ComboGliz Tsamaisa matlapa a 500

Lebitso la machabeng:Kombiglyze prolong

Sebopeho le mofuta oa tokollo

Litafole tsa Khatiso e Filimisitsoeng ea Filimi e Ncha. Letlapa le le leng le na le 1000 mg ea metformin, 2,5 mg ea saxagliptin.

Ho lithutsoana matlapa a 28 kapa a 56. E kentsoe ka lebokoseng la karete.

Letlapa le lokisitsoeng le hlahisitsoeng ka filimi, 1000 mg + 5 mg. Ka paketeng ea matlapa a 28 kapa a 56.

Letlapa le lokisitsoeng le hlahisitsoeng ka filimi, 500 mg + 5 mg. Ka paketeng ea matlapa a 28 kapa a 56.

Sehlopha sa tliliniki le meriana

Moriana oa molomo oa hypoglycemic

Sehlopha sa Pharmacotherapeutic

Moemeli ea kopaneng oa hypoglycemic bakeng sa tsamaiso ea molomo (dipeptidyl peptidase-4-inhibitor + biguanide)

Ketso ea pharmacological

Combogliz Prolong e kopanya lithethefatsi tse peli tsa hypoglycemic le mekhoa e tlatselletsang ea ho ntlafatsa taolo ea glycemic ho bakuli ba nang le mofuta oa 2 lefu la tsoekere mellitus (DM2): saxagliptin, dipeptyl peptidase 4 inhibitor (DPP-4), le metformin, moemeli oa sehlopha sa Biguanide.

Ha o arabela ho kenella ha lijo ho tsoa ka mpeng e nyane, lihormone tsa "incretin" li kenngoa maling, joalo ka glucagon-peptide-1 (GLP-1) le "insulinotropic polypeptide" (HIP) ea glucose. Lihormone tsena li khothaletsa ho tsoa ha insulin liseleng tsa pancreatic beta, ho latela bongata ba tsoekere maling, empa ha li ananele ke enzyme DPP-4 metsotso e 'maloa. GLP-1 e boetse e theola secretion ea tsoekere ho lisele tsa pancreatic alpha, e fokotsa tlhahiso ea glucose ea sebete. Ho bakuli ba nang le lefu la tsoekere la mofuta oa 2, khatello ea GLP-1 e ea theoha, empa karabelo ea insulin ho GLP-1 e ntse e le teng. Saxagliptin, kaha e le inhibitor ea thibelo ea DPP-4, e fokotsa ho kenella ha lihormone tsa "incretin", ka ho etsa joalo, e eketsang khatello ea bona maling le ho lebisa ho fokotseha ha tsoekere e potlakileng ka mor'a ho ja.

Metformin ke sethethefatsi sa hypoglycemic se ntlafatsang mamello ea tsoekere ho bakuli ba nang le lefu la tsoekere la 2, le ho fokotsa khatello ea tsoekere ea postprandial. Metformin e fokotsa tlhahiso ea tsoekere ke sebete, e fokotse ho monya ha tsoekere ka mpeng mme e phahamisa kutloisiso ea insulin, e eketsa ho kenella ka bongata le ts'ebeliso ea tsoekere. Ho fapana le litokisetso tsa sulfonylurea, metformin ha e bake hypoglycemia ho bakuli ba nang le lefu la tsoekere la mofuta oa 2 kapa batho ba phetseng hantle (ntle le maemong a ikhethang, bona likarolo tsa "Boitlhokomelo" le "Litaelo tse Khethehileng"), le hyperinsulinemia. Nakong ea phekolo ea metformin, secretion ea insulin e lula e sa fetohe, leha ho tsepamisa mohopolo oa insulin le ho arabela lijong tsa motšeare ho ka fokotseha.

Mofumahali

Pharmacokinetics ea saxagliptin le metabolite ea eona e sebetsang, 5-hydroxy-saxagliptin, e tšoana le ho baithaopi ba phetseng hantle le ho bakuli ba nang le lefu la tsoekere la mofuta oa 2. Boleng ba C max le sebaka se ka tlasa AUC curve ea saxagliptin le metabolite ea eona e sebetsang ho plasma e eketsehile ka tekanyo ea lethal dose ho tloha ho 2,5 mg ho isa ho 400 mg. Kamora taolo e le 'ngoe ea molomo ea saxagliptin ka tekanyetso ea 5 mg ke baithaopi ba phetseng hantle, litekanyetso tse tloaelehileng tsa AUC tsa saxagliptin le metabolite ea eona e ka sehloohong e ne e le 78 ng * h / ml le 214 ng * h / ml, le boleng ba C max ho plasma e ne e le 24 ng / ml le 47 ng / ml ho latela. Phapang e tloaelehileng ea AUC le C max ea saxagliptin le metabolite ea eona e sebetsang e ne e le ka tlase ho 25%.

Ka tšebeliso ea lithethefatsi khafetsa ka letsatsi ka tekanyo e itseng, ha ho na tlhahiso ea litebele ea saxagliptin kapa metabolite ea eona e sebetsang. Ha ho na ts'ehetso ea ho hlakisoa ha saxagliptin le metabolite ea eona e sebetsang le lethathamong la nako ha le sebelisoa matsatsi a 14 hang ka letsatsi ka tekanyetso ho tloha ho 2,5 mg ho isa ho 400 mg ea saxagliptin.

Ka max, tokollo e fetotsoeng ea metformin e fihlella ka nako ea lihora tse 7. Ho amoheloa ha metformin ho tsoa matlapeng a lokolotsoeng a lokolloang ho eketseha ka hoo e ka bang 50% ha ho nooa le lijo. Ka tekano, AUC le Cmax ea metformin e lokollotsoeng e ile ea eketseha e sa lekane ho tekanyetso ho lethal dose ho tloha ho 500 ho isa ho 2000 mg. Kamora ho tsamaisoa khafetsa, metformin e lokollotsoeng ha ea ka ea ipokellela plasma. Metformin ha e sa fetoloe ke liphio ebile ha e tšeloe sebeteng.

Kamora ho tsamaisoa ka molomo, bonyane 75% ea tekanyetso ea saxagliptin e ananeloa. Ho ja ha hoa ka ha ama haholo pharmacokinetics ea saxagliptin ho baithaopi ba phetseng hantle. Lijo tse nang le mafura a mangata ha lia ka tsa ama C max ea saxagliptin, ha AUC e eketsehile ka 27% ha e bapisoa le ho itima lijo. Nako ea ho fihlela C max (T max) bakeng sa saxagliptin e eketsehile ka lihora tse ka bang 0.5 ha o nka sethethefatsi ka lijo empa se bapisoa le ho itima lijo. Leha ho le joalo, liphetoho tsena ha li na bohlokoa ba kliniki.

Kamora taolo e le 'ngoe ea molomo ea tokollo e fetotsoeng ea metformin, C max e fihlelloa ka karolelano ea lihora tse 7, ho tloha lihora tse 4 ho isa ho tse 8. AUC le Cmax ea metformin e lokollotsoeng e ile ea eketseha e sa lekane le tekanyetso ea lethal dose ho tloha ho 500 ho isa ho 2000 mg. Palo e phahameng ea lithethefatsi ho plasma ea mali ke 0.6, 1.1, 1.4 le 1.8 μg / ml ha u nooa tekanyetso ea 500, 1000, 1500 le 2000 mg hang ka letsatsi. Le ha tekanyo ea ho amoheloa (e lekantsoeng ke AUC) ea metformin e tsoang litafoleng tsa metformin e lokisitsoeng e eketseha ka hoo e ka bang 50% ha e nkuoa ka lijo, takatso ea lijo ha e a ama C max le T max ea metformin. Lijo tse tlase le tse mafura a mangata li bile le phello e tšoanang ho li-pharmacokinetics tsa metformin e lokisitsoeng e lokisitsoeng.

Ho tlangoa ha saxagliptin le metabolite ea eona e ka sehloohong liprotheineng tsa serum ea mali ha ho na thuso, ka hona, ho ka nahanoa hore ho ajoa ha saxagliptin ka liphetoho phetohong ea protheine ea serum ea mali e bonngoeng ho hloleha ha hepatic kapa renal ha e na ho ba le liphetoho tse kholo.

Boithuto ba kabo ea metformin e lokollotsoeng ha boa ka ba etsoa, ​​leha ho le joalo, moqolo o hlakileng oa kabo ea metformin kamora taolo e le 'ngoe ea molomo ea matlapa a lokolloang hang hang ka li-850 mg ka karolelano ea 654 ± 358 L. Metformin e tlamahana le protheine ea plasma hanyane.

Saxagliptin e thehiloe haholo-holo ka ho nka karolo ha isoenzymes ea cytochrome P450 ZA4 / 5 (CYP3A4 / 5) ka sebopeho sa metabolite ea mantlha e sebetsang, phello ea thibelo eo khahlano le DPP-4 e fokolitsoeng makhetlo a 2 ho feta saxagliptin.

Boithuto bo nang le ts'ebetso e le 'ngoe e kenelletseng ea lithethefatsi ho baithaopi ba phetseng hantle bo bontša hore metformin ha e sa fetoloa ke liphio, ha e tšeloe ka har'a sebete (metabolites ha e fumanoe bathong),' me ha e epeloe ka mala.

Saxagliptin e epolloa ke liphio le mala. Kamora tekanyetso e le 'ngoe ea 50 mg e ngotsoeng 14 C-saxagliptin, 24% ea lethal dose e ile ea hlalosoa ke liphio e le saxagliptin e sa fetoheng le 36% e le metabolite e ka sehloohong ea saxagliptin. Radioage e felletseng e fumanoeng ka har'a moroto e lekana le 75% ea lethal dose le nkuoeng.

Tlhako e tloaelehileng ea renal ea saxagliptin e ne e ka ba 230 ml / min, boleng bo tloaelehileng ba filtration e ka bang 120 ml / min. Bakeng sa metabolite e ka sehloohong, ho hlakoloa ha renal ho ne ho bapisoa le litekanyetso tsa bohlokoa tsa bosholu ba glomerular. Ekaba 22% ea radioacaction eohle e fumanoeng mefuteng.

Ho hlakisoa ha molao ka molao ke nako e ka bang makhetlo a 3,5 ho feta clearinine clearance (CC), e leng se bonts'ang hore secretion ea tubular ke eona tsela e kholo ea excretion ea metformin.Kamora ho kenella, hoo e ka bang 90% ea moriana o kentsoeng o hloekisoa ke liphio nakong ea lihora tse 24 tsa pele, ka halofo ea bophelo ho tsoa ho plasma ea lihora tse ka bang 6.2. Meleng, halofo ea bophelo ke lihora tse ka bang 17.6, ka hona, boima ba sele e khubelu ea mali e kanna ea ba karolo ea phetiso.

Pharmacokinetics maemong a khethehileng a kliniki

Ha ho kgothaletswe ho sebelisa Combogliz Prolong ho bakuli ba nang le bothata ba ho phekoloa ka methapo (bona karolo "Contraindication").

Bakeng sa bakuli ba nang le ho hloleha ho ba le renal e bonolo, litekanyetso tsa AUC tsa saxagliptin le metabolite ea eona e sebetsang e ne e le 20% le 70% (ka ho latellana) e phahame ho feta litekanyetso tsa AUC ho bakuli ba nang le ts'ebetso e tloaelehileng ea renal. Kaha keketseho e joalo ea boleng ha e nkoe e le bohlokoa ba bongaka, ha ho kgothaletswe ho fetola tekanyetso ea saxagliptin ho bakuli ba nang le bothata bo fokolang ba renal.

Ho bakuli ba nang le ts'ebetso ea renal e sa sebetseng (ho latela liphetho tsa litekanyetso tsa QC), halofo ea bophelo ba metformin e tsoang ho plasma le bolelele ba mali le tumello ea renal ea fokotseha ka tekano ea phokotseho ea QC.

Bakeng sa bakuli ba nang le ts'oaetso e matla ea 'mele, e leka-lekaneng le e matla ea hepatic, ho ne ho se na liphetoho tse kholo litabeng tsa pharmacokinetics tsa saxagliptin, ka hona, ho lokisoa ha lethathamo la bakuli ba joalo ha ho hlokahale.

Ha ho na lithuto tse entsoeng ka pharmacokinetic tsa metformin ho bakuli ba nang le ho senyeha hoa hepatic.

Khalemelo ea tekanyetso ea saxagliptin ho latela bong ba bakuli ha e hlokehe.

Lithutong tsa bakuli ba nang le lefu la tsoekere la mofuta oa 2, phello ea hypoglycemic ea metformin ho banna le basali e ne e bapisoa.

Bakeng sa bakuli ba lilemo li 65-80, ho ne ho se na phapang e kholo litabeng tsa pharmacokinetics ea saxagliptin ha e bapisoa le bakuli ba lilemo tse nyane (lilemo tse 18 ho isa ho tse 40), ka hona, tokiso ea litekanyetso ho bakuli ba tsofetseng ha e hlokehe. Leha ho le joalo, re lokela ho hopola hore sehlopheng sena sa bakuli, ho fokotseha ha ts'ebetso ea liphio ho na le monyetla o mongata (sheba likarolo "Tekanyetso le tsamaiso" le "litaelo tse khethehileng").

Lintlha tse lekantsoeng tse tsoang lithutong tse laoloang tsa pharmacokinetics ea metformin ho baithaopi ba phetseng hantle ba fana ka tlhahiso ea hore botlalo ba plasma ba metformin bo fokotseha, T 1/2 e eketseha, 'me C e nyoloha ha e bapisoa le boleng ba litekanyetso tsena ho baithaopi ba bacha ba phetseng hantle. Ho ea ka lintlha tsena, phetoho ho li-pharmacokinetics ea metformin e nang le lilemo tse ntseng li eketseha e bakoa haholo ke phetoho mosebetsing oa liphio. Combogliz Prolong ha ea lokela ho laeloa bakuli ba ka holimo ho lilemo tse 80, ntle le ha ts'ebetso e tloaelehileng ea renal e netefatsoa ke liphetho tsa QC.

Lithuto tsa pharmacokinetics tsa saxagliptin ho bana ha li e-so tšoaroe.

Boithuto ba pharmacokinetics ba metformin e lokisitsoeng bo lokollotsoeng ho bana ha bo e-so tšoaroe.

Mofuta le Morabe

Ha ho kgothaletswe ho fetola tekanyetso ea saxagliptin ho latela morabe oa mokuli.

Ha ho na lithuto tsa "pharmacokinetics of metformin" ho latela mofuta oa bakuli.

Type 2 lefu la tsoekere le kopantsoe le lijo le boikoetliso ho ntlafatsa taolo ea glycemic.

Contraindication mabapi le ts'ebeliso ea lithethefatsi Combogliz Prolong

Ho eketsa kutloisiso ea motho ka mong ho karolo efe kapa efe ea lithethefatsi, diphetoho tse tebileng tsa hypersensitivity (anaphylaxis kapa angioedema) ho DPP-4 inhibitors, mofuta oa 1 lefu la tsoekere (o sa ithute), sebelisa ka insulin (ha e ithutoe), galgenose galactose tshoarella. glucose-galactose malabsorption, moimana, ho lactation, ka tlase ho lilemo tse 18 (polokeho le katleho e sa ithutoang), ho senyeha ha boea (serum creatinine ≥1.5 mg / dl bakeng sa banna, ≥1.4 mg / dl bakeng sa basali, ≥1.4 mg / dl bakeng sa basali cystin kapa fokotseha tumello ea "creatinine", ho kenyelletsa le tse bakoang ke ho se sebetse hantle ha pelo le pelo (ho ts'oha), mafu a hlobaetsang a myocardial le septicemia, mafu a hlobaetsang moo ho nang le kotsi ea ts'ebetso ea renal e sa sebetseng: ho omella (ka ho hlatsa, lets'ollo),feberu, mafu a tebileng a tšoaetsanoang, maemo a hypoxia (ho thothomela, sepsis, tšoaetso ea meno, mafu a bronchopulmonary), a hlobaetsang kapa a sa foleng a metabolic acidosis, ho kenyeletsoa le lefu la tsoekere la ketoacidosis, le kapa le se nang komello, lipontšo tse matla tsa bokuli le mafu a sa foleng a ka lebisang ho ona. nts'etsopele ea "hypoxia ea" tishu (ho hloleha ho hema, ho nyekeloa ke pelo, infraction ea myocardial e mpe), ho buoa ka matla le ho sithabela maikutlo (ha ho bonts'oa kalafo ea "insulin") ho lemalla joala bo sa foleng le chefo e matla ea ethanol, lactic acidosis (ho kenyelletsa nalane), nako ea bonyane lihora tse 48 pele le ka hare ho lihora tse 48 kamora ho etsa lithuto tsa radioisotope kapa radiology ka ho hlahisoa ha li-anti-iodine tse nang le iodine e tsamaeang le lijo tse nang le khalori e tlase (5% ea bakuli, ba amohetseng metformin e lokollotsoeng, 'me ba ntlafala khafetsa ho feta sehlopheng sa placebo, ba ne ba ts'oeroe ke lets'ollo le ho hlatsa.

Litlamorao tse latelang li tlalehiloe nakong ea ts'ebeliso ea morao-rao ea saxagliptin: pancreatitis e matla le karabelo ea hypersensitivity, ho kenyelletsa anaphylaxis, angioedema, rash le urticaria. Ho ke ke ha khoneha ho hakanya khafetsa tlhahiso ea liketsahalo tsena, hobane melaetsa e ile ea amoheloa ka boithatelo ho tsoa ho baahi ba boholo bo sa tsejoeng (bona likarolo "Contraindication" le "Litaelo tse ikhethang bakeng sa ho nka Combogliz Prolong»).

