Invocana® (300 mg) Kanagliflozin

Chonde musanagule mapiritsi a Invokana amaphimbidwa. 300 mg 30 ma PC., Pack., Yang'anani zambiri za izo ndi chidziwitso patsamba lovomerezeka la wopanga kapena tchulani mtundu wachitsanzo ndi woyang'anira kampani yathu!

Zomwe zikuwonetsedwa patsamba lino sizoperekedwa pagulu. Wopangayo ali ndi ufulu wosintha kapangidwe kake, kapangidwe kake ndi katengedwe ka katundu. Zithunzi zamalonda pazithunzi zomwe zaperekedwa pamndandanda wazomwe zili patsamba lino zimasiyana ndi zomwe zidachokera.

Zambiri pamutengo wa zinthu zomwe zawonetsedwa pamndandanda wa masamba tsambalo zingasiyane ndi zenizeni panthawiyo yokhazikitsa dongosolo la zomwe zikugwirizana.

Wopanga

Piritsi la 300 mg lomwe lophimbidwa muli:

306.0 mg wa canagliflozin hemihydrate, womwe ndi wofanana ndi 300.0 mg wa canagliflozin.
Othandizira (pakati): microcrystalline cellulose 117.78 mg, anactrous lactose 117.78 mg, croscarmellose sodium 36.00 mg, hyprolose 18.00 mg, magnesium stearate 4.44 mg.
Otsatsa (chipolopolo): Opadray II 85F18422 oyera oyera (polyvinyl mowa, pang'ono hydrolyzed, 40.00% titanium dioxide 25.00%, macrogol 3350 2020%, talc 14.80%) - 18.00 mg .

Zotsatira za pharmacological

Zawonetsedwa kuti odwala omwe ali ndi matenda a shuga amakhala ndi kuchuluka kwa impso, komwe kumapangitsa kuti shuga azikhala wolimba. Sodium glucose transport protein 2 (SGLT2), yodziwika mu proximal renal tubules, ndiyo imayambitsa kubwezeretsanso kwa shuga kuchokera ku tubule lumen.
Kanagliflozin ndi cholepheretsa mapuloteni oyendetsa sodium-glucose 2. Mwa kuletsa SGLT2, canagliflozin amachepetsa kubwezeretsanso kwa glucose wotsetsedwayo ndikuchepetsa gawo lachiwopsezo cha glucose (PPG), potero kuonjezera kuchepa kwa shuga m'magazi a shuga ndi insulin njira yodziyimira payokha mwa odwala matenda a shuga a 2.
Kuwonjezeka kwa glucose wa excretion kudzera mu chopinga cha SGLT2 kumathandizanso kuti osmotic diuresis, mphamvu yokhudza kukodzetsa kwa magazi imabweretsa kuchepa kwa magazi a systolic, kuwonjezeka kwa glucose exretion kumabweretsa kuchepa kwa zopatsa mphamvu ndipo, chifukwa chake, kuchepa kwa thupi.
Mu gawo lachitatu la maphunziro omwe mayeso osakanikirana a kadzutsa adachitika, kugwiritsa ntchito canagliflozin pa 300 mg kunayambitsa kutsika kwakukulu pamlingo wa postprandial glycemia kuposa mlingo wa 100 mg. Zotsatira zake zitha kukhala chifukwa cha kuletsa kwamatumbo a SGLT1, poganizira kuchepa kwakanthawi kwamatumbo a canagliflosin m'matumbo lumen musanafike mayamwidwe a mankhwala (canagliflosin ndi mphamvu yotsika ya SGLT1). Mu maphunziro, malabsorption sanapezeke ndikugwiritsa ntchito canagliflozin.
Zotsatira za Pharmacodynamic:
Pa matenda mayesero pambuyo limodzi kapena angapo pakamwa makonzedwe a canagliflozin ndi odwala matenda amisempha 2, njira aimpso kwa shuga anali kuchepa amadalira, ndipo kwamikodzo glucose kuchuluka. Mtengo woyambira wa impso kwa glucose unali pafupifupi 13 mmol / L, kutsika kwakukulu kwazowonjezera za maola 24 a shuga kumawonedwa ndi Mlingo wa 300 mg kamodzi patsiku ndikuchokera 4 mpaka 5 mmol / L, zomwe zikuwonetsa chiopsezo chochepa cha hypoglycemia pa mankhwala oyambira. Mu kafukufuku wazachipatala wokhudzana ndi kugwiritsa ntchito canagliflozin mu Mlingo wa 100 mpaka 300 mg kamodzi patsiku ndi odwala omwe ali ndi matenda a shuga a 2 kwa masiku 16, kuchepa kwa mawonekedwe aimpso kwa glucose komanso kuchuluka kwa mayamwidwe a shuga kwamkodzo kunali kosalekeza. Pankhaniyi, kuchuluka kwa shuga m'magazi am'magazi kunachepetsa mlingo-wodalirika patsiku loyamba logwiritsira ntchito, kenako kutsika kwamphamvu kwa glucose m'madzi am'magazi pamimba yopanda kanthu ndikatha kudya.
Kugwiritsa ntchito limodzi mlingo wa 300 mg wa canagliflozin musanadye zakudya zophatikiza zama calorie mwa odwala omwe ali ndi matenda amtundu wa 2 kunapangitsa kuchepa kwa mayamwidwe am'mimba m'matumbo komanso kuchepa kwa matenda a postprandial glycemia kudzera muimpso ndi njira zina zowonjezera.
M'mayesero azachipatala, odzipereka 60 wathanzi adalandira pakamwa limodzi lokha 300 mg ya canagliflozin, 1200 mg wa canagliflozin (4 times the maximum ilipandiswa mlingo), moxifloxacin, ndi placebo. Palibe kusintha kwakukulu pakanthawi ka QT komwe kamayesedwa ndi 300 mg kapena mlingo wa 1200 mg. Mukamagwiritsa ntchito mlingo wa 1200 mg, kuchuluka kwa plasma ndende ya canagliflozin kunali pafupifupi 1.4 peresenti kuposa kukondera kwa kufanana pakumatha kumwa 300 mg kamodzi patsiku.
Kuthamanga Glycemia:
M'mayesero azachipatala, kugwiritsa ntchito canagliflozin monga monotherapy kapena ngati adjunct pochiza ndi mankhwala amodzi kapena awiri amkamwa hypoglycemic imapangitsa kuti kusintha kwa glycemia kusunthe kwambiri poyerekeza ndi gawo loyambirira la placebo kuchokera -1.2 mmol / l mpaka -1.9 mmol / l mukamagwiritsa ntchito Mlingo wa 100 mg ndi kuchokera -1.9 mmol / l mpaka -2.4 mmol / l - mukamagwiritsa ntchito Mlingo wa 300 mg, motero. Zotsatira zake zinali pafupi kwambiri pambuyo pa tsiku loyamba la chithandizo ndipo zimapitilira nthawi yonse ya chithandizo.
Postprandial glycemia:
M'mayesero azachipatala ogwiritsira ntchito canagliflozin monga monotherapy kapena mankhwala othandizira amodzi kapena awiri amkamwa hypoglycemic, postprandial glycemia anayeza atagwiritsa ntchito mayeso olekerera ndi kadzutsa kosakaniza. Kugwiritsa ntchito canagliflozin kunayambitsa kuchepa kwapakati pa postprandial glycemia poyerekeza ndi gawo loyambirira pokhudzana ndi placebo kuchokera -1.5 mmol / L mpaka -2.7 mmol / L - mukamagwiritsa ntchito Mlingo wa 100 mg ndi kuchokera kwa 2,1 mmol / L mpaka -3,5 mmol / l - mukamagwiritsa ntchito Mlingo wa 300 mg, motero, chifukwa cha kuchepa kwa shuga m'magazi musanadye komanso kuchepa kwa kusinthasintha kwa gawo la postprandial glycemia.
Kulemera kwa thupi:
Kanagliflozin 100 mg ndi 300 mg monga monotherapy komanso monga zowirikiza kawiri kapena katatu zowonjezera zinapangitsa kuchepa kwakukulu kwa kuchuluka kwa thupi masabata 26, poyerekeza ndi placebo. Kwa masabata awiri 52 omwe amagwiritsidwa ntchito poyeserera kuyerekezera canagliflozin ndi glimepiride ndi sitagliptin, kutanthauza kuti kuchepa kwa peresenti ya kulemera kwa thupi kwa canagliflozin monga chithandizo cha adjunct kuti metformin anali -4.2% ndi -4,7% wa canagliflozin 100 mg ndi 300 mg, motsatana, poyerekeza ndi kuphatikiza kwa glimepiride ndi metformin (1.0%) ndi 2,5% ya canagliflozin 300 mg kuphatikiza ndi metformin ndi sulfonylurea, poyerekeza ndi sitagliptin kuphatikiza ndi metformin ndi sulfonylurea (0.3%).
Kupanikizika kwa magazi:
Pakufufuza komwe kumayendetsedwa ndi placebo, chithandizo cha canagliflozin 100 mg ndi 300 mg idapangitsa kutsika kwa magazi kwa systolic ya -3.9 mm Hg. ndi -5.3 mmHg motero, poyerekeza ndi placebo (-0.1 mm), komanso kuthana kwa magazi m'magazi a diastoli posintha mtengo wapakati pa canagliflozin 100 mg ndi 300 mg -2.1 mm Hg ndi 2,5 mmHg motero, poyerekeza ndi placebo (-0.3 mm).
Panalibe kusintha kwakukulu pamtima.
Ntchito ya cell ya Beta:
Kafukufuku wamagwiritsidwe ntchito a canagliflozin mwa odwala omwe ali ndi matenda a shuga 2 amawonetsa kusintha kwa ntchito ya cell ya beta, malinga ndi kuwunika kwa mawonekedwe a homeostasis pokhudzana ndi magwiridwe amtunduwu (HOMA2-% B) ndikuwongolera kwa kuchuluka kwa insulini pogwiritsa ntchito chiyeso chololerana ndi kadzutsa kosakaniza.

