Cov lus qhia rau kev siv "Invokany", muaj pes tsawg leeg, tshuaj yeeb yaj kiab yeeb tshuaj, tus nqi thiab tshuaj xyuas

Ntshav qab zib Hom 2 rau cov neeg laus ua ke nrog kev noj haus thiab kev tawm dag zog txhawm rau txhim kho glycemic tswj kom zoo:

• Kev Kho Mob Kho Mob
• Raws li ib feem ntawm kev sib xyaw ua ke nrog lwm cov tshuaj hypoglycemic, suav nrog insulin.

Invokana raug pom zoo rau kev siv qhov ncauj ib hnub ib zaug ua ntej noj tshais.

Rau cov neeg mob ntshav qab zib hom 2, koob tshuaj pom zoo ntawm Invokana yuav yog 100 mg lossis 300 mg ib hnub ib zaug.

Yog tias canagliflozin raug siv los ua qhov sib txuas rau lwm cov tshuaj (ntxiv rau cov tshuaj insulin lossis tshuaj uas txhim kho nws cov khoom lag luam), tom qab ntawd kev noj tshuaj qis dua tuaj yeem txo qhov muaj feem ntawm hypoglycemia.

Qee qhov xwm txheej, nws yuav muaj qhov siab txog ntawm qhov muaj qhov tshwm sim tsis zoo rau qhov tshuaj Invocana. Tej zaum lawv yuav cuam tshuam nrog txo qis hauv cov ntshav ntim hauv intravascular. Qhov no yuav yog tom qab zoo li kiv taub hau, txoj hlab ntshav lossis orthostatic hypotension.

Peb tab tom tham txog cov neeg mob uas:

1. tau txais diuretics nyob rau hauv tas li ntawd,
2. muaj teeb meem nrog kev ua haujlwm ntawm lub raum sim,
3. lawv muaj hnub nyoog laus (laus dua 75 xyoo).

Hauv kev pom ntawm qhov no, cov pawg no ntawm cov neeg mob yuav tsum haus cov canagliflozin hauv ib koob tshuaj 100 mg ib zaug ua ntej noj tshais.

Cov neeg mob uas yuav pom tshwm sim ntawm hypovolemia yuav raug kho mus rau hauv kev txiav txim siab kev hloov kho ntawm tus mob no ua ntej pib kho canagliflozin.

Cov neeg mob uas tau txais 100 ml ntawm Invokan tshuaj thiab ua siab ntev rau nws, thiab tseem xav tau kev tswj ntshav qab zib ntxiv, yuav pauv mus rau ib koob txog 300 mg ntawm canagliflozin.

Noj ntau dhau

Cov tsos mob Tsis muaj cov tsos mob tshwm sim uas paub tias muaj ntau tshaj ntawm canagliflozin. Ib koob tshuaj canagliflozin, nce mus txog 1600 mg rau cov neeg noj qab haus huv thiab 300 mg ob zaug ib hnub rau 12 lub lim tiam hauv cov neeg mob ntshav qab zib hom 2, feem ntau tau pom zoo.

Kev Kho Mob Yog tias muaj ntau dhau ntawm cov tshuaj, nws yog ib qho tsim nyog yuav tsum tau ua cov kev txhawb nqa ib txwm muaj, piv txwv, tshem tawm cov khoom tsis raug mob los ntawm lub plab zom mov, los ua kev soj ntsuam kev soj ntsuam thiab nqa tawm kev kho mob coj mus rau hauv tus neeg mob lub chaw kho mob. Canagliflozin tsis tau tawm ntawm kev lim ntshav 4-teev. Canagliflozin tsis xav tias yuav raug tshem tawm ntawm peritoneal lim ntshav.

Cov Tshuaj Tiv Thaiv:

Cov tshuaj Invokana tsis tuaj yeem siv rau hauv cov xwm txheej zoo li no:

• cov tshuaj tiv thaiv hypersensitivity rau canagliflozin lossis lwm yam khoom uas tau siv los ua tus pab,
• ntshav qab zib hom 1
• mob ketoacidosis,
• mob raum tsis ua haujlwm
• mob siab mob siab,
• cev xeeb tub thiab lactation,
• cov me nyuam hnub nyoog qis dua 18 xyoo

Thaum cev xeeb tub thiab pub niam mis, kev tshawb fawb ntawm lub cev qhov tshuaj tiv thaiv rau cov tshuaj Invocana tsis tau ua. Hauv kev sim tsiaj, nws tsis pom tias canagliflozin muaj qhov tsis ncaj lossis teebmeem lom rau lub cev yug menyuam.

Txawm li cas los xij, txawm li cas los xij, kev siv cov tshuaj los ntawm cov poj niam nyob rau lub sijhawm no ntawm lawv lub neej yog qhov tsis tau pom zoo, vim tias lub ntsiab tseem ceeb muaj peev xwm nkag mus rau cov kua mis thiab tus nqi ntawm cov kev kho mob ntawd yuav tsis ncaj.

Kev cuam tshuam nrog lwm yam tshuaj thiab dej caw:

Canagliflozin tsis tau ntxias cov lus qhia ntawm CYP450 system isoenzymes (3A4, 2C9, 2C19, 2B6 thiab 1A2) hauv kev coj noj coj ua ntawm tib neeg hepatocytes. Nws kuj tsis inhibit isoenzymes ntawm cytochrome P450 (1A2, 2A6, 2C19, 2D6 lossis 2E1) thiab tsis muaj zog tiv thaiv CYP2B6, CYP2C8, CYP2C9, CYP3A4, raws li kev soj ntsuam kuaj siv tib neeg lub siab microsomes. Hauv cov kev tshawb fawb hauv vitro tau pom tias canagliflozin yog lub zog ntawm cov tshuaj metabolizing enzymes UGT1A9 thiab UGT2B4 thiab cov tshuaj muaj tshuaj P-glycoprotein (P-gp) thiab MRP2. Canagliflozin yog qhov ua kom tsis muaj zog ntawm P-gp.

Canagliflozin undergoes tsis tshua muaj oxidative metabolism hauv. Yog li, thaj chaw kho mob tseem ceeb ntawm lwm cov tshuaj rau lub pharmacokinetics ntawm canagliflozin los ntawm cytochrome P450 system tsis zoo li.

Muaj pes tsawg leeg thiab lub zog:

Hauv 1 ntsiav tshuaj ntawm Invocan, zaj duab xis-coated 100 mg, muaj:

Cov khoom siv nquag: 102.0 mg ntawm canagliflozin hemihydrate, uas yog sib npaug rau 100.0 mg ntawm canagliflozin. Cov neeg muaj mob siab (tub ntxhais): microcrystalline cellulose 39.26 mg, anhydrous lactose 39.26 mg, croscarmellose sodium 12.00 mg, hyprolose 6.00 mg, magnesium stearate 1.48 mg. Cov plhaw (plhaub): Opadry II zas 85F92209 daj daj (ib feem ntawm cov dej cawv polyvinyl, qee qhov dej paug, 40.00%, titanium dioxide 24.25%, macrogol 3350 20.20%, talc 14.80%, hlau oxide daj ( E172) 0.75%) - 8.00 mg.

Hauv 1 ntsiav tshuaj ntawm Invocan, zaj duab xis-coated 300 mg, muaj:

306.0 mg ntawm canagliflozin hemihydrate, uas sib npaug rau 300.0 mg ntawm canagliflozin. Cov neeg siv dag zog (tub ntxhais): microcrystalline cellulose 117.78 mg, anhydrous lactose 117.78 mg, croscarmellose sodium 36.00 mg, hyprolose 18.00 mg, magnesium stearate 4.44 mg. Cov neeg raug tshem tawm (plhaub): Opadray II 85F18422 dawb xim (polyvinyl cawv, qee qhov hydrolyzed, 40.00% titanium dioxide 25.00%, macrogol 3350 20.20%, talc 14.80%) - 18.00 mg Cov.

Zaj duab xis-coated ntsiav tshuaj.

Tshuaj invokana yog qhov tsim nyog rau kev kho mob ntshav qab zib hom 2 rau cov neeg laus. Txoj kev kho yuav tsum muaj kev sib xyaw nrog kev noj zaub mov nruj, nrog rau kev tawm dag zog ib txwm.

Glycemia yuav tau txais txiaj ntsig zoo dua ua tsaug rau kev kho mob monotherapy, nrog rau kev kho mob ua ke nrog lwm tus neeg mob hypoglycemic.

Daim ntawv tso tawm

Cov tshuaj tau muab faib rau hauv cov qauv hauv cov ntsiav tshuaj coated nrog lub xim daj lossis dawb zaj duab xis txheej. Cov tshuaj ntsiav zoo li lub tshuaj sib txawv nyob ntawm seb ntau npaum li cas.

Yog tias cov khoom lag luam muaj 100 mg ntawm cov tshuaj nquag, lub ntsiav tshuaj yog xim daj. Ntawm ib sab muaj cov lus sau “CFZ”, ntawm lwm qhov tshuaj yog tshuaj. Yog tias cov tshuaj muaj 300 mg ntawm canagliflozin, tom qab ntawd cov tshuaj ntsiav tau xim dawb. Kev kos tau yog ua tiav raws li tus qauv ib txwm muaj.