Palo e felletseng ea li-lymphocyte

Saxagliptin

Ha u sebelisa saxagliptin, ho fokotseha ha tekanyo e thehiloeng ho litekanyetso ho palo e felletseng ea li-lymphocytee ho hlokometsoe. Ha ho hlahlojoa lintlha tse kopaneng tsa lithuto tse hlano tse lahleloang ka beke, 24, ho fokotseha ha palo ea lisele tse ka bang 100 le tse 120 / / tsa palo e felletseng ea li-lymphocyte tse tsoang ho palo ea pele ea lisele tsa 2200 / μl li ile tsa bonoa ka ts'ebeliso ea saxagliptin ka tekanyo ea 5 mg le 10 mg, ka ho bapisoa, ha ho bapisoa ka placebo. Phello e ts'oanang e ile ea bonoa ha ho ne ho nkoa saxagliptin ka tekanyetso ea 5 mg ka kopanong ea pele le metformin ha e bapisoa le metformin monotherapy. Ho ne ho se na phapang pakeng tsa 2,5 mg saxagliptin le placebo. Karolo ea bakuli eo palo ea li-lymphocyte e neng e le ≤ 750 lisele / μl e ne e le 0.5%, 1.5%, 1.4%, le 0.4% lihlopheng tsa kalafo tsa saxagliptin ka tekanyo ea 2,5 mg, ka tekanyo ea 5 mg , ka tekanyetso ea 10 mg le placebo, ka ho latellana. Ho bakuli ba bangata ba sebelisang saxagliptin khafetsa, ha ho na ho khutlisetsoa hape ho sena, le hoja ho bakuli ba bang palo ea li-lymphocyte e ile ea fokotseha hape ka ts'ebetso ea kalafo ka saxagliptin, e ileng ea lebisa ho feliseng saxagliptin. Ho fokotseha ha palo ea li-lymphocyte ho ne ho sa tsamaisane le lipontšo tsa bongaka.

Mabaka a ho fokotseha ha palo ea li-lymphocyte nakong ea kalafo ea saxagliptin ha a bapisoa le placebo ha a tsejoe. Haeba ho na le ts'oaetso e sa tloaelehang kapa ea nako e telele, ho hlokahala ho lekanya palo ea li-lymphocyte. Kameho ea saxagliptin palong ea li-lymphocyte ho bakuli ba nang le mahlaba ka bongata ka palo ea li-lymphocyte (mohlala, vaerase ea immunodeficiency virus) ha e tsejoe.

Saxagliptin

Saxagliptin e ne e se na phello ea bohlokoa tlhatlhobong kapa ho latela tatellano ea palo ea liplatelese maemong a ts'eletseng a mahlo a tšeletseng, a laoloang tleliniking ea ts'ireletso le ho sebetsa hantle.

Tlhatlhobo ea Vitamin B₁₂

Lithutong tsa bongaka tse laoloang tsa metformin tse nkang libeke tse 29, bakuli ba ka bang 7% ba bontšitse ho fokotseha ha serum pejana ho feta ho tsepamisa maikutlo ho vithamine B₁₂ ho boleng bo sa reroang ntle le lipontšo tsa bongaka. Leha ho le joalo, ho fokotseha ho joalo hangata ha ho tsamaisane le nts'etsopele ea anemia mme e fola kapele ka mor'a ho khaotsa metformin kapa tšebeliso e eketsehileng ea vithamine B₁₂.

Bokhachane le pelehi

Ka lebaka la hore ts'ebeliso ea lithethefatsi Combogliz Prolong nakong ea kemolo ha e so ithutoe, lithethefatsi ha lia lokela ho fanoa nakong ea kemolo.

Ha ho tsejoe hore na saxagliptin kapa metformin e fetela lebeseng la matsoele.Kaha monyetla oa ho kenella ha moriana oa Combogliz Prolong ka lebese la matsoele ha o qheleloe ka thoko, tšebeliso ea lithethefatsi nakong ea lebone e hanyetsoa.

Tšebeliso ea ts'ebetso ea sebete e sa sebetseng Ho sebelisoa ha moriana bakeng sa ts'ebetso ea sebete e sa holofalitsoeng ho sebelisoa.

Tšebeliso ea lithethefatsi baneng

Tšebeliso ea lithethefatsi e patiloe ho bana ba ka tlase ho lilemo tse 18 (polokeho le katleho ha e so ithutoe).

Sebelisa ho bakuli ba tsofetseng

Kaha saxagliptin le metformin li qepha ka tsela e itseng ke liphio, mme ho bakuli ba tsofetseng ho fokotseha ha ts'ebetso ea liphio ho ka etsahala, Combogliz Prolong e lokela ho sebelisoa ka hloko ho batho ba tsofetseng.

Litaelo tse ikhethang bakeng sa ho nka Combogliz Prolong

Lactic acidosis ke ntho e sa tloaelehang, e tebileng ea metabolic e ka hlahisoang ka lebaka la ho eketseha ha metformin nakong ea kalafo le Combogliz Prolong. Ka nts'etsopele ea lactic acidosis ka lebaka la ts'ebeliso ea metformin, ts'oaetso ea eona ho plasma ea mali e feta 5 μg / ml.

Ho bakuli ba nang le lefu la tsoekere, lactic acidosis hangata e ba le ho hloleha ho matla ha renal, ho kenyeletsoa ka lebaka la tšoaetso ea letsoalo le ho se sebetse hantle ha renal, haholo ha ho nooa lithethefatsi tse 'maloa. Ho bakuli ba nang le ho nyekeloa ke pelo, haholo-holo ho bakuli ba nang le angina e sa tsitsang kapa ho nyekeloa ke pelo haholo le kotsi ea hypoperfusion le hypoxemia, ho na le monyetla o eketsehileng oa lactic acidosis. Kotsi ea ho ba le lactic acidosis e eketseha ka tekanyo ho isa tekanyong ea ho se sebetse ha renal le lilemo tsa mokuli. Ho beha leihlo khafetsa bakeng sa ts'ebetso ea ho ba le fig ho bakuli ba nkang metformin ho lokela ho etsoa 'me ho lokela ho beoa tekanyetso e sebetsang ea metformin. Ho bakuli ba tsofetseng, ho hlokahala hore ho sebetsanoe le tšebetso ea liphio. Metformin ha ea lokela ho fuoa bakuli ba lilemo li 80 le ho feta haeba ts'ebetso ea kutlo e sa holofala (ho latela data ea QC), kaha bakuli bana ba tloaetse ho eketseha ha lactic acidosis. Ho feta moo, kalafo ea metformin e lokela ho khaotsa hang-hang haeba maemo a tsamaeang le hypoxemia, dehydration kapa sepsis a ntshetsa pele. Kaha ho hloleha ha sebete ho ka fokotsa bokhoni ba ho pepeta lactate, metformin ha ea lokela ho fuoa bakuli ba nang le lipontšo tsa lefu la sebete kapa la laboratori.

Ho qala ha lactic acidosis hangata ha ho hlokomeloe 'me ho tsamaisana le matšoao a sa foleng a kang malaise, myalgia, ho hloleha ho phefumoloha, ho otsela ho eketsehileng, bohloko le ho hlonama ka mpeng. Hypothermia, hypotension, le bradyarrhythmia e hananang le tsona li ka hlaha. Mokuli o lokela ho tlalehela ngaka hang-hang matšoao ana kaofela. Haeba matšoao a joalo a fumanoa, kalafo ea metformin e lokela ho khaotsa, ho shebeloa ha li-electrolyte tsa serum, 'mele ea ketone, tsoekere ea mali,' me haeba ho bontšitsoe, pH ea mali, mahloriso a lactate le mahloriso a metformin maling. Matšoao a ka mpeng a hlahang karolong ea morao ea kalafo ea metformin a ka bakoa ke lactic acidosis kapa lefu le leng.

Ho potlakisa venous plasma lactate mahloriso kaholimo ho maemo a holimo a holimo empa ka tlase ho 5 mmol / L ho bakuli ba nkang metformin ho ka supa tsoelo-pele ea lactic acidosis, mme hape e ka ba ka lebaka la lisosa tse ling, tse joalo ka lefu la tsoekere le sa foleng. mojaro.

Ho ba teng ha lactic acidosis ho lokela ho hlahlojoa ho bakuli bohle ba nang le lefu la tsoekere le metabolic acidosis ntle le matšoao a ketoacidosis (ketonuria le ketonemia). Lactic acidosis e hloka kalafo sepetlele. Haeba lactic acidosis e bonoa ho mokuli ea nkang metformin, o lokela ho emisa hang hang ho sebelisa lithethefatsi mme hang hang a qale mehato e tšehetsang e akaretsang.Ho khothaletsoa hore dialysis e qaloe hang-hang ho lokisa acidosis le metformin e hloahloa.

Joalokaha u tseba, joala bo hlahisa phello ea metformin ho lactate metabolism, e eketsang kotsi ea lactic acidosis. Fokotsa tšebeliso ea joala ha u ntse u nka Combogliz Prolong.

Combogliz Prolong ha e khothalletsoe ho bakuli ba nang le lipontšo tsa kliniki le tsa laboratori ea lefu la sebete ka lebaka la kotsi ea lactic acidosis.

Tlhahlobo ea ts'ebetso ea liphio

Pele o qala kalafo ka Combogliz Prolong le bonyane selemo le selemo ka mor'a moo, ho hlokahala hore a hlahlobe ts'ebetso ea liphio. Bakeng sa bakuli ba nang le ts'oaetso ea renal e sitisang mosebetsi, ts'ebetso ea liphio e lokela ho hlahlojoa khafetsa mme kalafo e nang le Combogliz Prolong e lokela ho emisoa haeba matšoao a ho hloleha ha a fig a hlaha.

U lokela ho emisa tšebeliso ea lithethefatsi ka nakoana Combogliz Prolong pele ho ts'ebetso leha e le efe ea ts'ebetso ea bongaka (ntle le lits'ebetso tse nyane tse sa amaneng le ho fokotsa ts'ebeliso ea lino le lino), 'me u se ke ua qalella ts'ebeliso ea eona ho fihlela mokuli a khona ho nka meriana kahare le ts'ebetso e tloaelehileng ea liphio e netefalitsoe. .

Fetoha maemong a bongaka ba bakuli ba nang le lefu la tsoekere la 2 le laoloang pele

Ho mokuli ea nang le T2DM, eo pele a neng a laoloa hantle nakong ea kalafo le Combogliz Prolong, ea bileng a khelohileng maemong a laboratori kapa a tšoaroa ke lefu (haholo-holo maemong a tlhahlobo e sa tsejoeng), matšoao a ketoacidosis kapa lactic acidosis a lokela ho hlahlojoa hanghang. Tlhahlobo e lokela ho kenyelletsa boikemisetso ba li-electrolyte tse serum ea mali, li-ketone, tsoekere ea mali, 'me haeba ho bontšoa, pH ea mali, likhakanyo tsa lactate, pyruvate le metformin. Haeba mofuta leha e le ofe oa acidosis o tsoetse pele, Combogliz Prolong e lokela ho hlakoloa hang-hang le lithethefatsi tse ling tse bitsoang hypoglycemic li fuoe.

Tšebeliso ea lithethefatsi tse ka bakang hypoglycemia

Lithethefatsi tse eketsang secretion ea insulin, joalo ka sulfonylureas, li ka baka hypoglycemia. Ka hona, ho fokotsa kotsi ea hypoglycemia ha e kopantsoe le saxagliptin, ho ka hlokahala ho fokotsa tekanyetso ea lithethefatsi tse eketsang secretion ea insulin.

Hypoglycemia ha e hlahe ho bakuli ba nkang metformin feela ka tsela e tloaelehileng, empa e ka nts'etsapele 'mele o sa lekaneng, ha ts'ebetso e sebetsang ea' mele e sa tlosoe ke tšebeliso ea lik'habohaedreite, kapa ka tšebeliso e kopaneng le lithethefatsi tse ling tsa hypoglycemic (joalo ka sulfonylureas le insulin. Batho ba baholo, ba kulang le ba kulang hampe kapa ba kulang hampe ebile bakuli ba nang le bothata ba ho hlonepha kapa ba tahi kapa ba tahi haholo ba amehile haholo ka litlamorao tsa hypoglycemic. Ho batho ba baholo le bakuli ba nkang beta-blocker, ho ka ba thata ho tseba hore na hypoglycemia e fumaneha joang.

Phekolo e kopanetsoeng e amang ts'ebetso ea renal kapa phetiso ea metformin

Meriana e kopanetsoeng (joalo ka lithethefatsi tsa cationic, e pepesitsoeng ke secretion ho li-renal tubules), e ka amang ts'ebetso ea liphio, ea lebisa ho liphetoho tsa bohlokoa tsa hemodynamic kapa tsa sitisa phetiso ea metformin (bona karolo "Ho sebelisana le lithethefatsi tse ling"), e lokela ho sebelisoa ka hloko.

Boithuto ba radiology ka tsamaiso ea methapo ea methapo ea iodinated phapang

Ha ho etsoa lithuto tsa radiology ka tsamaiso ea methapo ea methapo e tsamaisang iodine, ho ile ha fumanoa mathata a methapo ea pelo, a ka tsamaeang le nts'etsopele ea lactic acidosis ho bakuli ba fumanang metformin. Bakuli ba reretsoeng ho ithuta joalo ba tlameha ho hlakola kalafo ea Combogliz Prolong pele ho lihora tse 48 pele ba etsa ts'ebetso ena, ba hane ho sebelisa moriana ona nakong ea lihora tse 48 kamora ts'ebetso, mme ba qale hape kalafo kamora hore ts'ebetso e tloaelehileng ea liphio e netefatsoe.

Ho oa ha pelo le pelo (tšabo) ea tšimoloho efe kapa efe, ho nyekeloa ke pelo haholo, infarction ea methapo ea pelo le maemo a mang a tsamaeang le hypoxia le lactic acidosis li ka baka azotemia ea pelehi. Ka nts'etsopele ea liketsahalo tse joalo, ho hlokahala hore hang-hang u hlakole phekolo le Combogliz Prolong.

Glucose e holofetseng

Furu, ho sithabela maikutlo, ts'oaetso, ts'ebetso ea bongaka e ka lebisa tlolong ea "glucose" e ngata maling, eo pele e neng e khona ho laola ka thuso ea sethethefatsi Combogliz Prolong. Maemong ana, ho ka hlokahala ho tlosoa ha nakoana kalafo le ho fetisetsa mokuli kalafong ea insulin. Kamora ho tsitsisa khatello ea tsoekere maling le ho ntlafatsa boemo bo tloaelehileng ba mokuli, kalafo e nang le Combogliz Prolong e ka qala hape.

Nakong ea papatso ea ts'ebeliso ea saxagliptin, ho ile ha bonoa karabelo e tebileng ea hypersensitivity ho kenyeletsa anaphylaxis le angioedema. Ka nts'etsopele ea karabelo e matla ea hypersensitivity, ts'ebeliso ea lithethefatsi e lokela ho emisoa, mabaka a mang a ka 'nang a hlaha a nts'etsopele ea mohopolo a lokela ho hlahlojoa,' me ho lokela ho laetsoe kalafo e 'ngoe bakeng sa lefu la tsoekere (bona "Contraindication" le "Litlamorao»).

Tšebelisong ea morao-rao ea saxagliptin, ho se ho amohetsoe litlaleho tse qaqileng tsa linyeoe tsa pancreatitis e mpe. Bakuli ba nkang Combogliz Prolong e lokela ho tsebisoa ka matšoao a tšoaetso ea pancreatitis e bohloko: nako e telele, bohloko bo boholo mpeng. Haeba u belaella nts'etsopele ea pancreatitis, o lokela ho khaotsa ho sebelisa lithethefatsi Combogliz Prolong (bona likarolo "Ka tlhokomeliso" le "Litlamorao»).

Tšusumetso ho bokhoni ba ho khanna makoloi le litsamaiso tsa taolo

Patlisiso mabapi le phello ea saxagliptin mabapi le bokhoni ba ho khanna makoloi le mekhoa ea taolo ha e so etsoa.

Hopola hore saxagliptin e ka baka hlooho.

Bongata

Ka tšebeliso ea nako e telele ea lithethefatsi ho tekanyetso ho fihla ho makhetlo a 80 ho feta ho buelloa, matšoao a botahoa ha a hlalosoe.

Haeba ho na le overdose, kalafo ea matšoao e lokela ho sebelisoa. Saxagliptin le metabolite ea eona e ka sehloohong li hlahisoa ke hemodialysis (tekanyo ea excretion: 23% ea lethal dose ka lihora tse 4).

Ho bile le linyeoe tsa overdose ea metformin, ho kenyelletsa le ho nka li-g tse fetang 50. Hoo e ka bang 10% ea linyeoe hypoglycemia e tsoetseng pele, empa kamano ea eona ea mabaka le metformin ha e so theoe. Ho 32% ea linyeoe tse ngata tsa metformin e ngata, bakuli ba ne ba na le lactic acidosis. Metformin e hloekisoa nakong ea dialysis, ha tumello e fihla ho 170 ml / min.

Tšebelisano le Meriana e meng

Lithethefatsi tse ling li eketsa hyperglycemia (thiazide le li-diuretics tse ling, glucocorticosteroids, phenothiazines, litokisetso tsa li-hormone tsa qoqotho tse nang le iodine, li-estrogens, lithibela-pelehi tsa molomo, phenytoin, acid ea nicotinic, sympathomimetics, li-blocker tse liehang ho feta tsa calcium le isoniazid). Ha u fana ka litlhare kapa ho hlakola lithethefatsi tse joalo ho mokuli ea nkang Combogliz Prolong, hlokomela ka hloko ts'abo ea glucose maling. Tekanyo ea ho tlama metformin ho liprotheine tsa plasma ea mali e nyane, ka hona ha ho na monyetla oa hore e tla sebelisana le lithethefatsi tse tlameletsoeng haholo liprotheine tsa plasma, tse kang salicylates, sulfonamides, chloramphenicol le probenecid (ho fapana le litlamorao tsa sulfonylurea, tse tlangoang haholo. le liprotheine tsa serum).