Mtundu wachiwiri wa shuga mwa achikulire osakanikirana ndi zakudya komanso masewera olimbitsa thupi kuti muzitha kuyendetsa bwino glycemic control:

• Monotherapy
• Monga gawo la mankhwala ophatikiza ndi mankhwala ena a hypoglycemic, kuphatikizapo insulin.

Zotsatira zoyipa

Zambiri pazomwe zimachitika pakagwiritsidwe ntchito ka mayesero a testic1 a canagliflozin okhala pafupipafupi ndi ≥2% zimapangidwira mogwirizana ndi ziwalo zamitundu iliyonse malinga ndi kuchuluka komwe kumachitika pogwiritsa ntchito gulu:: pafupipafupi (≥1 / 10), pafupipafupi ((1 / 100,

Matenda am'mimba:
Pafupipafupi: kudzimbidwa, ludzu2, kamwa youma.

Kuphwanya impso ndi kwamikodzo thirakiti:
Pafupipafupi: polyuria ndi polakiuria3, kukodza kwa peremptory, matenda a kwamikodzo4, urosepsis.

Kuphwanya maliseche ndi chithokomole:
Pafupipafupi: balanitis ndi balanoposthitis 5, vulvovaginal candidiasis 6, matenda amkazi.

1 Kuphatikiza ndi monotherapy komanso kuwonjezera pa mankhwala omwe ali ndi metformin, metformin ndi sulfonylurea, komanso metformin ndi pioglitazone.
Gulu lomwe lili ndi ludzu limaphatikizanso mawu oti "ludzu", mawu akuti "polydipsia" nawonso ali m'gulu lino.
3 Gawo "polyuria kapena polakiuria" limaphatikizapo mawu akuti "polyuria", mawu oti "kuchuluka kwa mkodzo wambiri" ndi "nocturia" akuphatikizidwanso pagulu lino.
4 Gawo "matenda amkodzo 'limaphatikizanso mawu oti" kwamikodzo matenda amkodzo "ndipo limaphatikizanso mawu akuti" cystitis "ndi" matenda a impso ".
Gulu la "balanitis kapena balanoposthitis" limaphatikizanso mawu akuti "balanitis" ndi "balanoposthitis", komanso mawu akuti "candida balanitis" ndi "matenda oyamba ndi ziwalo".
Gawo loti "vulvovaginal candidiasis" limaphatikizapo mawu akuti "vulvovaginal candidiasis", "matenda a fungvovaginal fungus", "vulvovaginitis" komanso mawu oti "venvovaginal and genital fungal matenda".
Zina zoyipa zomwe zimachitika mu maphunziro a placebo olamulidwa ndi placebo ndi pafupipafupi a

