Atorvastatin (40 mg) Atorvastatin

Atorvastatin 40 mg - sethethefatsi se fokotsang lipid sehlopheng sa li-statins. Mochine oa ts'ebetso oa sethethefatsi o etselitsoe ho theola cholesterol ea mali

Letlapa le leng le koahetsoeng ka lifilimi le na le:

• ntho e sebetsang: atorvastatin calcium trihydrate (ho latela atorvastatin) - 40.0 mg,
• excipients: microcrystalline cellulose - 103.72 mg, lactose monohydrate - 100.00 mg, calcium carbonate - 20.00 mg, crospovidone - 15.00 mg, sodium carboxymethyl starch (sodium starch glycolate) - 9,00 mg, hyprolose (hydroxypropyl cellulose) - 6, .00 mg, magnesium stearate - 3,00 mg,
• Coating ea lifilimi: hypromellose - 4 500 mg, talc - 1,764 mg, hyprolysis (hydroxypropyl cellulose) - 1,746 mg, titanium dioxide - 0,990 mg kapa motsoako o omileng bakeng sa koaetso ea lifilimi e nang le hypromellose (50.0%), talc (19.6%), hyprolose (hydroxypropyl cellulose) (19.4%), titanium dioxide (11.0%) - 9,000 mg.

Matlapa a biconvex a pota-potileng, a koahetsoeng ka bo bosoeu kapa a soeufetse. Karolo ea sefapano sa mantlha e tšoeu kapa e batla e tšoeu.

Mofumahali

Atorvastatin ke inhibitor e khethiloeng ea HMG-CoA reductase, enzyme ea bohlokoa e fetolang 3-hydroxy-3-methylglutaryl-CoA ho mevalonate, selelekela sa li-steroid, ho kenyelletsa cholesterol. Synthetic lipid-e fokotsa moemeli.

Ho bakuli ba nang le homozygous le heterozygous Famer hypercholesterolemia, mekhoa eo e seng ea lelapa e amanang le hypercholesterolemia le dyslipidemia e kopaneng, atorvastatin e fokotsa khatello ea cholesterol e felletseng (pl) maling. Low-density lipoprotein cholesterol (Cs-LDL) le apolipoprotein B (apo-B), hammoho le pokello ea lipoprotein tse tlase haholo (Cs-VLDL) le triglycerides (TG), e baka keketseho ea khoholeho ea choleopolotein e phahameng-density (Cs-HD).

Atorvastatin e fokotsa mokokotlo oa Chs le Chs-LHNP ka plasma ea mali, e thibelang ho fokotsoa ha HMG-CoA le cholesterol ka har'a sebete le ho eketsa palo ea li-receptor tsa "LIL" tsa LDL holim'a sele, e lebisang ho ho nyoloheng le ho rarahana ha Chs-LDL.

Atorvastatin e fokotsa tlhahiso ea LDL-C le palo ea likaroloana tsa LDL, e baka keketseho e tsitsitseng le e phehellang ea tšebetso ea LDL-receptors hammoho le liphetoho tse ntle tsa boleng ba li-LDL-particle, hape e fokotsa khatello ea methapo ea LDL-C ho bakuli ba nang le lefu la homozygous heredicial Famal hypercholesterolemia. ho bolela.

Atorvastatin ka tekanyetso ea 10 ho isa ho 80 mg e fokotsa khatello ea Chs ka 30-46%, Chs-LDL - ka 41-61%, apo-B - ka 34-50% le TG - ka 14-33%. Liphetho tsa kalafo lia tšoana ho bakuli ba nang le heterozygous Familia hypercholesterolemia, mefuta eo e seng ea lelapa ea hypercholesterolemia le hyperlipidemia e kenyeletsang ho bakuli ba nang le lefu la tsoekere la mofuta oa 2.

Ho bakuli ba nang le hypertriglyceridemia e ka thoko, atorvastatin e fokotsa bongata ba cholesterol e felletseng, Chs-LDL, Chs-VLDL, apo-B le TG mme e eketsa bongata ba Chs-HDL. Ho bakuli ba nang le dysbetalipoproteinsemia, atorvastatin e theola khatello ea methapo ea methapo ea methapo ea methapo ea methapo ea methapo ea methapo ea methapo ea methapo ea methapo ea methapo ea methapo (Chs-STD).

Ho bakuli ba nang le mofuta oa IIa le IIb hyperlipoproteinemia ho latela sebopeho sa Fredrickson, boleng ba karolelano ea ho eketsa mahloriso a HDL-C nakong ea kalafo le atorvastatin (10-80 mg) ha bo bapisoa le boleng ba pele ke 5.1-8.7% mme ha bo itšetlehe ka tekanyetso. Ho na le ho fokotseha ho hoholo hoa tekanyo ea tekanyetso ho karolelano: cholesterol e felletseng / Chs-HDL le Chs-LDL / Chs-HDL ka 29-44% le 37-55%, ka ho latellana.

Atorvastatin ka tekanyo ea 80 mg e fokotsa haholo menyetla ea ho ba le mathata a ischemic le lefu ka 16% kamora thupelo ea libeke tse 16, le kotsi ea ho kenngoa sepetlele hape bakeng sa angina pectoris e tsamaeang le matšoao a ischemia ea myocardial ke 26%. Ho bakuli ba nang le mefuta e fapaneng ea mantlha ea LDL-C (e nang le myocardial infarction ntle le Q wave le angina e sa tsitsitseng ho banna, basali, le bakuli ba ka tlase ho lilemo tse 65), atorvastatin e baka ho fokotseha hoa menyetla ea mathata a ischemic le lefu.

Ho fokotseha ha methapo ea kutlo ea plasma ea LDL-C e kopantsoe hantle le lethalinyana la atorvastatin ho feta ka mahloriso a lona a plasma. Tekanyetso e khethoa ho latela ts'ebetso ea kalafo (bona karolo "Karolo le tsamaiso").

