Ọgwụ Lixumia: ntuziaka maka ojiji

Ngwọta maka nchịkwa sc bụ doo anya, enweghị agba.

Ndị pụrụ iche: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid solution 1 M ma ọ bụ sodium hydroxide solution 1 M - ruo pH 4.5, mmiri d / na - ruo 1 ml.

3 ml - katọn (1) - mkpịsị mkpụrụ sirinji (1) - ngwugwu nke kaadiboodu.

Ngwọta maka nchịkwa sc bụ doo anya, enweghị agba.

Ndị pụrụ iche: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid solution 1 M ma ọ bụ sodium hydroxide solution 1 M - ruo pH 4.5, mmiri d / na - ruo 1 ml.

3 ml - katọn (1) - mkpịsị mkpụrụ sirinji (1) - ngwugwu nke kaadiboodu.
3 ml - katọn (1) - mkpịsị mkpụrụ sirinji (2) - ngwugwu nke kaadiboodu.
3 ml - katọn (1) - mkpịsị mkpụrụ sirinji (6) - ngwugwu nke kaadiboodu.

Ngwọta maka nchịkwa sc bụ doo anya, enweghị agba.

Ndị pụrụ iche: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid solution 1 M ma ọ bụ sodium hydroxide solution 1 M - ruo pH 4.5, mmiri d / na - ruo 1 ml.

Ngwọta maka nchịkwa sc bụ doo anya, enweghị agba.

Ndị pụrụ iche: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid solution 1 M ma ọ bụ sodium hydroxide solution 1 M - ruo pH 4.5, mmiri d / na - ruo 1 ml.

3 ml - katridges (2) na ihe ngwọta nke 0.05 mg / ml (10 μg / dose) na 0.1 mg / ml (20 μg / dose) - pensụl sirinji (2) - ngwugwu nke kaadiboodu.

Ihe ngosi maka ojiji

Elldị nke abụọ nke ọrịa shuga mellitus na ndị okenye iji nweta njikwa glycemic na ndị ọrịa nke ọrịa mellitus na-adịghị achịkwa site na usoro hypoglycemic na-aga n'ihu.

E gosipụtara ebumnuche Lixumia yana ọgwụ hypoglycemic nke a:

- ọgwụ ọgwụ hypoglycemic nke ụdị sulfonylurea otu,

- nchikota ọgwụ ndia.

Edekwara Lixumia yana jikọta insulin basal:

- na nkwonkwo ọgwụ nke hypoglycemic ọgwụ nke sulfonylurea otu.

Ihe ngbanwe

- Mmụba uche n'otu n'otu na arụ ọrụ ma ọ bụ ihe ọ bụla nke ọgwụ ọgwụ.

- Oge ịgbara ya ara (inye ya ara).

- Ọrịa siri ike nke eriri afọ, tinyere eriri afọ.

- Nnukwu akwara gbasara akụrụngwa (mwepụ nke creatinine erughị 30 ml / min).

- Childrenmụaka na ụmụaka nọ n’agbata afọ iri na asatọ.

Site na akụkọ banyere ọrịa pancreatitis, a ga-eji Lixumia kpachara anya.

Etu esi eji: usoro onunu ogwu na usoro ọgwụgwọ

Ọgwụ nke Lixumia bụ 10 mcg otu ugboro kwa ụbọchị maka ụbọchị 14. Mgbe ahụ a ga-abawanye dose ahụ ka ọ bụrụ mmezi nke 20 mcg otu ugboro n'ụbọchị.

Mgbe agbakwunyere ọgwụ na usoro ọgwụgwọ metformin na-aga n'ihu, enwere ike ịga n'ihu metformin na-enweghị ịgbanwe ọgwụ ya.

Mgbe agbakwunyere Lixumia na ọgwụ a na-enwe na ọgwụ ọnụ hypoglycemic ọgwụ nke sulfonylurea ma ọ bụ na ngwakọta nke ọgwụ hypoglycemic ọgwụ nke sulfonylurea otu na insal basal, mbelata dose nke ọgwụ hypoglycemic ọgwụ nke sulfonylurea otu ma ọ bụ insulin basal nwere ike ịtụle iji belata ihe ize ndụ nke hypoglycemia.

Ojiji Lixumia achoghi nleba anya puru iche banyere nnabata glucose di n’ime obara. Agbanyeghị, mgbe ejikọtara ya na ọgwụ hypoglycemic ọgwụ nke sulfonylurea otu ma ọ bụ insal insulin, nlebara anya gbasara glucose ọbara ma ọ bụ nyocha onwe ya (njikwa site na onye ọrịa) nke ịgwọ glucose ọbara iji mezie ọnụọgụ hypoglycemic ọgwụ nke otu sulfonylurea ma ọ bụ insal insal.

Ndị otu ọrịa pụrụ iche

Childrenmụaka na ndị nọ n’agbata afọ 18: ugbu a, amụbeghị nchekwa na ịdị irè nke ọgwụ n’etiti ndị ọrịa a amụbeghị.

Agadi: ekwesighi imeghari dose dabere na afọ onye ọrịa dị.

Oria ndi nwere nsogbu imeju: ekwesighi imeghari ogwu na ndi ọrịa nwere oria.

Ndị ọrịa nwere ọdịda akụrụngwa: achọpụtaghị mmezi dose na ndị ọrịa nwere ọdịda akụrụngwa obere (mwepụ creatinine 50-80 ml / min) yana ọdịda akụrụngwa na-adịghị mma (mwepụ creatinine 30-50 ml / min). Enweghị ahụmịhe ọgwụgwọ na Lixumia na ndị ọrịa nwere nnukwu akụrụ oke (mwepụ nke creatinine erughị 30 ml / min) ma ọ bụ ọdịda okuku na njedebe, yabụ na ị ofụ ọgwụ ahụ na otu ndị ọrịa a ka nwere contraindicated.

A na-elekọta Lixumia otu oge kwa ụbọchị n'ime otu elekere tupu nri mbụ n'ụbọchị ma ọ bụ n'ime otu elekere tupu nri mgbede. Ọ bụrụ n ’usoro nke ọzọ achọrọ, aga-enye ya n’ime otu elekere tupu nri ọzọ.

A na-ahụ maka ọgwụ a n'okpuru ala n'apata ụkwụ, n'akụkụ afọ ma ọ bụ ubu. Lixumia ekwesighi iji ya mee intravenia ma ọ bụ intramuscularly.

Tupu ojiji, a ga-echekwa mkpụrụ ọnya Lixumia na friji na okpomọkụ nke 2-8 Celsius C na nkwakọ ngwaahịa ya iji kpuchido ya ka ekpughe ọkụ. Mgbe ojiji mbụ, mkpịsị sirinji kwesịrị ka echekwara ya na okpomọkụ agaghị akarị 30 Celsius. Mgbe ojiji ọ bụla, mkpịsị ọrịrị ga-ejikọrịrị ya iji kpuchido ya n'enwu ọkụ. Edekọghị mkpịsị sirinji na agịị. Ejila pen sirinji ma ọ bụrụ na agbajụọla.

A ga-ewepụ Lixumia Syringe Pen mgbe ụbọchị iri na anọ gachara.

Omume ọgwụ

Ngwa ọrụ Lixumia lixisenatide bụ ihe siri ike ma na-ahọta nke glucagon-like peptide receptors-1 (GLP-1). Ihe nnabata nke GLP-1 bu ihe nlere anya maka GLP-1 nke mbu, homonụ nke ime na-enyo enyo, nke na-eme ka glucose na-egbochi insulin glucose site na sel beta nke agwaetiti puru pan. Mmetụta nke lixisenatide nwere mmekọrịta ya na ndị na-anabata GLP-1, na-eduga n'ịba ụba ọdịnaya intracellular nke cyclic adenosine monophosphate (cAMP). Lixisenatide na-akpali mkpụrụ ndụ nke insulin site na mkpụrụ ndụ beta nke agwaetiti palọ na-aza na hyperglycemia. Mgbe itinye uche nke glucose n'ọbara na-agbadata n'omume nkịtị, mkpali nke insulin na-akwụsị, nke a na-ebelata ihe ize ndụ nke hypoglycemia. Na hyperglycemia, lixisenatide n'otu oge na-egbochi nzuzo nke glucagon, Otú ọ dị, mmeghachi omume nke glucagon zoro ezo na nzaghachi hypoglycemia na-adịgide.

E gosipụtara omume insulinotropic ọrụ nke lixisenatide, gụnyere mmụba nke insulin biosynthesis na mkpali nke mkpụrụ ndụ beta nke agwaetiti pancreatic. Lixisenatide na-eji nwayọ nwayọ agbanye mmiri, wee si na ibelata ọnụego mmụba glucose ọbara gachaa. Ihe ọ na - ebute na ịmịcha afọ na - enyekwa aka n'ibelata ibu.

Mgbe enyere ndị ọrịa nwere ụdị ọrịa shuga 2 ọrịa shuga otu ugboro n'ụbọchị, lixisenatide na-eme ka nchịkwa glycemic dịkwuo mma n'ihi mmụba ngwa ngwa mgbe nchịkwa ya na mbelata ogologo oge ịba ụba ọbara mgbe nri na afọ efu.

Leasedị ntọhapụ, ihe mejupụtara na nkwakọ

Ngwọta maka nchịkwa sc bụ doo anya, enweghị agba.

1 ml nke ihe ngwọta nwere:

ihe na-arụ ọrụ: lixisenatide - 0.05 mg,

ndị na - ahụkarị: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid solution 1 M ma ọ bụ sodium hydroxide solution 1 M - ruo pH 4.5, mmiri d / na - ruo 1 ml

3 ml - katọn (1) - mkpịsị mkpụrụ sirinji (1) - ngwugwu nke kaadiboodu.

Ngwọta maka nchịkwa sc bụ doo anya, enweghị agba.

1 ml nke ihe ngwọta nwere:

ihe na-arụ ọrụ: lixisenatide - 0.1 mg,

ndị na - ahụkarị: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid solution 1 M ma ọ bụ sodium hydroxide solution 1 M - ruo pH 4.5, mmiri d / na - ruo 1 ml

3 ml - katọn (1) - mkpịsị mkpụrụ sirinji (1) - ngwugwu nke kaadiboodu.
3 ml - katọn (1) - mkpịsị mkpụrụ sirinji (2) - ngwugwu nke kaadiboodu.
3 ml - katọn (1) - mkpịsị mkpụrụ sirinji (6) - ngwugwu nke kaadiboodu.

Ngwọta maka nchịkwa sc bụ doo anya, enweghị agba.

1 ml nke ihe ngwọta nwere:

ihe na-arụ ọrụ: lixisenatide - 0.05 mg,

ndị na - ahụkarị: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid solution 1 M ma ọ bụ sodium hydroxide solution 1 M - ruo pH 4.5, mmiri d / na - ruo 1 ml

Ngwọta maka nchịkwa sc bụ doo anya, enweghị agba.

1 ml nke ihe ngwọta nwere:

ihe na-arụ ọrụ: lixisenatide - 0.1 mg,

ndị na - ahụkarị: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid solution 1 M ma ọ bụ sodium hydroxide solution 1 M - ruo pH 4.5, mmiri d / na - ruo 1 ml

3 ml - katridges (2) na ihe ngwọta nke 0.05 mg / ml (10 μg / dose) na 0.1 mg / ml (20 μg / dose) - pensụl sirinji (2) - ngwugwu nke kaadiboodu.

Elldị nke abụọ nke ọrịa shuga mellitus na ndị okenye iji nweta njikwa glycemic na ndị ọrịa nke ọrịa mellitus na-adịghị achịkwa site na usoro hypoglycemic na-aga n'ihu.

E gosipụtara Lixumia yana ọgwụ ọgwụ hypoglycemic ndị a:

- ọgwụ ọgwụ hypoglycemic nke ụdị sulfonylurea otu,

- nchikota ọgwụ ndia.

