Lixumia mankhwala: malangizo ntchito

Njira yothetsera utsogoleri wa sc ndi yowonekera, yopanda utoto.

Othandizira: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid solution 1 M kapena sodium hydroxide solution 1 M - mpaka pH 4.5, madzi d / ndi - mpaka 1 ml.

3 ml - makatoni (1) - ma cholembera a syringe (1) - mapaketi a makatoni.

Njira yothetsera utsogoleri wa sc ndi yowonekera, yopanda utoto.

Othandizira: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid solution 1 M kapena sodium hydroxide solution 1 M - mpaka pH 4.5, madzi d / ndi - mpaka 1 ml.

3 ml - makatoni (1) - ma cholembera a syringe (1) - mapaketi a makatoni.
3 ml - makatoni (1) - ma cholembera a syringe (2) - mapaketi a makatoni.
3 ml - makatoni (1) - ma cholembera a syringe (6) - mapaketi a makatoni.

Njira yothetsera utsogoleri wa sc ndi yowonekera, yopanda utoto.

Othandizira: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid solution 1 M kapena sodium hydroxide solution 1 M - mpaka pH 4.5, madzi d / ndi - mpaka 1 ml.

Njira yothetsera utsogoleri wa sc ndi yowonekera, yopanda utoto.

Othandizira: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid solution 1 M kapena sodium hydroxide solution 1 M - mpaka pH 4.5, madzi d / ndi - mpaka 1 ml.

3 ml - makatoni (2) ndi yankho la 0,05 mg / ml (10 μg / mlingo) ndi 0,1 mg / ml (20 μg / mlingo) - ma syringe pensulo (2) - mapaketi a makatoni.

Zizindikiro zogwiritsidwa ntchito

Type 2 shuga mellitus mwa achikulire kuti akwaniritse kuwongolera kwa glycemic mwa odwala omwe matenda awo a shuga sawongoleredwa ndi hypoglycemic yothandizira.

Cholinga cha Lixumia kuphatikiza ndi mankhwala otsatirawa a hypoglycemic akuwonetsedwa:

- mankhwala apakamwa a hypoglycemic a gulu la sulfonylurea,

- kuphatikiza kwa mankhwalawa.

Lixumia imafotokozedwanso limodzi ndi insulin:

- kuphatikiza ndi mankhwala a m'kamwa a hypoglycemic a gulu la sulfonylurea.

Contraindication

- Kuchulukitsa chidwi kwa munthu wogwira ntchito kapena zilizonse zomwe zakupatsani.

- Nthawi ya mkaka wa yoyamwitsa (yoyamwitsa).

- Matenda akulu am'mimba, kuphatikizapo gastroparesis.

- Kulephera kwambiri kwaimpso (kulengedwa kwa creatinine kosakwana 30 ml / min).

- Ana ndi achinyamata osakwana zaka 18.

Pokhala ndi mbiri ya kapamba, Lixumia iyenera kugwiritsidwa ntchito mosamala.

Momwe mungagwiritsire ntchito: Mlingo ndi njira ya chithandizo

Mlingo woyamba wa Lixumia ndi 10 mcg kamodzi patsiku kwa masiku 14. Kenako mlingo uyenera kuwonjezeka ndikukonzanso mlingo wa 20 mcg kamodzi patsiku.

Mankhwala akawonjezeredwa ku mankhwala a metformin omwe akupitilira, metformin ikhoza kupitilizidwa popanda kusintha mlingo wake.

Lixumia ikangowonjezeredwa ku mankhwala omwe alipo ndi mankhwala a hypoglycemic omwe ali m'gulu la sulfonylurea kapena kuphatikiza kwa mankhwala ena amkamwa a hypoglycemic a gulu la sulfonylurea ndi insal insulini, kuchepetsedwa kwa mankhwala am'magazi a hypoglycemic a gulu la sulfonylurea kapena insal insulin ikhoza kuthandizidwa kuchepetsa chiopsezo cha hypoglycemia.

Kugwiritsa ntchito Lixumia sikufuna kuwunika kwapadera kwa kuchuluka kwa shuga m'magazi. Komabe, mukagwiritsidwa ntchito limodzi ndi mankhwala am'magazi a hypoglycemic a gulu la sulfonylurea kapena insal insulin, kuyang'anira kuchuluka kwa shuga wamagazi kapena kudziyang'anira nokha (kuwongolera wodwalayo) kwa kuphatikiza kwa shuga wamagazi kungafunike kusintha muyezo wa mankhwala a hypoglycemic a group la sulfonylurea kapena basal insulin.

Magulu apadera a odwala

Ana ndi achinyamata ochepera zaka 18: pakadali pano, chitetezo ndi luso la mankhwalawa m'gululi la odwala silinaphunzire.

Okalamba: kusintha kwa mankhwalawa sikofunikira kutengera zaka za wodwalayo.

Odwala omwe ali ndi vuto la chiwindi: Kusintha kwa mankhwalawa sikofunikira kwa odwala omwe ali ndi vuto la chiwindi.

Odwala aimpso kulephera: kusintha kwa mankhwalawa sikofunikira kwa odwala omwe ali ndi vuto lochepetsa aimpso (creatinine chilolezo cha 50-80 ml / min) ndi kulephera kwapakati kwaimpso (creatinine chilolezo 30-50 ml / min). Palibe zochizira ndi Lixumia mwa odwala omwe amalephera kwambiri aimpso (creatinine chilolezo chochepera 30 ml / min) kapena kulephera kwa impso, motero, kugwiritsa ntchito mankhwalawa pagulu la odwala kumatsutsana.

Lixumia amaperekedwa 1 kamodzi patsiku mkati mwa ola limodzi asanadye chakudya choyamba masana kapena mkati mwa ola limodzi asanadye chakudya chamadzulo. Ngati mlingo wotsatira utadumpha, uyenera kuperekedwa mkati mwa ola limodzi chakudya chotsatira chisanachitike.

Mankhwala chikuyendetsedwera subcutaneously mu ntchafu, khoma pamimba kapena phewa. Lixumia sayenera kutumikiridwa kudzera m'mitsempha kapena intramuscularly.

Musanagwiritse ntchito, cholembera cha Lixumia sichisungika mufiriji kuti chisenthe kwambiri ndi 2-8 ° C poika pake kuti chitetezedwe kuti chisawonekedwe. Mukatha kugwiritsa ntchito koyamba, cholembera cha syringe chimayenera kusungidwa pamtunda wosazizira 30 ° C. Mukatha kugwiritsa ntchito, cholembera chimakhala chotsekedwa ndi chipewa kuti chiziteteza ku kuwala. Cholembera sichingasungidwe ndi singano yomata. Osagwiritsa ntchito cholembera kuti chitauma.

Lixumia Syringe cholembera uyenera kutayidwa pambuyo masiku 14.

Zotsatira za pharmacological

Yogwira ntchito ya Lixumia lixisenatide ndi agonist wamphamvu komanso wosankha wa glucagon-ngati peptide receptors-1 (GLP-1). Cholandilira cha GLP-1 ndicholinga cha anthu omwe ali ndi chibadwa cha GLP-1, mahomoni obisika amkati, omwe amachititsa kuti shuga ayambe kudalira glucose kudzera maselo a beta-cell of pancreatic islets. Mphamvu ya lixisenatide imalumikizidwa ndi mgwirizano wake wapadera ndi zolandilira za GLP-1, zomwe zimayambitsa kuwonjezeka kwazinthu za cyclic adenosine monophosphate (cAMP). Lixisenatide imathandizira kubisalira kwa insulin ndi maselo a beta a pancreatic poyankha hyperglycemia. Pamene kuchuluka kwa shuga m'magazi kumatsika kukhala kwakhalidwe labwino, kukondoweza kwa insulin katemera kumatha, komwe kumachepetsa chiopsezo cha hypoglycemia. Mu hyperglycemia, lixisenatide nthawi imodzi imachepetsa kubisika kwa glucagon, komabe, chitetezo cha glucagon secretion poyankha hypoglycemia chatsala.

Chikhalidwe cha insulinotropic cha lixisenatide chikuwonetsedwa, kuphatikizapo kuwonjezeka kwa insulin biosynthesis ndi kukondoweza kwa maselo a beta a pancreatic islets mu nyama. Lixisenatide amachepetsa mphamvu ya m'mimba, potero amachepetsa kuchuluka kwa glucose wamagazi atatha kudya. Zotsatira zakutsuka kwa m'mimba zimathandizanso kuti muchepetse kunenepa.

Pakaperekedwa kamodzi patsiku kwa odwala omwe ali ndi matenda a shuga 2, lixisenatide imayendetsa bwino glycemic chifukwa imayamba kukhazikika pambuyo pakukhazikika kwake komanso kuchepa kwakukhazikika kwa magazi a shuga pambuyo pakudya komanso m'mimba yopanda kanthu.

Kutulutsa mawonekedwe, kapangidwe kake ndi ma CD

Njira yothetsera utsogoleri wa sc ndi yowonekera, yopanda utoto.

Mu 1 ml yankho lili:

yogwira mankhwala: lixisenatide - 0,05 mg,

excipients: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid solution 1 M kapena sodium hydroxide 1 M - mpaka pH 4.5, madzi d / ndi - mpaka 1 ml

3 ml - makatoni (1) - ma cholembera a syringe (1) - mapaketi a makatoni.

Njira yothetsera utsogoleri wa sc ndi yowonekera, yopanda utoto.

Mu 1 ml yankho lili:

yogwira mankhwala: lixisenatide - 0,5 mg,

excipients: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid solution 1 M kapena sodium hydroxide 1 M - mpaka pH 4.5, madzi d / ndi - mpaka 1 ml

3 ml - makatoni (1) - ma cholembera a syringe (1) - mapaketi a makatoni.
3 ml - makatoni (1) - ma cholembera a syringe (2) - mapaketi a makatoni.
3 ml - makatoni (1) - ma cholembera a syringe (6) - mapaketi a makatoni.

Njira yothetsera utsogoleri wa sc ndi yowonekera, yopanda utoto.

Mu 1 ml yankho lili:

yogwira mankhwala: lixisenatide - 0,05 mg,

excipients: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid solution 1 M kapena sodium hydroxide 1 M - mpaka pH 4.5, madzi d / ndi - mpaka 1 ml

Njira yothetsera utsogoleri wa sc ndi yowonekera, yopanda utoto.

Mu 1 ml yankho lili:

yogwira mankhwala: lixisenatide - 0,5 mg,

excipients: glycerol 85% - 18 mg, sodium acetate trihydrate - 3.5 mg, methionine - 3 mg, metacresol - 2.7 mg, hydrochloric acid solution 1 M kapena sodium hydroxide 1 M - mpaka pH 4.5, madzi d / ndi - mpaka 1 ml

3 ml - makatoni (2) ndi yankho la 0,05 mg / ml (10 μg / mlingo) ndi 0,1 mg / ml (20 μg / mlingo) - ma syringe pensulo (2) - mapaketi a makatoni.

Type 2 shuga mellitus mwa achikulire kuti akwaniritse kuwongolera kwa glycemic mwa odwala omwe matenda awo a shuga sawongoleredwa ndi hypoglycemic yothandizira.

Lixumia akuwonetsedwa limodzi ndi mankhwala otsatirawa a hypoglycemic:

- mankhwala apakamwa a hypoglycemic a gulu la sulfonylurea,

- kuphatikiza kwa mankhwalawa.

