Invocana® (300 mg) Canagliflozin

Thov ua ntej koj yuav Invokana ntsiav tshuaj yog them. 300 mg 30 pcs., Pob., Tshawb cov ntaub ntawv hais txog nws nrog cov ntaub ntawv ntawm lub vev xaib raug cai ntawm cov chaw tsim khoom lossis taw kev tshwj xeeb ntawm qauv tshwj xeeb nrog tus thawj tswj haujlwm ntawm peb lub tuam txhab!

Cov ntaub ntawv qhia ntawm lub xaib tsis yog pej xeem kev pom zoo. Lub chaw tsim khoom muaj txoj cai los hloov cov qauv tsim, tsim qauv thiab ntim khoom. Cov duab ntawm cov khoom hauv cov duab tau tshaj tawm hauv phau ntawv teev npe rau ntawm lub xaib yuav txawv ntawm cov hauv paus chiv keeb.

Cov ntaub ntawv ntawm tus nqi ntawm cov khoom tau hais hauv phau ntawv qhia rau ntawm lub xaib yuav txawv qhov tseeb ntawm ib tus neeg thaum lub sijhawm tso daim ntawv txiav txim rau cov khoom lag luam.

Chaw tsim tshuaj paus

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.
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 colorant (dej cawv polyvinyl, qee qhov hydrolyzed, 40.00% titanium dioxide 25.00%, macrogol 3350 20.20%, talc 14.80%) - 18.00 mg Cov.

Pharmacological kev txiav txim

Nws tau pom tias cov neeg mob ntshav qab zib mellitus muaj qhov nce ntxiv rau lub ntsej muag, uas tuaj yeem pab txhawb ntxiv kom cov ntshav qabzib ntau ntxiv. Sodium glucose thauj protein 2 (SGLT2), qhia nyob rau hauv qhov ze ntawm lub raum, yog lub luag haujlwm rau feem ntau ntawm cov rov ua kom cov kua nplaum tawm ntawm tubule lumen.
Kanagliflozin yog ib qho inhibitor ntawm sodium-glucose thauj protein 2. Los ntawm inhibiting SGLT2, canagliflozin txo qhov reabsorption ntawm lim tau cov ntshav qab zib thiab txo qis qis qis rau cov piam thaj (PPG), yog li ua kom cov ntshav qabzib tso zis ntau dhau, uas ua rau txo qis ntshav qabzib nrog kev insulin- ib txoj kev ywj pheej hauv cov neeg mob uas muaj ntshav qab zib hom 2.
Ib qho kev nce ntxiv ntawm cov ntshav qabzib hauv kev tso zis tawm los ntawm kev tsis txaus siab ntawm SGLT2 kuj ua rau osmotic diuresis, cov nyhuv diuretic ua rau txo cov ntshav hauv systolic, nce ntxiv ntawm cov zis nyob rau hauv lub cev ua rau cov calories poob thiab vim li ntawd, lub cev hnyav dua.
Hauv kev tshawb fawb nyob qib III hauv kev sim tshuaj tiv thaiv kev noj tshais ua ke, kev siv canagliflozin ntawm koob tshuaj 300 mg ua rau muaj kev cuam tshuam ntau ntxiv rau cov kev hloov pauv hauv qib ntawm postprandial glycemia dua li nrog 100 koob tshuaj. Cov nyhuv no yog qee vim yog nyob rau hauv zos inhibition ntawm cov hnyuv protein SGLT1, suav txog qhov hloov pauv ntau ntawm canagliflosin nyob rau hauv plab hnyuv lumen ua ntej kev nqus tshuaj (canagliflosin yog qhov muaj peev xwm tsawg SGLT1 inhibitor). Hauv kev tshawb nrhiav, malabsorption tsis pom pom nrog kev siv canagliflozin.
Cov teeb meem Pharmacodynamic:
Thaum kuaj mob 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 cov tshuaj noj ntau zuj zus, thiab cov zis ua kom tso zis ntau ntxiv. Thawj qhov txiaj ntsig ntawm lub raum rov qab rau cov piam thaj yog li 13 mmol / L, qhov siab tshaj plaws txo qis rau 24-teev nruab nrab lub raum pib rau cov piam thaj tau pom nrog kev noj tshuaj ntawm 300 mg ib hnub ib zaug thiab muaj li ntawm 4 txog 5 mmol / L, uas qhia tias muaj kev pheej hmoo tsawg kawg ntawm hypoglycemia ntawm kev kho mob tom qab. Hauv kev tshawb nrhiav qhov tseeb txog kev siv canagliflozin hauv koob tshuaj 100 mus rau 300 mg ib hnub ib zaug los ntawm cov neeg mob ntshav qab zib hom 2 rau 16 hnub, qhov kev poob qis rau lub raum feem ntau yog cov piam thaj thiab qhov nce ntawm cov zis nyob rau hauv lub cev yog qhov tas li. Hauv qhov no, cov ntsiab lus ntawm cov piam thaj hauv ntshav plasma poob qis-tso siab rau thawj hnub ntawm kev siv, tom qab ntawd qhov kev txo qis hauv cov concentration ntawm cov piam thaj hauv ntshav plasma ntawm ib lub plab khoob thiab tom qab noj mov.
Kev siv ib koob tshuaj 300 mg ntawm canagliflozin ua ntej noj mov ntawm cov khoom noj uas muaj calorie ntau hauv cov neeg mob ntshav qab zib hom 2 ua rau muaj kev ncua sij hawm ntawm kev nqus ntawm cov piam thaj hauv txoj hnyuv thiab txo qis postprandial glycemia los ntawm lub raum thiab cov kev ua haujlwm ntxiv.
Hauv kev sim tshuaj, 60 tus neeg tuaj yeem noj qab haus huv tau txais ib koob tshuaj 300 mg ntawm canagliflozin, 1200 mg ntawm canagliflozin (4 zaug qhov siab tshaj qhov pom zoo), moxifloxacin, thiab placebo. Tsis muaj qhov hloov pauv tseem ceeb hauv QT ncua tau pom nrog qhov koob pom zoo ntawm 300 mg lossis nrog koob ntawm 1200 mg. Thaum ua ntawv thov ntawm lub koob tshuaj 1200 mg, lub siab tshaj plaws ntshav plasma concentration ntawm canagliflozin yog kwv yees li 1.4 npaug siab dua qhov sib npaug ntawm qhov sib npaug ncau tom qab noj cov tshuaj ntawm 300 mg ib zaug ib hnub.
Kev Yoo Mov Glycemia:
Hauv kev sim tshuaj, kev siv canagliflozin li monotherapy lossis ua ib qho txuas rau kev kho nrog ib lossis ob lub qhov ncauj tshuaj hypoglycemic ua rau qhov nruab nrab ceev ceev glycemia hloov pauv piv nrog thawj qib txheeb ze rau cov placebo ntawm -1.2 mmol / l txog -1.9 mmol / l thaum thov kev noj ntau npaum li 100 mg thiab los ntawm -1.9 mmol / l txog -2.4 mmol / l - thaum thov kev noj ntau npaum li 300 mg, feem. Cov nyhuv no tau ze rau qhov siab tshaj plaws tom qab thawj hnub ntawm txoj kev kho thiab tau mob siab thoob plaws hauv lub sijhawm kho.
Tom qab cov glycemia:
Hauv kev sim kho mob ntawm kev siv canagliflozin raws li kev kho mob monotherapy lossis kho cov tshuaj rau ib lossis ob lub qhov ncauj hypoglycemic tus neeg sawv cev, postprandial glycemia tau ntsuas tom qab thov kev kuaj mob kam rau ua nrog kev noj tshais nrog cov qauv. Kev siv cov canagliflozin ua rau qhov nruab nrab txo qis ntawm qib postprandial glycemia piv nrog qib pib nrog kev hwm txog cov placebo los ntawm -1.5 mmol / L txog -2.7 mmol / L - thaum siv ntau npaum li 100 mg thiab los ntawm -2.1 mmol / L rau -3.5 mmol / l - thaum siv ntau npaum li 300 mg, feem, vim qhov txo cov piam thaj ua ntej noj mov thiab muaj qhov txawv txav ntawm cov qib ntawm postprandial glycemia.
Lub cev hnyav:
Canagliflozin 100 mg thiab 300 mg raws li kev kho mob monotherapy thiab raws li ob lossis peb npaug kev pabcuam ntxiv los ua rau muaj kev txo qis hauv cov kabmob lub cev nyhav tshaj li 26 lub lis piam, piv nrog cov placebo. Rau ob lub 52-lub limtiam nquag tswj kev sib piv sib piv canagliflozin nrog glimepiride thiab sitagliptin, qhov pab txhawb thiab cov ntsiab lus tseem ceeb txhais tau tias txo qis hauv lub cev feem pua ​​rau canagliflozin li qhov sib txuas rau metformin yog -4.2% thiab -4.7% rau canagliflozin 100 mg thiab 300 mg, feem, sib piv nrog kev sib xyaw ntawm glimepiride thiab metformin (1.0%) thiab -2.5% rau canagliflozin 300 mg hauv kev sib xyaw nrog metformin thiab sulfonylurea, piv nrog sitagliptin hauv kev sib xyaw nrog metformin thiab sulfonylurea (0.3%).
Ntshav siab:
Hauv qhov kev tshawb nrhiav tshuaj placebo, kev kho mob nrog canagliflozin 100 mg thiab 300 mg ua rau muaj qhov nruab nrab txo systolic ntshav siab ntawm -3.9 hli Hg. thiab -5.3 mmHg feem, piv nrog cov placebo (-0.1 hli), thiab cov nyhuv me dua ntawm cov ntshav diastolic nrog qhov hloov pauv ntawm tus nqi nruab nrab rau canagliflozin 100 mg thiab 300 mg -2.1 hli Hg thiab -2.5 mmHg feem, piv nrog cov placebo (-0.3 hli).
Tsis muaj kev hloov pauv hauv lub siab hloov pauv.
Beta cell ua haujlwm:
Kev tshawb fawb txog kev siv canagliflozin hauv cov neeg mob uas muaj ntshav qab zib hom 2 ntshav qab zib qhia txog kev txhim kho hauv beta cell ua haujlwm, raws li kev ntsuam xyuas tus qauv ntawm homeostasis hauv kev sib raug zoo nrog kev ua haujlwm ntawm cov hlwb no (HOMA2-% B) thiab kev txhim kho tus nqi ntawm insulin secretion siv thev kam rau kuaj nrog kev noj tshais.

