Fomu ya Mlingo - mapiritsi okhala ndi filimu: wojambula-kapangidwe kake, mbali imodzi yolemba "CFZ", gawo loyambira limakhala loyera kapena loyera, mulingo wa 100 mg - wachikasu, lolemba "100" mbali inayo, mulingo wa 300 mg - pafupifupi kapena zoyera, zolembedwa ndi "300" mbali inayo (pamakadi okhala ndi matuza 1, 3, 9 kapena 10 mapiritsi 10 ndi malangizo ogwiritsira ntchito Encokany).

Piritsi 1:

yogwira mankhwala: canagliflozin - 100 kapena 300 mg (mu mawonekedwe a canagliflozin hemihydrate - 102 kapena 306 mg, motero),
othandizira othandizira (100/300 mg): cellcrystalline cellulose - 39.26 / 117.78 mg, croscarmellose sodium - 12/36 mg, anactrous lactose - 39.26 / 117.78 mg, magnesium stearate - 1.48 / 4, 44 mg, hyprolose - 6/18 mg,
utoto wa makanema: mulingo wa 100 mg - utoto Opadry II 85F92209 chikasu (pang'ono hydrolyzed polyvinyl mowa - 40%, macrogol 3350 - 20.2%, titanium dioxide - 24.25%, talc - 14.8%, oxide wachikasu wachitsulo - 0, 75%) - 8 mg, Mlingo 300 mg - Opadry II 85F18422 utoto woyera (pang'ono hydrolyzed polyvinyl mowa - 40%, macrogol 3350 - 20.2%, titanium dioxide - 25%, talc - 14.8%) - 18 mg.

Mankhwala

Zinakhazikitsidwa kuti motsutsana ndi maziko a matenda a shuga a m'mellitus pali kuwonjezeka kwa impso, komwe kungayambitse kuchuluka kwa glucose. Mwa kubwezeretsanso kwa glucose kuchokera ku tubule lumen, SGLT2 (mtundu 2 sodium glucose cotransporter), yomwe ikufotokozedwa mu proximal renal tubules, ndiomwe amachititsa.

Kanagliflosin - chinthu chogwira ntchito cha Invokana - ndi amodzi mwa zoletsa za SGLT2. SGLT2 ikatsekereza, pamakhala kuchepa kwa kusungunuka kwa glucose komanso kuchepa kwa BCP (cholumikizira impso), zomwe zimathandiza kuwonjezera kuchuluka kwa glucose ndi impso, zomwe zimapangitsa kuchepa kwa plasma ya glucose m'magazi pogwiritsa ntchito insulin yodziyimira yokha mwa odwala omwe ali ndi mtundu wa 2 shuga. Komanso, chifukwa cha kuchuluka kwa shuga kwa impso kudzera mu kuletsa kwa SGLT2, kukula kwa osmotic diuresis kumadziwika, mphamvu ya diuretic imathandiza kuchepetsa kupanikizika kwa systolic. Kuphatikiza apo, motsutsana ndi maziko a kuchuluka kwa shuga kwa impso, pamakhala kuwonongeka kwa ma calorie, chifukwa, kuwonda.

Pochita maphunziro a gawo lachitatu, kugwiritsa ntchito mlingo wa 300 mg wa Invokana musanadye chakudya kumabweretsa kuchepa kwambiri kwa kuchuluka kwa glucose kuposa kumwa mankhwala a 100 mg. Popeza mozama pang'onopang'ono zinthu za m'matumbo lumen zisanayambe kuyamwa, zoterezi zitha kuphatikizidwa ndi chopinga cham'mimba cha SGLT1 (canagliflozin ndi choletsa SGLT1 yokhala ndi ntchito yochepa). Maphunziro ogwiritsa ntchito canagliflozin, malabsorption a glucose sanapezeke.

Pambuyo limodzi / angapo pakamwa makonzedwe a canagliflozin pa chipatala mayesero odwala 2 mtundu wa matenda a shuga, kuchepa kwa mlingo wa impso kwa glucose ndi kuwonjezeka kwa impso glucose. Kwa glucose, mtengo woyambirira wa impso ndi pafupifupi 13 mmol / l, kutsika kwakukulu kwa gawo latsiku lililonse laimpso kumawonedwa ndi 300 mg ya canagliflozin kamodzi patsiku ndipo ndi 4-5 mmol / l. Izi zikuwonetsa chiopsezo chochepa cha hypoglycemia panthawi ya mankhwala.

Pogwiritsa ntchito 100- 300 mg ya canagliflozin kamodzi patsiku kwa masiku 16, odwala omwe ali ndi matenda a shuga 2 amawonetsa kuchepa kwa njira ya aimpso ndi kuchuluka kwa impso. Pankhaniyi, kutsika kwa plasma ndende yamagazi m'magazi kunachitika mwanjira modalira tsiku loyamba la mankhwala ndipo anali ndi chizolowezi cham'tsogolo pamimba yopanda kanthu ndikatha kudya.

Mlingo umodzi wa 300 mg wa Advocana musanadye chakudya chosakanizika, unayambitsa kuchepa kwa shuga m'matumbo ndikuchepa kwa postprandial glycemia kudzera mu njira zowonjezera komanso aimpso.

Mukamachita kafukufuku wokhudza odzipereka 60 athanzi, zidapezeka kuti kumwa mlingo wa 300 ndi 1200 mg (nthawi 4 kuposa mulingo wambiri wazithandizo) sikuti kumabweretsa kusintha kwakukulu pakubwera kwa QTc. Pazipita plasma ndende ya canagliflozin m'magazi kugwiritsa ntchito 1200 mg kuposa kuti kamodzi ntchito 300 mg, pafupifupi 1.4 zina.

Kugwiritsa ntchito canagliflozin monga monotherapy kapena gawo limodzi la mankhwala ophatikiza (pogwiritsa ntchito othandizira 1-2 am'magazi a hypoglycemic), poyerekeza ndi placebo, pafupifupi kumabweretsa kusintha kwa glycemia mwachangu kuchokera ku gawo loyambirira kuchokera -1.2 mpaka-1.9 mmol / l ndi kuyambira -1.9 mpaka -2.4 mmol / l ndi 100 ndi 300 mg, motsatana. Zotsatira zake zinali pafupi kwambiri pambuyo pa tsiku loyamba la chithandizo ndipo zimapitilira nthawi yonse ya chithandizo.

Tinaphunziranso kugwiritsa ntchito canagliflozin monga monotherapy kapena ngati gawo limodzi la mankhwala ophatikiza (pogwiritsa ntchito mankhwala otsogolera pakamwa a 1-2) poyesa gypcemia ya postprandial atatha kuyesedwa kwa glucose povomerezera kadzutsa. Mankhwalawa, poyerekeza ndi gawo loyamba, adathandizira kuchepa kwapakati pa postprandial glycemia poyerekeza ndi placebo kuyambira -1.5 mpaka -2.7 mmol / L komanso kuyambira -2.1 mpaka -3,5 mmol / L mukamatenga 100 ndi 300 mg, motero, komwe kumalumikizidwa ndi kuchepa kwa shuga m'magazi musanadye komanso kuchepa kwa kusinthasintha kwa gawo la postprandial glycemia.

Malinga ndi kafukufuku omwe ali ndi odwala omwe ali ndi mtundu wachiwiri wa matenda a shuga, kugwiritsa ntchito canagliflozin kumapangitsa kuti ntchito ya cell ya beta (kutengera chitsanzo cha homeostasis molingana ndi ntchito ya maselo a beta) komanso kuthamanga kwa insulin secretion (malinga ndi kuyesedwa kwa glucose pakudya kadzutsa).

Pharmacokinetics

Mu maphunziro athanzi, pharmacokinetics ya canagliflozin ndi ofanana ndi magawo a pharmacokinetic a zinthu zomwe zili ndi odwala omwe ali ndi matenda a shuga a 2. Pambuyo pakukonzekera kamlomo kamodzi ka 100 ndi 300 mg ya Invokana ndi odzipereka athanzi, canagliflozin imatengedwa mwachangu, T_max (nthawi yokwanira kudziwa kuchuluka kwa chinthu) mu plasma ndi pafupifupi maola 1-2. Plasma C_max (pazinthu zambiri) ndi AUC (dera lomwe limapindika "nthawi yayitali") imawonjezeka mothandizidwa ndi canagliflozin muyezo wa 50-300 mg. Zowoneka kuti ndi T_1/2 (theka-moyo) mukamagwiritsa ntchito 100 ndi 300 mg ya canagliflozin ndi maola 10.6 ndi 13.1, motsatana. Chiyanjano chofanana chikufikiridwa patatha masiku 4-5 atayamba chithandizo.