Pharmacodynamics thiab pharmacokinetics

Cov tshuaj muaj zog yog ib qho inhibitor ntawm Na-dependent glucose transporter. Vim tias cov cuab yeej no, cov rov qab ua kom zoo dua ntawm cov piam thaj kom tsawg thiab txo qis rau kev siv qab zib kom tsawg. Raws li qhov tshwm sim, kev nthuav tawm ntawm cov carbohydrate hauv cov zis ntxiv. Thaum lub sij hawm kawm, thaum noj 300 mg ntawm cov tshuaj ua ntej noj mov hauv cov neeg mob ntshav qab zib hom 2, muaj kev poob qis hauv kev nqus hauv cov hnyuv thiab muaj suab thaj vim cov kua qog thiab ntshav ntxiv.

Tseem Ceeb! Qhov ua tau zoo ntawm cov tshuaj tsis yog nyob ntawm kev tau txais khoom noj.

Cov tshuaj yog tus cwj pwm los ntawm kev nqus. 60 feeb tom qab kev tswj hwm, qhov siab tshaj plaws ntawm cov khoom nquag tau pom. Lub sijhawm nws siv sijhawm los tshem tawm ib nrab cov tshuaj siv sijhawm li 10.5 teev yog tias koj noj 100 mg ntawm Invokana thiab 13 teev yog tias koj noj 300 mg. Lub bioavailability ntawm cov tshuaj yog 65%. Kev ua kom nruj rau cov protein yog kuj tau pom - 99%.

Kev taw qhia thiab contraindications

Qhov taw qhia ncaj qha rau kev siv tshuaj yog insulin-tiv thaiv ntshav qab zib mellitus. Kev siv yog ua tau rau hauv cov qauv ntawm cov kev kho mob thaum ua ke nrog kev tawm dag zog thiab kev noj zaub mov tshwj xeeb. Tsis tas li, cov tshuaj tau raug sau ua kev kho mob sib xyaw nrog lwm cov tshuaj tiv thaiv kev mob ntshav qab zib.

Cov tshuaj tiv thaiv kom siv nrog rau kev tsis haum rau cov tshuaj ntawm cov tshuaj. Nws kuj tseem tsis pom zoo kom siv cov tshuaj rau lub raum thiab daim siab ua haujlwm, mob plawv mob ntev. Cov menyuam yaus thiab tub ntxhais hluas, hom 1 mob ntshav qab zib mellitus, cev xeeb tub thiab lactation kuj tseem yog cov laj thawj rau kev tsis kam lees siv cov tshuaj no.

Sab sij huam

Qhov teebmeem tsis xav tau tshwm sim yooj yim - 2% ntawm cov neeg mob. Cov kev mob tshwm sim feem ntau tuaj yeem hu ua polyuria - nce ntxiv ntawm cov dej ntim ntawm cov zis tawm. Tsis tas li, tus neeg mob tuaj yeem yws txog xeev siab, nqhis dej ntau, cem quav.

Tsawg tsawg dua yog qhov mob tshwm sim ntawm cov kab mob genitourinary. Balanitis, vulvovaginitis, balanoposthitis, cystitis feem ntau pom. Cov pob khaus ntawm daim tawv nqaij, hypotension, tsis tshua muaj tshwm sim.

Tsuas tshuaj thiab tshaj

Txoj kev kho mob raug pom zoo kom pib nrog koob tshuaj 100 mg rau ib hnub. Yog tias tus neeg mob tau txais kev kho mob yam tsis muaj kev phiv, tab sis ua tiav kev tswj cov ntshav qab zib kom tsis ua tiav, qhov koob tshuaj yuav raug nce ntxiv rau 300 milligrams ib hnub. Yog tias Invokana tau siv los ua kev tiv thaiv kev sib xyaw ua ke, kev kho tshuaj ntau dua ntawm cov tshuaj sib txuas yog tsim nyog.

Overdose tshwm sim tsis tshua muaj neeg. Cov neeg mob uas muaj ntshav qab zib hom 2 zam txog 600 mg rau ib hnub. Yog tias qhov tsis zoo ntawm tus neeg mob lub sijhawm thaum noj cov tshuaj tseem tshwm sim, tom qab ntawd yuav tsum kho lub plab zom mov thiab siv cov kev muaj txiaj ntsig.

Kev sib txuam

Thaum ua ke nrog diuretins, kev nce ntxiv hauv lawv cov nyhuv raug pom. Qhov no yog ua kom pom los ntawm kev nce hauv diuresis, uas tuaj yeem ua rau lub cev qhuav dej. Tsis tas li, kev siv cov tshuaj nrog lwm tus neeg ua rau lub cev ntshav qab zib ua rau muaj kev pheej hmoo ntau ntxiv hauv cov ntshav qab zib.

Saib xyuas! Txhawm rau tiv thaiv cov ntshav qog ntshav qab zib, yuav tsum tau saib xyuas cov kua nplaum tas mus li thiab hloov qhov tshuaj ntau ntxiv.

Invokana cuam tshuam nrog cov enzyme inducers (barbiturates, Rifampicin, Phenytoin, Carbamazepine, Ritonavir). Qhov no yog ua kom pom los ntawm kev txo qis hauv cov nyhuv hypoglycemic.

Cov kev hloov hauv pharmacokinetics tsis pom thaum ua ke nrog cov tshuaj hauv qhov ncauj, Metformin. Yog li, cov nyiaj no tuaj yeem ua ke.

Tsuas muaj ib qho tshuaj yeeb yaj kiab tau tsim nyob hauv cov tshuaj nquag - Vokanamet. Hloov chaw rau kev nqis tes ua pharmacological raug txiav txim siab hauv cov lus piv txwv.

Lub npe tshuaj	Nquag tivthaiv	Kev pab kho siab kawg (teev)	Chaw tsim tshuaj paus
Vokanamet	Canagliflozin, metformin	24	Janssen Ortho LLS / Janssen-Silag S.p.A. rau "Johnson & Johnson, LLC", Tebchaws Asmeskas / Ltalis / Russia
Lub Neej	lisraglutide	24	Novo Nordisk, A / T, Denmark
Jardins	empagliflozin	24	Beringer Ingelheim Pharma GmbH & Co. KG, Lub Tebchaws Yelemees

Cov tshuaj no tsis zoo tshaj. Tab sis kev ywj siab xaiv cov tshuaj yog categorically tsis pom zoo.

Cov kev xav ntawm cov neeg mob uas tau siv tshuaj.

Cov tshuaj "Invokana" tau qhia rau kuv los ntawm tus kws kho keeb (endocrinologist). Tus nqi yog siab, tab sis cov nyhuv yog pom tau. Ntshav qab zib cov ntshav ntawm qhov txwv sab sauv ntawm qhov ib txwm thiab tsis nce, uas zoo heev!

Konstantin, 47 xyoo

Ob peb xyoos dhau los, Kuv tau kuaj pom tias mob ntshav qab zib hom 2. Nws raug kho los ntawm Metformin, tab sis tsis pab. Tom qab ntawd tus kws kho mob tau sau npe rau Invocana. Cov suab thaj theem tau ruaj khov thiab kuv zoo siab dua.

Kuv muaj ntshav qab zib tau ntev. Kuv tau sim ntau cov tshuaj, qee qhov tsis pab txhua. Tsis ntev los no, tus kws kho mob pom zoo cov tshuaj "Invokana". Thaum xub thawj tus nqi hem kuv, tab sis txiav txim siab yuav nws. Cov txiaj ntsig tau tsis ntev hauv kev los. Qab zib xyaum tsis nce, nws mloog zoo.

Valeria, 63 xyoo

Tus nqi ntawm cov tshuaj hauv rubles hauv qee lub nroog ntawm Lavxias Federation:

Lub nroog	Invokana 100 mg N30	Invokana 300 mg N30
Moscow	2653	4444
Chelyabinsk	2537,90	4226,10
Neeg dawb huv Petersburg	3010	4699
Ulyanovsk	2511,70	4211,10
Tomsk	2477	4185
Saratov	2531	4278

Tus nqi ntawm cov tshuaj muaj ntau. Qhov no rau ntau tus neeg mob ua lub laj thawj tsis kam lees kev kho mob nrog tshuaj.

Xaus

Txawm hais tias qhov tseeb tias Invokana yog cov tshuaj kim, nws yog kev vam meej ntawm cov neeg mob ntshav qab zib. Kev ua tau zoo thiab qhov tsawg ntawm cov kev mob tshwm sim yog qhov tseem ceeb ntawm cov tshuaj.

Mob ntshav qab zib xav tau txoj kev kho mob zoo. Cov txheej txheem ntawm cov tshuaj kho mob, khoom noj khoom haus thiab kev tawm dag zog ua kom muaj qhov teebmeem zoo hypoglycemic. Kev siv tshuaj tsis tu ncua thiab ua raws li txhua yam tshuaj ntawm tus kws endocrinologist yog tus yuam sij rau kev vam meej rau txhua tus neeg mob. Koj tuaj yeem paub cov ntaub ntawv ntau ntxiv los ntawm cov yeeb yaj kiab no:

Daim ntawv noj tshuaj:

Hauv ib qho 300 mg zaj duab xis-ntsiav tshuaj muaj:
306.0 mg ntawm canagliflozin hemihydrate, uas sib npaug rau 300.0 mg ntawm canagliflozin.
Excipients (tub ntxhais): microcrystalline cellulose 117.78 mg, anhydrous lactose 117.78 mg, croscarmellose sodium 36.00 mg, hyprolose 18.00 mg, magnesium stearate 4.44 mg.
Excipients (plhaub): Opadray II 85F18422 dawb zas xim (polyvinyl cawv, ib nrab hydrolyzed, 40.00% titanium dioxide 25.00%, macrogol 3350 20.20%, talc 14.80%) - 18.00 mg.