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.

Sab sij huam

Cov ntaub ntawv hais txog kev phiv tshuaj pom thaum lub sijhawm kuaj mob1 ntawm canagliflozin nrog zaus ntawm ≥2% yog cov systematized txheeb ze rau txhua qhov ntawm cov khoom hauv nruab nrog raws li cov zaus uas tshwm sim siv cov kev faib tawm hauv qab no: ntau heev (/1 / 10), nquag (≥1 / 100,

Kev mob plab zom mov:
Nquag: cem quav, nqhis2, qhov ncauj qhuav.

Ua txhaum ntawm ob lub raum thiab lub plab:
Nquag: polyuria thiab pollakiuria3, peremptory tso zis, mob txeeb zig mob khaub thuas4, tso zis.

Ua txhaum ntawm lub qau thiab lub qog mammary:
Nquag: balanitis thiab balanoposthitis 5, vulvovaginal candidiasis 6, mob rau lub paum.

1 suav nrog kev kho mob monotherapy thiab ntxiv rau kev kho mob nrog metformin, metformin thiab sulfonylurea derivatives, zoo li metformin thiab pioglitazone.
2 Cov qeb “nqhis dej” suav txog lo lus “nqhis dej”, lo lus “polydipsia” kuj muaj nyob rau hom no.
3 Cov qeb "polyuria lossis pollakiuria" suav nrog cov lus "polyuria", cov lus hais "nce hauv cov zis ntim tawm" thiab "nocturia" tseem muaj nyob hauv pawg no.
Hom "mob txeeb zig" suav nrog lo lus "mob txeeb zig" thiab suav nrog lo lus "cystitis" thiab "mob raum".
Cov qeb "balanitis lossis balanoposthitis" suav nrog cov lus "balanitis" thiab "balanoposthitis", nrog rau cov lus "candida balanitis" thiab "mob rau ntawm lub cev los ntawm kev mob fungal".
6 Cov lus "vulvovaginal candidiasis" suav nrog cov lus "vulvovaginal candidiasis", "vulvovaginal fungal infection", "vulvovaginitis" thiab cov lus "vulvovaginal thiab genital fungal infection".
Lwm qhov kev tshwm sim tsis zoo uas tau tsim nyob rau hauv cov kev tshawb fawb placebo ntawm canagliflozin nrog cov zaus ntawm

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 lub cev ntuag ntshav qab zib, orthostatic hypotension, mob ntshav qis, lub cev qhuav dej thiab tsaus muag) tau raws li cov txiaj ntsig ntawm kev ntsuas dav dav, hauv cov neeg mob uas tau txais "diuretics", cov neeg mob uas tsis ua haujlwm raum (GFR los ntawm 30 txog 2) thiab cov neeg mob ≥75 lub hnub nyoog, qhov ntau dua ntawm qhov tshwm sim tsis zoo no tau sau tseg. Thaum ua qhov kev tshawb fawb txog cov kev pheej hmoo ntawm lub plawv, qhov ntau zaus ntawm cov kev tsis haum loj uas cuam tshuam nrog kev txo qis hauv cov ntim hauv lub cev tsis tau nce ntxiv nrog kev siv canagliflozin, cov xwm txheej ntawm kev tsis kho vim qhov kev txhim kho ntawm qhov tshwm sim tsis zoo ntawm hom no tau tshwm sim.

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

Thaum siv canagliflozin los ua qhov sib txuas rau kev kho mob nrog insulin lossis sulfonylurea derivatives, kev txhim kho hypoglycemia tau tshaj tawm ntau dua. Qhov no zoo ib yam nrog cov kev cia siab ntxiv hauv qhov tshwm sim ntawm kev mob ntshav qab zib nyob rau hauv rooj plaub thaum cov tshuaj, kev siv uas tsis nrog kev txhim kho ntawm tus mob no, tau ntxiv rau cov tshuaj insulin lossis tshuaj uas txhim kho nws txoj kev zais (piv txwv li, sulfonylurea derivatives).

Kev hloov pauv hauv tsev kho mob

Muaj cov poov xab poom tshuaj ntau ntxiv
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. Qee zaum, qhov kev tshaj tawm ntawm cov poov tshuaj poov tshuaj muaj ntau ntxiv hauv cov neeg mob uas lub raum lub raum ua tau mob hnyav, uas yav dhau los muaj kev noj tshuaj potassium ntau ntxiv thiab / lossis leej twg tau txais ntau cov tshuaj uas txo cov poov tshuaj ntau ntxiv (potassium-sparing diuretics thiab angiotensin-hloov enzyme inhibitors (ACE)). Nyob rau hauv dav dav, qhov nce hauv poov tshuaj concentration yog thaj tsam thiab tsis tas yuav tsum tau kho tshwj xeeb.

Ua kom muaj cov ntshiab si creatinine thiab urea ntau
Hauv thawj rau lub lis piam tom qab pib kho, muaj qhov nruab nrab me ntsis ntawm creatinine concentration (Qhov sib piv ntawm cov neeg mob uas muaj qhov tseem ceeb txo qis hauv GFR (> 30%) piv nrog qib pib pom nyob rau txhua ntu ntawm kev kho yog 2.0% - nrog kev siv canagliflozin hauv ib koob 100 mg, 4.1% thaum siv cov tshuaj ntawm koob tshuaj 300 mg thiab 2.1% thaum siv cov tshuaj 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 raug pom hauv cov neeg mob tsawg dua. rau cov neeg mob uas tsis tshua mob raum, qhov kev faib ua feem ntawm cov neeg mob uas muaj qhov GFR ntau dua qhov tseem ceeb (> 30%) piv nrog qib pib pom nyob rau txhua theem ntawm kev kho yog 9.3% - nrog kev siv canagliflozin ntawm koob tshuaj 100 mg, 12.2 % - thaum siv ntawm koob tshuaj 300 mg, thiab 4.9% - thaum siv cov placebo. Tom qab siv cov tshuaj canagliflozin, cov kev hloov no hauv qhov ntsuas tsis tau zoo rau qhov hloov los yog rov qab mus rau lawv qib qub.

