Malangizo ogwiritsira ntchito "Encokany", kapangidwe kake, analogi ya mankhwala, mtengo ndi ndemanga

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.

Invokana amalimbikitsidwa kuti azigwiritsidwa ntchito pakamwa kamodzi patsiku ladzakudya.

Kwa odwala matenda ashuga a mtundu wa 2, mankhwalawa a Winokana azikhala 100 mg kapena 300 mg kamodzi tsiku lililonse.

Ngati canagliflozin amagwiritsidwa ntchito ngati adjunct ndi mankhwala ena (kuphatikiza insulin kapena mankhwala omwe amapangitsa kuti apangidwe), ndiye kuti kuchepetsa kochepetsetsa kumachepetsa mwayi wa hypoglycemia.

Nthawi zina, pakhoza kukhala vuto lalikulu lokhudzana ndi mankhwala a Invocana. Amatha kuphatikizidwa ndi kuchepa kwa kuchuluka kwa intravascular. Izi zitha kukhala kuzungulira kwa postural, ochepa kapena orthostatic hypotension.

Tikulankhula za odwala otere omwe:

1. adalandira zowonjezera zowonjezera,
2. kukhala ndi mavuto ndi impso zoyenera,
3. ali ndi ukalamba (woposa zaka 75).

Poona izi, magulu awa a odwala ayenera kumwa canagliflozin mu mlingo wa 100 mg kamodzi kadzutsa.

Odwala omwe akumana ndi vuto la hypovolemia adzalandiridwa poganizira kusintha kumeneku asanayambe mankhwala a canagliflozin.

Odwala omwe amalandira 100 ml ya mankhwala a Invokan ndikuwathandiza bwino, komanso amafunikira kuwongolera shuga, adzasamutsidwira ku mlingo wa 300 mg wa canagliflozin.

Bongo

Zizindikiro Palibe milandu yodziwika bwino ya canagliflozin. Mlingo umodzi wa canagliflozin, wofika 1600 mg mu anthu athanzi ndi 300 mg kawiri tsiku lililonse kwa milungu 12 kwa odwala omwe ali ndi matenda a shuga a 2, anali ambiri ololera.

Chithandizo cha mankhwala osokoneza bongo ngati mukumwa mankhwala ambiri, muyenera kuchita zinthu zothandizira, mwachitsanzo, kuchotsa zinthu zomwe sizinunkhe m'matumbo, kuchitira mozama kuchipatala ndikuyang'anira njira yokonzera poyang'anira matenda omwe wodwalayo ali nawo. Kanagliflozin sanatulutsidwe mkati mwa maola 4 oyimba. Kanagliflozin sayembekezeredwa kuchotsedwa kudzera mu peritoneal dialysis.

Zoyipa:

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.

Pa nthawi yoyembekezera komanso yoyamwitsa, maphunziro a momwe thupi limachitikira ndi mankhwala a Invocana 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.

Mogwirizana ndi mankhwala ena ndi mowa:

Kanagliflozin sanalimbikitse mawu a CYP450 system isoenzymes (3A4, 2C9, 2C19, 2B6 ndi 1A2) mu chikhalidwe cha hepatocytes aumunthu. Sanatilepheretsanso isoenzymes ya cytochrome P450 (1A2, 2A6, 2C19, 2D6 kapena 2E1) komanso analetsa CYP2B6, CYP2C8, CYP2C9, CYP3A4, malinga ndi kafukufuku wa zasayansi wogwiritsa 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 ya canagliflozin kudzera mu dongosolo la cytochrome P450 ndikosatheka.

Zopangidwa ndi katundu:

Piritsi limodzi la Invocan, filimu yopangidwa ndi 100 mg, ili ndi:

Mphamvu yogwira: 102.0 mg ya canagliflozin hemihydrate, omwe ali ofanana ndi 100.0 mg wa canagliflozin. Othandizira (pakati): microcrystalline cellulose 39.26 mg, anhydrous lactose 39.26 mg, croscarmellose sodium 12.00 mg, hyprolose 6.00 mg, magnesium stearate 1.48 mg. Otsatsa (chipolopolo): Opadry II utoto 85F92209 wachikasu (mwanjira yopangidwa ndi polyvinyl mowa, pang'ono hydrolyzed, 40.00%, titanium dioxide 24.25%, macrogol 3350 20.20%, talc 14.80%, iron oxide chikasu ( E172) 0,75%) - 8.00 mg.

Piritsi limodzi la Invocan, lomwe linapangidwa ndi 300 mg, lomwe lili ndi:

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 .

Mapiritsi okhala ndi mafilimu.

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

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

Kutulutsa Fomu

Mankhwalawa amagawidwa mwanjira ya mapiritsi ophimbidwa ndi utoto wamafuta wachikaso kapena oyera. Mapiritsi okhala ndi mawonekedwe a Capsule amasiyanasiyana kutengera mlingo.

Ngati mankhwalawo ali ndi 100 mg yogwira ntchito, piritsi ndi lachikasu. Kumbali ina kuli mawu akuti "CFZ", mbali inayo ndi mankhwala. Ngati mankhwalawa ali ndi 300 mg ya canagliflozin, ndiye kuti makapisozi ndi oyera. Kulemba zinthu mwachisawawa kumachitika molingana ndi mfundo zomwezi.

Pharmacodynamics ndi pharmacokinetics

Zinthu zomwe zimagwiritsidwa ntchito ndizoletsa transporter ya Na-glucose. Chifukwa cha nyumbayi, kubwezeretsedwanso kwa shuga woyengeka kumachepetsedwa ndipo cholowa chathu cha shuga chimachepa. Zotsatira zake, kuchuluka kwa mafuta amkodzo mumkodzo kumawonjezeka. Phunziroli, mutamwa 300 mg ya mankhwala musanadye odwala omwe ali ndi matenda a shuga a 2, panali kuchepa kwa mayamwidwe m'matumbo a shuga komanso kuchepa kwa glucose chifukwa cha impso komanso njira zina zowonjezera.

Zofunika! Kuchita bwino kwa mankhwalawa sikudalira chakudya.

Mankhwala amadziwika ndi kuyamwa mwachangu. Mphindi 60 atatha kutsata, pazowoneka bwino pazogwira ntchito zimawonedwa. Nthawi yomwe imatenga theka la mankhwalawa imatenga maola 10.5 ngati mutatenga 100 mg ya Invokana ndi maola 13 ngati mutatenga 300 mg. The bioavailability wa mankhwalawa 65%. Omwe amagwira mapuloteni amawonekanso - 99%.

Zizindikiro ndi contraindication

Chizindikiro chodziwika bwino chogwiritsira ntchito mankhwalawa ndi matenda a shuga a insulin. Kugwiritsa ndikotheka mu mawonekedwe a monotherapy kuphatikiza masewera olimbitsa thupi komanso zakudya zapadera. Komanso, mankhwalawa amayikidwa limodzi ndi mankhwalawa ndi mankhwala ena othandizira odwala matenda ashuga.

Contraindication yogwiritsira ntchito imaphatikizapo kusalolera pazigawo za mankhwala. Sitikulimbikitsidwanso kugwiritsa ntchito mankhwalawa kulephera kwa impso ndi chiwindi, matenda akulu amtima. Ana ndi achinyamata, mtundu 1 wa matenda a shuga, kutenga pakati komanso mkaka wa m'mawere ndi zifukwa zina zokanira mankhwalawa.