Lixumia akuwonetsedwa kuphatikiza ndi basal insulin:

- kuphatikiza ndi metformin,

- kuphatikiza ndi mankhwala a m'kamwa a hypoglycemic a gulu la sulfonylurea.

Kugwiritsa ntchito Lixumia pa nthawi yoyembekezera komanso mkaka wa m`mawere

Akazi azaka zaubala.
Lixumia siyikulimbikitsidwa kwa azimayi amsinkhu wobereka omwe sagwiritse ntchito njira zakulera.
Mimba
Palibe zosakwanira pakugwiritsa ntchito Lixumia mwa amayi apakati. Kafukufuku wammbuyo wasonyeza kuwopsa kwa kubereka.
Chiwopsezo chomwe chilipo kwa anthu sichikudziwika.
Lixumia sayenera kugwiritsidwa ntchito panthawi yomwe muli ndi pakati. M'malo mwake, insulin ikulimbikitsidwa.
Ngati wodwala akufuna kukhala ndi pakati kapena pakati pachitika, chithandizo ndi Lixumia ziyenera kusiyidwa.
Kuchepetsa.
Sizikudziwika ngati Lixumia amadutsa mkaka wa m'mawere a anthu. Lixumia sayenera kugwiritsidwa ntchito pazomwitsa.
Chonde.
Kafukufuku wammbuyo samawonetsa kuwononga kwachonde.

Lixisenatide ndi agonist yosankha ya GLP-1 receptors (glucagon-like peptide-1). Cholandilira cha GLP-1 ndicholinga cha majini obadwa nawo a GLP-1, mahomoni amkati mwa insulin omwe amatha kupatsa insulin modalira maselo a pancreatic beta.
Mphamvu ya lixisenatide imayang'aniridwa ndi kuyanjana kwina ndi GLP-1 receptors, zomwe zimapangitsa kuwonjezeka kwa intcacellular cyclic adenosine monophosphate (cAMP).
Lixisenatide imalimbitsa katemera wa insulin pamene kuchuluka kwa shuga m'magazi kumawonjezeka, koma osati ndi standardoglycemia, komwe kumachepetsa chiopsezo cha hypoglycemia.
Nthawi yomweyo, secretion wa glucagon imaponderezedwa. Ndi hypoglycemia, njira yopumira ya glucagon katulutsidwe imasungidwa.
Lixisenatide imachedwetsa kutuluka kwa m'mimba, kuchepetsa kuthamanga komwe glucose wopezeka ndi chakudya amakhala m'magazi.
Zotsatira za Pharmacodynamic.
Ikagwiritsidwa ntchito kamodzi patsiku kwa odwala omwe ali ndi matenda a shuga a 2, lixisenatide imathandizira kuwongolera kwa glycemic chifukwa chotsatira komanso nthawi yayitali yochepetsa kutsekeka kwa glucose mukatha kudya komanso m'mimba yopanda kanthu.
Zotsatira zam'magazi a postprandial zimatsimikiziridwa mu kafukufuku wamasabata a 4, poyerekeza ndi liraglutide 1.8 mg kamodzi patsiku kuphatikiza ndi metformin. Kuchepera kumayambiriro kwa chisonyezo cha PPK 0: 30–4: 30 h
shuga wa m'madzi atatha kudya mayeso:
–12.61 ora * mmol / L (-227.25 ola * mg / dL) m'gulu la lixisenatide ndi -4.04 ola * mmol / L (-72.83 ora * mg / dl) m'gulu liraglutide.
Izi zidatsimikizidwanso mu kafukufuku wa masabata a 8 poyerekeza ndi liraglutide wokhazikitsidwa musanadye kadzutsa pamodzi ndi insulin glargine wokhala ndi kapena wopanda metformin.
Mphamvu zamankhwala ndi chitetezo.
Zotsatira za Lixumia pa glycemic control poyerekeza ndi exenatide zidayesedwa m'mayeso asanu ndi limodzi osasinthika, akhungu awiri, mayeso olamulidwa ndi placebo ndi kafukufuku umodzi wosasankhidwa, wotseguka-wotseguka wolamulira.
Maphunzirowa adaphatikizapo 38 38 odwala omwe ali ndi matenda a shuga a mtundu wa 2 (odwala 2445 adasankhidwa kuti azigwiritsa ntchito lixisenatide), 48.2% ya amuna ndi azimayi 51.8%.
Odwala a 768 (447 osasankhidwa kuti azigwiritsa ntchito lixisenatide) anali ndi zaka ≥65, ndipo odwala 103 (57 osasankhidwa kuti azigwiritsa ntchito lixisenatide) anali ndi zaka ≥75.
Mu maphunziro omaliza a gawo la III, zidadziwika kuti kumapeto kwa nyengo yayikulu ya milungu 24, opitilira 90% ya odwala adakwanitsa kusunga mlingo wokonzanso wa Lixumia 20 μg kamodzi patsiku.
Glycemic control.
Zowonjezera kuphatikiza mankhwala ogwiritsira ntchito mankhwala oteteza pakamwa.
Kumapeto kwa nyengo yayikulu ya milungu 24, Lixumia osakanikirana ndi metformin, sulfonylurea, pioglitazone, kapena kuphatikiza kwa mankhwalawa kunawonetsa kuchepa kwakukulu kwa kusamba kwa plasma HbA1c, glucose yofulumira ya plasma ndi glucose ya maola awiri atatha kudya mayeso poyerekeza ndi placebo. Kuchepa kwa HbA1c kunali kofunikira kwambiri pamene mankhwalawa amaperekedwa kamodzi patsiku, ngakhale atagwiritsidwa ntchito m'mawa kapena madzulo.
Kuwonetsedwa koteroko ku HbA1c kudakhala kotenga nthawi yayitali m'maphunziro a nthawi yayitali mpaka masabata makumi asanu ndi limodzi.
Chithandizo chowonjezera kuphatikiza ndi metformin.
Gome 2: Maphunziro oyendetsedwa ndi placebo osakanikirana ndi metformin (zotsatira za masabata 24).
Pakufufuza komwe kumachitika pakumapeto kwa nyengo yayikulu ya masabata 24, kugwiritsa ntchito Lixumia kamodzi patsiku kunawonetsa kuchepa kwa HbA1c mlingo wa -0.79% poyerekeza ndi -0.96% mukamagwiritsa ntchito Exenatide kawiri patsiku, komanso kusiyana pakatikati 0,17% (95% chidaliro cholumikizira (CI): 0.033, 0.297) ndi kuchuluka komweko kwa odwala omwe akwaniritsa HbA1c osachepera 7% m'gulu la lixisenatide (48,5%)
ndi mgulu la exenatide (49.8%).
Munthawi yayikulu ya masabata 24, odwala nseru anali 24,5% pagulu la lixisenatide poyerekeza ndi 35.1% pagulu latsikuli kawiri pa tsiku, ndipo chidziwitso cha hypoglycemia ndi lixisenatide chinali 2,5% poyerekeza ndi 7,9% pagulu lakutali.
Mu kafukufuku wamasamba 24 wotseguka, lixisenatide idaperekedwa chakudya chisanachitike komanso sichinali chotsika pa lixisenatide yomwe idaperekedwa chakudya cham'mawa monga gawo la kuchepetsa.
HbA1c (kusintha kusintha kwa njira kuchokera pamlingo woyamba: -0.65% poyerekeza ndi 0.74%). Kutsika kofanana kwa HbA1c kunawonedwa ngakhale chakudya chachikulu (kadzutsa, nkhomaliro, kapena chakudya chamadzulo). Pamapeto pa phunziroli, 43.6% (magulu akuluakulu azakudya) ndi 42.8% (gulu lodyera m'mawa) odwala adakwanitsa zosakwana 7% HbA1c. Nusea idanenedwa mu 14.7% ndi 15.5% ya odwala, ndi dalili za hypoglycemia mu 5.8% ndi 2.2% ya odwala omwe ali m'magulu akulu a chakudya komanso chakudya cham'mawa, motero.
Zochizira zowonjezera pamodzi ndi sulfonylurea kapena kuphatikiza ndi metformin.
Gome 3: Kafukufuku woyendetsedwa ndi placebo wophatikizidwa ndi sulfonylurea (zotsatira za masabata 24).
Chithandizo chowonjezera kuphatikiza kokha ndi pioglitazone kapena kuphatikiza ndi metformin.
Pakafukufuku wazachipatala kwa odwala omwe sanakwaniritse kuwongolera pioglitazone, kuwonjezerapo kwa lixisenatide kwa pioglitazone osakanikirana ndi kapena popanda metformin kumapeto kwa nyengo yayikulu ya masabata 24 kunapangitsa kutsika kwa HbA1c kuchokera pachiwonetsero ndi 0.90% poyerekeza ndi kuchepa kuchokera pagawo loyamba la 0,34% pagulu la placebo. Kumapeto kwa nyengo yayikulu ya milungu 24, 52.3% ya odwala omwe amalandila lixisenatide anali ndi HbA1
c anali ochepera 7% poyerekeza ndi 26.4% pagulu la placebo.
Munthawi yayikulu ya masabata 24, nseru idapezeka 23,5% mu gulu la lixisenatide poyerekeza ndi 10.6% mu gulu la placebo, milandu ya hypoglycemia mu 3.4% ya odwala omwe adalandira lixisenatide, poyerekeza ndi 1.2% mu gulu la placebo.
Kuphatikiza kowonjezera kwa basal insulin Lixumia, yoikidwa limodzi ndi basal insulin yokha, kapena kuphatikiza ndi basulin insulin ndi metformin, kapena kuphatikiza kwa basal insulin ndi sulfonylurea, zimapangitsa kuchepa kwakukulu kwa HbA1c ndi 2-maola a postprandial glucose kudya motsutsana ndi placebo.
Gome 4: Maphunziro olamulidwa ndi placebo osakanikirana ndi basal insulin (zotsatira za masabata 24).
Kafukufuku wachipatala adachitika kwa odwala omwe sanalandire insulin m'mbuyomu, omwe sanathe kuyang'anira othandizira odwala matenda am'mimba. Kafukufukuyu adaphatikizapo nthawi ya kukonzekera kwa masabata 12 ndi insulin glargine management ndi titration komanso nyengo ya masabata a 24 pomwe odwala amalandila lixisenatide kapena placebo osakanikirana ndi insulin glargine ndi metformin kapena osaphatikizika ndi thiazolidinediones. Munthawi imeneyi, insulin glargine inkakhala yam'madzi nthawi zonse.
Mkati mwa sabata lokonzekera la masabata 12, kuwonjezera ndi kusindikiza kwa insulin glargine kunapangitsa kutsika kwa HbA1c pafupifupi 1%.
Kuphatikiza kwa lixisenatide kunayambitsa kuchepa kwakukulu kwa HbA1 kuchokera ku 0.71% pagulu la lixisenatide poyerekeza ndi 0.40% pagulu la placebo. Pakutha kwa sabata la 24 sabata, odwala 56.3% omwe amagwiritsa ntchito lixisenatide anali ndi HbA1 kuchuluka kochepera 7% poyerekeza ndi 38,5% pagulu la placebo.
Munthawi yamasabata 24 othandizira, 22.4% ya odwala omwe adalandira lixisenatide adanenanso hypoglycemia wodziwika bwino, poyerekeza ndi 13.5% pagulu la placebo.
Chiwopsezo cha hypoglycemia chinawonjezeka makamaka mkati mwa milungu 6 yoyambirira ya mankhwala m'gulu la lixisenatide, kenako anali wofanana ndi gulu la placebo.
Kusala madzi a m'magazi a plasma.
Pakufufuza komwe kumayendetsedwa ndi placebo kumapeto kwa nyengo ya masabata a 24, kusala kudya kwa glucose kosavuta kuchokera pazoyambira zomwe zakwaniritsidwa ndi chithandizo cha Lixumia kuyambira pa 0.42 mmol / L mpaka 1.19 mmol / L.
Mlingo wa postprandial glucose.
Mankhwala a Lixumia adapangitsa kutsika kwa glucose wa maola awiri pambuyo poti adyetsa, ali ndi ziwonetsero zapamwamba kuposa placebo, mosasamala kanthu za chithandizo choyambirira.
Mwambiri, m'maphunziro onse momwe milingo ya gluprose ya postprandial imayesedwa, ndi Lixumia kumapeto kwa nyengo ya sabata la 24, kutsitsa kuchokera pazomwe kunali pamlingo kuyambira 4.51 mpaka 7.96 mmol / L. Kuchokera pa 26.2% mpaka 46.8% ya odwala, kuchuluka kwa glucose kwa maola 2 anali pansi 7.8 mmol / L (140.4 mg / dl).
Kulemera kwa thupi.
Kumapeto kwa nyengo yayikulu ya masabata 24, mankhwala a Lixumia osakanikirana ndi metformin ndi / kapena sulfonylurea m'mayeso onse olamulidwa adayambitsa kusintha kwamphamvu kwa thupi kuyambira kuyambira -1.76 kg mpaka -2.96 kg. Kusintha kwa kulemera kwa thupi kuchokera pamlingo woyambira kuchokera pa -0.38 makilogalamu mpaka-1.80 makilogalamu kunawonekeranso kwa odwala omwe amalandila lixisenatide osakanikirana ndi mankhwala a insal insulin, kapena osakanikirana ndi metformin kapena sulfonylurea.
Odwala omwe anayamba kugwiritsa ntchito insulin, mgulu la lixisenatide, kulemera kwa thupi sikunasinthe, pomwe pagulu la placebo kuwonjezeka.
M'maphunziro amtundu wautali mpaka masabata makumi awiri ndi limodzi, kuchepa thupi kudali kokhazikika.
Kuchepetsa thupi sizidalira kuchuluka kwa mseru komanso kusanza.
Ntchito ya cell ya Beta.
Kafukufuku wa zamankhwala a Lixumia amawonetsa ntchito ya cell ya beta yowongoleredwa malinga ndi mtundu wa homeostatic beta cell test test (HOMO-β / HOMA-β).
Kubwezeretsanso gawo loyamba la insulin katulutsidwe ndikusintha kwachiwiri kwa insulin katulutsidwe poyambira jekeseni waubus wa glucose amawonetsedwa pambuyo pa gawo limodzi la Lixumia mwa odwala matenda a shuga 2 (n = 20).
Kuyesa kwa mtima.
M'mayesero onse oyendetsedwa ndi placebo a gawo lachitatu, odwala omwe ali ndi matenda a shuga a 2 sanawonetse kuchuluka kwa mtima.
Mu kafukufuku wotsogola wolowera wa placebo, panali kuchepa kwa kuthamanga kwa magazi kwa systolic ndi diastolic, motero, mpaka 2.1 mm RT. Art. mpaka 1.5 mmHg. Art.
Kuwunikira kwa zochitika zonse zodziyimira pawokha zamtima (kufa chifukwa cha mtima, kuvulala kwamatumbo osavulala, kugundidwa chifukwa cha kusakhazikika kwa angina, kugonekedwa m'chipatala chifukwa cha kulephera kwa mtima komanso kusinthanso kwa mitsempha ya coronary) m'ma mayeso 8 olamulidwa ndi placebo. omwe anaphatikiza odwala 2,673 omwe ali ndi matenda a shuga a 2 omwe amalandila lixisenatide ndi odwala 1,448 omwe alandila placebo adawonetsa chiopsezo cha 1,03 (95% chidule pakubwera 0.64, 1.66) kwa lixis Atid poyerekeza ndi placebo.
Chiwerengero cha zochitika m'mayesero azachipatala chinali chochepa (1.9% mwa odwala omwe amalandila lixisenatide ndi 1.8% mwa odwala omwe akulandira placebo), sizimalola malingaliro odalirika.
Zomwe zimachitika ndi zochitika zamtima payekha (lixisenatide versus placebo) zinali: imfa chifukwa cha zomwe zimayambitsa mtima (0.3% poyerekeza ndi 0.3%), infarction ya nonyo-myocardial (0.4% poyerekeza ndi 0.4 %), matenda osapweteka (0,7% poyerekeza ndi 0,4%), kugonekedwa kuchipatala chifukwa cha kusakhazikika kwa angina (0 kuyerekeza ndi 0,1%), kugonekedwa kuchipatala chifukwa cha kulephera mtima (0% kuyerekeza ndi 0) , coronary arterial revascularization (0.7% motsutsana 1.0%).
Pharmacokinetics: Mafuta.
Pambuyo subcutaneous makonzedwe kwa odwala mtundu 2 shuga, mayamwidwe kuchuluka kwa lixisenatide mofulumira, mosasamala kanthu mlingo kutumikiridwa. Osatengera mlingo komanso ngati lixisenatide idagwiritsidwa ntchito limodzi kapena zingapo, odwala omwe ali ndi matenda a shuga a 2, pafupifupi tmax imachokera ku 1 mpaka 3.5 maola. Mokhudzana ndi subcutaneous makonzedwe a lixisenatide pamimba, ntchafu kapena phewa, palibenso kusiyana kwakukulu pakumwedwa.
Kugawa.
Lixisenatide ali ndi digiri yolumikizira (55%) kumapuloteni amunthu.
Kuchulukitsa komwe kumawonekera pambuyo povomerezeka kwa lixisenatide (Vz / F) kuli pafupifupi 100 L.
Biotransfform ndi excretion.
Monga peptide, lixisenatide imachotsedwera ndi kusefera kwa glomerular ndikutsatiridwa kwa tubular ndikuwonjezeranso kuchepa kwa metabolic, zomwe zimayambitsa kupanga ma peptides ang'ono ndi ma amino acid, omwe amakhalanso ndi protein metabolism. Pambuyo makonzedwe angapo Mlingo wa odwala 2 matenda ashuga, pafupifupi kuthetsa theka-moyo anali pafupifupi 3 maola ndipo pafupifupi kuwonekera pafupifupi (CL / F) anali pafupifupi 35 l / h.
Chiwerengero Chapadera:
Odwala ndi mkhutu aimpso ntchito.
Odwala omwe ali ndi vuto lozungulira laimpso komanso odwala omwe ali ndi vuto laimpso wofatsa (mawonekedwe a creatinine amawerengedwa ndi njira yokhazikika ya Cockcroft-Gault, 50-80 ml / min), panalibe kusiyana kwakukulu mu Cmax ndi PPK ya lixisenatide. Odwala omwe ali ndi vuto laimpso zolimbitsa thupi (mawonekedwe a creatinine chilolezo cha 30-50 ml / min), cholembera cha AUC (malo omwe ali pansi pajika) chikuwonjezeka ndi 24%, ndipo mwa odwala omwe ali ndi vuto la aimpso (creatinine chilolezo cha 15-30 ml / min) - lolemba 46 %
Odwala omwe ali ndi vuto la chiwindi.
Popeza lixisenatide imagwiritsidwa ntchito kwambiri ndi impso, odwala omwe ali ndi vuto laimpso kapena matenda operewera sanachite nawo maphunziro a pharmacokinetic. Kukanika kwa hepatatic sikuyembekezeredwa kukhudza pharmacokinetics ya lixisenatide.
Paulo
Jenda ilibe gawo lalikulu pama pharmacokinetics a lixisenatide.
Mtundu.
Kutengera ndi zotsatira za kafukufuku wa pharmacokinetic mwa odwala amtundu wa Caucasian, Japan ndi China, ochokera kumayiko ena sakhala ndi vuto lililonse pa pharmacokinetics ya lixisenatide.
Odwala okalamba.
M'badwo sakhala ndi vuto lililonse pama pharmacokinetics a lixisenatide. Mu kafukufuku wa pharmacokinetic mwa okalamba omwe alibe odwala matenda ashuga, kugwiritsa ntchito lixisenatide 20 μg pagulu la odwala okalamba (odwala 11 azaka zapakati pa 65 mpaka 74 ndi odwala 7 wazaka ≥75), zomwe zimapangitsa kuchuluka kwapakati pa PPC ya lixisenatide ndi 29%, poyerekeza ndi odwala 18 azaka za 18 mpaka 45, mwina zimagwirizanitsidwa ndi kuchepa kwa impso m'gulu lakale.
Kulemera kwa thupi.
Kulemera kwa thupi kulibe vuto lililonse PPK chizindikiro cha lixisenatide.

