467:
957:
marboxil or a single dose of a placebo. Of these 607 subjects, 303 received baloxavir marboxil and 304 received the placebo. The trial's primary endpoint was the proportion of subjects who were infected with influenza virus and presented with fever and at least one respiratory symptom from day 1 to day 10. Of those who received baloxavir marboxil, 1% of subjects met these criteria, compared to 13% of subjects who received a placebo for the clinical trial.
31:
1904:
1942:
834:
3333:
3321:
1584:
1497:
1454:
1326:
1275:
1230:
1885:
929:(FDA) approved baloxavir marboxil based on evidence of its benefits and side effects from two clinical trials in adult and pediatric participants with uncomplicated influenza (Trial 1, 1518T0821 and Trial 2, NCT02954354), involving 1119 participants. Both trials included clinical sites and participants in Japan, with Trial 2 adding clinical locations in the United States.
953:
hours of experiencing flu symptoms. In both trials, subjects treated with baloxavir marboxil had a shorter time to alleviation of symptoms compared with subjects who took the placebo. In the second trial, there was no difference in the time to alleviation of symptoms between subjects who received baloxavir marboxil and those who received the other flu treatment.
1923:
956:
The safety and efficacy of baloxavir marboxil for post-flu exposure prevention is supported by one randomized, double-blind, controlled trial in which 607 subjects, twelve years of age and older who were exposed to a person with influenza in their household, received either a single dose of baloxavir
1961:
952:
The safety and efficacy of baloxavir marboxil, an antiviral drug taken as a single oral dose, was demonstrated in two randomized controlled clinical trials of 1,832 subjects where participants were assigned to receive either baloxavir marboxil, a placebo, or another antiviral flu treatment within 48
945:
for the treatment of acute, uncomplicated influenza in people twelve years of age and older at risk of influenza complications. In
November 2020, the FDA approved an updated indication to include post-exposure prevention of influenza (flu) for people twelve years of age and older after contact with
932:
Baloxavir marboxil was approved for sale in Japan in
February 2018. In October 2018, the FDA approved it for the treatment of acute uncomplicated influenza in people twelve years of age and older who have been symptomatic for no more than 48 hours. The FDA application of baloxavir marboxil was
885:
decreased more than in participants in either the oseltamivir or placebo groups; however, after five days, the effect on viral load of the single dose of baloxavir was indistinguishable from the effect observed following the complete, 5-day regimen of oseltamivir in its treatment group.
742:
to the drug, due to variants of the polymerase protein displaying substitutions of isoleucine-38, specifically, the I38T, I38M, or I38F mutations. There is continuing research into and clinical concern over the resistance appearing in recipients, in response to treatment with this drug.
760:
Common side effects following the single dose administration of baloxavir marboxil include diarrhea, bronchitis, common cold, headache, and nausea. Adverse events were reported in 21% of people who received baloxavir, 25% of those receiving placebo, and 25% of oseltamivir.
876:
As of
September 2018, in the only report of a Phase III randomized, controlled trial, baloxavir reduced the duration of influenza symptoms of otherwise healthy participants by about one day compared with a placebo treatment group, and comparable with what was seen for an
1741:
Imai M, Yamashita M, Sakai-Tagawa Y, Iwatsuki-Horimoto K, Kiso M, Murakami J, et al. (January 2020). "Influenza A variants with reduced susceptibility to baloxavir isolated from
Japanese patients are fit and transmit through respiratory droplets".
1902:, Kawai M, Tomita K, Akiyama T, Okano A, Miyagawa M, "Pharmaceutical composition containing polycyclic pyridone derivatives as cap-dependent endonuclease (CEN) inhibitors.", published 2017, assigned to Shionogi and Co., Ltd., Japan.
549:
1940:, Kawai M, Tomita K, Akiyama T, Okano A, Miyagawa M, "Preparation of polycyclic pyridone derivatives as cap-dependent endonuclease (CEN) inhibitors and prodrugs thereof.", published 2016, assigned to Shionogi and Co., Ltd., Japan
855:
in cells of the blood, liver, and lumen of the small intestine. The compound numbers for baloxavir marboxil and baloxavir acid used in publications by
Shionogi and others during discovery and development (prior to assignment of a
1605:
829:
and Co. of Japan (as well as others); the
Shionogi reports have appeared several times in the Japanese patent literature between 2016 and 2019, providing insight into possible industrial synthetic routes that may be in use.
1883:, Okamoto K, Ueno T, Hato Y, Hakogi T, Majima S, "Method for stereoselective preparation of substituted polycyclic pyridone derivative.", published 2019, assigned to Shionogi & Co., Ltd., Japan.
705:, for individuals who are twelve years of age or older, that have presented symptoms of this infection for no more than 48 hours. The efficacy of baloxavir marboxil administered after 48 hours has not been tested.