Zotsatira zoyipa zomwe zimakhudzana ndi kuchepa kwa magazi a intravascular vol

Kukula kwa mayankho onse obwera chifukwa chokhudzana ndi kuchepa kwa mtsempha wamitseko (postural kizungulire, orthostatic hypotension, ochepa hypotension, kuchepa madzi m'thupi ndi kukomoka) kunali Malinga ndi zotsatira za kuwunika kokwanira, mwa odwala omwe adalandira "loop" okodzetsa, odwala omwe amalephera kupweteka aimpso (GFR kuchokera ku 30 mpaka 2) ndi odwala ≥75 wazaka zambiri, pafupipafupi izi zimachitika modabwitsa. Popanga kafukufuku wokhudzana ndi ngozi zamtima, kuchuluka kwa zoyipa zomwe zimakhudzana ndi kuchepa kwa magazi mkati mwazinthu zamkati sizinachuluke ndikugwiritsira ntchito canagliflozin, milandu yotsitsa chithandizo chifukwa cha kusinthika kwatsoka kwamtunduwu kunali kovuta.

Hypoglycemia ikagwiritsidwa ntchito ngati adjunct kupita ku insulin mankhwala kapena othandizira omwe amapangitsa kuti pakhale secretion yake

Pogwiritsa ntchito canagliflozin monga adjunct kuti muchiritsidwe ndi insulin kapena zotumphukira za sulfonylurea, kukula kwa hypoglycemia kumanenedwa pafupipafupi. Izi zikugwirizana ndikuwonjezereka kwa kuchuluka kwa hypoglycemia pomwe mankhwala, kugwiritsa ntchito komwe sikumayendetsedwa ndi chitukuko cha chikhalidwechi, amawonjezeredwa ndi insulin kapena mankhwala omwe amalimbikitsa katulutsidwe kake (mwachitsanzo, zotumphukira za sulfonylurea).

Zosintha zasayansi

Kuchulukitsa kwa seramu potaziyamu
Milandu yowonjezereka ya seramu potaziyamu ndende (> 5.4 mEq / L ndi 15% kuposa momwe anali oyambira kale) idawonedwa mu 4.4% ya odwala omwe amalandila canagliflozin pa 100 mg, mu 7.0% ya odwala omwe amalandira canagliflozin pa mlingo wa 300 mg , ndi 4.8% ya odwala omwe akulandira placebo. Nthawi zina, kuchuluka kwakuchulukirapo kwa serum potaziyamu kumawonekera kwambiri kwa odwala omwe ali ndi vuto laimpso zolimbitsa thupi, omwe kale anali ndi kuchuluka kwa potaziyamu ndende ndi / kapena omwe adalandira mankhwala angapo omwe amachepetsa potaziyamu (potaziyamu-yosasinthika okodzetsa ndi angiotensin-akatembenuka enzyme inhibitors (ACE)). Pazonse, kuwonjezeka kwa ndende ya potaziyamu kunali kosakhalitsa ndipo sikunafunikire chithandizo chapadera.

Kuchulukitsa kwa serum creatinine ndi urea
M'milungu isanu ndi umodzi yoyambirira atangoyamba kumene chithandizo, panali kuwonjezeka kwapang'onopang'ono kwa ndende ya creatinine (Kuchulukitsa kwa odwala omwe amachepetsa kwambiri GFR (> 30%) poyerekeza ndi gawo loyambirira lomwe limapezeka panthawi iliyonse yamankhwala anali 2.0% - pogwiritsa ntchito canagliflozin muyezo 100 mg, 4.1% mukamagwiritsa ntchito mankhwalawa pa 300 mg ndi 2.1% mukamagwiritsa ntchito placebo Kuchepetsa kumeneku mu GFR nthawi zambiri kumakhala kochepa, ndipo kumapeto kwa kafukufukuyu, kutsika komweko kwa GFR kumaonedwa mwa odwala ochepa. kwa odwala omwe amalephera kupweteka aimpso, kuchuluka kwa odwala omwe ali ndi kuchepa kwakukulu kwa GFR (> 30%) poyerekeza ndi gawo loyambirira lomwe limapezeka panthawi iliyonse ya mankhwalawa anali 9,3% - pogwiritsa ntchito canagliflozin pa mlingo wa 100 mg, 12,2 % - mukamagwiritsa ntchito Mlingo wa 300 mg, ndi 4,9% - mukamagwiritsa ntchito placebo. Mukayimitsa canagliflozin, zosintha izi mu labotale zidapitilira zabwino kapena zidabwezedwa momwe zidakhalira.

Kuchulukitsa Kachulukidwe kakang'ono Lipoprotein (LDL)
Kukula kokhazikika kwa kuchuluka kwa zotsata za LDL kunawonedwa ndi canagliflozin. Kusintha kwapakati pa LDL ngati kuchuluka kwa koyambirira koyerekeza ndi placebo kunali 0.11 mmol / L (4.5%) ndi 0.21 mmol / L (8.0%) mukamagwiritsa ntchito canagliflozin mu Mlingo wa 100 mg ndi 300 mg, motsatana . Ambiri a LDL oyambira anali 2.76 mmol / L, 2.70 mmol / L ndi 2.83 mmol / L okhala ndi canagliflozin pa Mlingo wa 100 ndi 300 mg ndi placebo, motsatana.

Kuchulukitsa kwa hemoglobin
Pogwiritsa ntchito canagliflozin mu Mlingo wa 100 mg ndi 300 mg, kuwonjezeka pang'ono pa kusintha kwapakati pa hemoglobin ndende yochokera koyamba (3.5% ndi 3.8%, motsatana) kunawonedwa poyerekeza ndi kuchepa pang'ono kwa gulu la placebo (−1.1%). Kuwonjezeka pang'ono pang'onopang'ono pakusintha kwapakati pa chiwerengero cha maselo ofiira am'magazi ndi hematocrit kuchokera koyambira adawonedwa. Odwala ambiri adawonetsa kuwonjezeka kwa ndende ya hemoglobin (> 20 g / l), yomwe idachitika mu 6.0% ya odwala omwe amalandira canagliflozin pa 100 mg, mu 5.5% ya odwala omwe amalandira canagliflozin pa mlingo wa 300 mg, ndipo mu 1, 0% ya odwala omwe akulandira placebo. Mfundo zambiri zimakhalabe pamalire oyenera.