Zotsatira zoyipa za Liksumiya

Kufotokozera mwachidule mbiri yazachitetezo.
Odwala opitilira 2,600 mu maphunziro akulu akulu 8 olamulidwa ndi placebo kapena maphunziro a gawo lachitatu omwe ali ndi mphamvu yogwira adalandira Lixumia mwina mu monotherapy kapena kuphatikiza ndi metformin, sulfonylurea (yokhala ndi metformin) kapena basal insulin (yokhala ndi metformin kapena ya sulfonylurea kapena wopanda iye).
Zomwe zimachitika kawirikawiri pazovuta zamayendedwe azachipatala zinali mseru, kusanza, ndi kutsekula m'mimba. Maganizo ake anali ofatsa komanso osakhalitsa.
Pakhala pali milandu ya hypoglycemia (pomwe Lixumia idagwiritsidwa ntchito limodzi ndi sulfonylurea ndi / kapena basal insulin) ndi mutu.
Zotsatira zoyipa zimawonedwa mu 0.4% ya odwala omwe amagwiritsa ntchito Lixumia.
Pansipa pali zoyipa zomwe zimachitika ndi pafupipafupi> 5%, ngati pafupipafupi ndimomwe odwala adalandira Lixumia kuposa odwala omwe amalandila mankhwala onse oyerekeza, amaphatikizanso zovuta zomwe zimachitika pafupipafupi ndi ≥1% pagulu la odwala omwe amalandila Lixumia, ngati pafupipafupi zodzachitika anali 2 times kuposa pafupipafupi pakati pagulu la odwala omwe amalandila mankhwala onse oyerekeza.
Zotsatira zoyipa zomwe zimakhazikitsidwa poyesedwa kwa placebo komanso gawo lachitatu ndi kayendetsedwe kogwira nthawi yonse yamankhwala (kuphatikiza nthawi yopitilira nyengo yayikulu ya milungu 24 mu maphunziro omwe ali ndi ≥76 milungu yonse ya chithandizo chonse).
Nthawi zambiri (≥1 / 10):
- hypoglycemia (kuphatikiza ndi sulfonylurea ndi / kapena basulin insulin)
mutu
- nseru, kusanza, kutsekula m'mimba
Nthawi zambiri (≥1 / 100 isanakwane - chimfine, matenda am'mimba kupuma, cystitis, kachilombo
- hypoglycemia (kuphatikiza ndi metformin kokha)
- chizungulire, kugona
- dyspepsia
- kupweteka kumbuyo
- kuyabwa pa malo a jakisoni
Nthawi zambiri (≥1 / 1000 mpaka - anaphylactic reaction)
- urticaria