Zotsatira zoyipa

Zotsatira zosafunikira zimachitika pafupipafupi - 2% ya milandu. Zotsatira zoyipa kwambiri zimatchedwa polyuria - kuwonjezeka kwa mkodzo wothira. Komanso, wodwalayo amatha kudandaula chifukwa cha mseru, ludzu lalikulu, kudzimbidwa.

Zochepa zomwe zimatengera matenda otupa a genitourinary system. Balanitis, vulvovaginitis, balanoposthitis, cystitis nthawi zambiri zimawonedwa. Kuwala pakhungu, hypotension, sikumachitika kawirikawiri.

Mlingo ndi bongo

Chithandizo tikulimbikitsidwa kuti muyambe ndi mlingo wa 100 mg patsiku. Wodwala akalandira chithandizo popanda mavuto ena, koma kuwongolera kwathunthu kwa shuga m'magazi sikukwaniritsidwa, mlingowo ukhoza kuwonjezeka mpaka 300 milligrams patsiku. Ngati a Captokana amagwiritsidwa ntchito ngati gawo limodzi la chithandizo chophatikiza, kusintha kwa mankhwalawa kwa mankhwalawo ndikofunikira.

Mankhwala osokoneza bongo amapezeka kawirikawiri kwambiri. Odwala omwe ali ndi matenda a shuga a 2 amalekerera 600 mg tsiku lililonse. Ngati kuwonongeka kwa wodwalayo pakumwa mankhwalawo kumachitikabe, ndiye kuti pakufunikira kuphwanya kwam'mimba komanso kugwiritsa ntchito ma sorbents.

Kuchita

Akaphatikizidwa ndi diuretins, kuwonjezera kwawo kumawonedwa. Izi zikuwonetsedwa ndi kuwonjezeka kwa diuresis, komwe kumatha kupangitsa kuti madzi asungunuke. Komanso, kugwiritsa ntchito mankhwala omwe ali ndi othandizira ena a hypoglycemic kumawonjezera mwayi wokhala ndi shuga wambiri.

Yang'anani! Popewa hypoglycemia, kuwunika pafupipafupi shuga ndi kusintha kwa mlingo kumalimbikitsidwa.

Invokana amalumikizana ndi ma enzyme inducers (barbiturates, Rifampicin, Phenytoin, Carbamazepine, Ritonavir). Izi zimawonetsedwa ndi kuchepa kwa mphamvu ya hypoglycemic.

Zosintha mu pharmacokinetics sizimayang'aniridwa ndikuphatikizidwa ndi kulera kwapakamwa, Metformin. Chifukwa chake, ndalama izi zimatha kuphatikizidwa.

Pali analogue imodzi yokha yamankhwala yomwe imapangidwa mu mankhwala othandizira - Vokanamet. Zogwiritsira ntchito za pharmacological zimaganiziridwa pakufotokozera kofanizira.

Dzina lamankhwala	Chogwira ntchito	Zolemba mankhwalawa (maola)	Wopanga
Vokanamet	Kanagliflozin, metformin	24	Janssen Ortho LLS / Janssen-Silag S.p.A. ya "Johnson & Johnson, LLC", USA / Italy / Russia
Victoza	liraglutide	24	Novo Nordisk, A / T, Denmark
Jardins	empagliflozin	24	Beringer Ingelheim Pharma GmbH & Co KG, Germany

Mankhwalawa amagwiranso ntchito. Koma kudzisankhira pawokha kwa mankhwala sikofunikira kwenikweni.

Maganizo a odwala omwe adagwiritsa ntchito mankhwalawa.

Mankhwala "Attokana" adalangizidwa kwa ine ndi endocrinologist. Mtengo ndi wokwera, koma zotsatira zake zikuwonekera. Mwazi wamagazi pamlingo wapamwamba wabwinobwino ndipo suwonjezereka, zomwe zimakhala zabwino kwambiri!

Konstantin, wazaka 47

Zaka zingapo zapitazo, ndinapezeka kuti ndine matenda a shuga a 2. Anamuchitira Metformin, koma sizinathandize. Kenako adotolo adatulutsa Invocana. Mlingo wa shuga wakhazikika ndipo ndikumva bwino.

Ndili ndi matenda ashuga kwa nthawi yayitali. Ndidayesa mankhwala ambiri, ena sanathandize konse. Posachedwa, adotolo adalimbikitsa mankhwalawa "Attokana". Poyamba mtengo wake unkandiwopsa, koma anaganiza zogula. Zotsatira zake sizinatenge nthawi. Shuga mwina samachuluka, amamva bwino.

Valeria, wazaka 63

Mtengo wa mankhwalawa m'm ruble ina ya Russian Federation:

Mzinda	Invokana 100 mg N30	Attokana 300 mg N30
Moscow	2653	4444
Chelyabinsk	2537,90	4226,10
Saint Petersburg	3010	4699
Ulyanovsk	2511,70	4211,10
Tomsk	2477	4185
Saratov	2531	4278

Mtengo wa mankhwalawo ndiwokwera. Izi kwa odwala ambiri zimakhala chifukwa chokana chithandizo ndi mankhwalawa.

Pomaliza

Ngakhale kuti Invokana ndi mankhwala odula, ndi opambana pakati pa anthu odwala matenda ashuga. Kuchita bwino ndi zotsatira zoyipa zingapo ndizothandiza zamankhwala.

Matenda a shuga amafunikira chithandizo choyenera. Kuphatikizika kwa mankhwala othandizira, kupatsa thanzi komanso kuchita masewera olimbitsa thupi kumakhala ndi zotsatira zabwino za hypoglycemic. Mankhwala pafupipafupi komanso kutsatira malangizo onse a endocrinologist ndiye njira yothandizira wodwala aliyense. Mutha kudziwa zambiri pa vidiyo iyi:

Fomu ya Mlingo:

Piritsi la 300 mg lomwe lophimbidwa muli:
306.0 mg wa canagliflozin hemihydrate, womwe ndi wofanana ndi 300.0 mg wa canagliflozin.
Zabwino (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.
Othandizira (chipolopolo): Utoto woyera wa Opadray II 85F18422 (mowa wamphamvu wa polyvinyl, waphatikiza hydrolyzed, 40.00% titanium dioxide 25.00%, macrogol 3350 20.20%, talc 14.80%) - 18.00 mg.

Kufotokozera:
Mlingo wa 100 mg: mapiritsi okhala ndi mawonekedwe a kapisozi *, wokutidwa ndi utoto wamafuta achikasu, olembedwa mbali imodzi ndi CFZ ndipo enawo ndi 100.
* Pamtanda, pakati penipeni pali zoyera kapena pafupifupi zoyera.
Mlingo 300 mg: mapiritsi okhala ndi mawonekedwe a kapisozi okhala ndi utoto wa filimu yoyera kapena pafupifupi yoyera, cholembedwa mbali imodzi ndi CFZ ndi enanso 300.