Kev piav qhia:
Dosage 100 mg: ntsiav tshuaj zoo li ntxau ntsiav tshuaj *, coated nrog rau xim daj zaj duab xis txheej, txua ntawm ib sab nrog CFZ thiab sab nraud nrog 100.
* Ntawm kev hla ntu, cov ntsiav tshuaj tub ntxhais yog dawb lossis yuav luag dawb.
Dosage 300 mg: ntsiav tshuaj zoo li lub hau ntsiav tshuaj coated nrog zaj duab xis daim nyias nyias ntawm cov xim dawb lossis yuav luag dawb, sau rau ntawm ib sab nrog CFZ thiab ntawm 300.

Cov yam ntxwv Pharmacological:

Cov teeb meem Pharmacodynamic
Hauv kev sim tshuaj, tom qab ib leeg thiab ntau qhov ncauj tswj tau canagliflozin los ntawm cov neeg mob uas muaj ntshav qab zib hom 2, lub raum pib rau cov piam thaj yog koob tshuaj-txo tsawg, thiab cov kua nplaum tawm ntawm lub raum nce ntxiv. Thawj qhov txiaj ntsig ntawm lub raum rov qab rau cov piam thaj yog li 13 mmol / L, qhov siab tshaj plaws nyob rau hauv 24-teev qhov nruab nrab lub ntsej muag pib ntawm cov piam thaj tau pom nrog kev siv canagliflozin ntawm koob tshuaj 300 mg ib hnub ib zaug thiab ntev li ntawm 4 txog 5 mmol / L, uas qhia tias muaj kev pheej hmoo tsawg tshwm sim hypoglycemia thaum kho. Hauv theem kuv kawm txog cov neeg mob ntshav qab zib hom 2 uas tau txais canagliflozin ntawm koob ntawm 100 mg lossis 300 mg, qhov poob qis rau lub raum rov qab rau cov piam thaj tau ua rau muaj kev nce ntxiv hauv cov ntshav qabzib los ntawm lub raum los ntawm 77-119 g / hnub, qhov pom kev tsis txaus siab ntawm qabzib los ntawm lub raum tau ua rau poob ntawm 308 476 kcal / hnub. Kev txo qis rau lub raum pib rau cov piam thaj thiab kev nce ntxiv ntawm cov ntshav qabzib los ntawm lub raum tau mob siab rau thaum 26-lub lim tiam kho mob hauv cov neeg mob uas muaj mob ntshav qab zib 2 mob ntshav qab zib. Muaj kev nce nrawm ntawm cov zis ntim txhua hnub (Quav
Qhov nruab nrab txog kev txiav txim siab nruab nrab ntawm canagliflozin yog kwv yees li 65%. Noj cov zaub mov muaj roj ntau hauv lub cev tsis muaj kev cuam tshuam cov pharmacokinetics ntawm canagliflosin, yog li canagliflosin tuaj yeem noj nrog lossis tsis noj mov. Txawm li cas los xij, coj mus rau hauv tus account lub peev xwm ntawm canagliflozin kom txo tau qhov nce ntxiv ntawm postprandial glycemia vim tias kev ua kom qeeb ntawm kev nqus ntawm cov piam thaj hauv txoj hnyuv, nws tau pom zoo kom noj canagliflozin ua ntej noj mov thawj zaug

Kev xa Khoom
Qhov nruab nrab ntawm kev faib tawm ntawm canagliflozin hauv kev sib npaug tom qab ib leeg ntawm cov leeg ntshav ntawm cov tib neeg noj qab haus huv yog 83,5 L, uas qhia tau hais tias nthuav dav dav hauv cov ntaub so ntswg. Canagliflosin lom zem ntau cuam tshuam nrog cov protein plasma (99%), feem ntau yog nrog albumin. Kev sib txuas lus nrog cov protein tsis nyob ntawm qhov kev nyeem ntawm canagliflozin hauv ntshav. Kev sib txuas lus nrog cov ntshav protein tsis hloov pauv ntau hauv cov neeg mob lub raum lossis hepatic tsis txaus.

Kev zom zaub mov
O-glucuronidation yog txoj kev loj rau cov metabolism hauv canagliflozin. Glucuronidation feem ntau tshwm sim nrog kev koom tes ntawm UGT1A9 thiab UGT2B4 ntawm ob qhov tsis muaj zog O-glucuronide metabolites. Kev nce ntxiv ntawm AUC ntawm canagliflozin (los ntawm 26% thiab 18%) tau pom hauv cov neeg mob nqa khoom ntawm UGT1A9 * 3 thiab UGT2B4 * 2 alleles, ntsig txog. Cov txiaj ntsig no tsis tau muaj qhov tseem ceeb tshawb nrhiav. CYP3A4-mediated (oxidative) metabolism ntawm canagliflozin hauv tib neeg lub cev yog qhov tsawg (kwv yees 7%).

Chaw Sau Ntawv
Tom qab noj ib koob tshuaj 14C-canagliflozin los ntawm cov neeg ua haujlwm pab lub cev kom noj qab haus huv, 41.5%, 7.0% thiab 3.2% ntawm kev muab tshuaj rau lub cev raug kuaj pom hauv cov quav li canagliflosin, hydroxylated metabolite thiab O-glucuronide metabolite, ntsig txog.Kev nkag mus ntawm canagliflozin yog qhov tseem ceeb.
Kwv yees li 33% ntawm cov koob tshuaj uas tau muab tshuaj rau hauv lub cev tau pom hauv cov zis, feem ntau yog O-glucuronide metabolites (30.5%). Tsawg dua li 1% ntawm koob tshuaj yog tawm ua qhov tsis hloov pauv canagliflozin los ntawm lub raum. Kev tshem tawm phom sij nrog kev siv cov canagliflozin hauv koob tshuaj 100 mg thiab 300 mg thaj tsam li ntawm 1.30 txog 1.55 ml / min.
Kanagliflozin hais txog cov tshuaj uas muaj cov kev ua kom tsawg tsawg, qhov nruab nrab ntawm qhov kev ua kom tsis muaj paug yog kwv yees li 192 ml / min hauv cov neeg noj qab haus huv tom qab kev siv tshuaj.

Cov pab pawg neeg tshwj xeeb
Cov neeg mob uas lub raum tsis ua hauj lwm zoo
Cmax ntawm canagliflozin nce nce pes nrab los ntawm 13%, 29%, thiab 29% hauv cov neeg mob uas lub raum tsis ua haujlwm, muaj mob me me, thiab mob hnyav, feem, tab sis tsis yog rau cov neeg mob ntawm hemodialysis. Piv rau cov neeg ua haujlwm noj qab haus huv, canagliflozin ntshiab AUC tau nce li 17%, 63% thiab 50% hauv cov neeg mob uas tsis tshua mob, qis thiab tawv nqaij lub raum tsis ua haujlwm, feem, tab sis zoo ib yam rau cov neeg tuaj yeem noj qab haus huv thiab cov neeg mob raum tsis ua haujlwm (CRF) )
Kev tshem tawm ntawm canagliflozin ntawm kev lim ntshav tsawg heev.

Cov neeg mob uas muaj lub siab ua haujlwm tsis zoo
Tom qab siv canagliflozin nyob rau hauv ib koob ntawm 300 mg, ib zaug piv nrog cov neeg mob lub siab ua haujlwm hauv cov neeg mob uas tsis muaj qib A daim siab ua haujlwm raws li Child-Pugh nplai (kev tsis txaus siab lub siab ua haujlwm), Cmax thiab AUC∞ nce li 7% thiab 10%, ntsig txog, thiab txo qis li 4% thiab nce li ntawm 11%, feem ntau, hauv cov neeg mob uas muaj qib B lub siab ua haujlwm raws li Child-Pugh nplai (kev mob siab ua haujlwm tsis zoo ntawm qhov mob hnyav). Cov kev sib txawv no tsis pom tias yog kab mob tseem ceeb. Koob tshuaj yuav tau hloov kho hauv cov neeg mob lub siab me me los yog mob nyhav daim siab tsis ua haujlwm. Tsis muaj kev sim kho mob nrog kev siv cov tshuaj hauv cov neeg mob uas muaj mob tsis txaus ntshai (chav C ntawm qhov Me Nyuam-Pugh nplai), yog li ntawd, kev siv canagliflozin hauv pawg neeg mob no yog sib kis.

Cov neeg laus (≥65 xyoo)
Raws li cov txiaj ntsig ntawm cov pej xeem pharmacokinetic tsom xam, lub hnub nyoog tsis muaj kev cuam tshuam loj hauv kev kho mob ntawm pharmacokinetics ntawm canagliflozin.

Cov Me Nyuam (
Cov kev tshawb fawb ntawm pharmacokinetics ntawm canagliflozin hauv cov menyuam yaus tsis tau ua.