Kutsika seramu uric acid ndende
Pogwiritsa ntchito canagliflozin mu Mlingo wa 100 mg ndi 300 mg, kuchepa kwapakati pa uric acid kuchokera kumayambiriro oyambira (−10.1% ndi −10.6%, motero) kunawonedwa poyerekeza ndi placebo, ndikugwiritsa ntchito komwe kukwera pang'ono pakati pamagawo oyambira (1.9%). Kuchepa kwa kuchuluka kwa seramu uric acid m'magulu a canagliflozin anali okwanira kapena pafupi kwambiri ndi sabata 6 ndikulimbikira panthawi yonse ya mankhwala. Kukula kwakanthawi kwa uric acid mumkodzo kunadziwika. Malinga ndi zotsatira za kuphatikiza kophatikizira kwa canagliflozin mu Mlingo wa 100 mg ndi 300 mg, zidawonetsedwa kuti zochitika za nephrolithiasis sizinachuluke.

Kuteteza Mtima
Panalibe chiwopsezo cha mtima ndi canagliflozin poyerekeza ndi gulu la placebo.

Kuchita

Zochita Zamankhwala (mu vitro data)

Kanagliflozin sanalimbikitse mawu a CYP450 system isoenzymes (3A4, 2C9, 2C19, 2B6 ndi 1A2) mu chikhalidwe cha hepatocytes aumunthu.Sizinalepheretsenso cytochrome P450 isoenzymes (1A2, 2A6, 2C19, 2D6 kapena 2E1) ndikulephera mofatsa CYP2B6, CYP2C8, CYP2C9, CYP3A4, malinga ndi maphunziro a labotale omwe amagwiritsa ntchito ma microsomes a chiwindi cha anthu. Kafukufuku wa in vitro awonetsa kuti canagliflozin ndi gawo lapansi la mankhwala omwe amapanga enzymes UGT1A9 ndi UGT2B4 ndionyamula mankhwala a P-glycoprotein (P-gp) ndi MRP2. Kanagliflozin ndi choletsa chofooka cha P-gp.

Kanagliflozin imagwidwa ndi ochepa oxidative metabolism. Chifukwa chake, kuchuluka kwakanema kwamankhwala ena pa pharmacokinetics of canagliflozin kudzera P450 cytochrome system ndizokayikitsa.

Zotsatira za mankhwala ena pa canagliflozin

Zambiri zamankhwala zimawonetsa kuti chiopsezo chokhudzana ndi mankhwala ochepetsa nkhawa ndizochepa.

Mankhwala osokoneza bongo omwe amapangitsa banja la UDF-glucuronyl kusamutsa (UGT) onyamula ndi mankhwala onyamula

Kugwiritsa ntchito munthawi yomweyo ndi rifampicin, zosankha zingapo za banja la UGT ndionyamula mankhwala, kuphatikiza UGT1A9, UGT2B4, P-gp, ndi MRP2 adachepetsa ma canagliflozin. Kuwonetsedwa kwakanthawi kwa canagliflozin kungayambitse kuchepa kwake. Ngati n`koyenera kupereka inducer wa UGT banja michere ndi onyamula mankhwala (mwachitsanzo, rifampicin, phenytoin, phenobarbital, ritonavir) munthawi yomweyo canagliflozin, n`kofunika kuyang'anira ndende ya glycated hemoglobin НbА1c odwala kulandira canagliflozin mlingo wa 100 mg wa kuchuluka / mlingo wa kuchuluka kwa mphindi 100 mg canagliflozin mpaka 300 mg 1 nthawi / tsiku, ngati kuwongolera glycemic koyenera ndikofunikira.

Mankhwala omwe amalepheretsa ma enzyme a banja la UDF-glucuronyl kusamutsa (UGT) ndionyamula mankhwala

Probenecid: Kuphatikiza kwa canagliflozin ndi phenenecid, choletsa chosakanizira cha ma enzymes angapo a banja la UGT komanso onyamula mankhwala, kuphatikiza UGT1A9 ndi MRP2, sizinawakhudze kwambiri pharmacokinetics ya canagliflozin. Popeza canagliflozin ndi glucuronidate awiri michere yama banja a UGT, ndipo glucuronidation imadziwika ndi ntchito yayikulu / kutsika kochepa, kukulira kwa zotsatira zamankhwala zamankhwala ena pa pharmacokinetics ya canagliflozin ndi glucuronidation ndizokayikitsa.

Cyclosporin: Mankhwala ofunikira kwambiri a pharmacokinetic mogwirizana ndi munthawi yomweyo kugwiritsa ntchito canagliflozin ndi cyclosporine, choletsa wa P-glycoprotein (P-gp), CYP3A MRP2 sinawonedwe. Kupanga kwa "kuwunika" kosasinthika, kwakanthawi kumadziwika pogwiritsa ntchito munthawi yomweyo canagliflozin ndi cyclosporine. Kusintha kwa mlingo wa canagliflozin osavomerezeka. Palibe kuyanjana kwakukulu kwa mankhwala ndi ma P-gp inhibitors ena omwe amayembekezeredwa.

Momwe mungatenge, njira ya makonzedwe ndi kumwa

Kanagliflozin tikulimbikitsidwa kuti timwe pakamwa kamodzi patsiku, makamaka tisanadye chakudya cham'mawa.