Nce tsawg kawg Lipoprotein (LDL)
Kev txhaj tshuaj tiv thaiv kab mob nce siab hauv LDL ntau tau pom nrog canagliflozin. Qhov nruab nrab ntawm kev hloov pauv hauv LDL raws li feem pua ​​ntawm kev pib tsom nrog 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 Cov. Qhov nruab nrab thaum pib qhov LDL siab yog 2.76 mmol / L, 2.70 mmol / L thiab 2.83 mmol / L nrog canagliflozin ntawm koob tshuaj 100 thiab 300 mg thiab placebo, feem.

Muaj kev hemoglobin ntau ntxiv
Thaum siv canagliflozin hauv koob tshuaj 100 mg thiab 300 mg, nce me ntsis ntawm qhov nruab nrab feem ntau pauv hauv hemoglobin concentration los ntawm theem pib (3.5% thiab 3.8%, feem) tau pom sib piv nrog qhov txo qis me ntsis hauv cov pawg placebo (−1.1%). 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. Feem ntau ntawm cov neeg mob tau qhia tias muaj kev nce siab ntawm hemoglobin concentration (> 20 g / l), uas tau tshwm sim hauv 6.0% ntawm cov neeg mob tau txais canagliflozin ntawm koob tshuaj 100 mg, hauv 5.5% ntawm cov neeg mob tau txais canagliflozin ntawm koob tshuaj 300 mg, thiab hauv 1, 0% ntawm cov neeg mob tau txais cov placebo. Feem ntau cov nuj nqis tseem nyob hauv kev txwv.

Txo cov ntshav uric acid ua kom tsawg
Nrog rau kev siv canagliflozin 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 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 canagliflozin pawg yog qhov feem ntau lossis ze rau qhov siab kawg ntawm lub lim tiam 6 thiab pheej mob thoob plaws hauv kev kho. 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.

Kev sib txuam

Kev sib txuam tshuaj (hauv cov ntaub ntawv hauv vitro)

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 cytochrome P450 isoenzymes (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 P450 cytochrome system tsis zoo li.

Cov nyhuv ntawm lwm cov tshuaj ntawm canagliflozin

Cov ntaub ntawv soj ntsuam qhia tau hais tias qhov kev pheej hmoo ntawm kev cuam tshuam loj nrog cov tshuaj concomitant muaj tsawg.

Cov tshuaj uas txhib tau cov enzymes ntawm UDF-glucuronyl transferase (UGT) tsev neeg thiab cov tshuaj muaj yees

Kev siv tib lub sijhawm nrog rifampicin, tus xaiv tsis yog qhov sib txuam ntawm ntau tus enzymes ntawm UGT tsev neeg thiab cov neeg nqa tshuaj, suav nrog UGT1A9, UGT2B4, P-gp, thiab MRP2 txo qis kis rau ntawm canagliflozin. Kev txo qis raug rau canagliflozin tuaj yeem ua rau txo qis ntawm nws cov hauj lwm zoo. Yog tias nws yog qhov yuav tsum tau muab lub zog tsim ntawm UGT tsev neeg enzymes thiab cov tshuaj nqa tshuaj (piv txwv, rifampicin, phenytoin, phenobarbital, ritonavir) ib txhij nrog canagliflozin, nws yog qhov yuav tsum tau los tswj kev ua kom haum ntawm glycated hemoglobin НbА1c hauv cov neeg mob uas tau txais canagliflozin hauv ib koob tshuaj / ntau hnub canagliflozin txog 300 mg 1 zaug / hnub, yog tias yuav tsum tau tswj glycemic ntxiv.

Cov tshuaj uas thim cov enzymes ntawm tsev neeg ntawm UDF-glucuronyl transferases (UGT) thiab cov tshuaj muaj yees

Probenecid: Kev siv sib xyaw ua ke ntawm canagliflozin nrog probenecid, uas tsis yog xaiv cov tshuaj tiv thaiv ntawm ntau yam UGT tsev neeg enzymes thiab cov tshuaj nqa tshuaj, suav nrog UGT1A9 thiab MRP2, tsis muaj kev cuam tshuam loj hauv kev kho mob ntawm pharmacokinetics ntawm canagliflozin. Txij li thaum canagliflozin yog glucuronidated los ntawm ob qhov txawv enzymes ntawm UGT tsev neeg, thiab glucuronidation yog tus cwj pwm los ntawm kev ua haujlwm siab / tsis tshua muaj txiaj ntsig, txoj kev loj hlob ntawm qhov kev cuam tshuam loj hauv kev kho mob ntawm lwm cov tshuaj ntawm pharmacokinetics ntawm canagliflosin los ntawm glucuronidation tsis zoo li.

Cyclosporine: Kev sib txuam tseem ceeb ntawm cov khw muag tshuaj sib txuam nrog kev siv canagliflozin sib xyaw nrog cyclosporine, ib qho inhibitor ntawm P-glycoprotein (P-gp), CYP3A thiab ntau lub chaw muag tshuaj, suav nrog MRP2 tsis pom. Kev txhim kho ntawm qhov tsis raug, tsis hloov "kub tshwm" yog sau tseg nrog kev siv canagliflozin thiab cyclosporine tib lub sijhawm. Tsis pom zoo kev hloov tshuaj ntawm canagliflozin tsis pom zoo. Tsis muaj kev cuam tshuam cov tshuaj tseem ceeb nrog lwm P-gp inhibitors yog qhov cia siab.

Yuav ua li cas coj, chav kawm ntawm kev tswj hwm thiab ntau npaum li cas

Canagliflozin raug pom zoo kom noj qhov ncauj ib hnub ib zaug, nyiam dua ua ntej noj tshais.

Cov neeg laus (≥18 xyoo)
Qhov pom zoo koob tshuaj canagliflozin yog 100 mg lossis 300 mg ib hnub ib zaug, nyiam dua noj ua ntej noj tshais.
Thaum siv canagliflozin los ua ib qho txuas rau kev kho tshuaj insulin lossis los ntawm kev txhim kho nws txoj kev zais cia (piv txwv li, sulfonylurea derivatives), kev noj tshuaj qis dua cov tshuaj saum toj no tuaj yeem suav tias yog txo qis kev pheej hmoo ntawm hypoglycemia.
Canagliflozin muaj cov nyhuv diuretic. Cov neeg mob kho nrog diuretics, cov neeg mob uas lub raum lub raum tsis ua haujlwm ntawm kev mob hnyav nrog lub ntsej muag glomerular limtiam (GFR) ntawm 30 txog 2, lossis cov neeg mob hnub nyoog showed75 xyoo, tau pom ntau dua kev loj hlob ntawm cov kev tsis zoo cuam tshuam nrog kev txo qis hauv lub ntim hauv lub hlwb (piv txwv li, tom qab zoo li kiv taub hau orthostatic hypotension lossis arterial hypotension). Yog li, hauv cov neeg mob no, kev siv canagliflozin hauv thawj koob ntawm 100 mg ib hnub ib zaug yog kev pom zoo. Hauv cov neeg mob uas muaj cov hypovolemia, nws raug pom zoo tias cov xwm txheej no yuav tau kho ua ntej kev kho mob nrog canagliflozin. Hauv cov neeg mob uas tau txais canagliflozin ntawm ib koob ntawm 100 mg nrog kev thev taus zoo, uas xav tau kev tswj hwm glycemic ntxiv, nws raug nquahu kom nce lub koob tshuaj mus rau 300 mg.

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 Neeg Mob Tshwj Xeeb Pawg

Cov menyuam yaus hnub nyoog 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 xyoos uas muaj hnub nyoog yuav tsum tau txhaj 100 mg ib hnub ib zaug raws li thawj qhov tshuaj pib. Nrog kev txhaj tshuaj zoo rau ntawm 100 mg, nws raug nquahu rau cov neeg mob uas xav tau kev tswj glycemic ntxiv kom nce qhov koob tshuaj mus rau 300 mg.

