I-Cabozantinib Iindaba eziPhumeleleyo kunyango lweCaner-AASraw
I-AASraw ivelisa i-Cannabidiol (CBD) ipowder kunye ne-Hemp ebalulekileyo yeoyile ngobuninzi!

ICabozantinib

 

    1. Inkcazo yeCabozantinib
    2. Inkqubo yeCabozantinib yokuSebenza
    3. Iziphumo zeCabozantinib
    4. Uphuhliso lwakutsha nje lweCabozantinib
    5. Unyango lweCabozantinib lwaMabali eeMpumelelo
    6. isishwankathelo

 

ICabozantinib inkcazelo

ICabozantinib (i-CAS:849217-68-1) isetyenziselwa ukunyanga isifo somhlaza sezintso, ngamanye amaxesha ngokudibana nelinye iyeza elibizwa ngokuba yi-nivolumab. I-Cabozantinib ikwasetyenziselwa ukunyanga umhlaza wesibindi kubantu ababekhe baphathwa nge-sorafenib. I-Cabozantinib isetyenziselwa ukunyanga umhlaza we-thyroid osasazeke kwamanye amalungu omzimba. I-Cabozantinib inokusetyenziselwa iinjongo ezingadweliswanga kwesi sikhokelo sonyango.

 

ICabozantinib Indlela yokusebenza

Unyango ekujoliswe kulo sisiphumo seminyaka engama-100 yophando enikezelwe ekuqondeni umahluko phakathi kweeseli zomhlaza kunye neeseli eziqhelekileyo. Ukuza kuthi ga ngoku, unyango lomhlaza lujolise ikakhulu ekubulaleni iiseli ezahlula ngokukhawuleza kuba inqaku elinye leseli zomhlaza kukuba zahlule ngokukhawuleza. Ngelishwa, ezinye zeeseli zethu eziqhelekileyo zahlula ngokukhawuleza nazo, zibangela iziphumo ebezingalindelekanga ezininzi.

Ulwaphulo olujoliswe kulo lu malunga nokuchonga ezinye iimpawu zeseli zomhlaza. Iingcali zenzululwazi zikhangelelanisa iimeko ezahlukeneyo kumaseli omhlaza kunye neeseli eziqhelekileyo. Le ngcaciso isetyenziselwa ukudala unyango olujoliswe ekuhlaseleni amangqamuzana omhlaza ngaphandle kokulimaza iiseli eziqhelekileyo, ngaloo ndlela zikhokelela kwimiphumo emibini yecala. Uhlobo ngalunye lonyango olujoliswe kuyo lusebenza kancinci kodwa lugxininise ukukwazi ukukhula, ukwahlula, ukulungiswa kunye / okanye ukunxibelelana namanye amaseli.

Kukho iintlobo ezahlukeneyo zonyango olujoliswe kuyo, ezichazwe kwiindidi ezintathu ezibanzi. Ezinye iinkqubo ezijoliswe kuzo zijolise kumacandelo angaphakathi kunye nomsebenzi weselfini somhlaza. Iipilisi ezijoliswe kuzo zisebenzisa i-molecule ezincinci ezingena kwiseli kwaye ziphazamise umsebenzi weeseli, zibangela ukuba zife. Kukho iintlobo ezininzi zonyango olujoliswe kuzo ezijolise kwiindawo zangaphakathi zeeseli. Ezinye iithagethi ezijoliswe kuzo zijoliswe kwii-receptors ezingaphandle kweseli. Iipilisi ezijoliswe kwizifunyenwe ziyakwaziwa njengama-antibodies e-monoclonal. I-Antiangiogenesis inhibitors ijolise kwimithambo yegazi eyenza i-oksijeni kwiiseli, ekugqibeleni ibangela ukuba iiselingi zilambile.

I-Cabozantinib lonyango ekujoliswe kulo olujolise kwaye lubophelel I-tyrosine kinase receptors kunye ne-inhibits Umsebenzi wee-tyrosine kinases ezininzi, kubandakanya i-RET, MET, kunye ne-VEGF kumphezulu weseli. Ngokuzibophelela kwezi receptors, i-cabozantinib ibhloka kwiindlela ezibalulekileyo ezikhuthaza ukwahlulwa kweseli.