Lwm pab pawg neeg mob
Tsis tas yuav tsum muaj qhov hloov kho nyob rau poj niam txiv neej, haiv neeg / haiv neeg los yog lub cev qhov ntsuas ntawm lub cev. Cov yam ntxwv no tsis muaj kev cuam tshuam loj hauv lub chaw muag tshuaj ntawm canagliflozin, raws li kev soj ntsuam cov tshuaj pharmacokinetic pej xeem tsom xam.

Cov Yuav Tsum Muaj

• Hypersensitivity rau canagliflozin lossis lwm yam tshuaj ntawm cov tshuaj,
• ntshav qab zib hom 1
• mob ketoacidosis,
• lub raum tsis ua hauj lwm nrog glomerular pom tus nqi (GFR) 2,
• daim siab ua hauj lwm hnyav
• lactose intolerance, lactase deficiency, qabzib-galactose malabsorption,
• mob plawv tsis ua haujlwm III - IV chav kawm ua haujlwm (NYHA kev faib tawm),
• cev xeeb tub thiab lub sijhawm pub mis niam, menyuam muaj hnub nyoog qis dua 18 xyoo.

Nrog saib xyuas
Nrog keeb kwm ntawm ntshav qab zib ketoacidosis

Siv thaum cev xeeb tub thiab thaum pub niam mis

Lub sijhawm pub mis niam
Kev siv cov canagliflozin yog sib kis rau cov poj niam thaum pub niam mis. Raws li cov ntaub ntawv pharmacodynamic / toxicological los ntawm cov kev tshawb fawb tsiaj, canagliflozin hla mus rau hauv niam mis. Nws tsis paub meej tias canagliflozin kis mus rau tib neeg cov kua mis.

Tsuas tshuaj thiab tswj hwm

Koob hla
Yog tias ib qho tshuaj ploj, nws yuav tsum ua kom sai li sai tau, txawm li cas los xij, ib zaug tshuaj ob zaug yuav tsum tsis txhob noj nyob hauv ib hnub.

Cov kev tshwj xeeb ntawm cov neeg mob
Cov me nyuam qis dua 18 xyoo
Cov kev nyab xeeb thiab kev ua tau zoo ntawm canagliflozin hauv cov menyuam yaus tseem tsis tau kawm.

Cov neeg laus cov neeg mob
Cov neeg mob> 75 xyoo rov hauv yuav tsum tau txhaj 100 mg ib hnub ib zaug raws li thawj koob tshuaj. Lub raum ua haujlwm thiab kev phom sij ntawm hypovolemia yuav tsum tau txiav txim siab.

Lub raum khiav tsis zoo
Hauv cov neeg mob uas tsis tshua mob raum (kwv yees li glomerular limtration npaum li cas (GFR) los ntawm 60 txog 90 ml / min / 1.73 m 2), tsis tas yuav tsum kho kom haum.
Hauv cov neeg mob uas lub raum tsis ua haujlwm nrog GFR los ntawm 45 txog 60 ml / min / 1.73 m 2, kev siv tshuaj hauv ib koob ntawm 100 mg ib hnub ib zaug yog kev pom zoo.
Kanagliflozin tsis pom zoo rau cov neeg mob uas lub raum tsis ua haujlwm nrog GFR 2, qhov kawg-mob raum tsis ua haujlwm (CRF), lossis hauv cov neeg mob rau kev lim ntshav, vim nws xav tias canagliflozin yuav tsis muaj txiaj ntsig hauv cov neeg mob no.

Sab sij huam

Cov kev tsis zoo cuam tshuam nrog qhov txo qis hauv cov ntshav ntim hauv intravascular
Qhov ntau zaus ntawm txhua qhov kev tsis haum siab uas cuam tshuam nrog kev txo qis hauv cov ntshav hauv lub cev (tom qab zoo li lub taub hau, orthostatic hypotension, mob ntshav qis, lub cev qhuav dej thiab tsaus muag) yog 1.2% thaum siv canagliflozin ntawm koob ntawm 100 mg, 1.3% thaum siv canagliflosin ntawm koob ntawm 300 mg thiab 1.1% nrog cov tso placebo. Qhov ntau zaus cov kev mob tshwm sim cuam tshuam nrog qhov txo qis hauv cov ntshav hauv lub cev thaum siv cov tshuaj Invokana ® tau sib piv rau cov uas thaum siv cov tshuaj sib piv hauv ob txoj kev sim tshuaj.
Hauv kev kawm txog kev pheej hmoo ntawm cov hlab plawv, nyob rau hauv uas cov neeg mob laus uas muaj qhov nruab nrab ntawm cov kab mob sib xyaw ua ke koom nrog, qhov tshwm sim ntawm cov kev mob tshwm sim cuam tshuam nrog kev txo qis ntawm cov ntim hauv intravascular yog 2.8% thaum siv canagliflozin ntawm ib koob ntawm 100 mg, 4 , 6% thaum siv canagliflozin ntawm koob tshuaj 300 mg thiab 1.9% thaum siv cov placebo.
Raws li cov ntsiab lus ntawm kev ntsuam xyuas dav dav, cov neeg mob tau txais "voj" diuretics, cov neeg mob uas tsis tshua mob raum (GFR los ntawm 30 rau 60 ml / min / 1.73 m 2) thiab cov neeg mob hnub nyoog> 75 xyoo muaj qhov tshwm sim ntau dua ntawm cov tsis xav tau kev tawm tsam. Hauv cov neeg mob uas tau txais "voj" diuretics, qhov raug ntau yog 3.2% thaum siv canagliflozin ntawm koob ntawm 100 mg, 8.8% ntawm koob tshuaj 300 mg thiab 4.7% hauv pawg tswj hwm. Hauv cov neeg mob nrog lub hauv paus GFR 2, qhov zaus yog 4.8% thaum siv canagliflozin ntawm koob tshuaj 100 mg, 8.1% ntawm koob tshuaj 300 mg, thiab 2.6% hauv pawg tswj hwm. Hauv cov neeg mob 75 xyoo thiab laus dua, qhov ntau zaus yog 4.9% thaum siv canagliflozin ntawm koob tshuaj 100 mg, 8.7% ntawm koob tshuaj 300 mg thiab 2.6% hauv pawg tswj hwm.
Thaum ua kev tshawb fawb txog cov kev pheej hmoo ntawm cov hlab plawv, qhov ntau zaus ntawm kev tshem tawm cov tshuaj vim qhov tshwm sim ntawm cov kev phiv tshuaj uas cuam tshuam nrog txo qis ntawm cov ntim hauv intravascular, thiab qhov ntau zaus ntawm qhov kev tsis haum siab loj nrog kev siv canagliflozin tsis tau nce ntxiv.

Kev siv tshuaj hypoglycemia thaum siv los ua qhov sib txuas rau insulin kho lossis cov neeg sawv cev uas txhim kho nws qhov kev tso ntshav
Qhov tshwm sim ntawm kev mob ntshav qab zib tsawg tsawg (100 mg, 300 mg thiab placebo ®, feem; ntshav qab zib tsawg kawg tau pom hauv 1.8%, 2.7% thiab 2.5% ntawm cov neeg mob tau txais Invocana ® ntawm 100 mg, 300 mg thiab placebo, ntsig txog.Thaum siv canagliflozin los ua qhov tshuaj rau sulfonylurea derivatives, hypoglycemia tau pom nyob rau hauv 4.1%, 12.5% ​​thiab 5.8% ntawm cov neeg mob uas tau txais Invocana ® ntawm ib koob ntawm 100 mg, 300 mg thiab placebo, ntsig txog.

Cov kab mob mob ntsws ntawm lub qau
Tus mob Candidiasis vulvovaginitis (suav nrog rau kev ua rau tus neeg mob vulvovaginitis thiab vulvovaginal tawm tsam) tau pom nyob hauv 10.4%, 11.4% thiab 3.2% ntawm cov poj niam uas tau txais cov tshuaj Invokana ® ntawm 100 mg, 300 mg thiab placebo. Feem ntau cov lus ceeb toom ntawm vulvovaginal candidiasis ntsig txog thawj plaub lub hlis tom qab pib kho canagliflozin. Ntawm cov neeg mob kho nrog canagliflozin, 2.3% muaj ntau dua ib ntu kev kis tus kab mob. 0.7% ntawm tag nrho cov neeg mob tsis noj cov canagliflozin vim muaj neeg vwm tsis txaus.
Candidiasis balanitis lossis balanoposthitis tau pom nyob rau hauv 4.2%, 3.7% thiab 0.6% ntawm tus txiv neej uas tau txais tshuaj Invokana ® ntawm 100 mg, 300 mg thiab placebo. Ntawm cov neeg mob kho nrog canagliflozin, 0.9% muaj ntau dua ib ntu kev kis tus kab mob. 0.5% ntawm tag nrho cov neeg mob tsis noj cov canagliflozin vim yog candida balanitis lossis balanoposthitis. Phimosis tau tshaj tawm nyob rau hauv 0.3% ntawm cov txiv neej uas tsis ua kev cai txiav. Hauv 0.2% ntawm cov neeg mob, cov neeg mob uas tau txais canagliflozin tau ua kevcai txiav.