Phello ea kalafo e fumanoa libeke tse 2 kamora ho qala kalafo, e fihla hofihlella kamora libeke tse 4 mme e phehella nakong eohle ea kalafo.

Suction

Atorvastatin e kenella ka potlako ka mor'a taolo ea molomo: nako ea ho fihlela khatello ea eona e phahameng (TCmax) plasma ea mali ke lihora tse 1-2. Ho basali, tekanyo e phahameng ea atorvastatin (Cmax) e phahame ka 20%, 'me sebaka se tlas'a mookotaba oa nako ea mahloriso (AUC) se tlase ka 10% ho feta ho banna. Tekanyo ea ho amoheloa le ho kenngoa ha plasma ea mali e eketseha ka tekanyo ea lethal dose. Bioavailability e felletseng e ka ba 14%, 'me ts'ebetso ea bioavailability ea ts'ebetso ea inhibitory e khahlano le HMG-CoA reductase e ka ba 30%. Bioavailability e tlase e bakoa ke metabolism ea "presystemic metabolism" mucous membrane ea makhophong a ka mpeng le / kapa nakong ea "karolo ea mantlha" ka har'a sebete. Ho ja hanyane ho fokotsa sekhahla le tekanyo ea ho amoheloa ha atorvastatin (ka 25% le 9%, ka ho latellana, joalo ka ha ho pakoa ke litholoana tsa qeto ea Cmax le AUC), leha ho le joalo, ho fokotseha ha LDL-C ho tšoana le ha atorvastatin ka mpeng e se nang letho. Leha taba ea hore kamora ho nka atorvastatin ka shoalane khatello ea eona ea plasma e tlase (Cmax le AUC ka 30%) ho feta kamora ho e nka hoseng, ho fokotseha hoa khatello ea LDL-C ha hoa itšetleha ka nako ea letsatsi leo moriana o nooang ka lona.

Metabolism

Atorvastatin e thehiloe ka mokhoa o matla ho theha litokollo tsa ortho- le para-hydroxylated le lihlahisoa tse fapaneng tsa beta-oxidation. In vitro, ortho- le para-hydroxylated metabolites li na le phello e thibelang ho fokotsoa ha HMG-CoA, ho bapisoa le atorvastatin. Ts'ebetso ea inhibitory Khahlano le HMG-CoA reductase e batla e le 70% ka lebaka la ts'ebetso ea metabolites ea potoloho. Liphuputso tsa in vitro li bontša hore lera la enzyme CYP3A4 le bapala karolo ea bohlokoa ho metabolism ea atorvastatin. Sena se netefatsoa ke keketseho ea khatello ea atorvastatin maling a mali a motho ha a ntse a nka erythromycin, e leng thibelo ea isoenzyme ena.

Boithuto ba inro le bona bo bonts'itse hore atorvastatin ke inhibitor e fokolang ea CYP3A4 isoenzyme. Atorvastatin e ne e se na phello e kholo ea bongaka molemong oa plasma ea terfenadine, e ntlafalitsoeng haholo ke CYP3A4 isoenzyme, ka hona, phello ea eona e kholo ho li-pharmacokinetics tsa likarolo tse ling tsa CYP3A4 isoenzyme ha e na monyetla (bona karolo "Tšebelisano le lithethefatsi tse ling").

Atorvastatin le metabolites ea eona li qhekelloa haholo ka bile kamora metabolism ea hepatic le / kapa extrahepatic (atorvastatin ha e ts'oaroe ka mokhoa o matla oa ho bala. Bophelo ba halofo (T1 / 2) e ka ba lihora tse 14, ha phello ea inoritastatin mabapi le phokotso ea HMG-CoA e batla e le 70% e hlalositsoeng ke ts'ebetso ea potoloho ea metabolites mme e nka lihora tse ka bang 20-30 ka lebaka la boteng ba eona. Kamora ho sebelisa moriana ka moroto, ho fumanoe ka tlase ho 2% ea litekanyetso tsa moriana tse amoheloang.

Matšoao a ho sebelisoa

• e le tlatsetso ea lijo ho fokotsa cholesterol e phahameng e phahameng, LDL-C, apo-B, le triglycerides ho batho ba baholo, bacha le bana ba lilemo tse 10 kapa ho feta ba nang le hypercholesterolemia, ho kenyeletsa hypercholesterolemia ea lelapa (mofuta oa heterozygous) kapa mofuta o kopaneng (hyperlipidemia ( mefuta IIa le IIb ho latela sehlopha sa Fredrickson), ha karabelo ea lijo le litlhare tse ling tse sa sebeliseng lithethefatsi li sa lekana,
• ho fokotsa cholesterol e felletseng, LDL-C ho batho ba baholo ba nang le homozygous Famal hypercholesterolemia e le adjunct ho mefuta e meng ea phekolo e fokotsang lipid (isib. LDL-apheresis) kapa, haeba kalafo tse joalo li sa fumanehe.

Thibelo ea Maloetse a amanang le pelo le pelo:

• thibelo ea liketsahalo tsa pelo ho bakuli ba baholo ba kotsing e kholo ea ho etsa liketsahalo tsa mantlha tsa pelo, ho kenyelletsa khalemelo ea mabaka a mang a kotsi.
• Thibelo ea bobeli ea mathata a pelo le pelo ho bakuli ba nang le lefu la pelo hore a fokotse palo ea batho ba shoang, lefu la myocardial, stroke, ho kenella sepetlele bakeng sa angina pectoris le tlhokeho ea ho nchafatsoa.