Akuluakulu (≥18 wazaka)
Mlingo wovomerezeka wa canagliflozin ndi 100 mg kapena 300 mg kamodzi patsiku, womwe umayenera kutengedwa musanadye chakudya cham'mawa.
Mukamagwiritsa ntchito canagliflozin monga adjunct kuti mupeze insulin kapena mu njira yolimbikitsira katulutsidwe kake (mwachitsanzo, zotumphukira za sulfonylurea), Mlingo wotsika wa mankhwala omwe ali pamwambawa angaganiziridwe kuti muchepetse chiopsezo cha hypoglycemia.
Kanagliflozin ali ndi diuretic. Odwala odwala okodzetsa, odwala mkhutu aimpso ntchito zolimbitsa kukula kwa kusefukira mlingo (GFR) wa 30 mpaka 2, kapena odwala wazaka ≥75, anasonyeza pafupipafupi kukula zoyipa zimachitika chifukwa cha kuchepa kwamitsempha yamagazi (mwachitsanzo, chizungulire chaposachedwa orthostatic hypotension kapena ochepa hypotension. Chifukwa chake, mwa odwala awa, kugwiritsa ntchito canagliflozin koyamba kwa 100 mg kamodzi patsiku ndikulimbikitsidwa. Odwala omwe ali ndi vuto la hypovolemia, tikulimbikitsidwa kuti asinthe asanafike pochiza ndi canagliflozin. Odwala omwe amalandira canagliflozin pa mlingo wa 100 mg ndi kulekerera kwabwino, omwe amafunikira kuwongolera glycemic, ndikofunika kuwonjezera mlingo mpaka 300 mg.

Mlingo
Ngati mlingo wakusowa, uyenera kumwedwa mwachangu, komabe, kawiri mlingo sayenera kumwedwa mkati mwa tsiku limodzi.

Magulu apadera a odwala

Ana ochepera zaka 18
Chitetezo ndi luso la canagliflozin mwa ana sizinaphunzire.

Odwala okalamba
Odwala ≥75 wazaka zoyenera ayenera kupatsidwa 100 mg kamodzi tsiku lililonse ngati mlingo woyambirira. Ndi kulolera wabwino kwa 100 mg, ndikofunikira kwa odwala omwe akufunika kuwongolera glycemic kuti achulukitse mlingo mpaka 300 mg.

Matenda aimpso
Odwala omwe ali ndi vuto lofooka la impso (pafupifupi glomerular filtration rate (GFR) kuyambira 60 mpaka 2), kusintha kwa mlingo sikofunikira.
Odwala ndi mkhutu aimpso ntchito zolimbitsa zovuta, kugwiritsa ntchito mankhwala koyamba mlingo wa 100 mg kamodzi patsiku tikulimbikitsidwa. Ndi kulolera wabwino kwa 100 mg, ndikofunikira kwa odwala omwe akufunika kuwongolera glycemic kuti achulukitse mlingo mpaka 300 mg.
Kanagliflozin sichikulimbikitsidwa kwa odwala omwe ali ndi vuto lowononga aimpso (GFR 2), a-end-solid renal kulephera (CRF), kapena kwa odwala omwe akudwala dialysis, monga zikuyembekezeredwa kuti canagliflozin sikhala othandiza pakadali pano odwala.

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 amtundu wa 2. Pambuyo pakamwa limodzi pakamwa 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 kwofananira) 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 chiwongolero 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, ndi kuchuluka kwa kusefera kwa glomerular (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 Zoyipa") .

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 osokoneza bongo

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").

Zotsatira za 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 inducers (monga St. John wa wort Hypericum perforatum, rifampicin, barbiturates, phenytoin, carbamazepine, ritonavir, efavirenz) amatha kuchepetsa zotsatira za 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 kotereku kumatha kutsitsa kuchepa kwa 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: kugwiritsa ntchito nthawi yomweyo canagliflozin pa 300 mg kamodzi patsiku kwa masiku 7 ndi kugwiritsa ntchito limodzi kwa 0,5 mg wa digoxin wotsatira mlingo wa 0.25 mg tsiku lililonse kwa masiku 6 kunapangitsa kuwonjezeka kwa AUC kwa digoxin ndi 20% komanso kuchuluka kwa Cmax 36%, mwina chifukwa cha kuletsa kwa P-gp. Kanagliflozin yapezeka kuti ikulepheretsa P-gp mu vitro. Odwala omwe amatenga digoxin ndi mtima wama glycosides ena (mwachitsanzo, digitoxin) amayang'aniridwa moyenera.

Dabigatran: Ntchito zophatikizira za canagliflozin (pulogalamu yofooka ya P-gp) ndi dabigatran etexilate (P-gp gawo lapansi) sizinaphunzire. 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: kugwiritsa ntchito kwa 300 mg ya canagliflozin kamodzi patsiku kwa masiku 6 ndi kugwiritsa ntchito kamodzi kwa 40 mg ya simvastatin (gawo laling'ono la CYP3A4) kunapangitsa kukuwonjezeka kwa AUC ya simvastatin ndi 12% komanso kuwonjezeka kwa Cmax ndi 9%, komanso kuwonjezeka kwa AUC ya simvastatin acid ndi 18% komanso kuchuluka Cmax ya simvastatinic acid pa 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, ena mwa ma statos 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.

Malangizo apadera

Kugwiritsira ntchito canagliflozin sikunaphunzitsidwe kwa odwala omwe ali ndi matenda amtundu wa 1, motero sikulimbikitsidwa kuti aikidwe mu gulu ili la odwala.

Mankhwalawa sangathe kugwiritsidwa ntchito pochiza matenda ashuga a ketoacidosis, chifukwa chithandizo chotere sichingagwire ntchito munthawi zamatendawa.

Gwiritsani ntchito odwala omwe ali ndi vuto laimpso

Mphamvu ya canagliflozin imadalira ntchito yaimpso, ndipo mphamvu yake imachepetsedwa mwa odwala omwe amalephera kupweteka aimpso ndipo mwina sangakhale mwa odwala omwe amalephera kwambiri aimpso (onani gawo "Mlingo ndi Administration").

Odwala omwe ali ndi kuchuluka kwa kusefera kwa 30%), koma pambuyo pake, eGFR inachuluka komanso kuchotsedwa kwakanthawi kwa kanniflosin kunali kofunikira nthawi zina (onani gawo "Zotsatira zoyipa").

Odwala ayenera kulangizidwa za kuchepa kwa madzi m'thupi. Kanagliflozin sichikulimbikitsidwa kwa odwala omwe amatenga mafuta m'thupi (onani gawo la "Mankhwala Osokoneza bongo"), kapena akuvutika ndi madzi am'mimba, mwachitsanzo, pokhudzana ndi matenda oopsa (monga matenda am'mimba).