Kufotokozera kwamomwe munthu amachitikira:
Hypoglycemia.
Odwala omwe amatenga Lixumia mu monotherapy, hypoglycemia yodziwika imapezeka mu 1.7% ya odwala omwe amalandila lixisenatide, ndipo mwa 1.6% ya odwala omwe akulandira placebo. Pamene Lixumia amagwiritsidwa ntchito limodzi ndi metformin panthawi yonse ya chithandizo, hypoglycemia yodziwika bwino inachitika mu 7.0% ya odwala omwe amalandila lixisenatide ndi 4,8% ya odwala omwe akulandira placebo.
Odwala omwe amatenga Lixumia limodzi ndi sulfonylurea ndi metformin, zizindikiro za hypoglycemia zimachitika mu 22.0% ya odwala omwe amalandila lixisenatide ndi 18.4% ya odwala omwe akulandira placebo (kusiyana kwakukulu kwa 3.6%) panthawi yonse ya chithandizo. Pamene Lixumia adagwiritsidwa ntchito limodzi ndi basal insulin yokhala ndi metformin kapena wopanda metformin panthawi yonse ya chithandizo, chizindikiro cha hypoglycemia chinachitika mu 42.1% ya odwala omwe amathandizidwa ndi lixisenatide komanso 38,9% ya omwe adalandira placebo (3.2% ya kusiyana kwathunthu).
Pamene Lixumia idagwiritsidwa ntchito limodzi ndi sulfonylurea nthawi yonse ya chithandizo, Hypoglycemia yodziwika imapezeka mu 22.7% ya odwala omwe amalandila lixisenatide, poyerekeza ndi 15.2% omwe amalandila placebo (kusiyana kwakukulu kwa 7.5%). Pamene Lixumia idagwiritsidwa ntchito limodzi ndi sulfonylurea ndi basal insulin, hypoglycemia yodziwika bwino inachitika mu 47.2% ya odwala omwe amalandila lixisenatide, poyerekeza ndi 21.6% yolandila placebo (25,6% ya kusiyana kwathunthu).
Mwambiri, munthawi yonse ya chithandizo cha maphunziro omwe amayendetsedwa ndi placebo a gawo lachitatu, zochitika za hypoglycemia zowopsa kwambiri zinali zochepa (0.4% mwa odwala omwe amathandizidwa ndi lixisenatide ndi 0,2% mwa odwala omwe amathandizidwa ndi placebo).
Kuphwanya kwam'mimba thirakiti.
Munthawi yayikulu ya masabata 24, kusanza ndi kusanza ndizomwe zimadziwika kwambiri. Zomwe zimachitika ndi vuto la mseru zidakwera kwambiri pagulu la lixisenatide (26.1%) poyerekeza ndi gulu la placebo (6.2%), ndipo zonena za kusanza zinali zochulukirapo pagulu la lixisenatide (10.5%) poyerekeza ndi gulu la placebo (1.8 %).
Zotsatira zake zidali zofatsa komanso zosakhalitsa ndipo zidachitika mkati mwa milungu itatu itangoyamba kumene chithandizo. Pambuyo pake, m'masabata otsatira, pafupipafupi amachepetsa.
Zokhudza malo jakisoni.
Munthawi yayikulu ya milungu 24, machitidwe omwe amapezeka jakisoni amapezeka mu 3.9% ya odwala omwe amalandila Lixumia, ndipo zomwe zimachitika pamalo operekera jakisoni zimapezekanso mu 1.4% ya odwala omwe akulandira placebo.
Machitidwe ambiri anali ofatsa kwambiri ndipo nthawi zambiri samasiya kulandira chithandizo.
Immunogenicity
Chifukwa cha kuthekera kwakukulu kwa mankhwala omwe ali ndi mapuloteni kapena ma peptides, atalandira chithandizo ndi Lixumia, odwala amatha kupanga ma antibodies mpaka lixisenatide, ndipo kumapeto kwa nthawi yayikulu ya masabata a 24 m'maphunziro olamulidwa ndi placebo mu 69.8% ya odwala omwe amalandila lixisenatide, zabwino antibody adakhazikitsidwa. Pomaliza nyengo yonse ya masabata 76, kuchuluka kwa odwala seropositive kunali kofanana. Kumapeto kwa nyengo yayikulu ya milungu 24, mu 32,2% ya odwala omwe ali ndi anti-antibody, ndende ya antibody inali yopanda malire, ndipo kumapeto kwa nyengo yonse ya masabata 76 mwa 44.7% ya odwala, ndende ya antibody inali pamwamba pa malire otsika. . Pambuyo pakuchotsa chithandizo, kuwunika kwa odwala angapo a seropositive adapitilirabe, mkati mwa miyezi itatu kuchuluka kwake kunatsika mpaka pafupifupi 90%, ndipo patatha miyezi 6 kapena kupitilira - mpaka 30%.
Kusintha kwa HbA1c kuchokera pachiwonetsero kunali kofanana mosasamala momwe anti anti (abwino kapena amakhalira).
Mwa odwala omwe ali ndi HbA1c muyeso omwe adalandira lixisenatide, 79.3% anali ndi mtundu wotsutsa wa antibody kapena ndende ya antibody inali yochepera kuposa malire otsika, ndipo otsala a 20.7% anali ndi kuchuluka kwamankhwala othana nawo.Mu gulu laling'ono la odwala (5.2%) omwe ali ndi kuchuluka kwambiri kwamankhwala osokoneza bongo, kuchuluka kwa kusintha kwa HbA1c sabata 24 ndi sabata 76 kunali mkati mwazofunikira kwambiri poyeza, komabe, panali kusiyanasiyana koyankha, ndipo 1.9% inalibe kuchepa HbA1c.
Mkhalidwe wama antibodies (zabwino kapena zoipa) samalola kuneneratu kuchepa kwa HbA1c mwa wodwala aliyense.
Panalibe kusiyana kulikonse pamawonekedwe otetezeka mwa odwala, mosasamala kanthu za momwe munthu angagwiritsire ntchito antibody, kupatula kuwonjezeka kwa kuchuluka kwa zosankha kumalo opangira jakisoni (munthawi yonse ya chithandizo, 4,7% mwa odwala omwe ali ndi anti antioja, poyerekeza ndi 2,5% mu odwala a seronegative). Zambiri zomwe zimachitika jekeseni malo anali ofatsa, ngakhale atakhala kuti ali ndi antibody.
Panalibe kuyambukira pamtunda poyerekeza ndi glucagon wachilengedwe kapena mtundu wobadwira wa GLP-1.
Thupi lawo siligwirizana.
Munthawi yayikulu ya milungu 24 mu 0.1% ya odwala omwe akulandira placebo.
Zotsatira za anaphylactic zidakhazikitsidwa mu 0.2% ya odwala omwe amalandira lixisenatide, poyerekeza ndi kusapezeka kwa gulu la placebo.
Zambiri mwa zoyipa zomwe zimakhudzidwa m'zovuta zinali zochepa. Mlandu umodzi wa anaphylactoid anachita unakhazikitsidwa pazoyesedwa zamankhwala a lixisenatide.
Kufika pamtima.
M'maphunziro okhudzana ndi odzipereka athanzi, kuwonjezeka kwapang'onopang'ono kwa kugunda kwa mtima kumawonedwa pambuyo pakupereka 20 μg ya lixisenatide. Cardiac arrhythmia, makamaka, tachycardia (0.8% poyerekeza ndi kusiya mankhwala.
Munthawi yayikulu ya masabata 24, chithandizo chodziletsa chifukwa cha zovuta zake chinali 7.4% mgulu la Lixumia poyerekeza ndi 3.2% m'gululo la placebo. Zotsatira zoyipa zomwe zimapangitsa kuti asiye kumwa mankhwalawa m'gulu la lixisenatide anali mseru (3.1%) ndi kusanza (1.2%).
Tikuwuza anthu omwe akuwakayikira.
Ndikofunika kufotokozera anthu omwe akuwaganizira kuti adakumana ndi vuto lolembetsa utatha mankhwala. Izi zimakuthandizani kuti mupitirize kuwunika momwe mankhwalawo amathandizira / kuwopsa kwa mankhwalawa. Ogwira ntchito yazaumoyo apemphedwa kuti afotokoze zoyipa zilizonse zomwe zikukayikiridwa kudzera mu njira yofotokozera dziko.