Contraindication

Contraindication mabapi le tšebeliso ea atorvastatin ke:

• hypersensitivity ho atorvastatin le / kapa eng kapa eng ea likarolo tsa moriana,
• lefu le mafolofolo la sebete kapa tšebetso e eketsehang ea "sebete" transaminase maling a mali a sa tsejoeng makhetlo a fetang a mararo ha a bapisoa le moeli o holimo oa tloaelo.
• cirrhosis ea sebete sa etiology efe kapa efe,
• sebelisa basali ba lilemo tsa ho ba le bana ba sa sebeliseng mekhoa e lekaneng ea ho thibela pelehi,
• Tšebeliso e kopane le fusidic acid,
• lilemo ho isa ho lilemo tse 10 - bakeng sa bakuli ba nang le heterozygous Familyal hypercholesterolemia,
• lilemo ho fihlela lilemo tse 18 ha li sebelisoa ho latela lipontšo tse ling (ho sebetsa hantle le polokeho ea tšebeliso ha li e-so theoe),
• boimana, ho anyesa
• ho se mamelle lactose, khaello ea lactase, malabsorption ea glucose-galactose.

Atorvastatin e ka fuoa mosali ea lilemo tsa ho ba le bana ha feela ho tsebahala hore ha a ima le ho tsebisoa ka kotsi e ka bang teng ea lithethefatsi ho lesea.

Ka tlhokomeliso: tšebeliso e mpe ea joala, nalane ea lefu la sebete, ho bakuli ba nang le mabaka a ho ba le rhabdomyolysis (ts'ebetso ea mokokotlo oa mokokotlo, hypothyroidism, lefu la mesifa ea lefutso ho bakuli ba nang le nalane kapa nalane ea lelapa, litlamorao tse chefo tsa HMG reductase inhibitors kapa fibrate ka mesifa e se e bile tishu, lilemo tse fetang lilemo tse 70, tšebeliso e le 'ngoe ka lithethefatsi tse eketsang kotsi ea myopathy le rhabdomyolysis

Tekanyetso le tsamaiso

Ka hare. Nka ka nako efe kapa efe ea letsatsi, ho sa tsotelehe lijo tse jang.

Pele o qala kalafo le Atorvastatin, o lokela ho leka ho fihlela taolo ea hypercholesterolemia o sebelisa ho ja, ho ikoetlisa le ho theola boima ba 'mele ho bakuli ba nang le botenya, hammoho le kalafo ea lefu lena le tlase.

Ha u fana ka litlhare, mokuli o lokela ho buella phepo e tloaelehileng ea hypocholesterolemic, eo a tlamehang ho e latela nako eohle ea kalafo.

Tekanyo ea lithethefatsi e fapana ho tloha ho 10 mg ho isa ho 80 mg hang ka letsatsi mme e kenyelitsoe ho latela khatello ea mantlha ea LDL-Xc, sepheo sa pheko le phello ea motho ka mong kalafong. Tekanyetso e phahameng ea letsatsi le letsatsi ea lithethefatsi ke 80 mg.

Qalong ea kalafo le / kapa nakong ea keketseho ea tekanyetso ea Atorvastatin, ho hlokahala hore ho be le ho lekola mokokotlo oa lipids ka har'a plasma ea mali ka mor'a libeke tse ling le tse ling tse 2 le ho fetola lethal dose ho latela.

Heterozygous Familia hypercholesterolemia

Motsoako oa pele ke 10 mg ka letsatsi. Tekanyetso e lokela ho khethoa ka bonngoe le ho lekola ho tšoaneleha ha eona libeke tse ling le tse ling tse nne ka keketseho e ka bang teng ea 40 mg ka letsatsi. Ebe moriana o ka eketsoa ho fihla ho 80 mg ka letsatsi, kapa motsoako oa li-acid tse sebelisitsoeng ka nako e le 'ngoe ka ts'ebeliso ea atorvastatin ka tekanyetso ea 40 mg ka letsatsi e ka khonahala.

Sebelisa ho bana le lilemong tsa bocha ho tloha ho lilemo tse 10 ho isa ho tse 18 ka heterozygous Familyal hypercholesterolemia

Motsoako oa ho qala o khothalelitsoeng ke 10 mg hang ka letsatsi. Tekanyetso e ka eketsoa ho 20 mg ka letsatsi, ho latela phello ea kliniki. Phihlelo ea lethal dose e fetang 20 mg (e lekanang le tekanyetso ea 0.5 mg / kg) e lekanyelitsoe. Hoa hlokahala ho kenyelletsa lethal dose la moriana ho latela sepheo sa ho fokotsa lipid. Phetoho ea litekanyetso li lokela ho etsoa nako le nako ka nako ea 1 ka libeke tse 4 kapa ho feta.

Sebelisa hammoho le lithethefatsi tse ling

Haeba ho hlokahala, ts'ebeliso e le 'ngoe le cyclosporine, telaprevir kapa motsoako oa tipranavir / ritonavir, tekanyetso ea lithethefatsi Atorvastatin ha ea lokela ho feta 10 mg ka letsatsi.

Ho lokela hore ho sebelisoe tlhokomeliso 'me ho sebelisoe lethalose le sebetsang ka ho fetisisa la atorvastatin ha le ntse le sebelisoa le li-inhibitors tsa HIV, hepatitis C virusase protease inhibitors (boceprevir), clarithromycin le itraconazole.