Mob txeeb zig
Cov kab mob txeeb zig tau pom muaj nyob rau hauv 5.9%, 4.3% thiab 4.0% ntawm cov neeg mob uas tau txais cov tshuaj Invokana ® ntawm 100 mg, 300 mg thiab placebo. Feem ntau ntawm cov mob tau mob me me lossis mob nyhav, qhov zaus ntawm cov kev txhaum loj heev tsis tau nce ntxiv. Cov neeg mob tau teb rau cov qauv kev kho mob thiab txuas ntxiv tau txais kev kho canagliflozin. Cov zaus ntawm kev rov muaj dua tus mob tsis nce ntxiv nrog kev siv canagliflozin.

Cov pob txha lov
Hauv kev kawm txog cov kev mob plawv rau hauv 4,327 cov neeg mob uas muaj tus kab mob rau lub plawv los yog mob ntshav siab ntau, qhov tshwm sim ntawm cov pob txha pob txha yog 16.3, 16.4, thiab 10.8 rau 1,000 tus neeg mob-100 mg koob tshuaj ntawm Invocana mg. thiab 300 mg thiab cov tso tso, feem. Qhov tsis txaus ntawm qhov xwm txheej ntawm pob txha lov tshwm sim hauv thawj 26 lub lis piam ntawm kev kho.
Hauv kev sib koom ua ke ntawm lwm qhov kev tshawb fawb ntawm cov tshuaj Invokana ®, uas suav txog 5800 cov neeg mob uas muaj ntshav qab zib hom 2 los ntawm cov pej xeem sawv daws, tsis muaj qhov sib txawv ntawm kev pheej hmoo ntawm pob txha lov nrog rau kev tswj hwm.
Tom qab 104 lub lim piam ntawm kev kho mob, canagliflozin tsis muaj kev cuam tshuam tsis zoo rau cov pob txha ntxhia pob zeb.

Kev hloov pauv hauv tsev kho mob
Muaj cov poov xab poom tshuaj ntau ntxiv
Qhov nruab nrab ntawm kev hloov pauv ntawm qhov kev xav ntawm cov ntshav poov tshuaj los ntawm thawj tus nqi yog 0.5%, 1.0% thiab 0.6% thaum siv cov tshuaj Invokana ® hauv koob tshuaj 100 mg, 300 mg thiab placebo, feem. Cov xwm txheej ntawm nce cov ntshiab poov tshuaj concentration (> 5.4 mEq / L thiab 15% siab dua qhov pib siab) tau pom nyob rau hauv 4.4% ntawm cov neeg mob tau txais canagliflozin ntawm koob ntawm 100 mg, hauv 7.0% ntawm cov neeg mob tau txais canagliflozin ntawm koob ntawm 300 mg , thiab 4.8% ntawm cov neeg mob tau txais cov placebo. Hauv kev dav dav, qhov nce ntxiv ntawm cov poov tshuaj concentration yog me ntsis (® ntawm 100 mg, 300 mg thiab placebo, feem ntau. Qhov nruab nrab qhov hloov pauv hauv kev xav ntawm urea nitrogen los ntawm tus nqi pib yog 17.1%, 18.0% thiab 2.7% thaum siv tshuaj Invokana ® koob tshuaj ntawm 100 mg, 300 mg thiab placebo, feem. Cov kev hloov pauv no feem ntau pom nyob rau hauv 6 lub lis piam los ntawm kev pib kho. Tom qab ntawd, qhov tshuaj lom ntawm creatinine maj mam poob qis rau nws cov nqi qub, thiab cov concentration ntawm urea nitrogen tseem nyob ruaj khov.
Qhov feem ntawm cov neeg mob uas muaj qhov kev txo qis ntau dua hauv GFR (> 30%) piv nrog qib pib pom nyob rau txhua theem ntawm kev kho mob yog 2.0% thaum siv canagliflozin ntawm koob tshuaj 100 mg, 4.1% thaum siv tshuaj ntawm koob tshuaj 300 mg thiab 2 , 1% nrog cov placebo. Cov kev txo qis hauv GFR feem ntau yog cov hloov pauv, thiab thaum kawg ntawm txoj kev tshawb nrhiav, qhov kev txo qis zoo sib xws hauv GFR tau pom nyob hauv cov neeg mob tsawg dua: 0.7% thaum siv canagliflozin ntawm koob tshuaj 100 mg, 1.4% thaum siv cov tshuaj ntawm koob tshuaj 300 mg thiab 0.5% ntawm cov ntawv thov placebo
Tom qab siv ceev xwmphem canagliflozin, cov kev hloov pauv hauv chav kuaj pom tau muaj qhov hloov zoo lossis rov qab mus rau lawv qib qub.

Hloov hauv cov roj (concentration)
Qhov kev hloov pauv txhais tau li cas hauv LDL los ntawm thawj qhov kev sib piv piv nrog cov placebo yog 0.11 mmol / L (4.5%) thiab 0.21 mmol / L (8.0%) thaum siv canagliflozin hauv koob tshuaj 100 mg thiab 300 mg, feem. Muaj qhov nce me dua nyob rau hauv qhov kev coj ua ntawm tag nrho cov cholesterol los ntawm thawj tus nqi piv nrog placebo - 2.5% thiab 4.3% thaum siv canagliflozin hauv koob tshuaj 100 mg thiab 300 mg, feem. Qhov nce hauv HDL los ntawm qhov pib ua ke piv nrog cov placebo yog 5.4% thiab 6.3% thaum siv canagliflozin hauv koob tshuaj 100 mg thiab 300 mg, feem. Qhov kev nce siab ntawm cov concentration cov roj (cholesterol) tsis cuam tshuam nrog HDL los ntawm tus nqi thaum pib piv nrog cov placebo yog 0.05 mmol / L (1.5%) thiab 0.13 mmol / L (3.6%) thaum siv canagliflozin hauv koob tshuaj 100 mg thiab 300 mg, ntsig txog. Qhov piv ntawm LDL / HDL tsis hloov nrog kev siv tshuaj Invokana ® piv nrog cov tshuaj placebo. Qhov kev sib xyaw ntawm apolipoprotein B, cov lej ntawm LDL thiab cov concentration ntawm cov roj (cholesterol) uas tsis cuam tshuam nrog HDL nce rau qhov tsawg dua li piv nrog kev hloov hauv LDL concentration.

Muaj kev hemoglobin ntau ntxiv
Qhov hloov nruab nrab ntawm hemoglobin concentration los ntawm thawj tus nqi yog 4.7 g / l (3.5%), 5.1 g / l (3.8%) thiab 1.8 g / l (-1.1%) thaum thov canagliflozin hauv koob tshuaj 100 mg, 300 mg thiab placebo, feem. Tau pom tias qhov hloov me ntsis ntawm qhov feem pua ​​nruab nrab tau hloov pauv hauv cov neeg muaj ntshav liab thiab hematocrit los ntawm lub hauv paus tau pom. Qhov kawg ntawm kev kho mob, 4.0%, 2.7% thiab 0.8% ntawm cov neeg mob tau txais kev kho mob nrog Invocana ® ntawm kev txhaj tshuaj ntawm 100 mg, 300 mg thiab placebo, ntsig txog, muaj hemoglobin concentration siab dua li cov kev txwv siab ntawm ib txwm muaj.

Ua kom muaj cov ntsev phosphate ntau ntxiv
Thaum siv cov tshuaj Invokana ®, qhov tshuaj tiv thaiv kab mob nce ntxiv nyob rau hauv kev saib xyuas ntawm cov ntshiab phosphate tau pom. Hauv 4 qhov kev tshawb fawb soj ntsuam, kev hloov pauv nruab nrab hauv kev saib xyuas ntawm cov dej ntsev yog 3.6%, 5.1% thiab 1.5% thaum siv canagliflozin hauv koob tshuaj 100 mg, 300 mg thiab placebo, feem. Cov neeg mob uas nce serum phosphate ntau dua 25% ntawm thawj qhov txiaj ntsig tau pom nyob hauv 0.6%, 1.6% thiab 1.3% ntawm cov neeg mob uas tau txais kev kho nrog Invocana ® hauv koob tshuaj 100 mg, 300 mg thiab placebo, feem.

Txo cov ntshav uric acid ua kom tsawg
Nrog rau kev siv canagliflozin nyob rau hauv koob tshuaj 100 mg thiab 300 mg, qhov txo qis hauv qhov nruab nrab concentration ntawm uric acid los ntawm thawj theem (−10.1% thiab −10.6%, feem) tau pom sib piv nrog cov placebo, nrog kev siv uas qhov nce me ntsis hauv nruab nrab cov concentration ntawm thawj zaug (1.9%). Kev txo qis ntawm cov ntshav uric acid concentration hauv pawg canagliflozin yog qhov ntau los yog ze rau qhov siab kawg ntawm lub lim tiam 6 thiab pheej mob thoob plaws kev kho mob. Ib qho kev hloov pauv sai ntawm cov uric acid concentration hauv cov zis tau sau tseg. Raws li kev soj ntsuam los ntawm kev sib tham ua ke ntawm kev siv canagliflozin hauv koob tshuaj 100 mg thiab 300 mg, nws tau qhia tias qhov tshwm sim ntawm nephrolithiasis tsis tau nce ntxiv.

Kev ruaj ntseg plawv
Tsis muaj kev nce siab hauv kev mob plawv nrog canagliflozin piv nrog cov placebo pab pawg.