941:& Co., Ltd. in October 2018. Specifically, the FDA approved the use of baloxavir marboxil for people at high risk of developing influenza-related complications. In October 2019, the FDA approved an updated
751:
Baloxavir marboxil should not be co-administered with dairy products, calcium-fortified beverages, or laxatives, antacids, or oral supplements containing calcium, iron, magnesium, selenium, aluminum or zinc.
1689:
715:
In
November 2020, the FDA approved an updated indication to include post-exposure prevention of influenza (flu) for people twelve years of age and older after contact with an individual who has the flu.
719:
In August 2022, the FDA approved an updated indication to include post-exposure prevention of influenza (flu) for people five years of age and older after contact with an individual who has the flu.
2288:
1439:
591:
InChI=1S/C27H23F2N3O7S/c1-36-27(35)39-14-38-25-19(33)8-9-31-24(25)26(34)30-10-11-37-12-21(30)32(31)23-15-6-7-18(28)22(29)17(15)13-40-20-5-3-2-4-16(20)23/h2-9,21,23H,10-14H2,1H3/t21-,23+/m1/s1
1601:
722:
In the EU, baloxavir marboxil is indicated for the treatment of uncomplicated influenza and for post-exposure prophylaxis of influenza in individuals aged twelve years of age and older.
1921:, Shibahara S, Fukui N, Maki T, "Polycyclic pyridone derivative, crystal and preparation method thereof.", published 2017, assigned to Shionogi and Co., Ltd., Japan.
242:
2742:
2737:
146:
1055:
864:(carbonate) moiety of the prodrug—shown in the lower left-hand corner of the image above—was prepared during discovery and development research from a late stage 2-hydroxy-
1104:
1215:
1681:
1569:
2192:
197:
1260:
112:
2280:
738:
In 2.2% of baloxavir recipients in the Phase II trial and in about 10% of baloxavir recipients in the Phase III trial, the infecting influenza strain had
2897:
1308:
1431:
1023:
2041:"Molecular Dynamics Simulation reveals the mechanism by which the Influenza Cap-dependent Endonuclease acquires resistance against Baloxavir marboxil"
2318:
3138:
1375:"In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit"
1959:, Zhu X, Jiang W, "Process for preparation of substituted polycyclic carbamoylpyridone derivative and its prodrug.", published 2018
1159:
Text was copied from this source which is copyright
European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
3378:
908:. The names under which baloxavir marboxil and baloxavir acid appear in Shionogi research reporting are S-033188 and S-033447, respectively.
61:
2004:
Hughes DL (June 2019). "Review of the Patent
Literature: Synthesis and Final Forms of Antiviral Drugs Tecovirimat and Baloxavir Marboxil".
1719:
563:
2341:"Genentech Announces FDA Approval of Xofluza (Baloxavir Marboxil) for People at High Risk of Developing Influenza-Related Complications"
625:. It may reduce the duration of flu symptoms by about a day, but is prone to selection of resistant mutants that render it ineffectual.
2227:
1146:
1045:
2348:
3187:
1529:
2463:
1096:
712:
for the treatment of acute, uncomplicated influenza in people twelve years of age and older at risk of influenza complications.
3293:
922:
129:
3383:
3298:
2257:
2250:"A Study of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir in Otherwise Healthy Patients With Influenza"
1207:
2834:
2546:
2508:
993:
2865:
1482:
1351:
3353:
3037:
3032:
2839:
583:
142:
1561:
3145:
3100:
2183:
987:
3125:
2732:
2727:
2722:
1252:
296:
227:
93:
621:. It was approved for medical use both in Japan and in the United States in 2018, and is taken as a single dose
3393:
3358:
2911:
2809:
2752:
2717:
2712:
2707:
2702:
2697:
2692:
2687:
2682:
2677:
2672:
2667:
2662:
2657:
2652:
2647:
2642:
2637:
2632:
2627:
2622:
2617:
2311:"Xofluza (Baloxavir Marboxil) Tablets 10mg/20mg Approved For The Treatment Of Influenza Types A And B In Japan"
781:
activity, one of the activities of the virus polymerase complex. In particular, it inhibits a process known as
739:
2100:"Evaluation of Drug-Drug Interaction Potential between Baloxavir Marboxil and Oseltamivir in Healthy Subjects"
1297:
1015:
3408:
3388:
1937:
1918:
1899:
1565:
1478:
1435:
1304:
1256:
1211:
926:
686:
406:
1169:
789:
from host cell RNA transcripts, which it then uses for polymerase-catalyzed synthesis of its needed viral
2926:
2844:
2829:
2310:
2139:
Yang J, Huang Y, Liu S (May 2019). "Investigational antiviral therapies for the treatment of influenza".