Lixumia egosiputara na insulin basal:

- yana ngwakọta na metformin,

- na nkwonkwo ọgwụ nke hypoglycemic ọgwụ nke sulfonylurea otu.

Ojiji nke Lixumia n’oge di ime na n’ara nku

Womenmụ nwanyị dị afọ iri.
A naghị atụ aro Lixumia maka ụmụ nwanyị ịmụ nwa na-adịghị eji ọgwụ mgbochi afọ.
Ime
Enweghi data zuru oke banyere iji Lixumia n'ime ụmụ nwanyị dị ime. Ihe omumu omumu omumu egosila ututu omumu.
Amaghị ihe mmadụ nwere ike isi mee ya.
Ekwesighi iji Lixumia mee n'oge afọ ime. Kama, a na-atụ aro insulin.
Ọ bụrụ na onye ọrịa chọrọ ịtụrụ ime ma ọ bụ tụtara ime, a ga-akwụsị ịhapụ Lixumia.
Lactation.
Amabeghị ma Lixumia na-abanye na mmiri ara ara mmadụ. Ekwesighi iji Lixumia mee ihe n'oge a na-enye ya ara.
Ọmụmụ.
Ọmụmụ banyere ọmụmụ adịghị egosi mmetụta na-emerụ ahụ na ọmụmụ nke ọmụmụ.

Lixisenatide bụ agonist nhọrọ nke ndị na-anabata GLP-1 (glucagon-like peptide-1). Ihe nnabata nke GLP-1 bu ihe nlere anya maka GLP-1, homonụ nke ime mmụọ nke na-eme ka insulin na-egbochi glucose site na mkpụrụ ndụ beta pancreatic.
Mmetụta nke lixisenatide na-agbagha site na mmekọrịta dị n'etiti ya na ndị na-anabata GLP-1, na-eduga na mmụba intracellular cyclic adenosine monophosphate (cAMP).
Lixisenatide na-akpali mmiri ọgwụ insulin mgbe ọ̀tụ̀tụ̀ shuga dị n'ọbara na-amụba, ma ọ bụghị na Normoglycemia, nke na-egbochi ihe ize ndụ nke hypoglycemia.
N'otu oge ahụ, a na-ebelata glucagon nzuzo. Site na hypoglycemia, a na-edozi usoro nchekwa nke glucagon zoro ezo.
Lixisenatide na-egbochi iwepu afọ ya, na -ebelata ọsọ nke glucose na-enweta site na nri dị n'ọbara.
Ngwọta ọgwụ.
Mgbe a na-eji ya otu ugboro kwa ụbọchị na ndị ọrịa nwere ụdị shuga 2, lixisenatide na-eme ka nchịkwa glycemic dị mma n'ihi nsonaazụ ozugbo na ogologo oge nke belata nsị glucose mgbe nri gasịrị na afọ efu.
Ekwenye mmetụta a na glucose postprandial n'ọmụmụ izu anọ, iji tụnyere Liraglutide 1.8 mg otu ugboro kwa ụbọchị yana njikọta na metformin. Mbelata site na ọkwa nke PPK egosi 0: 30–4: 30 h
plasma glucose mgbe nri ulere bụ:
–12.61 hour * mmol / L (-227.25 hour * mg / dL) na otu lixisenatide na –4.04 hour * mmol / L (–72.83 hour * mg / dl) na otu liraglutide.
Ekwenyekwara na nke a n'ọmụmụ izu asatọ ma e jiri ya tụnyere Liraglutide edepụtara tupu nri ụtụtụ agụnyere insulin glargine yana ma ọ bụ na-enweghị metformin.
Ọgwụ arụmọrụ na nchekwa.
A tụlere nsonaazụ Lixumia na njikwa glycemic ma e jiri ya tụnyere exenatide na nyocha isii, nke gbara mbọ abụọ, ọnwụnwa na-achịkwa achịkwa na otu usoro nyocha, mepere emepe na njikwa arụ ọrụ.
Ọmụmụ ihe ahụ gụnyere ndị ọrịa 3825 nwere ụdị ọrịa shuga 2 (ndị ọrịa 2445 nwere usoro iji lixisenatide), 48.2% ụmụ nwoke na 51.8% nke ụmụ nwanyị.
Ndị ọrịa 768 (447 na-emeghị emezi iji lixisenatide) bụ ndị dị afọ 65,65, yana ndị ọrịa 103 (57 na-echeghị iji lixisenatide) bụ ndị dị afọ 75.
N'ime usoro ọmụmụ nke III dechara, achọpụtara na na njedebe nke oge ọgwụgwọ 24 izu bụ isi, ihe karịrị 90% nke ndị ọrịa nwere ike ịnọgide na-enwe usoro mmezi nke Lixumia 20 μg otu ugboro n'ụbọchị.
Njikwa glycemic.
Usoro ọgwụgwọ agbakwunyere na-eji ọgwụ antidiabetic ọnụ.
Na ngwụsị nke usoro ọgwụgwọ izu iri abụọ na anọ, Lixumia na metformin, sulfonylurea, pioglitazone, ma ọ bụ ngwakọta nke ọgwụ ndị a gosipụtara ọnụ ọgụgụ dị ukwuu nke ọbara HbA1c ọnụ ọgụgụ na-ebu ọnụ, glucose plasma glucose na glucose awa 2 awa mgbe nri ule jiri ya tụnyere placebo. Mbelata nke HbA1c dị mkpa mgbe enyere ọgwụ a otu ugboro n'ụbọchị, n'agbanyeghị ma eji ya n'ụtụtụ ma ọ bụ n'anyasị.
Ngosipụta dị otú ahụ na HbA1c agbatịwo n'ọmụmụ ogologo oge na-adịgide ruo izu 76.
Ọgwụ ndị ọzọ na mgbakwunye naanị na metformin.
Tebụl 2: Mmụta ndị na-achịkwa placebo na metformin (nsonso iri abụọ na anọ).
N'ime ọmụmụ na njikwa na-arụ ọrụ na njedebe nke oge ọgwụgwọ 24-izu, ojiji nke Lixumia otu ugboro kwa ụbọchị gosipụtara mbelata HbA1c nke -0.79% ma e jiri ya tụnyere -0.96% mgbe ị na-eji Exenatide ugboro abụọ n'ụbọchị, yana nkezi ọdịiche na ọgwụgwọ 0.17% (nkeji oge ntụkwasị obi 95% (CI): 0.033, 0.297) na pasent yiri nke ndị ọrịa nwetere ọkwa HbA1c erughị 7% na otu lixisenatide (48.5%)
na na exenatide otu (49.8%).
N'ime oge ọgwụgwọ 24 izu bụ isi, ihe kpatara ọgbụgba bụ 24.5% n'ime otu lixisenatide ma e jiri ya tụnyere 35.1% n'ime ìgwè exenatide ugboro abụọ n'ụbọchị, yana omume nke hypoglycemia Symptomatic na lixisenatide bụ 2.5% ma e jiri ya tụnyere 7.9% n'ime ìgwè exenatide.
N'ime ọmụmụ mmeghe izu iri abụọ na anọ, enyere isiiisenatide tupu nri bụ isi, ọ dịkwa ala karịa nke isiiisenatide tupu nri ụtụtụ dịka akụkụ nke mbelata ahụ.
HbA1c (mgbanwe na njedebe nke ihe pụtara site na ọkwa mbụ: -0.65% ma e jiri ya tụnyere 0.74%). A hụrụ mbelata yiri nke ahụ na HbA1c n'agbanyeghị isi nri (nri ụtụtụ, nri ehihie, ma ọ bụ nri abalị). Na njedebe nke ọmụmụ a, 43.6% (otu isi nri) na 42.8% (otu nri ụtụtụ) nke ndị ọrịa nwetara erughị 7% HbA1c. A kọrọ ọgbụgba na 14.7% na 15.5% nke ndị ọrịa, yana ọrịa hypoglycemia na 5.8% na 2.2% nke ndị ọrịa na isi nri na otu nri ụtụtụ, n'otu n'otu.
Ọgwụ ndị ọzọ na ngwakọta naanị na sulfonylurea ma ọ bụ na njikọta yana metformin.
Tebụl 3: Ọmụmụ ihe na-achịkwa placebo yana njikọ mmanụ na nsị (izu iri abụọ na anọ).
Ọgwụ ndị ọzọ na ngwakọta naanị na pioglitazone ma ọ bụ na njikọta na metformin.
N'ime nyocha ụlọ ọgwụ na ndị ọrịa na-enwetaghị nchịkwa na pioglitazone, mgbakwunye nke lixisenatide na pioglitazone na njikọta ma ọ bụ na-enweghị metformin na njedebe nke usoro ọgwụgwọ izu 24 bụ nke kpatara mgbada HbA1c site na ntọala site na 0.90% ma e jiri ya tụnyere mbelata site na ọkwa mbụ nke 0.34% na otu placebo. Na ngwụcha oge usoro ọgwụgwọ izu 24, 52.3% nke ndị ọrịa na-anata lixisenatide nwere HbA1
c erughi 7% ma e jiri ya tụnyere 26.4% n'ime placebo otu.
N'ime oge ọgwụgwọ 24 izu bụ isi, a chọtara ọgbụgba na 23.5% na otu lixisenatide ma e jiri ya tụnyere 10.6% na placebo otu, ikpe nke hypoglycemia na 3.4% nke ndị ọrịa e mesoro lixisenatide, ma e jiri ya tụnyere 1.2% na otubobo.
Ọgwụ mgbakwunye na insulin basal Lixumia, nke edobere ya na insulin basal naanị, ma ọ bụ na njikọta ya na insulin basal na sọlfọlu, butere ọnụ ọgụgụ pụtara mma na HbA1c yana glucose post-2 awa mgbe nyocha ahụ. na-eri nri dị ka placebo.
Tebụl 4: Ọmụmụ ihe na-achịkwa placebo yana insulin basal (nsonso iri abụọ na anọ).
Emere nnyocha banyere ụlọ ọgwụ na ndị ọrịa na-enwetabeghị insulin, ndị na-enweghị akara nke ndị na-aicụ ọgwụ na-egbu egbu. Ọmụmụ ihe a gụnyere oge nkwado izu 12 na insulin glargine nchịkwa na titings na oge izu 24 ka ndị ọrịa natara ma ọ bụ sitisenatide ma ọ bụ placebo na njikọ insulin glargine na metformin ma ọ bụ na enweghị thiazolidinediones. N'oge a, glargine na - edenyekarị aha.
N'ime oge nkwado izu 12, mgbakwunye na titration insulin glargine butere mgbada na HbA1c nke dị ka 1%.
Ihe mgbakwunye nke lixisenatide kpatara mbelata nke ukwuu na HbA1 site na 0.71% na otu nke lixisenatide ma e jiri ya tụnyere 0.40% na otu placebo. Na ngwụsị nke oge izu 24, 56.3% nke ndị ọrịa na-eji lixisenatide nwere akara HbA1 erughị 7% ma e jiri ya tụnyere 38.5% na placebo otu.
N'ime oge ọgwụgwọ 24-izu, 22.4% nke ndị ọrịa lebara lixisenatide kọrọ na opekata mpe otu hypoglycemia, ma e jiri ya tụnyere 13.5% n'ime placebo otu.
Ọnọdụ nke hypoglycemia mụbara tumadi n'ime izu isii mbụ nke ọgwụgwọ na lixisenatide otu, ma emesia yiri nke ahụ.
Na-ebu ọnụ glukpu plasma.
N'ime ọmụmụ ihe a na-achịkwa oge ọgbụgba izu iri abụọ na anọ, iji Mbelata plasma glucose na-ebu ọnụ site na ihe a na-enweta na usoro Lixumia sitere na 0.42 mmol / L ruo 1.19 mmol / L.
Ọkwa glucose postprandial.
Ọgwụ Lixumia butere mgbatị glucose post-2 postprandial mgbe elekere abụọ gachara mgbe nri ule gachara, ọnụọgụgụ kachasị na placebo, agbanyeghị ọgwụgwọ bụ isi.
Na mkpokọta, n'ọmụmụ ihe niile eji atụpụta ọkwa glucose postprandial, na Lixumia na ngwụsị oge izu iri abụọ na anọ, mbelata site na ihe ndabere dị na 4.51 ruo 7.96 mmol / L. Site na 26.2% ruo 46.8% nke ndị ọrịa, ọkwa glucose elekere 2 awa postprandial dị n'okpuru 7.8 mmol / L (140.4 mg / dl).
Ikpa ahu.
Na ngwụsị nke oge ọgwụgwọ 24 izu, ọgwụ Lixumia na njikọta metformin na / ma ọ bụ sulfonylurea na ọnwụnwa niile a na-achịkwa dugara na mgbanwe mgbanwe na ịdị arọ nke anụ ahụ sitere na -1.76 n'arọ ruo –2.96 n'arọ. A hụkwara mgbanwe mgbanwe n’arụ ahụ site na ọkwa mbụ n’ime oke sitere –0.38 kg ruo –8080 ka ahụrụ n’arụ ndị ọrịa na-anata lixisenatide na mgbakwunye insulin steal na-akwụghị ọtọ, ma ọ bụ na metformin ma ọ bụ sulfonylurea.
N'ime ndị ọrịa bidoro ị insụ ọgwụ insulin, n'ime mkpụrụ nke sitisenatide, ịdị arọ nke anụ ahụ nọgidere na-agbanweghi agbanwe, ebe a gosipụtara mmụba na placebo.
N'ime ihe ọmụmụ ogologo oge na-adigide ruo izu izu 76, ịdị arọ ahụ kwụ ọtọ.
Iwetulata ibu anaghị adabere na oge ọgbụgbọ na ọgbụgbọ.
Ọrụ beta.
Ọmụmụ nyocha nke Lixumia na-egosi arụmọrụ beta cell ka arụpụtara dị ka nha nha site na usoro ntule arụmọrụ mkpụrụ ndụ beta (HOMO-β / HOMA-β).
Mgbake nke usoro mbu nke insulin na mmelite nke usoro nke insulin nke abụọ na nzaghachi na nsonye ọbara bolus nke glucose hụrụ mgbe otu Lixumia na ndị ọrịa nwere ụdị shuga 2 (n = 20).
Nyocha nke sistem.
N'ime ule niile na - achịkwa placebo nke frasi nke III, ndị ọrịa nwere ụdị ọrịa shuga 2 egosighi mmụba n'ọtụtụ mkpụrụ obi.
N'ime ọmụmụ nke a na - achịkwa usoro III, enwere mbelata nke nkezi systolic na ọbara mgbali, otu, ruo 2.1 mm RT. Art. na ruo 1.5 mm RT. Art.
Meta-nyocha nke ihe omume obi ike guzobere onwe ya (ọnwụ n'ihi ihe obi ụbụrụ, infarction nontialal ụbụrụ, ọrịa nna, ọrịa n'ụlọ ọgwụ n'ihi angina na-akwụghị nkwụ, ụlọ ọgwụ n'ihi nkụchi obi na nkwalite nke akwara akwara) na ọnwụnwa 8 na-achịkwa mpaghara III, nke gunyere ndị ọrịa 2,673 nwere ụdị ọrịa shuga 2 na-anata lixisenatide yana ndị ọrịa 1,448 na-anata placebo gosipụtara ihe ize ndụ nke 1.03 (95% ntụkwasị obi etiti oge 0.64, 1.66) maka lixis Atid tụnyere placebo.
Onu ogugu nke ihe omume na nnwale nke ulo ogwu di obere (1.9% na ndi oria na anata isiiisenatide na 1.8% na ndi oria anata placebo), odighi anabata nkwubi okwu ekwesiri.
Ihe kpatara akụrụngwa obi ọ bụla (lixisenatide na placebo) bụ: ọnwụ n'ihi ihe na-akpata obi (0.3% ma e jiri ya tụnyere 0.3%), ọrịa infarction myocardial na-adịghị egbu egbu (0.4% ma e jiri ya tụnyere 0.4) %), ọrịa ọnya na-egbu egbu (0.7% ma e jiri ya tụnyere 0.4%), ụlọ ọgwụ n'ihi angina na-akwụghị chịm (0 tụnyere 0.1%), ụlọ ọgwụ n'ihi nkụchi obi (0.1% ma e jiri ya tụnyere 0) , nkwonkwo akwara gbasara akwara (0.7% vesos 1.0%).
Pharmacokinetics: Absorption.
Mgbe nchịkwa subcutaneous nye ndị ọrịa nwere ọrịa shuga nke 2, ọnụ ọgụgụ nnabata nke lixisenatide na-adị ngwa ngwa, agbanyeghị usoro enyere ya. Na agbanyeghị etu a siri jiri sitisenatide mee ihe otu ugboro ma ọ bụ n'ọtụtụ, na ndị ọrịa nwere ụdị shuga 2, nkezi tmax sitere na 1 ruo 3.5 awa. N'ihe banyere sistemụ subcutaneous nke lixisenatide rue afọ, apata ụkwụ ma ọ bụ ubu, enweghị ọdịiche pụtara ìhè dị na ọnụego mmiri.
Nkesa.
Lixisenatide nwere ogo nke ejikọtara ọnụ (55%) na protein mmadụ.
Olu pụtara oke mgbe nchịkwa subisiaatide (Vz / F) dị ihe dịka 100 L.
Biotransformation na excretion.
Dị ka peptide, sitisenatide na-agbaze site na nzacha zuru ụwa ọnụ na-esote tubular reabsorption na mmebi metabolic ọzọ, na-eduga na ịkpụbe obere peptides na amino acid, nke a na-etinye ọzọ na metabolism protein. Mgbe nchịkwa nke ọtụtụ onunu ogwu na ndị ọrịa nwere ụdị shuga 2, ọkara ọkara iwepụ ọkara ndụ bụ ihe dịka awa 3 na nkezi mwepụ (CL / F) bụ ihe dịka 35 l / h.
Onu ogugu puru iche:
Ndị ọrịa nwere ọrụ mgbazinye nsogbu.
N'ime ndị ọrịa nwere ọrụ gbasara akụrụngwa nkịtị yana ndị ọrịa nwere obere ọrụ mkpo ya na-arụ ọrụ (mwepụta creatinine nke Cockcroft-Gault formula, 50-80 ml / min), enweghị nnukwu ọdịiche na Cmax na PPK nke lixisenatide. N'ime ndị ọrịa nwere ọrụ mgbazi na-adịghị mma (mwepụ nke 30-50 ml / min), akara ngosi AUC (mpaghara n'okpuru usoro) mụbara site na 24%, na ndị ọrịa nwere nnukwu akụrụ mkpali (mwepụ nke mkpụrụ osisi 15-30 ml / min) - site na 46 %
Ndị ọrịa nwere ọria imeju.
Ebe ọ bụ na lixisenatide bụ akụrụ nwere akụrụ, ndị ọrịa nwere oke akụrụ ọrụ na arụ ọrụ esonyeghi na ọmụmụ ọgwụ. Achọpụtaghị na ọrịa ịba ọcha n'anya ga-emetụta ọgwụ ọgwụ nke lixisenatide.
Paul
Inwe nwoke na nwanyi enweghi mmetụta di nkpa na ogwu banyere pharmacokinetics nke sitisenatide.
Ọsọ.
Dabere na nsonaazụ nke ọmụmụ pharmacokinetic na ndị ọrịa nke agbụrụ Caucasian, Japanese na Chinese, agbụrụ enweghị mmetụta dị ukwuu na ọgwụ ọgwụ nke lixisenatide.
Ndị okenye na-arịa ọrịa.
Afọ anaghị enwe mmetụta dị egwu n’ụlọ ọgwụ na ọgwụ ọgwụ nke lixisenatide. Na nyocha nke pharmacokinetic na ndị agadi anaghị arịa ọrịa shuga, ojiji nke 20 μg nke lixisenatide n'ime otu ndị ọrịa agadi (ndị ọrịa 11 dị afọ 65 ruo afọ 74 na ndị ọrịa dị afọ 75 ruo afọ 75), na-eduga na mmụba dị elu na LPC nke lixisenatide site na 29%, ma e jiri ya tụnyere ndị ọrịa 18 dị afọ 18 ruo afọ 45, ọ nwere ike jikọtara ya na ọrụ ebugharị belata na ndị agadi.
Ikpa ahu.
Ikike anụ ahụ enweghị mmetụta dị ukwuu na clinical na PPK egosi nke lixisenatide.