Palibe chochiritsika chogwiritsidwa ntchito ndi lixisenatide kwa odwala omwe ali ndi matenda a shuga 1; sayenera kugwiritsidwa ntchito mwa odwalawa.
Lixisenatide sayenera kugwiritsidwa ntchito pochiza matenda ashuga a ketoacidosis.
Pachimake kapamba.
Kugwiritsa ntchito kwa glucagon-like peptide-1 receptor agonists (GLP-1) kwalumikizidwa ndi chiopsezo chokhala ndi pancreatitis yayikulu.
Zochitika zingapo za pancreatitis pachimake zanenedwapo ndi kugwiritsidwa ntchito kwa lixisenatide, ngakhale ubale wapakati sunakhazikitsidwe.
Ndikofunikira kudziwitsa odwala za zomwe zimachitika ndi chifuwa chachikulu cha kapamba: kulimbikira, kupweteka kwambiri pamimba. Ngati pancreatitis ikukayikira, ndikofunikira kusiya kugwiritsa ntchito lixisenatide, ngati pancreatitis yovuta imatsimikiziridwa, kugwiritsa ntchito lixisenatide sikuyenera kuyambiranso. Chenjezo liyenera kugwiritsidwa ntchito ngati mugwiritsa ntchito odwala kapamba.
Matenda akulu am'mimba.
Kugwiritsa ntchito agonists a GLP-1 receptors atha kuphatikizidwa ndi zovuta kuzinthu zam'mimba.
Lixisenatide sichinawerengeredwe mwa odwala omwe ali ndi matenda am'mimba kwambiri, kuphatikizapo gastroparesis woopsa, ndipo chifukwa chaichi, kugwiritsa ntchito lixisenatide sikulimbikitsidwa.
Matenda aimpso.
Palibe achire othandiza kwa odwala omwe ali ndi vuto lowonongeka aimpso impso. Odwala omwe ali ndi vuto laimpso lokwanira, Lixumia iyenera kugwiritsidwa ntchito mosamala. Odwala omwe ali ndi vuto la impso kapena odwala omwe ali ndi vuto la matenda a impso, osavomerezeka sayenera kugwiritsidwa ntchito (onani "Mlingo ndi Administration" ndi "Pharmacokinetics").
Hypoglycemia.
Odwala omwe amalandila Lixumia ndi sulfonylurea kapena basal insulin atha kukhala ndi chiopsezo chowonjezereka cha hypoglycemia. Kuchepetsa chiopsezo cha hypoglycemia, ndizotheka kuchepetsa mlingo wa sulfonylurea kapena basal insulin (onani "Mlingo ndi Administration"). Lixumia sayenera kugwiritsidwa ntchito limodzi ndi basal insulin ndi sulfonylurea chifukwa chowonjezera cha hypoglycemia.
Mankhwala Olumikizana
Kuchepetsa kuthamangitsidwa kwa zam'mimba zomwe zimagwiritsidwa ntchito ndi lixisenatide kumachepetsa kuyamwa kwa mankhwala omwe amaperekedwa pakamwa. Odwala omwe amalandila mankhwala amkamwa omwe amafunikira mayamwidwe am'mimba, kuwunika kwachipatala, kapena mankhwala okhala ndi index yochepetsetsa yothandizira, Lixumia iyenera kugwiritsidwa ntchito mosamala. Malangizo apadera okhudzana ndi kugwiritsa ntchito mankhwalawa amaperekedwa mu gawo la "Mankhwala Osokoneza bongo".
Zopanda anthu.
Lixisenatide sanaphunziridwe limodzi ndi dipeptidyl peptidase-4 (DPP-4) zoletsa.
Pali zambiri zomwe zimachitika kwa odwala omwe ali ndi mtima wofooka.
Kuthetsa madzi m'thupi.
Odwala omwe amalandila chithandizo ndi Lixumia ayenera kudziwitsidwa za ngozi yotha kusowa madzi m'thupi chifukwa cha zovuta zomwe zimachitika kuchokera m'matumbo am'mimba ndikuwonetsetsa kuti kupewa hypovolemia.
Othandizira.
Mankhwalawa ali ndi metacresol, omwe angayambitse kuyanjana.
Akazi azaka zaubala.
Lixumia siyikulimbikitsidwa kwa azimayi amsinkhu wobereka omwe sagwiritse ntchito njira zakulera.
Mimba
Palibe zosakwanira pakugwiritsa ntchito Lixumia mwa amayi apakati. Kafukufuku wammbuyo wasonyeza kuwopsa kwa kubereka.
Chiwopsezo chomwe chilipo kwa anthu sichikudziwika.
Lixumia sayenera kugwiritsidwa ntchito panthawi yomwe muli ndi pakati. M'malo mwake, insulin ikulimbikitsidwa.
Ngati wodwala akufuna kukhala ndi pakati kapena pakati pachitika, chithandizo ndi Lixumia ziyenera kusiyidwa.
Kuchepetsa.
Sizikudziwika ngati Lixumia amadutsa mkaka wa m'mawere a anthu. Lixumia sayenera kugwiritsidwa ntchito pazomwitsa.
Chonde.
Kafukufuku wammbuyo samawonetsa kuwononga kwachonde.
Zomwe zimachitika chifukwa cha mankhwalawa amatha kuyendetsa galimoto kapena njira zoopsa.
Lyskumia siyimakhudza kapena imakhala yovuta pang'ono pakutha kuyendetsa galimoto kapena makina. Mankhwala akaphatikizidwa ndi sulfonylurea kapena basal insulin, ayenera kuthandizidwa kuti azisamala popewa hypoglycemia poyendetsa kapena kugwiritsa ntchito makina.

Malo osungira.
Sungani pa kutentha kwa madigiri 2 mpaka 8 madigiri C pamalo amdima. Osamawuma. Khala kutali ndi mufiriji.
Mukatha kugwiritsa ntchito koyamba, cholembera cha syringe chitha kugwiritsidwa ntchito masiku 14 pa kutentha kosaposa 30 digiri C. Osamawuma.
Pewani kufikira ana.

Malangizo ogwiritsira ntchito cholembera Lixumia
Musanagwiritse ntchito cholembera cha Lixumia, werengani malangizo ake mosamala.
Sungani malangizo awa azachipatala kuti mugwiritse ntchito m'tsogolo.
Lixumia ndi cholembera chodzaza ndi jakisoni jakisoni 14. Mlingo uliwonse umakhala ndi 10 μg kapena 20 μg wa lixisenatide mu 0,5 ml.
• Pakani jakisoni imodzi patsiku.
• P cholembera chilichonse cha Lixumium sichikhala ndi Mlingo 14 wodzazidwa. Mlingo uliwonse suyenera.
• Musanagwiritse ntchito cholembera, gwiritsani ntchito ndi dotolo wanu momwe mungapangire mankhwalawo.
• Ngati nkosatheka kutsatira malangizowo nokha, kapena ngati simungathe kuthira cholembera (mwachitsanzo, ngati mukukhala ndi vuto), tengani thandizo kunja.
• Cholembera ichi ndi cha munthu m'modzi yekha. Kugawana nkoletsedwa.
• Nthawi zonse muzilemba zilembo kuti muwonetsetse kuti ma syringe a Lixumia sakusakanikirana. Onaninso zosungira zomwe zatha.
Kugwiritsa ntchito mankhwala olakwika kungavulaze.
• Musayesetse kuchotsa madzimadzi mu cartridge pogwiritsa ntchito syringe. Zambiri za singano (posankha)
• Gwiritsani ntchito singano zokha zovomerezeka kuti mugwiritse ntchito ndi Lixumia. Gwiritsani ntchito singano zotaya kuchokera pa 29 mpaka 32 mu cholembera cha syllinge ya Lixumia. Zingakhale bwino ngati mutafunsa dokotala za kutalika ndi singano.
• Ngati mukubayidwa ndi thandizo lakunja, chisamaliro chimayenera kuthandizidwa kuti musavulaze wina ndi singano. Kupanda kutero, kufalitsa matenda ndikotheka.
• Pabakisoni aliyense, gwiritsani ntchito singano yatsopano kuti mupewe kuipitsa kwa Lixumia komanso kugula.

Zisonyezero za mankhwala Lixumia

Type 2 shuga mellitus mwa achikulire kuti akwaniritse kuwongolera kwa glycemic mwa odwala omwe matenda awo a shuga sawongoleredwa ndi hypoglycemic yothandizira.

Lixumia akuwonetsedwa limodzi ndi mankhwala otsatirawa a hypoglycemic:

• metformin
• mankhwala a hypoglycemic a pakamwa a gulu la sulfonylurea,
• kuphatikiza kwa mankhwalawa.

Lixumia akuwonetsedwa kuphatikiza ndi basal insulin:

• mu monotherapy,
• kuphatikiza ndi metformin,
• kuphatikiza ndi mankhwala amkamwa a hypoglycemic a gulu la sulfonylurea.

Mlingo

Mlingo woyambirira ndi ma 10 makilogalamu a Lixumia kamodzi patsiku kwa masiku 14.

Kenako mlingo wa Lixumia uyenera kukulitsidwa mpaka 20 mcg kamodzi patsiku. Mlingowu umandithandizira.

Lixumia ikawonjezeredwa ku mankhwala a metformin omwe alipo, Metformin ikhoza kupitilizidwa popanda kusintha mlingo wake.

Lixumia ikawonjezeredwa ku mankhwala omwe alipo ndi mankhwala a hypoglycemic omwe ali m'gulu la sulfonylurea kapena kuphatikiza kwa mankhwala a hypoglycemic a gulu la sulfonylurea ndi insal insulin, kuti muchepetse chiopsezo cha hypoglycemia, mutha kuganizira kuchepetsa kuchuluka kwa mankhwala a hypoglycemic a group la sulfonylurea kapena gawo la basal insulin. Malangizo apadera ").

Kugwiritsa ntchito mankhwala Lixumia sikufuna kuwunika kwapadera kwa kuchuluka kwa shuga m'magazi. Komabe, mukagwiritsidwa ntchito limodzi ndi mankhwala am'magazi a hypoglycemic a gulu la sulfonylurea kapena insal insulin, kuyang'anira kuchuluka kwa shuga wamagazi kapena kudziyang'anira nokha (kuwongolera wodwalayo) kwa kuphatikiza kwa shuga wamagazi kungafunike kusintha muyezo wa mankhwala a hypoglycemic a group la sulfonylurea kapena basal insulin.

Magulu apadera a odwala

Ana ndi achinyamata ochepera zaka 18

Pakadali pano, chitetezo ndi kugwiritsa ntchito bwino kwa mankhwala a Lixumia mwa odwala osakwana zaka 18 sizinaphunzire.

Anthu okalamba

Palibe kusintha kwa mlingo komwe kumafunikira malinga ndi zaka za wodwalayo.

Odwala omwe ali ndi vuto la chiwindi

Palibe kusintha kwa mlingo kumene kwa odwala omwe ali ndi chiwindi.

Odwala omwe ali ndi vuto la impso

Kusintha kwa Mlingo sikofunikira kwa odwala omwe ndi ofatsa aimpso kulephera (kulengedwa kwa creatinine 50-80 ml / min) ndi kulephera kwapakati kwaimpso (creatinine clear 30-50 ml / min).

Palibe chochitika chogwiritsa ntchito Lixumia kwa odwala omwe amalephera kwambiri aimpso (creatinine chilolezo chochepera 30 ml / min) kapena kulephera kwa impso, motero, kugwiritsa ntchito kwa Lixumia m'gulu lino la odwala kumatsutsana.

Mankhwala a Lixumia amaperekedwa 1 kamodzi patsiku mkati mwa ola limodzi musanadye chakudya choyamba masana kapena mkati mwa ola limodzi musanadye chakudya chamadzulo. Ngati mlingo wotsatira utadumpha, uyenera kuperekedwa mkati mwa ola limodzi chakudya chotsatira chisanachitike. Mankhwala Lixumia chikuyendetsedwera subtaneane mu ntchafu, pamimba khoma kapena phewa. Mankhwala a Lixumia sangathe kutumikiridwa kudzera m'mitsempha ndi intramuscularly. Musanagwiritse ntchito, cholembera cha Lixumia sichisungika mufiriji kuti chisenthe kwambiri ndi 2-8 ° C poika pake kuti chitetezedwe kuti chisawonekedwe. Mukatha kugwiritsa ntchito koyamba, cholembera cha lixumia cha Lixumia chizisungidwa pa kutentha osaposa 30 ° C. Mukatha kugwiritsa ntchito, cholembera cha Lixumium sichikhala chotsekedwa ndi chipewa kuti chiziteteza ku kuwala. Lixumia Syringe cholembera siyenera kusungidwa ndi singano yomata. Osagwiritsa ntchito cholembera cha Lixumia ngati chazirala.

Lixumia Syringe cholembera uyenera kutayidwa pambuyo masiku 14.

Zotsatira zoyipa

Pafupipafupi pazochitika zoyipa (HP) zimatsimikiziridwa motere: pafupipafupi: ≥10%, nthawi zambiri: ≥1% - masabata 76) zimachitika ndimafupipafupi a> 5% (ngati pafupipafupi anali odwala kwambiri omwe amatenga Lixumia poyerekeza ndi odwala kumwa mankhwala ena onse ofananitsa, kuphatikizapo placebo, komanso pafupipafupi a> 1% odwala omwe ali mgululi la Lixumia, ngati kuwirikiza kwawo kudali kochulukirapo koposa kawiri kawiri kawiri ka HP mwa odwala omwe amalandila mankhwala aliwonse ofananizira (kuphatikizapo placebo) .

Matenda opatsirana komanso parasitic

Influenza, chapamwamba kupuma thirakiti matenda.

Matenda a metabolism komanso zakudya

Hypoglycemia yomwe imachitika ndi zizindikiro zamankhwala (pamene Lixumia imagwiritsidwa ntchito limodzi ndi mankhwala amkamwa a hypoglycemic a gulu la sulfonylurea ndi / kapena basal insulin).