Kugwiritsira ntchito canagliflozin sikulimbikitsidwa kwa odwala omwe amalandila zotupa (onani gawo "Drug Interaction") kapena mwa anthu omwe ali ndi vuto lotha magazi, mwachitsanzo, pokhudzana ndi matenda opweteka kwambiri (mwachitsanzo, thirakiti la m'mimba).

Kwa odwala omwe amamwa mankhwala a Captokana®, pakachitika zinthu zomwe zingayambitse matenda am'madzi (mwachitsanzo, matenda am'mimba), ndikofunikira kuwunika mosamala kuchuluka kwa kuchepa kwa madzi (mwachitsanzo, kupima thupi, kuwongolera kuthamanga kwa magazi, kuyesedwa kwa ma labot, kuphatikizapo kuwunika kwa aimpso ntchito) ndi misempha yama-serum electrolyte. Odwala omwe ataya madzi m'thupi la mankhwala la Invocana®, ayenera kuthandizanso kuleka Invocana® kwakanthawi mpaka zinthu zitayamba bwino. Pofuna kusiya mankhwala, ndikofunikira kuti kuwunikira kuchuluka kwa glucose pafupipafupi.

M'maphunziro azachipatala komanso otsatsa malonda kwa odwala omwe amatenga ma SGLT2 zoletsa, kuphatikiza canagliflozin, milandu yochepa ya chitukuko cha matenda ashuga ketoacidosis (DKA), kuphatikizapo milandu ya DKA yoopsa. Mwambiri, zochitika za atypical zafotokozedwa, kuwonjezeka kwapang'onopang'ono kwa ndende yamagazi osaposa 14 mmol / L (250 mg dl). Zomwe zimachitika ku DKA ndi Mlingo wambiri wa canagliflozin sizikudziwika.

Chiwopsezo cha kukhala ndi matenda ashuga a ketoacidosis amayenera kuganiziridwa ngati pali zifukwa zosapindika monga mseru, kusanza, kupweteka kwam'mimba, kupweteka kwam'mimba, ludzu lalikulu, kupuma movutikira, kusokonezeka, kutopa kwapadera kapena kugona. Ngati zizindikirozi zikuchitika, odwala amayenera kuwunika mwachangu za ketoacidosis, mosasamala kuchuluka kwa shuga m'magazi.

Ngati akukayikira kukonzekera kwa DKA, komanso ngati ingadziwike, odwala ayenera kusiya chithandizo ndi Invocana®.

Chithandizo chiyenera kuyimitsidwa kwakanthawi kwa odwala omwe agonekedwa kuchipatala kuti achitidwe opaleshoni yayikulu kapena kuchulukitsa matenda oopsa. M'njira zonsezi, mutakhazikika wodwalayo, chithandizo ndi Invocana® chitha kuyambiranso.

Asanayambe chithandizo ndi Invocana ®, zinthu zonse zolembedwa mu mbiri ya wodwala zomwe zingapangitse kukula kwa ketoacidosis ziyenera kuganiziridwa.

Izi ndi monga:

● kufooka kwa malo okhala ndi beta-cell (mwachitsanzo, odwala omwe ali ndi matenda a shuga 2 omwe amakhala ndi matenda otsika a C-peptide kapena latent autoimmune shuga mwa akulu (LADA) kapena odwala omwe ali ndi mbiri ya kapamba)

● Zoletsa zakudya kapena kusowa kwamphamvu madzi

● odwala omwe achedwa mlingo wa insulin

● odwala omwe akuwonetsedwa kuchuluka kwa insulin chifukwa cha chitukuko cha matenda am'mimba, opaleshoni kapena uchidakwa

Chenjezo limalangizidwa kuti lipereke ziletso za SGLT2 mwa odwalawa.

Sitikulimbikitsidwa kuyambiranso chithandizo ndi SGLT2 inhibitor pankhani yotsogola ya DKA pogwiritsa ntchito SGLT2 zoletsa mpaka chizindikiritso ndi kuthetseratu kwa zinthu zonse zowonekeratu.

Kutetezeka ndi kugwiritsa ntchito bwino kwa canagliflozin mwa odwala matenda ashuga 1 sikunayambike ndipo kugwiritsa ntchito mankhwalawa Invokana® kwa odwala omwe ali ndi matenda amtundu wa 1 sikulimbikitsidwa. Zoyesa zochepa zamankhwala azachipatala zimatsimikizira kuti DKA imatha kukulira odwala omwe ali ndi matenda amtundu wa 1 omwe akutenga ma SGLT2 inhibitors.

Pogwiritsa ntchito canagliflozin, kuwonjezeka kwa hematocrit kunawonedwa (onani gawo "Zotsatira zoyipa"), chifukwa chake, odwala omwe ali ndi hematocrit okwera kale ayenera kusamala.

Wakale (≥ wa zaka 65)

Okalamba atha kukhala pachiwopsezo chachikulu cha kusowa kwamadzi, amatha kulandira zimbudzi, ndipo amakhala ndi vuto la impso. Odwala ≥ wazaka 75, kugwiritsa ntchito canagliflozin anali wofotokozera zovuta zomwe zimakhudzana ndi kuchepa kwa madzi (mwachitsanzo, chizungulire chaposachedwa, orthostatic hypotension, hypotension. Kuphatikiza apo, mwa odwala otere, kuchepa kwakukulu kwa eGFR kunanenedwa (onani magawo "Mlingo ndi Ulamuliridwe" ndi "Zotsatira Zotsatira").

Matenda oyamba ndi maliseche

Chifukwa cha limagwirira a canagliflozin yolumikizidwa ndi potransporter wa sodium 2 (SGLT2), kuletsa kuchuluka kwa hepatitis B m'mayesero azachipatala ogwiritsira ntchito canagliflozin akuti kwa azimayi omwe ali ndi vuto la khungu la venvovaginal candidiasis ndi balanitis kapena balanoposthitis ) Amuna ndi akazi omwe ali ndi mbiri yakale ya matenda opatsirana mwa maliseche amatenga matenda. Balanitis kapena balanoposthitis amawonetsedwa makamaka mwa amuna omwe sanachite mdulidwe. Nthawi zina, kuoneka kwa phimosis kumanenedwa ndipo kuyesa kwa khungu. Odwala ambiri omwe ali ndi matenda oyamba ndi ziwalo zoberekera amalandila chithandizo cham'mimba monga momwe akuwunikira akuchipatala kapena kuwagwiritsa ntchito pawokha osasiya mankhwala a Captokana®.

