clarithromycin, anti-fungal drugs from the group of azoles, NICOTINAMIDE atorvastatin concentration in plasma is increased, that increases the risk of myopathy.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 2 year. Do not use after the date of, indicated on the package.