Kusokonezeka kwamanjenje

Matenda Am'mimba

Kusanza, kusanza, kutsekula m'mimba.

Kusokonezeka kwa minofu ndi mafupa

Odwala omwe amalandila Lixumia mu monotherapy kapena osakanikirana ndi metformin, hypoglycemia yokhala ndi mawonetsedwe azachipatala nthawi zambiri amakula, ndipo pafupipafupi odwala omwe amalandila Lixumia anali ofanana ndi a placebo panthawi yonse ya chithandizo.

Odwala omwe adapatsidwa Lixumia limodzi ndi mankhwala am'magazi a hypoglycemic a gulu la sulfonylurea kapena insal insulin, zochitika za hypoglycemia, zomwe zimayendera limodzi ndi zizindikiro zamankhwala, zinali pafupipafupi.

Munthawi yonse ya chithandizo ndi Lixumia, zochitika za hypoglycemia zomwe zimapezeka ndi matenda azachipatala zinali zapamwamba pang'ono kuposa ndi placebo, pomwe Lixumia adagwiritsidwa ntchito limodzi:

• ndi mankhwala amkamwa a hypoglycemic a gulu la sulfonylurea ndi metformin,
• Ndi basal insulin monotherapy,
• kuphatikiza kwa basulin insulin ndi metformin.

Munthawi yonse ya chithandizo pamene Lixumia adagwiritsidwa ntchito limodzi ndi monotherapy ndi mankhwala amkamwa a hypoglycemic a gulu la sulfonylurea, hypoglycemia yokhala ndi mawonetsedwe azachipatala inachitika mu 22.7% ya odwala omwe adathandizidwa ndi Lixumia komanso mu 15.2% ya odwala omwe adalandira placebo.Pamene Lixumia adagwiritsidwa ntchito kuphatikiza katatu ndi mankhwala amkamwa a hypoglycemic a gulu la sulfonylurea ndi insal insulin, hypoglycemia yodziwonetsa pazachipatala inachitika mu 47.2% ya odwala omwe amathandizidwa ndi lixisenatide, ndipo mu 21.6% ya odwala omwe amathandizidwa ndi placebo.

Mokulira, munthawi yonse yomwe mankhwalawa amamwa mankhwalawa panthawi yayitali, kuyeza kwambiri kwa matenda a hypoglycemia ofanana ndi kuchepa kwa "infrequent" mu 0.4% mwa odwala omwe amalandila Lixumia komanso 0,2% mwa odwala omwe akulandira placebo) .

Matenda Am'mimba

Kuchepetsa mseru komanso kusanza kunali kotchuka kwambiri kwa HP mkati mwa milungu 24. Zovuta zamiseru zimachulukanso mwa odwala omwe amathandizidwa ndi Lixumia (26.1%) kuposa odwala omwe amathandizidwa ndi placebo (6.2%). Kuchuluka kwa kusanza kunalinso kwakukulu kwa odwala omwe amathandizidwa ndi Lixumia (10.5%) kuposa odwala omwe amathandizidwa ndi placebo (1.8%). Ma HP amenewa anali ofatsa komanso osakhalitsa ndipo anapezeka mkati mwa milungu itatu itangoyamba kumene chithandizo. M'milungu yotsatira, pang'onopang'ono adachepa.

Odwala omwe amathandizidwa ndi Lixumia, kuchuluka kwa nseru kumakhala kotsika (24,5%) kuposa kwa odwala omwe amachitidwa ndi extenatide 2 kawiri patsiku (35.1%), komanso pafupipafupi ya HP ina yam'mimba m'matumbo onse magulu azachipatala anali ofanana.

Zokhudza malo jakisoni

Zomwe zimachitika jekeseni mkati mwa sabata la 24 la mankhwala zimawonedwa mu 3.9% ya odwala omwe amalandila Lixumia, pomwe odwala amalandila placebo, amawonekera pafupipafupi ndi 1.4%. Machitidwe ambiri anali ofatsa kwambiri ndipo nthawi zambiri samasiya kulandira chithandizo.

Chifukwa cha mankhwala omwe amatha kukhala ndi mankhwala omwe ali ndi mapuloteni kapena ma peptides, atalandira chithandizo ndi Lixumia odwala, mapangidwe a antibodies ku lixisenatide ndi otheka. Pamapeto pa nyengo ya masabata a 24 othandizira, mu maphunziro oyendetsedwa ndi placebo, 69.4% ya odwala omwe amathandizidwa ndi lixisenatide anali ndi zotsatirapo zabwino za kukhalapo kwa ma antibodies a lixisenatide. Komabe, kusintha kwa index ya HbA 1c, poyerekeza ndi yomwe isanayambe kugwiritsidwa ntchito kwa lixisenatide, inali yemweyo, osasamala zabwino kapena zoyipa zomwe zimawunikira pakuwunika kwa ma antibodies kuti lixisenatide. Mwa odwala omwe amathandizidwa ndi lixisenatide omwe anali ndi vuto la HbA 1c, 79.3% adakhala ndi mayeso olakwika pakubwera kwa ma antibodies kuti lixisenatide kapena gawo la antibodies kuti lixisenatide linali pansi pamunsi pamunsi pakutha kwake, pomwe 207% odwala anali kuchuluka kwa ma antibodies kuma lixisenatide.

Panalibe kusiyana kulikonse pa chitetezo pamankhwala mwa odwala malinga ndi momwe ma antibodies amapezeka ndi lixisenatide, kupatula kuwonjezereka kwa pafupipafupi pamalo opangira jakisoni odwala osavomerezeka. Zambiri zomwe zimachitika jekeseni malo anali ofatsa, mosasamala kanthu za kukhalapo kapena kusakhalapo kwa ma antibodies a lixisenatide.

Panalibe kuyambukira kwachilendo ndi glucagon wachilengedwe kapena mtundu wa GLP-1.

Zotsatira zoyipa zomwe zimagwirizanitsidwa ndi kugwiritsidwa ntchito kwa lixisenatide (monga anaphylactic reaction, angioedema, ndi urticaria) munthawi yayikulu ya masabata 24 amawonetsedwa mu 0.4% ya odwala omwe adachitidwa ndi Lixumia, poyerekeza ndi odwala osakwana 0.1% pagulu la placebo.

Kukhazikika kwa mankhwalawa

Pafupipafupi pakulekanitsidwa kwa mankhwalawa chifukwa cha zovuta zomwe zimachitika anali 7.4% m'gulu la Lixumia ndi 3.2% m'gululo la placebo. Ma HP omwe amapezeka pafupipafupi omwe amatsogolera pakuchotsedwa kwa chithandizo mu gulu la Lixumia anali ndi mseru (3.1%) ndi kusanza (1.2%).

Mlingo

Njira yothetsera jakisoni 0,05 mg / ml ndi 0,5 mg / ml

1 ml yankho lili:

yogwira mankhwala - lixisenatide 0,05 mg kapena 0,10 mg

zotuluka: 85% glycerin, sodium acetate trihydrate, L-methionine, metacresol, hydrochloric acid, sodium hydroxide, madzi a jekeseni.

Transparent colorless madzi.

Mankhwala

Pambuyo subcutaneous makonzedwe kwa odwala mtundu 2 shuga, mayamwidwe kuchuluka kwa lixisenatide mofulumira, mosasamala kanthu mlingo kutumikiridwa. Osatengera mlingo komanso ngati lixisenatide idagwiritsidwa ntchito limodzi kapena zingapo, odwala omwe ali ndi matenda a shuga a 2, pafupifupi tmax imachokera ku 1 mpaka 3.5 maola. Mokhudzana ndi subcutaneous makonzedwe a lixisenatide pamimba, ntchafu kapena phewa, palibenso kusiyana kwakukulu pakumwedwa.

Lixisenatide ali ndi digiri yolumikizira (55%) kumapuloteni amunthu.

Kuchulukitsa komwe kumawonekera pambuyo povomerezeka kwa lixisenatide (Vz / F) kuli pafupifupi 100 L.

Biotransformation ndi chimbudzi

Monga peptide, lixisenatide imachotsedwera ndi kusefera kwa glomerular ndikutsatiridwa kwa tubular ndikuwonjezeranso kuchepa kwa metabolic, zomwe zimayambitsa kupanga ma peptides ang'ono ndi ma amino acid, omwe amakhalanso ndi protein metabolism.

Pambuyo makonzedwe angapo Mlingo wa odwala 2 matenda ashuga, pafupifupi kuthetsa theka-moyo anali pafupifupi 3 maola ndipo pafupifupi kuwonekera pafupifupi (CL / F) anali pafupifupi 35 l / h.

Odwala ndi mkhutu aimpso ntchito

Odwala omwe ali ndi vuto lochepa (mawonekedwe a creatinine omwe amawerengedwa ndi njira yokhazikitsidwa ndi Cockcroft-Gault, anali 60-90 ml / min), zolimbitsa thupi (kuvomerezeka kwa creatinine anali 30-60 ml / min) komanso kuvulala kwambiri kwa aimpso (kuvomerezedwa kwa creatinine kunali 15-30 ml / mphindi), AUC (dera lomwe limakhala ndi nthawi yopindikira) idakwera ndi 46%, 51% ndi 87%, motsatana.

Odwala omwe ali ndi vuto la chiwindi

Popeza lixisenatide imagwiritsidwa ntchito kwambiri ndi impso, odwala omwe ali ndi vuto laimpso kapena matenda operewera sanachite nawo maphunziro a pharmacokinetic. Kukanika kwa hepatatic sikuyembekezeredwa kukhudza pharmacokinetics ya lixisenatide.

Jenda ilibe gawo lalikulu pama pharmacokinetics a lixisenatide.

Kutengera ndi zotsatira za kafukufuku wa pharmacokinetic mwa odwala amtundu wa Caucasian, Japan ndi China, ochokera kumayiko ena sakhala ndi vuto lililonse pa pharmacokinetics ya lixisenatide.

M'badwo sakhala ndi vuto lililonse pama pharmacokinetics a lixisenatide. Mu kafukufuku wa pharmacokinetic mwa okalamba omwe alibe odwala matenda ashuga, kugwiritsa ntchito lixisenatide 20 μg pagulu la odwala okalamba (odwala 11 azaka zapakati pa 65 mpaka 74 ndi odwala 7 azaka zapakati pa 75 ndi 75), zomwe zimapangitsa kuchuluka kwapakati pa PPK ya lixisenatide ndi 29%, poyerekeza ndi odwala 18 azaka za 18 mpaka 45, mwina zimagwirizanitsidwa ndi kuchepa kwa impso m'gulu lakale.

Kulemera kwa thupi kulibe vuto lililonse PPK chizindikiro cha lixisenatide.

Lixisenatide ndi agonist yosankha ya GLP-1 receptors (glucagon-like peptide-1). Cholandilira cha GLP-1 ndicholinga cha majini obadwa nawo a GLP-1, mahomoni amkati mwa insulin omwe amatha kupatsa insulin modalira maselo a pancreatic beta.

Mphamvu ya lixisenatide imayang'aniridwa ndi kuyanjana kwina ndi GLP-1 receptors, zomwe zimapangitsa kuwonjezeka kwa intcacellular cyclic adenosine monophosphate (cAMP). Lixisenatide imalimbitsa katemera wa insulin pamene kuchuluka kwa shuga m'magazi kumawonjezeka, koma osati ndi standardoglycemia, komwe kumachepetsa chiopsezo cha hypoglycemia.