Litlamorao

Ha u nka Atorvastatin, litla-morao tse latelang li ka hlaha:

• Ho tsoa ts'ebetsong ea methapo: ho hloka boroko, ho opeloa ke hlooho, asthenic syndrome, malaise, kizunguzungu, peripheral neuropathy, amnesia, paresthesia, hypesthesia, khatello ea maikutlo.
• Ho tsoa ho tsamaiso ea tšilo ea lijo: ho nyekeloa ke pelo, lets'ollo, bohloko ba ka mpeng, dyspepsia, flatulence, ho qhekella, ho hlatsa, ho ipolaisa tlala, hepatitis, pancreatitis, cholestatic jaundice.
• Ho tsoa ts'ebetsong ea musculoskeletal: myalgia, bohloko ba morao, arthralgia, mesifa ea mokokotlo, myositis, myopathy, rhabdomyolysis.
• Litlamorao: urticaria, pruritus, lekhopho la letlalo, lekhopho le bolaeang, anaphylaxis, polymorphic exudative erythema (ho kenyeletsoa le Stevens-Johnson syndrome), lefu la Laille.
• Ho tsoa lithong tsa hemopoietic: thrombocytopenia.
• Ho tloha lehlakoreng la metabolism: hypo- kapa hyperglycemia, ts'ebetso e eketsehileng ea serum CPK.
• Ho tsoa ts'ebetsong ea endocrine: lefu la tsoekere "mellitus" - khafetsa ea nts'etsopele e tla ipapisa le ho ba teng kapa ho se be teng hoa lintho tse ka behang kotsi (glucose e potlakileng ≥ 5.6, index ea 'mele> 30 kg / m2, keketseho ea li-triglycerides, nalane ea khatello ea mali e matla).
• Tse ling: tinnitus, mokhathala, ho hlobaela ka thobalano, edema e potolohang, boima ba sefuba, bohloko ba sefuba, alopecia, linyeoe tsa nts'etsopele ea maloetse a mahareng, haholo-holo ka ts'ebeliso ea nako e telele, lefu la hemorrhagic (ha le nooa ka tekanyetso e phahameng le ka CYP3A4 inhibitors). ho hloleha.

Matšoao a overdose

Matšoao a khethehileng a overdose ha a e-so fumanoe. Matšoao a ka kenyelletsa bohloko sethong sa sebete, ho hloleha ha renal haholo, tšebeliso ea nako e telele ea myopathy le rhabdomyolysis.

Haeba ho na le overdose, ho hlokahala mehato e latelang ka kakaretso: ho lekola le ho boloka mesebetsi ea bohlokoa ea 'mele, le ho thibela ho ts'oaroa ha lithethefatsi ka mokhoa o mong (gastric lavage, ho nka mashala a ts'ebetso kapa a laxatives).

Ka nts'etsopele ea myopathy, e lateloang ke rhabdomyolysis le ho hloleha ha methapo ea methapo, setlhare se lokela ho hlakoloa hang-hang mme infusion ea diuretic le sodium bicarbonate e qale. Rhabdomyolysis e ka lebisa ho hyperkalemia, e hlokang tsamaiso e kenang ea tharollo ea calcium chloride kapa tharollo ea calcium gluconate, infusion ea tharollo ea 5% ea lialuma (glucose) ka insulin, le ts'ebeliso ea li-resine tsa potasiamo.

Kaha lithethefatsi li tlama liprotheine tsa plasma ka botlalo, hemodialysis ha e sebetse.

Foromo ea litekanyetso

Matlapa a koahetsoeng 10 mg, 20 mg le 40 mg

Letlapa le leng le na le:

ntho e sebetsang - atorvastatin (e le letsoai la khalsiamo ea trihydrate) 10 mg, 20 mg le 40 mg (10.85 mg, 21.70 mg le 43.40 mg),

Baeti: calcium carbonate, crospovidone, sodium lauryl sulfate, silicon dioxide, colloidal anhydrous, talc, microcrystalline cellulose,

Ho hlophisoa ha khetla: Opadry II pinki (talc, polyethylene glycol, titanium dioxide (E171), joala ba polyvinyl, tšepe (III) oxide mose (E172), tšepe (III) oxide e khubelu (E172), tšepe (III) oxide e ntso (E172).

Letlapa le koahetsoeng ka mmala o bosehla bo nang le biconvex

Melemo ea pharmacological

Mofumahali

Atorvastatin e kenella ka potlako ka mor'a ho tsamaisoa ka molomo, khatello ea eona ea plasma e fihla boemong bo phahameng bakeng sa lihora tse 1 - 2. Tekanyo e ts'oanang ea bioavailability ea atorvastatin ke 95-99%, e felletseng - 12-14%, systemic (e fanang ka thibelo ea phetoho ea HMG-CoA) - e ka bang 30 % Bioavailability e tlase e hlalosoa ke ho hlakisoa ha kemiso kahara mucous membrane ea "gastrointestinal" le "kapa" metabolism nakong ea khaolo ea pele ka sebete. Ho kenella le khatello ea plasma ho eketseha ka tekanyo ea tekanyetso ea moriana. Leha ho na le taba ea hore ha e nkuoa ka lijo, ho kenngoa ha moriana hoa fokotseha (boholo ba mahloriso le AUC li ka ba 25 le 9%, ka ho latellana), ho fokotseha ha cholesterol ea LDL ha hoa itšetleha ka atorvastatin e nkuoeng ka lijo kapa che. Ha u nka atorvastatin ka shoalane, mahloriso a eona a plasma a ne a le tlase (hoo e batlang e le 30% bakeng sa mahloriso a phahameng le AUC) ho feta ha a e nka hoseng. Leha ho le joalo, ho fokotseha ha boemo ba cholesterol ea LDL ha hoa itšetleha ka nako ea ho sebelisa moriana.

Ho feta 98% ea lithethefatsi li tlama ho protheine ea plasma. Tekanyo ea erythrocyte / plasma e batla e le 0,25, e bonts'ang phallo e fokolang ea moriana liseleng tse khubelu tsa mali.

Atorvastatin e tšeloa metsoako ea li-ortho- le para-hydroxylated le lihlahisoa tse fapaneng tsa beta-oxidised. Phello ea inhibitory ea setho sa lithethefatsi ho HMG-CoA reductase e ka bang 70% e lemohuoa ka lebaka la ts'ebetso ea metabolites ea potoloho. Atorvastatin e fumanoe e le inhibitor e fokolang ea cytochrome P450 ZA4.