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 2), tsis tas yuav tau kho kom haum.
Hauv cov neeg mob uas lub raum lub raum tsis ua haujlwm ntawm kev mob hnyav, kev siv cov tshuaj hauv qhov pib ntawm 100 mg ib zaug ib hnub yog pom zoo. Nrog kev txhaj tshuaj zoo rau ntawm 100 mg, nws raug nquahu rau cov neeg mob uas xav tau kev tswj glycemic ntxiv kom nce qhov koob tshuaj mus rau 300 mg.
Kanagliflozin tsis pom zoo rau cov neeg mob uas lub raum tsis zoo (GFR 2), kev mob raum tsis ua haujlwm (CRF), lossis cov neeg mob qog ntshav, vim tias canagliflozin cia siab tias tsis muaj txiaj ntsig hauv cov neeg mob no.

Dosage daim ntawv

100 mg thiab 300 mg zaj duab xis-ntsiav tshuaj

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

102 mg ntawm canagliflozin hemihydrate yog sib npaug rau 100 mg ntawm canagliflozin.

Excipients (tub ntxhais): microcrystalline cellulose, anhydrous lactose, croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate.

Excipients (plhaub): Opadry II 85F92209 daj: polyvinyl cawv, ib nrab hydrolyzed, titanium dioxide (E171), macrogol / polyethylene glycol 3350, talc, hlau oxide daj (E172).

Hauv ib qho 300 mg zaj duab xis-ntsiav tshuaj muaj:

306 mg ntawm canagliflozin hemihydrate yog sib npaug rau 300 mg ntawm canagliflozin.

Excipients (tub ntxhais): microcrystalline lactose anhydrous cellulose, croscarmellose sodium, hydroxypropyl cellulose, magnesium stearate.

Excipients (plhaub): Opadry II 85F18422 dawb: cawv

polyvinyl, qee cov hydrolyzed, titanium dioxide (E171), macrogol / polyethylene glycol 3350, talc.

Rau qhov ntau npaum ntawm 100 mg: ntsiav tshuaj, zaj duab xis-coated xim daj, tshuaj ntsiav zoo li tus duab, engraved nrog "CFZ" ntawm ib sab thiab "100" ntawm lwm yam.

Rau qhov ntau npaum ntawm 300 mg: zaj duab xis-ntsiav tshuaj los ntawm dawb mus rau yuav luag dawb, tshuaj ntsiav zoo li tus, txho nrog "CFZ" ntawm ib sab thiab "300" ntawm lwm yam.

Cov chaw muag tshuaj

Cov Tshuaj Pharmacokinetics

Cov kws kho mob ntawm canagliflozin hauv cov neeg muaj kev noj qab haus huv zoo ib yam li cov pharmacokinetics ntawm canagliflozin hauv cov neeg mob ntshav qab zib hom 2. Tom qab kev noj tshuaj ib qhov ncauj ntawm 100 mg thiab 300 mg los ntawm cov neeg ua haujlwm noj qab haus huv, canagliflozin nrawm nrawm, qhov siab tshaj plaws ntshav ntshav (nruab nrab Tmax) tau tiav 1-2 teev tom qab koob tshuaj. cov tshuaj. Qhov ntshav siab tshaj plaws ntawm Cmax thiab AUC ntawm canagliflozin ntau ntxiv nrog kev siv cov koob tshuaj ntawm 50 mg rau 300 mg. Pom meej kawg ib nrab-lub neej (t1 / 2) (qhia raws li iation qauv kev sib txawv) yog 10.6 ± 2.13 teev thiab 13.1 ± 3.28 teev thaum siv tshuaj 100 mg thiab 300 mg, ntsig txog. Qhov sib luag siab zoo tau ncav cuag 4-5 hnub tom qab pib txoj kev kho canagliflozin ntawm koob tshuaj 100-300 mg ib hnub ib zaug.

Lub pharmacokinetics ntawm canagliflozin tsis nyob ntawm lub sijhawm. Kev sib txuam ntawm cov tshuaj hauv plasma ncav cuag 36% tom qab kev rov ua dua.

Xuas

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, ua tib zoo xav txog kev muaj peev xwm ntawm canagliflozin los txo cov kev hloov pauv hauv postprandial glycemia vim tias kev qeeb ntawm kev nqus ntawm cov piam thaj hauv txoj hnyuv, nws raug nquahu kom noj canagliflozin ua ntej noj mov thawj zaug.

Kev xa Khoom

Qhov nruab nrab siab tshaj plaws ntawm canagliflozin hauv kev sib npaug tom qab ib leeg ntawm cov leeg ntshav ntawm cov tib neeg noj qab haus huv yog 119 l, uas qhia tau hais tias muaj kev faib tawm ntau hauv cov ntaub so ntswg. Canagliflosin lom zem ntau cuam tshuam nrog cov protein plasma (99%), feem ntau yog nrog albumin. Kev cog lus tiv thaiv protein yog ywj siab ntawm ntshav concentration ntawm canagliflozin. Plasma protein khi tsis hloov pauv ntau hauv cov neeg mob raum lossis mob rau daim siab.

Kev zom zaub mov

Txoj hauv kev tseem ceeb ntawm metabolic excretion ntawm canagliflozin yog O-glucuronidation, uas tau ua los ntawm UGT1A9 thiab UGT2B4 ntau rau ob qho tsis muaj zog O-glucuronide metabolites. Cov metabolism hauv ntawm canagliflozin sib kho los ntawm CYP3A4 (oxidative metabolism) hauv tib neeg yog qhov tsis lees paub (kwv yees li 7%).

Hauv kev tshawb fawb hauvvitro canagliflozin tsis tiv thaiv qhov kev tawm tsam ntawm cytochrome P450 system CYP1A2, CYP2A6, CYP2C19, CYP2D6 lossis CYP2E1, CYP2B6, CYP2C8, CYP2C9 thiab tsis paub CYP1A2, CYP2 Clinically tseem ceeb ua rau lub siab ntawm CYP3A4 hauvvivo tsis tau pom (saib Tshooj "Kev sib tshuam tshuaj").

Chaw Sau Ntawv

Tom qab ib qho kev tswj hwm ntawm qhov ncauj ntawm 14C canagliflozin hauv cov neeg tuaj yeem noj qab haus huv, 41.5%. 7.0% thiab 3.2% ntawm cov koob tshuaj uas lees txais tau raug tso nrog quav hauv daim ntawv canagliflozin, hydroxylated metabolite thiab O-glucuronide metabolite, feem. Enterohepatic recirculation ntawm canagliflozin yog qhov tsis lees paub.

Kwv yees li 33% feem pua ​​ntawm cov tshuaj kua hluav taws xob tau lees tawm hauv cov zis, feem ntau yog siv O-glucuronide metabolites (30.5%). Tsawg dua li 1% ntawm kev noj tshuaj tau muab tshem tawm uas tsis pauv li canagliflozin hauv cov zis. Lub raum tshem tawm ntawm canagliflozin thaum siv nyob rau hauv koob tshuaj 100 mg thiab 300 mg thaj tsam li ntawm 1.30 ml / min txog 1.55 ml / min.

Canagliflozin yog ib qho khoom siv nrog kev tshem tawm tsawg tsawg, thaum nruab nrab qhov nruab nrab ntawm kev tshem tawm hauv cov neeg tuaj yeem noj qab haus huv tom qab kev tso dej tawm yog li 192 ml / min.

Cov pab pawg neeg tshwj xeeb

Cov neeg mob uas lub raum tsis ua hauj lwm zoo

Hauv kev qhib ib qho kev tshawb nrhiav ib zaug, cov pharmacokinetics ntawm canagliflozin tau kawm thaum thov ntawm 200 koob tshuaj rau cov neeg mob uas lub raum tsis ua haujlwm ntawm qhov sib txawv (raws li kev faib tawm raws qib ntawm kev tsim cov tshuaj tawm tswv yim los ntawm cov mis Cockcroft-Gault) piv nrog cov neeg noj qab haus huv. Txoj kev tshawb no koom nrog 8 cov neeg mob uas lub raum lub cev rov ua haujlwm (creatinine tshem tawm ≥ 80 ml / min), 8 tus neeg mob raum tsis ua haujlwm me me (creatinine tshem tawm 50 ml / min -10% thiab ≤12%

Hauv kev tshawb nrhiav nrog cov neeg mob uas muaj qhov theem qis HbA1c> 10% thiab ≤ 12% thaum siv canagliflozin raws li kev kho mob monotherapy, qhov txo qis hauv HbA1c qhov tseem ceeb piv rau lub hauv paus (tsis muaj kev kho cov placebo) los ntawm -2.13% thiab -2.56% rau canagliflozin hauv koob tshuaj ntawm 100 mg thiab 300 mg, ntsig txog.