Katundu

Zotsatira za Pharmacodynamic
M'mayesero azachipatala, pakatha vuto limodzi pakapita kamodzi komanso kangapo kamvekedwe ka canagliflozin ndi odwala omwe ali ndi matenda amtundu wa 2, njira yotsitsimutsa ya glucose idachepetsedwa modalira, ndipo kutuluka kwa shuga kwa impso kumakulanso. Mtengo woyambira wa impso kwa glucose unali pafupifupi 13 mmol / L, kutsika kwakukulu kwazowonjezera za maola 24 a shuga kumawonedwa ndikugwiritsa ntchito canagliflozin pa mlingo wa 300 mg kamodzi patsiku ndipo unachokera ku 4 mpaka 5 mmol / L, womwe umawonetsa chiopsezo chotsika. hypoglycemia pa mankhwala. Mchigawochi ndimaphunzira odwala omwe ali ndi matenda a shuga a mtundu wa 2 omwe adalandira canagliflozin pa 100 mg kapena 300 mg, kuchepa kwa njira yaimpso kunapangitsa kuti shuga awonjezeke ndi impso ndi 77-119 g / tsiku, kutulutsa kwa shuga kwa impso komwe kumayenderana ndi 308 mpaka 476 kcal / tsiku. Kutsika kwa chiwopsezo chaimpso ndi kuchuluka kwa shuga ndi impso kumapitilira mkati mwa sabata la 26 la mankhwala kwa odwala omwe ali ndi matenda a shuga 2. Panali kuwonjezeka kwapang'onopang'ono kwa voliyumu ya mkodzo tsiku lililonse (Suction
Ambiri mtheradi bioavailability wa canagliflozin pafupifupi 65%. Kudya zakudya zamafuta kwambiri sizinakhudze pharmacokinetics ya canagliflosin, kotero canagliflosin akhoza kumwa kapena wopanda chakudya. Komabe, poganizira luso la canagliflozin kuti achepetse kuchuluka kwa glycemia ya postprandial chifukwa kuchepa kwakamwa kwa glucose m'matumbo, tikulimbikitsidwa kutenga canagliflozin asanafike chakudya choyamba.

Kugawa
Pafupifupi kuchuluka kwa kagawidwe ka canagliflozin pamlingo wofanana pambuyo pa kulowetsedwa kamodzi kwa anthu athanzi kunali 83,5 L, komwe kumawonetsa kufalikira kwamankhwala. Kanagliflosin imagwirizanitsidwa kwambiri ndi mapuloteni a plasma (99%), makamaka ndi albumin. Kuyankhulana ndi mapuloteni sizimadalira kuchuluka kwa canagliflozin mu plasma. Kulumikizana ndi mapuloteni a plasma sikusintha kwenikweni kwa odwala omwe ali ndi impso kapena hepatic.

Kupenda
O-glucuronidation ndiye njira yayikulu yogwiritsira ntchito canagliflozin metabolism. Glucuronidation imachitika makamaka ndikutenga nawo gawo kwa UGT1A9 ndi UGT2B4 mpaka awiri osagwira O-glucuronide metabolites. Kuwonjezeka kwa AUC kwa canagliflozin (pofika 26% ndi 18%) kunawonedwa mwa onyamula odwala a UGT1A9 * 3 ndi UGT2B4 * 2, motsatana. Zotsatira izi sizikuyembekezeka kukhala ndizofunikira zamankhwala. CYP3A4-mediated (oxidative) kagayidwe ka canagliflozin m'thupi la munthu ndi kocheperako (pafupifupi 7%).

Kuswana
Mutatenga muyezo umodzi wa 14C-canagliflozin ndi odzipereka pakamwa, 41,5%, 7.0% ndi 3.2% ya mlingo woyamwa wopezeka ndi matendawa adapezeka mu ndowe ngati canagliflosin, hydroxylated metabolite ndi O-glucuronide metabolite, motero.Kufalikira kwamkati mwa canagliflozin kunali kosadziwika.
Pafupifupi 33% ya mlingo woyamwa wopezeka mu mkodzo, umapezeka mu mkodzo, makamaka ngati O-glucuronide metabolites (30,5%). Pansi pa 1% ya mlingo wa mankhwalawa amamuwonetsa kuti ndi impso. Chilolezo chotsogola ndi kugwiritsa ntchito canagliflozin mu Mlingo wa 100 mg ndi 300 mg kuchokera pa 1.30 mpaka 1.55 ml / min.
Kanagliflozin amatanthauza mankhwala ochepera chilolezo, pafupifupi mwatsatanetsatane chilolezo pafupifupi 192 ml / mphindi mwa athanzi pambuyo pokonzekera makosi.

Magulu apadera a odwala
Odwala ndi mkhutu aimpso ntchito
Cmax ya canagliflozin inakulirakulira pang'ono ndi 13%, 29%, ndi 29% mwa odwala omwe ali ndi vuto la Impso, odziletsa, komanso oopsa, koma osati mwa odwala omwe ali ndi hemodialysis. Poyerekeza ndi odzipereka athanzi, canagliflozin serum AUC idakwera pafupifupi 17%, 63% ndi 50% mwa odwala omwe amalephera pang'ono, aimpso, koma, anali ofanana mwa odzipereka athanzi komanso odwala omwe ali ndi vuto loti aimpso amalephera (CRF) )
Kuchotsa canagliflozin kudzera mu dialysis kunali kochepa.

Odwala omwe ali ndi vuto la chiwindi
Pambuyo kugwiritsa ntchito canagliflozin pa mlingo wa 300 mg kamodzi poyerekeza ndi odwala omwe ali ndi chiwindi chokwanira kwa odwala omwe ali ndi vuto la chiwindi A chiwindi ntchito molingana ndi Child-Pugh wadogo (kuphwanya chiwindi ntchito), Cmax ndi AUC∞ kuchuluka ndi 7% ndi 10%, motero, ndi kutsika ndi 4% ndikuwonjezeka ndi 11%, motero, odwala omwe ali ndi vuto la chiwindi B chiwindi malinga ndi kukula kwa chiwindi cha ana (Puff chiwindi). Kusiyanaku sikuwonedwa ngati kofunika kwambiri m'chipatala. Mlingo kusintha kwa odwala ofatsa kapena olimbitsa chiwindi kulephera sikufunika. Palibe zovuta zamankhwala zokhudzana ndi kugwiritsa ntchito mankhwalawa kwa odwala omwe ali ndi vuto loopsa la hepatic (kalasi C pa kukula kwa Mwana-Pugh), motero, kugwiritsa ntchito canagliflozin m'gululi la odwala ndi kutsutsana.

Okalamba okalamba (≥65 zaka)
Malinga ndi zotsatira za kuwunika kwa anthu omwe ali ndi pharmacokinetic, zaka sizinakhale ndi chiyambukiro chachikulu pa pharmacokinetics ya canagliflozin.

Ana (
Maphunziro a pharmacokinetics a canagliflozin mwa ana sanachitike.

Magulu ena odwala
Palibe kusintha kwa mankhwalawa malinga ndi jenda, mtundu / fuko kapena cholozera chachikulu cha thupi. Makhalidwewa sanakhale ndi chiwopsezo chachikulu pa pharmacokinetics ya canagliflozin, malinga ndi zotsatira za kuwunika kwa anthu a pharmacokinetic.

Contraindication

• Hypersensitivity kuti canagliflozin kapena aliyense wokonda mankhwala,
• mtundu 1 shuga
• matenda ashuga ketoacidosis,
• kulephera kwa aimpso ndi kuchuluka kwa kusefedwa kwa msana (GFR) 2,
• kulephera kwambiri kwa chiwindi
• lactose tsankho, kufupika kwa lactase, shuga-galactose malabsorption,
• aakulu mtima kulephera III - IV gulu lothandiza (gulu la NYHA),
• mimba ndi nthawi yoyamwitsa, ana ochepera zaka 18.