Uphando luyaqhubeka luchonga ukuba yiyiphi i-cancer ingaphathwa kakubi ngezilwanyana ezijoliswe kuyo kunye nokuchonga iithagethi ezongezelelweyo zezinye iintlobo zomhlaza.

 

ICabozantinib Imiphumela

Fumana uncedo lwezonyango loxakeka xa unemiqondiso yokumelana nomonakalo: imihlathi; ukuphefumula okunzima; ukuvuvukala kobuso bakho, imilomo, ulwimi, okanye umqala.

I-Cabozantinib inokubangela ukugqobhoza (umngxunya okanye iinyembezi) okanye i-fistula (indlela engaqhelekanga) esiswini sakho okanye emathunjini. Biza ugqirha wakho ukuba unesifo esibuhlungu esiswini, okanye ukuba uziva ngathi uyaminxa kwaye uyagungqa xa usitya okanye usela.

Shayela ugqirha wakho ngokukhawuleza ukuba unayo:

▪ Intloko ebuhlungu, ukungaboni kakuhle, ukubetha entanyeni okanye ezindlebeni;

▪ Ukugabha, urhudo, okanye ukuqhina okunzima nokuqhubekayo;

▪ Ukudumba ezandleni, iingalo, imilenze okanye iinyawo;

▪ Ukutyumka ngokulula okanye ukopha (ukuphuma kweempumlo, ukopha kweentsini, ukopha okunzima ukuya exesheni, okanye ukopha okungayi kuyeka);

▪ Izitulo ezinegazi okanye zokuma, khohlela ngefinyila enegazi okanye ukugabha okungathi yindawo yekofu;

▪ IJaundice (ukuba tyheli kolusu okanye amehlo);

▪ Ubuhlungu, amadyungudyungu, ukopha, okanye irhashalala ezintendeni zezandla zakho okanye phantsi kweenyawo zakho;

▪ Ukudideka, iingxaki zokucinga, ukuba buthathaka, ukutshintsha kombono, ukuxhuzula;

▪ Imvakalelo ekhanyayo, ngathi ungaphuma kuyo;

▪ Intlungu yomhlathi okanye ukuba ndindisholo, iintsini ezibomvu okanye ezidumbileyo, amazinyo aqaqambayo, okanye ukuphola kancinci emva kokusebenza kwamazinyo;

▪ Iseli yegazi emhlophe iphantsi ukubala –umkhuhlane, izilonda zomlomo, izilonda kulusu, umqala obuhlungu, ukukhohlela, ukuphefumla nzima;

▪ Iingxaki zedlala le-adrenal – isicaphucaphu, ukugabha, ukudinwa kakhulu, isiyezi, ukuba buthathaka, nokudinwa; okanye

▪ Iimpawu zokubethwa sistroke okanye igazi elijiyileyo-ngesiquphe ukuba ndindisholo okanye ukuba buthathaka kwelinye icala lomzimba wakho, iingxaki ngombono okanye ukulinganisela, ukungakwazi ukuthetha okanye ukuqonda okutshiwo kuwe, iintlungu esifubeni, ubunzima bokuphefumla, ukudumba okanye iintlungu engalweni okanye emlenzeni .

Amayeza akho exesha elizayo e-cabozantinib anokulibaziseka okanye ayeke ngokusisigxina ukuba uneziphumo ebezingalindelekanga ezithile.

 

Iziphumo eziqhelekileyo ziquka:

▪ Ukuqaqanjelwa sisisu, isicaphucaphu, ukugabha, ukungabi namdla, urhudo, ukuqhina;

▪ Ubuhlungu, ukuba bomvu, ukudumba, okanye izilonda emlonyeni okanye emqaleni;

▪ Ukuthetha nzima, ukutshintsha incasa;

▪ Iimpawu ezibandayo ezifana nokuxinana kwempumlo, ukuthimla, umqala obuhlungu, ukukhohlela;

▪ irhashalala;

▪ Ubuhlungu kwimisipha, emathanjeni nasemalungwini akho;

▪ Iimvavanyo ezingaqhelekanga zomsebenzi wesibindi okanye olunye uvavanyo lwegazi;

▪ Ndiziva ndidiniwe;

▪ Ukwehla kobunzima; okanye

▪ Umbala weenwele uqaqamba.

Oku akusiyo uluhlu olupheleleyo lweempembelelo kwaye abanye bangenzeka. Shayela ugqirha wakho kwiingcebiso zonyango malunga nemiphumo emibi. Ungabika iziphumo ezimbi kwi-FDA kwi-1-800-FDA-1088.