Lub Koom Haum European rau Kev Tshuaj Ntsuam Xyuas Qhov Zoo ntawm Cov Tshuaj tso cai muaj txoj cai tsis muab cov txiaj ntsig ntawm kev tshawb fawb ntawm cov tshuaj Invocana® nyob rau txhua pawg neeg ntawm cov menyuam yaus uas muaj ntshav qab zib hom 2 (cov ntaub ntawv hais txog kev siv hauv cov menyuam yaus raug nthuav tawm hauv nqe "Txoj Kev Siv thiab Koob Tshuaj").

Kev ntsuas rau siv

Txhim kho glycemic tswj hauv kev kho mob hom 2 mob ntshav qab zib rau cov neeg mob laus:

- rau cov kev noj haus uas tsis zoo thiab kev tawm dag zog lub cev tsis muab glycemic tswj tau txaus thiab kev siv cov metformin yog suav tias yog qhov tsis tsim nyog lossis cuam tshuam.

- raws li ib qho khoom siv ntxiv nrog rau lwm cov tshuaj ua kom ntshav qab zib, nrog rau cov insulin, thaum lawv, ua ke nrog kev noj zaub mov zoo thiab ua haujlwm lub cev, tsis muaj kev tswj glycemic txaus.

Tsuas tshuaj thiab tswj hwm

Invocana® yuav tsum noj qhov ncauj ib hnub ib zaug, nyiam dua ua ntej noj mov thawj zaug.

Cov neeg muaj hnub nyoog (≥ 18 xyoo)

Qhov pom zoo kom pib koob Invocan® yog 100 mg ib hnub ib zaug. Cov neeg mob uas zam 100 mg ntawm cov tshuaj zoo ib hnub ib zaug rau tus neeg uas kwv yees tus nqi glomerular pom (rSCF) ≥ 60 ml / min. / 1.73 m2 lossis creatinine tshem tawm (CrCl) ≥ 60 ml / min., Thiab leej twg xav tau kev nruj dua ntshav qabzib tswj, koob tshuaj yuav raug nce ntxiv rau 300 mg ib hnub ib zaug (saib hauv tshooj "Cov lus qhia tshwj xeeb").

Nws yog ib qho tsim nyog yuav tau soj ntsuam qhov nce ntxiv ntawm cov tshuaj rau cov neeg mob hnub nyoog ≥ 75 xyoo, cov neeg mob uas muaj kab mob ntawm cov hlab plawv, lossis lwm tus neeg mob rau tus neeg mob thawj zaug mob los ntawm kev noj Invokana® yog qhov muaj pheej hmoo (saib ntu "Cov Lus Qhia Tshwj Xeeb"). Rau cov neeg mob uas lub cev qhuav dej, pom zoo kom kho tus mob no ua ntej noj tshuaj Invokana® (saib nqe lus "Cov lus qhia tshwj xeeb").

Thaum siv cov tshuaj Invokana® los ua cov tshuaj rau cov tshuaj insulin lossis cov tshuaj tiv thaiv cov tshuaj tiv thaiv kab mob (piv txwv li, sulfonylurea kev npaj), txhawm rau txo kev pheej hmoo ntawm hypoglycemia, kev siv tshuaj qis ntawm cov tshuaj saum toj no yuav raug txiav txim siab (saib ntu "Kev Sib Cuam Tshuam Tshuaj" thiab "Cov Kev Phom Ntawm Sab") Cov.

Cov neeg laus cov neeg mob ≥ 65 xyoo

Kev ua haujlwm hauv lub raum thiab qhov kev pheej hmoo ntawm lub cev qhuav dej yuav tsum tau suav rau hauv (saib "Cov Lus Qhia Tshwj Xeeb").

Cov neeg mob raum tsis ua haujlwm

Rau cov neeg mob eGFR ntawm 60 ml / min / 1.73 m2 txog 30%) txhua lub sijhawm thaum kho yog 9.3%, 12.2% thiab 4.9% ntawm cov uas noj 100 mg, 300 mg canagliflozin thiab cov placebo, ntsig txog. Thaum kawg ntawm txoj kev tshawb no, qhov kev txo qis hauv tus nqi no tau pom nyob hauv 3.0% ntawm cov neeg mob uas tau noj 100 mg ntawm canagliflozin, 4.0% ntawm cov uas noj 300 mg, thiab 3.3% ntawm cov placebo (saib Ntu "Cov Lus Qhia Tshwj Xeeb").

Cov tshuaj sib cuam tshuam

Canagliflozin tuaj yeem txhim kho cov nyhuv ntawm diuretics, zoo li ua rau muaj kev pheej hmoo ntawm lub cev qhuav dej thiab mob hypotension (saib ntu "Cov lus qhia tshwj xeeb").

Kev tsim cov tshuaj insulin thiab insulin secretion

Kev tsim tshuaj insulin thiab tshuaj insulin secretion, xws li sulfonylureas, tuaj yeem ua rau mob ntshav qab zib tsawg.

Yog li, txhawm rau txo cov ntshav qog ntshav qab zib, nws yog ib qho tsim nyog yuav tau txo qhov koob tshuaj insulin lossis kev txhawb zog ntawm insulin secretion thaum siv ua ke nrog canagliflozin (saib ntu "Dosage thiab Administration" thiab "Side Effects").

Cov nyhuv ntawm lwm cov tshuaj ntawm canagliflozin

Kev zom zaub mov ntawm canagliflozin yog feem ntau vim yog kev sib txuas nrog glucuronides, kev sib kho los ntawm UDP-glucuronyl transferase 1A9 (UGT1A9) thiab 2B4 (UGT2B4). Canagliflozin yog nqa los ntawm P-glycoprotein (P-gp) thiab cov protein tiv thaiv mob cancer mis (BCRP).

Enzyme inducers (xws li St. John lub wort Hypericum perforatum, rifampicin, barbiturates, phenytoin, carbamazepine, ritonavir, efavirenz) tuaj yeem txo cov kev cuam tshuam ntawm canagliflozin. Tom qab tib lub sijhawm siv canagliflozin thiab rifampicin (ib qho inducer ntawm ntau cov neeg thauj khoom nquag thiab cov enzymes koom nrog tshuaj metabolism), qhov txo qis ntawm cov kab ke ntawm canagliflozin los ntawm 51% thiab 28% (thaj chaw nkhaus, AUC) thiab qhov siab tshaj (concentration) (Cmax). Xws li ib qho kev txo qis tuaj yeem ua rau txo qis ntawm qhov txiaj ntsig ntawm canagliflozin.

Yog tias nws yog ib qho tsim nyog yuav tsum tau siv ib lub inducer ntawm cov UDP enzymes thiab thauj cov protein thiab canagliflozin, nws yog qhov tsim nyog los tswj qib qabzib kom soj ntsuam cov lus teb rau canagliflozin. Yog tias nws yuav tsum tau siv qhov inducer ntawm cov UDF enzymes ua ke nrog canagliflozin, qhov koob tshuaj tau nce rau 300 mg ib hnub ib zaug, yog tias muaj kev zam zoo los ntawm cov neeg mob 100 mg ntawm canagliflozin ib zaug ib hnub, lawv tus nqi rSCF yog ≥ 60 ml / min. / 1,73 m2 los yog CrCl ≥ 60 ml / min., thiab lawv xav tau kev tswj ntxiv ntawm cov piam thaj hauv ntshav. Rau cov neeg mob uas muaj eGFR ntawm 45 ml / min / 1.73 m2 lossis tsawg dua 60 ml / min / 1.73 m2 lossis CrCl ntawm 45 ml / min. thiab tsawg dua 60 ml / min., thiab uas siv 100 mg ntawm canagliflozin, thiab tseem yauv ua kev kho mob nrog UDF-enzyme stimulator, thiab leej twg xav tau tswj ntshav qabzib ntxiv, lwm hom kev kho yuav tsum raug txiav txim siab kom txo cov ntshav qabzib (saib ntu "Dosage thiab administration" thiab "Cov lus qhia tshwj xeeb").