Ndi chisamaliro
Ndi mbiri ya matenda ashuga ketoacidosis

Gwiritsani ntchito pa nthawi yoyembekezera komanso nthawi yoyamwitsa

Nthawi yoyamwitsa
Kugwiritsidwa ntchito kwa canagliflozin kumapangidwira akazi panthawi yoyamwitsa. Malinga ndi data yomwe ikupezeka mu kafukufuku wa ziweto, canagliflozin amadutsa mkaka wa m'mawere. Sizikudziwika ngati canagliflozin amadutsa mkaka wa munthu.

Mlingo ndi makonzedwe

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> azaka 75 ayenera kupatsidwa 100 mg kamodzi tsiku lililonse ngati mlingo woyambirira. Ntchito ya impso ndi chiopsezo cha hypovolemia ziyenera kuganiziridwanso.

Matenda aimpso
Odwala omwe ali ndi vuto lofooka la impso (pafupifupi glomerular filtration rate (60) mpaka 90 ml / mphindi / 1.73 m 2), kusintha kwa mlingo sikofunikira.
Odwala omwe ali ndi vuto la impso ndi GFR kuchokera pa 60 mpaka 60 ml / mphindi / 1.73 mamita 2, kugwiritsa ntchito mankhwalawa mlingo wa 100 mg kamodzi patsiku tikulimbikitsidwa.
Kanagliflozin sichikulimbikitsidwa kwa odwala omwe ali ndi vuto la impso ndi GFR 2, end-site aakulu aimpso kulephera (CRF), kapena odwala omwe ali ndi dialysis, chifukwa chikuyembekezeka kuti canagliflozin sangachite bwino pamagulu odwalawa.

Zotsatira zoyipa

Zotsatira zoyipa zomwe zimakhudzana ndi kuchepa kwa magazi a intravascular vol
Kukula kwa mayankho onse osagwirizana ndi kuchepa kwamitsempha yamagazi (kupuma kwa chizungulire, orthostatic hypotension) 1.1% yokhala ndi placebo. Pafupipafupi zomwe zimachitika pokhudzana ndi kuchepa kwa magazi a intravascular volume pogwiritsa ntchito mankhwala a Captokana ® anali ofanana ndi omwe amagwiritsidwa ntchito poyerekeza mankhwala m'mayesero awiri olamulidwa mwachangu.
Pakufufuza kwa chiwopsezo cha mtima, chomwe chimakhudza odwala ambiri okalamba komanso matenda ochulukirapo, kuchuluka kwa zovuta zomwe zimakhudzana ndi kuchepa kwa kuchuluka kwamitsempha kunali 2.8% mukamagwiritsa ntchito canagliflozin pa 100 mg, 4 , 6% mukamagwiritsa ntchito canagliflozin pa 300 mg ndi 1.9% mukamagwiritsa ntchito placebo.
Malinga ndi zotsatira za kafukufuku waposachedwa, odwala omwe amalandila zotupa “zotsekemera”, odwala omwe amalephera kupweteka aimpso (GFR kuyambira 30 mpaka 60 ml / mphindi / 1.73 m 2) ndi odwala azaka za 75 zaka zambiri. zimachitika. Odwala omwe adalandira "loop" okodzetsa, pafupipafupi anali 3,2% akamagwiritsa ntchito canagliflozin pa 100 mg, 8.8% pa mlingo wa 300 mg ndi 4,7% pagulu loyendetsa. Odwala omwe ali ndi GFR 2 yoyambira, pafupipafupi anali 4.8% akamagwiritsa ntchito canagliflozin pa 100 mg, 8.1% pa mlingo wa 300 mg, ndi 2.6% pagulu lolamulira. Odwala azaka zapakati pa 75 ndi kupitirira, pafupipafupi anali 4.9% akamagwiritsa ntchito canagliflozin pa 100 mg, 8.7% pa mlingo wa 300 mg ndi 2.6% pagulu lolamulira.
Mukamachita kafukufuku wokhudzana ndi ngozi zamtima, kuchuluka kwa mankhwala obwera chifukwa cha zomwe zimachitika pokhudzana ndi kuchepa kwa magazi mkati mwazinthu, komanso pafupipafupi zoterezi zimachitika chifukwa chogwiritsa ntchito canagliflozin sichinawonjezeke.

Hypoglycemia ikagwiritsidwa ntchito ngati adjunct kupita ku insulin mankhwala kapena othandizira omwe amapangitsa kuti pakhale secretion yake
Kuchuluka kwa hypoglycemia kunali kotsika (100 mg, 300 mg ndi placebo ®, motero; hypoglycemia yayikulu imawonedwa mu 1.8%, 2.7% ndi 2.5% ya odwala omwe amalandira Invocana ® pa mlingo wa 100 mg, 300 mg ndi Pogwiritsa ntchito canagliflozin monga adjunct ofunsa sulfonylurea, hypoglycemia imawonedwa mu 4.1%, 12,5% ndi 5.8% ya odwala omwe adalandira Invocana ® pa mlingo wa 100 mg, 300 mg ndi placebo, motero.

Matenda oyamba ndi maliseche
Candidiasis vulvovaginitis (kuphatikizapo vulvovaginitis ndi kachilombo ka fungvovaginal fungal) idawonedwa mu 10,4%, 11.4% ndi 3.2% azimayi omwe adalandira mankhwalawa a Captokana ® pa mlingo wa 100 mg, 300 mg ndi placebo. Malipoti ambiri a vulvovaginal candidiasis okhudzana ndi miyezi inayi yoyamba atayamba kulandira chithandizo cha canagliflozin. Mwa odwala omwe amathandizidwa ndi canagliflozin, 2,3% adadwala matenda ambiri. 0,7% ya odwala onse anasiya kumwa canagliflozin chifukwa chaRevvovavoitis.
Candidiasis balanitis kapena balanoposthitis adawonedwa mu 4,2%, 3,7% ndi 0,6% ya amuna omwe adalandira mankhwalawa a Invokana ® pa 100 mg, 300 mg ndi placebo. Mwa odwala omwe amathandizidwa ndi canagliflozin, 0,9% anali ndi gawo loposa limodzi la matenda. 0.5% ya odwala onse anasiya kumwa canagliflozin chifukwa cha candida balanitis kapena balanoposthitis. Phimosis adanenedwa kuti 0.3% ya amuna omwe sanachite mdulidwe. Mu 0.2% ya milandu, odwala omwe adalandira canagliflozin anali odulidwa.

Matenda amitsempha
Matenda a urinary thirakiti adawonedwa mu 5.9%, 4,3% ndi 4.0% ya odwala omwe adalandira mankhwalawa a Invokana ® pa mlingo wa 100 mg, 300 mg ndi placebo. Matenda ambiri anali ochepetsetsa kapena osasamala kwenikweni; Odwala adalandira chithandizo chamanthawi zonse ndikupitiliza kulandira canagliflozin. Pafupipafupi matenda obwera mobwerezabwereza sanawonjezeke ndi kugwiritsa ntchito canagliflozin.