Pharmacokinetics ya canagliflozin sichimadalira nthawi; atagwiritsidwa ntchito mobwerezabwereza, kudzikundikira kwa thunthu m'madzi a m'magazi kumafika pa 36%.

The pafupifupi mwamtheradi bioavailability wa canagliflozin pafupifupi 65%. Kugwiritsa ntchito zakudya zamafuta ambiri sikukhudza ma pharmacokinetics a canagliflozin, kotero Invokana angagwiritsidwe ntchito ndi kapena popanda chakudya. Komabe, anapatsidwa mphamvu ya canagliflozin kuti achepetse kuchuluka kwa matenda a postprandial glycemia chifukwa cha kuchepa kwake kwa glucose m'matumbo, tikulimbikitsidwa kuti ayambe kudya asanayambe.

Mwa anthu athanzi, atalandira kulowetsedwa kamodzi kwa mtsempha, V_d (voliyumu yogawa) ya canagliflozin mu ofanana ndi 119 L, womwe ndi umboni wakugawika kwambiri mu minofu. Thupi limamangiriza mapuloteni a plasma, makamaka ndi albumin, pamlingo waukulu (pamlingo wa 99%). Kuyankhulana ndi mapuloteni sizimadalira kuchuluka kwa plasma ya canagliflozin. Poyerekeza ndi kumbuyo kwa kulephera kwa impso / chiwindi, ubale ndi mapuloteni a plasma sasintha kwenikweni.

Njira yayikulu ya canagliflozin metabolism ndi O-glucuronidation. Njirayi imachitika makamaka ndikutenga gawo kwa UGT1A9 ndi UGT2I34 ndikupanga awiri osagwira a O-glucuronide metabolites. Mwa anthu, oxidative (SURZA4-mediated) kagayidwe ka canagliflozin ndi kocheperako (pafupifupi 7%).

Pambuyo pakamwa limodzi lokha 14 C-canagliflozin ndi odzipereka athanzi, 3.2, 7 ndi 41,5% ya mankhwala omwe amaperekedwa mwanjira ya O-glucuronide metabolite, hydroxylated metabolite ndi canagliflozin, motero, adapezeka mu ndowe. Kufalikira kwazinthu za interohepatic ndikosatheka.

Pafupifupi 33% ya muyeso wa radioactive imapezeka mkodzo, makamaka mawonekedwe a O-glucuronide metabolites (30,5%). Osakwana 1% ya mlingo umachotsedwa ndi impso ngati chinthu chosasinthika. Mukamagwiritsa ntchito 100 ndi 300 mg ya canagliflozin, chilolezo cha impso chili m'malo osiyanasiyana a 1,3-1,55 ml / min.

Kanagliflozin ndi mankhwala osachepera chilolezo, pambuyo pakukonzekera kwa odwala wathanzi, chiwonetsero chazaka pafupifupi 192 ml / min.

Kugwiritsira ntchito canagliflozin mu kulephera kwambiri kwaimpso, gawo lothana ndi matenda aimpso, komanso odwala omwe ali ndi dialysis, silikulimbikitsidwa, chifukwa sizikuyembekezeredwa kuti mankhwalawa azitha kugwira ntchito m'gulu la odwala. Pa dialysis, kuchepa kachegliflozin kumadziwika.

Pofatsa pang'ono kwa chiwopsezo cha hepatic, kusintha kwa Invokana sikofunikira. Odwala omwe ali ndi vuto loopsa la hepatic (Child-Pugh wadogo class C) samadziwika ndi mankhwalawa, chifukwa cha kusowa kwa chidziwitso pakugwiritsa ntchito kwake m'gulu la odwala.

Ma paracokinetic magawo a canagliflozin mwa ana sanaphunzire.

Attokana, malangizo ogwiritsira ntchito: njira ndi mlingo

Mapiritsi a Invokan ayenera kumwedwa pakamwa, makamaka asanadye kadzutsa, nthawi 1 patsiku.

Mlingo wovomerezeka tsiku lililonse ndi 100 kapena 300 mg.

Ngati a Captokana amagwiritsidwa ntchito ngati cholumikizira insulin kapena othandizira omwe amatulutsa katulutsidwe (makamaka, mankhwala a sulfonylurea), kuti muchepetse chiopsezo cha hypoglycemia, mankhwalawa atha kutumikiridwa mu mlingo wotsikirapo.

Kanagliflozin ali ndi diuretic. Odwala omwe amathandizira okodzetsa, komanso anthu omwe ali ndi vuto la Impso zolimbitsa thupi (okhala ndi kusefukira kwa msambo 30 mpaka 60 ml / mphindi / 1.73 m 2) ndi odwala omwe ali ndi zaka zopitilira 75, zomwe zimachitika pafupipafupi. ndi kuchepa kwa kuchuluka kwa intravascular (mwachitsanzo, ochepa / orthostatic hypotension, chizungulire chaposachedwa). Gulu la odwala likulimbikitsidwa kuti liyambe mankhwala ndi tsiku lililonse 100 mg. Odwala omwe ali ndi zizindikiro za hypovolemia asanayambe chithandizo ndi canagliflozin akulimbikitsidwa kuti azikonza izi. Ngati mlingo wa 100 mg umalekeredwa bwino ndipo kuwonjezeranso kuwongolera kwa glycemia ndikofunikira, ndikofunikira kuti mupeze mlingo mpaka 300 mg.

Ngati muphonya mulingo wotsatira wa Invokana, muyenera kuudya nthawi yomweyo, koma osamwa kawiri patsiku limodzi.

Zotsatira zoyipa

Zotsatira zosafunikira zomwe zimawonedwa pakuyesa kuchipatala (monotherapy ndikugwiritsa ntchito metformin, sulfonylurea zotumphukira ndi metformin, komanso metformin ndi pioglitazone) pafupipafupi ndi ≥ 2% (idapangidwa malinga ndi kuchuluka kwa zomwe zimachitika molingana ndi gulu lotsatira: pafupipafupi - ≥ 1/10, nthawi zambiri - ≥ 1/100 ndi 2), komanso motsutsana ndi maziko ogwiritsira ntchito ophatikizidwa ndi zida zotumphukira pamwambapa. Mukamachita kafukufuku wokhudzana ndi ngozi zam'mtima, kuchuluka kwa zoyipa zomwe zimakhudzana ndi kuchepa kwa magazi mkati mwazinthu zam'mimba sikunawonjezeke ndikugwiritsa ntchito Invokana. Zochitika zoyipa izi zidapangitsa kuti pakufunika kuletsa chithandizo chochepa kwambiri.

Kukula kwa hypoglycemia panthawi ya mankhwala ndi Invocana kuwonjezera pa insulin kapena sulfonylurea zotumphukira kumanenedwa pafupipafupi, zomwe zimagwirizana ndi kuwonjezereka kwa pafupipafupi kwa hypoglycemia milandu pomwe mankhwala omwe amagwiritsidwa ntchito osagwirizana ndi chitukuko cha mankhwalawa amawonjezeredwa ndi insulin kapena mankhwala omwe amathandizira kubisika kwake.

Mu 4,4% ya odwala omwe amalandira 100 mg ya canagliflozin, mu 7% ya odwala omwe amalandira 300 mg ya canagliflozin, ndipo mu 4.8% ya odwala a placebo, panali kuwonjezeka kwa serum potaziyamu ndende (> 5.4 mEq / L komanso kuposa kupsinjika koyambirira kwa 15%). Odwala omwe ali ndi vuto laimpso kuwonda pang'ono nthawi zina amawonetsa kuchuluka kwa seramu potaziyamu (nthawi zambiri pagulu la odwala pamakhala kuchuluka kwa potaziyamu, ndipo / kapena amalandila mankhwala angapo omwe amachepetsa zotulukazo za potaziyamu - potaziyamu - osasinthika a encyme inhibitors). Mwambiri, kuphwanya kumeneku kumakhala kwachilengedwe ndipo sikutanthauza chithandizo chapadera.