Zomwe zakugwiritsa ntchito mankhwalawa kwa anthu omwe ali ndi vuto la mtima la kalasi III molingana ndi gulu la New York Heart Association (NYHA) ndizochepa, ndipo maphunziro a zamankhwala a canagliflozin mu NYHA kalasi ya IV ya mtima akulephera.

Urinalysis

Pokhudzana ndi limagwirira a canagliflozin, odwala omwe amamwa mankhwala a Captokana®, shuga mu mkodzo adzatsimikizika.

Mapiritsiwo ali ndi lactose. Odwala omwe ali ndi vuto lodana ndi galactose, kuperewera kwa lactase, kapena shuga ndi galactose malabsorption sayenera kumwa mankhwalawa.

Palibe chidziwitso pakugwiritsa ntchito canagliflozin mwa amayi apakati.

Kafukufuku wazinyama awonetsa kawopsedwe kabala. Invokana® sayenera kugwiritsidwa ntchito panthawi yoyembekezera. Mimba ikakhazikitsidwa, chithandizo ndi Invocana® chiyenera kusiyidwa.

Sizikudziwika ngati canagliflozin ndi / kapena ma metabolites ake adachotsedwa mkaka wa m'mawere.

Zambiri zopezeka mu pharmacodynamic / toxicological zomwe zimapezeka mu nyama zimawonetsa kuti canagliflozin / metabolites amachotseredwa mkaka ndikuti zotsatira zamtundu wa pharmacologically zimawonedwa mwa ana omwe amapatsidwa bere komanso makoswe osakhazikika omwe amakhala ndi canagliflozin. Chiwopsezo cha akhanda / makanda sichingadziwike kuti. Invokana® sayenera kugwiritsidwa ntchito pa nthawi ya mkaka.

Zotsatira za canagliflozin pa kubereka kwa anthu sizinaphunzire.

Mu maphunziro a nyama, palibe zotsatira za canagliflozin pa chonde.

Zomwe zimachitika chifukwa cha mankhwalawa amatha kuyendetsa galimoto kapena njira zoopsa

Attokana® ilibe kapena imakhala ndi mphamvu pang'ono poyendetsa galimoto ndikugwiritsa ntchito makina.

Komabe, odwala ayenera kudziwitsidwa za chiopsezo cha hypoglycemia akagwiritsa ntchito Invokana® ngati mankhwala othandizira omwe ali ndi insulin kapena insulin secretion, komanso chiopsezo chowonjezeka chokhudzana ndi kusowa kwamadzi, monga chizungulire cha postural (onani magawo chizungulire " Mlingo ndi makonzedwe "," Malangizo apadera "ndi" Zotsatira zoyipa ").

Bongo

Kugwiritsidwa ntchito kamodzi kwa canagliflozin mu Mlingo mpaka 1600 mg wa anthu athanzi komanso kugwiritsa ntchito canagliflozin pa 300 mg kawiri patsiku kwa masabata 12 mwa odwala omwe ali ndi matenda a shuga a 2 anali ambiri ololera.

Ngati mankhwala osokoneza bongo akuchulukirachulukira, ndikofunika kuchita mankhwalawa pokonza mankhwala, mwachitsanzo, kuti achitepo kanthu pochotsa chinthu chomwe sichinamwetse m'matumbo, kuwonetsetsa momwe alili kuchipatala ndikupereka chithandizo chamankhwala malinga ndi momwe wodwalayo alili. Njira yothandiza kwambiri yothana ndi lactate ndi metformin ndi hemodialysis. Kanagliflozin adangotuluka pang'ono mkati mwa maola anayi a hemodialysis. Kanagliflozin sayembekezeka kuti adzachotsedwa pakhungu.

Malangizo apadera

Kugwiritsa ntchito canagliflozin mwa odwala matenda a shuga 1 sikunaphunzire, chifukwa chake, kugwiritsidwa ntchito kwake kumatsutsana mu gulu ili la odwala.
Kugwiritsidwa ntchito kwa canagliflozin kumaphatikizidwa ndi matenda ashuga a ketoacidosis, mwa odwala omwe ali ndi vuto losatha aimpso kulephera (CRF) kapena odwala omwe akudwala dialysis, chifukwa chithandizo chotere sichingagwire ntchito pazamankhwala.

Carcinogenicity ndi mutagenicity
Zambiri zam'mbuyo sizikuwonetsa kuwopsa kwa anthu, malinga ndi zotsatira za kafukufuku wama pharmacological, kuwopsa kwa Mlingo wobwereza, genotoxicity, kubereka komanso kawopsedwe.

Chonde
Zotsatira za canagliflozin pa chonde chaumunthu sizinaphunzire. Zotsatira zanyama sizinawononge zotsatira za chonde.

Hypoglycemia yogwiritsidwa ntchito nthawi imodzi ndi mankhwala ena a hypoglycemic
Zawonetsedwa kuti kugwiritsa ntchito canagliflozin monga monotherapy kapena ngati adjunct kwa othandizira a hypoglycemic (kugwiritsidwa ntchito komwe sikuyenda ndi hypoglycemia), sikunayambitse kukula kwa hypoglycemia. Amadziwika kuti ma insulin ndi othandizira a hypoglycemic omwe amathandizira kubisika kwake (mwachitsanzo, zotumphukira za sulfonylurea) amachititsa kukula kwa hypoglycemia. Mukamagwiritsa ntchito canagliflozin monga cholumikizira mankhwala a insulin kapena pogwiritsa ntchito njira zake zowonjezera katulutsidwe (mwachitsanzo, zotumphukira za sulfonylurea), zochitika za hypoglycemia zinali zapamwamba kuposa ndi placebo.
Chifukwa chake, kuti muchepetse chiopsezo cha hypoglycemia, tikulimbikitsidwa kuti muchepetse mlingo wa insulin kapena ma othandizira omwe amathandizira katulutsidwe wake.