Nthawi yomweyo, secretion wa glucagon imaponderezedwa. Ndi hypoglycemia, njira yopumira ya glucagon katulutsidwe imasungidwa. Lixisenatide imachedwetsa kutuluka kwa m'mimba, kuchepetsa kuthamanga komwe glucose wopezeka ndi chakudya amakhala m'magazi.

Ikagwiritsidwa ntchito kamodzi patsiku kwa odwala omwe ali ndi matenda a shuga a 2, lixisenatide imathandizira kuwongolera kwa glycemic chifukwa chotsatira komanso nthawi yayitali yochepetsa kutsekeka kwa glucose mukatha kudya komanso m'mimba yopanda kanthu.

Zotsatira zam'magazi a postprandial zimatsimikiziridwa mu kafukufuku wamasabata a 4, poyerekeza ndi liraglutide 1.8 mg kamodzi patsiku kuphatikiza ndi metformin. Kutsika kwa gawo loyambirira la PPC index ya 0: 30–4: 30 h wa glucose wa plasma chakudya chisanafike:

-12.61 maola * mmol / L (-227.25 maola * mg / dL) m'gulu la lixisenatide ndi

- maola 4.04 * mmol / L (-72.83 maola * mg / dL) m'gulu la liraglutide. Izi zidatsimikizidwanso mu kafukufuku wa masabata a 8 poyerekeza ndi liraglutide wokhazikitsidwa musanadye kadzutsa pamodzi ndi insulin glargine wokhala ndi kapena wopanda metformin.

Kuchita Mwachipatala ndi Chitetezo

Mu maphunziro omaliza a gawo la III, zidadziwika kuti kumapeto kwa nyengo yayikulu ya milungu 24, opitilira 90% ya odwala adakwanitsa kusunga mlingo wokonzanso wa Lixumia 20 μg kamodzi patsiku.

Zowonjezera kuphatikiza mankhwala ndi mankhwala amkamwa antidiabetes

Kumapeto kwa nyengo yayikulu ya milungu 24 ndi Lixumia, kuphatikiza ndi metformin, sulfonylurea, pioglitazone, kapena kuphatikiza kwa mankhwalawa, kukuwonetsa kuchepa kwakukulu kwa kusamba kwa plasma HbA1c ndi glucose ya maola 2 atatha kudya mayeso poyerekeza ndi placebo. Kuchepa kwa HbA1c kunali kofunikira kwambiri pamene mankhwalawa amaperekedwa kamodzi patsiku, ngakhale atagwiritsidwa ntchito m'mawa kapena madzulo. Kuwonetsedwa koteroko ku HbA1c kudakhala kotenga nthawi yayitali m'maphunziro a nthawi yayitali mpaka masabata makumi asanu ndi limodzi.

Mlingo wa gluprose wa postprandial

Lixumia

Kumapeto kwa nyengo yayikulu ya masabata 24, mankhwala a Lixumia osakanikirana ndi metformin ndi / kapena sulfonylurea m'mayeso onse olamulidwa adayambitsa kusintha kwamphamvu kwa thupi kuyambira kuyambira -1.76 kg mpaka -2.96 kg.

Kusintha kwa kulemera kwa thupi kuchokera pamlingo woyambira kuchokera pa 0,38 makilogalamu mpaka -1.80 makilogalamu adawonekeranso mu odwala omwe amalandila lixisenatide osakanikirana ndi mankhwala a insal insulin, kapena osakanikirana ndi metformin kapena sulfonylurea.

Odwala omwe anayamba kugwiritsa ntchito insulin, mgulu la lixisenatide, kulemera kwa thupi sikunasinthe, pomwe pagulu la placebo kuwonjezeka. M'maphunziro amtundu wautali mpaka masabata makumi awiri ndi limodzi, kuchepa thupi kudali kokhazikika.

Kafukufuku wa zamankhwala a Lixumia amawonetsa ntchito ya cell ya beta yowongoleredwa malinga ndi mtundu wa homeostatic beta cell test test (HOMO-β / HOMA-β).

Kuunika kwamtima

M'mayesero onse oyendetsedwa ndi placebo a gawo lachitatu, odwala omwe ali ndi matenda a shuga a 2 sanawonetse kuchuluka kwa mtima.

Anthu okalamba

Anthu azaka zapakati pa ≥70

Mankhwala a Lixisenatide anakulitsa kwambiri glycated hemoglobin (HbA1c) (-0.64% poyerekeza ndi placebo, chidaliro cha 95% chidaliro (CI): -0.810% mpaka -0.464%, p

Zotsatira zoyipa za Lixumium solution

Chidule cha Mbiri Yachitetezo

Odwala opitilira 2,600 m'maphunziro 8 olamulidwa ndi placebo akulu kapena maphunziro a gawo lachitatu omwe ali ndi mphamvu yogwira adalandira Lixumia mwina mu monotherapy kapena kuphatikiza ndi metformin, sulfonylurea (yokhala ndi metformin kapena ya metformin kapena ya sformonylurea) kapena popanda icho).

Zomwe zimachitika kawirikawiri pazovuta zamayendedwe azachipatala zinali mseru, kusanza, ndi kutsekula m'mimba. Maganizo ake anali ofatsa komanso osakhalitsa.

Pakhala pali milandu ya hypoglycemia (pomwe Lixumia idagwiritsidwa ntchito limodzi ndi sulfonylurea ndi / kapena basal insulin) ndi mutu. Zotsatira zoyipa zimawonedwa mu 0.4% ya odwala omwe amagwiritsa ntchito Lixumia.

Pansipa pali zoyipa zomwe zimachitika ndi pafupipafupi> 5%, ngati pafupipafupi ndimomwe odwala amalandira Lixumia kuposa odwala omwe amalandila mankhwala onse oyerekeza, amaphatikizanso zovuta zina ndi ency 1% pagulu la odwala omwe amalandila Lixumia, ngati pafupipafupi zodzachitika anali 2 times kuposa pafupipafupi pakati pagulu la odwala omwe amalandila mankhwala onse oyerekeza.

Zotsatira zoyipa zomwe zimakhazikitsidwa poyesedwa kwa placebo ndi gawo lachitatu ndi kayendetsedwe kogwira nthawi yonse yamankhwala (kuphatikiza nthawi yopitilira nyengo yayikulu ya milungu 24 mu maphunziro ndi studies milungu makumi asanu ndi awiri a chithandizo chonse).

• hypoglycemia (kuphatikiza ndi sulfonylurea ndi / kapena basulin insulin)

• mutu

• kusanza, kusanza, kutsekula m'mimba

Nthawi zambiri (≥ 1/100 mpaka 5% mafuta amalipira tsiku la balsan zhalymsyz reactionar berylgen, mlenje payda boli zhіlіgі barlyқ salistyru mankhwala taryn alғan edelushіler toptara arasynda zhіlіlіndydydelda 1%

Placebo-baқılanatyn әne belsendi baқylanatyn III gawo ғ zertteulerde bүkіl emdela kezeңi boyina (bүkіl emdeudің ≥ 78 aptasynda zertteulerde negizy-24

Malangizo apadera

Odwala omwe amalandila Lixumia mu monotherapy kapena osakanikirana ndi metformin, hypoglycemia yokhala ndi mawonetsedwe azachipatala nthawi zambiri amakula, ndipo pafupipafupi odwala omwe amalandila Lixumia anali ofanana ndi a placebo panthawi yonse ya chithandizo.

Odwala omwe adapatsidwa Lixumia limodzi ndi mankhwala am'magazi a hypoglycemic a gulu la sulfonylurea kapena insal insulin, zochitika za hypoglycemia, zomwe zimayendera limodzi ndi zizindikiro zamankhwala, zinali pafupipafupi.

Munthawi yonse ya chithandizo ndi Lixumia, zochitika za hypoglycemia zomwe zimapezeka ndi matenda azachipatala zinali zapamwamba pang'ono kuposa ndi placebo, pomwe Lixumia adagwiritsidwa ntchito limodzi:

- ndi mankhwala a pakamwa a hypoglycemic a gulu la sulfonylurea ndi metformin,

- ndi monotherapy ya basal insulin,

- ndi kuphatikiza kwa basulin insulin ndi metformin.

Munthawi yonse ya chithandizo pamene Lixumia adagwiritsidwa ntchito limodzi ndi monotherapy ndi mankhwala amkamwa a hypoglycemic a gulu la sulfonylurea, hypoglycemia yokhala ndi mawonetsedwe azachipatala inachitika mu 22.7% ya odwala omwe adathandizidwa ndi Lixumia komanso mu 15.2% ya odwala omwe adalandira placebo. Pamene Lixumia adagwiritsidwa ntchito kuphatikiza katatu ndi mankhwala amkamwa a hypoglycemic a gulu la sulfonylurea ndi insal insulin, hypoglycemia yodziwonetsa pazachipatala inachitika mu 47.2% ya odwala omwe amathandizidwa ndi lixisenatide, ndipo mu 21.6% ya odwala omwe amathandizidwa ndi placebo.

Mwambiri, munthawi yonse ya kumwa mankhwalawa mu gawo loyesedwa la chipatala III, zimachitika kuti matenda oopsa a hypoglycemia omwe ali ndi chiwonetsero chazachipatala ofanana ndi "infrequent" gradation.

Chifukwa cha mankhwala omwe amatha kukhala ndi mankhwala omwe ali ndi mapuloteni kapena ma peptides, atalandira chithandizo ndi Lixumia odwala, mapangidwe a antibodies ku lixisenatide ndi otheka. Kumapeto kwa nyengo ya masabata a 24, mu maphunziro omwe amayendetsedwa ndi placebo, 69.4% ya odwala omwe amathandizidwa ndi lixisenatide anali ndi zotsatirapo zabwino za kukhalapo kwa ma antibodies a lixisenatide.Komabe, kusintha kwa index ya HbA1c, kuyerekeza ndi komwe ntchito isanagwiritsidwe ntchito kwa lixisenatide, inali yemweyo, mosasamala kanthu za zabwino kapena zoyipa zomwe zimawunikira pakupezeka kwa ma antibodies kuti lixisenatide. Mwa odwala omwe amathandizidwa ndi lixisenatide omwe ali ndi kuchuluka kwa HbA1c, 79.3% adakhala ndi mayeso osayenera chifukwa cha kupezeka kwa ma antibodies kuti lixisenatide kapena gawo la antibodies kuti lixisenatide linali pansi pamunsi pamunsi mwa malire ake, ndipo otsala a 20.7% anali ndi kuchuluka zopezeka za antibodies kuti lixisenatide.

Panalibe kusiyana kulikonse pa chitetezo pamankhwala mwa odwala malinga ndi momwe ma antibodies amapezeka ndi lixisenatide, kupatula kuwonjezereka kwa pafupipafupi pamalo opangira jakisoni odwala osavomerezeka. Zambiri zomwe zimachitika jekeseni malo anali ofatsa, mosasamala kanthu za kukhalapo kapena kusakhalapo kwa ma antibodies a lixisenatide.

Panalibe kuyambukira kwachilendo ndi glucagon wachilengedwe kapena mtundu wa GLP-1.

Mlingo ndi makonzedwe

Mlingo woyamba: Mlingo umayamba ndi 10 mcg Lixumia kamodzi patsiku kwa masiku 14.