Matšoao a isoenzymes CYP3A4 / 5

Rifampicin e fokotsa haholo tlhahiso ea saxagliptin ntle le ho fetola AUC ea metabolite ea eona e sebetsang, 5-hydroxy-saxagliptin. Rifampicin ha e ame ho thibeloa ha DPP-4 plasma ea mali nakong ea phekolo ea lihora tse 24.

CYP3A4 / 5 Isoenzyme Inhibitors

Diltiazem e ntlafatsa phello ea saxagliptin ha e sebelisoa hammoho.Keketseho ea ho kenella ha saxagliptin ka plasma ea mali e lebelletsoe ka tšebeliso ea amprenavir, aprepitant, erythromycin, fluconazole, fosamprenavir, lero la morara le verapamil, leha ho le joalo, tekanyetso ea saxagliptin ha e khothalletsoe. Ketoconazole e eketsa haholo khatello ea saxagliptin ho plasma. Keketseho e ts'oanang ea keketseho ea saxagliptin ka plasma ea mali e lebelletsoe ha ho sebelisoa li-inhibitors tse ling tse matla tsa nzoenzymes CYP3A4 / 5 (mohlala, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir le telithromycin). Ha e kopantsoe le inhibitor e matla ea CYP3A4 / 5 isoenzymes, tekanyetso ea saxagliptin e lokela ho fokotsoa ho 2,5 mg.

Lithethefatsi tsa cationic (kk., Amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterone, trimethoprim kapa vancomycin), tse ntlafalitsoeng ke liphio ka ho fafatsa ka glomerular, li ka sebelisanang hantle le metformin, tse hlolisang litsamaiso tse tloaelehileng tsa lipompo. Boithutong ba ts'ebelisano ea lithethefatsi ea metformin le cimetidine le tsamaiso e le 'ngoe le e pheta-phetoang ea lithethefatsi, ho sebelisana ha metformin le cimetidine bakeng sa tsamaiso ea molomo ho baithaopi ba phetseng hantle ho hlokometsoe, ka keketseho e kholo ea 60% ea metformin ho plasma le mali kaofela le keketseho ea 40% ea AUC ea metformin ho plasma le botlalo madi. Nakong ea lipatlisiso ka tekanyetso e le 'ngoe ea moriana, ha ho na phetoho ho halofo-ea bophelo. Metformin ha e ame pharmacokinetics ea cimetidine. Ho khothalletsoa ho beha leihlo bakuli ka hloko, 'me haeba ho hlokahala, fetola lethal dose ho bakuli ba noang lithethefatsi tsa cationic tse hlahisoang ka har'a sistimi ea pronalimal renal.

Phuputsong ea ho sebelisana le tekanyetso e le 'ngoe ea lithethefatsi ho bakuli ba nang le lefu la tsoekere la 2, ts'ebeliso e kopaneng ea metformin le glibenclamide ha e ame pharmacokinetics kapa pharmacodynamics.

Phuputsong e mabapi le tšebelisano ea lithethefatsi ea metformin le furosemide ka tekanyetso e le 'ngoe ea lithethefatsi, e entsoeng ho baithaopi ba phetseng hantle, tšebelisano ea bona ea pharmacokinetic e ile ea senoloa. Furosemide e eketsa C_max metformin ho plasma le mali ka 22% le AUC maling ka 15% ntle le phetoho e kholo ea renal clearance of metformin. Ha e nkuoa le metformin C_max le AUC ea furosemide e fokotsehile ka 31% le 12%, ka ho latellana, 'me bophelo ba halofo bo fokotsehile ka 32% ntle le phetoho e hlakileng ea ho hlaka ha reishene ea furosemide. Ha ho na data mabapi le tšebelisano ea metformin le furosemide ka tšebeliso ea nako e telele e kopaneng.

Phuputsong e mabapi le tšebelisano ea lithethefatsi ea metformin le nifedipine ka tekanyetso e le 'ngoe ea moriana, e entsoeng ho baithaopi ba phetseng hantle, nifedipine e eketsa C_max metformin ho plasma ka 20% le AUC ka 9%, mme e eketsa tlhahiso ea liphio. T_max le T_1/2 ha ea fetoha. Nifedipine e eketsa ho monya metformin. Metformin ha e na phello ho pharmacokinetics ea nifedipine.

Saxagliptin le Metformin

Ts'ebeliso e kopaneng ea litekanyetso tse le 'ngoe tsa saxagliptin (100 mg) le metformin (1000 mg) ha e ame haholo pharmacokinetics ea saxagliptin kapa metformin ho baithaopi ba phetseng hantle.

Ha ho lithuto tse khethehileng tsa pharmacokinetic tsa ts'ebelisano ea lithethefatsi le ts'ebeliso ea Combogliz Prolong li entsoe, leha lithuto tse joalo li entsoe ka likarolo tsa eona tse ikhethang: saxagliptin le metformin.

Matla a lithethefatsi tse ling ho saxagliptin

Glibenclamide: Ts'ebeliso e le 'ngoe e kopaneng ea saxagliptin (10 mg) le glibenclamide (5 mg), karolo e kaholimo ea isoenzyme CYP2C9, e eketse C_max saxagliptin ka 8%, leha ho le joalo, saucagliptin AUC ha e fetohe.

Pioglitazone: Ts'ebeliso e kopaneng ea saxagliptin hang ka letsatsi (10 mg) le pioglitazone (45 mg), karolo e kaholimo ea isoenzyme CYP2C8 (e matla) le CYP3A4 (e fokolang), ha e ame li-pharmacokinetics tsa saxagliptin.

Digoxin: Ts'ebeliso e kopaneng ea saxagliptin hang ka letsatsi (10 mg) le digoxin (0.25 mg), karolo e ka tlase ea P-glycoprotein, ha e ame pharmacokinetics ea saxagliptin.

Simvastatin: Ts'ebeliso e kopaneng ea saxagliptin hang ka letsatsi (10 mg) le simvastatin (40 mg), karolo e kaholimo ea CYP3A4 / 5 isoenzymes, e ile ea eketsa C_max saxagliptin ka 21%, empa saxagliptin AUC ha e fetohe.

Diltiazem: Ts'ebeliso e le 'ngoe e kopaneng ea saxagliptin (10 mg) le diltiazem (360 mg nako e telele ea litekanyetso ka ho lekana), inhibitor e leka-lekaneng ea CYP3A4 / 5 isoenzymes, e eketsa C_max saxagliptin ka 63%, le AUC - makhetlo a 2.1. Sena se tsamaisana le ho fokotseha ho lekanang ha C_max le AUC ea metabolite e sebetsang ka 44% le 36%, ka ho latellana.

Ketoconazole: Ts'ebeliso e kopaneng ea tekanyetso e le 'ngoe ea saxagliptin (100 mg) le ketoconazole (200 mg ka nako e' ngoe le e 'ngoe ka lihora tse 12 ho lekana), ea eketseha_max le AUC ea saxagliptin 2.4 le makhetlo a 3.7, ka ho latellana. Sena se tsamaisana le ho fokotseha ho lekanang ha C_max le AUC ea metabolite e sebetsang ka 96% le 90%, ka ho latellana.

Rifampicin: Ts'ebeliso e kopaneng ea tekanyetso e le 'ngoe ea saxagliptin (5 mg) le rifampicin (600 mg hang ka letsatsi ka tekano) li-lowers_max le AUC ea saxagliptin ka 53% le 76%, ka ho latellana, ka keketseho e lekanang ea C_max(39%), empa ntle le phetoho e kholo ho AUC ea metabolite e sebetsang.

Omeprazole: Ts'ebeliso e ngata e kopaneng ea saxagliptin ka tekanyetso ea 10 mg hang ka letsatsi le omeprazole ka tekanyo ea 40 mg, karolo e ka tlase ea isoenzyme CYP2C19 (e matla) le isoenzyme CYP3A4 (e fokolang), inhibitor ea isoenzyme CYP2C19 le inducer MRP-saok.

Aluminium hydroxide + magnesium hydroxide + simethicone: Ts'ebeliso e kopaneng ea litekanyetso tse le 'ngoe tsa saxagliptin (10 mg) le ho emisoa ho nang le aluminium hydroxide (2400 mg), magnesium hydroxide (2400 mg) le simethicone (240 mg) le tlase tsa C._max saxagliptin ka 26%, leha ho le joalo saxagliptin AUC ha e fetohe.

Famotidine: Ho nka tekanyetso e le 'ngoe ea saxagliptin (10 mg) lihora tse 3 kamora tekanyetso e le' ngoe ea famotidine (40 mg), inhibitor ea hOCT-1, hOCT-2, le hOCT-3, e eketsa C_max saxagliptin ka 14%, leha ho le joalo, saucagliptin AUC ha e fetohe.

Lipehelo tsa Maemo a Phomolo ea meriana

Setlhare ke ngaka.

Lipehelo le maemo a polokelo

Ka mocheso o sa feteng 30 ° C. Qoba hole le bana. Bophelo ba Shelf ke lilemo tse 3.

Ts'ebeliso ea lithethefatsi Combogliz e atoloha feela joalo ka ha u laetsoe ke ngaka, thuto e fanoa bakeng sa ho buuoa!

Fomu ea tokollo, sebopeho le sephutheloana

E fumaneha ka mefuta e meraro ea litaba tsa likarolo tse sebetsang (mg):

• metformin - 1000, saxagliptin - 2,5,
• metformin - 1000, saxagliptin - 5.0,
• metformin - 500, saxagliptin - 5.0.

E kenyellelitsoe:

• magnesium stearate,
• carmellose sodium
• hypromellose.

Ho na le matlapa a 7 ka blister, ka har'a pakete ea karete e nang le taolo ea pele ea ho bula ho ka ba le lilakane tse 4 kapa tse 8.

Ketso ea pharmacological

Matlapa a nang le ts'ebetso e kopaneng, tokollo e fetotsoeng le litaba tsa lisebelisoa tse peli tse sebetsang tse tlatsanang.

Metformin ke biguanide. E thibela gluconeogenesis, e kenella ho oxidation ea mafura mme e eketsa kutloisiso ea li-receptors ho insulin. Ts'ebeliso ea tsoekere ea sele le eona e qalile. Karolo eo ha e ame litaba tsa "insulin" maling ka boeona, ha e bake hypoglycemia. E boetse e tsosa motsoako oa glycogen. Keketseho ea tsoekere e ngata ka lebaka la ho pepesehela lisele. Ho feta moo, ntho ena e khona ho fokotsa sekhahla sa ho kenngoa ha tsoekere ka mpeng ea mpa, ka lebaka leo ho nang le phello ea ho theola boima ba 'mele. E ka ntlafatsa mali a mang.

Saxagliptin e eketsa tokollo ea li-hormone tse khethehileng - li-insretin. Li khothalletsa ho ntšoa ha insulin liseleng tsa beta tsa manyeme le ho fokotsa tlhahiso ea glucagon ho eona. Bokhoni bo ka sehloohong ba saxagliptin ke ho fokotsa tsoekere maling ka mpeng e se nang letho le ka lijo.Hape, ho ntšoa ha mpa hoa thibeloa, e le hore ho ka fumanoa phello e teletsana. E boetse e thusa ho fokotsa boima ba 'mele ba lefu la tsoekere.

Ka lebaka la tokollo e fetotsoeng, menyetla ea litla-morao tse tsoang mpeng ea mpeng e ea fokotseha.

Contraindication

• Hypersensitivity ho likarolo,
• Nalane ea anaphylactic,
• Type 1 lefu la tsoekere
• Lactose mamello,
• Phekolo ea insulin
• Patlisiso e sebelisang lintho tse thehiloeng ho iodine (lihora tse 48 pele le kamora),
• Ho senyeha ha renal le hepatic,
• Mafu a bolaeang, a sa foleng le a tšoaetsanoang,
• Lefu la tsoekere la ketoacidosis
• Nalane ea komisi
• Kotsi ea hypoxia ea linama,
• Nalane ea lactic acidosis,
• Lijo tse tlase tsa khalori
• Bokhachane le pelehi
• Tlas'a lilemo tse 18
• Bokhoba ba tahi

Litaelo tsa ho sebelisoa (mokhoa le litekanyetso)

E khethoa ka bonngoe ho latela bopaki.

Nka nako e le 'ngoe ka letsatsi ka nako e le' ngoe. Khetla ha ea tlameha ho rojoa, kaha sena se ama sekhahla sa tokollo. Noa metsi a mangata.

Phekolo e qala ka matlapa a 500 + 2,5 mg, ebe a ka eketsoa ho 1000 + 5 mg. Boholo - 2000 + 5 mg. Eketsa lethal dose butle-butle ho fokotsa litlamorao tse sa batleheng.

Haeba pele ho mona mokuli a ne a phekoloa ka li-agents tse nang le lintho tsena, empa ka thoko, litekanyetso li khethoa ho latela ea pele. Tšusumetso ho 'mele oa phetoho ho tsoa ho lithethefatsi tse ling tsa hypoglycemic ho ea moriana ona ha e so ithutoe.

Litlamorao

• Ho opeloa ke hlooho, migraines,
• Tšoaetso ea lefu la setho
• Bohloko ba ka mpeng
• Sinusitis
• Ho nyekeloa ke pelo le ho hlatsa
• Letšollo
• Ho ruruha
• Hypoglycemia (ho tloha saxagliptin),
• Urticaria,
• Thrombocytopenia
• Litla-morao
• Nasopharyngitis,
• Gastroenteritis
• Pancreatitis
• Mathata a ho latsoa
• Mochela.

Li tlosoa ka ho fetola litekanyetso, kapa ka ho tlohela lithethefatsi.

Bongata

Haeba ho tloaelehileng ho feta, lactic acidosis e ka hlaha. Sena se na le litlamorao tse mpe - esita le lefu. Haeba ho na le lipelaelo leha e le life tsa kholo ea kholo ea eona, mokuli o lokela ho kena sepetlele. Sepetlele se fana ka phekolo ea hemodialysis le matšoao a kalafo.

• myalgia
• ho hloleha ho phefumoloha
• ho otsela ho eketsehileng
• bohloko ba ka mpeng
• monko oa acetone e tsoang molomong.

Ha u sebelisa lithethefatsi tse ling, haholo-holo tse thehiloeng ho sulfonylurea, kotsi ea hypoglycemia ea eketseha. Matšoao a eona: bofokoli, pallor ea letlalo, letsoalo le sa sisinyeheng (ho fihlela ho ba komisi), tlala, ho teneha le ba bang. Foromo e bonolo e tlosa ho kenella ha lijo tse monate. E leka-lekaneng ebile e matla - ente ea glucagon kapa tharollo ea dextrose. Ho bohlokoa ho tsebisa motho, ebe o botsa ngaka bakeng sa phetoho ea litekanyetso.

Ho sebelisana le lithethefatsi

E ntlafatsa ts'ebetso ea likarolo tse sebetsang:

• aluminium hydroxide,
• pioglitazone
• magnesium hydroxide,
• rifampicin
• GKS,
• nicotinic acid
• simethicone
• estrogens
• thiazide diuretics,
• lihormone tsa qoqotho.
• isoniazid
• phenothiazines,
• phenytoin
• kutloelo-bohloko
• li-blockers tsa liteishene tsa calcium tse liehang ho feta.

Fokotsa katleho ea lintho tse sebetsang:

• diltiazem
• fluconazole
• amprenavir
• verapamil
• erythromycin
• ketoconazole,
• aprepitant
• glibenclamide,
• sulfonylurea derivatives,
• lero la morara
• homotidine
• isoenzymes CYP3A4 / 5,
• furosemide
• litokisetso tsa cationic
• nifedipine
• ethanol.

Ngaka e eang teng e lokela ho tseba kalafo ka lintho tsena ha e fana ka maikutlo a kalafo.

Litaelo tse khethehileng

Kaha moriana o hloekisoa ke liphio, ho khothaletsoa ho etsa tlhahlobo khafetsa le ho lekola maemo a tsona e le ho thibela mathata. Sena ke 'nete ka ho khetheha ka batho ba baholo.

Ho bakuli kamora lilemo tse 60, lactic acidosis e etsahala khafetsa. Ho tsamaisoa khafetsa ke setsebi hoa hlokahala.

Monyetla oa ho ba le pancreatitis o eketseha. Letšoao le ka sehloohong ke bohloko bo bohloko ba nako e telele ka mpeng.

Mokuli o lokela ho tseba matšoao a litla-morao mme a tsebe ho fana ka thuso ea pele.

Haeba ho hlokahala, ts'ebetso ea ts'ebetso ea motho ea ho buoa e fetisetsoa ho insulin.

Ha ho lithuto tse entsoeng tse mabapi le phello ea bokhoni ba ho khanna koloi. Leha ho le joalo, ka kalafo e kopaneng, kotsi ea hypoglycemia e lokela ho hopoloa. Saxagliptin le eona e ka baka hlooho le hlooho. Qeto mabapi le monyetla oa ho khanna koloi kapa ho sebetsa ka mekhoa e entsoe ke setsebi.

Ho bapisoa le li-analogues

Setlhare sena se na le makhetho a 'maloa mabapi le sebopeho le thepa. Ho tla ba molemo ho itloaetsa bona.