 

Uphuhliso lwamva nje lwe ICabozantinib 

UCabozantinib wanikwa inqanaba lenkedama leziyobisi yi-US Food and Drug Administration (FDA) ngo-Novemba ngo-2010 nangoFebruwari 2017.

U-Exelixis wafaka isicelo esitsha seziyobisi kwi-FDA kwisiqingatha sokuqala sika-2012 kwaye nge-29 kaNovemba ngo-2012 i-cabozantinib ekwakhiweni kwayo njenge-capsule yanikwa imvume yokuthengisa yi-US FDA phantsi kwegama elithi Cometriq yokunyanga abaguli abanomhlaza wamadlala we-medullary. yamkelwe kwi-European Union ngenjongo efanayo ngo-2014.

Ngo-Matshi 2016 u-Exelixis onikwe ilayisensi kwi-Ipsen yamalungelo ehlabathi (ngaphandle kwe-US, Canada, ne Japan) kwintengiso ye cabozantinib.

Iziphumo zovavanyo lweSigaba III se-Exelixis zovavanyo lwechiza kwizintso umhlaza Epapashwe kwi-NEJM ngo-2015. Ngo-Epreli ka-2016 i-FDA yanika imvume yokuthengisa ukwenziwa kwethebhulethi njengonyango lwesibini lwezintso umhlaza kwaye kwavunywa okufanayo kwi-European Union ngo-Septemba waloo nyaka.

Nge-Disemba ka-2017, i-FDA yanika imvume kwi-cabozantinib (Cabometyx, Exelixis, Inc.) kunyango lwabantu abane-renal cell carcinoma (RCC). Ukuvunywa bekusekwe kwidatha evela kwi-CABOSUN (NCT01835158), isifundo esingenamkhethe, esivulekileyo selebheli yesibini yokufunda kwi-157 yabathathi-nxaxheba abanomngcipheko ophakathi kunye nomngcipheko ophantsi owayenganyangwa RCC.

NgoJanuwari 2019, i I-FDA ivume i-cabozantinib (I-Cabometyx, Exelixis, Inc.) yabantu abane-hepatocellular carcinoma (HCC) ababekhe banyangwa nge-sorafenib. Ukuvunywa kwakusekwe kwi-CELESTIAL (NCT01908426), i-randomised (2: 1), blind-blind, control-placebo, multicenter trial in nxaxheba kwi-HCC eyayifumene i-sorafenib ngaphambili kwaye yayinomntwana u-Pugh Class A ukukhubazeka kwesibindi.

I-Cabozantinib isaphandwa ngokusebenza kakuhle njengonyango lwe-neurofibromatosis yohlobo 1.

Ukutya kunye noLawulo lweeDrug (FDA) kutsha nje kuvunyiwe i-cabozantinib kunyango lwe-hepatocellular carcinoma kwizigulana ezazifumene i-sorafenib ngaphambili.

I-Cabozantinib yi-tyrosine kinases inhibitor yomlomo ye-MET, i-VEGFR, kunye ne-AXL. Isamkeli se-tyrosine kinases sidlala indima ebalulekileyo kuzo zombini iinkqubo zeselfowuni kunye neenkqubo ze-pathologic, kubandakanya i-oncogenesis, i-metastasis, i-tumor angiogenesis, kunye ne-tumor microenvelo yolondolozo.

I-FDA yokuqala yamkela i-cabozantinib kunyango lwe-medullary umdlavuza wekroroid. Emva kwexesha, i-FDA ivume ukusetyenziswa kwayo kwi-renal cell carcinoma.

 

Unyango lweCabozantinib lwaMabali eeMpumelelo 

Ibali 1: ICabozantinib Yonyango Unyango lokuqala lwe-Renal Cell Carcinoma

NgoDisemba 19, 2017, i-US Food and Drug Administration (FDA) yanika imvume rhoqo kwi-cabozantinib (Cabometyx) kunyango lwezigulana ezine-renal cell carcinoma (RCC).