Mlingo wa makonzedwe okhazikika a 20 mcg Lixumia kamodzi patsiku uyamba pa tsiku la 15.

Mankhwala okonza, Lixumia jakisoni wa 20 mcg amagwiritsidwa ntchito. Pa mlingo woyambira, yankho la 10 μg Lixumia jakisoni likugwiritsidwa ntchito.

Liksumiya imayambitsidwa kamodzi patsiku, ola limodzi asanadye. Makamaka, jakisoni wa Lixumia amachitidwa tsiku lililonse chakudya chisanachitike, pomwe nthawi yabwino kwambiri yoyendetsera imasankhidwa. Ngati mlingo wa Lixumia wasowa, jakisoni amayenera kupangidwa ola limodzi chakudya chotsatira chisanachitike.

Popereka Lixumia, kuwonjezera pakulandila chithandizo ndi metformin, mlingo wa metformin womwe ungakhalepo wosasinthika.

Popanga Lixumia, kuwonjezera pakulandila ndi sulfonylurea kapena basal insulin, mlingo wa sulfonylurea kapena basal insulin ungachepetse kuchepetsa chiopsezo cha hypoglycemia.

Lixumia sayenera kutumizidwa limodzi ndi basal insulin ndi sulfonylurea chifukwa chowonjezera chiopsezo cha hypoglycemia (onani "Malangizo apadera").

Kugwiritsa ntchito Lixumia sikufuna kuwunika mwapadera kwamishuga yamagazi. Komabe, mukagwiritsidwa ntchito limodzi ndi sulfonylurea kapena basal insulin, kuwunika shuga wamagazi kapena kudziyang'anira nokha shuga kungakhale kofunikira kuti muthe kusintha kwa sulfonylurea kapena basal insulin.

Kutengera zaka, kusintha kwa mankhwala sikofunikira.

Odwala ndi mkhutu aimpso ntchito

Odwala omwe ali ndi vuto laimpso wofatsa kapena wolimbitsa thupi, kusintha kwa mankhwala sikofunikira. Palibe zochizira odwala omwe ali ndi vuto la impso kwambiri (creatinine chilolezo chochepera 30 ml / min) kapena odwala omwe ali ndi vuto la impso, ndipo pachifukwa ichi, Lixumia ali osavomerezeka m'magulu a odwala.

Odwala omwe ali ndi vuto la chiwindi

Kwa odwala omwe ali ndi vuto la chiwindi, kusintha kwa mankhwalawa sikofunikira. Chiwerengero cha ana

Chitetezo ndi kuyendetsa bwino kwa lixisenatide mwa ana ndi achinyamata ochepera zaka 18 sizinakhazikitsidwe. Palibe zambiri zomwe zilipo.

Njira zoyendetsera

Lycumum akuwonetsedwa kuti ikwaniritse kayendetsedwe ka ntchafu, ntumbo kapena phewa. Simungathe kulowa mkati kapena kudzera m'mitsempha.

Lixumia sayenera kugwiritsidwa ntchito ngati yazizira. Liksumiya itha kugwiritsidwa ntchito ndi singano zotayika kuchokera pa 29 mpaka 32 calter cholembera. Ma singano a syringe sanaphatikizidwe.

Ndikofunikira kulamula wodwalayo kutaya singano itatha ntchito iliyonse malinga ndi zofunikira zamalamulo akunyumba otayidwa ndikusunga cholembera popanda singano yosayilidwa. Izi zimathandiza kupewetsa kuipitsidwa ndi kubisala kwa singano. Cholembera adapangira kuti azigwiritsidwa ntchito ndi wodwala m'modzi yekha.

Chithandizo chilichonse chosagwiritsidwa ntchito kapena zotayidwa ziyenera kutayidwa malinga ndi malamulo akunyumba.

Pakakhala maphunziro othandizira, mankhwalawa sayenera kukhala osakanikirana ndi mankhwala ena.

Zochita zamankhwala osokoneza bongo

Lixisenatide ndi peptide yomwe siinapangidwe pochita cytochrome P450. M'maphunziro a in vitro, lixisenatide sizinakhudze zomwe zimayesedwa cytochrome P450 isoenzymes kapena anthu onyamula.

Kuchepetsa kuthamangitsidwa kwa zam'mimba zomwe zimagwiritsidwa ntchito ndi lixisenatide kumachepetsa kuyamwa kwa mankhwala omwe amaperekedwa pakamwa. Kusamalidwa kuyenera kuchitika mosamala kuti odwala azilandira mankhwala omwe ali ndi kalozera kakang'ono ka mankhwala kapena mankhwala omwe amafunikira kuyang'aniridwa kuchipatala, makamaka poyambira chithandizo ndi lixisenatide. Kwa lixisenatide, mankhwalawa amayenera kumwa mwachizolowezi. Ngati mankhwala oterowo ayenera kumwa ndi zakudya, odwala ayenera kulangizidwa kuti azimwa nawo zakudya nthawi iliyonse yomwe zingagwiritsidwe ntchito ngati lixisenatide sigwiritsidwa ntchito.

Mankhwala amkamwa, monga maantibayotiki, omwe, makamaka pokhudzana ndi kugwira ntchito, amadalira poyambira, odwala ayenera kulangizidwa kuti atenge ola limodzi asanafike kapena maola 4 atabayidwa jekeseni wa lixisenatide.

Mlingo wa enteric-sungunuka wokhala ndi zinthu zokhudzana ndi chimbudzi m'mimba uyenera kugwiritsidwa ntchito ola limodzi musanadye kapena maola 4 mutabayidwa jekeseni wa lixisenatide.

Paracetamol adagwiritsidwa ntchito ngati mankhwala osokoneza bongo kuti athe kuwunika momwe lixisenatide imathandizira kutuluka kwam'mimba. Mlingo umodzi wa paracetamol 1000 mg utagwiritsidwa ntchito, dera lomwe lili pansi pajika (PPC) ndi t1 / 2 ya paracetamol silinasinthe, mosasamala kanthu nthawi yomwe limagwiritsidwira ntchito (jekeseniatide isanachitike kapena itatha. Pomwe idagwiritsidwa ntchito ola limodzi kapena maola 4 pambuyo pa 10 μg ya lixisenatide, gawo la Cmax la paracetamol lidatsika, motsatana, ndi 29% ndi 31%, ndipo mtengo wa tmax udachepetsedwa, motsatana, ndi maola a 2.0 ndi 1.75. Pogwiritsa ntchito mlingo wa 20 μg yokonza, kuchepa kwapang'onopang'ono kwa tmax ndi kuchepa kwa Cmax ya paracetamol kunanenedweratu.

Panalibe zovuta pa Cmax ndi tmax ya paracetamol pamene paracetamol imagwiritsidwa ntchito ola limodzi musanagwiritse ntchito lixisenatide.

Poganizira izi pamwambapa, palibe chifukwa chosinthira Mlingo wa paracetamol, koma kukulitsa kwa Tmax komwe kumawonedwa pomwe paracetamol idakonzedwa patatha maola 1-4 mutatha kutenga lixisenatide iyenera kuganiziridwa ngati pakufunika kuchitapo kanthu mwachangu.

Pambuyo pakugwiritsa ntchito limodzi mlingo wa kulera kwapakamlomo (ethinyl estradiol 0,03 mg / levonorgestrel 0,15 mg) 1 ora lisanachitike kapena maola 11 mutatha kugwiritsa ntchito 10 μg ya lixisenatide, Smax, PPC, t1 / 2 ndi tmax ya ethinyl estradiol ndi levonorgestrel sanasinthe.

Kugwiritsira ntchito kulera kwapakamwa kwa ola limodzi kapena maola 4 atatha kugwiritsa ntchito lixisenatide sikunakhudze AUC ndi t1 / 2 ya ethinyl estradiol ndi levonorgestrel, pomwe Cmax ya ethinyl estradiol idatsika, motsatana, 52% ndi 39%, ndi Cmax ya levonorgestrel idatsika ndi 46%, motero ndi 20%, ndipo phindu la tmax limatsitsidwa ndi maola 1-3.

Kutsika kwa Cmax kumakhala ndikufunika kokwanira kuchipatala, komanso kusintha kwa njira yothetsera kubereka kwamlomo sikofunikira.

Mukamagwiritsa ntchito 20 μg ya lixisenatide osakanikirana ndi 40 mg ya atorvastatin m'mawa kwa masiku 6, zotsatira za atorvastatin sizinasinthe, pomwe Cmax inatsika ndi 31% ndi tmax inakula ndi maola 3.25.

Kukula kotere kwa tmax sikunawonedwe ngati atorvastatin amagwiritsidwa ntchito madzulo, ndi lixisenatide m'mawa, koma PPK ndi Cmax ya atorvastatin, motsatana, idakwera 27% ndi 66%.

Kusintha kumeneku sikofunikira kuchipatala, motero kusintha kwa atorvastatin sikofunikira mukamagwiritsidwa ntchito ndi lixisenatide.

Warfarin ndi zotumphukira zina za coumarin

Pambuyo pakugwiritsira ntchito 25 mg wa warfarin ndi milingo yambiri ya lixisenatide 20 μg, sizinatheke pa AUC kapena INR (chiwembu chapadziko lonse), pomwe Cmax idatsika ndi 19% ndipo tmax idakwera mpaka maola 7.

Kutengera ndi izi, kusintha kwa mankhwalawa kwa warfarin sikuyenera kugwiritsidwa ntchito limodzi ndi lixisenatide, komabe, kuwunika pafupipafupi kwa INR kwa odwala omwe akutenga warfarin ndi / kapena coumarin akutengedwa pakayambira kapena kutha kwa chithandizo cha lixisenatide.

Pambuyo pa kuphatikiza kwa lixisenatide 20 μg ndi 025 mg wa digoxin mu boma lofanana, PPC ya digoxin sizinasinthe. Mtengo wa tmax wa digoxin ukuwonjezeka ndi maola 1.5, ndipo mtengo wa Cmax umatsika ndi 26%.

Kutengera ndi izi, kusintha kwa digoxin sikofunikira pakugwiritsidwa ntchito limodzi ndi lixisenatide.

Pambuyo pa kuphatikiza kwa lixisenatide 20 μg ndi 5 mg ya ramipril kwa masiku 6, ramPril ya PPK idakula ndi 21%, pomwe Cmax idatsika ndi 63%. Zizindikiro za PPC ndi Cmax ya metabolite yogwira (ramiprilat) sizinasinthe. Kuchuluka kwa ramipril ndi ramiprilat kumawonjezeka pafupifupi maola 2,5.

Kutengera ndi izi, kusintha kwa ramipril sikofunikira pamene kumagwiritsidwa ntchito limodzi ndi lixisenatide.

Bongo

Panthawi yamayesero azachipatala, Mlingo wa lixisenatide mpaka 30 mcg unkaperekedwa kawiri tsiku lililonse kwa odwala omwe ali ndi matenda a shuga a 2 mu kafukufuku wamasabata 13. Chiwopsezo chowonjezeka cha kusokonezeka m'mimba chinawonedwa.

Ngati mankhwala osokoneza bongo, molingana ndi zizindikiro ndi zizindikiro zake, wodwalayo ayenera kuyamba kulandira chithandizo chokwanira, ndipo mlingo wa lixisenatide uyenera kuchepetsedwa kwa mlingo womwe waperekedwa.