Cov kev tsis zoo hauv cov pawg neeg mob tshwj xeeb
Cov neeg laus cov neeg mob
Kev nyab xeeb kev nyab xeeb hauv cov neeg laus cov laus feem ntau ua raws li ntawd rau cov neeg mob hluas. Cov neeg mob uas muaj hnub nyoog laus dua 75 xyoo muaj qhov tshwm sim ntau dua los ntawm qhov kev tsis zoo uas cuam tshuam nrog kev txo qis ntawm cov dej ntim hauv lub cev (mob taub hau, txha caj qaum, ntshav tsis txaus), 4,45%, 8.7% thiab 2.6% thaum siv tshuaj Invokana ® 100 mg, 300 mg thiab placebo, feem. Muaj qhov txo qis hauv GFR los ntawm 3.6%, 5.2% thiab 3.0% thaum siv cov tshuaj Invokana ® hauv koob tshuaj 100 mg, 300 mg thiab placebo, ntsig txog.

Cov neeg mob nrog GFR los ntawm 45 txog 60 ml / min / 1.73 m 2
Hauv cov neeg mob nrog qhov pib GFR tus nqi ntawm 45-60 ml / min / 1.73 m 2, qhov ntau zaus ntawm qhov xwm txheej tsis zoo cuam tshuam nrog kev txo qis ntawm cov ntim hauv intravascular yog 4.6%, 7.1% thiab 3.4% thaum siv tshuaj Invokana ® hauv koob tshuaj 100 mg, 300 mg thiab placebo, feem. Ntshav dej creatinine lub zog nce ntxiv 4.9%, 7.3% thiab 0.2% thaum siv cov tshuaj Invokana ® hauv koob tshuaj 100 mg, 300 mg thiab placebo, ntsig txog. Cov ntshiab urea nitrogen nce ntxiv 13.2%, 13.6% thiab 0.7% thaum siv cov tshuaj Invokana ® hauv koob tshuaj 100 mg, 300 mg thiab placebo, ntsig txog. Qhov feem ntawm cov neeg mob uas muaj qhov kev txo qis hauv GFR (> 30%) txhua lub sijhawm hauv kev kho mob yog 6.1%, 10.4% thiab 4.3% thaum siv cov tshuaj Invocana ® hauv koob tshuaj 100 mg, 300 mg thiab placebo, feem.Thaum kawg ntawm txoj kev tshawb no, qhov kev faib ua feem no yog 2.3%, 4.3% thiab 3.5% thaum siv cov tshuaj Invokana ® hauv kev txhaj tshuaj ntawm 100 mg, 300 mg thiab placebo, feem.
Qhov ntau zaus nce ntxiv qhov concentration ntawm ntshiab poov tshuaj (> 5.4 mEq / L thiab 15% ntawm tus nqi pib) yog 5.2%, 9.1% thiab 5.5% thaum siv cov tshuaj Invocana ® hauv koob tshuaj 100 mg, 300 mg thiab placebo, feem Cov. Tsis tshua muaj ntau dua, nce ntxiv ntawm cov poov tshuaj poov tshuaj concentration tau pom nyob hauv cov neeg mob uas tsis tshua mob plab raum uas yav dhau los tau nce siab ntau ntawm cov poov tshuaj potassium thiab / lossis tau raug kho nrog ntau cov tshuaj los txo cov potassium excretion, xws li potassium-sparing diuretics thiab angiotensin-converting enzyme inhibitors. Nyob rau hauv dav dav, qhov no nce nyob rau hauv concentration yog transient thiab tsis xav tau kev kho mob tshwj xeeb.
Qhov tshuaj ntawm cov ntshiab phosphate tau nce los ntawm 3.3%, 4.2% thiab 1.1% thaum siv cov tshuaj Invokana ® hauv koob tshuaj 100 mg, 300 mg thiab placebo, ntsig txog. Qhov ntau zaus ntawm kev nce siab hauv kev saib xyuas ntawm cov dej ntshiab ntsev (> 1.65 mmol / L thiab 25% siab dua li tus nqi pib) yog 1.4%, 1.3% thiab 0.4% thaum siv cov tshuaj Invokana ® hauv koob tshuaj 100 mg, 300 mg thiab placebo , raws li. Nyob rau hauv dav dav, qhov no nce nyob rau hauv concentration yog transient thiab tsis xav tau kev kho mob tshwj xeeb.

Cov ntaub ntawv sau npe tom qab tiav
Cov lus 1 qhia txog cov xwm txheej tsis zoo uas tau sau tseg thaum lub sijhawm soj ntsuam tom qab soj ntsuam tas. Cov xwm txheej tsis zoo yog cov kab ke sib xyaw rau txhua qhov ntawm cov khoom nruab nrog cev raws li qhov muaj ntau zaus siv cov kev faib tawm hauv qab no: ntau zaus (> 1/10), feem ntau (> 1/100,> 1/1000,> 1/10000,

Noj ntau dhau

Kev Kho Mob
Yog tias muaj kev noj ntau dhau, nws yog qhov yuav tsum tau ua los ua cov kev txhawb nqa ib txwm muaj, piv txwv li, tshem tawm cov khoom tsis raug tshem tawm ntawm lub plab, ua kev soj ntsuam kev soj ntsuam thiab nqa tawm kev saib xyuas kev kho mob coj mus rau hauv tus txheej txheem kho mob ntawm tus neeg mob. Canagliflozin tsis tau tawm ntawm kev lim ntshav 4-teev. Canagliflozin tsis xav tias yuav raug tshem tawm ntawm peritoneal lim ntshav.

Kev cuam tshuam nrog lwm yam tshuaj
Hauv kev txheeb xyuas nyob hauv vitro
Cov metabolism hauv ntawm canagliflozin feem ntau tshwm sim los ntawm glucuronidation ntawm UDF-glucuronosyltransferases UGT1A9 thiab UGT2B4.
Hauv kev tshawb fawb hauv vitro canagliflozin tsis tau inhibit isoenzymes ntawm cytochrome P450 (1A2, 2A6, 2C19, 2D6, 2E1, 2B6, 2C8, 2C9) thiab tsis tau ntxias isoenzymes 1A2, 2C19, 2B6, 3A4 .. Canagliflozin tsis muaj zog hauv vitrotxawm li cas los xij, hauv kev kho mob hauv tsev kho mob tsis muaj kev cuam tshuam loj hauv qhov chaw tshawb pom. Canagliflozin tsis xav kom hloov pauv kev zom zaub mov kom meej meej uas siv cov tshuaj metabolized los ntawm cov isoenzymes no.
Canagliflozin yog qhov khoob ntawm P-glycoprotein (P-gp) thiab tsis muaj zog tiv thaiv P-gp-mediated digoxin thauj.

Hauv vivo kev ntsuam xyuas sib cuam tshuam
Cov nyhuv ntawm lwm cov tshuaj ntawm canagliflozin
Cyclosporine, hydrochlorothiazide, tshuaj tiv thaiv qhov ncauj (levonorgestrel + ethinyl estradiol), metformin, thiab probenecid tsis muaj qhov cuam tshuam loj hauv kev kho mob ntawm pharmacokinetics ntawm canagliflozin.
RifampicinCov. Kev siv phom ib txhij, ib qho tsis yog xim xaiv los ntawm ntau cov enzymes ntawm UGT tsev neeg thiab cov tshuaj nqa tshuaj, suav nrog UGT1A9, UGT2B4, P-gp thiab MRP2, txo qhov kev cuam tshuam ntawm canagliflozin, uas tuaj yeem ua rau txo qis nws cov txiaj ntsig. Yog tias nws yog qhov yuav tsum tau muab los ua tus tsim kev ntawm UGT tsev neeg enzymes thiab cov tshuaj nqa tshuaj (piv txwv, rifampicin, phenytoin, barbiturates, phenobarbital, ritonavir, carbamazepine, efavirenz, St. John lub wort perforated) ib txhij nrog canagliflozin, nws yog qhov yuav tsum tau soj ntsuam qhov tshuaj ntawm glycated 100 mg. ib hnub ib zaug, thiab muab rau kev muaj peev xwm nce ntxiv koob tshuaj canagliflozin rau 300 mg ib hnub ib zaug, yog tias yuav tsum tau tswj glycemic ntxiv. Rau cov neeg mob GFR los ntawm 45 txog 60 ml / min / 1.73 m 2, tau txais cov tshuaj Evokana ® hauv qhov tshuaj ntawm 100 mg thiab qhov tshuaj tiv thaiv ntawm UGT tsev neeg ntawm cov enzymes, thiab leej twg xav tau ntxiv glycemic tswj, kev txiav txim siab yuav tsum tau muab rau kev teem caij ntawm lwm tus neeg sawv cev hypoglycemic.