Atorvastatin le metabolites ea eona li qhekelloa haholo ka bile ka mor'a metabolite ea hepatic le / kapa metabolism. Leha ho le joalo, sethethefatsi ha se angoe ke ho kenella hape ka matla. Nako e khutsitseng ea halofo ea bophelo ba atorvastatin e batla e le lihora tse 14, empa nako ea mesebetsi e thibelitsoeng khahlanong le HMG-CoA reductase ka lebaka la ho potoloha ha metabolite e sebetsang ke lihora tse 20-30. Ka tlase ho 2% ea tekanyetso ea molomo ea atorvastatin e pepesitsoe ka har'a moroto.

Kakaretso ea plasma ea atorvastatin ho batho ba baholo ba phetseng hantle (ba fetang 65) e phahame (hoo e ka bang 40% bakeng sa mahloriso a phahameng le 30% bakeng sa AUC) ho feta ho bacha. Ho ne ho se na phapang ea katleho ea kalafo le atorvastatin ho bakuli ba tsofetseng le bakuli ba lihlopha tse ling tsa lilemo.

Keketseho ea atorvastatin ho plasma ea mali ho basali e fapana le khatello ea plasma ea mali ho banna (ho basali, khatello e phahameng e batla e le 20% e phahameng, mme AUC - 10% e tlase). Leha ho le joalo, ha ho phapang e kholo ea bongaka e fumanoeng phello ea maemo a lipid ho banna le basali.

Lefu la liphio ha le ame khatello ea bongata ba lithethefatsi ho plasma kapa phello ea atorvastatin maemong a lipid, ka hona ha ho na tlhoko ea tokiso ea lethal dose ho bakuli ba nang le ho hlleha ha a liphio. Lithuto ha li a ka tsa koahela bakuli ba nang le ho hloleha ha methapo ea methapo ea pheletso; mohlomong, hemodialysis ha e fetole ka ho hlaka ho hlakileng ha atorvastatin, kaha sethethefatsi se batla se kopane ka botlalo ho liprotheine tsa plasma ea mali.

Keketseho ea atorvastatin ka plasma ea mali e eketseha haholo (boholo ba mahloriso - hoo e ka bang makhetlo a 16, AUC - makhetlo a 11) ho bakuli ba nang le lefu la cirrhosis la sebete sa etiology.

Mofumahali

Atorvastatin ke inhibitor e ikhethileng ea HMG-CoA reductase-enzyme, e laolang phetoho ea HMG-CoA ho mevalonate, sethathamisi sa li-sterols (ho kenyelletsa cholesterol (cholesterol)). Ho bakuli ba nang le homozygous le heterozygous Famer hypercholesterolemia, mofuta o futsitsoeng oa hypercholesterolemia le dyslipidemia e kopaneng, atorvastatin e theola khatello ea kholo ea cholesterol, density lipoproteins e tlase (LDL) le apolipoprotein B (Apo B). Atorvastatin e boetse e fokotsa ho kopana ha lipoprotein tse fokolang haholo (VLDL) le triglycerides (TG), mme hape e eketsa hanyane dikahare tsa cholesterol high density lipoproteins (HDL).

Atorvastatin e theola boemo ba cholesterol le lipoprotein maling a mali ka ho thibela ho fokotsoa ha HMG-CoA, motsoako oa k'holeseterole ka har'a sebete le ho eketsa palo ea li-receptor tsa LDL ka holim'a li-hepatocytes, tse tsamaeang le ho eketseha le ho eketseha hoa matla ha LDL. Atorvastatin e fokotsa tlhahiso ea LDL, e baka keketseho e boletsoeng le e tšoarellang mosebetsing oa LDL receptor. Atorvastatin ka katleho e theola litekanyetso tsa LDL ho bakuli ba nang le homozygous Famal hypercholesterolemia, e sa amaneng le kalafo e tloaelehileng ka lithethefatsi tse fokotsang lipid.

Sebaka sa mantlha sa tšebetso ea atorvastatin ke sebete, se etsang karolo e kholo ho kopaneng ea cholesterol le clearance ea LDL. Ho fokotseha hoa boemo ba cholesterol ea LDL ho ikamahanya le lethalinyana la lithethefatsi le khatello ea lona 'meleng.

Atorvastatin ka tekanyetso ea 10-80 mg e fokotsitse boemo ba cholesterol e felletseng (ka 30-46%), LDL cholesterol (ka 41-61%), Apo B (ka 34-50%) le TG (ka 14-31%). Sephetho sena se tsitsitse ho bakuli ba nang le heterozygous Familia hypercholesterolemia, mofuta o fumanoeng oa hypercholesterolemia le mofuta o kopaneng oa hyperlipidemia, ho kenyelletsa le bakuli ba nang le lefu la tsoekere le sa tsitsang insulin.

Ho bakuli ba nang le hypertriglyceridemia e ka thoko, atorvastatin e fokotsa boemo ba cholesterol e felletseng, cholesterol ea LDL, cholesterol ea VLDL, Apo B, TG mme e eketsa boemo ba cholesterol ea HDL hanyane. Ho bakuli ba nang le dysbetalipoproteinemia, atorvastatin e fokotsa boemo ba sebete bo theolang cholesterol.

Ho bakuli ba nang le mofuta oa IIa le IIb hyperlipoproteinemia (ho latela sehlopha sa Fredrickson), tekanyo ea karo-karolelano ea HDL-C le atorvastatin ka tekanyo ea 10-80 mg e ne e le 5.1-8,7%, ho sa natsehe hore na tekanyo e kae. Ntle le moo, ho bile le phokotso e kholo e thehiloeng ho lethal dose ea tekanyo ea cholesterol e felletseng / HDL cholesterol le HDL cholesterol. Ts'ebeliso ea atorvastatin e fokotsa kotsi ea ischemia le lefu ho bakuli ba nang le myocardial infarction ntle le Q wave le angina e sa tsitsang (ho sa tsotelehe bong le lilemo) e lekana ka kotloloho le boemo ba cholesterol ea LDL.