Nsonaazụ nke Liksumiya

Nkọwa dị mkpirikpi banyere profaịlụ nchekwa.
Ihe karịrị ndị ọrịa 2,600 na nnukwu ọmụmụ 8 na-achịkwa placebo ma ọ bụ ọmụmụ III nke nwere njikwa ike natara Lixumia ma ọ bụ na monotherapy ma ọ bụ na njikọta metformin, sulfonylurea (na ma ọ bụ na-enweghị metformin) ma ọ bụ insulin basal (ya na ma ọ bụ na-enweghị metformin ma ọ bụ na sulfonylurea ma ọ bụ na-enweghị ya).
Mmeghachi omume kachasị na-akọkarị n'oge ule ụlọ ọgwụ bụ ọgbụgbọ, ọgbụgbọ, na afọ ọsịsa. Mmeghachi omume ndị ahụ na-adịkarị nwayọọ ma dịkwa obere.
Enweelakwa ọrịa nke hypoglycemia (mgbe e jiri Lixumia mee ihe na njikọta nke sulfonylurea na / ma ọ bụ insulin basal) yana isi ọwụwa.
A hụrụ mmeghachi omume nfụkasị na 0.4% nke ndị ọrịa na-eji Lixumia.
N'okpuru bụ mmeghachi omume dị njọ nke mere na otutu nke> 5%, ọ bụrụ na ugboro ole nke ihe dị elu n'etiti ndị ọrịa na-anata Lixumia karịa n'etiti ndị ọrịa na-anata ọgwụ niile atụnyere, gụnyere mmeghachi omume ọjọọ na ugboro ole with1% na otu ndị ọrịa na-anata Lixumia, ọ bụrụ na ugboro ugboro nke ihe a mere ugboro abụọ karịa ugboro ole n’etiti otu ndị ọrịa na-anata ọgwụ ntụnyere niile.
Mmeghachi omume ọjọọ guzobere na nchịkwa placebo na usoro III nke nwere njikwa ike n'oge oge ọgwụgwọ niile (gụnyere oge gafere oge ọgwụgwọ 24-izu mbụ na ọmụmụ with7 izu nke ọgwụgwọ niile).
Ọtụtụ mgbe (≥1 / 10):
- hypoglycemia (ya na insulinlurea na / ma obu insulin basal)
isi ọwụwa
- ọgbụgbọ, ọgbụgbọ, afọ ọsịsa
Ọtụtụ mgbe (≥1 / 100 tupu - flu, ọrịa okuku ume na elu, ọrịa cystitis, nje malitere ịrịa
- hypoglycemia (yana yana metformin naanị)
- ire ​​ure, ura
- dyspepsia
- azu mgbu
- itching na ntụtụ ahụ
Nleta oge (≥1 / 1000 ruo - mmeghachi omume anaphylactic]
- urticaria