Cholestyramine tuaj yeem txo qis qis canagliflozin ntau. Canagliflozin yuav tsum noj tsawg kawg ib teev ua ntej lossis 4-6 teev tom qab siv cov kua tsib tsib ntu ua kom tsawg li qhov cuam tshuam ntawm lawv qhov kev nqus.

Kev tshawb fawb los ntawm kev sib piv tau qhia tias metformin, hydrochlorothiazide, tshuaj tiv thaiv qhov ncauj (ethinyl estradiol thiab levonorgestrol), cyclosporine thiab / lossis probenecid tsis cuam tshuam rau pharmacokinetics ntawm canagliflozin.

Cov nyhuv ntawm canagliflozin ntawm lwm cov tshuaj

Digoxin: kev siv tib lub sijhawm ntawm canagliflozin ntawm koob tshuaj 300 mg ib zaug ib hnub rau 7 hnub nrog ib daim ntawv thov ntawm 0.5 mg ntawm digoxin ua raws li kev noj tshuaj ntawm 0.25 mg ib hnub rau 6 hnub ua rau muaj kev nce ntxiv hauv AUC ntawm digoxin los ntawm 20% thiab nce Cmax 36%, tej zaum vim yog kev tiv thaiv ntawm P-gp. Canagliflozin tau pom tias inhibit P-gp hauv vitro. Cov neeg mob noj digoxin thiab lwm yam kev mob plawv glycosides (piv txwv li, digitoxin) yuav tsum tau kuaj xyuas kom haum.

Dabigatran: Kev siv ua ke ntawm canagliflozin (qhov tsis muaj zog P-gp inhibitor) thiab dabigatran etexilate (P-gp substrate) tsis tau kawm. Txij li thaum lub siab ntawm dabigatran tuaj yeem nce hauv muaj cov canagliflozin, nrog rau kev siv ua keigatran thiab canagliflozin tib lub sijhawm, nws yog ib qhov tsim nyog los soj ntsuam tus neeg mob (kom tshem tawm cov cim los ntshav lossis ntshav liab).

Simvastatin: kev sib xyaw ua ke ntawm 300 mg ntawm canagliflozin ib zaug ib hnub rau 6 hnub thiab ib daim ntawv thov ntawm 40 mg ntawm simvastatin (substrate CYP3A4) ua rau muaj kev nce ntxiv hauv AUC ntawm simvastatin los ntawm 12% thiab nce Cmax li ntawm 9%, thiab ntxiv rau AUC ntawm simvastatin acid los ntawm 18% thiab nce ntxiv Cmax ntawm simvastatinic acid ntawm 26%. Xws li nce hauv simvastatin thiab simvastatin acid ntau tsis suav hais tias yog kev kho mob tseem ceeb.

Kev txwv tsis pub muaj cov kab mob qog mis tiv thaiv kab mob cancer mis (BCRP) nyob rau hauv kev cuam tshuam ntawm canagliflozin nyob rau hauv txoj hnyuv tsis tuaj yeem tswj tau, thiab yog li nws muaj peev xwm nce qhov kev nce siab ntawm cov tshuaj thauj los ntawm BCRP, piv txwv li, qee yam statins, xws li rosuvastatin thiab qee cov tshuaj anticancer.

Hauv kev kawm txog kev sib cuam tshuam ntawm canagliflozin hauv kev muaj peev xwm sib npaug, tsis muaj kev cuam tshuam los ntawm lub chaw muag tshuaj ntawm metformin, tshuaj tiv thaiv qhov ncauj (ethinyl estradiol thiab levonorgestrol), glibenclamide, paracetamol, hydrochlorothiazide thiab warfarin.

Kev sib cuam tshuam rau yeeb tshuaj / cuam tshuam rau kev sim tau

Kev suav ntawm 1,5-AG

Kev nce ntxiv tso zis tawm thaum siv canagliflozin tuaj yeem ua rau kev tsim cov qib tsis txaus ntseeg ntawm 1,5-anhydroglucite (1,5-AH), vim qhov kev tshawb nrhiav 1,5-AH poob lawv qhov kev cia siab rau kev soj ntsuam kev tswj glycemic. Hauv qhov no, qhov kev txiav txim siab ntau ntau ntawm 1,5-AH yuav tsum tsis txhob siv los ua qauv rau kev ntsuas ntsuas glycemia tswj nyob rau hauv cov neeg mob tau txais Invokana®. Yog xav paub cov ntaub ntawv ntxaws ntxiv, nws raug nquahu kom tiv toj cov tuam ntxhab ntawm cov tshuab ntsuas kom paub txiav txim 1,5-AH.

Cov lus qhia tshwj xeeb

Kev siv cov canagliflozin tsis tau kawm txog cov neeg mob ntshav qab zib hom 1, yog li ntawd nws tsis pom zoo kom sau ntawv rau nws hauv cov neeg mob no.

Cov tshuaj tsis tuaj yeem siv los kho tus kab mob ntshav qab zib ketoacidosis, vim tias kev kho mob zoo li no yuav tsis muaj txiaj ntsig hauv cov kev mob no.

Siv rau hauv cov neeg mob uas lub raum tsis ua haujlwm

Cov hauj lwm zoo ntawm canagliflozin nyob ntawm lub raum muaj nuj nqi, thiab qhov kev ua tau raug txo qis hauv cov neeg mob uas mob raum tsis txaus thiab feem ntau tsis yog nyob rau hauv cov neeg mob uas mob raum tsis ua haujlwm loj (saib Ntu "Kev Noj Tshuaj thiab Txoj Cai Tswj Xyuas").

Hauv cov neeg mob uas tau laij glomerular ntawm tus nqi 30%), tab sis tom qab ntawd, eGFR ntau zog thiab kev tshem tawm canniflosin ib ntus yog tseev kom muaj tsawg zaus (saib ntu "Phiv")

Cov neeg mob yuav tsum paub zoo txog cov tsos mob ntawm lub cev qhuav dej. Canagliflozin tsis pom zoo rau cov neeg mob siv cov diuretics (saib ntu "Kev Sib Cuam Tshuam Hauv Tshuaj"), lossis kev txom nyem los ntawm lub cev qhuav dej, piv txwv li, muaj feem rau mob hnyav (xws li mob plab hnyuv).

Kev siv cov canagliflozin tsis pom zoo rau cov neeg mob uas tau txais lub voj diuretics (saib ntu "Kev Sib Cuam Tshuam Tshuaj") lossis hauv cov neeg muaj lub cev qhuav dej, piv txwv li, muaj kev sib txuas nrog cov mob hnyav (piv txwv li lub plab zom mov).

Rau cov neeg mob noj tshuaj Invokana®, thaum lub sijhawm sib cuam tshuam uas tuaj yeem ua rau lub cev qhuav dej (piv txwv li, cov kab mob ntawm lub plab zom mov), nws yuav tsum ua tib zoo saib xyuas qhov ntsuas ntawm lub cev qhuav dej (piv txwv li kev kuaj mob lub cev, tswj ntshav siab, kuaj ntshav, suav nrog kev ntsuam xyuas ntawm lub raum kev ua haujlwm) thiab ntsuas cov qib electrolyte. Hauv cov neeg mob uas muaj lub cev qhuav dej thaum kho nrog Invocana®, yuav tsum muaj kev txiav txim siab ua ntu zus mus rau Invocana® kom txog thaum tus mob rov zoo li qub. Yog tias tshem tawm cov tshuaj, nws raug nquahu kom kuaj xyuas cov piam thaj kom ntau.

Hauv cov kev tshawb fawb soj ntsuam thiab tom qab kev lag luam hauv cov neeg mob noj SGLT2 inhibitors, suav nrog canagliflozin, qee qhov xwm txheej tsawg kawg ntawm kev txhim kho mob ntshav qab zib ketoacidosis (DKA), suav nrog cov xwm txheej ntawm txoj sia taus DKA, tau tshaj tawm. Hauv ntau qhov teeb meem, cov mob atypical tau piav qhia, nrog cov ntshav nce ntxiv hauv cov ntshav tsis dhau 14 mmol / L (250 mg dl). Qhov tshwm sim ntawm DKA nrog kev txhaj tshuaj ntau dua ntawm canagliflozin tseem tsis tau paub.