I-FDA eyayivume ngaphambili i-cabozantinib kwi-2016 yonyango lwezigulana ezine-RCC ehambileyo ethe yafumana unyango lwangaphambili lwe-antiangiogenic. Ukuvunywa kwanamhlanje kubonelela ngonyango kwiseti yomgca wokuqala.ICabozantinib

Olu lwamkelo lwalusekwe kwidatha evela kuvavanyo lweCABOSUN, isifundo esingenamkhethe, esivulekileyo seelebhile II kwizigulana ze-157 ezinomngcipheko ophakathi- kunye nomngcipheko ophantsi owayenganyangwa RCC. Izigulana zifumene i-cabozantinib (n = 79) 60 mg ngomlomo yonke imihla okanye i-sunitinib (Sutent) (n = 78) 50 mg ngomlomo yonke imihla (iiveki ezi-4 kunyango olulandelwa ziiveki ezi-2) kude kube kukuqhubela phambili kwesifo okanye ityhefu engamkelekanga. Uqikelelo lokusinda okungahambelani nenkqubela phambili (njengoko kuvavanywa yikomiti yokuphononongwa kwe-radiology ezimeleyo) kwizigulana ezithatha i-cabozantinib yayiziinyanga eziyi-8.6 (95% isithuba sokuzithemba [CI] = 6.8-14.0) xa kuthelekiswa neenyanga ezi-5.3 (95% CI = 3.0-8.2) ye abaguli abathatha i-sunitinib (umngcipheko wengozi = 0.48; 95% CI = 0.31-0.74; P = .0008).

Ezona zixeliweyo zixela (≥ iipesenti ezingama-25) ezingalunganga kwinkqubo yeklinikhi ye-cabozantinib sisifo sohudo, ukudinwa, isicaphucaphu, ukunciphisa ukutya, uxinzelelo lwegazi, i-erythrodysesthesia yesundu, ukunciphisa umzimba, ukugabha, isifo sokuqaqanjelwa sisisu, kunye nesifo sokuqaqamba kwesisu.

Olona hlobo luqhelekileyo lwe-3-4 yeempendulo ezingalunganga (≥ 5%) kwizigulana ezanyangwa nge-cabozantinib kwi-CABOSUN yayingoxinzelelo lwegazi, urhudo, i-hyponatremia, i-hypophosphatemia, i-erythrodysesthesia yesundu, ukudinwa, ukwanda kwe-ALT, ukunciphisa ukutya, isifo se-stomatitis, iintlungu, i-hypotension, kunye syncope. Idosi ekhuthazwayo ye-cabozantinib yi-60 mg ngomlomo, kanye yonke imihla.

ICabozantinib ikwavunyiwe kunyango lwe medullary umhlaza wedlala lengqula Kwaye kuthengiswa phantsi kwegama lorhwebo elithi Cometriq. ICometriq kunye neCabometyx baneefomathi ezahlukeneyo kwaye azitshintshi.

 

ibali 2: I-Cabozantinib yonyango lwe-Medullary Cancer Cancer

I-FDA yamkele i-cabozantinib (Cometriq) ukunyanga umhlaza we-metastatic medullary cancer (MTC) ngo-Novemba ka-2012. Abathathi-nxaxheba kufuneka babonakalise ukuqhubela phambili kwesifo ngaphakathi kweenyanga ezili-330 ngaphambi kokungena kufundo, okwaqinisekiswa ngekomiti yokuphononongwa kweeradiology ezimeleyo okanye ugqirha onyangayo.

Izigulana zazikhethwe ngokungenamkhethe ukuba zifumane i-cabozantinib 140 mg okanye i-placebo ngomlomo kube kanye yonke imihla kude kube nezifo eziqhubekayo okanye ukunganyamezeleki kwetyhefu. Ukwenza i-Randomization kwahlulwa ngokweminyaka <65 iminyaka vs> 65 iminyaka kunye nokusetyenziswa kwangaphambili kwe-tyrosine kinase inhibitor.ICabozantinib

Iincopho zokuphela kweprayimari kukusinda okungahambelani nenkqubela (PFS), impendulo yenjongo (OKANYE), kunye nexesha lokuphendula kusetyenziswa iindlela zokuguqula i-RECIST. Izigulana kwiqela le-cabozantinib zaye zanexesha elide i-PFS xa kuthelekiswa nezo zifumana i-placebo (P <.0001). Ngokukodwa, i-median PFS kwingalo ye-cabozantinib yayiziinyanga ezili-11.2 kwaye i-median PFS kwingalo ye-placebo yayiziinyanga ezi-4.0.