M'milungu isanu ndi umodzi yoyambirira ya mankhwalawa, pang'ono (30%) adawonedwa, poyerekeza ndi gawo loyambirira lomwe limapezeka panthawi iliyonse ya mankhwalawa, adalipo 2 ndi 4.1% akamagwiritsa ntchito 100 ndi 300 mg ya canagliflozin, motero, mukamagwiritsa ntchito placebo - 2.1%. Nthawi zambiri matendawa anali osakhalitsa, ndipo kumapeto kwa kafukufuku amadziwika mwa ochepa odwala. Kutengera kupenda kwapadera kwa odwala omwe ali ndi vuto lochepa mwamphamvu la impso, kuchuluka kwa odwala omwe amachepetsa kwambiri kuchuluka kwa kusefedwa kwa glomerular (> 30%), poyerekeza ndi gawo loyambirira lomwe likuwoneka pa gawo lililonse la chithandizo, anali 9.3 ndi 12,2% akamagwiritsa ntchito 100 ndi 300 mg ya canagliflozin, motero, mukamagwiritsa ntchito placebo - 4,9%. Kusintha kwa magawo a labu atatha kuvomereza kuti a Encokany anali ndi malingaliro abwino kapena kuti abwerera ku zoyambira zawo.

Pa maziko a mankhwala a canagliflozin, kuwonjezeka kwa mlingo wa ndende ya LDL (low lowens lipoproteins) kunawonedwa. Kusintha kwapakati pa chizindikirochi monga kuchuluka kwa kuchuluka koyambirira, poyerekeza ndi placebo, kunali 0.11 mmol / L (4.5%) ndi 0.21 mmol / L (8%) mukamagwiritsa ntchito 100 ndi 300 mg ya canagliflozin, motsatana. Mitundu yoyambira ya LDL yoyambira ndi 100 ndi 300 mg ya canagliflozin ndi placebo inali 2.76, 2.7 ndi 2.83 mmol / L, motsatana.

Kuchulukitsa kwa 100 ndi 300 mg ya canagliflozin kunapangitsa kuwonjezeka pang'ono pa kusintha kwapakati pa hemoglobin ndende (3.5 ndi 3.8%, motsatana), poyerekeza ndi kuchepa pang'ono kwa gulu la odwala omwe adagwiritsa ntchito placebo (1.1%). Kuwonjezeka pang'ono pang'onopang'ono pakusintha kwapakati pa chiwerengero cha maselo ofiira a m'magazi ndi hematocrit adadziwika. Odwala ambiri, kuchuluka kwa hemoglobin kumawonjezeka (> 20 g / l), kuphwanya kumeneku kunawonedwa mwa 6% ya odwala omwe amalandira 100 mg ya canagliflozin, ndipo mwa 5.5% ya odwala omwe amalandira 300 mg ya canagliflozin, komanso 1% ya odwala omwe amathandizidwa ndi placebo. Zambiri mwazitsulo sizinapite pazomwe zinali zofunikira.

Kugwiritsa ntchito 100 ndi 300 mg ya canagliflozin kunapangitsa kuchepa kwapakati pa uric acid ambiri (mwa 10,1 ndi 10,6%, motsatana), poyerekeza ndi placebo, kugwiritsidwa ntchito komwe kunawonetsa kuchuluka kwa ndende yayikulu ndi 1.9% yoyamba. Matendawa anali okulirapo kapena pafupi kwambiri ndi sabata lachisanu ndi chimodzi la mankhwala ndipo amapitiliza kugwiritsidwa ntchito kwa Invokana. Kuwonjezereka kwakanthawi kwa uric acid m'mikodzo kunawonedwanso. Malinga ndi zotsatira za kuphatikiza pakuphatikizidwa kwa canagliflozin mu Mlingo woyenera, chiwonetsero cha nephrolithiasis sichinawonjezeke.

Bongo

Milandu yama bongo a Captokana osadziwika. Anthu athanzi omwe amatenga muyezo umodzi wa canagliflozin, kufikira 1600 mg, ndi odwala mtundu wachiwiri wa matenda ashuga - 600 mg patsiku mu Mlingo wotalikirana wa masabata 12 nthawi zambiri anali kulolera.

Chithandizo: zikuwonetsedwa kuti njira zothandizira zomwe zimachitika mwachizolowezi zimatengedwa, mwachitsanzo, kuchotsedwa kwa chinthu chosasinthika kuchokera mundawo ya m'mimba, kuyang'aniridwa kwachipatala ndikusamalidwa, poganizira momwe wodwalayo alili.

Pakupima kwa maola anayi, canagliflozin satiwachotsa. Pogwiritsa ntchito dialysis ya peritoneal, chinthucho sichiyembekezereka kuchotsedwa.

Malangizo apadera

Kugwiritsa ntchito kwa Callokana kwa odwala omwe ali ndi matenda a shuga 1 sikunaphunzire, chifukwa chake, kuyikidwa kwa odwala omwe ali mgululi ndi motsutsana.

Malinga ndi zotsatira za kafukufuku wa zamankhwala chitetezo, kuwopsa kwa Mlingo wobwerezabwereza, genotoxicity, kugengenetic komanso kubereka kawopsedwe, Attokana siziwopseza anthu.

Zotsatira za canagliflozin pa chonde chaumunthu sizinaphunzire. M'maphunziro a nyama, palibe chonde chomwe chinawonedwa.

Zawonetsedwa kuti canagliflozin pamene imagwiritsidwa ntchito ngati monotherapy kapena kuphatikiza mankhwala a hypoglycemic, omwe samatsatiridwa ndi chitukuko cha hypoglycemia, kawirikawiri amatsogolera ku hypoglycemia. Zakhazikitsidwa kuti ma insulin ndi othandizira a hypoglycemic omwe amathandizira pakubisika kwake amathandizira kuti hypoglycemia ipangidwe. Ndi mankhwala a Invoquana, kuphatikiza pa mankhwalawa, zochitika za hypoglycemia, poyerekeza ndi placebo, ndizambiri. Chifukwa chake, kuti muchepetse kuthekera kwa hypoglycemia, tikulimbikitsidwa kuchepetsa mlingo wa insulin kapena kukulitsa katulutsidwe ake.

Kanagliflozin, chifukwa cha kuchuluka kwa shuga kwa impso, imakhudzanso diuretic ndipo imayambitsa osmotic diuresis, yomwe ingayambitse kuchepa kwa kuchuluka kwa intravascular. Mu kliniki maphunziro a canagliflozin, kuwonjezeka kwa pafupipafupi kokhudzana ndi vutoli kunawonekera kawirikawiri m'miyezi itatu yoyambirira ya chithandizo ndi 300 mg ya Invocana. Odwala omwe ali ndi vuto losagwirizana ndi kuchepa kwa mitsempha yamitsempha amaphatikizanso odwala omwe ali ndi zaka zopitilira 75, odwala omwe amalandila zotupa, komanso odwala omwe ali ndi vuto laimpso zolimbitsa thupi.

Zizindikiro zamankhwala zakuchepa kwa kuchuluka kwa magazi amitsempha yamavuto ziyenera kudziwitsidwa kwa dokotala. Nthawi zambiri izi zimabweretsa kuchotsedwa kwa Encokany. Ndi kupitiriza kugwiritsa ntchito canagliflozin, kukonza kwa mankhwala a antihypertensive (kuphatikizapo okodzetsa) nthawi zambiri kumafunika. Asanalandire chithandizo, odwala omwe ali ndi kuchepa kwa kuchuluka kwa intravascular amafunika kusintha izi.

Kafukufuku wachipatala adanenanso za kuchuluka kwa matenda ovomerezeka a vulvovaginitis (kuphatikizapo venvovaginal fungal matenda opatsirana ndi venvovaginitis) mwa amayi omwe amalandila canagliflozin poyerekeza ndi gulu la placebo. Odwala omwe ali ndi mbiri ya candidiasis vulvovaginitis atha kukhala ndi matendawa. Mwa azimayi omwe amathandizidwa ndi canagliflozin, 2,3% awo adawonetsa chitukuko cha zochulukirapo. Nthawi zambiri, matendawa amapezeka m'miyezi inayi yoyambilira ndi Invocana. Mankhwalawa anathetsedwa chifukwa cha veral vulvovaginitis 0,7% ya odwala onse. M'maphunziro azachipatala, mphamvu ya mankhwala amkamwa kapena a antifungal mankhwala omwe adalembedwa ndi dokotala kapena ikuchitika modziyimira pawokha popitiliza kuperekera canagliflozin.

Candidiasis balanoposthitis kapena balanitis amawonetsedwa kawirikawiri mwa odwala omwe amalandira Mlingo wa Mlingo wolimbikitsidwa, poyerekeza ndi gulu la placebo. Choyamba, matendawa amapezeka mwa amuna omwe sanachite mdulidwe, ndipo nthawi zambiri - mwa odwala omwe ali ndi mbiri yolemetsa. Munthawi yamankhwala, 0,9% ya odwala anali ndi gawo loposa limodzi la matendawa. Mu 0.5% ya milandu yonse, canagliflozin adachotsedwa chifukwa cha candida balanoposthitis kapena balanitis. M'mayesero azachipatala, matendawa ankalandira chithandizo cha mankhwala a antifungal a m'dokotala kapena kumwa okha, osalephera a Attokana. Pali zambiri zokhudzana ndi milandu yachilendo ya phimosis, nthawi zina opaleshoni yodulidwa imafunikira.