Txoj kev pheej hmoo ntawm kev tsim muaj cov kab mob ntshav qab zib ketoacidosis yuav tsum tau txiav txim siab yog qhov tsis zoo tshwj xeeb xws li xeev ntuav, ntuav, tsis nco qab, mob plab, nqhis dej, ua pa nyuaj, tsis meej pem, nkees nkees lossis tsaug zog. Yog tias cov tsos mob no tshwm sim, cov neeg mob yuav tsum tau kuaj tam sim ntawd rau ketoacidosis, tsis hais txog qib ntawm cov piam thaj hauv cov ntshav.

Yog tias muaj kev xoom xaim ntawm kev txhim kho ntawm DKA, nrog rau thaum muaj nws daim ntawv pov thawj, cov neeg mob yuav tsum tso tseg kev kho sai nrog Invocana®.

Txoj kev kho yuav tsum tau muab ncua ib ntus hauv cov neeg mob pw hauv tsev kho mob loj rau kev phais lossis exacerbation ntawm cov kab mob loj. Hauv ob qho xwm txheej no, tom qab tus neeg mob lub chaw nyob khov kho, kev kho nrog Invocana® tuaj yeem rov pib dua.

Ua ntej pib kho nrog Invocana®, txhua yam tau sau tseg hauv tus neeg mob keeb kwm uas tuaj yeem ua rau ketoacidosis yuav tsum xav txog.

Tej yam no suav nrog:

Pl Tso tawm cov beta-cell tshwj xeeb (piv txwv li, cov neeg mob ntshav qab zib hom 2 uas muaj C-peptide tsawg lossis ua rau cov ntshav muaj ntshav qab zib tsis txaus rau cov neeg laus (LADA) lossis cov neeg mob uas muaj keeb kwm ua kab mob pancreatitis)

Conditions kev txwv cov zaub mov lossis lub cev qhuav dej tsis txaus

Cov neeg mob uas tau txo qis koob tshuaj insulin

Cov neeg mob uas pom tias muaj cov tshuaj insulin nce ntxiv vim kev loj hlob ntawm tus mob pathology, phais mob lossis haus dej cawv

Kev ceev faj yog qhia kom sau ntawv cia SGLT2 inhibitors hauv cov neeg mob no.

Nws tsis pom zoo kom rov pib kho nrog SGLT2 inhibitor thaum muaj kev txhim kho yav dhau los ntawm DKA nrog kev siv SGLT2 inhibitors kom txog rau thaum kev txheeb xyuas thiab tshem tawm txhua qhov tshwm sim pom tseeb.

Kev nyab xeeb thiab ua haujlwm ntawm canagliflozin hauv cov neeg mob ntshav qab zib hom 1 tseem tsis tau tsim thiab kev siv cov tshuaj Invokana® hauv cov neeg mob ntshav qab zib hom 1 tsis pom zoo. Cov ntaub ntawv txhaj tshuaj tsawg tsawg qhia tias DKA muaj feem ntau txhim kho hauv cov neeg mob ntshav qab zib hom 1 uas tab tom noj SGLT2 inhibitors.

Thaum siv canagliflozin, ib qho kev nce ntxiv ntawm hematocrit tau saib (saib ntu "Cov Kev Phiv"), yog li ntawd, hauv cov neeg mob uas twb muaj ntshav ntau lawm, yuav tsum ceev faj.

Cov Neeg Laus (≥ 65 xyoo)

Cov neeg laus yuav yog ib qho teeb meem ntawm lub cev qhuav dej ntau dua, lawv feem ntau yuav tau txais diuretics, thiab lawv muaj feem ntau ua rau lub raum tsis ua haujlwm. Hauv cov neeg mob ≥ 75 xyoo, siv cov canagliflozin ntau tshaj tawm cov kev phiv tsis zoo uas cuam tshuam nrog lub cev qhuav dej (piv txwv li, dias postural, orthostatic hypotension, hypotension). Tsis tas li ntawd, nyob rau hauv cov neeg mob zoo li no, qhov tseem ceeb tshaj qhov txo qis hauv eGFR tau qhia (saib tshooj "Dosage and Administration" thiab "Side Effects").

Cov kab mob pwm ntawm tus qau

Vim yog lub tshuab ntawm kev txiav txim siab ntawm canagliflozin sib kho los ntawm sodium-dependant cotransporter ntawm cov piam thaj 2 (SGLT2), kev txwv tsis pub muaj cov kabmob siab B ntau ntau hauv kev sim tshuaj siv canagliflozin tau tshaj tawm rau cov poj niam nrog vulvovaginal candidiasis thiab balanitis lossis balanoposthitis rau cov txiv neej (saib ntu "Cov Kev Mob tshwm sim") ) Tus txiv neej thiab poj niam uas muaj keeb kwm kis mob fungal ntawm lub chaw mos chaw ntau yog tus muaj tus kab mob. Balanitis lossis balanoposthitis tau tsom xam feem ntau ntawm cov txiv neej uas tsis yauv ua kevcai txiav. Tsawg tsawg zaus, cov tsos ntawm phimosis tau qhia tawm thiab kev zam ntawm lub ntsej muag yog qee zaum tau ua. Cov neeg mob feem ntau muaj mob ua npaws ntawm lub chaw mos tau txais cov tshuaj tua kab mob hauv zos raws li cov kws kho mob tau siv lossis siv lawv tus kheej yam tsis tau txiav cov tshuaj Invokana®.

Cov kev paub ntawm kev siv cov tshuaj hauv cov neeg muaj hoob III lub plawv tsis ua haujlwm raws li kev faib tawm ntawm New York Lub Plawv Koom Tes (NYHA) muaj tsawg, thiab kev tshawb fawb soj ntsuam ntawm canagliflozin hauv NYHA chav IV lub plawv tsis tau ua.

Mob Lub Hlaus

Hauv kev sib txuas nrog cov txheej txheem ntawm kev ua ntawm canagliflozin, hauv cov neeg mob noj cov tshuaj Invokana®, cov piam thaj hauv cov zis yuav txiav txim.

Cov ntsiav tshuaj muaj lactose. Cov neeg mob uas muaj tus mob ua tsis taus ntshav, tsis haum lactase, lossis ntshav qabzib thiab galactose malabsorption syndrome yuav tsum tsis txhob noj cov tshuaj no.

Tsis muaj ntaub ntawv qhia txog kev siv canagliflozin hauv cov poj niam cev xeeb tub.

Cov kev tshawb fawb tsiaj tau pom tias muaj tshuaj lom neeg muaj tsiaj txhu. Invokana® yuav tsum tsis txhob siv thaum cev xeeb tub. Thaum cev xeeb tub tau tsim, kev kho mob nrog Invocana® yuav tsum tsis ua mus ntxiv.

Nws tsis paub meej tias canagliflozin thiab / lossis nws cov khoom noj tiv thaiv tau tawm hauv cov kua mis.

Muaj cov ntaub ntawv pharmacodynamic / toxicological tau hauv cov tsiaj qhia tau tias canagliflozin / metabolites raug ntuav tawm hauv cov mis thiab cov tshuaj noj uas muaj kev sib kis tau pom muaj nyob rau hauv cov menyuam uas tau pub mis thiab tsis muaj tus kabmob nas uas kis tau canagliflozin. Qhov uas phom sij rau cov menyuam mos / menyuam mos yuav tsis tuaj yeem tawm. Invokana® yuav tsum tsis txhob siv thaum lactation.

Cov nyhuv ntawm canagliflozin rau tib neeg kev ua me nyuam yaus tseem tsis tau kawm.

Hauv kev tshawb xyuas tsiaj, tsis muaj qhov tshwm sim ntawm canagliflozin ntawm kev muaj menyuam hauv lub cev.

Cov yam ntxwv ntawm cov nyhuv ntawm cov tshuaj ntawm lub peev xwm tsav lub tsheb lossis cov phom sij phom sij

Invokana® tsis muaj lossis cuam tshuam me ntsis ntawm kev muaj peev xwm tsav lub tsheb thiab tsav tshuab.