Hypercholesterolemia e amanang le Heterozygous ho bana. Ho bashanyana le banana ba lilemo tse 10-17 ba nang le heterozygous Familia hypercholesterolemia kapa hypercholesterolemia e matla, atorvastatin ka tekanyo ea 10-20 mg hang ka letsatsi o fokotse haholo boemo ba cholesterol e felletseng, LDL cholesterol, TG le Apo B ho plasma ea mali. Leha ho le joalo, ha ho na phello e kholo khōlong le bohlankaneng ho bashanyana kapa nakong ea kemaro ea ho ea matsatsing a banana. Tšireletseho le katleho ea methapo e kaholimo ho 20 mg bakeng sa kalafo ea bana ha e so ithutoe. Tšusumetso ea nako ea kalafo ea atorvastatin bongoaneng mabapi le phokotso ea ho fokola ha mmele le lefu ka ho ba motho e moholo ha e e-so theoe.

Tekanyetso le tsamaiso

Pele o qala kalafo ea Atorvastatin, ho hlokahala ho tseba hore na cholesterol e maling e khahlano le semelo sa phepo e nepahetseng, fana ka boikoetliso 'meleng le ho nka mehato e reretsoeng ho fokotsa boima ba' mele ho bakuli ba nang le botenya, le ho tsamaisa kalafo ea mafu a ka tlase. Nakong ea kalafo le atorvastatin, bakuli ba lokela ho khomarela mokhoa o tloaelehileng oa hypocholesterolemic. Lithethefatsi li fanoe ka tekanyetso ea 10-80 mg hang ka letsatsi letsatsi le letsatsi, ka nako e le ngoe, empa ka nako e ts'oanang ea letsatsi, ho sa tsotelehe ho ja lijo. Litekanyetso tsa pele le tsa tlhokomelo li ka fetoloa ka bomong ho latela boemo ba cholesterol ea qalong ea LDL, lipheo le katleho ea kalafo. Kamora libeke tse 2-4 ho tloha ho qala ha kalafo le / kapa tokiso ea litheko le Atorvastatin, setšoantšo sa lipid se lokela ho nkuoa mme lethal dose le fetoloe ka nepo.

Hypercholesterolemia ea mantlha le hyperlipidemia e kopaneng. Maemong a mangata, ho lekane ho fana ka moriana ka tekanyetso ea 10 mg hang ka letsatsi letsatsi le letsatsi. Phello ea kalafo e ba teng kamora libeke tse peli, phello e phahameng - kamora libeke tse 4. Liphetoho tse ntle li tšehetsoa ke tšebeliso ea nako e telele ea lithethefatsi.

Homozygous Familia hypercholesterolemia. Lithethefatsi li fanoe ka tekanyetso ea 10 ho isa ho 80 mg hang ka letsatsi letsatsi le leng le le leng, ka nako efe kapa efe, ho sa tsotelehe tšebeliso ea lijo. Litekanyetso tsa pele le tsa tlhokomelo li beoa ka bonngoe. Maemong a mangata, ho bakuli ba nang le homozygous Familyal hypercholesterolemia, sephetho se fihlelleha ka tšebeliso ea Atorvastatin ka tekanyo ea 80 mg hang ka letsatsi.

Heterozygous Familia hypercholesterolemia ho bana (bakuli ba lilemo tse 10-17). Atorvastatin e khothalletsoa tekanyetso ea pele.

10 mg makhetlo a 1 ka letsatsi letsatsi le letsatsi. Tekanyo e kholo e khothalletsoang ke 20 mg hang ka letsatsi letsatsi le leng le le leng (tekanyetso e fetang 20 mg ha e so ithutoe ho bakuli ba sehlopha sena sa lilemo). Tekanyetso e beoa ka bonngoe, ho latela sepheo sa kalafo, tekanyetso e ka fetoloa le nako ea libeke tse 4 kapa ho feta.

Sebelisa ho bakuli ba nang le lefu la liphio le ho hloleha ha rebo. Boloetse ba liphio ha bo ame khatello ea mali ea atorvastatin kapa ho fokotseha ha cholesterol ea plasma LDL, ka hona ha ho na tlhoko ea tokiso ea litekanyetso.

Sebelisa ho bakuli ba tsofetseng. Ha ho na phapang phapusing ea katleho le tšebeliso ea lithethefatsi kalafong ea hypercholesterolemia ho bakuli ba tsofetseng le bakuli ba baholo kamora lilemo tse 60.

Bakuli ba nang le ts'ebetso ea sebete e sa sebetseng moriana o laetsoe ka hloko mabapi le ho thefuleha hoa phallo ea moriana 'meleng. Taolo ea methapo ea bongaka le ea laboratori e bonts'itsoe, mme haeba liphetoho tse kholo tsa pathological li fumanoa, tekanyo e lokela ho fokotsoa kapa kalafo e lokela ho emisoa.

Haeba qeto e etsoa ho tsamaiso e kopaneng ea Atorvastatin le CYP3A4 inhibitors, joale:

Kamehla qala kalafo ka bonyane lethal dose (10 mg), etsa bonnete ba ho beha serum lipids pele o kenya lethal dose.

O ka emisa ka nakoana ho nka Atorvastatin haeba li-inhibitors tsa CYP3A4 li laetsoe thupelong e khuts'oane (mohlala, khoso e khutšoane ea lithibela-mafu tse kangcacithromycin).