"Yanumet." Theko - ho tloha ho li-ruble tse 2830 bakeng sa matlapa a 56. Moetso o kenyelletsa metformin le sitagliptin. E hlahisa k'hamphani Merck Sharp le Dome, USA. E ka sebelisoa hammoho le insulin, leha ho le joalo, litla-morao tse ngata le li-contraindication. Ha e ngoletsoe bana le basali ba bakhachane. Batho ba bangata ba ngola hore moriana o fokotsa boima ba 'mele kapele.

Galvus Met. Litšenyehelo - li-ruble tse 1500 le kaholimo. E na le metformin le vildagliptin. Mohlahisi - "Novartis", Switzerland. E theko e tlase, leha thepa ea eona e sa fapana haholo le "Comboglize". Lethathamo la lipapatso le tšoana.

"Comboglize Xr." E na le sebopeho se tšoanang. E fanoe ke k'hamphani ea AstraZeneca, Great Britain. Pilime e tla bitsa li-ruble tse 1650 ka pakete e ngoe le e ngoe. Analogue e haufi haholo ka thepa. Litla-morao tsohle le li-contraindication li tšoana.

Glibomet. Motsoako o entsoeng ke k'hamphani "Berlin Chemie", Jeremane. Theko - li-ruble tse 350 ka sephutheloana. Lithako tse sebetsang - glibenclamide le metformin. Ha e loketse motho e mong le e mong. Lintho tse ngata tse thibeloang ho sebelisoa.

Bagomet. Matlapa a nang le Metformin le glibenclamide. Theko - ho tloha ho li-ruble tse 160. Li na le ketso e atolositsoeng, li hlahisoa ke k'hamphani Chemistry Montpellier, Argentina. Sesebelisoa se ka sehloohong ke theko e tlase ka thepa e tšoanang. Contraindication e tšoana.

Qeto ea ho fetohela moriana o mong e etsoa ke ngaka. Ho ikoetlisa ho thibetsoe!

Boholo ho na le maikutlo a nepahetseng a moriana. E mpe feela ke litšenyehelo tse phahameng. Hape litlhahlobisong ho hlokometsoe hore ba nkileng pele ho metformin ena ha ba bapisoa le boemo bo fetileng ba bile le litlamorao tse fokolang. Ho fokotsa boima ba 'mele ho boetse ho bonoa, empa feela ka lijo.

Victor: “Ke qetile lilemo tse ngata ke nka matlapa a entsoeng ka metformin. Ba khaolitse ho fana ka takatso eo a e batlang, ngaka e ile ea laela hore ho be le tokiso e kopaneng ea "Combogliz Prolong". Seo ke se ratang: ka potlako fana ka sephetho, e-noa senoelo se le seng ka letsatsi. E boloka litekanyo tse tloaelehileng tsa mmele le tsoekere. Seo ke sa se rateng: ho na le litla-morao, haholo ha o tlohela lijo. E thusa haholo, leha e bitsa chelete e ngata. ”

Alexandra: “Ke lefu la tsoekere le boiphihlelo bo bongata. Lilemong tsa morao tjena, ke sebelisa lithethefatsi tse tsoang kantle ho naha feela. Hona joale ke amohela Combogliz Prolong. Setlhare se hantle, ha ke na litla-morao. E bonolo kamohelong, kamohelo ea theko / boleng e ntatela ka botlalo. "

Qeto

Setlhare sena se sebetsa haholo. Ka lebaka la likarolo tsa tokollo, e thusa ho qoba nts'etsopele ea mathata ka pampitšana ea mala. Litlhahlobo tse tsoang ho basebelisi ba lithethefatsi le litsebi li ntle haholo. Ntho feela e mpe ke litšenyehelo tse phahameng le tlhoko ea ho odara ho meriana. Ho seng joalo, ke sethethefatsi se setle sa lefu la tsoekere.

Mokhoa oa kopo

Bakeng sa batho ba baholo: Ke nka ka molomo 1 nako / letsatsi nakong ea lijo tsa mantsiboea. Tekanyetso e lokela ho khethoa ka bonngoe.
Ka tloaelo, kalafo e kopaneng e nang le saxagliptin le metformin, tekanyo ea saxagliptin ke 5 mg 1 nako / letsatsi. Tekanyetso ea pele ea khothalletso ea metformin e lokollotsoeng ke 500 mg 1 nako / letsatsi, e ka eketsoa ho 2000 mg 1 nako / letsatsi.
Tekanyetso ea metformin e eketseha butle butle ho fokotsa kotsi ea litlamorao ho tsoa mpeng ea mpa.
Sekhahla se seholo sa letsatsi le letsatsi: saxagliptin 5 mg le metformin 2000 mg e fetotsoeng.

- Type 2 lefu la tsoekere le kopantsoe le lijo le boikoetliso ho ntlafatsa taolo ea glycemic.

Foromo ea boholo:

Letlapa le le leng le koahetsoeng ka filimi le nang le tokollo e fetotsoeng

1000 mg + 2,5 mg e na le.

Lintho tse sebetsang: metformin hydrochloride 1000 mg + saxagliptin 2,5 mg

Bohlokoa ba letlapa: metformin hydrochloride e kopantsoeng le 0.5% magnesium stearate 1005.0 mg (1000.0 mg metformin hydrochloride + 5.0 mg magnesium stearate), sodium carmellose 50.0 mg, hypromellose 2208 393.0 mg, magnesium stearate 2.0 mg

Karolo ea pele ea ho koahela ka likhetla: Opadry II tšoeu (% m / m) 130,5 mg polyvinyl joala hanyane hydrolyzed 40.00%, titanium dioksi 25,00%, macrogol 3350 20.20%, talc 14.80%, 1 M tharollo ea hydrochloric acid ho pH 2 , 0 ± 0.3 *,

mokato oa bobeli oa ho koahela ka khetla (e sebetsang): saxagliptin 2,5 mg, Opadray II e tšoeu 20,0 mg, tharollo ea 1 M ea hydrochloric acid ho pH 2.0 ± 0.3 *,

film shell (karolo ea boraro ea koae ('mala)): Opadry II mosehla (% m / m) 48.0 mg polyvinyl joala hanyane hydrolyzed 40.00%, titanium dioksi 24.25%, macrogol 3350 20.20%, talc 14.80%, dae oxide e putsoa 0,75% , Tharollo ea 1 M ea hydrochloric acid ho pH 2.0 ± 0.3 *,

ink bakeng sa ho ngola: inkacode blue> (% m / m) 0,03 mg indigo carmine aluminium varnish 16.00%, shellac

45% (20% esterified) ho ethanol 55.40%, butanol 15.00%, propylene glycol 10.50%, isopropanol 3.00%, 28% tharollo ea ammonium hydroxide 0.10%.

Letlapa le koahetsoeng ka filimi e 500 500 + 5 mg e na le.

Lintho tse sebetsang: metformin hydrochloride 500 mg + saxagliptin 5 mg

Bohlokoa ba letlapa: metformin hydrochloride ka motsoako o nang le 0.5% magnesium stearate 502.5 mg (500.0 mg metformin hydrochloride + 2,5 mg magnesium stearate), sodium carmellose 50.0 mg, hypromellose 2208 358.0 mg, hypromellose 2910 10.0 mg, microcrystalline cellulose 102.0 mg, le magnesium stearate 1.0 mg,

Karolo ea pele ea ho koahela ka likhetla: Opadry II e tšoeu (% m / m) 99.0 mg polyvinyl joala hanyane hydrolyzed 40.00%, titanium dioksi 25,00%, macrogol 3350 20.20%, talc 14.80%, 1 M tharollo ea hydrochloric acid ho pH 2 , 0 ± 0.3 *, bi bobeli mokelikeli o kopaneng (o sebetsang): saxagliptin 5.0 mg, Opadry II tšoeu 20,0 mg, tharollo ea 1 M ea hydrochloric acid ho pH 2.0 ± 0.3 *,

film shell (karolo ea boraro ea koae ('mala)): Opadry II tawny (% m / m) 33.0 mg polyvinyl joala hanyane hydrolyzed 40.00%, macrogol 3350 20.20%, titanium dioxide 19.58%, talc 14.80%, dae oxide yellowide 5, 00% le dae oxideide e khubelu 0,42%, tharollo ea 1 M ea hydrochloric acid ho pH 2.0 ± 0.3 *,

ink bakeng sa ho ngola: inkacode blue> (% m / m) 0,03 mg indigo carmine aluminium varnish 16.00%, shellac

45% (20% esterified) ho ethanol 55.40%, butanol 15.00%, propylene glycol 10.50%, isopropanol 3.00%, 28% tharollo ea ammonium hydroxide 0.10%.

Letlapa le koahetsoeng ka filimi e le 'ngoe la 1000 mg + 5 mg le na le:

Lintho tse sebetsang: hydrochloride 1000 mg + saxagliptin 5 mg Bohlokoa ba letlapa: metformin hydrochloride e kopantsoeng le 0.5% magnesium stearate 1005.0 mg (1000.0 mg metformin hydrochloride + 5.0 mg magnesium stearate), sodium carmellose 50.0 mg, hypromellose 2208 393.0 mg, magnesium stearate 2.0 mg

Karolo ea pele ea ho koahela ka likhetla: Opadry II tšoeu (% m / m) 130,5 mg polyvinyl joala hanyane hydrolyzed 40.00%, titanium dioksi 25,00%, macrogol 3350 20.20%, talc 14.80%, 1 M tharollo ea hydrochloric acid ho pH 2 , 0 ± 0.3 *,

mokato oa bobeli oa ho koahela ka khetla (e sebetsang): saxagliptin 5.0 mg, Opadry II tšoeu 20,0 mg, tharollo ea 1 M hydrochloric acid ho pH 2.0 ± 0.3 *,

film shell (karolo ea boraro ea koae ('mala)): Opadry II pinki (% m / m) 48.0 mg polyvinyl joala hanyane hydrolyzed 40.00%, titanium dioxide 24.25%, macrogol 3350 20.20%, talc 14.80%, dae oxide red red , Tharollo ea 1 M ea hydrochloric acid ho pH 2.0 ± 0.3 *,

ink bakeng sa ho ngola: inkacode blue> (% m / m) 0,03 mg indigo carmine aluminium varnish 16.00%, shellac

45% (20% esterified) ho ethanol 55.40%, empaanol 15.00%, propylene glycol 10.50%, isopropanol 3.00%, 28% tharollo ea ammonium hydroxide 0.10%.

* Haeba ho hlokahala, tharollo ea sodium hydroxide ea 1 M e ka sebelisoa ho fetola pH.
** Haeba ho hlokahala, joala ba isopropanol bo eketsoa ka enke nakong ea ho ngola. Matšoao a indigo carmine aluminium varnish le shellac a lula matlapeng ha a ne a ngoloa. Li-sol sol tse kenyelelitsoeng ka enke li tlosoa nakong ea tlhahiso nakong ea ho omisa.

Matlapa a 1000 mg + 2,5 mg:

Matlapa a biconvex a bopehileng joaloka Capsule, filimi e koahetsoeng ho tloha ho 'mala o mosehla ho isa ho' mala o moputsoa ka 'mala, ha mantsoe ana a le "2,5 / 1000" ka lehlakoreng le leng, ka enke e putsoa.

Matlapa a 500 mg + 5 mg:
Matlapa a biconvex a bopehileng ka sebopeho sa Capsule, a kopantsoeng ho tloha ho brown sootho ho ea sootho, mantsoe a "5/500" a le ka lehlakoreng le leng le "4221" ka lehlakoreng le leng, ka enke e putsoa.

Matlapa a 1000 mg + 5 mg:
Matlapa a biconvex a bopehileng joaloka Capsule, a koahetsoeng ka 'mala oa filimi ea pinki, a nang le mantsoe "5/1000" ka lehlakoreng le leng le "4223" ka lehlakoreng le leng, ka enke e putsoa.

TLHALOSO MABAKA

Pharadodynamics

Mokhoa oa ketso
Combogliz Prolong® e kopanya lithethefatsi tse peli tsa hypoglycemic le mekhoa e tlatselletsang ea ts'ebetso ho ntlafatsa taolo ea glycemic ho bakuli ba nang le mofuta oa 2 lefu la tsoekere mellitus (T2DM): saxagliptin, dipeptidyl peptidase 4 inhibitor (DPP-4), le metformin, moemeli oa sehlopha sa Biguanide.

Saxagliptin
Ha o arabela ho kenella ha lijo ho tsoa ka mpeng e nyane, lihormone tsa "incretin" li kenngoa maling, joalo ka glucagon-peptide-1 (GLP-1) le "insulinotropic polypeptide" (HIP) ea glucose. Lihormone tsena li khothaletsa ho tsoa ha insulin liseleng tsa pancreatic beta, ho latela bongata ba tsoekere maling, empa ha li ananele ke enzyme DPP-4 metsotso e 'maloa. GLP-1 e boetse e theola secretion ea tsoekere ho lisele tsa pancreatic alpha, e fokotsa tlhahiso ea glucose ea sebete. Ho bakuli ba nang le lefu la tsoekere la mofuta oa 2, khatello ea GLP-1 e ea theoha, empa karabelo ea insulin ho GLP-1 e ntse e le teng. Saxagliptin, kaha e le inhibitor ea thibelo ea DPP-4, e fokotsa ho kenella ha lihormone tsa "incretin", ka ho etsa joalo, e eketsang khatello ea bona maling le ho lebisa ho fokotseha ha tsoekere e potlakileng ka mor'a ho ja.

Metformin
Metformin ke sethethefatsi sa hypoglycemic se ntlafatsang mamello ea tsoekere ho bakuli ba nang le lefu la tsoekere la 2, le ho fokotsa khatello ea tsoekere ea postprandial. Metformin e fokotsa tlhahiso ea tsoekere ke sebete, e fokotse ho monya ha tsoekere ka mpeng mme e phahamisa kutloisiso ea insulin, e eketsa ho kenella ka bongata le ts'ebeliso ea tsoekere. Ho fapana le litokisetso tsa sulfonylurea, metformin ha e bake hypoglycemia ho bakuli ba nang le lefu la tsoekere la mofuta oa 2 kapa batho ba phetseng hantle (ntle le maemong a ikhethang, bona likarolo tsa "Boitlhokomelo" le "Litaelo tse Khethehileng"), le hyperinsulinemia. Nakong ea phekolo ea metformin, secretion ea insulin e lula e sa fetohe, leha ho tsepamisa mohopolo oa insulin le ho arabela lijong tsa motšeare ho ka fokotseha.

Ts'ebetso ea Kliniki le Polokeho

Saxagliptin Litekong tsa mahlo tsa bongaka tse sa sebetseng hantle, tse sa sebetseng, tse laoloang, kalafo ea saxagliptin e amohetse bakuli ba fetang 17,000 ba nang le T2DM.

Liphetho tsa pelo
Phuputso e entsoeng ke SAVOR (Tlhahlobo ea Phetho ea methapo ea lefu la pelo ho Bakuli ba Lefu la Ts'oaetso ea Saxagliptin) e hlahlobile sephetho sa pelo ho bakuli ba 16492 ba nang le T2DM (bakuli ba 12959 ba nang le lefu la pelo le netefalitsoeng (CVD), bakuli ba 3533 ba nang le mabaka a mangata a kotsi ea pelo. mathata a methapo ea methapo) le boleng ba 6.5% ≤ HbA1c 14 C-saxagliptin 24% ea lethal dose e ile ea hlalosoa ke liphio e le saxagliptin e sa fetoheng le 36% e le metabolite ea mantlha ea saxagliptin. Radioage e felletseng e fumanoeng ka har'a moroto e lekana le 75% ea lethal dose le nkuoeng. Tlhako e tloaelehileng ea renal ea saxagliptin e ne e ka ba 230 ml / min, boleng bo tloaelehileng ba filtration e ka bang 120 ml / min. Bakeng sa metabolite e ka sehloohong, ho hlakoloa ha renal ho ne ho bapisoa le litekanyetso tsa bohlokoa tsa bosholu ba glomerular. Ekaba 22% ea radioacaction eohle e fumanoeng mefuteng.

Metformin
Ho hlakisoa ha molao ka molao ke nako e ka bang makhetlo a 3,5 ho feta clearinine clearance (CC), e leng se bonts'ang hore secretion ea tubular ke eona tsela e kholo ea excretion ea metformin.Kamora ho kenella, hoo e ka bang 90% ea moriana o kentsoeng o hloekisoa ke liphio nakong ea lihora tse 24 tsa pele, ka halofo ea bophelo ho tsoa ho plasma ea lihora tse ka bang 6.2. Meleng, halofo ea bophelo ke lihora tse ka bang 17.6, ka hona, boima ba sele e khubelu ea mali e kanna ea ba karolo ea phetiso.

Pharmacokinetics maemong a khethehileng a kliniki

Ho hloleha hape
Ha ho kgothaletswe ho sebelisa Combogliz Prolong® ho bakuli ba nang le bothata ba ho phekoloa ke liphiri (bona karolo "Contraindication").

Saxagliptin
Bakeng sa bakuli ba nang le ho hloleha ho ba le renal e bonolo, litekanyetso tsa AUC tsa saxagliptin le metabolite ea eona e sebetsang e ne e le 20% le 70% (ka ho latellana) e phahame ho feta litekanyetso tsa AUC ho bakuli ba nang le ts'ebetso e tloaelehileng ea renal. Kaha keketseho e joalo ea boleng ha e nkoe e le bohlokoa ba bongaka, ha ho kgothaletswe ho fetola tekanyetso ea saxagliptin ho bakuli ba nang le bothata bo fokolang ba renal.

Metformin
Ho bakuli ba nang le ts'ebetso ea renal e sa sebetseng (ho latela liphetho tsa litekanyetso tsa QC), halofo ea bophelo ba metformin e tsoang ho plasma le bolelele ba mali le tumello ea renal ea fokotseha ka tekano ea phokotseho ea QC.