Mafupa owundana
Mu kafukufuku wazotsatira zam'mtima mwa odwala 4,327 omwe ali ndi vuto la mtima kapena chiwopsezo chachikulu cha mtima, chiwopsezo cha kufooka kwa mafupa chinali 16,3, 16.4, ndi 10,8 pazaka zopirira za 100 mg za 100 mg ya Invocana ®. ndi 300 mg ndi placebo, motsatana. Vuto lina lodziwika bwino lomwe limachitika mu sabata 26 zoyambirira zamankhwala.
Pakuwunikira komwe kafukufuku wina wamankhwala a Captokana ®, omwe adaphatikiza pafupifupi odwala 5800 omwe ali ndi matenda amtundu wa 2 kuchokera kwa anthu wamba, panalibe kusiyana kwazovuta zokhudzana ndi kuwonongeka.
Pambuyo pa masabata 104 a mankhwala, canagliflozin sizinakhudze kuwonongeka kwa mafupa.

Zosintha zasayansi
Kuchulukitsa kwa seramu potaziyamu
Kusintha kwapakati pa seramu potaziyamu kuchokera ku mtengo woyambira kunali 0,5%, 1.0% ndi 0,6% mukamagwiritsa ntchito mankhwala a Captokana ® mu Mlingo wa 100 mg, 300 mg ndi placebo, motero. 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. Pazonse, kuwonjezeka kwa ndende ya potaziyamu kunali pang'ono (® pa Mlingo wa 100 mg, 300 mg ndi placebo, motsatana) Kusintha kwapakati pa urea nitrogen kuchokera ku mtengo woyambira kunali 17.1%, 18,0% ndi 2.7% mukamagwiritsa ntchito mankhwala a Captokana ® Mlingo wa 100 mg, 300 mg ndi placebo, motsatana. Kusinthaku nthawi zambiri kumawonedwa pakadutsa milungu 6 kuchokera poyambira chithandizo.
Gawo la odwala omwe ali ndi kuchepa kwakukulu kwa GFR (> 30%) poyerekeza ndi gawo loyambirira lomwe limapezeka panthawi iliyonse ya chithandizo anali 2.0% akamagwiritsa ntchito canagliflozin pa 100 mg, 4.1% mukamagwiritsa ntchito mankhwala pa 300 mg ndi 2 , 1% yokhala ndi placebo. Kuchepetsa kumeneku mu GFR nthawi zambiri kumakhala kwakanthawi, ndipo kumapeto kwa kafukufukuyu, kutsika komweko mu GFR kumaonedwa mwa odwala ochepa: 0.7% mukamagwiritsa ntchito canagliflozin pa 100 mg, 1.4% mukamagwiritsa ntchito mankhwala pa 300 mg ndi 0,5% pa ntchito ya placebo.
Atayimitsa canagliflozin, zosintha izi mu labotale zidapitilira zabwino kapena zidabwezeretsa kale.

Kusintha mu mafuta a cholesterol
Zosintha mu LDL kuchokera poyambira koyambirira poyerekeza ndi placebo anali 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. Panali kuwonjezeka kocheperako pakukula kwa cholesterol yathunthu kuchokera ku mtengo woyambirira poyerekeza ndi placebo - 2,5% ndi 4,3% mukamagwiritsa ntchito canagliflozin mu Mlingo wa 100 mg ndi 300 mg, motsatana. Kukula kwa HDL kuchokera ku ndende yoyambirira poyerekeza ndi placebo kunali 5.4% ndi 6.3% mukamagwiritsa ntchito canagliflozin mu Mlingo wa 100 mg ndi 300 mg, motsatana. Kuwonjezeka kwa kuchuluka kwa cholesterol kosagwirizana ndi HDL kuchokera pamtengo woyambirira poyerekeza ndi placebo kunali 0,05 mmol / L (1.5%) ndi 0.13 mmol / L (3.6%) mukamagwiritsa ntchito canagliflozin mu Mlingo wa 100 mg ndi 300 mg, motero. Chiwerengero cha LDL / HDL sichinasinthe pogwiritsa ntchito mankhwala a Captokana ® poyerekeza ndi placebo. Kuchuluka kwa apolipoprotein B, kuchuluka kwa tinthu ta LDL komanso kuchuluka kwa mafuta m'thupi omwe samagwirizanitsidwa ndi HDL kwawonjezeka pang'ono poyerekeza ndi kusintha kwa ndende ya LDL.

Kuchulukitsa kwa hemoglobin
Kusintha kwakukulu kwa kuchuluka kwa hemoglobin kuchokera ku mtengo woyambira kunali 4.7 g / l (3.5%), 5.1 g / l (3.8%) ndi 1.8 g / l (-1.1%) akagwiritsidwa ntchito canagliflozin mu Mlingo wa 100 mg, 300 mg ndi placebo, motero. Kuwonjezeka pang'ono pang'onopang'ono pakusintha kwapakati pa chiwerengero cha maselo ofiira am'magazi ndi hematocrit kuchokera koyambira adawonedwa. Kumapeto kwa chithandizo, 4.0%, 2.7% ndi 0,8% ya odwala omwe amalandira chithandizo ndi Invocana ® pa Mlingo wa 100 mg, 300 mg ndi placebo, motero, anali ndi hemoglobin yomwe inali yayitali kuposa malire apamwamba.

Kuchulukitsa seramu phosphate
Mukamagwiritsa ntchito mankhwala a Captokana ®, kuwonjezeka kwa mlingo wa seramu phosphate kunawonedwa. M'maphunziro 4 azachipatala, kusintha kwapakati pa seramu phosphate kunali 3,6%, 5.1% ndi 1.5% mukamagwiritsa ntchito canagliflozin mu Mlingo wa 100 mg, 300 mg ndi placebo, motsatana. Milandu yowonjezera seramu phosphate ndende yoposa 25% ya mtengo woyambirira imawonedwa mu 0.6%, 1.6% ndi 1.3% ya odwala omwe adalandira chithandizo ndi Invocana ® mu Mlingo wa 100 mg, 300 mg ndi placebo, motsatana.

Anachepetsa 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.

Zotsatira zovuta m'magulu apadera odwala
Odwala okalamba
Mbiri ya chitetezo kwa odwala okalamba nthawi zambiri imagwirizana ndi zomwe zimachitika kwa odwala achichepere. Odwala omwe ali ndi zaka zopitilira 75 adakhala ndi zochitika zambiri zoyipa zomwe zimakhudzana ndi kuchepa kwa mtsempha wamitsempha wamitsempha yamagazi (postural kizungulire, orthostatic hypotension) 100 mg, 300 mg ndi placebo, motsatana. Panali kuchepa kwa GFR ndi 3.6%, 5.2% ndi 3.0% mukamagwiritsa ntchito mankhwala a Captokana ® mu Mlingo wa 100 mg, 300 mg ndi placebo, motsatana.