Mukamachita kafukufuku wazotsatira zamtima mu odwala a 4327 omwe ali ndi matenda amtima wodalirika kapena amakhala ndi chiopsezo chamtima kwambiri, kuchuluka kwa mafupa anali 16.3, 16.4, ndi 10.8 pa zaka 1000 za odwala omwe adagwiritsa ntchito Invokana pa Mlingo wa 100 ndi 100. 300 mg ndi gulu la placebo, motsatana. Kusagwirizana kwa zomwe zimachitika pakatha milungu 26 yoyambirira yamankhwala.

Pakufufuza kophatikizidwa kwina kwa mankhwalawa, komwe kunaphatikizapo pafupifupi 5800 odwala omwe ali ndi matenda a shuga kuchokera kwa anthu ambiri, ndi mankhwala a Invocana mu Mlingo wa 100 ndi 300 mg komanso mu gulu la placebo, chiwopsezo cha kufooka kwa mafupa chinali 10,8, 12 ndi 14.1 pa odwala 1000 zaka motsatana.

Pakati pa milungu 104 ya mankhwala, mankhwalawa sanakhudze kuwonongeka kwa mafupa ochepa.

Kukopa pa kuthekera koyendetsa magalimoto ndi njira zowerengeka

Mukamayendetsa magalimoto, ndikofunikira kuganizira za chiopsezo cha hypoglycemia pankhani yogwiritsira ntchito Invokana kuwonjezera insulin kapena mankhwala omwe amathandizira kubisalira kwake, chiopsezo chowonjezereka cha zotsatira zosakhudzana ndi kuchepa kwa kuchuluka kwa intravascular (kuphatikiza chizungulire chaposachedwa), ndi kuchepa kwa kuyendetsa magalimoto ndi chitukuko cha zosafunikira zimachitika.

Mimba komanso kuyamwa

Kugwiritsa ntchito kwa canagliflozin mwa amayi apakati sikunafufuzidwe. M'maphunziro a nyama, palibe zoyipa kapena zowopsa panjira yolera zomwe zakhazikitsidwa. Komabe, Invocana sinafotokozeredwe nthawi yapakati.

Malinga ndi zomwe zapezeka mu pharmacodynamic / toxicological zomwe zimapezeka pa maphunziro a preclinical, canagliflozin amadutsa mkaka wa m'mawere. Pankhani imeneyi, poyamwitsa, kugwiritsa ntchito invokany kumatsutsana.

Ndi mkhutu aimpso ntchito

Ma mapiritsi a Invokan oopsa aimpso amatsutsana.

Pa matenda ashuga a ketoacidosis, kulephera kwa matenda a impso komanso odwala omwe ali ndi dialysis, kugwiritsidwa ntchito kwa Invokana sikungathandize, chifukwa chake, gulu ili la odwala ndilosayenera.

Kuyanjana kwa mankhwala

Kanagliflozin muchikhalidwe cha hepatocytes chaumunthu sichikulimbikitsa kufotokozera kwa CYP450 system isoenzymes (ZA4, 2C9, 2C19, 1A2 ndi 2B6). Komanso, malinga ndi kafukufuku wa zasayansi wogwiritsa ntchito ma microsomes a chiwindi cha anthu, samalepheretsa cytochrome P isoenzymes₄₅₀ (IA2, 2A6, 2C19, 2E1 kapena 2B6) ndipo amalepheretsa CYP2B6, CYP2C8, CYP3A4, CYP2C9. Kanagliflozin ndi gawo laling'ono la UGT2B4 ndi UGTIA9 ma enzymes omwe amapanga mankhwala, komanso omwe amayendetsa mankhwala P-gp (P-glycoprotein) ndi MRP2. Kanagliflozin ndi imodzi mwazoletsa kwambiri za P-gp. Thupi limadutsa oxidative kagayidwe pang'ono. Chifukwa chake, kuchuluka kwakukalamba kwa mankhwala ena kudzera mu cytochrome P kachitidwe sikungatheke₄₅₀ pa pharmacokinetics ya canagliflozin.

Kutengera ndi kuchuluka kwa zamankhwala, zitha kuganiziridwa kuti kuthekera kokuchita kwakukulu ndi mankhwala omwe amamwa pamodzi ndi Invocana ndikotsika.

Pogwiritsa ntchito munthawi yomweyo ndi rifampicin, kuwonetsa kwa canagliflozin ndipo, chifukwa chake, mphamvu yake imachepa. Ngati ndi kotheka kugwiritsa ntchito nthawi yomweyo ndi rifampicin ndi zina zoyambitsa banja la UGT la michere ndi mankhwala onyamula (kuphatikizapo phenytoin, phenobarbital, ritonavir) mwa odwala omwe amalandila 100 mg ya canagliflozin, ndikofunikira kuthana ndi kuchuluka kwa hemoglobin Нb_{Ma A1}. Ngati glycemic yowonjezera ikufunika, lingalirani kuchuluka kwa canagliflozin mpaka 300 mg.

M'mayesero azachipatala, canagliflozin sanakhudze kwambiri magawo a pharmacokinetic a metformin, njira zakulera zamkamwa (ethinyl estradiol ndi levonorgestrel), simvastatin, glibenclamide, warfarin kapena paracetamol.

Kanagliflozin ikaphatikizidwa ndi digoxin imakhudza pang'ono ndende yake ya plasma, yomwe imafunikira kuwunika koyenera.

Mafanizo a Attokany ndi Forsyga, Jardins.

Mlingo

100 mg ndi 300 mg mapiritsi okhala ndi mafilimu

Piritsi limodzi, filimu wopangidwa ndi 100 mg ali ndi:

102 mg ya canagliflozin hemihydrate ndi ofanana ndi 100 mg ya canagliflozin.

Zabwino (pakati): microcrystalline cellulose, anactrous lactose, croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate.

Zabwino (chipolopolo): Opadry II 85F92209 chikasu: mowa wa polyvinyl, waphatikiza hydrolyzed, titanium dioxide (E171), macrogol / polyethylene glycol 3350, talc, iron oxide chikasu (E172).

Piritsi la 300 mg lomwe lophimbidwa muli:

306 mg wa canagliflozin hemihydrate ndi wofanana ndi 300 mg wa canagliflozin.

Zabwino (pakati): microcrystalline lactose anhydrous cellulose, croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate.

Zabwino (chipolopolo): Opadry II 85F18422 loyera: mowa

polyvinyl, pang'ono hydrolyzed, titanium dioxide (E171), macrogol / polyethylene glycol 3350, talc.

Mlingo wa 100 mg: mapiritsi, achikaso achikhatoni amakanema, chowoneka ngati kapisozi, cholemba "CFZ" mbali imodzi ndi "100" mbali inayo.

Mlingo wa 300 mg: mapiritsi okhala ndi filimu kuyambira oyera mpaka pafupi oyera, okhala ndi mawonekedwe a kapisozi, olembedwa "CFZ" mbali imodzi ndi "300" mbali inayo.

Mankhwala

Pharmacokinetics

Pharmacokinetics ya canagliflozin mwa anthu athanzi ndi ofanana ndi pharmacokinetics ya canagliflozin odwala omwe ali ndi matenda a mtundu wa 2. Pambuyo pakamwa limodzi lokha la 100 mg ndi 300 mg ndi odzipereka athanzi, canagliflozin amatengedwa mwachangu, kuchuluka kwakukulu kwa plasma (Median Tmax) kufikiridwa patatha maola 1-2 atatha kumwa mankhwala. Kutalika kwambiri kwa plasma kwa Cmax ndi AUC ya canagliflozin kumakulirakulirabe ndi kugwiritsidwa ntchito kwa Mlingo kuchokera 50 mg mpaka 300 mg. The theka lomaliza lamoyo (t1 / 2) (lofotokozedwa ngati ± kupatuka kwadongosolo) linali ma 10.6 ± 2.13 maola ndi 13.1 ± 3.28 maola mukamagwiritsa ntchito Mlingo wa 100 mg ndi 300 mg, motsatana. Kuyanjana kwamankhwala ofanana kunakwaniritsidwa patatha masiku 4-5 atangoyamba canagliflozin mankhwala pa 100 mpaka 300 mg kamodzi patsiku.