Nkọwapụta mmeghachi omume ọjọọ nke onwe onye:
Hypoglycemia.
N'ime ndị ọrịa na-ewere Lixumia na monotherapy, hypoglycemia Symptomatic mere na 1.7% nke ndị ọrịa na-anata lixisenatide, na 1.6% nke ndị ọrịa na-anata placebo. Mgbe ejiri Lixumia mee ihe na njikọ naanị na metformin n'oge oge ọgwụgwọ niile, hypoglycemia Symptomatic mere na 7.0% nke ndị ọrịa na-anata lixisenatide na 4.8% nke ndị ọrịa na-anata placebo.
N'ime ndị ọrịa na-ewere Lixumia na sulfonylurea na metformin, hypoglycemia Symptomatic mere na 22.0% nke ndị ọrịa na-anata lixisenatide na 18.4% nke ndị ọrịa na-anata placebo (3.6% zuru oke) n'oge usoro ọgwụgwọ dum. Mgbe ejiri Lixumia jikọta ya na insulin basal na ma ọ bụ na-enweghị metformin n'oge oge ọgwụgwọ niile, hypoglycemia Symptomatic mere na 42.1% nke ndị ọrịa na-anata lixisenatide na na 38.9% nke ndị natara placebo (3.2% nke ọdịiche zuru oke).
Mgbe ejiri Lixumia jikọtara ya na sulfonylurea naanị n'oge ọgwụgwọ niile, hypoglycemia Symptomatic mere na 22.7% nke ndị ọrịa na-anata lixisenatide, ma e jiri ya tụnyere 15.2% na-enweta placebo (7.5% zuru oke). Mgbe ejiri Lixumia mee ihe na njikọta nke sulfonylurea na basal insulin, hypoglycemia Symptomatic mere na 47.2% nke ndị ọrịa na-anata lixisenatide, ma e jiri ya tụnyere 21.6% na-enweta placebo (25.6% nke ọdịiche zuru oke).
Na mkpokọta, n'oge oge ọgwụgwọ dum na ọmụmụ ihe na-achịkwa oge nke III, ọnọdụ nke hypoglycemia siri ike adịghị ala (0.4% na ndị ọrịa e mesoro lixisenatide na 0.2% na ndị ọrịa agwọ ọrịa placebo).
Mmebi nke eriri afọ.
N'ime oge ọgwụgwọ izu 24 gara aga, ọgbụgbọ na ọgbụgbọ bụ ọnụnọ kachasị akọkarị. Ọnọdụ ọgbụgbọ dị elu na lixisenatide otu (26.1%) ma e jiri ya tụnyere placebo otu (6.2%), ihe ọgbụgba nke vomiting dị elu na lixisenatide otu (10.5%) ma e jiri ya tụnyere ndị placebo otu (1.8 %).
Mmeghachi omume ahụ na-adịkarị nwayọ ma na-adịte aka ma na-eme n'ime izu atọ izizi ka ịmalite ọgwụgwọ. Mgbe nke ahụ gasịrị, n’izu izu ndị na-esote, a na-eji nwayọọ nwayọọ kwụsịlata ugboro ugboro.
Mmeghachi omume na ebe ntụtụ.
N'ime oge ọgwụgwọ 24 izu bụ isi, a hụrụ mmeghachi omume na saịtị ịgba ahụ na 3.9% nke ndị ọrịa na-anata Lixumia, a na-ahụkwa mmeghachi omume na ebe ntụtụ ahụ na 1.4% nke ndị ọrịa na-enweta placebo.
Ọtụtụ mmeghachi omume ahụ dị nro na ike ma ọ kwụsịghị ọgwụgwọ.
Immunogenicity
N'ihi ikike nke immunogenic nke ọgwụ nwere protein ma ọ bụ peptides, mgbe ọgwụgwọ Lixumia gasịrị, ndị ọrịa nwere ike ịmalite ọgwụ mgbochi lixisenatide, na njedebe nke oge izu iri abụọ na anọ izu abụọ n'ọmụmụ ihe nchịkwa placebo na 69.8% nke ndị ọrịa na-emeso lixisenatide, E gosipụtara ọnọdụ antibody ziri ezi. Na ngwụsị nke usoro ọgwụgwọ izu asaa 76, pasent nke ndị ọrịa seropositive yiri. Na ngwụsị nke oge ọgwụgwọ 24-izu 24, na 32.2% nke ndị ọrịa nwere ezigbo ọnọdụ antibody, ịta ahụhụ dị karịa ọnụ ala, na njedebe nke oge izu asaa izu asaa na 44,7% nke ndị ọrịa, ịta ụta na-adịkarị n'okpuru obere njupụta ịda. . Mgbe kwụsịchara ọgwụgwọ, nlebara anya nke ọtụtụ ndị ọrịa seropositive gara n'ihu, n'ime ọnwa 3 pasent belatara ruru ihe dịka 90%, na mgbe ọnwa isii ma ọ bụ karịa - ruru 30%.
Mgbanwe nke HbA1c sitere na ntọala bụ otu ihe n'agbanyeghị agbanyeghị ọkwa nwoke na nwanyị (nke dị mma ma ọ bụ nke na-adịghị mma).
N'ime ndị ọrịa nwere nha HbA1c natara lixisenatide, 79.3% nwere ma ọ bụ ọnọdụ antibody na-adịghị mma ma ọ bụ ịta ahụhụ antibody dị ala karịa njedebe nke quantification, ihe fọdụrụnụ 20.7% nke ndị ọrịa ahụ nwere ịta ahụhụ mgbochi antibody.Na mpaghara ndị ọrịa (5.2%) na ntinye uche kachasị elu, nhazigharị HbA1c na izu 24 na izu 76 nọ na nha nha ahụike, etu ọ dị, mgbanwe mgbanwe glycemic na-agbanwe, na 1.9% enweghị mbelata HbA1c.
Ọnọdụ ọgwụ mgbochi (nke dị mma ma ọ bụ nke na-adịghị mma) anaghị ekwe ịkọ ịkọ mbelata HbA1c na ndị ọrịa n'otu n'otu.
Enweghị ọdịiche dị na profaịlụ nchekwa nchekwa n'ozuzu ndị ọrịa, n'agbanyeghị ọnọdụ antibody, ma e wezụga mmụba nke ọnụ ọgụgụ mmeghachi omume na saịtị ịgba ọgwụ (oge dum usoro ọgwụgwọ, 4.7% na ndị ọrịa nwere ezigbo antibody ọnọdụ, ma e jiri ya tụnyere 2.5% ndị ọrịa seronegative). Ọtụtụ mmeghachi omume na saịtị ịgba ahụ dị nro, n'agbanyeghị ọnọdụ antibody.
Enweghi mmeghariri nke ozo ma e jiri ya tụnyere glucagon ala di iche ma obu GLP-1 endogenous.
Mmeghachi omume nfụkasị ahụ.
N'ime oge ọgwụgwọ 24 izu bụ isi, a na-ahụta mmeghachi omume nfụkasị nwere njikọ metụtara lixisenatide (dị ka mmeghachi omume anaphylactic, angioedema, na urticaria) na 0.4% nke ndị ọrịa e mesoro lixisenatide, ebe enwere ike nfụkasị ahụ mere ihe na-erughị. n'ime 0.1% nke ndị ọrịa na-anata placebo.
A malitere mmeghachi omume anaphylactic na 0.2% nke ndị ọrịa na-anata lixisenatide, ma e jiri ya tụnyere enweghị mmeghachi omume na ndị otu placebo.
Ọtụtụ n'ime mmeghachi omume nfụkasị ahụ akọwapụtara na ogo siri ike. Otu okwu mmeghachi omume anaphylactoid guzobere n'oge ọnwụnwa nke ụlọ ọgwụ lixisenatide.
Oku obi.
N'ime ihe ọmụmụ ndị metụtara ndị ọrụ afọ ofufo siri ike, a chọpụtara na-enwekwu ịrị elu obi obi mgbe nchịkwa 20 μg nke lixisenatide. Cardiac arrhythmia, karịchaa, tachycardia (0.8% ma e jiri ya tụnyere mwepụ ọgwụ).
N'ime oge ọgwụgwọ 24 izu bụ isi, ihe kpatara nkwụsị n'ihi ihe ọjọọ bụ 7.4% na Lixumia otu ma e jiri ya tụnyere 3.2% na placebo otu. Mmeghachi omume kachasị njọ nke dugara na ịkwụsị ọgwụgwọ na otu nke isiiisenatide bụ ọgbụgbọ (3.1%) na vomiting (1.2%).
Kpesa mmeghachi omume ọjọọ ndị a na-enyo enyo.
Ọ dị mkpa ịkpesa mmeghachi omume na-enyo enyo mgbe ịdenye aha ọgwụ. Nke a ga - enyere gị aka ịga n'ihu na ịchekwa oke nha uru / ọghọm nke ọgwụ. A na-arịọ ndị ọrụ ahụike ka ha kọọ mmeghachi omume ọ bụla nke a na-enyo enyo site na sistemụ mba.

Enweghị ahụmịhe ọgwụgwọ maka ojiji nke lixisenatide n'ime ndị ọrịa nwere ụdị ọrịa shuga mellitus nke 1; ekwesighi iji ya mee ndị ọrịa a.
Ekwesighi iji Lixisenatide na-agwọ ketoacidosis mamịrị.
Ọrịa pancreatitis.
Ejikọtara ojiji nke glucagon-like peptide-1 recepor agonists (GLP-1) na ihe egwu nke ibute ọrịa ụjọ.
Achọpụtala ọtụtụ ihe dị iche iche metụtara nnukwu ọrịa ọria pancreatitis site n'iji lixisenatide, n'agbanyeghị na enwebeghị mmekọrịta dị na-akpata.
Ọ dị mkpa iji mee ka ndị ọrịa mara banyere ihe mgbaàmà ọ na-egosi na ọ na-arịa ọria mgbu: ịnọgidesi ike, mgbu afọ. Ọ bụrụ na a na-enyo enyo pancreatitis, ọ dị mkpa ịkwụsị ojiji nke lixisenatide, ọ bụrụ na ekwenyela na ọ bụrụ na ọ bụrụ na a chọpụta na ọ bụrụ na ọ bụrụ na a chọpụta na ọ bụrụ na ọ pụta ihe ọ bụla, a gaghị enwe ike ịmaliteghachi ojiji ahụ. Ekwesịrị iji nlezianya mee ihe mgbe ejiri ya na ndị ọrịa mgbe ọrịa pancreatitis gasịrị.
Ọrịa eriri afọ.
Ojiji nke agonists nke ndị na-anabata GLP-1 nwere ike jikọta mmeghachi omume na-adịghị mma site na eriri afọ.
Achọpụtaghị Lixisenatide na ndị ọrịa nwere nnukwu eriri afọ, gụnyere gastroparesis siri ike, na maka nke a, akwadoghị ojiji nke sitisenatide.
Alrụ ọrụ na-arụ ọrụ na ụlọ.
Onweghi ihe nlere anya di nma na ndi oria nwere nsogbu nkpuru oru ha aru oru (nwechara ikike 30-50 ml / min), onweghi ihe nlere anya di nma na ndi oria nwere nsogbu ezigharia nke oma (nwepu ihe oma kari 30 ml / min) ma obu na ndi oria n’azu oria nke oria. akụrụ. N'ime ndị ọrịa nwere ọrụ akwara adịghị mma, ekwesịrị iji Lixumia kpachara anya. N'ime ndị ọrịa nwere nnukwu ọrụ gbasara akụrụngwa ma ọ bụ na ndị ọrịa nọ n'ọgbọ nke ọrịa akụrụ, akwadoghị ojiji (lee "usoro onunu ogwu na nchịkwa" na "Pharmacokinetics").
Hypoglycemia.
Ndị ọrịa na-anata Lixumia nke nwere sulfonylurea ma ọ bụ insulin insal nwere ike ịnwe ohere dị elu nke hypoglycemia. Iji belata ihe ize ndụ nke hypoglycemia, ọ ga-ekwe omume belata ọgwụ nke sulfonylurea ma ọ bụ insulin basal (lee "Usoro Ọgwụ na Nchịkwa"). Ekwesighi iji Lixumia jikọtara ya na insulin basal na sulfonylurea n'ihi ụba ọrịa hypoglycemia.
Ọgwụ Ndị Na-eme Mgbako
Iji nwayọ na-ewepu ihe dị n’ime afọ na iji lixisenatide nwere ike belata mmịpụta nke ọgwụ ndị a na-eji ọnụ nye. N'ime ndị ọrịa na-anata ọgwụ a na-achọ ọnụ ga-achọ ka a na-anabata eriri afọ, ngwa ngwa nlebara anya, ma ọ bụ ọgwụ nwere obere usoro ọgwụgwọ, Lixumia kwesịrị iji nlezianya mee ihe. A na-enye ndụmọdụ pụrụ iche banyere ojiji ọgwụ ndị dị na ngalaba "Mmekọrịta Ọgwụ".
Onu ogugu ndi mmadu.
A amụbeghị Lixisenatide na njikọ ndị dipeptidyl peptidase-4 (DPP-4).
Onweghi ihe nlele di na ndi ọrịa nwere nsogbu obi.
Akpịrị ịkpọ nkụ.
A ga-adụ ndị ọrịa na-enye ọgwụgwọ Lixumia nsogbu nke akpịrị ịkpọ nkụ n'ihi mmeghachi omume akwara na eriri afọ ma na-akpachara anya iji zere hypovolemia.
Ndị pụrụ iche.
Ọgwụ nwere metacresol, nke nwere ike ibute mmeghachi ahụ nfụkasị.
Womenmụ nwanyị dị afọ iri.
A naghị atụ aro Lixumia maka ụmụ nwanyị ịmụ nwa na-adịghị eji ọgwụ mgbochi afọ.
Ime
Enweghi data zuru oke banyere iji Lixumia n'ime ụmụ nwanyị dị ime. Ihe omumu omumu omumu egosila ututu omumu.
Amaghị ihe mmadụ nwere ike isi mee ya.
Ekwesighi iji Lixumia mee n'oge afọ ime. Kama, a na-atụ aro insulin.
Ọ bụrụ na onye ọrịa chọrọ ịtụrụ ime ma ọ bụ tụtara ime, a ga-akwụsị ịhapụ Lixumia.
Lactation.
Amabeghị ma Lixumia na-abanye na mmiri ara ara mmadụ. Ekwesighi iji Lixumia mee ihe n'oge a na-enye ya ara.
Ọmụmụ.
Ọmụmụ banyere ọmụmụ adịghị egosi mmetụta na-emerụ ahụ na ọmụmụ nke ọmụmụ.
Akụkụ nke nsonaazụ ọgwụ ahụ nwere ike ịnya ụgbọ ma ọ bụ usoro nwere ike ibute.
Lyskumia emetụtaghị ma ọ bụ nwee obere mmetụta na ịkwọ ụgbọala ma ọ bụ igwe. Mgbe ejikọtara ya na ọgwụ insulinlurea ma ọ bụ insulin, a gwara ndị ọrịa ka ha kpachara anya iji zere hypoglycemia mgbe ha na-anya ụgbọala ma ọ bụ na-eji igwe.