Odwala omwe ali ndi GFR kuchokera pa45 mpaka 60 ml / mphindi / 1.73 m 2
Odwala omwe ali ndi GFR yoyambirira ya 45-60 ml / mphindi / 1.73 m 2, pafupipafupi pazinthu zovuta zomwe zimakhudzana ndi kuchepa kwa magazi a intravascular vol 4 anali 4,6%, 7.1% ndi 3.4% mukamagwiritsa ntchito mankhwala a Captokana ®. 100 mg, 300 mg ndi placebo, motsatana. Ndende ya Serum creatinine inakwera ndi 4.9%, 7.3% ndi 0,2% mukamagwiritsa ntchito mankhwala a Captokana ® mu Mlingo wa 100 mg, 300 mg ndi placebo, motero. Seramu urea nayitrogeni ndende inachuluka ndi 13.2%, 13.6% ndi 0,7% mukamagwiritsa ntchito mankhwala a Captokana ® mu Mlingo wa 100 mg, 300 mg ndi placebo, motero. Gawo la odwala omwe ali ndi kuchepa kwakukulu kwa GFR (> 30%) nthawi iliyonse mankhwalawa anali 6.1%, 10,4% ndi 4.3% mukamagwiritsa ntchito mankhwala Invocana ® mu Mlingo wa 100 mg, 300 mg ndi placebo, motero.Pamapeto pa kafukufukuyu, chiwerengerochi chinali 2.3%, 4.3% ndi 3.5% mukamagwiritsa ntchito mankhwala a Captokana ® mu Mlingo wa 100 mg, 300 mg ndi placebo, motsatana.
Pafupipafupi kuchuluka kwa seramu potaziyamu (> 5.4 mEq / L ndi 15% ya mtengo woyambira) anali 5.2%, 9.1% ndi 5.5% mukamagwiritsa ntchito mankhwala Invocana ® mu Mlingo wa 100 mg, 300 mg ndi placebo, motero . Pafupipafupi, kuchuluka kwambiri kwa seramu potaziyamu kumawonekera mwa odwala omwe ali ndi vuto la aimpso omwe kale anali ndi kuchuluka kwa seramu potaziyamu ndipo / kapena amathandizidwa ndimankhwala angapo kuti achepetse potaziyamu, monga potaziyamu osasamala okodzetsa komanso zotupa za angiotensin. Kwakukulu, kuwonjezeka kwa ndende kumeneku kunali kwakanthawi ndipo sikunafunike chithandizo chamankhwala.
The kuchuluka kwa seramu phosphate kuchuluka ndi 3,3%, 4,2% ndi 1.1% mukamagwiritsa ntchito mankhwala a Captokana ® mu Mlingo wa 100 mg, 300 mg ndi placebo, motero. Pafupipafupi kuchuluka kwa seramu phosphate (> 1.65 mmol / L ndi 25% kuposa mtengo woyambira) kunali 1.4%, 1.3% ndi 0.4% mukamagwiritsa ntchito mankhwala a Captokana ® mu Mlingo wa 100 mg, 300 mg ndi placebo , motero. Kwakukulu, kuwonjezeka kwa ndende kumeneku kunali kwakanthawi ndipo sikunafunike chithandizo chamankhwala.

Zotsatira zalembetsedwe
Gome 1 ikuwonetsa zochitika zoyipa zomwe zinajambulidwa polemba ntchito. Zochitika zoyipa zimapangidwa mwanjira yolingana ndi iliyonse yamakina a ziwalo molingana ndi maulendo omwe amapezeka pogwiritsa ntchito magulu awa: nthawi zambiri (> 1/10), nthawi zambiri (> 1/100,> 1/1000,> 1/10000,

Bongo

Chithandizo
Pankhani ya mankhwala osokoneza bongo, ndikofunikira kuchita zinthu zothandizira, mwachitsanzo, kuchotsa zinthu zosagwiritsidwa ntchito m'matumbo, kuyang'anira matenda ndikumugwiritsa ntchito ngati mukumvera zomwe wodwala ali nazo. Kanagliflozin sanatulutsidwe mkati mwa maola 4 oyimba. Kanagliflozin sayembekezeredwa kuchotsedwa kudzera mu peritoneal dialysis.

Kuchita ndi mankhwala ena
Kuunika kwa vitro mogwirizana
Kagayidwe ka canagliflozin kumachitika makamaka ndi glucuronidation kudzera UDF-glucuronosyltransferase UGT1A9 ndi UGT2B4.
M'maphunziro mu vitro canagliflozin sanalepheretse isoenzymes ya cytochrome P450 (1A2, 2A6, 2C19, 2D6, 2E1, 2B6, 2C8, 2C9) ndipo sanatanthauze isoenzymes 1A2, 2C19, 2B6, 3A4 .. Kanagliflozin kuchepera CYPAA3 mu vitroKomabe, mayesero azachipatala palibe kuyanjana kwakukulu kwachipatala komwe kunapezeka. Kanagliflozin sayembekezeredwa kusintha kagayidwe kachakudya ka mankhwala omwe amagwiritsidwa ntchito kale omwe amapangidwa ndi ma isoenzymes.
Kanagliflozin ndi gawo lapansi la P-glycoprotein (P-gp) ndipo limaletsa pang'onopang'ono kuyendetsa kwa P-gp-Mediated digoxin.

Mu kuyesa kwa mgwirizano wa vivo
Zotsatira za mankhwala ena pa canagliflozin
Cyclosporine, hydrochlorothiazide, kulera kwamkamwa (levonorgestrel + ethinyl estradiol), metformin, ndi probenecid sizinawakhudze kwambiri pharmacokinetics ya canagliflozin.
Rifampicin. Kugwiritsa ntchito munthawi yomweyo rifampicin, njira yosagwiritsa ntchito ma enzyme angapo a banja la UGT komanso onyamula mankhwala, kuphatikiza UGT1A9, UGT2B4, P-gp ndi MRP2, kuchepetsa kupezeka kwa canagliflozin, komwe kungapangitse kuchepa kwa ntchito yake. Ngati ndi kotheka kuti mupeze inducer wa UGT ma enzyme ndi onyamula mankhwala (mwachitsanzo, rifampicin, phenytoin, barbiturates, phenobarbital, ritonavir, carbamazepine, efavirenz, St. John wa wort mafuta ophatikizika) munthawi yomweyo ndi canagliflozin, ndikofunikira kuyang'anira kuchuluka kwa hemog a 100mp ya gmp ya hemog ya 100mp ya gmp ya gmp ya gmp ya gmp ya hemog ya 100m. kamodzi pa tsiku, ndikuwapatsa mwayi kuti muwonjezere mlingo wa canagliflozin mpaka 300 mg kamodzi patsiku, ngati pakufunika kowonjezera glycemic control. Kwa odwala omwe ali ndi GFR kuchokera pa 45 mpaka 60 ml / mphindi / 1.73 m 2, kulandira mankhwalawa Evokana ® mu mlingo wa 100 mg ndi mankhwala osokoneza bongo a UGT banja la ma enzymes, ndipo omwe akufunika kuwongolera glycemic, kuganiziridwanso kuyenera kuperekedwa poika ena othandizira a hypoglycemic.