Keletso mabapi le boholo ba tekanyetso ea Atorvastatin ha o sebelisa:

ka cyclosporine - lethal dose ha ea lokela ho feta 10 mg,

kacacithromycin - lethal dose ha ea lokela ho feta 20 mg,

le itraconazole - lethal dose ha ea lokela ho feta 40 mg.

Ho sebelisana le lithethefatsi

Monyetla oa myopathy o eketseha nakong ea kalafo ka lithethefatsi tse ling tsa sehlopha sena ha ts'ebeliso ea cyclosporine, e tsoang ho fibric acid, erythromycin, antifungals e amanang le azoles, le nicotinic acid.

Li-antacid: Ho kenella ka nako e le 'ngoe ho emisoe ho nang le magnesium le aluminium hydroxide ho fokotsitse khatello ea atorvastatin ka plasma ea mali ka 35%, leha ho le joalo, tekanyo ea ho fokotseha ha cholesterol ea LDL ha ea ka ea fetoha.

Antipyrine: Atorvastatin ha e ame li-pharmacokinetics tsa antipyrine, ka hona, ho sebelisana le lithethefatsi tse ling tse lokiselitsoeng ke cytochrome isoenzymes e sa lebelloang.

Amlodipine: Phuputsong e amanang le tšebelisano ea lithethefatsi ho batho ba phetseng hantle, tsamaiso e le 'ngoe ea atorvastatin ka tekanyo ea 80 mg le amlodipine ka tekanyo ea 10 mg e lebisitse keketseho ea phello ea atorvastatin ka 18%, e neng e se bohlokoa ba kliniki.

Gemfibrozil: ka lebaka la kotsi e eketsehileng ea ho ba le myopathy / rhabdomyolysis ka ts'ebeliso e ts'oanang ea li-inhibitors tsa HMG-CoA reductase tse nang le gemfibrozil, tsamaiso e ts'oanang ea lithethefatsi tsena e lokela ho qojoa.

Meetso e meng: ka lebaka la kotsi e eketsehang ea myopathy / rhabdomyolysis ka tšebeliso e ts'oanang ea li-inhibitors tsa HMG-CoA reductase tse nang le li-fibrate, atorvastatin e lokela ho laeloa ka hloko ha e nka fiber.

Nicotinic acid (niacin): menyetla ea ho ba le myopathy / rhabdomyolysis e ka eketsoa ha ho sebelisoa atorvastatin hammoho le nicotinic acid, ka hona, maemong ana, ho lokela ho fanoa ka maikutlo a ho fokotsa litekanyetso tsa atorvastatin.

Colestipol: le tšebeliso ea nako e tšoanang ea colestipol, karolelano ea atorvastatin plasma ea mali e fokotsehile ka 25%. Leha ho le joalo, phello e fokotsang lipid ea ho kopana ha atorvastatin le colestipol e ne e feta ea lithethefatsi ka bomong.

Colchicine: ka tšebeliso e tšoanang ea atorvastatin e nang le colchicine, linyeoe tsa myopathy li tlalehiloe, ho kenyeletsa le rhabdomyolysis, ka hona tlhokomeliso e lokela ho sebelisoa ha ho fanoa ha atorvastatin e nang le colchicine.

Digoxin: le taolo e khutsitseng ea digoxin le atorvastatin ka tekanyo ea 10 mg, mokokotlo oa tekano ea digoxin ka plasma ea mali ha oa ka oa fetoha. Leha ho le joalo, ha digoxin e ne e sebelisoa hammoho le atorvastatin ka tekanyo ea 80 mg / ka letsatsi, khatello ea "digoxin" e eketsehile ka hoo e ka bang 20%. Bakuli ba fumanang digoxin hammoho le atorvastatin ba hloka ho hlahlojoa ka nepo.

Erythromycin / clarithromycin: ka tšebeliso e tšoanang ea atorvastatin le erythromycin (500 mg makhetlo a mane ka letsatsi) kapa clarithromycin (500 mg habeli ka letsatsi), e thibelang cytochrome P450 ZA4, keketseho ea khatello ea atorvastatin plasma ea mali e ile ea bonoa.

Azithromycin: le tšebeliso e tšoanang ea atorvastatin (10 mg hang ka letsatsi) le azithromycin (500 mg / hang ka letsatsi), khatello ea atorvastatin ka plasma ha e ea fetoha.

Terfenadine: ka tšebeliso e le 'ngoe ea atorvastatin le terfenadine, liphetoho tsa bohlokoa litabeng tsa pharmacokinetics tsa terfenadine ha lia ka tsa fumanoa.

Lithibela-pelehi tsa molomo: ha u ntse u sebelisa atorvastatin le contracilos ea molomo e nang le norethindrone le ethinyl estradiol, ho bile le keketseho e kholo ho AUC ea norethindrone le ethinyl estradiol ka 30% le 20%, ka ho latellana. Tšusumetso ena e lokela ho nahanoa ha u khetha lithibela-pelehi tsa molomo bakeng sa mosali ea noang atorvastatin.

Warfarin: ha re ithuta ho sebelisana ha atorvastatin le warfarin, ha ho matšoao a ts'ebelisano ea bohlokoa ka ho fetisisa ka kliniki a fumanoeng.

Cimetidine: ha re ithuta ho sebelisana ha atorvastatin le cimetidine, ha ho na matšoao a ts'ebelisano e bohlokoa ea kliniki a fumanoeng.

Protease Inhibitors: tšebeliso ea nako e tšoanang ea atorvastatin e nang le li-inhibitors tsa cytechrome P450 ZA4 e ne e tsamaisana le keketseho ea plasma ea likhopolo tsa atorvastatin.

Malebela mabapi le tšebeliso e kopaneng ea li-atorvastatin le HIV proteinase inhibitors:

Sokolla foromo le sebopeho

Sehlahisoa sa litlhare se fanoa ka mokhoa oa matlapa a litlhare. Ntho e sebetsang ea lithethefatsi ke atorvastatin calcium calcium (40 mg ka ho e 'ngoe le e ngoe).