Ma pharmacokinetics a canagliflozin samatengera nthawi. Kuchuluka kwa mankhwalawa m'madzi a m'magazi kumafika pa 36% pambuyo pobwereza.

Zogulitsa

Ambiri mtheradi bioavailability wa canagliflozin pafupifupi 65%. Kudya zakudya zamafuta kwambiri sizinakhudze pharmacokinetics ya canagliflosin, kotero canagliflosin akhoza kumwa kapena wopanda chakudya. Komabe, poganizira kuthekera kwa canagliflozin kuti achepetse kusinthika kwa postprandial glycemia chifukwa cha kutsika kwa mayamwidwe a shuga m'matumbo, tikulimbikitsidwa kutenga canagliflozin isanachitike chakudya choyamba.

Kugawa

Chiwonetsero chachikulu cha canagliflozin chofanana ndi kulowetsedwa kamodzi mwa anthu athanzi chinali 119 l, zomwe zikuwonetsa kufalikira kwamankhwala. Kanagliflosin imagwirizanitsidwa kwambiri ndi mapuloteni a plasma (99%), makamaka ndi albumin. Mapuloteni omanga amapezeka palokha popanda plasma ndende ya canagliflozin. Kumanga kwa mapuloteni a Plasma sikumasintha kwenikweni kwa odwala omwe ali ndi impso kapena hepatic.

Kupenda

Njira yayikulu ya metabolic excretion ya canagliflozin ndi O-glucuronidation, yomwe imachitika makamaka ndi UGT1A9 ndi UGT2B4 kwa awiri osagwira a O-glucuronide metabolites. Metabolism ya canagliflozin yapakati ndi CYP3A4 (oxidative metabolism) mwa anthu imalephera kuzungulira (pafupifupi 7%).

M'maphunziro muvitro canagliflozin sanalepheretse michere ya cytochrome P450 dongosolo CYP1A2, CYP2A6, CYP2C19, CYP2D6 kapena CYP2E1, CYP2B6, CYP2C8, CYP2C9 komanso CYP1A2, CYP2C, CYP2C, CYP1C, CYP1, CYP1, CYP1, CYP. Makamaka kwambiri pa ndende ya CYP3A4 muvivo osawonedwa (onani gawo "Kuchita ndi Mankhwala").

Kuswana

Pambuyo pakamwa limodzi 14C canagliflozin mwaumoyo odzipereka, 41,5%. 7.0% ndi 3,2% ya mlingo wovomerezeka wama radio unaikidwa mu ndowe mu mawonekedwe a canagliflozin, hydroxylated metabolite ndi O-glucuronide metabolite, motero. Enterohepatic recirculation ya canagliflozin sichinadziwike.

Pafupifupi 33% ya mlingo wovomerezeka wa radioactive unachotsedwa mkodzo, makamaka mu mawonekedwe a O-glucuronide metabolites (30,5%). Osakwana 1% ya mlingo womwe unatengedwa udafukusidwa ngati canagliflozin osasinthika mumkodzo. Kuvomerezeka kwa impso kwa canagliflozin pamene mugwiritsidwa ntchito Mlingo wa 100 mg ndi 300 mg kuchokera pa 1,30 ml / min mpaka 1.55 ml / min.

Kanagliflozin ndi chinthu chotsika chilolezo, pomwe chiwonetsero chazomwe zimachitika mwa odzipereka omwe ali ndi thanzi labwino chimatha pafupifupi 192 ml / mphindi.

Magulu apadera a odwala

Odwala ndi mkhutu aimpso ntchito

Mu kafukufuku wotseguka limodzi, pharmacokinetics ya canagliflozin anaphunziridwa atagwiritsidwa ntchito pa mlingo wa 200 mg mwa odwala omwe amalephera kupweteka a kusiyanasiyana (malinga ndi kufotokozaku kutengera kuchotsera kwa forminine kuwerengeka ndi njira ya Cockcroft-Gault) poyerekeza ndi anthu athanzi. Kafukufukuyu adakhudza odwala 8 omwe ali ndi vuto lachilendo (creatinine chilolezo cha 80 ml / min), odwala 8 omwe amalephera kupweteka kwapafupa (kulekera chilolezo cha 50 ml / mphindi - -10% ndi ≤12%

Pakafukufuku wokhudza odwala omwe ali ndi misinkhu ya HbA1c> 10% ndi ≤ 12%, mukamagwiritsa ntchito canagliflozin monga monotherapy, kuchepa kwa mfundo za HbA1c poyerekeza ndi basement (popanda kukonza kwa placebo) ndi -2.13% ndi -2.56% ya canagliflozin Mlingo wa 100 mg ndi 300 mg, motero.

European Agency for the Evaluation of Quality of Medicines inapereka ufulu wosapereka zotsatira za kafukufuku wa mankhwala Invocana® m'magulu onse aana omwe ali ndi matenda a shuga 2 (chidziwitso pakugwiritsa ntchito kwa ana chawonetsedwa mu gawo la "Njira Yogwiritsira Ntchito ndi Kutulutsa").

Zizindikiro zogwiritsidwa ntchito

Kuwongolera glycemic control mankhwalawa amtundu wa 2 odwala akulu akulu:

- Zomwe kudya ndi kuchita zolimbitsa thupi sizipereka chiwonetsero chokwanira cha glycemic komanso kugwiritsa ntchito metformin kumawonedwa ngati kosayenera kapena kotsutsana.

- ngati chida chowonjezera ndi mankhwala ena ochepetsa shuga, kuphatikiza insulin, pomwe, limodzi ndi zakudya komanso zolimbitsa thupi, samapereka chiwongolero chokwanira cha glycemic.

Mlingo ndi makonzedwe

Invocana ® iyenera kumwedwa kamodzi pa tsiku, makamaka asanadye kaye.

Akuluakulu (≥ wazaka 18)

Mlingo woyambira wa Invocan® ndi 100 mg kamodzi tsiku lililonse. Odwala omwe amalekerera 100 mg ya mankhwalawa kamodzi patsiku, kwa omwe amachepetsa kuchuluka kwa kusefera kwa mafuta (rSCF) ≥ 60 ml / mphindi / 1.73 m2 kapena chilolezo cha creatinine (CrCl) ≥ 60 ml / mphindi. kuchuluka kwa shuga wamagazi, mlingo wa mankhwalawa ukhoza kuwonjezeka mpaka 300 mg kamodzi patsiku (onani gawo "Malangizo apadera").

Ndikofunikira kuyang'anira kuwonjezeka kwa mlingo wa mankhwalawa kwa odwala azaka zapakati pa 75 ndi makumi asanu ndi awiri, odwala omwe ali ndi matenda amtima wamatenda, kapena odwala ena omwe mayendedwe oyamba chifukwa cha kutenga Captokana® ndi chiopsezo (onani gawo "Malangizo Apadera"). Kwa odwala omwe ali ndi vuto losowa madzi m'mimba, tikulimbikitsidwa kukonza izi musanamwe mankhwala a Captokana® (onani gawo "Malangizo apadera").

Mukamagwiritsa ntchito mankhwala a Captokana® monga cholumikizira mankhwala a insulin kapena chothandizira kuphatikiza (mwachitsanzo, kukonzekera kwa sulfonylurea), kuchepetsa chiopsezo cha hypoglycemia, mwayi wogwiritsa ntchito mankhwala ocheperawa ungaganizidwe (onani zigawo "Zokhudzana ndi Mankhwala Osokoneza bongo" ndi "Zotsatira Zotsatira") .

Odwala okalamba ≥ Zaka 65

Ntchito yeniyeni ndi chiwopsezo cha kusowa kwamadzi ziyenera kukumbukiridwa (onani "Malangizo Apadera").

Odwala omwe ali ndi vuto la impso

Kwa odwala omwe ali ndi eGFR ya 60 ml / mphindi / 1.73 m2 mpaka 30%) nthawi iliyonse panthawi yamankhwala anali 9,3%, 12,2% ndi 4.9% mwa iwo omwe amatenga 100 mg, 300 mg canagliflozin ndi placebo, motero. Pamapeto pa kafukufukuyu, kuchepa kwa mtengowu kumaonedwa mu 3.0% ya odwala omwe amatenga 100 mg ya canagliflozin, 4.0% mwa omwe adatenga 300 mg, ndi 3.3% ya placebo (onani gawo "Maupangiri Apadera").

Zochita zamankhwala

Kanagliflozin imatha kupititsa patsogolo kukodzetsa, komanso kuonjezera chiwopsezo cha kuchepa madzi komanso kuthamanga kwa magazi (onani gawo "Malangizo apadera").