Gome 2: Zotsatira za mgwirizano wa mankhwala pakukhudzana kwa canagliflozin

Mankhwala onga	Mlingo Wofanizira 1	Mlingo wa canagliflozin 1	Gawo lachiyero lotanthauza kuti (chiwerengero cha zizindikiro poyang'anira chithandizo chamankhwala / popanda icho) Palibe zotsatira = 1.0
			AUC 2 (90% CI)	Max (90% CI)
Pankhani zotsatirazi, kusintha kwa canagliflozin sikofunikira:
Cyclosporin	400 mg	300 mg 1 nthawi patsiku kwa masiku 8	1,23 (1,19–1.27)	1,01 (0,91–1,11)
Levonorgestrel + Ethinyl Estradiol	levonorgestrel 0,15 mg ethinyl estradiol 0,03 mg	200 mg 1 nthawi patsiku kwa masiku 6	0,91 (0,88–0,94)	0,92 (0,84–0,99)
Hydrochlorothiazide	25 mg 1 nthawi patsiku kwa masiku 35	300 mg 1 nthawi patsiku kwa masiku 7	1,12 (1,08–1,17)	1,15 (1,06–1,25)
Metformin	2000 mg	300 mg 1 nthawi patsiku kwa masiku 8	1,10 (1,05–1,15)	1,05 (0,96–1,16)
Khalid	500 mg 2 kawiri patsiku kwa masiku atatu	300 mg 1 nthawi patsiku kwa masiku 17	1,21 (1,16–1,25)	1,13 (1,00–1,28)
Rifampicin	600 mg 1 nthawi patsiku kwa masiku 8	300 mg	0,49 (0,44–0,54)	0,72 (0,61–0,84)

1. Mlingo wa unit, pokhapokha utawonetsedwa.
2. AUCinf pokonzekera limodzi mlingo ndi AUC₂₄ - Mankhwala kufotokoza mankhwala angapo Mlingo.

Zotsatira za canagliflozin pa mankhwala ena
M'mayesero azachipatala odzipereka athanzi, canagliflozin sanakhale ndi mwayi wofanana pa pharmacokinetics ya metformin, njira zothandizira pakamwa (levonorgestrel + ethinyl estradiol), glibenclamide, simvastatin, paracetamol, hydrochlorothiazide ndi warfarin.
Digoxin. Kugwiritsa ntchito kuphatikiza kwa canagliflozin (300 mg kamodzi pa tsiku kwa masiku 7) ndi digoxin (0.5 mg patsiku la 1 ndi 0,25 mg m'masiku 6 otsatirawa) kunapangitsa kuwonjezeka kwa AUC ndi Cmax a digoxin ndi 20% ndi 36 %, motsatana, mwina chifukwa cha kulumikizidwa kwa P-gp. Odwala omwe amatenga digoxin kapena glycosides ena a mtima (mwachitsanzo, digitoxin) amayang'aniridwa bwino.

Gome 3: Zotsatira za Kanagliflozin Pakukhudzidwa kwa Mankhwala Ovuta

Mankhwala onga	Mlingo Wofanizira 1	Mlingo wa canagliflozin 1	Gawo lachiyero lotanthauza kuti (chiwerengero cha zizindikiro poyang'anira chithandizo chamankhwala / popanda icho) Palibe zotsatira = 1.0
			AUC 2 (90% CI)	Max (90% CI)
Mu milandu yotsatirayi, kusintha kwa mankhwalawa kwa mankhwala ophatikizana sikofunikira:
Digoxin	0,5 mg 1 nthawi yoyamba pa tsiku la 1, ndiye 0,25 mg 1 nthawi patsiku kwa masiku 6	300 mg kamodzi tsiku lililonse m'masiku 7	digoxin	1,20 (1,12–1,28)	1,36 (1,21–1,53)
Levonorgestrel + Ethinyl Estradiol	levonorgestrel 0,15 mg ethinyl estradiol 0,03 mg	200 mg kamodzi tsiku lililonse m'masiku 6	levonorgestrel	1,06 (1,00–1,13)	1,22 (1,11–1,35)
			ethinyl estradiol	1,07 (0,99–1,15)	1,22 (1,10–1,35)
Glibenclamide	1.25 mg	200 mg kamodzi tsiku lililonse m'masiku 6	glibenclamide	1,02 (0,98–1,07)	0,93 (0,85–1,01)
Hydrochlorothiazide	25 mg kamodzi tsiku lililonse pasanathe masiku 35	300 mg kamodzi tsiku lililonse m'masiku 7	hydrochlorothiazide	0,99 (0,95–1,04)	0,94 (0,87–1,01)
Metformin	2000 mg	300 mg kamodzi tsiku lililonse m'masiku 8	metformin	1,20 (1,08–1,34)	1,06 (0,93–1,20)
Paracetamol	1000 mg	300 mg kawiri pa tsiku m'masiku 25	paracetamol	1,06 3 (0,98–1,14)	1,00 (0,92–1,09)
Simvastatin	40 mg	300 mg kamodzi tsiku lililonse m'masiku 7	simvastatin	1,12 (0,94–1,33)	1,09 (0,91–1,31)
Warfarin	30 mg	300 mg kamodzi tsiku lililonse m'masiku 12	(R) - warfarin	1,01 (0,96–1,06)	1,03 (0,94–1,13)
			(S) -warfarin	1,06 (1,00–1,12)	1,01 (0,90–1,13)
			INR	1,00 (0,98–1,03)	1,05 (0,99–1,12)

1. Mlingo wa unit, pokhapokha utawonetsedwa
2. AUC_inf kukonzekera kwa mlingo umodzi ndi AUC_24h - Mankhwala zotchulidwa ngati Mlingo wambiri
3. AUC_0-12h

Zotsatira pazotsatira zoyesa zasayansi
Kusanthula pa 1,5-AG
Kuchulukitsidwa kwa shuga kwa impso mothandizidwa ndi canagliflozin kungayambitse kuchepa kwabodza kwa anthu 1,5-anhydroglucitol (1,5-AG) ndikupangitsa magwiridwe ake kukayikira. Chifukwa chake, zozama za 1,5-AG siziyenera kugwiritsidwa ntchito kuyesa kuwongolera glycemic kwa odwala omwe amalandira Invocana ®. Kuti mumve zambiri, ndikulimbikitsidwa kuti mulumikizane ndi wopanga mayeso a 1.5-AG.

Kusanthula kwa mkodzo
Popeza momwe limagwirira ntchito ya canagliflozin, mwa odwala omwe amalandiridwa ndi mankhwala a Captokana ®, zotsatira za kuyesedwa kwa shuga mumkodzo zimakhala zabwino.

Malangizo apadera

Diabetesic ketoacidosis (DKA)
Odwala omwe ali ndi mbiri ya matenda ashuga ketoacidosis samachotsedwa pamayesero azachipatala. Chenjezo limalangizidwa kugwiritsa ntchito mankhwala a Captokana ® odwala omwe ali ndi mbiri ya DKA. Mwa odwala ambiri, mikhalidwe idapezeka yomwe imakulitsa chiopsezo cha DKA (mwachitsanzo, matenda, kulekeka kwa insulin mankhwala).

Mtundu woyamba wa shuga
Odwala omwe ali ndi matenda amtundu wa 1 omwe akumwa mankhwalawa a Captokana ®, chiwopsezo cha DKA. M'mayesero azachipatala a 18, DKA idachitika mwa 5.1% (6/117), 9.4% (11/117), ndi 0,0% (0/117) odwala akamagwiritsa ntchito mankhwala a Captokana ® mu Mlingo wa 100 mg, 300 mg ndi placebo, motero. Pokhudzana ndi kupezeka kwa DKA, kugonekedwa kwa odwala 12 m'chipatala, mwa asanu mwaiwo kuchuluka kwa glucose m'magazi kunali pansi pa 13.9 mmol / L.