Zizigulana kuphela ezithatha i-cabozantinib ezinamava okuphendula (27% vs 0; P <.0001). Ngaphaya koko, ixesha eliphakathi le-OR yayiziinyanga ze-14.7 kwabo baphathwa ngamayeza. Akukho mahluko ubalulekileyo ekusindeni ngokubanzi waqwalaselwa phakathi kweengalo.

Ku-2019 meta- kunye nohlalutyo lwezoqoqosho lokuvavanya ukusetyenziswa kwe-cabozantinib kunye ne-vandetanib kwizigulana zeNkonzo yeSizwe yezeMpilo eNgilane, uTappenden et al. Kugqityiwe.

“Uvavanyo oluchongiweyo lubonisa ukuba i-cabozantinib kunye ne-vandetanib ziphucula i-PFS ngaphezulu kwe-placebo; Nangona kunjalo, izibonelelo ezibalulekileyo ze-OS aziboniswanga. Uhlalutyo lwezoqoqosho lubonisa ukuba ngaphakathi kwelebheli yabemi be-EU, ii-ICERs (ukunyuka kokusebenza ngokulinganayo kwendleko) ye-cabozantinib kunye ne-vandetanib zi> £ 138,000 nge-QALY (unyaka wobomi obulungelelaniswe nomgangatho) ofunyenweyo. Ngaphakathi kubabhali be-EU (i-European Union), i-ICER ye-vandetanib kulindeleke ukuba ibe yi- £ 66,000 nge-QALY nganye efumeneyo. ”

 

ibali 3Unyango lweCabozantinib IHepatocellular Carcinoma

NgoJanuwari 2019, i-FDA yavuma iipilisi ze-cabozantinib kwizigulana ezine i-hepatocellular carcinoma (HCC) iphathwe ngaphambili nge-sorafenib. Ukuvunywa bekusekwe kwiziphumo zolingo lwe-CELESTIAL.

Kwi-randomised (2: 1), blind-blind, control-placebo, multicenter trial, izigulane zazingeniswa kwi-cabozantinib 60 mg ngomlomo kanye yonke imihla (n = 470) okanye i-placebo (n = 237) kude kube lixesha lokuqhubela phambili kwesifo okanye ukungamkeleki Ityhefu.ICabozantinib

Indawo yokuphela ephambili yayiyi-OS. I-PFS kunye ne-ORR, kuvavanywa abaphandi besebenzisa i-RECIST 1.1, nabo balinganiswa. Ukusetyenziswa kweCabozantinib kunxulunyaniswa ne-OS ephakathi yeenyanga ezili-10.2 (95% CI: 9.1-12.0) vs 8 iinyanga (95% CI: 6.8-9.4) kwabo bafumana i-placebo (HR 0.76; 95% CI: 0.63, 0.92; P = .0049). I-Median PFS yayiziinyanga ezi-5.2 (4.0-5.5) kwingalo ye-cabozantinib xa kuthelekiswa ne-1.9 iinyanga (1.9-1.9) kwingalo ye-placebo (HR 0.44; 95% CI, 0.36, 0.52; P <.001). I-ORR yayiyi-4% (95% CI, 2.3, 6.0) kwabo bathatha i-cabozantinib vs 0.4% (95% CI, 0.0, 2.3) kwabo bathatha i-placebo.

Iziganeko ezibi zeBakala 3 okanye 4 beziphezulu kwizigulana ezithatha i-cabozantinib (68%) kunalezo zithatha i-placebo (36%).

Ababhali bolingo lwe-CELESTIAL baqukumbela ngoku kulandelayo: “Phakathi kwezigulana ezazinyangwe ngaphambili i-hepatocellular carcinoma, unyango lwe-cabozantinib lwakhokelela ekusindeni ixesha elide kunye nokuqhubeka ngaphandle kokuhamba endaweni ye-placebo. Iqondo leziganeko ezichaseneyo ezikudidi oluphezulu kwiqela le-cabozantinib beliphantse laphindeka kabini kwiqela le-placebo. ”

 

isishwankathelo

I-Cabozantinib yi-tyrosine kinase inhibitor esetyenziselwa ukunyanga i-renal cell carcinoma, i-hepatocellular carcinoma, kunye nomhlaza we-medullary cancer. ICabozantinib yavunywa okokuqala kwi-2012 kwaye ayiyiyo ekhethekileyo i-tyrosine kinase inhibitor. Kwaqala kwamkelwa e-US phantsi kwegama lebrendi elithi Cometriq, eliboniswe kunyango lwe-metastatic medullary cancer ye-thyroid.Ikhabhathi) yamkelwe kunyango lwe-renal cell carcinoma, kwaye le fomathi efanayo yafumana imvume eyongezelelweyo e-US nase-Canada ngo-2019 kunyango lwe-hepatocellular carcinoma kwizigulana ezanyangwa ngaphambili.