Saxagliptin
Bakeng sa bakuli ba nang le ts'oaetso e matla ea 'mele, e leka-lekaneng le e matla ea hepatic, ho ne ho se na liphetoho tse kholo litabeng tsa pharmacokinetics tsa saxagliptin, ka hona, ho lokisoa ha lethathamo la bakuli ba joalo ha ho hlokahale.

Metformin
Ha ho na lithuto tsa "pharmacokinetic" tsa metformin ho bakuli ba nang le mathata a hepatic.

Saxagliptin
Khalemelo ea tekanyetso ea saxagliptin ho latela bong ba bakuli ha e hlokehe.

Metformin
Lithutong tsa bakuli ba nang le lefu la tsoekere la mofuta oa 2, phello ea hypoglycemic ea metformin ho banna le basali e ne e bapisoa.

Saxagliptin
Bakeng sa bakuli ba lilemo li 65-80, ho ne ho se na phapang e kholo litabeng tsa pharmacokinetics ea saxagliptin ha e bapisoa le bakuli ba lilemo tse nyane (lilemo tse 18 ho isa ho tse 40), ka hona, tokiso ea litekanyetso ho bakuli ba tsofetseng ha e hlokehe. Leha ho le joalo, re lokela ho hopola hore sehlopheng sena sa bakuli, ho fokotseha ha ts'ebetso ea liphio ho na le monyetla o mongata (sheba likarolo "Tekanyetso le tsamaiso" le "litaelo tse khethehileng").

Metformin
Lintlha tse lekantsoeng tse tsoang lithutong tse laoloang tsa pharmacokinetics ea metformin ho baithaopi ba phetseng hantle ba fana ka tlhahiso ea hore botlalo ba plasma ba metformin bo fokotseha, halofo ea bophelo e eketseha, 'me Cmax e eketseha ha e bapisoa le boleng ba litekanyetso tsena ho baithaopi ba bacha ba phetseng hantle. Ho ea ka lintlha tsena, phetoho ho li-pharmacokinetics ea metformin e nang le lilemo tse ntseng li eketseha e bakoa haholo ke phetoho mosebetsing oa liphio. Combogliz Prolong® ha ea lokela ho fuoa bakuli ba lilemo li kaholimo ho 80, ntle le haeba ts'ebetso e tloaelehileng ea renal e netefalitsoe ke liphetho tsa QC.

Saxagliptin
Lithuto tsa pharmacokinetics tsa saxagliptin ho bana ha li e-so tšoaroe.

Metformin
Boithuto ba pharmacokinetics ba metformin e lokisitsoeng bo lokollotsoeng ho bana ha bo e-so tšoaroe.

Mofuta le Morabe

Saxagliptin Ha ho kgothaletswe ho fetola tekanyetso ea saxagliptin ho latela morabe oa mokuli.

Metformin
Ha ho na lithuto tsa "pharmacokinetics of metformin" ho latela mofuta oa bakuli.

Type 2 lefu la tsoekere le kopantsoe le lijo le boikoetliso ho ntlafatsa taolo ea glycemic.

TLHOKOMELLO

• Ho eketsa kutloisiso ea motho ka mong ho karolo efe kapa efe ea lithethefatsi,
• Liphetoho tse tebileng tsa hypersensitivity (anaphylaxis kapa angioedema) ho li-inhibitors tsa DPP-4,
• Mofuta oa 1 lefu la tsoekere (se sa ithutoang)
• Sebelisa ka insulin (ha e ithutoe)
• Congenital galactose ho hloka mamello, khaello ea lactase le malabsorption ea glucose-galactose,
• Boimana, ho nyeka,
• Nete ​​ho fihlela lilemo tse 18 (polokeho le katleho ha e ithutoe),
• Mosebetsi o sa sebetseng oa renal (serum creatinine ≥1.5 mg / dL bakeng sa banna, ≥1.4 mg / dL bakeng sa basali kapa tumello e fokolitsoeng ea creatinine), ho kenyelletsa le ho bakoang ke ho se sebetse hantle ha pelo le methapo (sefuba), infraction ea myocardial e mpe le septicemia,
• Maloetse a hlobaetsang moo ho nang le monyetla oa ho ba le bothata ba ho hlaphoheloa ke lefu la mokokotlo: ho omella (ka ho hlatsa, lets'ollo), feberu, mafu a tebileng a tšoaetsanoang, maemo a hypoxia (ho thothomela, sepsis, tšoaetso ea liphio, mafu a bronchopulmonary),
• Acute kapa e sa foleng ea metabolic acidosis, ho kenyeletsa lefu la tsoekere la ketoacidosis, le kapa le se nang komisi
• Matšoao a boletsoeng ka nepo a mafu a hlobaetsang le a sa foleng a ka lebisang ho nts'etsopele ea tishu hypoxia (ho hloleha ho phefumoloha, ho nyekeloa ke pelo, infarction ea myocardial e mpe).
• Ho buoa hampe le ho lemala (ha ho bontšoa kalafo ea insulin)
• Ts'ebetso ea sebete e sa sebetseng,
• Ho lemalla joala bo sa feleng le chefo e matla ea ethanol,
• Lactic acidosis (ho kenyeletsoa le nalane),
• Nako bonyane lihora tse 48 pele le ka hare ho lihora tse 48 kamora ho etsa lithuto tsa radioisotope kapa x-ray ka ho hlahisoa ha li-agents tse fapaneng tsa iodine,
• Ho latela Lijo tse nang le "Low-calorie" (Bakuli ba baholo
  Kaha saxagliptin le metformin li qepha ka tsela e itseng ke liphio, 'me ho bakuli ba tsofetseng ho fokotseha hoa ts'ebetso ea liphio ho ka etsahala, Combogliz Prolong® e lokela ho sebelisoa ka hloko ho batho ba tsofetseng.

Saxagliptin
Ha ho liphapang tse ka bang teng polokelong kapa ho katleho ea lithethefatsi ho bakuli ba lilemo li 65,> le lilemo tse 75, le bakuli ba banyenyane.
Metformin
Lithuto tsa bongaka tse laoloang tsa metformin ha li kenyeletse palo e lekaneng ea bakuli ba tsofetseng ho khetholla liphapang tsa karabelo kalafong ha li bapisoa le bakuli ba banyenyane, leha boiphihlelo ba kliniki bo sa hlahise liphapang tsa karabelo ho bakuli ba tsofetseng le ba banyenyane. Joalo ka ha le tseba, metformin e pepesoa haholo ke liphio, ka hona ho na le monyetla oa ho ba le liketsahalo tse mpe ho bakuli ba nang le bothata ba ho phekoloa ke lefu la masapo. Comboglyz Prolong® e lokela ho fuoa feela bakuli ba nang le ts'ebetso e tloaelehileng ea renal. Litekanyetso tsa pele le tsa tlhokomelo ea metformin li lokela ho fuoa bakuli ba tsofetseng, ho nahanela ho fokotseha ho teng ha ts'ebetso ea liphio. Phetoho leha e le efe ea litekanyetso e lokela ho etsoa ka mor'a tlhahlobo e hlokolosi ea ts'ebetso ea renal.

Tšireletseho le katleho ea lithethefatsi ho bakuli ba ka tlase ho lilemo tse 18 ha li e-so ithutoe.

PUSELETSO MAHALA

Karabelo e fapaneng lithutong tsa taolo ea glycemic ha e sebelisoasaxagliptin ho monotherapy le ha e eketsoa ho lithethefatsi tse ling

Saxagliptin
Lethathamo la 1 le akaretsa liketsahalo tse bohloko tse hlokometsoeng nakong ea liteko tsa tleliniki (ho sa tsotelehe hore na mofuputsi o hlahlobile kamano ea causal) ho ≥5% ea bakuli ba fumanang saxagliptin 5 mg, le khafetsa ho feta sehlopha sa placebo, ho latela tlhahlobo e kopaneng ea lithuto tsa libeke tse 24 .

Lethathamo 1. Liketsahalo tse bohloko

Saxagliptin5mgN = 882

Sebaka sa sebakaN = 799

Mafu a tšoaetsanoang ka ho fetesisa a phefumoloho

Tšoaetso ea pampitšana ea urinary

Lithuto tse 5 tse laoloang ke placebo tse kenyellelitsoeng tlhahlobisong ena ke lithuto tse peli tsa monotherapy le thuto e le 'ngoe ea phekolo e kopantsoeng le tlatsetso ea saxagliptin ho metformin, thiazolidinedione kapa glibenclamide. Ho bakuli ba nkang saxagliptin ka tekanyetso ea 2,5 mg, hlooho ea hlooho (6.5%) e ne e le ketsahalo e mpe feela e boletsoeng khafetsa ka 5%, 'me e ntlafalitsoe khafetsa ho feta sehlopheng sa placebo.

Ho latela tlhahlobo e le 'ngoe e kopaneng, liketsahalo tse bohloko tse boneng ho> 2% ea bakuli ba nkang saxagliptin ka tekanyetso ea 2,5 mg kapa saxagliptin ka tekanyo ea 5 mg le ho nts'etsapele> 1% khafetsa ho feta sehlopheng sa placebo se kenyelletsa sinusitis (2, 9% le 2.6% bapisoa le 1.6%, ka tatellano), bohloko ba ka mpeng (2.4% le 1.7% bapisoa le 0.5%), gastroenteritis (1.9% le 2.3) % ha e bapisoa le 0.9%) le ho hlatsa (2.2% le 2.3% ha li bapisoa le 1.3%).

Ts'ebetso ea ho robeha ha liso e ne e le 1.0 le 0,6 ka lilemo tse lekholo tsa mokuli, ka ho latellana, ha a nka saxagliptin (tlhahlobo e kopaneng ea tekanyetso ea 2,5 mg, 5 mg le 10 mg) le placebo. Khafetsa ea li-fractures ho bakuli ba nkang saxagliptin ha ea ka ea eketseha ha nako e ntse e tsamaea. Ha ho kamano ea caasm e se e thehiloe, 'me lithuto tsa preclinical ha li bonts'e phello e sa rateheng ea saxagliptin lithong tsa masapo.

Nakong ea lenaneo la kliniki, nts'etsopele ea thrombocytopenia e tsamaellanang le tlhahlobo ea idiopathic thrombocytopenic purpura e ile ea bonoa. Khokahano pakeng tsa nts'etsopele ea ketsahalo ena le tsamaiso ea saxagliptin ha e tsejoe.

Liketsahalo tse bohloko tse amanang le tsamaiso ea kopanelo ea saxagliptin le metformin kalafong ea bakuli ba nang le lefu la tsoekere la mofuta oa 2 ba sa kang ba fumana kalafo lithutong tsa taolo ea glycemicSaxagliptin
Lethathamo la 2 le akaretsa liketsahalo tse bohloko tse hlokometsoeng (ho sa tsotelehe kamano ea moferefere ke mofuputsi) ho% 5% ea bakuli ba nkang karolo thutong e eketsehileng ea libeke tse 24 ka taolo e sebetsang ea taolo e kopaneng ea saxagliptin le metformin ho bakuli ba neng ba sa amohela kalafo pele.

Lethathamo la 2. Liketsahalo tse bohloko

Boholo(%)ea bakuli

Saxagliptin5mg+metformin*N = 320

Metformin* N = 328

* Tekanyetso ea pele ea metformin 500 mg / ka letsatsi e ile ea eketsoa ka tekanyo e phahameng ea 2000 mg / ka letsatsi.

Ho bakuli ba fumanang saxagliptin ntle le kalafo ea metformin kapa kalafo ea mantlha ea ho kopanya, lets'ollo e ne e le ketsahalo e mpe ea mpa e hlahileng ho ≥ 5% ea bakuli sehlopheng sefe kapa sefe. Ts'oaetso ea lets'ollo e ne e le 9.9%, 5.8% le 11.2% sehlopheng sa saxagliptin 2,5 mg, saxagliptin 5 mg le placebo, ka tatellano, lithutong tsa tlatsetso ea saxagliptin ho metformin, liketsahalo tsa lets'ollo e ne e le 6.9% le 7.3% sehlopheng sa phekolo ea kopanya le saxagliptin 5 mg le metformin le sehlopha sa metformin monotherapy thutong ea kalafo ea motsoako ea pele le metformin.

Hypoglycemia

Saxagliptin
Tlhahisoleseling mabapi le hypoglycemia joalo ka ketsahalo e mpe e ile ea bokelloa motheong oa litlaleho tsa hypoglycemia; ha ho hlokahale tekanyo e tšoanang ea khatello ea tsoekere. Ts'ebetso ea hypoglycemia ka ts'ebeliso ea saxagliptin 2,5 mg, saxagliptin 5 mg le placebo (kaofela joalo ka monotherapy) e ne e le 4%, 5.6% le 4.1%, ka tatellano, le 7.8%, 5.8% le 5 %, ka ho latellana, le kenyelletso ea metformin. Kotsi ea hypoglycemia e ne e le 3,4% ho bakuli ba sa phekoloang ba neng ba nkile saxagliptin ka tekanyetso ea 5 mg hammoho le metformin, le 4% ho bakuli ba amanang le metformin monotherapy.

Boitšoaro ba Hypersensitivity

Saxagliptin
Tlhahlobisong ea lithuto tse hlano tse kentsoeng, liketsahalo tse bohloko tse amanang le hypersensitivity (joalo ka urticaria le sefahleho edema) li ile tsa bonoa ho 1.5%, 1.5% le 0.4% ea bakuli ba fumanang saxagliptin ka tekanyetso ea 2,5 mg, saxagliptin ka tekanyetso. 5 mg le placebo, ka ho latellana. Ho ea ka bafuputsi, ha ho le e 'ngoe ea liketsahalo tsena ho bakuli ba fumanang saxagliptin e hlokang sepetlele mme ha ea ka ea sokela bophelo ba bakuli. Thutisong ena ea tlhaiso-leseling, mokuli a le mong ea fumaneng saxagliptin ha a qheleloa ka thoko thutong ka lebaka la nts'etsopele ea urticaria le edema ea sefahleho.

Matšoao a ts'ebetso ea 'mele

Saxagliptin
Ho bakuli ba fumaneng saxagliptin e le monotherapy kapa hammoho le metformin, ha ho liphetoho tse kholo tsa kliniki tse ileng tsa senoloa.

Monotherapy

Metformin
Lithutong tse laoloang ke placebo, liketsahalo tse mpe tse atileng ho feta tse hlokometsoeng> 5% ea bakuli ba fumanang metformin e lokisitsoeng e lokolloang khafetsa ho feta sehlopheng sa placebo ba ne ba ts'oeroe ke lets'ollo le ho hlatsa.

Likarohano tse fapaneng tsa Saxagliptin ho TSOHLE Thutong ea SAVOR

Phuputsong ea SAVOR, bakuli ba 8240 ba ile ba fumana saxagliptin ka tekanyetso ea 2,5 mg kapa 5 mg hang ka letsatsi, mme bakuli ba 8173 ba amohetse placebo.Nako e tloaelehileng ea kalafo ea saxagliptin, ho sa tsotelehe litšitiso tsa kalafo, e bile lilemo tse 1,8. Ho bakuli ba 3698 (45%), nako ea kalafo ea saxagliptin e ne e le lilemo tse 2-3. Keketseho e akaretsang ea liketsahalo tse bohloko thutong ena sehlopheng sa bakuli ba nkang saxagliptin (72,5%) e ne e bapisoa le maemo a liketsahalo tse bohloko sehlopheng sa placebo (72,2%).

Khafetsa ea ho khaotsa ho phekoloa ka lebaka la liketsahalo tse bohloko e ne e ka bapisoa le ho bakuli ba nkang saxagliptin (4,9%) le placebo (5%). Boithuto ba SAVOR bo hlahlobile phello ea saxagliptin litheko tsa mathata a pelo le pelo. Ho kenyelletsa saxagliptin ho kalafo ha ho e-so bontšoe ho eketsa kotsi ea mathata a pelo (joalo ka lefu la pelo, infarction ea nonfatal myocardial, stroke ea nonfatal ischemic) ho bakuli ba nang le T2DM bapisoa le placebo (RR 1.00, 95% CI 0, 89, 1.12, P Palo e phethahetseng ea li-lymphocyte

Saxagliptin
Ha u sebelisa saxagliptin, ho fokotseha ha tekanyo e thehiloeng ho litekanyetso ho palo e felletseng ea li-lymphocytee ho hlokometsoe. Ha ho hlahlojoa lintlha tse kopaneng tsa lithuto tse hlano tse lahleloang ka beke, 24, ho fokotseha hoo e ka bang 100 le lisele tse 120 / μ tsa palo e felletseng ea li-lymphocyte tse tsoang ho palo ea pele ea lisele tsa 2200 / μl li ile tsa bonoa le saxagliptin ka tekanyo ea 5 mg le 10 mg, ka ho bapisoa le placebo . Phello e ts'oanang e ile ea bonoa ha ho ne ho nkoa saxagliptin ka tekanyetso ea 5 mg ka kopanong ea pele le metformin ha e bapisoa le metformin monotherapy. Ho ne ho se na phapang lipakeng tsa kalafo ea saxagliptin ea 2,5 mg le placebo. Karolo ea bakuli eo palo ea li-lymphocyte e neng e le ≤ 750 lisele / μl e ne e le 0.5%, 1.5%, 1.4%, le 0.4% lihlopheng tsa kalafo tsa saxagliptin ka tekanyo ea 2,5 mg, ka tekanyo ea 5 mg , ka tekanyetso ea 10 mg le placebo, ka ho latellana. Ho bakuli ba bangata ba sebelisang saxagliptin khafetsa, ha ho na ho khutlisetsoa hape ho sena, le hoja ho bakuli ba bang palo ea li-lymphocyte e ile ea fokotseha hape ha ba ntse ba qala phekolo ka saxagliptin, e lebisitseng ho feliseng saxagliptin. Ho fokotseha ha palo ea li-lymphocyte ho ne ho sa tsamaisane le lipontšo tsa bongaka.