Insulin ndi insulin katulutsidwe

Zosangalatsa za insulin ndi insulin, monga sulfonylureas, zimatha kuyambitsa hypoglycemia.

Chifukwa chake, kuti muchepetse chiwopsezo cha hypoglycemia, ndikofunikira kuti muchepetse kuchuluka kwa insulini kapena chosangalatsa cha insulin pamene mugwiritsidwa ntchito limodzi ndi canagliflozin (onani magawo "Mlingo ndi Ulamuliro" ndi "Zotsatira Zowopsa").

Mphamvu mankhwala ena pa canagliflozin

Kagayidwe ka canagliflozin makamaka chifukwa cholumikizana ndi glucuronides, yolumikizidwa ndi UDP-glucuronyl transferase 1A9 (UGT1A9) ndi 2B4 (UGT2B4). Kanagliflozin imanyamula P-glycoprotein (P-gp) ndi mapuloteni odana ndi khansa ya m'mawere (BCRP).

Enzyme Inductors (monga St. John Wort Hypericumperforatum, rifampicin, barbiturates, phenytoin, carbamazepine, ritonavir, efavirenz) zingayambitse kuchepa kwa kukhudzana ndi canagliflozin. Pambuyo kugwiritsa ntchito munthawi yomweyo canagliflozin ndi rifampicin (wokonza zinthu zosiyanasiyana zoyeserera ndi ma enzymes okhudzana ndi kagayidwe kamankhwala), kuchepa kwa dongosolo la canagliflozin ndi 51% ndi 28% (curve area, AUC) and maximum maximum (Cmax). Kutsika koteroko kumatha kubweretsa kuchepa kwa mphamvu ya canagliflozin.

Ngati kuli kofunikira kugwiritsa ntchito nthawi yomweyo kugwiritsa ntchito ma Enzymer a UDP ndi mapuloteni onyamula ndi canagliflozin, ndikofunikira kuwongolera kuchuluka kwa shuga kuti athe kuyang'ana momwe angayankhire canagliflozin. Ngati kuli kofunikira kugwiritsa ntchito kukopa kwa ma enzymes a UDF awa limodzi ndi canagliflozin, mlingo umakulitsidwa mpaka 300 mg kamodzi patsiku, ngati kulekerera kwabwino kwa odwala 100 mg a canagliflozin kamodzi patsiku, mtengo wawo wa rSCF ndi ≥ 60 ml / mphindi / 1.73 m2 kapena CrCl ≥ 60 ml / min., ndipo amafunikira kuwongolera kwakulu kwa glucose m'magazi. Kwa odwala omwe ali ndi eGFR ya 45 ml / mphindi / 1.73 m2 kapena ochepera 60 ml / mphindi / 1.73 m2 kapena CrCl ya 45 ml / min. ndi ochepera 60 ml / mphindi., ndipo amatenga 100 mg ya canagliflozin, komanso opanikizika ndi othandizira a UDF-enzyme, ndipo omwe amafunikira kuwongolera shuga wamagazi, mitundu ina ya mankhwalawa imayenera kuganiziridwa kuti muchepetse kuchuluka kwa shuga (onani magawo "Mlingo ndi kasamalidwe" ndi "Malangizo apadera").

Cholestyramine ikhoza kutsitsa kuzama kwa canagliflozin. Kanagliflozin iyenera kutengedwa osachepera ola limodzi kapena maola 4-6 mutatha kugwiritsa ntchito bile acid sequestrants kuti muchepetse zovuta zomwe zimayamwa.

Kafukufuku wowerengeka awonetsa kuti metformin, hydrochlorothiazide, kulera kwamlomo (ethinyl estradiol ndi levonorgestrol), cyclosporine ndi / kapena probenecid sizikhudza pharmacokinetics ya canagliflozin.

Zotsatira za canagliflozin pa mankhwala ena

Digoxin: munthawi yomweyo kugwiritsa ntchito canagliflozin pa 300 mg kamodzi patsiku kwa masiku 7 ndi kugwiritsa ntchito kamodzi kwa 0,5 mg wa digoxin wotsatira mlingo wa 0,25 mg wa patsiku kwa masiku 6, kwapangitsa kuchuluka kwa AUC kwa digoxin ndi 20% komanso kuchuluka kwa Cmax ndi 36 %, mwina chifukwa cha kuletsa kwa P-gp. Kanagliflozin yasonyezedwa kuti imaletsa P-gp muvitro. Odwala omwe amatenga digoxin ndi mtima wama glycosides ena (mwachitsanzo, digitoxin) amayang'aniridwa moyenera.

Dabigatran: kugwiritsidwa ntchito kophatikizira kwa canagliflozin (ofooka wa P-gp inhibitor) ndi dabigatran etexilate (P-gp gawo lapansi) sikunaphunzire. Popeza kuchuluka kwa dabigatran kungachuluke pamaso pa canagliflozin, ndikugwiritsa ntchito munthawi yomweyo dabigatran ndi canagliflozin, ndikofunikira kuwunika momwe wodwalayo alili (kuthetsa zizindikiro za magazi kapena kuchepa magazi).

Simvastatin: kuphatikiza 300 mg ya canagliflozin kamodzi pa tsiku kwa masiku 6 ndi kugwiritsa ntchito kamodzi kwa 40 mg ya simvastatin (gawo lapansi CYP3A4) zinapangitsa kuti AUC ya simvastatin ikhale 12% komanso kuwonjezeka kwa Cmax ndi 9%, komanso kuwonjezeka kwa AUC ya simvastatin acid ndi 18% komanso kuwonjezeka kwa Cmax ya simv acid ndi 26%. Kuwonjezeka kotereku kwa simvastatin ndi simvastatin acid sikuti kumaonedwa kukhala kofunika kwambiri.

Kuletsa kwa mapuloteni odana ndi khansa ya m'mawere (BCRP) motsogozedwa ndi canagliflozin pamatumbo sikungathe kudziwika, chifukwa chake ndizotheka kuwonjezera kuchuluka kwa mankhwala omwe amayendetsedwa ndi BCRP, mwachitsanzo, ma statin ena, monga rosuvastatin ndi mankhwala ena a anticancer.

Mu maphunziro a machitidwe a canagliflozin mu kufanana kwa magawo, panalibe zovuta zambiri pa pharmacokinetics ya metformin, njira zothandizira pakamwa (ethinyl estradiol ndi levonorgestrol), glibenclamide, paracetamol, hydrochlorothiazide ndi warfarin.

Kuyanjana Ndi Mankhwala / Zotsatira pa Zotsatira za Laborator

Mayankho a 1,5-AG

Kuchulukitsa kwa shuga kwamkodzo pogwiritsira ntchito canagliflozin kungayambitse kukhazikitsidwa kwa milingo yoposa 1,5-anhydroglucite (1,5-AH), chifukwa cha zomwe maphunziro a 1,5-AH amalephera kudalirika pakuwongolera glycemic control. Pamenepa, kutsimikiza kwa 1,5-AH sikuyenera kugwiritsidwa ntchito ngati njira yowunikira glycemia mwa odwala omwe alandira Invokana®. Kuti mumve zambiri, ndikofunikira kulumikizana ndi omwe amapanga mayeso machitidwe kuti adziwe 1,5-AH.

Wopanga

Janssen-Ortho LLC, Gurabo, Puerto Rico

Packer

Janssen-Silag S.p.A., Italy

Mwiniwake wa satifiketi yolembetsa:

Johnson & Johnson LLC, Russia.

Adilesi ya bungweli kulandira zovomerezeka kuchokera kwa ogula pamalonda a zinthu (katundu) komanso omwe amayang'anira kuyang'anira kuyang'anira chitetezo cha mankhwala m'dera la Republic of Kazakhstan

Nthambi ya LLC Johnson & Johnson ku Republic of Kazakhstan

050040, Almaty, St. Timiryazev, 42, phalepo No. 23 "A"

Attokana (canagliflozin): malangizo, ndemanga

Mankhwala a Invokana ndi ofunikira kuthandizira odwala matenda a shuga a mtundu 2. Chithandizo cha mankhwalawa chimaphatikizapo kuphatikiza zakudya zowonjezera, komanso kuchita masewera olimbitsa thupi nthawi zonse.

Glycemia idzasinthidwa kwambiri chifukwa cha monotherapy, komanso ndi mankhwala othandizirana ndi othandizira ena a hypoglycemic.