Ọnọdụ nchekwa.
Chekwaa n 'okpomoku okpukpo abuo rue C ka 8 n’ebe anara oji. Emela ifriizi. Zere friza.
Mgbe ojiji nke mbụ, enwere ike iji mkpịsị sirinji ụbọchị iri na anọ mgbe ọ na-adịkarịghị ogo 30. Emela ifriizi.
Ekwela ka ụmụaka ghara iru ya.

Ntuziaka maka pen Lixumia sirinji
Tupu iji mkpịsị mkpụrụ Lixumia, gụọ ntuziaka ndị a.
Weghachite ntuziaka ọgwụ maka ike ọgwụ maka akwụkwọ maka ọdịnihu.
Lixumia bụ mkpịsịwọ mkpụrụ eji agbaji mkpụrụeji ka eji dochie ya. Usoro ọ bụla nwere 10 μg ma ọ bụ 20 μg nke lixisenatide na 0.2 ml.
• Mee naanị otu ntụtụ kwa ụbọchị.
• Mkpịsị mkpụrụ sirinji Lixumium nke ọ bụla nwere 14 usoro ihe jupụtara. Achọghị usoro nke ọ bụla.
• Tupu iji mkpịsị sirinji, gwa dọkịta gị ka ị ga-esi nye ọgwụ ahụ.
• Ọ bụrụ na ịnweghị ike ịgbaso ntuziaka ahụ n'onwe gị, ma ọ bụ na ịnweghị ike ijikwa mkpụrụ edemede sirinji (dịka ọmụmaatụ, ọ bụrụ na ị nwere nsogbu ọhụụ), nyere enyemaka n'èzí.
• Mkpịsị akwụkwọ a bụ maka naanị otu onye. Amachibidoro ịkekọrịta.
• Na-elebanye anya mgbe niile iji hụ na ọdịiche ahụ adịghị Lixumia. Leleekwa maka nchekwa emebiela.
Iji ọgwụ ọjọọ eme ihe nwere ike ibute ahụike gị.
• Anwakwala wepu mmiri mmiri na kateeti na iji sirinji. Ozi agịga (nhọrọ)
• Jiri naanị agịga akwadoro maka iji Lixumia. Jiri agịga a pụrụ ịtụfu site na 29 ruo 32 na mkpụrụ edemede Lixumia .. Ọ ga-aka mma ma ọ bụrụ na ị jụọ dọkịta gị banyere ogologo na nha nke agịga.
• Ọ bụrụ na etinye ya na enyemaka n'èzí, aga-elerịrị anya ka ọ ghara imerụ onye ọ bụla were anya. Ma ọ bụghị ya, ikesa ọrịa ga-ekwe omume.
• Maka ọgwụ nke ọ bụla, jiri agịga ọhụrụ iji gbochie mmerụ Lixumia yana ịzụta enwere ike.

Ngosipụta nke ọgwụ Lixumia

Elldị nke abụọ nke ọrịa shuga mellitus na ndị okenye iji nweta njikwa glycemic na ndị ọrịa nke ọrịa mellitus na-adịghị achịkwa site na usoro hypoglycemic na-aga n'ihu.

E gosipụtara Lixumia yana ọgwụ ọgwụ hypoglycemic ndị a:

• metformin
• ọgwụ ọgwụ hypoglycemic nke ụdị sulfonylurea otu,
• nchikota ọgwụ ndia.

Lixumia egosiputara na insulin basal:

• na monotherapy,
• yana metformin,
• yana ọgwụ onodu hypoglycemic nke ụdị sulfonylurea otu.

Usoro usoro onunu ogwu

Ọgwụ izizi bụ 10 microgram nke Lixumia otu ugboro kwa ụbọchị maka ụbọchị 14.

Mgbe ahụ a ga-abawanye dose nke Lixumia na 20 mcg otu ugboro n'ụbọchị. Mkpụrụ ọgwụ a na-akwado.

Mgbe agbakwunye Lixumia na usoro ọgwụgwọ metformin dị, Metformin nwere ike ịga n'ihu na-enweghị ịgbanwe usoro ya.

Mgbe agbakwunye Lixumia na ọgwụ eji eme ọgwụ hypoglycemic ọgwụ nke sulfonylurea ma ọ bụ na ngwakọta nke ọgwụ hypoglycemic ọgwụ nke sulfonylurea otu na insal basal, iji belata ihe ize ndụ nke hypoglycemia, ị nwere ike ịtụle iwelata dose nke ọgwụ hypoglycemic ọgwụ nke ngalaba sulfonylurea ma ọ bụ basal insulin. Ntụziaka pụrụ iche ”).

Iji ọgwụ Lixumia achọghị nleba anya pụrụ iche nke mkpụkọ glucose dị n'ọbara. Agbanyeghị, mgbe ejikọtara ya na ọgwụ hypoglycemic ọgwụ nke sulfonylurea otu ma ọ bụ insal insulin, nlebara anya gbasara glucose ọbara ma ọ bụ nyocha onwe ya (njikwa site na onye ọrịa) nke ịgwọ glucose ọbara iji mezie ọnụọgụ hypoglycemic ọgwụ nke otu sulfonylurea ma ọ bụ insal insal.

Ndị otu ọrịa pụrụ iche

Childrenmụaka na ndị nọ n’agbata afọ iri na asatọ

Ka ọ dị ugbu a, amụbeghị nchekwa na ịdị irè nke ọgwụ Lixumia na ndị ọrịa na-erubeghị afọ 18.

Ndị okenye

Onweghi mgbanwe ndozi ọgwụ dabere na afọ onye ọrịa ahụ.

Ndị ọrịa nwere ọrịa imeju

Ọ dịghị mgbanwe ndozi ọgwụ chọrọ ka ndị ọrịa nwere ọrịa imeju daa.

Ọrịa enweghị akụrụ

Achọghị ndozigharị onwa n'ime ndị ọrịa nwere obere ọdịda akụrụngwa (mwepụ creatinine 50-80 ml / min) yana ọdịda akụrụngwa obere (mwepụ nke mkpụrụ osisi 30-50 ml / min).

Enweghị ahụmịhe ọgwụgwọ eji ọgwụ Lixumia eme ihe na ndị ọrịa nwere nnukwu akụrụ gbasara ọdịda (mwepu creatinine erughị 30 ml / min) ma ọ bụ enweghị njedebe akụrụngwa njedebe, yabụ na iji ọgwụ Lixumia eme ihe na ìgwè ndị ọrịa a ka amachibidoro.

A na-enye ọgwụ Lixumia 1 otu oge kwa ụbọchị n'ime 1 awa tupu nri mbụ n'ụbọchị ma ọ bụ n'ime otu elekere tupu nri mgbede. Ọ bụrụ n ’usoro nke ọzọ achọrọ, aga-enye ya n’ime otu elekere tupu nri ọzọ. A na-ahụ maka ọgwụ Lixumia subcutaneously na apata ụkwụ, mgbidi afọ ma ọ bụ ubu. Enweghị ike inye ọgwụ Lixumia ahụ intravenously na intramuscularly. Tupu ojiji, a ga-echekwa mkpụrụ ọnya Lixumia na friji na okpomọkụ nke 2-8 Celsius C na nkwakọ ngwaahịa ya iji kpuchido ya ka ekpughe ọkụ. Mgbe ojiji mbụ, mkpịsị ọrịị nke Lixumia kwesịrị ịchekwa ya mgbe ọ na-adịghị ihe karịrị 30 Celsius. Mgbe ojiji ọ bụla, mkpịsị ọrịị nke Lixumium kwesịrị iji okpu kpuchie ya ka ọ ghara ịcha ọkụ. Ekwesịrị ịchekwa Lixumia Syringe Pen site na iji agịkọta agbakwunye. Ejila mkpụrụ edemede Lixumia sirinji ma ọ bụrụ na agbazee.

A ga-ewepụ Lixumia Syringe Pen mgbe ụbọchị iri na anọ gachara.

Mmetụta akụkụ

E kpebiri ugboro ole mmeghachi omume ọjọọ (HP) dị ka ndị a: oge ​​mgbe: ≥10%, ọtụtụ mgbe: ≥1% - 76 izu) mere na ọnụọgụ nke> 5% (ma ọ bụrụ na oge ha dị elu na ndị ọrịa na-ewere Lixumia ma e jiri ya tụnyere ndị ọrịa. na-a allụ ọgwụ ndị ọzọ atụnyere, gụnyere placebo), yana yana nke> 1% na ndị ọrịa nọ na Lixumia otu, ma ọ bụrụ na ugboro ole ha ji okpukpu abụọ karịa nke ọrịa HP a na ndị ọrịa na-anata ọgwụ ntụnyere (gụnyere placebo) .

Ọrịa na nje

Arịa, ọrịa akụkụ okuku ume na nke elu.

Ọrịa metabolism na nri nri

Ọbara hypoglycemia nke na-arịa ọrịa mgbaàmà (mgbe a na-eji Lixumia eme ihe na ọgwụ ọnụ hypoglycemic nke ụdị sulfonylurea otu na / ma ọ bụ insulin basal).