Phuputsong ea SAVOR, ho fokotseha ha palo ea li-lymphocyte sehlopheng sa saxagliptin ho ile ha bonoa ho 0.5% ea bakuli, sehlopheng sa placebo - ho 0,4% ea bakuli.

Mabaka a ho fokotseha ha palo ea li-lymphocyte nakong ea kalafo ea saxagliptin ha a bapisoa le placebo ha a tsejoe. Haeba ho na le ts'oaetso e sa tloaelehang kapa ea nako e telele, ho hlokahala ho lekanya palo ea li-lymphocyte. Kameho ea saxagliptin palong ea li-lymphocyte ho bakuli ba nang le mahlaba ka bongata ka palo ea li-lymphocyte (mohlala, vaerase ea immunodeficiency virus) ha e tsejoe.

Saxagliptin
Saxagliptin e ne e se na phello ea bohlokoa tlhatlhobong kapa ho latela tatellano ea palo ea liplatelese maemong a ts'eletseng a mahlo a tšeletseng, a laoloang tleliniking ea ts'ireletso le ho sebetsa hantle.

Tlhatlhobo ea Vitamin B12

Lithutong tsa bongaka tse laoloang tsa metformin tse nkang libeke tse 29, bakuli ba ka bang 7% ba bontšitse ho fokotseha ha serum pejana ho feta tekanyo e tloaelehileng ea vithamine B12 ho boleng bo botle ntle le lipontšo tsa kliniki. Leha ho le joalo, ho fokotseha ho joalo hangata ha ho tsamaisane le nts'etsopele ea phokolo ea mali 'me e fola kapele ka mor'a ho khaotsa metformin kapa tšebeliso e eketsehileng ea vithamine B12.

PUSELETSO

Ka tšebeliso ea nako e telele ea lithethefatsi ho tekanyetso ho fihla ho makhetlo a 80 ho feta ho buelloa, matšoao a botahoa ha a hlalosoe.

Haeba ho na le overdose, kalafo ea matšoao e lokela ho sebelisoa. Saxagliptin le metabolite ea eona e ka sehloohong li hlahisoa ke hemodialysis (tekanyo ea excretion: 23% ea lethal dose ka lihora tse 4).

Metformin
Ho bile le linyeoe tsa overdose ea metformin, ho kenyelletsa le ho nka li-g tse fetang 50. Hoo e ka bang 10% ea linyeoe hypoglycemia e tsoetseng pele, empa kamano ea eona ea mabaka le metformin ha e so theoe. Ho 32% ea linyeoe tse ngata tsa metformin e ngata, bakuli ba ne ba na le lactic acidosis. Metformin e hloekisoa nakong ea dialysis, ha tumello e fihla ho 170 ml / min.

HO SEBELISANA LE LITLHAKI TSE LING TSE LING TSA BOPHELO

Saxagliptin metabolism e kopantsoe haholo le cytochrome P450 3A4 / 5 isoenzyme system (CYP3A4 / 5). Liphuputso tsa in vitro li bontšitse hore saxagliptin le metabolite ea eona ea mantlha ha e thibele CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 le 3A4 isoenzymes mme ha e qobelle CYP1A2, 2B6, 2C9, le 3A4 isoenzymes. Ka hona, phello ea saxagliptin ho hlakisoa ha metabolic ea lithethefatsi metabolism eo li-isoenzymes tsena li amehang ha e lebelloe ha li sebelisoa hammoho. Saxagliptin ha se inhibitor ea bohlokoa kapa inducer ea P-gp.

Metformin
Lithethefatsi tse ling li eketsa hyperglycemia (thiazide le li-diuretics tse ling, glucocorticosteroids, phenothiazines, litokisetso tsa li-hormone tsa qoqotho tse nang le iodine, li-estrogens, lithibela-pelehi tsa molomo, phenytoin, acid ea nicotinic, sympathomimetics, li-blocker tse liehang ho feta tsa calcium le isoniazid). Ha ho fana kapa ho hlakola lithethefatsi tse joalo ho mokuli ea nkang Combogliz Prolong®, khatello ea tsoekere maling e lokela ho behoa leihlo ka hloko. Tekanyo ea ho tlama metformin ho liprotheine tsa plasma ea mali e nyane, ka hona ha ho na monyetla oa hore e tla sebelisana le lithethefatsi tse tlameletsoeng haholo liprotheine tsa plasma, tse kang salicylates, sulfonamides, chloramphenicol le probenecid (ho fapana le litlamorao tsa sulfonylurea, tse tlangoang haholo. le liprotheine tsa serum).

Matšoao a isoenzymes CYP3A4 / 5

Saxagliptin
Rifampicin e fokotsa haholo tlhahiso ea saxagliptin ntle le ho fetola AUC ea metabolite ea eona e sebetsang, 5-hydroxy-saxagliptin. Rifampicin ha e ame ho thibeloa ha DPP-4 plasma ea mali nakong ea phekolo ea lihora tse 24.

CYP3A4 / 5 Isoenzyme Inhibitors

Saxagliptin
Diltiazem e ntlafatsa phello ea saxagliptin ha e sebelisoa hammoho. Keketseho ea ho kenella ha saxagliptin ka plasma ea mali e lebelletsoe ka tšebeliso ea amprenavir, aprepitant, erythromycin, fluconazole, fosamprenavir, lero la morara le verapamil, leha ho le joalo, tekanyetso ea saxagliptin ha e khothalletsoe.

Ketoconazole e eketsa haholo khatello ea saxagliptin ho plasma. Keketseho e ts'oanang ea keketseho ea saxagliptin ka plasma ea mali e lebelletsoe ha ho sebelisoa li-inhibitors tse ling tse matla tsa CYP3A4 / 5 isoenzymes (mohlala, atazanavir, clearithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir le telithromycin). Ha e kopantsoe le inhibitor e matla ea CYP3A4 / 5 isoenzymes, tekanyetso ea saxagliptin e lokela ho fokotsoa ho 2,5 mg.

Metformin
Lithethefatsi tsa cationic (kk., Amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamteren, trimethoprim kapa vancomycin), tse hlahisoang ke liphio ka ho fafatsa ka glomerular, li ka sebelisanang hantle le metformin, ka tlholisano ea methapo ea methapo e tloaelehileng. Lithutong tsa ts'ebelisano ea lithethefatsi ea metformin le cimetidine ka tsamaiso e le 'ngoe le e pheta-phetoang ea lithethefatsi, metformin le cimetidine li ile tsa bonoa ha li fanoa ka molomo ho baithaopi ba phetseng hantle, ka keketseho e kholo ea 60% ea metformin ho plasma le mali ohle le keketseho ea 40% ho AUC ea metformin ho plasma le botlalo madi. Nakong ea lipatlisiso ka tekanyetso e le 'ngoe ea moriana, ha ho na phetoho ho halofo-ea bophelo. Metformin ha e ame pharmacokinetics ea cimetidine. Ho khothalletsoa ho beha leihlo bakuli ka hloko, 'me haeba ho hlokahala, fetola lethal dose ho bakuli ba noang lithethefatsi tsa cationic tse hlahisoang ka har'a sistimi ea pronalimal renal.

Metformin
Phuputsong ea ho sebelisana le tekanyetso e le 'ngoe ea lithethefatsi ho bakuli ba nang le lefu la tsoekere la 2, ts'ebeliso e kopaneng ea metformin le glibenclamide ha e ame pharmacokinetics kapa pharmacodynamics.

Metformin
Phuputsong e mabapi le tšebelisano ea lithethefatsi ea metformin le furosemide ka tekanyetso e le 'ngoe ea lithethefatsi, e entsoeng ho baithaopi ba phetseng hantle, tšebelisano ea bona ea pharmacokinetic e ile ea senoloa. Furosemide e eketsa Cmax ea metformin ho plasma le mali ka 22% le AUC maling ka 15% ntle le phetoho e kholo ea renal clearance ea metformin. Ha e kopantsoe le metformin, Cmax le AUC ea furosemide e fokotseha ka 31% le 12%, ka ho latellana, 'me halofo ea bophelo e fokotseha ka 32% ntle le phetoho e hlokomelehang ho hlakolo ea renal ea furosemide. Ha ho na data mabapi le tšebelisano ea metformin le furosemide ka tšebeliso ea nako e telele e kopaneng.

Metformin
Phuputsong e mabapi le tšebelisano ea lithethefatsi ea metformin le nifedipine ka tekanyetso e le 'ngoe ea moriana, o entsoeng ka ho nka karolo ha baithaopi ba phetseng hantle, nifedipine e eketsa Cmax ea plasma metformin ka 20% le AUC ka 9%, mme e eketsa tlhahiso ea liphio. Tmax le pheletso ea halofo ea bophelo ha ea ka ea fetoha. Nifedipine e eketsa ho monya metformin. Metformin ha e na phello ho pharmacokinetics ea nifedipine.

Saxagliptin le Metformin
Ts'ebeliso e kopaneng ea litekanyetso tse le 'ngoe tsa saxagliptin (100 mg) le metformin (1000 mg) ha e ame haholo pharmacokinetics ea saxagliptin kapa metformin ho baithaopi ba phetseng hantle. Ha ho lithuto tse khethehileng tsa pharmacokinetic tsa ts'ebelisano ea lithethefatsi le ts'ebeliso ea Combogliz Prolong® li entsoe, leha lithuto tse joalo li se li entsoe ka likarolo tsa eona tse ikhethang: saxagliptin le metformin.

Matla a lithethefatsi tse ling ho saxagliptin

Glibenclamide: Ts'ebeliso e le 'ngoe e kopaneng ea saxagliptin (10 mg) le glibenclamide (5 mg), karolo e kaholimo ea CYP2C9 isoenzyme, e ile ea eketsa Cmax ea saxagliptin ka 8%, empa AUC ea saxagliptin ha ea ka ea fetoha.
Pioglitazone: Ts'ebeliso e kopaneng ea saxagliptin hang ka letsatsi (10 mg) le pioglitazone (45 mg), karolo e kaholimo ea isoenzyme CYP2C8 (e matla) le CYP3A4 (e fokolang), ha e ame li-pharmacokinetics tsa saxagliptin.
Digoxin: Ts'ebeliso e kopaneng ea saxagliptin hang ka letsatsi (10 mg) le digoxin (0.25 mg), karolo e ka tlase ea P-glycoprotein, ha e ame pharmacokinetics ea saxagliptin.
Simvastatin: Ts'ebeliso e kopaneng ea saxagliptin hang ka letsatsi (10 mg) le simvastatin (40 mg), karolo e ka tlase ea CYP3A4 / 5 isoenzymes, e ekelitse Stax ea saxagliptin ka 21%, empa AUC ea saxagliptin ha ea ka ea fetoha.
Diltiazem: Ts'ebeliso e le 'ngoe ea saxagliptin (10 mg) le diltiazem (360 mg nako e telele ea litekanyetso ka ho lekana), inhibitor e leka-lekaneng ea CYP3A4 / 5 isoenzymes, e eketsa Stax ea saxagliptin ka 63%, le AUC ka makhetlo a 2.1. Sena se tsamaisana le ho fokotseha ho lekanang ho Stax le AUC ea metabolite e sebetsang ka 44% le 36%, ka ho latellana.
Ketoconazole: Ts'ebeliso e kopaneng ea tekanyetso e le 'ngoe ea saxagliptin (100 mg) le ketoconazole (200 mg ka nako e' ngoe le e 'ngoe ka lihora tse 12 ka tekano) e eketsa Stax le AUC ea saxagliptin 2.4 le makhetlo a 3.7, ka ho latellana. Sena se tsamaisana le ho fokotseha ho lekanang ho Stax le AUC ea metabolite e sebetsang ka 96% le 90%, ka ho latellana.
Rifampicin: Ts'ebeliso e kopaneng ea tekanyetso e le 'ngoe ea saxagliptin (5 mg) le rifampicin (600 mg hang ka letsatsi ka tekano) e fokotsa Stax le AUC ea saxagliptin ka 53% le 76%, ka ho latellana, ka keketseho e lekanang ea Stax (39%), empa ntle le phetoho e kholo ho AUC metabolite e sebetsang.
Omeprazole: Ts'ebeliso e ngata e kopaneng ea saxagliptin ka tekanyetso ea 10 mg hang ka letsatsi le omeprazole ka tekanyo ea 40 mg, karolo e ka tlase ea isoenzyme CYP2C19 (e matla) le isoenzyme CYP3A4 (e fokolang), inhibitor ea isoenzyme CYP2C19 le inducer MRP-3lok ha e ame.

Aluminium hydroxide + magnesium hydroxide + simethicone:
Ts'ebeliso e kopaneng ea litekanyetso tse le 'ngoe tsa saxagliptin (10 mg) le ho emisoa tse nang le aluminium hydroxide (2400 mg), magnesium hydroxide (2400 mg) le simethicone (240 mg) ho fokotsa Stax ea saxagliptin ka 26%, leha ho le joalo, saxagliptin AUC ha e fetohe.

Famotidine: Ho nka tekanyetso e le 'ngoe ea saxagliptin (10 mg) lihora tse 3 kamora tekanyetso e le' ngoe ea famotidine (40 mg), inhibitor ea hOCT-1, hOCT-2, le HOCT-3, e eketsa Cmax ea saxagliptin ka 14%, leha ho le joalo, saxagliptin AUC ha e fetohe.

Sokolla foromo le sebopeho

Foromo ea litekanyetso - matlapa a lokolotsoeng a ntlafalitsoeng, lifilimi tse koahetsoeng (ka karete ea likarete tse 4 tsa matlapa a 7 le litaelo tsa Combolize Prolong, ho ekelletsa litafoleng tsa 1000 + 2,5 mg - lilakane tse 8 tsa matlapa a 7):

• dosage 1000 mg + 2,5 mg: capsule e bopehile joaloka biconvex, koaeha filimi ho tloha ho 'mala o mosehla ho isa ho o mosehla o khanyang, ka enke e' mala o moputsoa ka lehlakoreng le leng e ngotsoe "2,5 / 1000", lehlakoreng le leng - "4222",
• litekanyetso 500 mg + 5 mg: hempe e bopehile joaloka biconvex, kobo ea filimi ho tloha ho sootho ho isa ho sootho, ka enke e putsoa ka lehlakoreng le leng e ngotsoe "5/500", ka lehlakoreng le leng - "4221",
• litekanyetso li-1000 mg + 5 mg: sebopeho-sebopeho, biconvex, kobo e pinki ea enke, enke e putsoa ka lehlakoreng le leng e ngotsoe "5/1000", ka lehlakoreng le leng - "4223".

Lintho tse sebetsang tse thathamisitsoeng letlapeng le le leng:

• metformin hydrochloride - 1000 mg + saxagliptin - 2,5 mg,
• metformin hydrochloride - 500 mg + saxagliptin - 5 mg,
• metformin hydrochloride - 1000 mg + saxagliptin - 5 mg.

Ho hlophisoa letlapeng le le leng le nang le tlhahiso e fetotsoeng, filimi e koahetsoeng (1000 mg + 2,5 mg / 500 mg + 5 mg / 1000 mg + 5 mg):

• methapo ea methapo: metformin hydrochloride ka motsoako o nang le stearate e nang le 0.5% - 1005 / 502.5 / 1005 mg, sodium carmellose - 50/50/50 mg, hypromellose 2208 - 393/358/393 mg, hypromellose 2910 - 0/10 / 0 mg, magnesium stearate - 2/1/2 mg, microcrystalline cellulose - 0/102/0 mg,
• seaparo sa pele sa kobo (se sirelletsang): Opadry II e tšoeu (% m / m) - 130,5 / 99 / 130.5 mg (karolo e nang le hydrolyzed polyvinyl e nooang - 40%, "titanium" - 25%, macrogol 3350 - 20.2% , talc - 14.8%), 1M hydrochloric acid tharollo - ho fihlela ho pH 2 ± 0.3,
• mokelikeli oa bobeli oa koae e koahelang (e sebetsang): saxagliptin - 2,5 / 5/5 mg, Opadry II e tšoeu - 20/20/20 mg, tharollo ea 1M ea hydrochloric acid - ho fihlela ho pH 2 ± 0.3,
• ink bakeng sa mongolo: Opacode blue ink (% m / m) - 0,03 / 0,03 / 0,03 mg (indigo carmine aluminium varnish - 16%, shellac

45% ho ethanol - 55,4%, butanol - 15%, propylene glycol - 10,5%, isopropanol - 3%, 28% tharollo ea ammonium hydroxide - 0,1%.

Karolo ea boraro ('mala) ea koae e bolokiloeng:

• 1000 + 2,5 mg: Opadry II mosehla (% m / m) - 48 mg (karolo e nang le hydrolyzed polyvinyl e nyane - 40%, titanium diamusi - 24.25%, macrogol 3350 - 20.2%, talc - 14.8% , dae e nang le oksijene ea daen - 0,75%), tharollo ea 1M ea hydrochloric acid - ho fihlela ho pH 2 ± 0.3,
• 1000 + 5 mg: Opadry II tan (% m / m) - 33 mg (karolo e lekanyelitsoeng ea hydrolyzed polyvinyl - 40%, macrogol 3350 - 20.2%, "titanium" - 19.58%, talc - 14.8% , dae e nang le "oxide" ea dae e mosehla - 5%, e nang le oxide e khubelu - 0,42%), tharollo ea 1M ea hydrochloric acid - ho fihlela ho pH 2 ± 0.3,
• 500 + 5 mg: Opadry II pinki (% m / m) - 48 mg (karolo e nang le hydrolyzed polyvinyl e nyane - 40%, titanium dioxide - 24.25%, macrogol 3350 - 20.2%, talc - 14.8%, bofubelu dae iron oxide - 0,75%), tharollo ea 1M ea hydrochloric acid ho pH ea 2 ± 0.3.