Contraindication ndi mawonekedwe ogwiritsa ntchito

Mankhwala a Invokana sangathe kugwiritsidwa ntchito ngati:

Hypersensitivity to canagliflozin kapena chinthu china chomwe chimagwiritsidwa ntchito ngati chothandizira,
mtundu 1 shuga
matenda ashuga ketoacidosis,
kulephera kwambiri kwaimpso
kulephera kwambiri kwa chiwindi,
Mimba ndi kuyamwa
ana ochepera zaka 18.

Panthawi yapakati komanso yoyamwitsa, maphunziro amomwe thupi limayankhira mankhwalawo sanachitike. Poyeserera nyama, sizinapezeke kuti canagliflozin ili ndi njira yosawonekera kapena yoyipa yazokhudza dongosolo la kubereka.

Komabe, momwemo, kugwiritsa ntchito mankhwalawa ndi amayi nthawi imeneyi kumalimbikitsidwa kwambiri, chifukwa chopangira chofunikira kwambiri chimatha kulowa mkaka wa m'mawere ndipo mtengo wa chithandizo chotere ungakhale wopanda chifukwa.

Kutulutsa mafomu ndi kapangidwe kake

Kuphatikizika kwa mapiritsiwa kumaphatikiza canagliflozin hemihydrate mu gawo lofanana ndi 100-300 mg wa canagliflozin. Zomwe zimapangidwira zimathandizira kuphatikiza zinthu zomwe zimapangitsa kapangidwe kake piritsi ndikuthandizira kugawa zinthu zogwira ntchito mthupi.

Amapezeka mu mapiritsi a 100 kapena 300 mg, filimu yokutidwa ndi tint yachikasu. Piritsi lililonse lili ndi chiopsezo chosinthana ndi kusweka.

Zotsatira za pharmacological

Ili ndi vuto la hypoglycemic. Kanagliflozin ndi mtundu wa 2 sodium glucose cotransporter inhibitor. Pakangotha mlingo umodzi, mankhwalawa amathandizira kuphipha kwa glucose ndi impso, zomwe zimathandiza kuchepetsa kuchepa kwake m'magazi. Mankhwalawa ndi othandizadi pochiza matenda osokoneza bongo omwe amadalira shuga. Siziwonjezera katemera wa insulin.

Mankhwalawa ndi othandizadi pochiza matenda osokoneza bongo omwe amadalira shuga.

Kuchulukitsa diuresis, komwe kumapangitsanso kuchepa kwa ndende yamagazi. Kafukufuku wachipatala akuwonetsa kuti kugwiritsa ntchito mankhwalawa tsiku lililonse kumachepetsa mphamvu ya shuga komanso kupangitsa kuti ikhale yokhazikika. Kugwiritsa ntchito mankhwala a canagliflozin amachepetsa glycemia atatha kudya. Imathandizira kuchotsedwa kwa glucose m'matumbo.

M'maphunziro, zidatsimikizika kuti kugwiritsa ntchito Singokana ngati monotherapy kapena ngati adjunct pochiza ndi mankhwala ena a hypoglycemic, poyerekeza ndi placebo, kumathandizira kuchepetsa glycemia musanadye ndi 1.9-2.4 mmol pa lita.

Kugwiritsa ntchito mankhwalawa kumathandizira kuchepetsa glycemia pambuyo poyesa kulekerera kapena kadzutsa. Kugwiritsa ntchito canagliflozin kumachepetsa shuga ndi 2.1-3,5 mmol pa lita. Pankhaniyi, mankhwalawa amathandizira kusintha magawo a beta cell mu kapamba ndikuwonjezera chiwerengero chawo.

Kuchokera kwamikodzo

Mwinanso kuphwanya kwa magwiridwe antchito a impso mu mawonekedwe okoka pafupipafupi komanso kumasulidwa kwamadzi ambiri. Malangizo omwe wodwalayo amamwa pa izi amasintha, ndipo amayamba kugwiritsa ntchito madzi ambiri. Zilimbikitso zosayenera zitha kuchitika, bola ngati mkodzo mulibe.

Mwinanso kuphwanya kwa magwiridwe antchito a impso mu mawonekedwe okoka pafupipafupi komanso kumasulidwa kwamadzi ambiri.

Pa mbali ya chiwindi ndi biliary thirakiti

Sichimayambitsa kuwonongeka kwa chiwindi komanso kusintha kwa ntchito ya ma enzymes a chiwindi.

Nthawi zina, zimathandizira kuti thupi lanu lizigundana mokhazikika ngati zotupa pakhungu kapena edema.

Nthawi zina, zimathandizira kuti thupi lizigwirizana chifukwa cha chotupa cha pakhungu.

Gwiritsani ntchito panthawi yoyembekezera komanso mkaka wa m`mawere

Cholinga cha mankhwalawa panthawi ya gestation ndi yoyamwitsa sichimachitika. Ngakhale maphunziro azinyama sanawonetse vuto la mwana pa mwana wosabadwayo, akatswiri azachipatala ndi othandizira salimbikitsa kugwiritsa ntchito mapiritsi ali ndi mwana.

Mankhwala osokoneza bongo amaletsedwanso panthawi ya mkaka wa m'mawere, chifukwa mapiritsi omwe amatha kugwira ntchito amatha kulowa mkaka wa m'mawere ndikuchita thupi la wakhanda.

Mankhwala osokoneza bongo amaletsedwanso panthawi ya mkaka wa m'mawere, chifukwa mapiritsi omwe amatha kugwira ntchito amatha kulowa mkaka wa m'mawere ndikuchita thupi la wakhanda. Mphamvu ya mankhwalawa pachonde sichinaphunzire.

Kuchita ndi mankhwala ena

Mankhwalawa amasintha pang'ono kuchuluka kwa digoxin m'madzi a m'magazi. Anthu omwe amamwa mankhwalawa amayenera kukhala osamala kwambiri ndikusintha Mlingo wake pa nthawi yake.

Tisinthe pang'ono mayamwidwe ndi kagayidwe ka Levonorgestrel, Glibenclamide, Hydrochlorothiazide, Metformin, Paracetamol.

Odwala apadera

Monga tanena kale, ana a Encokan samalimbikitsidwa kuti azigwiritsa ntchito chifukwa luso ndi chitetezo chamtunduwu sichinakhazikitsidwe.

Mukakalamba, mlingo woyambirira wa mankhwalawa uzikhala 100 mg kamodzi. Ngati kulolerana ndikokhutiritsa, ndiye kuti odwala ayenera kusinthana ndi mlingo wofika 300 ml, koma malinga ndi kuwonjezereka kwa glycemia.

Panthawi ya vuto laimpso, palibe chifukwa chosinthira kuchuluka kwa mankhwalawa.

Ngati pali kuwonongeka kwakukulu kwa ntchito ya impso (zolimbitsa mwamphamvu), dokotala amalimbikitsa mankhwala a Invokana mu koyamba kwa 100 mg patsiku. Ndi kulekerera kokwanira komanso kuwongolera kowonjezera shuga m'magazi, odwala adzasamutsidwira ku mlingo wofika 300 mg wa canagliflozin. Ndikofunikira kuti muchepetse shuga. kugwiritsa ntchito chipangizo kuyeza. Koma kodi glucometer yabwino kwambiri yomwe mungagwiritse ntchito, zomwe talemba patsamba lino zithandiza.

Mankhwalawa adapangidwa kuti agwiritsidwe ntchito ndi gulu la odwala omwe matenda aimpso ofooka kwambiri. Ngati gawo la maphunziro a aimpso kulephera ndi kudwala, ndiye kuti kugwiritsa ntchito canagliflozin sizingathandize. Lamuloli limagwiranso ntchito kwa odwala omwe akupita dialysis nthawi zonse.

Zotsatira zoyipa za mankhwalawa

Kafukufuku wapadera wa zamankhwala adachitidwa kuti akhazikitse mfundo zokhudzana ndi zovuta zomwe zimagwiritsidwa ntchito ndi mankhwalawa. Zomwe zidalandilidwa zidakonzedwa malinga ndi dongosolo lililonse komanso pafupipafupi zomwe zimachitika.

Iyenera kuganizira zovuta zomwe zimadza chifukwa chogwiritsa ntchito canagliflozin:

kugaya chakudya cham'mimba (kudzimbidwa, ludzu, pakamwa pouma),
kuphwanya impso ndi kwamikodzo thirakiti (urosepsis, matenda opatsirana kwamkodzo, polyuria, polakiuria, chilimbikitso cha peremptory kutulutsa mkodzo),
mavuto kuchokera ku tchire ta mammary ndi ziwalo zam'mimba (balanitis, balanoposthitis, matenda amkazi, vulvovaginal candidiasis).