Ọrịa nke sistem

Ọrịa ọgbụgba

Nausea, vomiting, afọ ọsịsa.

Ọkpụkpụ akwara na uru ahụ

N'ime ndị ọrịa na-anata Lixumia na monotherapy ma ọ bụ na njikọta na metformin, hypoglycemia nke nwere ngosipụta nke ụlọ ọgwụ na-etolite ugboro ugboro, oge nke ya na ndị ọrịa natara Lixumia yiri nke ahụ na paịlị n'oge oge ọgwụgwọ niile.

N'ime ndị ọrịa butere Lixumia na ọgwụ ọnụ nke hypoglycemic ọgwụ nke sulfonylurea otu ma ọ bụ insalul basal, ọnọdụ nke hypoglycemia nke na-egosi na mgbaàmà nke ụlọ ọgwụ na-adịkarị ala.

N'ime oge ọgwụgwọ Lixumia dum, ọrịa hypoglycemia nke na-arịa ọrịa mgbaàmà dịtụ elu karịa nke nwere nkụda mmụọ, mgbe ejiri Lixumia na-agakọta:

• ya na ogwu hypoglycemic ọgwụ nke sulfonylurea otu na metformin,
• ya na basal insulin monotherapy,
• yana ngwakọta nke insulin basal na metformin.

N'ime oge ọgwụgwọ ahụ dum, mgbe ejiri Lixumia mee ihe na njikọta na monotherapy na ọgwụ hypoglycemic nke ọgwụ sulfonylurea, hypoglycemia nwere ngosipụta nke ụlọ ọgwụ mere na 22.7% nke ndị ọrịa lebara Lixumia na 15.2% nke ndị ọrịa natara placebo.Mgbe ejiri Lixumia mee ihe nrị atọ ugboro na ọgwụ ọnụ nke hypoglycemic ọgwụ nke sulfonylurea otu na insal basal, hypoglycemia nke nwere ngosipụta nke ụlọ ọgwụ mere na 47.2% nke ndị ọrịa e mesoro lixisenatide, na 21.6% nke ndị ọrịa na-agwọ ya.

Na mkpokọta, n'ofe oge ị takingụ ọgwụ ahụ n'oge a na-achịkwa usoro nyocha nke ụlọ ọgwụ III, nnwale nke nnukwu hypoglycemia na ngosipụta nke ụlọ ọgwụ kwekọrọ na gradation “ugboro ugboro” (na 0.4% na ndị ọrịa na-anata Lixumia na 0.2% na ndị ọrịa na-anata placebo) .

Ọrịa ọgbụgba

Ọ bụ ọgbụgbọ na ọgbụgbọ bụ ihe kachasị na-akọ HP n'oge usoro ọgwụgwọ izu iri abụọ na anọ. Ọnọdụ ọgbụgba dị elu na ndị ọrịa a na-agwọ Lixumia (26.1%) karịa ndị ọrịa a na-emeso placebo (6.2%). Ọrịa ọgbụgba dịkwa elu na ndị ọrịa a na-agwọ Lixumia (10.5%) karịa ndị ọrịa a na-emeso placebo (1.8%). Ndi umuaka ndi a bu ndi aru ojoo ma nwekwaa udiri oge ha mere n’ime izu ato izizi ha bidoro ọgwụgwọ. N'ime izu ndị na-esote, ha jiri nwayọ belata.

N'ime ndị ọrịa a na-agwọ Lixumia, ọrịa ọgbụgbọ dị ala (24.5%) karịa ndị ọrịa a na-eji exenatide ugboro 2 n'ụbọchị (35.1%), ugboro ole HP ndị ọzọ si na eriri afọ. otu ịgwọ ọrịa bụ otu.

Mmeghachi omume na ebe ntụtụ

A hụrụ mmeghachi omume na ebe ịgba ọgwụ ihe karịrị izu 24 ka enwere na 3.9% nke ndị ọrịa na-anata Lixumia, ebe ndị ọrịa na-anata ọgwụ, ha na-ahụ ugboro ole 1.4%. Ọtụtụ mmeghachi omume ahụ dị nro na ike ma ọ kwụsịghị ọgwụgwọ.

N'ihi ikike nke immunogenic nwere ọgwụ ndị nwere protein ma ọ bụ peptides, mgbe ọgwụgwọ Lixumia dị na ndị ọrịa, ịmepụta ọgwụ mgbochi na lixisenatide ga-ekwe omume. Na ngwụsị nke oge izu 24, n'ọmụmụ ihe na-achịkwa placebo, 69.4% nke ndị ọrịa e mesoro lixisenatide nwere nsonaazụ dị mma maka ọnụnọ ọgwụ mgbochi na lixisenatide. Agbanyeghị, mgbanwe dị na ntaneti HbA 1c, ma e jiri ya tụnyere nke ahụ tupu ojiji nke lixisenatide, bụ otu, n'agbanyeghị nsonaazụ ọma ma ọ bụ nke na-adịghị mma nke nyocha maka ọnụnọ ọgwụ mgbochi na lixisenatide. N'ime ndị ọrịa e mesoro lixisenatide ndị nwere akara HbA 1c, 79.3% nwere ule na-adịghị mma maka ọnụnọ nke mgbochi na lixisenatide ma ọ bụ titer nke mgbochi na lixisenatide dị n'okpuru obere njedebe maka nyocha ya, ebe ndị ọzọ ọrịa 20.7% nwere ọnya nke na - egbochi ọgwụ mgbochi isii.

Enweghị ọdịiche dị na profaịlụ nchekwa nchekwa n'ozuzu ndị ọrịa dabere na ọnọdụ mgbochi na lixisenatide, belụsọ maka mmụba ugboro ole nke mmeghachi omume na saịtị ịgba ahụ na ndị ọrịa nwere mmerụ ahụ. Imirikiti mmeghachi omume na saịtị ịgba ahụ dị nro, n'agbanyeghị ọnụnọ ma ọ bụ enweghị mgbochi na lixisenatide.

Enweghi mmegharị ọgwụ mgbochi nwere glucagon ala ma ọ bụ GLP-1 endogenous.

A hụrụ mmeghachi omume nfụkasị ahụ na ojiji nke lixisenatide (dị ka mmeghachi omume anaphylactic, angioedema na urticaria) n'oge ọgwụgwọ 24-izu bụ isi ka a hụrụ na 0.4% nke ndị ọrịa lebara Lixumia, ma e jiri ya tụnyere ihe na-erughị 0.1% nke ndị ọrịa n'ime otu placebo.

Ọgwụ ịkwụsị ọgwụ

Oge nkwụsị nke ọgwụ n'ihi ihe mmeghachi omume bụ 7.4% na Lixumia otu yana 3.2% n'ime ìgwè placebo. Ihe ndị kacha egbu egbu na-ebute HPD na-eduga n'iwepụta ọgwụgwọ n'òtù Lixumia bụ ọgbụgbọ (3.1%) na ọgbụgbọ (1.2%).

Mpempe usoro onunu ogwu

Ngwọta maka ntụtụ 0.05 mg / ml na 0.1 mg / ml

1 ml nke ihe ngwọta nwere:

ihe na - arụ ọrụ - lixisenatide 0.05 mg ma ọ bụ 0.10 mg

ndị na - ahụkarị: 85% glycerin, sodium acetate trihydrate, L-methionine, metacresol, hydrochloric acid, sodium hydroxide, mmiri maka injection.

Pipe mmiri na-enweghị ntụ.

Ngwongwo ogwu

Mgbe nchịkwa subcutaneous nye ndị ọrịa nwere ọrịa shuga nke 2, ọnụ ọgụgụ nnabata nke lixisenatide na-adị ngwa ngwa, agbanyeghị usoro enyere ya. Na agbanyeghị etu a siri jiri sitisenatide mee ihe otu ugboro ma ọ bụ n'ọtụtụ, na ndị ọrịa nwere ụdị shuga 2, nkezi tmax sitere na 1 ruo 3.5 awa. N'ihe banyere sistemụ subcutaneous nke lixisenatide rue afọ, apata ụkwụ ma ọ bụ ubu, enweghị ọdịiche pụtara ìhè dị na ọnụego mmiri.

Lixisenatide nwere ogo nke ejikọtara ọnụ (55%) na protein mmadụ.

Olu pụtara oke mgbe nchịkwa subisiaatide (Vz / F) dị ihe dịka 100 L.

Biotransformation na excretion

Dị ka peptide, sitisenatide na-agbaze site na nzacha zuru ụwa ọnụ na-esote tubular reabsorption na mmebi metabolic ọzọ, na-eduga na ịkpụbe obere peptides na amino acid, nke a na-etinye ọzọ na metabolism protein.

Mgbe nchịkwa nke ọtụtụ onunu ogwu na ndị ọrịa nwere ụdị shuga 2, ọkara ọkara iwepụ ọkara ndụ bụ ihe dịka awa 3 na nkezi mwepụ (CL / F) bụ ihe dịka 35 l / h.

Ndị ọrịa nwere ọrụ mgbazinye nsogbu

N'ime ndị ọrịa nwere obere (mwepụta nke mkpụrụedemede nke Cockcroft-Gault gbakọrọ, ọ bụ 60-90 ml / min), na-agafeghị oke (mwepụta nke creatinine bụ 30-60 ml / min) yana nnukwu nrụpụta gbasara akụrụ (mwepụta nke creatinine bụ 15-30 ml / min), AUC (mpaghara dị n'okpuru oge ịta ahụhụ n'oge usoro) ji 46%, 51% na 87% mụbaa.

Ndị ọrịa nwere ọria imeju

Ebe ọ bụ na lixisenatide bụ akụrụ nwere akụrụ, ndị ọrịa nwere oke akụrụ ọrụ na arụ ọrụ esonyeghi na ọmụmụ ọgwụ. Achọpụtaghị na ọrịa ịba ọcha n'anya ga-emetụta ọgwụ ọgwụ nke lixisenatide.

Inwe nwoke na nwanyi enweghi mmetụta di nkpa na ogwu banyere pharmacokinetics nke sitisenatide.

Dabere na nsonaazụ nke ọmụmụ pharmacokinetic na ndị ọrịa nke agbụrụ Caucasian, Japanese na Chinese, agbụrụ enweghị mmetụta dị ukwuu na ọgwụ ọgwụ nke lixisenatide.

Afọ anaghị enwe mmetụta dị egwu n’ụlọ ọgwụ na ọgwụ ọgwụ nke lixisenatide. Na nyocha nke pharmacokinetic na ndị ọrịa anaghị arịa ọrịa shuga, ojiji nke lixisenatide 20 μg n'ime ndị ọrịa nwere agadi (ndị ọrịa 11 dị afọ 65 ruo afọ 74 na ndị ọrịa dị afọ 75 ruo afọ 75), na-eduga na mmụba dị elu na PPK nke lixisenatide site na 29%, ma e jiri ya tụnyere ndị ọrịa 18 dị afọ 18 ruo afọ 45, ọ nwere ike jikọtara ya na ọrụ ebugharị belata na ndị agadi.

Ikike anụ ahụ enweghị mmetụta dị ukwuu na clinical na PPK egosi nke lixisenatide.

Lixisenatide bụ agonist nhọrọ nke ndị na-anabata GLP-1 (glucagon-like peptide-1). Ihe nnabata nke GLP-1 bu ihe nlere anya maka GLP-1, homonụ nke ime mmụọ nke na-eme ka insulin na-egbochi glucose site na mkpụrụ ndụ beta pancreatic.

Mmetụta nke lixisenatide na-agbagha site na mmekọrịta dị n'etiti ya na ndị na-anabata GLP-1, na-eduga na mmụba intracellular cyclic adenosine monophosphate (cAMP). Lixisenatide na-akpali mmiri ọgwụ insulin mgbe ọ̀tụ̀tụ̀ shuga dị n'ọbara na-amụba, ma ọ bụghị na Normoglycemia, nke na-egbochi ihe ize ndụ nke hypoglycemia.