Txawm li cas los xij, cov neeg mob yuav tsum paub txog kev pheej hmoo ntawm kev mob ntshav qab zib thaum siv Invokana® los kho kev kho mob nrog insulin lossis insulin secretion stimulants, nrog rau kev pheej hmoo ntawm kev phiv tshuaj uas cuam tshuam nrog lub cev qhuav dej, xws li kev tso dag tom qab (saib ntu “ Muab koob tshuaj thiab cov thawj coj "," Cov lus qhia tshwj xeeb "thiab" Cov Kev Phiv ".

Noj ntau dhau

Kev siv ib zaug ntawm canagliflozin nyob rau hauv cov koob tshuaj txog 1600 mg rau hauv cov neeg noj qab haus huv thiab kev siv canagliflozin ntawm koob tshuaj 300 mg ob zaug ib hnub rau 12 lub lis piam hauv cov neeg mob uas muaj ntshav qab zib hom 2 feem ntau tau tiv thaiv zoo.

Thaum noj tshuaj ntau dhau, yuav tsum tau saib xyuas kev kho kom zoo, piv txwv, siv kev ntsuas los tshem tawm cov khoom tsis muaj pa tshuaj los ntawm lub plab zom mov, soj ntsuam kev kho mob thiab muab kev kho mob raws li tus neeg mob kho mob. Qhov kev ua tau zoo tshaj plaws ntawm kev tshem tawm lactate thiab metformin yog hemodialysis. Canagliflozin tsuas yog tso tawm me ntsis thaum lub sijhawm 4-teev hemodialysis kev sib kho. Canagliflozin tsis tuaj yeem xav tawm thaum lub sijhawm tso ntshav tawm peritoneal.

Cov lus qhia tshwj xeeb

Kev siv cov canagliflozin hauv cov neeg mob ntshav qab zib hom 1 tsis tau kawm, yog li ntawd, nws txoj kev siv yog contraindicated hauv pawg no ntawm cov neeg mob.
Kev siv cov canagliflozin yog contraindicated nyob rau hauv cov ntshav qab zib ketoacidosis, hauv cov neeg mob uas lub davhlau ya nyob twg mob raum tsis ua hauj lwm (CRF) lossis hauv cov neeg mob qog ntshav, vim tias cov kev kho no yuav tsis muaj txiaj ntsig hauv cov kev kuaj mob no.

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, txhawm rau txo qis 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 tso 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 ntim.Hauv kev tshawb fawb soj ntsuam ntawm canagliflozin, ib qho kev nce ntxiv ntawm cov zaus ntawm kev phiv tshuaj uas cuam tshuam nrog txo qis ntawm cov ntim hauv intravascular (piv txwv li, dias postural, orthostatic hypotension lossis arterial hypotension) tau pom ntau dua nyob rau thawj peb lub hlis nrog kev siv canagliflozin ntawm koob ntawm 300 mg. Cov neeg mob uas yuav ua rau muaj kev phiv tshuaj ntau ntxiv nrog rau kev txo qis hauv cov hlab ntim ntau ntxiv suav nrog cov neeg mob tau txais "voj" diuretics, cov neeg mob uas tsis ua haujlwm lub raum tsis ua haujlwm ntawm mob hnyav, thiab cov neeg mob hnub nyoog ≥75 xyoo.
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 feem ntau ua rau qhov tsis muaj teeb meem ntawm kev siv canagliflozin thiab feem ntau nrog kev siv txuas ntxiv ntawm canagliflozin raug kho los ntawm kev hloov pauv ntawm kev noj tshuaj tiv thaiv kab mob 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.
Hauv thawj rau lub lis piam ntawm kev kho canagliflozin, muaj qee qhov kev poob qis me ntsis ntawm kev kwv yees tus nqi glomerular filtration npaum li cas (GFR) 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 qhia saum toj no, muaj qee zaum muaj qhov tseem ceeb ntau dua hauv GFR (> 30%), uas tau daws tom qab thiab qee zaum yuav tsum cuam tshuam nrog kev kho canagliflozin.

Cov kab mob pwm ntawm tus qau
Hauv cov kev tshawb fawb soj ntsuam, qhov tshwm sim ntawm candidal vulvovaginitis (suav nrog vulvovaginitis thiab vulvovaginal fungal mob) tau ntau dua hauv cov poj niam uas tau txais canagliflozin piv nrog cov pab pawg placebo. Cov neeg mob uas muaj keeb kwm tsis txaus siab uas tau txais kev kho mob canagliflozin muaj feem ntau yuav muaj tus mob no. Ntawm cov neeg mob kho nrog canagliflozin, 2.3% muaj ntau dua ib ntu kev kis tus kab mob. Feem ntau cov lus ceeb toom ntawm vulvovaginal candidiasis ntsig txog thawj plaub lub hlis tom qab pib kho canagliflozin. 0.7% ntawm tag nrho cov neeg mob tsis noj cov canagliflozin vim muaj neeg vwm tsis txaus. Kev kuaj mob ntawm tus neeg mob candidal vulvovaginitis, raws li txoj cai, tau tsim tsa tsuas yog los ntawm cov tsos mob. Hauv cov kev tshawb fawb soj ntsuam, qhov ua tau zoo ntawm kev kho mob hauv zos lossis hauv qhov ncauj, tiv thaiv los ntawm tus kws kho mob lossis coj ntawm nws tus kheej ntawm keeb kwm ntawm kev kho mob tsis tu ncua nrog canagliflozin, tau sau tseg.
Hauv cov kev tshawb fawb soj ntsuam, candida balanitis lossis balanoposthitis tau pom ntau dua hauv cov neeg mob kho canagliflozin hauv koob tshuaj 100 mg thiab 300 mg, piv nrog pab pawg placebo. Balanitis lossis balanoposthitis feem ntau yog tsim los ntawm cov txiv neej uas tsis tau ua kev txiav tawv nqaij, thiab feem ntau tshwm sim hauv cov txiv neej muaj tus kabmob balanitis lossis tus kabmob balanoposthitis. Hauv 0.9% ntawm cov neeg mob kho nrog canagliflozin, ntau tshaj ib ntu kev kis tau tus mob. 0.5% ntawm tag nrho cov neeg mob tsis noj cov canagliflozin vim yog candida balanitis lossis balanoposthitis. Hauv kev sim kho mob, feem ntau, kev kis tus kab mob tau kho nrog cov tshuaj tua kab mob hauv zos los ntawm tus kws kho mob lossis coj lawv tus kheej tawm tsam cov keeb kwm ntawm kev kho mob txuas ntxiv nrog canagliflozin. Tsis tshua muaj neeg mob phimosis tau qhia tawm, qee zaum ua kev cai txiav.

Cov pob txha lov
Hauv kev kawm txog cov kev mob plawv hauv 4327 cov neeg mob uas tau kuaj pom tus kab mob plawv los yog mob ntshav siab, qhov tshwm sim ntawm cov pob txha pob txha yog 16.3, 16.4, thiab 10.8 rau 1,000 tus neeg mob-xyoo siv Invocana® ntawm koob tshuaj 100 mg thiab 300 mg thiab cov placebo, 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 tshuaj ntsuam xyuas ua ke ntawm lwm txoj kev tshawb fawb ntawm Invokana®, uas suav txog 5800 cov neeg mob ntshav qab zib los ntawm cov pej xeem sawv daws, qhov tshwm sim ntawm pob txha pob txha yog 10.8, 12.0, thiab 14.1 rau 1,000 tus neeg mob-xyoo siv Invokana® hauv koob tshuaj ntawm 100 mg thiab 300 mg thiab placebo, ntsig txog.
Nyob rau 104 lub lim tiam ntawm kev kho, canagliflozin tsis ua rau muaj kev cuam tshuam tsis zoo rau cov pob txha ntxhia.

Muaj feem xyuam rau kev muaj peev xwm tsav tsheb thiab cov txheej txheem

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 ib qho txuas rau kev kho tshuaj insulin lossis cov tshuaj uas ua kom nws txoj kev tso cia, ntawm kev pheej hmoo ntawm kev tsim cov kev tsis zoo uas cuam tshuam nrog qis ntawm cov ntshav qis (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.