Zotsatira zoyipa za thupi zimachokera ku mototherapy, komanso chithandizo chomwe mankhwalawa adathandizidwa ndi pioglitazone, komanso sulfonylurea.

Kuphatikiza apo, zovuta zomwe wodwalayo ali ndi mtundu wachiwiri wa matenda ashuga zimaphatikizanso zomwe zimapangidwa poyeserera kwa canagliflozin poyeserera pafupipafupi 2 peresenti. Tikukamba za zosakhudzika zosakhudzana zomwe zimakhudzana ndi kuchepa kwa mitsempha yamitsempha, komanso urticaria ndi totupa pakhungu. Tiyenera kudziwa kuti kuwonetsa khungu pakokha ndi matenda a shuga siachilendo.

Zizindikiro zazikulu za mankhwala osokoneza bongo

Muzochita zachipatala, mpaka pano, milandu ya kumwa kwambiri wa canagliflozin sichinafotokozedwebe. Ngakhale madontho amodzi okhawo omwe amafikira 1600 mg mu anthu athanzi ndi 300 mg patsiku (kwa masabata 12) mwa odwala omwe ali ndi matenda a shuga a 2 amaloledwa nthawi zonse.

Ngati mankhwalawa awonjezeka, ndiye kuti mtengo wake ndikuwukhazikitsa njira zothandizira.

Njira yochizira bongo ndi kuchotsera zotsalira za chinthu chogwiritsa ntchito m'magazi, komanso kukhazikitsa kuyan'ana ndi chithandizo chachipatala, poganizira momwe alili.

Kanagliflosin sangathe kuchotsedwa pa nthawi ya maola 4 oyimba. Poona izi, palibe chifukwa chonenera kuti chinthucho chidzapukutidwa kudzera mu peritoneal dialysis.

Kufotokozera ndi malangizo ogwiritsira ntchito mankhwala a Captokana

Mankhwala a hypoglycemic amapezeka mu mawonekedwe a mapiritsi onenepa yokutidwa ndi chipolopolo chamafuta achikasu, omwe cholinga chake ndi kutsata pakamwa mokwanira. Odwala amatha kugwiritsa ntchito mankhwala a Invokan ngati chithandizo chodziimira payekha, kapena ngati gawo limodzi la zovuta popanga mankhwala a insulin.

Yogwira ntchito ya Invocan ndi canagliflozin hemihydrate, yomwe imayambitsa kuchuluka kwa shuga m'magazi. Cholinga chake kwa wodwala ndichoyenera mtundu wa matenda ashuga a 2. Koma ndi matenda amtundu woyamba wamtunduwu, kuikidwa kwake kumatsutsana kwambiri. Zomwe zimapangidwa mu mawonekedwe a Invocan amapangidwa mozama mu kayendedwe ka kayendedwe kazinthu, zimafalikira m'chiwindi, ndipo zimatsitsidwa ndi impso mkodzo.

Attokana samalimbikitsidwa kuti azigwiritsidwa ntchito ndi amayi panthawi yoyembekezera komanso pakubala. Zoletsa zamankhwala zimagwiranso ntchito pazotsatira zamankhwala zotsatirazi:

Hypersensitivity kwa yogwira zinthu,
matenda ashuga ketoacidosis,
zoletsa zaka mpaka 18,
Kulephera kovuta kwa aimpso,
kulephera kwa mtima
kulephera kwambiri kwa chiwindi.

Payokha, ndikofunikira kuwunikira zoletsa zokhudzana ndi odwala pakati komanso amayi oyamwitsa. Kafukufuku wamankhwala wokhudzana ndi mankhwala a Attokana am'magulu awa sanachitidwire, chifukwa chake madotolo amangoopa kusankhidwa kwawo chifukwa cha umbuli. Ngati chithandizo chikufunika, palibe choletsa malinga ndi malangizo a Attokan, ndikungoti wodwalayo ayenera kuyang'aniridwa mosamala panthawi ya chithandizo kapena prophylactic. Phindu kwa mwana wosabadwayo liyenera kukhala lokwera kuposa momwe lingasokonezere chitukuko cha intrauterine - pokhapokha pokhapokha kuikidwa ndikothandiza.

Mankhwalawa amatha kusinthika mthupi, koma kumayambiriro kwenikweni kwa chithandizo chamankhwala kumatha kuyambitsa mavuto. Nthawi zambiri imakhala kugayikana mu mawonekedwe a chotupa cha hemorrhagic komanso kuyabwa kwambiri pakhungu, chizindikiro cha dyspepsia ndi mseru. Pankhaniyi, makina a Invocan ayenera kusiidwa, limodzi ndi katswiri, sankhani analogue, sinthani othandizira. Milandu yambiri imakhala yangozi kwa wodwalayo, chifukwa amafunika chithandizo cham'mbuyo posachedwa.

Njira ntchito, tsiku lililonse Mlingo wa mankhwala akuti

Mlingo wa tsiku ndi tsiku wa mankhwala a Invokana ndi 100 mg kapena 300 mg ya canagliflozin hemihydrate, omwe amawonetsedwa kamodzi patsiku. Kukonzekera kwa pakamwa kwa odwala opitirira zaka 18 kukuwonetsedwa musanadye kadzutsa - kokha pamimba yopanda kanthu. Kuphatikiza ndi insulin, Mlingo wa tsiku ndi tsiku uyenera kusinthidwa payekhapayekha kuti muchepetse ndikuchepetsa kwambiri chiopsezo cha hypoglycemia.

Ngati wodwalayo adayiwala kumwa kamodzi, ndiye kuti ndikofunikira kumwa piritsi mukakumbukira kaye kaye za panjira. Ngati chidziwitso chodumpha mlingo chinangofika pa tsiku lachiwiri, kumwa kawiri pamlomo kumangokhala kotsutsana. Ngati mankhwalawa amalembera ana, achinyamata kapena opuma pa zaka 75, ndikofunikira kuchepetsa mlingo wa tsiku ndi tsiku kufika pa 100 mg.

Popeza mankhwalawa amathandizira pakukonzekera kwina kwa magazi, ndizosatheka kudyetsa mowonjezereka miyezo yatsiku ndi tsiku ya Invokan. Kupanda kutero, wodwalayo amayembekeza kuti azisanza pamatumbo chifukwa cha kusanza kwachidziwikire, kudya zina zowonjezera, chithandizo chamankhwala chifukwa cha zamankhwala.

Mndandanda wa mankhwala a Captokana

Mankhwala omwe adalankhulidwawo sakhala oyenera kwa odwala onse, ndipo mndandanda wazotsatira zomwe zikuwonetsedwa m'malangizo amatsimikiziranso kuopsa kwa nthawi yayitali ngati akuphwanya malangizo a chipatala. Pakufunika kugula ma analogues, omwe mankhwalawa adatsimikizira bwino:

Ndemanga za Callokana

Mankhwalawa ndiwodziwika pakati pa odwala omwe ali ndi matenda a shuga a mtundu wachiwiri. Aliyense amalemba pamabwalo azachipatala za kuthekera kwambiri kwa Attokan, kwinaku akukumbukira kuti adadzidzimuka pamiyeso yododometsa. Mtengo wa mankhwalawa ndiwokwera, pafupifupi ma ruble 1,500, kutengera mzinda wogula ndi mtundu wa mankhwala. Omwe adapeza izi adakhutira ndi zomwe adatenga, popeza shuga adakhala wolimba mwezi umodzi.

Odwala omwe ali ndi matenda a shuga akuti ngati mankhwala a Attokan satsimikiza kuti achira, komabe, kuwonekera kwakukulu mwa omwe ali ndi "matenda ashuga" ndikwachidziwikire. Zizindikiro zingapo zosasangalatsa zimasowa, mwachitsanzo, ma membala owuma a mucous ndikumangokhala ndi ludzu, ndipo wodwalayo amadzimvanso kuti ndi munthu wokhazikika. Odwala ambiri omwe ali ndi matenda ashuga amafotokoza milandu ikakhungu pakadutsa khungu ndipo mantha amkati amwalira.

Zolemba zoyipa za Attokana zimapezeka pazocheperako, ndipo pazomwe zimapezeka pazachipatala zimangowonetsa mtengo wokwera wa mankhwalawa, kukhalapo osati m'mafakitala onse amzindawu. Pazonse, mankhwalawa ndi abwino, chifukwa amathandiza wodwala matenda ashuga kuthana ndi magazi, kupewa kukokomeza kosafunikira, zovuta komanso kudwala matenda ashuga.