N'otu oge ahụ, a na-ebelata glucagon nzuzo. Site na hypoglycemia, a na-edozi usoro nchekwa nke glucagon zoro ezo. Lixisenatide na-egbochi iwepu afọ ya, na -ebelata ọsọ nke glucose na-enweta site na nri dị n'ọbara.

Mgbe a na-eji ya otu ugboro kwa ụbọchị na ndị ọrịa nwere ụdị shuga 2, lixisenatide na-eme ka nchịkwa glycemic dị mma n'ihi nsonaazụ ozugbo na ogologo oge nke belata nsị glucose mgbe nri gasịrị na afọ efu.

Ekwenye mmetụta a na glucose postprandial n'ọmụmụ izu anọ, iji tụnyere Liraglutide 1.8 mg otu ugboro kwa ụbọchị yana njikọta na metformin. Mbelata site na ọkwa mbụ nke pPC nke 0: 30-4: 30 h nke glucose plasma mgbe nri ule ahụ bụ:

–12.61 awa * mmol / L (-227.25 awa * mg / dL) n'ime otu lixisenatide na

- 4.04 awa * mmol / L (–72.83 awa * mg / dL) na otu liraglutide. Ekwenyekwara na nke a n'ọmụmụ izu asatọ ma e jiri ya tụnyere Liraglutide edepụtara tupu nri ụtụtụ agụnyere insulin glargine yana ma ọ bụ na-enweghị metformin.

Arụmọrụ arụmọrụ yana nchekwa

N'ime usoro ọmụmụ nke III dechara, achọpụtara na na njedebe nke oge ọgwụgwọ 24 izu bụ isi, ihe karịrị 90% nke ndị ọrịa nwere ike ịnọgide na-enwe usoro mmezi nke Lixumia 20 μg otu ugboro n'ụbọchị.

Usoro ọgwụgwọ ndị ọzọ ejikọtara ọnụ na ọgwụ mgbochi antidiabetic

Na ngwụsị nke usoro ọgwụgwọ izu 24 zuru ezu na Lixumia, yana metformin, sulfonylurea, pioglitazone, ma ọ bụ ngwakọta nke ọgwụ ndị a, gosipụtara ọnụ ọgụgụ dị ukwuu na-ebu ọnụ na plasma na-ebu ọnụ HbA1c na glucose post-2 awa mgbe nri ule ka e jiri ya tụnyere placebo. Mbelata nke HbA1c dị mkpa mgbe enyere ọgwụ a otu ugboro n'ụbọchị, n'agbanyeghị ma eji ya n'ụtụtụ ma ọ bụ n'anyasị. Ngosipụta dị otú ahụ na HbA1c agbatịwo n'ọmụmụ ogologo oge na-adịgide ruo izu 76.

Ọkwa glucose Postprandial

Ọgwụ Lixumia butere mgbatị glucose post-2 postprandial mgbe elekere abụọ gachara mgbe nri ule gachara, ọnụọgụgụ kachasị elu na placebo, agbanyeghị ọgwụgwọ bụ isi.

Na ngwụsị nke oge ọgwụgwọ 24 izu, ọgwụ Lixumia na njikọta metformin na / ma ọ bụ sulfonylurea na ọnwụnwa niile a na-achịkwa dugara na mgbanwe mgbanwe na ịdị arọ nke anụ ahụ sitere na -1.76 n'arọ ruo –2.96 n'arọ.

Mgbanwe n’arụ ahụ sitere na ọkwa mbụ n’ime oke si - 0.38 kg ruo -1.80 kg hụkwara n’etiti ndị ọrịa na-anata lixisenatide na mgbakwunye na insulin basal na-akwụghị ọtọ, ma ọ bụ na metformin ma ọ bụ sulfonylurea.

N'ime ndị ọrịa bidoro ị insụ ọgwụ insulin, n'ime mkpụrụ nke sitisenatide, ịdị arọ nke anụ ahụ nọgidere na-agbanweghi agbanwe, ebe a gosipụtara mmụba na placebo. N'ime ihe ọmụmụ ogologo oge na-adigide ruo izu izu 76, ịdị arọ ahụ kwụ ọtọ.

Ọmụmụ nyocha nke Lixumia na-egosi arụmọrụ beta cell ka arụpụtara dị ka nha nha site na usoro ntule arụmọrụ mkpụrụ ndụ beta (HOMO-β / HOMA-β).

Ntụle obi

N'ime ule niile na - achịkwa placebo nke frasi nke III, ndị ọrịa nwere ụdị ọrịa shuga 2 egosighi mmụba n'ọtụtụ mkpụrụ obi.

Ndị okenye

Ndị mmadụ gbara afọ 70

Lixisenatide nyere mmụba dị ukwuu na haemoglobin glycated (HbA1c) (mgbanwe site na -0.64% ma e jiri ya tụnyere placebo, etiti ntụkwasị obi 95% (CI): site -0.810% ka -0.464%, p

Nsonaazụ nke Lixumium ngwọta

Nchịkọta profaịlụ Nche

Ihe karịrị ndị ọrịa 2,600 na nnukwu ọmụmụ 8 na-achịkwa placebo ma ọ bụ ọmụmụ III nke nwere njikwa ike natara Lixumia ma ọ bụ na monotherapy ma ọ bụ na njikọta metformin, sulfonylurea (na ma ọ bụ na-enweghị metformin) ma ọ bụ insulin basal (yana ma ọ bụ na-enweghị metformin ma ọ bụ na ọ na-enwe sulfonylurea) ma ọ bụ na-enweghị ya).

Mmeghachi omume kachasị na-akọkarị n'oge ule ụlọ ọgwụ bụ ọgbụgbọ, ọgbụgbọ, na afọ ọsịsa. Mmeghachi omume ndị ahụ na-adịkarị nwayọọ ma dịkwa obere.

Enweelakwa ọrịa nke hypoglycemia (mgbe e jiri Lixumia mee ihe na njikọta nke sulfonylurea na / ma ọ bụ insulin basal) yana isi ọwụwa. A hụrụ mmeghachi omume nfụkasị na 0.4% nke ndị ọrịa na-eji Lixumia.

N'okpuru bụ mmeghachi omume dị njọ nke mere na otutu nke> 5%, ọ bụrụ na ugboro ugboro nke ihe dị elu n'etiti ndị ọrịa na-anata Lixumia karịa n'etiti ndị ọrịa na-anata ọgwụ ntụnyere niile, gụnyere mmeghachi omume ọjọọ na oge nke ≥ 1% na ìgwè ndị ọrịa na-anata Lixumia, ọ bụrụ na ugboro ugboro nke ihe a mere ugboro abụọ karịa ugboro ole n’etiti otu ndị ọrịa na-anata ọgwụ ntụnyere niile.

Mmeghachi omume ọjọọ guzobere na nchịkwa placebo na usoro III nke nwere njikwa ike n'oge oge ọgwụgwọ niile (gụnyere oge gafere oge ọgwụgwọ 24-izu mbụ na ọmụmụ with 76 izu nke ọgwụgwọ niile).

• hypoglycemia (ya na insulinlurea na / ma obu insal insal)

• isi ọwụwa

• ọgbụgbọ, vomiting, afọ ọsịsa

Ọtụtụ mgbe (≥ 1/100 to 5% fat payday bolsan zhalymsyz reactionar berylgen, dinta payda boli zhіlіgі barlyқ salistyru ọgwụ taryn alғan edelushіler toptara arasynda zhіlіlіndydydelda 1%

Posbo-baқılanatyn әne belsendi baқylanatyn III frasi ғ zertteulerde bүkіl emdela kezeңi boyina (bүkіl emdeudің ≥ 76 aptasynda zertteulerde negizy-24

Ntụziaka pụrụ iche

N'ime ndị ọrịa na-anata Lixumia na monotherapy ma ọ bụ na njikọta na metformin, hypoglycemia nke nwere ngosipụta nke ụlọ ọgwụ na-etolite ugboro ugboro, oge nke ya na ndị ọrịa natara Lixumia yiri nke ahụ na paịlị n'oge oge ọgwụgwọ niile.

N'ime ndị ọrịa butere Lixumia na ọgwụ ọnụ nke hypoglycemic ọgwụ nke sulfonylurea otu ma ọ bụ insalul basal, ọnọdụ nke hypoglycemia nke na-egosi na mgbaàmà nke ụlọ ọgwụ na-adịkarị ala.

N'ime oge ọgwụgwọ Lixumia dum, ọrịa hypoglycemia nke na-arịa ọrịa mgbaàmà dịtụ elu karịa nke nwere nkụda mmụọ, mgbe ejiri Lixumia na-agakọta:

- ya na ọgwụ hypoglycemic ọgwụ nke sulfonylurea otu na metformin,

- na monotherapy na basal insulin,

- yana ngwakọta nke insulin basal na metformin.

N'ime oge ọgwụgwọ ahụ dum, mgbe ejiri Lixumia mee ihe na njikọta na monotherapy na ọgwụ hypoglycemic nke ọgwụ sulfonylurea, hypoglycemia nwere ngosipụta nke ụlọ ọgwụ mere na 22.7% nke ndị ọrịa lebara Lixumia na 15.2% nke ndị ọrịa natara placebo. Mgbe ejiri Lixumia mee ihe nrị atọ ugboro na ọgwụ ọnụ nke hypoglycemic ọgwụ nke sulfonylurea otu na insal basal, hypoglycemia nwere ngosipụta nke ụlọ ọgwụ malitere na 47.2% nke ndị ọrịa e mesoro lixisenatide, na 21.6% nke ndị ọrịa na-agwọ ya.

Na mkpokọta, oge niile ị theụ ọgwụ ahụ n'oge ọnwụnwa ụlọ ọgwụ III a na-achịkwa, nnabata nke nnukwu hypoglycemia na ngosipụta nke ụlọ ọgwụ kwekọrọ na gradation “ugboro ugboro.

N'ihi ikike nke immunogenic nwere ọgwụ ndị nwere protein ma ọ bụ peptides, mgbe ọgwụgwọ Lixumia dị na ndị ọrịa, ịmepụta ọgwụ mgbochi na lixisenatide ga-ekwe omume. Na ngwụsị nke oge izu 24, n'ọmụmụ ihe na-achịkwa placebo, 69.4% nke ndị ọrịa e mesoro lixisenatide nwere nsonaazụ dị mma maka ọnụnọ ọgwụ mgbochi na lixisenatide.Agbanyeghị, ngbanwe ntụpọ HbA1c, atụnyere nke ahụ tupu ojiji nke lixisenatide, bụ otu, n'agbanyeghị nsonaazụ ọma ma ọ bụ nke na-adịghị mma nke nyocha maka ọnụnọ ọgwụ mgbochi na lixisenatide. N'ime ndị ọrịa e mesoro lixisenatide jiri akara HbA1c, 79.3% nwere ule na-adịghị mma maka ọnụnọ nke mgbochi na lixisenatide ma ọ bụ titer nke mgbochi na lixisenatide dị n'okpuru obere njedebe nke quantification ya, na ndị ọzọ 20.7% nke ndị ọrịa nwere ọnụọgụ. na - achọpụta mkpụrụ ndụ ihe mgbochi nke isiitienatide.

Enweghị ọdịiche dị na profaịlụ nchekwa nchekwa n'ozuzu ndị ọrịa dabere na ọnọdụ mgbochi na lixisenatide, belụsọ maka mmụba ugboro ole nke mmeghachi omume na saịtị ịgba ahụ na ndị ọrịa nwere mmerụ ahụ. Imirikiti mmeghachi omume na saịtị ịgba ahụ dị nro, n'agbanyeghị ọnụnọ ma ọ bụ enweghị mgbochi na lixisenatide.