Kuchepetsa kwa kuchuluka kwa magazi m'thupi
Kanagliflozin ali ndi diuretic zotsatira zowonjezera kuchuluka kwa shuga ndi impso, ndikupangitsa osmotic diuresis, yomwe ingayambitse kuchepa kwa kuchuluka kwa intravascular.M'maphunziro azachipatala a canagliflozin, kuwonjezereka kwa pafupipafupi komwe kumachitika chifukwa chakuchepa kwa kuchuluka kwa intravascular vol., Mwachitsanzo, chizungulire chaposachedwa, kapena orstialatic hypotension. Odwala omwe amatha kutengeka ndi zovuta zomwe zimagwirizanitsidwa ndi kuchepa kwa intravascular voliyumu amaphatikizapo odwala omwe amalandila "zotupa" zodwala, odwala omwe ali ndi vuto laimpso olimbitsa, komanso odwala azaka zapakati pa 75.7.
Odwala ayenera kufotokozera zaumoyo wa kuchepa kwamitsempha yamavuto. Zotsatira zoyipa izi nthawi zambiri zimayambitsa kukakamira kugwiritsa ntchito canagliflozin ndipo nthawi zambiri pogwiritsa ntchito canagliflozin adakonzedwa ndikusintha kwa regimen kumwa mankhwala a antihypertensive (kuphatikizapo okodzetsa). Odwala omwe ali ndi kuchepa kwa kuchuluka kwa intravascular, izi zimayenera kusinthidwa musanafike mankhwalawa canagliflozin.
M'milungu isanu ndi umodzi yoyambirira ya chithandizo cha canagliflozin, panali zochitika zina zotsika pang'ono pang'onopang'ono pa kuchuluka kwa kusefedwa kwa glomerular (GFR) chifukwa chakuchepa kwa kuchuluka kwa intravascular. Odwala omwe akuyembekezeka kuchepa kwambiri kwa kuchuluka kwa intravascular, monga momwe tafotokozera pamwambapa, nthawi zina panali kuchepa kwakukulu kwa GFR (> 30%), komwe pambuyo pake kunathetsedwa ndipo nthawi zina kunafunikira kusokonezedwa mu chithandizo cha canagliflozin.

Matenda oyamba ndi maliseche
M'maphunziro azachipatala, kuchuluka kwa matenda ovomerezeka a vulvovaginitis (kuphatikizapo venvovaginitis ndi matenda operewera kwa mafupa) kunali kwakukulu mwa azimayi omwe amalandila canagliflozin poyerekeza ndi gulu la placebo. Odwala omwe ali ndi mbiri yodziwika bwino ya whvovaginitis omwe adalandira canagliflozin mankhwala amatha kupezeka ndi matendawa. Mwa odwala omwe amathandizidwa ndi canagliflozin, 2,3% adadwala matenda ambiri. Malipoti ambiri a vulvovaginal candidiasis okhudzana ndi miyezi inayi yoyamba atayamba kulandira chithandizo cha canagliflozin. 0,7% ya odwala onse anasiya kumwa canagliflozin chifukwa chaRevvovavoitis. Kuzindikiritsa kwa vervevaginitis, monga lamulo, kunakhazikitsidwa pokhapokha pazizindikiro. M'maphunziro azachipatala, kugwiritsa ntchito mankhwala a antifungal kwawoko kapena pakamwa, komwe madokotala amadziwitsa kapena kumayamwa pawokha pamankhwala omwe akupitilira ndi canagliflozin, adadziwika.
M'maphunziro azachipatala, candida balanitis kapena balanoposthitis amawonetsedwa pafupipafupi odwala omwe ali ndi canagliflozin mu Mlingo wa 100 mg ndi 300 mg, poyerekeza ndi gulu la placebo. Balanitis kapena balanoposthitis amapangidwa makamaka mwa amuna omwe sanachite mdulidwe, ndipo amapezeka kwambiri mwa amuna omwe ali ndi balanitis kapena balanoposthitis mu anamnesis. Mu 0.9% ya odwala omwe amathandizidwa ndi canagliflozin, gawo loposa limodzi la matenda linadziwika. 0.5% ya odwala onse anasiya kumwa canagliflozin chifukwa cha candida balanitis kapena balanoposthitis. M'mayesero azachipatala, nthawi zambiri, matendawa ankathandizidwa ndi othandizira antifungal omwe madokotala amawalembera kapena adawatenga paokha motsutsana ndi maziko a chithandizo cha canagliflozin. Nthawi zambiri phimosis amanenedwapo, nthawi zina mdulidwe unkachitika.

Mafupa owundana
Pakafukufuku wazotsatira zam'mtima mwa odwala 4327 omwe ali ndi vuto la mtima kapena chiwopsezo cha mtima, chiwopsezo cha mafupa anali 16.3, 16.4, ndi 10.8 pa zaka 1,000 za odwala omwe adagwiritsa ntchito Invocana® pa Mlingo wa 100 mg ndi 300 mg ndi placebo, motsatana. Vuto lina lodziwika bwino lomwe limachitika mu sabata 26 zoyambirira zamankhwala.
Pakufufuza kophatikizidwa kwina kwa kafukufuku wina wa Captokana®, yomwe idaphatikizapo pafupifupi 5800 odwala omwe ali ndi matenda ashuga kuchokera ku anthu ambiri, zochitika za mafupa zidawonongeka ndi 10.8, 12,0, ndi 14.1 pa zaka chikwi za odwala omwe adagwiritsa ntchito Invokana® ku Mlingo wa 100 mg ndi 300 mg ndi placebo, motero.
Pakati pamasabata 104 a mankhwala, canagliflozin sizinakhudze kwambiri minofu ya mafupa.

Zokhudza mphamvu pakutha kuyendetsa magalimoto ndimakina

Sizinakhazikitsidwe kuti canagliflozin ikhoza kukhudza kuyendetsa magalimoto ndikugwira ntchito ndi makina. Komabe, odwala ayenera kudziwa kuopsa kwa hypoglycemia akamagwiritsa ntchito canagliflozin monga cholumikizira insulin kapena mankhwala omwe amapangitsa kuti pakhale chobisalira, pangozi yowonjezereka yomwe imachitika chifukwa chokhudzana ndi kuchepa kwamitsempha yama cell (chizungu) magalimoto ndi njira zopangira zoyipa zimachitika.