Type 2 shuga
Mukamagwiritsa ntchito mankhwala a Captokana ® odwala omwe ali ndi matenda a shuga 2, milandu ya DKA imanenedwa. Malinga ndi kafukufuku wazachipatala, kukhazikika kwa zovuta zoyipa, monga matenda ashuga ketoacidosis, ketoacidosis, metabolic acidosis, akuti 0,09% (10/10687) ya odwala omwe amalandila chithandizo ndi Invocana ®, odwala onse adagonekedwa m'chipatala. Milandu ya matenda ashuga a ketoacidosis omwe amachitika mwa odwala omwe ali ndi shuga wamagazi omwe ali pansi pa 13.9 mmol / L adalembedwanso pakuyang'anira.
Chifukwa chake, mwa odwala omwe ali ndi mtundu wa 2 matenda a shuga omwe ali ndi metabolic acidosis, kupezedwa kwa DKA kuyenera kuganiziridwa, ngakhale magazi a shuga ali pansi pa 13.9 mmol / L. Pofuna kupewa matenda omwe amachedwa komanso kuonetsetsa kuti wodwala akuwatsogolera bwino, odwala omwe amalandiridwa ndi mankhwalawa, a Captokana ® amayenera kuyesedwa ma ketones kuti muone ngati ali ndi vuto la kupuma, nseru, kusanza, kupweteka pamimba, chisokonezo, zipatso kupuma koipa, kutopa kosazolowereka ndi kugona.
Odwala omwe ali ndi matenda a shuga a mtundu wa 2 omwe ali ndi DKA, muyenera kusiya kugwiritsa ntchito mankhwalawa Invokana ®. Kuganiziridwanso kuyenera kuthandizidwenso kusiya mankhwala ndi Invocana ® odwala omwe ali ndi matenda a shuga 2 omwe amapita kuchipatala kuti achite opaleshoni yayikulu kapena ngati ali ndi matenda oopsa. Mankhwalawa ndi Invocana ® amatha kuyambiranso ngati mkhalidwe wa wodwalayo ukhazikika.

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
Zinawonetsedwa 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. Odwala omwe atha kutengeka mosavuta ndi zovuta zomwe zimakhudzana ndi kuchepa kwamitsempha yamagalimoto zimaphatikizapo odwala omwe amalandila zotupa za "loop", odwala omwe ali ndi vuto laimpso olimbitsa, komanso odwala azaka za 75 zaka.
M'maphunziro azachipatala a canagliflozin, kuwonjezereka kwa pafupipafupi pokhudzana ndi kuchepa kwamitsempha yama cell (mwachitsanzo, chizungulire chaposachedwa, orthostatic hypotension, kapena orterial hypotension) nthawi zambiri zimawonedwa m'miyezi itatu yoyambirira pamene 300 mg ya canagliflozin imagwiritsidwa ntchito. M'milungu isanu ndi umodzi yoyambirira ya chithandizo cha canagliflozin, panali zochitika zina za kuchuluka kwapadera kwa serum creatinine ndi kuchepa kwapakati pa GFR chifukwa cha kuchepa kwa kuchuluka kwa magazi mkati. 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.
Odwala ayenera kufotokozera zaumoyo wa kuchepa kwamitsempha yamavuto. Kusintha kwodabwitsaku nthawi zambiri kumapangitsa kuti ntchito yogwiritsa ntchito canagliflozin iyambike ndipo nthawi zambiri pogwiritsa ntchito canagliflozin adakonzedwa ndikusintha kwa regimen ya kumwa mankhwala a antihypertensive (kuphatikizapo okodzetsa). Odwala omwe ali ndi kuchepa kwa kuchuluka kwa intravascular, izi zimayenera kusinthidwa musanafike mankhwalawa canagliflozin. Musanalembe mankhwala a Captokana ®, ndikofunikira kuyesa ntchito ya impso. Ndikulimbikitsidwa kuti kuwunikira pafupipafupi kwa aimpso odwala omwe ali ndi GFR osakwana 60 ml / mphindi / 1.73 m 2. Kugwiritsira ntchito canagliflozin mwa odwala omwe ali ndi GFR osakwana 45 ml / mphindi / 1.73 m 2 ali otsutsana.
Chenjezo liyenera kugwiritsidwa ntchito ndi canagliflozin mwa odwala omwe kuchepa kwa mankhwalawa chifukwa cha kumwa mankhwalawa kungakhale pachiwopsezo, mwachitsanzo, odwala omwe ali ndi matenda amtima, mwa odwala a IGFR 2, odwala omwe amamwa mankhwala a antihypertensive, omwe ali ndi hypotension yotsika mtima mu mbiri ya odwala omwe amatenga diopture okalamba mu odwala okalamba (> zaka 65).

Kuchuluka kwa hematocrit
Poyerekeza ndi kugwiritsa ntchito canagliflozin, kuchuluka kwa hematocrit kumaonedwa, motero muyenera kusamala mukagwiritsa ntchito mankhwalawa odwala omwe ali ndi hematocrit okwera.

Matenda oyamba ndi maliseche
Popeza kuletsa kwa mtundu wachiwiri wa glucose wodalira wa sodium kumayendera limodzi ndi kuwonjezeka kwa kuchuluka kwa impso ndi impso, kupezeka kwa femal vevavaitisitis mwa azimayi ndi balanitis ndi balanoposthitis kumanenedwa mwa amuna kumanenedwa mu maphunziro azachipatala. Odwala (abambo ndi amayi) omwe anali ndi mbiri ya matenda oyamba ndi ziwalo zoberekera amatha kupezeka ndi matendawa. Balanitis kapena balanoposthitis adayambika, choyamba, mwa amuna omwe sanachite mdulidwe, milandu ya phimosis imanenedwanso. Mu 0.2% ya milandu, odwala amadulidwa. Nthawi zambiri, matendawa ankathandizidwa ndi othandizira antifungal wothandizidwa ndi adotolo kapena amatengera iwo eni motsutsana ndi maziko a mankhwala a canagliflozin.

Kulephera kwa mtima
Zomwe tikugwiritsa ntchito mankhwalawa chifukwa cha kulephera kwa mtima kwa gulu lachitatu la magwiridwe antchito (malinga ndi gulu la NYHA) ndizochepa. Palibe zokuchitikirani ndi kugwiritsa ntchito mankhwalawa nthawi yayitali chifukwa cha kulephera kwa mtima IV (gulu la NYHA).

Kukopa kuyendetsa galimoto ndikugwira ntchito ndi makina
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.

Mankhwala Okhala Pamalo a Pharmacy

Wopanga
Kupanga fomu yomalizira:
Janssen-Ortho LLC, 00778, State Road, 933 km 01.1 Maimi Ward, Gurabo, Puerto Rico.
Kulongedza, kulongedza ndi kuyendetsa magetsi:
Janssen-Silag S.p.A., Italy,
Adilesi yazamalamulo: Cologno Monzeze, Milan, ul. M. Buonarotti, 23.
Adilesi yeniyeni: 04100, Borgo San Michele, Latina, ul. S. Janssen.

Woyang'anira Setifiketi Yamalembetsa, Organisation Organisation
Johnson & Johnson LLC, Russia, 121614, Moscow, ul. Krylatskaya, 17/2

Malangizo awa ndi othandizira kuyambira pa 04.29.2016