TLHOKOMELISO LITLHAKISO

Lactic acidosis

Lactic acidosis ke ntho e sa tloaelehang, e tebileng ea metabolic e ka hlahisoang ka lebaka la ho eketseha ha metformin nakong ea kalafo le Combogliz Prolong®. Ka nts'etsopele ea lactic acidosis ka lebaka la ts'ebeliso ea metformin, ts'oaetso ea eona ho plasma ea mali e feta 5 μg / ml.

Ho bakuli ba nang le lefu la tsoekere, lactic acidosis hangata e ba le ho hloleha ho matla ha renal, ho kenyeletsoa ka lebaka la tšoaetso ea letsoalo le ho se sebetse hantle ha renal, haholo ha ho nooa lithethefatsi tse 'maloa. Ho bakuli ba nang le ho nyekeloa ke pelo, haholo-holo ho bakuli ba nang le angina e sa tsitsang kapa ho nyekeloa ke pelo haholo le kotsi ea hypoperfusion le hypoxemia, ho na le monyetla o eketsehileng oa lactic acidosis. Kotsi ea ho ba le lactic acidosis e eketseha ka tekanyo ho isa tekanyong ea ho se sebetse ha renal le lilemo tsa mokuli.

Ho beha leihlo khafetsa bakeng sa ts'ebetso ea ho ba le fig ho bakuli ba nkang metformin ho lokela ho etsoa 'me ho lokela ho beoa tekanyetso e sebetsang ea metformin. Ho bakuli ba tsofetseng, ho hlokahala hore ho sebetsanoe le tšebetso ea liphio. Metformin ha ea lokela ho fuoa bakuli ba lilemo li 80 le ho feta haeba ts'ebetso ea kutlo e sa holofala (ho latela data ea QC), kaha bakuli bana ba tloaetse ho etsa lactic acidosis.Ho feta moo, kalafo ea metformin e lokela ho khaotsa hang-hang haeba maemo a tsamaeang le hypoxemia, dehydration kapa sepsis a ntshetsa pele. Kaha ho hloleha ha sebete ho ka fokotsa bokhoni ba ho pepeta lactate, metformin ha ea lokela ho fuoa bakuli ba nang le lipontšo tsa lefu la sebete kapa la laboratori.

Ho qala ha lactic acidosis hangata ha ho hlokomeloe 'me ho tsamaisana le matšoao a sa foleng a kang malaise, myalgia, ho hloleha ho phefumoloha, ho otsela ho eketsehileng, bohloko le ho hlonama ka mpeng. Hypothermia, hypotension, le bradyarrhythmia e hananang le tsona li ka hlaha. Mokuli o lokela ho tlalehela ngaka hang-hang matšoao ana kaofela. Haeba matšoao a joalo a fumanoa, kalafo ea metformin e lokela ho khaotsa, ho shebeloa ha li-electrolyte tsa serum, 'mele ea ketone, tsoekere ea mali,' me haeba ho bontšitsoe, pH ea mali, mahloriso a lactate le mahloriso a metformin maling. Matšoao a ka mpeng a hlahang karolong ea morao ea kalafo ea metformin a ka bakoa ke lactic acidosis kapa lefu le leng.

Ho potlakisa venous plasma lactate mahloriso kaholimo ho maemo a holimo a holimo empa ka tlase ho 5 mmol / L ho bakuli ba nkang metformin ho ka supa tsoelo-pele ea lactic acidosis, hape e ka ba ka lebaka la lisosa tse ling, tse joalo ka lefu la tsoekere le sa foleng. mojaro.

Ho ba teng ha lactic acidosis ho lokela ho hlahlojoa ho bakuli bohle ba nang le lefu la tsoekere le metabolic acidosis ntle le matšoao a ketoacidosis (ketonuria le ketonemia).

Lactic acidosis e hloka kalafo sepetlele. Haeba lactic acidosis e bonoa ho mokuli ea nkang metformin, o lokela ho emisa hang hang ho sebelisa lithethefatsi mme hang hang a qale mehato e tšehetsang e akaretsang. Ho khothaletsoa hore dialysis e qaloe hang-hang ho lokisa acidosis le metformin e hloahloa.

Joalokaha u tseba, joala bo hlahisa phello ea metformin ho lactate metabolism, e eketsang kotsi ea lactic acidosis. Fokotsa tšebeliso ea joala ha u ntse u nka Combogliz Prolong®.

Ho hloleha ha sebete

Ts'ebeliso ea lithethefatsi Combogliz Prolong® e tšoaetsanoe ho bakuli ba nang le matšoao a kliniki le a laboratori ea lefu la sebete ka lebaka la kotsi ea lactic acidosis.

Tlhahlobo ea ts'ebetso ea liphio

Pele o qala kalafo ka Combogliz Prolong® le bonyane selemo le selemo ka mor'a moo, ho hlokahala hore a hlahlobe ts'ebetso ea liphio. Bakeng sa bakuli ba nang le ts'oaetso ea ho hlaka ea renal e belaelloang, ts'ebetso ea renal e lokela ho hlahlojoa khafetsa mme kalafo e nang le Combogliz Prolong® e lokela ho emisoa haeba matšoao a ho hloleha ha a fig a hlaha.

Mekhoa ea ho buoa

U lokela ho emisa ka nakoana ho nka Combogliz Prolong® pele ho ts'ebetso leha e le efe ea ho buuoa (ntle le lits'ebetso tse nyane tse sa amaneng le ho fokotsa lijo le metsi), 'me u se ke ua qalella ho li sebelisa ho fihlela mokuli a khona ho sebelisa meriana kahare le ts'ebetso e tloaelehileng e netefalitsoe. liphio.

Fetoha maemong a bongaka ba bakuli ba nang le lefu la tsoekere la 2 le laoloang pele

Ho mokuli ea nang le T2DM, eo pele a neng a laoloa hantle nakong ea phekolo le Combogliz Prolong ® ea bileng a khelohileng maemong a laboratori kapa a tšoaroa ke lefu (haholo-holo maemong a tlhahlobo e sa hlaka), matšoao a ketoacidosis kapa lactic acidosis a lokela ho hlahlojoa hanghang. Tlhahlobo e lokela ho kenyelletsa boikemisetso ba li-electrolyte tse serum ea mali, li-ketone, tsoekere ea mali, 'me haeba ho bontšoa, pH ea mali, likhakanyo tsa lactate, pyruvate le metformin. Haeba mofuta leha e le ofe oa acidosis o tsoetse pele, o lokela ho tlohela Combogliz Prolong® hang-hang 'me u fane ka litlhare tse ling tsa hypoglycemic.

Tšebeliso ea lithethefatsi tse ka bakang hypoglycemia

Saxagliptin
Liphetho tsa sulfonylureas le insulin li ka baka hypoglycemia.Ka hona, ho fokotsa kotsi ea hypoglycemia ka tšebeliso ea nako e le 'ngoe le saxagliptin, ho ka hlokahala hore ho fokotsoe tekanyetso ea sulfonylurea kapa insulin.
Metformin
Hypoglycemia ha e hlahe ho bakuli ba nkang metformin feela ka tsela e tloaelehileng, empa e ka nts'etsapele 'mele o sa lekaneng, ha ts'ebetso e sebetsang ea' mele e sa tlosoe ke tšebeliso ea lik'habohaedreite, kapa ka tšebeliso e kopaneng le lithethefatsi tse ling tsa hypoglycemic (joalo ka sulfonylureas le insulin. Batho ba baholo, ba kulang le ba kulang hampe kapa ba kulang hampe ebile bakuli ba nang le bothata ba ho hlonepha kapa ba tahi kapa ba tahi haholo ba amehile haholo ka litlamorao tsa hypoglycemic. Ho batho ba baholo le bakuli ba nkang beta-blocker, ho ka ba thata ho tseba hore na hypoglycemia e fumaneha joang.

Phekolo e kopanetsoeng e amang ts'ebetso ea renal kapa phetiso ea metformin

Tlhokomeliso e eletsoa ho sebelisa lithethefatsi tse kopaneng (joalo ka lithethefatsi tsa cationic tse hlahisoang ke secretion ho li-renal tubules), tse ka amang ts'ebetso ea liphio, tsa lebisa ho liphetoho tse kholo tsa hemodynamic kapa tsa sitisa phetiso ea metformin (bona karolo "Ho sebelisana le lithethefatsi tse ling").

Boithuto ba radiology ka tsamaiso ea methapo ea methapo ea iodinated phapang

Ha ho etsoa lithuto tsa radiology ka tsamaiso ea methapo ea methapo e tsamaisang iodine, ho ile ha fumanoa mathata a methapo ea pelo, a ka tsamaeang le nts'etsopele ea lactic acidosis ho bakuli ba fumanang metformin. Bakuli ba reretsoeng ho ithuta joalo ba lokela ho hlakola kalafo ea Combogliz Prolong® nakong ea lihora tse 48 pele ba etsa ts'ebetso ena, ba hane ho nka moriana nakong ea lihora tse 48 kamora ts'ebetso, mme ba qale hape kalafo kamora ho netefatsa ts'ebetso e tloaelehileng ea liphio.

Maemo a Hypoxic

Ho oa ha pelo le pelo (tšabo) ea tšimoloho efe kapa efe, ho nyekeloa ke pelo haholo, infarction ea methapo ea pelo le maemo a mang a tsamaeang le hypoxia le lactic acidosis li ka baka azotemia ea pelehi. Ka nts'etsopele ea liketsahalo tse joalo, ho hlokahala hore hang-hang u khaotse ho phekoloa le Combogliz Prolong®.

Phetoho khorong ea tsoekere ea mali

Furu, ho sithabela maikutlo, ts'oaetso, ts'ebetso ea bongaka e ka lebisa phetoho ea khatello ea tsoekere maling, eo pele e neng e khona ho laola ts'ebeliso ea lithethefatsi Combogliz Prolong®. Maemong ana, ho ka hlokahala ho tlosoa ha nakoana kalafo le ho fetisetsa mokuli kalafong ea insulin. Kamora ho tsitsisa khatello ea tsoekere maling le ho ntlafatsa boemo bo tloaelehileng ba mokuli, kalafo e nang le Combogliz Prolong® e ka qala hape.

Boitšoaro ba Hypersensitivity

Liphetoho tse tebileng tsa hypersensitivity, ho kenyelletsa anaphylaxis le angioedema, li tlalehiloe nakong ea ts'ebeliso ea morao-rao ea saxagliptin. Haeba ho ba le karabelo e matla ea hypersensitivity, o lokela ho emisa ho sebelisa lithethefatsi, ho hlahloba lisosa tse ling tsa nts'etsopele ea ketsahalo ena, le ho fana ka litlhare tse ling tsa kalafo ea "mellitus" (bona likarolo tsa "Contraindication" le "Side Athible").

Pancreatitis

Tšebelisong ea morao-rao ea saxagliptin, ho se ho amohetsoe litlaleho tse qaqileng tsa linyeoe tsa pancreatitis e mpe. Bakuli ba nkang Combogliz Prolong® ba lokela ho tsebisoa ka matšoao a tšoaetso ea pancreatitis e bohloko: ho ba nako e telele, bohloko bo boholo mpeng. Haeba u belaella nts'etsopele ea pancreatitis, o lokela ho khaotsa ho sebelisa lithethefatsi Combogliz Prolong® (bona likarolo "Ka tlhokomeliso" le "litla-morao".
Tekanyo ea pancreatitis thutong ea SAVOR, e netefalitsoeng ho latela protocol ea thuto, e ne e le 0,3% ho saxagliptin le lihlopha tsa placebo ho palo ea bakuli bohle ba sa sebetseng.

Bakuli ba baholo

Ho bakuli ba 16492 ba khethiloeng thutong ea SAVOR, bakuli ba 8561 (51.9%) ba ne ba le lilemo li 65 kapa ho feta, mme bakuli ba 2330 (14.1%) ba ne ba le lilemo li 75 kapa ho feta. Ho bana, bakuli ba 4290 ba lilemo li 65 le ho feta le bakuli ba 1169 ba lilemo li 75 le ho feta ba fumane saxagliptin. Ho latela liphuputso tsa tliliniki, matšoao a sebetsang hantle le a polokeho ho bakuli ba lilemo li 65 le ho feta, lilemo tse 75 le ho feta ha a fapana le matšoao a tšoanang ho bakuli ba lilemong tse tlase.

Ho nyekeloa ke pelo

Phuputso ea SAVOR e hlokometse keketseho ea ho kenella sepetlele bakeng sa ho hloleha ha pelo sehlopheng sa saxagliptin ha ho bapisoa le sehlopha sa placebo, leha kamano ea mabaka e se e sa thehoa. Ho lokela hore ho sebelisoe tlhokomeliso ha ho sebelisoa Combogliz Prolong® ho bakuli ba nang le mabaka a ho ba le bothata ba ho nyekeloa ke pelo, joalo ka nalane ea ho se sebetse hantle ha renal kapa ho ba le mathata a tebileng. Bakuli ba lokela ho tsebisoa ka matšoao a ho hlobaela ha pelo le ka tlhoko ea ho tlaleha matšoao a joalo hang-hang (bona Pharmacodynamics, Clinical ufanisi le polokeho).

Arthralgia

Litlaleho tsa morao-rao li hlalosa bohloko bo kopaneng, ho kenyelletsa le bohloko bo boholo, ha u sebelisa li-inhibitors tsa DPP-4. Ho bakuli, phokotso ea matšoao e ile ea bonoa kamora ho khaotsa ho sebelisa moriana, mme ho bakuli ka bonngoe matšoao a ile a bonoa ha a qala ts'ebeliso ea mofuta o le mong kapa e 'ngoe ea DPP-4 inhibitor. Ho qala hoa matšoao ka mor'a ho qala ts'ebeliso ea moriana ho ka potlaka kapa ho hlokomeleha khahlano le semelo sa kalafo ea nako e telele. Ka nts'etsopele ea bohloko bo boholo ba kopaneng, ho tšoaneleha ha ho tsoela pele ho sebelisa lithethefatsi ka bonngoe ho lokela ho hlahlojoa (bona karolo "Litlamorao").

HO SIRELETSA TABENG EA HO HLOKA HO ETSA LIQETSI LE HO SEBELISA LE MeCHANISMS

Boithuto mabapi le matla a saxagliptin mabapi le bokhoni ba ho khanna makoloi le mekhoa ea taolo ha e so etsoa. Hopola hore saxagliptin e ka baka hlooho.

Pharadodynamics

Combogliz Prolong e kopanya baemeli ba babeli ba hypoglycemic le mohato o lumellanang oa ts'ebetso o etselitsoeng ho ntlafatsa taolo ea glycemic ho bakuli ba nang le lefu la tsoekere la mofuta oa 2 (mofuta oa lefu la tsoekere la 2): saxagliptin, inhibitor ea DPP-4 (dipeptidyl peptidase 4), le metformin, eo e leng ea sehlopha biguanides.

Saxagliptin

Ho tloha ka mpeng e nyane, ho arabela tšebeliso ea lijo, lihormone, li-insretin, tse kang GLP-1 (glucagon-kama peptide-1) le HIP (glucose-insulinotropic polypeptide) e tsoa maling.

Hormones-incretin e khothalletsa ho ntšoa ha insulin liseleng tsa beta tsa manyeme, ho latela bongata ba glucose maling, empa li entsoe metsotso e 'maloa ke enzyme DPP-4. Ketso ea GLP-1 e boetse e etselitsoe ho fokotsa sekhahla sa tsoekere liseleng tsa alpha tsa manyeme, e lebisang ho fokotseheng ha tlhahiso ea tsoekere maling. Ts'oants'o ea bongata ba GLP-1 ho bakuli ba nang le lefu la tsoekere la 2 ea fokotseha, empa karabelo ea insulin ho GLP-1 e bolokiloe. Saxagliptin, joalo ka sebapali sa tlholisano ea DPP-4, e fokotsa ho kenella ha lihormone tsa "incretin", ka tsela eo, e eketsa tsitsipano ea mali, mme e lebisa ho fokotseha hoa khatello ea glucose ka mpeng e se nang letho le kamora ho ja.

Metformin ke sethethefatsi sa hypoglycemic se ntlafatsang mamello ea tsoekere ho bakuli ba nang le lefu la tsoekere la mofuta oa 2 (ka ho theola sekhahla sa tsoekere ea glucose le postprandial).

Ts'ebetso ea bongaka ea metformin ke ho fokotsa tlhahiso ea tsoekere ke sebete, e fokolisa ho ruruha ha tsoekere ka mpeng, le ho phahamisa kutloisiso ea "insulin" le tšebeliso ea tsoekere ea tsoekere).

Metformin, ho fapana le litokisetso tsa sulfonylurea, ha e bake hyperinsulinemia le hypoglycemia ho bakuli ba nang le lefu la tsoekere la 2 kapa batho ba phetseng hantle (mokhelo ke maemo a ikhethang). Secretion ea "insulin" nakong ea kalafo ea metformin ha e fetohe, leha ho ka ba le phokotseho ea khatello ea "insulin" ka mpeng e se nang letho le karabelo ea lijo nakong ea mots'eare.

TLHOKOMELISO MOTSAMAI

Matlapa a kopantsoeng a filimi a 1000

Matlapa a 7 ka blister e ngoe ea aluminium foil, lilakane tse 4 kapa tse 8 tse nang le litaelo

bakeng sa tšebeliso ka lebokoseng la karete e nang le mokhoa oa ho bula.