Cov lus 2: Qhov cuam tshuam ntawm kev sib koom tes ntawm cov tshuaj ntawm canagliflozin raug

Qaug tshuaj heev	Rov Sib Tham Sij Hawm 1	Koob tshuaj ntawm canagliflozin 1	Geomet txhais piv (piv txwv ntawm qhov ntsuas ntawm cov sij hawm tau ntsib kho tsis raws cai / tsis muaj nws) Tsis muaj teebmeem = 1.0
			AUC 2 (90% CI)	Max (90% CI)
Hauv cov xwm txheej hauv qab no, kev kho kom haum ntawm canagliflozin tsis tas yuav tsum muaj:
Cyclosporin	400 mg	300 mg 1 lub sijhawm ib hnub rau 8 hnub	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 lub sijhawm ib hnub rau 6 hnub	0,91 (0,88–0,94)	0,92 (0,84–0,99)
Hydrochlorothiazide	25 mg 1 lub sijhawm nyob rau ib hnub rau 35 hnub	300 mg 1 lub sijhawm ib hnub rau 7 hnub	1,12 (1,08–1,17)	1,15 (1,06–1,25)
Metformin	2000 mg	300 mg 1 lub sijhawm ib hnub rau 8 hnub	1,10 (1,05–1,15)	1,05 (0,96–1,16)
Probenecid	500 mg 2 zaug ib hnub rau 3 hnub	300 mg 1 lub sijhawm ib hnub rau 17 hnub	1,21 (1,16–1,25)	1,13 (1,00–1,28)
Rifampicin	600 mg 1 lub sijhawm ib hnub rau 8 hnub	300 mg	0,49 (0,44–0,54)	0,72 (0,61–0,84)

1. Chav txais koob tshuaj, tshwj tsis yog muaj lwm yam cim.
2. AUCinf rau kev npaj tshuaj ib zaug thiab AUC₂₄ - rau cov tshuaj uas tau sau tseg nyob hauv daim ntawv ntawm ntau koob tshuaj.

Cov nyhuv ntawm canagliflozin ntawm lwm cov tshuaj
Hauv kev sim kho mob hauv cov neeg tuaj yeem noj qab haus huv, canagliflozin tsis muaj lub zog tseem ceeb ntawm cov tshuaj pharmacokinetics ntawm metformin, tshuaj tiv thaiv qhov ncauj (levonorgestrel + ethinyl estradiol), glibenclamide, simvastatin, paracetamol, hydrochlorothiazide thiab warfarin.
DigoxinCov. Kev siv ntawm kev sib xyaw ntawm canagliflozin (300 mg ib hnub ib zaug rau 7 hnub) thiab digoxin (0.5 mg rau hnub 1 thiab 0.25 mg hauv 6 hnub tom ntej) ua rau muaj kev nce ntxiv ntawm AUC thiab Cmax ntawm digoxin los ntawm 20% thiab 36 %, feem, tejzaum nws vim muaj kev sib tshuam P-gp-mediated. Cov neeg mob noj digoxin lossis lwm yam kev mob plawv glycosides (piv txwv, digitoxin) yuav tsum tau tshuaj xyuas kom zoo.

Cov lus 3: Qhov cuam tshuam ntawm Canagliflozin ntawm Kev Raug Txheem rau Cov Tshuaj Txhaum Cai

Qaug tshuaj heev	Rov Sib Tham Sij Hawm 1	Koob tshuaj ntawm canagliflozin 1	Geomet txhais piv (piv txwv ntawm qhov ntsuas ntawm cov sij hawm tau ntsib kho tsis raws cai / tsis muaj nws) Tsis muaj teebmeem = 1.0
			AUC 2 (90% CI)	Max (90% CI)
Hauv cov xwm txheej nram qab no, kev kho cov tshuaj concomitant tsis tas yuav tsum muaj:
Digoxin	0.5 mg 1 lub sijhawm nyob rau 1 hnub, tom qab ntawd 0.25 mg 1 lub sijhawm ib hnub rau 6 hnub	300 mg ib hnub ib zaug hauv 7 hnub	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 ib hnub ib zaug tsis pub dhau 6 hnub	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 ib hnub ib zaug tsis pub dhau 6 hnub	glibenclamide	1,02 (0,98–1,07)	0,93 (0,85–1,01)
Hydrochlorothiazide	25 mg ib hnub ib zaug hauv 35 hnub	300 mg ib hnub ib zaug hauv 7 hnub	hydrochlorothiazide	0,99 (0,95–1,04)	0,94 (0,87–1,01)
Metformin	2000 mg	300 mg ib hnub ib zaug tsis pub dhau 8 hnub	metformin	1,20 (1,08–1,34)	1,06 (0,93–1,20)
Paracetamol	1000 mg	300 mg 2 zaug ib hnub tsis pub dhau 25 hnub	tshuaj paracetamol	1,06 3 (0,98–1,14)	1,00 (0,92–1,09)
Simvastatin	40 mg	300 mg ib hnub ib zaug hauv 7 hnub	simvastatin	1,12 (0,94–1,33)	1,09 (0,91–1,31)
Warfarin	30 mg	300 mg ib hnub ib zaug tsis pub dhau 12 hnub	(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. Chav txais koob tshuaj, tshwj tsis yog muaj lwm yam cim
2. AUC_inf rau kev npaj ib-koob thiab AUC_24h - rau cov tshuaj raws li tau siv ntau lub zog
3. AUC_0-12h

Ua rau ntawm kev kuaj pom
Kev tsom xam ntawm 1,5-AG
Kev nce ntxiv ntawm cov ntshav qabzib los ntawm lub raum nyob rau hauv kev cuam tshuam ntawm canagliflozin tuaj yeem ua rau qhov tsis zoo ntawm qhov kev tso tawm ntawm 1,5-anhydroglucitol (1,5-AG) thiab ua rau nws ua haujlwm tsis txaus ntseeg. Yog li, qhov ntau ntawm 1,5-AG yuav tsum tsis txhob siv los ntsuas glycemic tswj hauv cov neeg mob uas tau txais Invocana ®. Yog xav paub ntxiv, nws raug nquahu kom koj tiv toj rau 1.5-AG kuaj cov chaw tsim khoom.

Kev tsom xam cov piam thaj
Muab cov txheej txheem ntawm kev ua ntawm canagliflozin, hauv cov neeg mob tau txais tshuaj Invokana ®, qhov tshwm sim ntawm kev kuaj ntshav qabzib hauv cov zis yuav zoo.

Cov lus qhia tshwj xeeb

Tus kab mob ntshav qab zib ketoacidosis (DKA)
Cov neeg mob uas muaj keeb kwm ntawm ketoacidosis uas mob ntshav qab zib tau raug cais tawm ntawm kev sim tshuaj. Ceev faj yog qhia kom siv cov tshuaj Invokana ® hauv cov neeg mob uas muaj keeb kwm ntawm DKA. Hauv ntau tus neeg mob, cov xwm txheej tau pom tias ua rau muaj kev pheej hmoo ntau dua ntawm DKA (piv txwv li, kev kis kab mob, txuas ntxiv ntawm kev kho mob insulin).

Yam 1 ntshav qab zib
Cov neeg mob uas muaj ntshav qab zib hom 1 uas tau noj tshuaj Invokana ®, kev pheej hmoo ntau dua ntawm DKA. Hauv 18-lub lim tiam kuaj mob, DKA tshwm sim hauv 5.1% (6/117), 9.4% (11/117), thiab 0.0% (0/117) cov neeg mob thaum siv tshuaj Invokana ® hauv koob tshuaj 100 mg, 300 mg thiab cov placebo, feem. Hauv kev sib txuas nrog qhov tshwm sim ntawm DKA, kev mus pw hauv tsev kho mob ntawm 12 tus neeg mob yuav tsum tau, hauv 5 ntawm lawv cov ntsiab lus ntawm cov piam thaj hauv cov ntshav tau qis dua 13.9 mmol / L.

Mob ntshav qab zib Hom 2
Thaum siv tshuaj yeeb tshuaj Invokana ® hauv cov neeg mob hom 2 mob ntshav qab zib mellitus, feem ntau ntawm DKA tau tshaj tawm. Raws li kev tshawb fawb soj ntsuam, kev txhim kho ntawm qhov muaj kev phiv tshuaj ntau, xws li mob ntshav qab zib ketoacidosis, ketoacidosis, metabolic acidosis, tau tshaj tawm txog 0.09% (10/10687) ntawm cov neeg mob tau txais kev kho mob nrog Invocana ®, tag nrho cov neeg mob tau pw hauv tsev kho mob. Cov kab mob ntshav qab zib ketoacidosis uas tau tshwm sim rau cov neeg mob ntshav qab zib qis qis dua 13.9 mmol / L kuj tseem tau sau tseg thaum soj ntsuam tom qab sau npe tas.
Yog li, hauv cov neeg mob uas muaj hom 2 mob ntshav qab zib mellitus nrog metabolic acidosis, kev kuaj mob ntawm DKA yuav tsum xav, txawm tias cov ntshav qabzib ntshav qis dua 13.9 mmol / L. Txhawm rau tiv thaiv kev kuaj mob lig thiab xyuas kom muaj kev tswj hwm tus neeg mob kom zoo, cov neeg mob uas tau txais cov tshuaj Invokana ® yuav tsum tau kuaj rau ketones thaum muaj cov tsos mob ntawm metabolic acidosis, xws li ua pa luv, xeev siab, ntuav, mob plab, tsis meej pem, fruity ua pa tsw phem, txawv txawv thiab nkees nkees.
Hauv cov neeg mob uas muaj hom 2 mob ntshav qab zib mellitus nrog DKA, koj yuav tsum tam sim ntawd tsis siv tshuaj Invokana immediately. Kev txiav txim siab yuav tsum muab rau kev txiav tsis siv tshuaj nrog Invocana ® hauv cov neeg mob ntshav qab zib hom 2 mob ntshav qab zib pw tsev kho mob loj rau kev phais mob lossis thaum muaj mob hnyav. Kev kho mob nrog Invocana be tuaj yeem rov ua dua tshiab yog tias tus neeg mob tus mob.