Lisebelisoa tse ling: cellcose ea cellcose, calcium carbonate, StarKap 1500 (setlama se kopantsoeng le setlolo sa poone), aerosil, stearate ea magnesium, diode ea titanium, talc, macrogol, dae e khubelu, oxide ea iron, dae e mosehla, oxide ea tšepe, polyvinyl joala).

Sephutheloana sena se na le lilakane tse 1,2 kapa 3 tsa matlapa a 10,15 kapa a 30.

Ho sebelisana le lithethefatsi

Ts'ebeliso e tšoanang le li-antibacterial agents (erythromycin ,cacithromycin), lithethefatsi tsa antifungal (fluconazole, ketoconazole, itraconazole), cyclosporine, li-derivatives tsa fibroic acid li eketsa khatello ea atorvastitis le kotsi ea ho ba le myalgia.

Ts'ebeliso e ts'oanang ka nako e le ngoe le lipelaelo, tse neng li kenyelletsa magnesium le aluminium, li kentse letsoho ho fokotseha ha khatello ea atorvastatin. Sena ha sea ka sa ama boemo ba ho fokotsa cholesterol le lipoprotein tse tlaase.

Basali ba nkang lithibela-pelehi tsa molomo ba lokela ho nahana hore atorvastatin e ka eketsa bongata ba ethinyl estradiol le norethindrone.

Motsoako o hlokang tlhokomeliso: motsoako oa atorvastatin le lithethefatsi tse thusang ho fokotsa bongata ba lihormone tsa steroid (spironolactone, ketoconazole).

Litšebelisano tse sa rateheng tsa atorvastatin e nang le lithethefatsi tsa antihypertensive ha lia ka tsa bonoa.

Ts'ebetso ea pharmacological ea atorvastatin 40

Ntho e sebetsang ea lithethefatsi e phatlalalitse ts'ebetso ea ho fokotsa lipid mme ke karolo ea sehlopha sa "statins". Karolo ena e thibela ho fokotsoa ha HMG-CoA, enzyme e khethehileng e fetolang mofuta oa hydroxymethylglutaryl coenzyme ho mevalonic acid.

Moriana o fokotsa sebopeho sa LDL (lipilisi tse tlaase tsa methapo ea methapo) mme o eketsa boemo ba tšebetso ea li-receptor tsa LDL. Ntle le moo, ho bakuli ba nang le hypercholesterolemia, lithethefatsi li fokotsa LDL.

Ho feta moo, sethethefatsi se theola boemo ba Ho (cholesterol e felletseng mme se eketsa k'holeseterole ea lipoproteins tse phahameng) (HDL).

Atorvastatin e na le monko o phahameng haholo. Statin ho plasma e fumana boholo ba khatello ea eona ka metsotso e 60-120. Ho ja hanyane ho fokotsa nako ea ho amoheloa ha moriana.

Ntho ena e na le bioavailability ea 12%. Ntho ena e na le metsoako ea 'mele linthong tsa sebete. Setlhare sena se hlakoloa hammoho le bile. Bophelo ba halofo ea atorvastatin ke lihora tse 14. Hoo e ka bang 2% ea moriana o hlahisoa ke liphio. Hemodialysis ha e ame profaele ea pharmacokinetic ea lithethefatsi.

Litaelo tse khethehileng

Atorvastatin e ka baka keketseho ea serum CPK, e lokelang ho tsotelloa tlhokomelong e khethollang ea bohloko ba sefuba. Re lokela ho hopola hore keketseho ea KFK ka makhetlo a 10 ha e bapisoa le tloaelo, e tsamaeang le bofokoli ba myalgia le mesifa e ka amahanngoa le myopathy, kalafo e lokela ho emisoa.

Ka tšebeliso e tšoanang ea atorvastatin e nang le cytochrome CYP3A4 proteinase inhibitors (cyclosporine ,cacithromycin, itraconazole), lethal dose la pele le lokela ho qalisoa ka 10 mg, ka netefatso ea kalafo ea lithibela-mafu, atorvastatin e lokela ho emisoa.

Hoa hlokahala ho hlokomela matšoao a ts'ebetso ea sebete pele ho kalafo, libeke tse 6 le tse 12 kamora ho qala ha moriana kapa kamora ho eketsa tekanyetso, le nako le nako (likhoeli tse ling le tse ling tse 6) ka nako eohle ea ts'ebeliso (ho fihlela boemo bo tloaelehileng ba bakuli bao maemo a bona a transaminase a fetang tloaelehileng ) Keketseho ea "transpase" ea "hepatic" e shebeloa haholo likhoeling tse 3 tse qalang tsa taolo ea lithethefatsi. Ho khothalletsoa ho hlakola lithethefatsi kapa ho fokotsa tekanyetso ka keketseho ea AST le ALT makhetlo a fetang a 3. Ts'ebeliso ea atorvastatin e lokela ho emisoa ka nakoana ha ho etsoa matšoao a bongaka a fanang ka maikutlo a ho ba teng ha myopathy ea hlobaetsang, kapa boteng ba lintho tse rerang pele ho nts'etsopele ea ho hlaphoheloa ke matla a methapo ka lebaka la rhabdomyolysis (ts'oaetso e matla, ho fokotseha ha khatello ea mali, ts'ebetso e kholo ea ts'ebetso ea methapo, metabolic, endocrine kapa likhathatso tse matla tsa electrolyte) . Bakuli ba lokela ho lemosoa hore ba lokela ho ea ngakeng hang-hang haeba ho ba le bohloko bo sa hlalosoang kapa bofokoli ba mesifa, haholoholo haeba bo tsamaisana le malaise kapa feberu.