500 mg + 5 mg matlapa a kopaneng a filimi
Matlapa a 7 ka blister e 'ngoe le e' ngoe e entsoeng ka foil ea aluminium, lilakane tse 4 tse nang le litaelo tsa tšebeliso ea lebokose la karete e nang le taolo ea ho bula ha pele.

Letlapa le koahetsoeng ka filimi ea 1000 mg + 5 mg
Matlapa a 7 ka blister e 'ngoe le e' ngoe e entsoeng ka foil ea aluminium, lilakane tse 4 tse nang le litaelo tsa tšebeliso ea lebokose la karete e nang le taolo ea ho bula ha pele.

Ka mocheso o sa feteng 30 ° C. Qoba hole le bana.

MOTSOALI, MOKHATLO OA HO FIHLA (PRIMARY PackING), PACKER (SEBAKA SA BOTSOALLE (BONYETSI), HO BUA TOKA EA BOPHELO

AstraZeneca Pharmaceuticals LP, USA
4601 Highway 62 East, Mount Vernon, Indiana, 47620, USA
AstraZeneca Pharmaceuticals LP, USA
4601 Highway 62 East, Mount Vernon, Indiana, 47620, USA

Lebitso, aterese ea mokhatlo e lumelletsoeng ke motsamaisi kapa mong'a lengolo la setifikeiti sa bongaka bakeng sa ts'ebeliso ea bongaka ho amohela likopo ho moreki

Moemeli oa AstraZeneca UK Limited, UK, ho la Moscow le AstraZeneca Pharmaceuticals LLC
125284 Moscow, st. Ho baleha, 3, leq. 1.

Litlhare tsa motsoako oa lithethefatsi

Combogliz Prolong ke kopanyo e tsitsitseng ea saxagliptin le metformin, e fa lingaka le baoki ba lefu la tsoekere monyetla o mocha oa ho laola boemo ba bona ba glycemic.

Katleho ea Combogliz: litaelo tsa tšebeliso

Ngaka e khetha kemiso ea tsamaiso le litekanyetso ka bonngoe, ho nahanela matšoao a glucometer, bophelo bo botle ka kakaretso, lilemo tsa lefu la tsoekere, karabelo ea motho ka mong litafoleng. Ka kakaretso, thupelo e fana ka likhothaletso tse joalo.

Moriana oa nako e telele hangata o nooa 1 r. / Letsatsi. ka nako e tšoanang.

- Nala letlapa hoseng kapa mantsiboea ntle le ho silila. Bakeng sa mekhoa e lokollotsoeng ea tokollo, botšepehi ba shell bo bapala karolo e ikhethang.

Litekanyetso ke motho ka mong, ha e le moitlami oa ho qala e ka ba letlapa le le leng (500 mg ea metformin + 2,5 mg ea saxagliptin), haeba taolo e felletseng ea glycemic e ke ke ea fumaneha, tekanyetso e eketseha ho matlapa a 2 (1000 mg ea metformin + 5 mg ea saxagliptin).

Ka tšebeliso e tšoanang ea meriana bakeng sa kalafo ea mafu a kopaneng, liphetho tsa ts'ebelisano ea bona li lokela ho ananeloa. Haholo-holo, ka tsamaiso e le 'ngoe ea li-inhibitors tsa CYP3A4 / 5 isoenzymes (Indinavir, Ketoconazole, Nefazodon, Itraconazole, Atazanavir), tekanyetso e nyane ea saxagliptin e boletsoe - 2,5 mg.

Lithethefatsi tse thehiloeng ho Metformin ka nako e telele ea litlamorao tse sa rateheng ka mokhoa oa mathata a dyspeptic li fokola haholo ho feta analogues ka tokollo e potlakileng. E le hore mmele o fetohe maemong a macha, ha ho utloahale ho hang bakeng sa tšilo ea lijo, tekanyetso titration lokela ho ho etsahala butle-butle, mong le e mong libeke tse 2.

Phetoho efe kapa efe ea mokhoa oa bophelo e lokela ho tsotelloa ha ho lokisoa tloaelo ea bongaka, ka hona ho bohlokoa ho tsebisa ngaka ka bona ka nako e nepahetseng.

Analogs Kombiglyce Prolong

Bakeng sa Combogliz Prolong, analogue e nang le sete e tšoanang ea metsoako e sebetsang e kanna ea ba Comboglis XR, e hlahisoang Italy le UK. Theko ea analogue e tsoa ho li-ruble tse 1650. (Matlapa a 28 a 1000 mg ea metformin le 2,5 mg ea saxagliptin).

Litlamorao tse kopaneng tsa kalafo tsa Avandamet, Yanumet, Glimecomb, GalvusMet le Bagomet hammoho le phello e tšoanang ea kalafo.

Fana ka lithethefatsi ho latela motsoako o le mong o sebetsang o kang Glyformin Prolong, Glucofage, Metadiene, Sofamet, Diaformin Od, Ongliza, Matospanin, Metfogamma, Siofora.

Ke mang ea bontšitsoeng moriana?

Katleho ea Combogliz e laetsoe mofuta oa lefu la tsoekere la 2 hore e fetole taolo ea glycemic e le tlatsetso ea lijo tse tlase tsa carb le boikoetliso bo lekaneng ba 'mele, haeba phetoho ea mokhoa oa bophelo e sa fane ka liphetho tse lakatsehang le ho kopana ha saxagliptin ka metformin ho loketse mokuli.

Liphoso tse phethahetseng le tse amanang

Le moriana o nang le ts'ireletso e phahameng haholo, e leng Combogliz Prolong, ha o fuoe ho se mamellane le ho kenella ka matla linthong tsa motsoako.

1. Moriana ha o bontšoa bo-'mè baimana le ba anyang (ba fetisetsoa ho insulin ka nakoana), ka lebaka la ho haella ha bopaki bo lekaneng bakeng sa ts'ebetso ea ona, ha e fuoe bana.
2. Setlhare ha se a loketse bakuli ba lefu la tsoekere ba mofuta oa 1 oa lefu lena.
3. Ka dysfunctions tsa renal, hammoho le maemo a li khopisang, mori le ona ha o fuoe.
4. Se ke ua sebelisa litlhare ho phekola bakuli ba nang le li-pathologies tse bakang tlala ea moea ea li-tishu.
5. Ka ketoacidosis (mofuta oa lefu la tsoekere) e nang le ho akheha kapa ho hloka komisi, meriana ha e nkuoe ka nakoana.
6. Lipilisi lia hlakoloa nakong ea ts'ebetso, le likotsi tse mpe, ho chesoa ho hoholo. Tlhahlobo ea X-ray e nang le matšoao a nang le iodine ka tsoekere e ka senya liphio, ka hona e fetoloa hape ka insulin. Ka kakaretso, kalafo ea "insulin" e bontšoa lihora tse 48 pele le lihora tse 48 kamora lits'ebetso, haholoholo, kaofela ho latela boemo ba liphio le boiketlo ba mokuli ka kakaretso.
7. Li-pathologies tsa sebete, lactic acidosis le ho itšetleha ka joala le tsona li lethathamong la li-contraindication. U ke ke ua fana ka litlhare ho bakuli ba nang le lefutso la galactose.

Ho lebisoa tlhokomelo e khethehileng ho batho ba nang le lefu la tsoekere la lilemo tse butsoitseng, haholo-holo ka khaello ea phepo e nepahetseng, pancreatitis le ho ikoetlisa ka ho lekaneng tse ka bakang hypoglycemia.

Lits'ebetso tse sa batleheng le ho fetella

Saxagliptin e nang le maemo a fapaneng a khonahala e khona ho baka maemo:

• Sinusitis
• Gastroenteritis
• Ho ruruha sefahlehong,
• Pancreatitis
• Urticaria.

Boithuto ba laboratori bo bontšitse ho fokotseha ha ho kenngoa ha vithamine B12 ka tšebeliso ea nako e telele ea lithethefatsi, hammoho le ho fokotseha ha palo ea li-lymphocyte. Ho na le maemo a sebelisang overdose e ngata, hangata ho etsahalang ka saxagliptin nako e telele. Setlhare ha se bake ho tahoa, ka lithethefatsi tse ngata, hemodialysis e sebetsa. Ka ho bapisa, kalafo ea matšoao e etsoa.

Tekanyetso e feteletseng ea metformin e atile haholo, ntho e kotsi ka ho fetisisa ke lactic acidosis.. O ka lemoha boemo ka matshwao a latelang:

1. Karohano
2. Ho hema hanyane
3. Bohloko ba ka mpeng
4. Khatello ea mali e tlase
5. Hypothermia,
6. Mokokotlo oa mesifa
7. Pherekano ea morethetho oa pelo.

Boemong bo thata, ho ferekana kelellong, ho akheha, ho hlohlona le ho holofala hoa ntlafala. Motho ea hlokahalitsoeng o hloka ho kena sepetlele ka potlako, ntle le tlhokomelo e lekaneng ea bongaka, a ka shoa. Metformin e feteletseng e boetse e tlosoa ke hemodialysis, ho bohlokoa ho nahana hore tumello ea creatinine e fihla ho 170 ml / min.

Ha motho ea nang le lefu la tsoekere a etsa litlhahiso tsohle tsa ngaka ka nepo, o ka fokotsa monyetla oa mathata a tebileng. Tabeng ea Combogliz ea nako e telele, ha ho thata ho latela kemiso ea ho nka moriana.

Likhetho tsa ho sebelisana le meriana e meng

Ha o theha mofuta oa kalafo bakeng sa Combogliz Prolong, ho bohlokoa ho lemosa endocrinologist ka lithethefatsi tsohle tseo lefu la tsoekere le li sebelisang ho phekola maloetse a kopaneng. Ba bang ba bona ba khona ho ntlafatsa bokhoni ba ho fokotsa tsoekere Comboglize, ba bang ba sitisa mesebetsi ea eona.

Bakeng sa mohopolo o akaretsang, o ka sheba tafole.

Matlafatso ea phello ea Hyperglycemic

Rifampicin, Pioglitazone, Magnesium le Aluminium Hydroxides / SimethiconeGCS, diuretics, nicotinic acid

lihormone tsa qoqotho, isoniazid, sympathomimetics, phenothiazines, estrogens, phenytoin, calcium blockers

Fana ka maemo a hypoglycemic

Amprenavir, Diltiazem, Erythromycin, Fluconazole, Aprepitant, Verapamil, lero la morara, Ketoconazole, lithethefatsi tsa sulfonylurea, Glibenclamide, Ketoconazole, CYP3A 4/5 isoenzymes, FamotidineLithethefatsi tsa Cationic, Furosemide, meriana e thehiloeng ho ethanol, Nifedipine

Amprenavir, Diltiazem, Erythromycin, Fluconazole, Aprepitant, Verapamil, lero la morara, Ketoconazole, lithethefatsi tsa sulfonylurea, Glibenclamide, Ketoconazole, CYP3A 4/5 isoenzymes, Famotidine
Lithethefatsi tsa Cationic, Furosemide, meriana e thehiloeng ho ethanol, Nifedipine

Ho totobetse hore liteko tsa ho itlhahloba le ho iphekola ka Combogliz Prolong li ka ba le litlamorao tse mpe tsa bophelo bo botle.

Katleho ea Combogliz: Litlhahlobo tsa batho ba lefu la tsoekere

Lingaka tse lekolang katleho ea kalafo ka moriana oa Combogliz Prolong li hlokomela ho ikhetholla ha eona, mme ba nang le lefu la tsoekere ha ba na lipelaelo ka bokhoni ba eona.

Tsamaiso e felletseng ea lefu la tsoekere e hloka mokhoa o kopanetsoeng: phepo e fokolang ea carb, ho lekola letsatsi le letsatsi ho baloa ha glucometer, ho ikoetlisa ka ho lekaneng 'meleng le tšehetso ea lithethefatsi. Ke ka kopanyo ena feela moo re ka lekang phello ea 100% ea Combogliz Prolong.

Ka video, moprofesa-endocrinologist A.S. Ametov o bua ka melao-motheo ea sejoale-joale ea taolo ea lefu la tsoekere la mofuta oa 2.

Mofumahali

Bioequivalence le phello ea lijo ho kopantsoeng ha lintho tse sebetsang tsa Comboglize Prolong e bontšitsoe ke bakuli ba latelang lijo tse nang le khalori e tlase, tse fanang ka 324 kcal ka sebopeho sa lijo mme e na le liprotheine - 11.1%, mafura - 10,5%, lik'habohaedreite - 78,4%. Tlas'a maemo ana a phepo e nepahetseng, lithutong tse phetseng hantle, ho latela sephetho sa lipatlisiso, bioequivalence ea pharmacokinetics ea motsoako oa metformin + saxagliptin matlapeng le matlapa a motho ka mong a lokolloang saxagliptin le metformin ka litekanyetso tse tšoanang.

Maemo a khethehileng a kliniki

Ts'ebeliso ea Combogliz Prolong e nang le ho fokolisa ha renal le ts'ebetso ea sefuba ha e khothalletsoe.

Bakeng sa bakuli ba lilemo tse 65-80, ha ho liphapang tse ngata tsa bongaka tsa meriana tsa saxagliptin tse fumanoeng ha li bapisoa le bakuli ba lilemo tse nyane (18-25 ea lilemo tse), ka hona, tokiso ea litekanyetso ho bakuli ba tsofetseng ha e hlokehe. Le ha ho le joalo, ho lokela ho tsotelloa hore sehlopheng sena sa bakuli, ho fokotseha ha ts'ebetso ea liphio ho na le monyetla o moholo. Nako efe kapa efe, ha ho hlokahale ho fana ka Combogliz Prolong ho fihlela ts'ebetso e tloaelehileng ea menoana e netefalitsoe.

Bakuli ba kaholimo ho lilemo tse 80 ba qhekelloa ka ho sebelisa moriana, ntle le haeba ts'ebetso e tloaelehileng ea renal e netefatsoa ke tekanyo ea tumello ea creatinine.

Boithuto ba pharmacokinetics ba dintho tse sebetsang Comboglyz Prolong ho bana ha e so etsetsoe.

Litla-morao tse sa fetoheng ho saxagliptin tse tlalehiloeng thutong ea SAVOR

Karolo ea bakuli ba ileng ba ba le hypoglycemia e matla nakong ea kalafo (hypoglycemia, e hlokang thuso ea batho ba boraro) e ne e phahame sehlopheng sa saxagliptin ha se bapisoa le sehlopha sa placebo.

Kotsi e eketsehileng ea ho ba le hypoglycemia ka kakaretso, hammoho le hypoglycemia e matla sehlopheng sa saxagliptin, e ne e bonoa haholo ho bakuli ba fumaneng litokisetso tsa sulfonylurea, empa eseng ho bakuli ba fumaneng metformin kapa insulin e le eona kalafo e ka sehloohong.

Ka kakaretso, kotsi e eketsehileng ea hypoglycemia, hammoho le hypoglycemia e matla, e hlokomeloa haholo ho bakuli ba nang le basel glycated hemoglobin (HbAlc) e ka tlase ho 7%.

Ts'ebeliso ea papatso

Nakong ea tlhahlobo ea morao-rao ea ho bapatsa, nts'etsopele ea karabelo e latelang e sa thabiseng: pancreatitis e matla, maikutlo a hypersensitivity (ho kenyeletsa anaphylaxis, angioedema, rash le urticaria) le arthralgia. Ho ka se khonehe ho sekaseka khafetsa ntlafatso ea liketsahalo tsena.

Ka tšebeliso ea saxagliptin, ho fokotseha ho fokotsoang ka sekhahla se fokotsang palo e felletseng ea li-lymphocyte.Maemong a mangata, ka tšebeliso e sa khaotseng ea saxagliptin, ha ho ts'oaetso e ileng ea bonoa hape, le ha ho bakuli ba bang palo ea li-lymphocyte e ile ea fokotseha hape ka mor'a ho qala kalafo ka saxagliptin, e ileng ea lebisa ho khaotseng lithethefatsi. Phokotseho ea palo ea li-lymphocyte ha e tsamaisane le lipontšo tsa bongaka. Lisosa tsa tlolo ena ha li tsejoe. Tabeng ea tšoaetso ea nako e telele kapa e sa tloaelehang, palo ea li-lymphocyte e lokela ho lekanngoa. Kameho ea saxagliptin palong ea li-lymphocyte ho bakuli ba nang le mahlaba ka bongata ka palo ea bona (ho kenyeletsa le vaerase ea immunodeficiency virus) ha e tsejoe.

Lithutong tsa bongaka tsa metformin, bakuli ba ka bang 7% ba bontšitse ho fokotseha ha maemo a vithamine ea serum B₁₂ (e neng e le ntho e tloaelehileng) ho boleng bo sa tloaelehang bo sa tsamaeang le lipontšo tsa kliniki. Ho feta moo, phokotso e joalo ea nts'etsopele ea anemia e tsamaisana le seoelo haholo, kamora ho felisoa ha metformin kapa tšebeliso e eketsehileng ea vithamine B₁₂ hlaphoheloa kapele.

Ka mosebetsi o sa sebetseng oa renal

Contraindication mabapi le ts'ebeliso ea Comboglize Prolong ho tloha lehlakoreng la ts'ebetso ea a renal.

• ts'ebetso e sa sebetseng ea renal (serum creatinine: banna ≥ 1.5 mg / dl, basali ≥1.4 mg / dl kapa tumello e fokotsehileng ea creatinine), ho kenyelletsa le tse amanang le septicemia, infarction ea myocardial e hlobaetsang, ho hloleha ha pelo le pelo (ho sisinyeha) ,
• maloetse a hlobaetsang, ao ho nang le kotsi ea ts'ebetso ea ho hlaphoheloa ha renal.