Carcinogenicity thiab mutagenicity
Cov ntaub ntawv tshaj tawm tsis qhia tseeb txog kev phom sij rau tib neeg, raws li cov txiaj ntsig ntawm kev tshawb fawb pharmacological ntawm kev nyab xeeb, tshuaj lom ntawm rov qab noj tshuaj dua, genotoxicity, deev thiab ontogenetic toxicity.

Cuam Tshuam
Cov nyhuv ntawm canagliflozin ntawm tib neeg kev muaj peev xwm tsis tau kawm. Tsis muaj dab tsi cuam tshuam txog kev muaj me nyuam tau pom hauv kev tshawb nrhiav tsiaj.

Kev siv tshuaj hypoglycemia nrog siv ua ke nrog lwm cov tshuaj hypoglycemic
Nws tau qhia tias kev siv cov canagliflozin li kev kho mob monotherapy lossis ua ib qho txuas rau cov tshuaj tiv thaiv hypoglycemic (kev siv uas tsis nrog kev txhim kho hypoglycemia), tsis tshua muaj kev coj ua rau kev txhim kho hypoglycemia. Nws paub tias insulin thiab hypoglycemic cov neeg sawv cev uas txhim kho nws qhov tsis zais (piv txwv li, sulfonylurea derivatives) ua rau kev txhim kho ntawm hypoglycemia. Thaum siv canagliflozin los ua qhov txuas rau kev kho tshuaj insulin lossis los ntawm kev txhim kho nws txoj kev zais (piv txwv li, sulfonylurea derivatives), qhov tshwm sim ntawm hypoglycemia tau siab dua nrog cov placebo.
Yog li, thiaj li yuav txo tau qhov kev pheej hmoo ntawm hypoglycemia, nws raug nquahu kom txo qis cov tshuaj insulin lossis cov neeg sawv cev uas txhim kho nws qhov kev zais cia.

Txo hauv cov ntim hauv intravascular
Canagliflozin muaj cov nyhuv diuretic los ntawm kev nce lub zam ntawm cov kua nplaum los ntawm ob lub raum, ua rau osmotic diuresis, uas tuaj yeem ua rau txo qis hauv cov ntshav hauv lub cev. Cov neeg mob uas yuav ua rau muaj kev phiv tshuaj ntau ntxiv nrog rau kev txo qis hauv cov ntshav hauv lub cev muaj xws li cov neeg mob tau txais cov "diuretics", cov neeg mob lub cev tsis ua hauj lwm los ntawm mob hnyav, thiab cov neeg mob hnub nyoog> 75 xyoo.
Hauv cov kev tshawb fawb soj ntsuam ntawm canagliflozin, kev nce ntxiv ntawm cov zaus ntawm kev phiv tshuaj uas cuam tshuam nrog qhov txo qis hauv cov ntim ntim hauv nruab nrog (piv txwv li, tom qab kiv taub hau, orthostatic hypotension, lossis hypotension arterial) tau pom ntau dua thaum thawj peb lub hlis thaum 300 mg ntawm canagliflozin tau siv. Nyob rau thawj thawj rau lub lim tiam ntawm kev kho canagliflozin, muaj qhov xwm txheej me ntsis ntawm cov ntshav creatinine thiab qhov nce qis hauv GFR kwv yees vim tias qhov txo qis hauv intravascular ntim. Hauv cov neeg mob predisposed kom txo qis ntau dua nyob rau hauv intravascular ntim, raws li tau hais los saum no, muaj qee zaum muaj ntau dua qhov tseem ceeb hauv GFR (> 30%), uas tau daws tom qab thiab qee zaum yuav tsum muaj kev cuam tshuam hauv kev kho canagliflozin.
Cov neeg mob yuav tsum tshaj tawm cov kev mob tshwm sim los ntawm qhov txo qis hauv lub cev ntau ntau. Cov kev tsis zoo no tshwm sim ua rau qhov kev txiav tsis siv los ntawm kev siv canagliflozin thiab feem ntau nrog kev txuas ntxiv ntawm kev siv canagliflozin raug kho los ntawm kev hloov pauv ntawm kev noj tshuaj antihypertensive (suav nrog diuretics). Hauv cov neeg mob uas txo qis hauv lub ntim hauv intravascular, tus mob no yuav tsum tau kho ua ntej kev kho mob nrog canagliflozin. Ua ntej yuav muab tshuaj rau Invokana ana, nws yog qhov yuav tsum tau soj ntsuam lub raum muaj nuj nqi. Nws raug nquahu kom kuaj xyuas lub raum ua haujlwm ntau dua hauv cov neeg mob GFR tsawg dua 60 ml / min / 1.73 m 2. Kev siv cov canagliflozin hauv cov neeg mob GFR tsawg dua 45 ml / min / 1.73 m 2 yog contraindicated.
Kev ceev faj yuav tsum siv nrog canagliflozin hauv cov neeg mob rau tus neeg txo qis ntshav siab vim noj tshuaj yuav ua rau muaj kev pheej hmoo, piv txwv li, hauv cov neeg mob uas paub cov kab mob plawv, hauv cov neeg mob eGFR 2, hauv cov neeg mob noj tshuaj antihypertensive, nrog kev mob ntshav siab rau hauv keeb kwm ntawm cov neeg mob noj cov voj diuretics hauv cov neeg laus (> 65 xyoo).

Muaj hematocrit ntau ntxiv
Tawm tsam keeb kwm yav dhau los ntawm kev siv canagliflozin, kev nce ntxiv ntawm hematocrit, yog li ntawd yuav tsum tau ceev faj thaum siv cov tshuaj hauv cov neeg mob uas muaj lub siab hematocrit.

Cov kab mob mob ntsws ntawm lub qau
Txij li kev txiav txim siab ntawm sodium-depend type 2 glucose transporter yog nrog los ntawm kev nce ntxiv hauv lub cev tawm ntawm cov kua nplaum los ntawm lub raum, qhov tshwm sim ntawm candidal vulvovaginitis rau cov poj niam thiab tus mob balanitis thiab balanoposthitis hauv cov txiv neej tau qhia hauv kev tshawb fawb soj ntsuam. Cov neeg mob (cov txiv neej thiab poj niam) uas tau muaj keeb kwm los ntawm kev mob fungal ntawm cov kab mob ntawm chaw mos tau ntau dua tus kab mob no yuav kis tau. Tus mob Balanitis lossis tus mob balanoposthitis tau pib txhim kho, ua ntej ntawm txhua tus, cov txiv neej uas tsis muaj kev coj khaub ncaws, raug mob phimosis thiab. Hauv 0.2% ntawm tus neeg mob, cov neeg mob tau txiav daim tawv. Feem ntau, qhov mob tau kho nrog cov tshuaj tua kab mob hauv zos los ntawm kws kho mob lossis coj lawv tus kheej tawm tsam keeb kwm ntawm txuas ntxiv kev kho canagliflozin.

Lub plawv tsis ua hauj lwm
Cov kev paub ntawm kev siv cov tshuaj nyob rau hauv lub plawv mob ua tsis tiav ntawm III chav kawm ua haujlwm (raws li NYHA kev faib tawm) yog muaj tsawg. Tsis muaj kev paub dhau los ntawm kev siv cov tshuaj hauv cov tshuaj tiv thaiv lub plawv tsis ua haujlwm IV ua haujlwm hauv chav kawm (kev faib tawm NYHA).

Cawv ntawm kev tsav tsheb thiab ua haujlwm nrog cov ກົນ
Nws tsis tau tsim tsa tias canagliflozin tuaj yeem cuam tshuam rau kev muaj peev xwm tsav tsheb thiab ua haujlwm nrog cov txheej txheem.Txawm li cas los xij, cov neeg mob yuav tsum paub txog kev pheej hmoo ntawm hypoglycemia thaum siv canagliflozin los ua qhov txuas rau kev kho tshuaj insulin lossis cov tshuaj uas ua kom nws txoj kev zais, ntawm kev pheej hmoo ntawm kev tsim cov kev tsis zoo uas cuam tshuam nrog txo qis ntim hauv lub cev (postural kiv taub hau) thiab lub peev xwm tswj tsis taus. lub tsheb thiab cov txheej txheem rau kev txhim kho cov nyom tshwm sim.

Cov Cai Siv Tshuaj So

Chaw tsim tshuaj paus
Kev tsim cov tshuaj tiav ntawm daim ntawv no:
Janssen-Ortho LLC, 00778, Xeev Txoj Kev, 933 km 0.1 Maimi Ward, Gurabo, Puerto Rico.
Kev ntim, ntim thiab tswj pa:
Janssen-Silag S.p.A., Ltalis,
Chaw nyob raug cai: Cologno Monzeze, Milan, ul. M. Buonarotti, 23.
Qhov chaw nyob tseeb: 04100, Borgo San Michele, Latina, ul. S. Janssen.

Daim Ntawv Tso Npe Sau Npe, Lub Koom Haum Pabcuam
Johnson & Johnson LLC, Russia, 121614, Moscow, ul. Krylatskaya, 17/2

Daim qauv ntawm cov lus qhia no siv tau txij lub 04.29.2016