Enweghi mmegharị ọgwụ mgbochi nwere glucagon ala ma ọ bụ GLP-1 endogenous.

Usoro onunu ogwu na nhazi

Usoro ọgwụgwọ mbu: usoro onunu ogwu amalite na Lixumia 10 mcg otu ugboro n ’ụbọchị iri na anọ.

Igosi ndozi: nchịkwa nke onodu ndozi nke 20 mcg Lixumia otu ugboro n’ụbọchị amalite n’ụbọchị iri na ise.

Maka usoro mmezi, a na-eji mmiri ọgwụ Lixumia nke 20 mcg eme ihe. Maka usoro ịmalite, a ga-eji ọgwụ 10 μg Lixumia injection mee ihe.

A na-ewebata Liksumiya otu ugboro n'ụbọchị, otu awa tupu nri ọ bụla. Ọ kachasị mma, a na-eme ọgwụ Lixumia kwa ụbọchị tupu otu nri, mgbe ahọpụtara oge ọchịchị kachasị adaba. Ọ bụrụ n ’ọgwụ Lixumia na-efu ụzọ, a ga-emerịrị ọgwụ tupu otu elekere.

Mgbe ị na-ede Lixumia, na mgbakwunye na ịnata ọgwụgwọ na metformin, dose nke metformin dị ugbu a nwere ike agaghị agbanwe agbanwe.

Mgbe ị na-edepụta Lixumia, na mgbakwunye na ị nweta ọgwụgwọ na sulfonylurea ma ọ bụ insal insulin, enwere ike belata dose nke sulfonylurea ma ọ bụ insulin insal iji belata ihe ize ndụ nke hypoglycemia.

Ekwesighi iji ọgwụ Lixumia tinye ya na insulin basal na sulfonylurea n'ihi oke nsogbu hypoglycemia (lee “ntuziaka pụrụ iche”).

Ojiji nke Lixumia achoghi nlebara anya puru iche nke uzo glucose obara. Agbanyeghị, mgbe ejikọtara ya na insulin nke mmiri ma ọ bụ insulin basal, inyocha glucose ọbara ma ọ bụ nyocha onwe gị nke glucose ọbara nwere ike ịdị mkpa iji mezie ọnụọgụ nke sulfonylurea ma ọ bụ insulin basal.

Site na afọ, ọ naghị achọ ndozigharị dose.

Ndị ọrịa nwere ọrụ mgbazinye nsogbu

N'ime ndị ọrịa nwere ọrụ mkpado na-adịghị ala ma ọ bụ na-agafeghị oke, a naghị achọ ndozi dose. Enweghị ahụmịhe ọgwụgwọ na-arịa ndị ọrịa nwere nnukwu ọrụ na-arụ ọrụ na-arụ ọrụ nke ukwuu (nwechapụ ihe na-erughị 30 ml / min) ma ọ bụ na ndị ọrịa nwere ọrịa akụrụ nwere njedebe, na maka nke a, a naghị akwado ọgwụ Lixumia maka ìgwè ndị ọrịa a.

Ndị ọrịa nwere ọria imeju

Maka ndị ọrịa nwere nsogbu imeju na-adịghị mma, ọ dịghị mkpa ịgbanwe ndozi dose. Onu ogugu nke umuaka

Emebebeghị nchekwa na ịdị mma nke lixisenatide na ụmụaka na ndị nọ n'afọ iri na asatọ. Enweghị data ọ bụla.

Ofzọ nlekọta

E gosipụtara Lycumum maka nchịkwa subcutaneous na apata ụkwụ, afọ ma ọ bụ ubu. Can gaghị abanye na intravenously ma ọ bụ intramuscularly.

Ekwesighị iji Lixumia mee ihe ma ọ bụrụ na agbazere ya. Enwere ike iji liksumiya na mkpanaka mkpofu sitere na 29 ruo 32 caliber maka mkpịsị sirinji. Agaghị agịga mkpịsị mkpụrụ edemede.

Ọ dị mkpa ịkụziri onye ọrịa ka ọ tụfuo agịga mgbe ojiji nke ọ bụla dabere na iwu nke mkpofu mpaghara wee debe mkpịsị mkpụrụ na-enweghị ntinye. Nke a na - enyere aka igbochi mmetọ na ntachi nke agịga. Ọ bụ naanị otu onye ọrịa dere akwụkwọ a.

A ga-ekpofu ọgwụ ọ bụla ma ọ bụ ihe mkpofu ọ bụla na-eji ya eme ihe dịka iwu mkpofu mpaghara.

Na enweghị ọmụmụ ọmụmụ nnabata, ọgwụ agaghị agwakọta ya na ọgwụ ndị ọzọ.

Mkparịta ụka ọgwụ ọjọọ

Lixisenatide bụ peptide nke anaghị metabolized na ntinye cytochrome P450. N'ime nyocha nke vitro, lixisenatide emetụtaghị ọrụ nke ndị nọ na-anọchi anya nke cytochrome P450 ma ọ bụ ndị na-ebugharị mmadụ.

Iji nwayọ na-ewepu ihe dị n’ime afọ na iji lixisenatide nwere ike belata mmịpụta nke ọgwụ ndị a na-eji ọnụ nye. Ekwesịrị iji nlezianya nyochaa ndị ọrịa na-enweta ọgwụ na ntinye ọgwụgwọ dị warara ma ọ bụ ọgwụ chọrọ nlekọta anya, karịsịa mgbe ịmalite ọgwụgwọ na lixisenatide. Maka lixisenatide, ekwesịrị ị drugsụ ọgwụ ndị a n'ụzọ ọ bụla. Ọ bụrụ na a ga-eji ọgwụ ndị dị otú a were nri, a ga-adụ ndị ọrịa ọdụ ka ha were ya nri mgbe ọ bụla o kwere omume mgbe ejighị lixisenatide.

Maka ọgwụ ọnụ, dị ka ọgwụ nje, nke, karịsịa n'ihe banyere arụmọrụ, dabere na ntinye ọnụ ụzọ, a ga-adụ ndị ọrịa ọdụ ka ha were opekata mpe elekere 1 tupu ma ọ bụ 4 awa mgbe agba nke lixisenatide.

A ga-eji ụdị usoro ọgwụ gubanyere mmiri nwere ọgwụ nwere ike ị gwuo nri afọ n'ime elekere 1 tupu ma ọ bụ awa 4 emesịa ọgwụ isii.

Ejiri Paracetamol dị ka ihe atụ iji chọpụta mmetụta nke lixisenatide na mkpopụ nke ọdịnaya gastric. Mgbe ejiri otu paracetamol 1000 mg mee ihe, mpaghara dị n'okpuru usoro (PPC) na t1 / 2 nke paracetamol agbanweghị, n'agbanyeghị oge eji ya (tupu ma ọ bụ mgbe ịgba ọgwụ isii nke sitisenatide). Mgbe ejiri ya otu elekere 1 ma ọ bụ awa 4 mgbe 10 eng nke lixisenatide, Cmax nke paracetamol belatara, otu ụzọ, site na 29% na 31%, na ọkara nke tmax belatara, karị, site na 2.0 na 1.75 awa. Site n'iji 20 μg nke otu mmezi ahụ, a na-ebu amụma mbelata nke tmax na mbelata Cmax nke paracetamol.

Enweghi mmetụta na Cmax na tmax nke paracetamol mgbe ejiri paracetamol mee ihe elekere 1 tupu ojiji nke lixisenatide.

N'inye data dị n'elu, ọ dịghị mkpa idozi usoro nke paracetamol, mana ndọtị Tmax nke a hụrụ mgbe emere paracetamol awa 1-4 ka ewere lixisenatide kwesịrị ịmalite mgbe achọrọ ngwa ngwa iji rụọ ọrụ.

Mgbe etinyere otu ọgwụ mgbochi ọgwụ a na-ekwu n’ọnụ (ethinyl estradiol 0.03 mg / levonorgestrel 0.15 mg) 1 awa tupu ma ọ bụ elekere 11 mgbe etinyere 10 μg nke lixisenatide, Smax, PPC, t1 / 2 na tmax nke ethinyl estradiol na levonorgestrel agbanwebeghị.

Ojiji nke ọgwụ mgbochi 1 awa ma ọ bụ awa anọ mgbe ojiji nke lixisenatide emetụtaghị AUC na t1 / 2 nke etinyl estradiol na levonorgestrel, ebe Cmax nke ethinyl estradiol belatara, n'otu n'otu, site na 52% na 39%, Cmax nke levonorgestrel belatara 46% na 20%, na nkezi uru nke tmax ji nwayọ gbadaa site na awa 1-3.

Mbelata nke Cmax enweela mkpa gbasara ọgwụgwọ, ọ dịkwa mkpa idozigharị ọgwụ mgbochi afọ a.

Mgbe ị na-eji 20 μg nke lixisenatide na 40 mg nke atorvastatin n'ụtụtụ maka ụbọchị 6, mmetụta nke atorvastatin agbanweghị, ebe Cmax belatara site na 31% na tmax mụbara site na awa 3.25.

Achọpụtaghị mmụba dị otú ahụ maka tmax ma ọ bụrụ na ejiri atorvastatin na mgbede, na lixisenatide n'ụtụtụ, mana PPK na Cmax nke atorvastatin, otu aka ahụ, mụbara site na 27% na 66%.

Mgbanwe ndị a abụghị ihe dị mkpa n’ụlọ ọgwụ, ya mere, ọ dịghị mkpa ịgbanwere dose nke atorvastatin mgbe ejiri ya na sitisenatide.

Warfarin na ihe ndi ozo nke coumarin

Mgbe ojiji 25% nke warfarin jiri otutu onyunyo nke lixisenatide 20 μg, enweghị mmetụta ọ bụla na AUC ma ọ bụ INR (oke ijikọ ụwa ọnụ), ebe Cmax belatara site na 19% na tmax mụbara ruo awa 7.

Dabere na nsonaazụ ndị a, a chọghị ịgbanwe ọgwụ nke warfarin mgbe ejiri ya na lixisenatide, na-agbanyeghị, a na-atụ aro nnwale INR na ndị ọrịa na-a warụ ọgwụ warfarin na / ma ọ bụ coumarin n'oge mmalite ma ọ bụ njedebe nke ọgwụgwọ lixisenatide.

Ka ejikọtara ojiji nke lixisenatide 20 μg na 0.25 mg nke digoxin na steeti ịha nhata, PPC nke digoxin agbanweghị. Uru tmax nke digoxin mụbara site na awa 1.5, ọnụ ahịa Cmax belatara site na 26%.

Dabere na nsonaazụ ndị a, a chọghị imegharị digoxin mgbe eji ya na lixisenatide.

Ka ejikọtara ojiji nke lixisenatide 20 μg na 5 mg nke ramipril maka ụbọchị 6, PPK ramipril mụbara site na 21%, ebe Cmax belatara site na 63%. Ihe PPC na Cmax nke metabolite na-arụ ọrụ (ramiprilat) agbanweghị. Tmaxril ramipril na ramiprilat mụbara site n'ihe dị ka awa 2.5.

Dabere na nsonaazụ ndị a, a chọghị ndozi nke ramipril mgbe ejiri ya na lixisenatide.

Dodoụbiga ya ókè

N'oge nnwale ụlọ ọgwụ, a na-enye onyunyo nke lixisenatide ruo 30 mcg ugboro abụọ kwa ụbọchị nye ndị ọrịa nwere ụdị shuga 2 n'ọmụmụ izu 13. A hụrụ ihe na-akpata nsogbu nke eriri afọ.

N'ihe banyere oke ịdoụbiga mmanya ókè, dabere na akara ngosipụta na akara ọrịa, onye ọrịa ahụ kwesịrị ịmalite nkwado nkwado kwesịrị ekwesị, yana ịgbanye dose nke lixisenatide na usoro enyere ọgwụ.