 

isingqiniso

[1] IChoueiri TK, i-Escudier B, iiPowles T, okqhubekayo. I-Cabozantinib xa ithelekiswa ne-everolimus kwi-renal cell carcinoma (METEOR): iziphumo zokugqibela ezivela kwilebheli engahleliwe, evulekileyo, kwinqanaba lesithathu. ILancet Oncol. Ngo-3; 2016: 17-917.

[2] UTappenden P, uCarroll C, uHamilton J, et al. I-Cabozantinib kunye ne-vandetanib ye-cancer engathethekiyo ekuhlaleni okanye ye-metastatic medullary cancer: uphononongo olucwangcisiweyo kunye nemodeli yoqoqosho. Uvavanyo lweTekhnoloji yezeMpilo. Ngo-2019; 23: 1-144.

[3] UGeorge DJ, uHessel C, uHalabi S, et al. I-Cabozantinib xa ithelekiswa ne-sunitinib kwizigulana ezinganyangekiyo ezine-renal cell carcinoma yomngcipheko ophakathi okanye omncinci: uhlalutyo lweqela elincinci lovavanyo lwe-Alliance A031203 CABOSUN. Oncologist. Ngo-2019; 24: 1-5.

[4] UKurzrock R, uSherman SI, ibhola ye-DW, i-Forastiere AA, uCohen RB, uMehra R, uPfister DG, uCohen EE, uJanisch L, uNauling F, uHong DS, uNG, u-L, uGagel RF, uFrye J, uMuller T, uRatain MJ , I-Salgia R: Umsebenzi we-XL184 (Cabozantinib), umlomo we-tyrosine kinase inhibitor, kwizigulana ezinomhlaza we-thyroid. J Ikliniki ye-Oncol. Ngo-2011 ngoJulayi 1; 29 (19): 2660-6. ikhonkco: 10.1200 / JCO.2010.32.4145. Epub 2011 ngoMeyi 23.

[5] UAbou-Alfa GK, uMeyer T, uCheng AL, et al. I-Cabozantinib kwizigulana ezine-carcinoma ye-hepatocellular carcinoma. N Engl J Med. Ngo-2018; 379: 54-63.

[6] Ulawulo lwezoKutya kunye noLawulo lweziyobisi. I-FDA ivuma i-cabozantinib ye-hepatocellular carcinoma. Ifumaneka kwi: https://www.fda.gov/drugs/fda-approves-cabozantinib-hepatocellular-carcinoma Ifikeleleke ngo-Agasti 28, 2019.

[7] Yakes FM, Chen J, Tan J, Yamaguchi K, Shi Y, Yu P, Qian F, Chu F, Bentzien F, Cancilla B, Orf J, Wena A, Laird AD, Engst S, Lee L, Lesch J, Chou YC , Joly AH: I-Cabozantinib (XL184), inoveli ye-MET kunye ne-VEGFR2 inhibitor, kwangaxeshanye icinezela i-metastasis, i-angiogenesis, kunye nokukhula kwethumba. Umhlaza Cancer Ther. NgoDisemba ka-2011; 10 (12): 2298-308. ikhonkco: 10.1158 / 1535-7163.MCT-11-0264. Epub 2011 Sep 16.

[8] "Iziyobisi zomhlaza wedlala cabozantinib yongeza i-PFS". Kugciniwe kwinto yoqobo ngowama-2012-04-02. Ukufunyanwa kwe-24 ka-Okthobha ngo-2011.

[9] "I-Cabozantinib Orphan yokuNyulwa kweziyobisi kunye nokuVunywa". Ulawulo lwezoKutya kunye noLawulo lweziyobisi (FDA). Nge-29 kaNovemba ka-2010. Ibuyiswa nge-11 Novemba 2020.

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