1880:
860:(USAN)) were, respectively, S-033188 and S-033447. As reported in a review of the patent literature, the
446:
1956:
3311:
857:
786:
881:
treatment group. On the first day after baloxavir was started in its treatment group of participants,
825:
family, whose chemical synthesis has been reported in a number of ways by the company discovering it,
3368:
3272:
2887:
1140:
690:
462:
107:
2451:
1711:
3363:
844:
Baloxavir marboxil (BXM) is a prodrug whose active agent, baloxavir acid (BXA) is released rapidly
798:
797:
activity catalyzes its cleavage "after 10–13 nucleotides". As such, its mechanism is distinct from
3229:
3115:
3085:
3080:
2974:
2779:
2501:
183:
43:
1602:"Genentech Announces FDA Approval of Xofluza to Treat Influenza in Children Aged Five and Older"
3288:
3090:
2892:
2860:
2795:
1837:
O'Hanlon R, Shaw ML (April 2019). "Baloxavir marboxil: the new influenza drug on the market".
395:
3418:
3373:
2870:
2374:
Ikematsu H, Hayden FG, Kawaguchi K, Kinoshita M, de Jong MD, Lee N, et al. (July 2020).
1682:"Roche's flu med Xofluza drives drug resistance and may be a bad choice for kids, study says"
942:
709:
330:
2216:
1135:
3413:
3398:
2880:
2340:
2052:
793:. A polymerase subunit binds to the host pre-mRNAs at their 5' caps, then the polymerase's
415:
1632:
Hayden FG, Sugaya N, Hirotsu N, Lee N, de Jong MD, Hurt AC, et al. (September 2018).
1521:
1373:
Noshi T, Kitano M, Taniguchi K, Yamamoto A, Omoto S, Baba K, et al. (December 2018).
466:
71:
8:
2940:
2824:
2541:
861:
822:
622:
321:
190:
2056:
1344:"Baloxavir Marboxil for Uncomplicated Influenza: Mechanism of Action & Side Effects"
3072:
2761:
2531:
2494:
2471:
2217:"A flu drug — shown to reduce the duration of symptoms — could upend treatment in U.S."
2164:
2075:
2021:
1862:
1811:
1786:
1767:
1663:
960:
Baloxavir marboxil was approved for medical use in the
European Union in January 2021.
157:
2427:
2410:
1975:
355:
3403:
3095:
3024:
2582:
2536:
2432:
2397:
2168:
2156:
2121:
2080:
2025:
1854:
1816:
1771:
1759:
1655:
1396:
905:
618:
614:
266:
254:
85:
1866:
1667:
1391:
1374:
730:
Baloxavir marboxil is available in tablet form and as granules for mixing in water.
3237:
3182:
3172:
3110:
2774:
2597:
2592:
2587:
2577:
2422:
2387:
2148:
2111:
2070:
2060:
2013:
1846:
1806:
1798:
1751:
1645:
1386:
770:
653:
637:
483:
210:
22:
2249:
2152:
3325:
3210:
3194:
1936:
1898:
1850:
934:
3337:
2949:
2556:
2222:
2065:
2040:
949:
Baloxavir marboxil was approved for medical use in Australia in February 2020.
897:
774:
641:
2116:
2099:
1755:
3347:
3242:
3105:
2017:
1879:
1588:
1501:
1458:
1343:
1330:
1279:
1234:
1050:
982:
838:
782:
649:
571:
O=C(OCOC(C(C=C1)=O)=C(N1N(2C3=CC=CC=C3SCC4=C(F)C(F)=CC=C24)5()N6CCOC5)C6=O)OC
2376:"Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts"
1471:
3252:
2875:
2551:
2436:
2401:
2160:
2125:
2084:
1858:
1820:
1763:
1659:
1400:
794:
778:
645:
205:
2392:
2375:
1740:
1650:
1634:"Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents"
1633:
3257:
2984:
2979:
2967:
2769:
1432:"FDA Expands Approval of Influenza Treatment to Post-Exposure Prevention"
1253:"Drug Approval Package: Xofluza Film-Coated Tablets (Baloxavir marboxil)"
901:
878:
852:
802:
79:
1802:
375:
3215:
3133:
3009:
2962:
2957:
2561:
882:
865:
769:
Baloxavir marboxil is an influenza therapeutic agent, specifically, an
667:
656:
525:
386:
111:
3267:
3262:
3042:
3001:
2994:
2989:
2517:
2344:
806:
702:
675:
341:
65:
30:
2314:
938:
890:
826:
818:
679:
663:
435:
366:
124:
2098:
Kawaguchi N, Koshimichi H, Ishibashi T, Wajima T (November 2018).
2097:
548:
3177:
1587:
This article incorporates text from this source, which is in the
1528:. American Society of Health-System Pharmacists. 19 August 2019.
1500:
This article incorporates text from this source, which is in the
1457:
This article incorporates text from this source, which is in the
1329:
This article incorporates text from this source, which is in the
1278:
This article incorporates text from this source, which is in the
1233:
This article incorporates text from this source, which is in the
629:
2373:
3047:
671:
3247:
937:
in the United States, and approval of Xofluza was granted to
894:
849:
539:
3332:
2486:
1917:
1559:
1372:
833:
451:
983:"Xofluza Australian prescription medicine decision summary"
868:
precursor by treatment with chloromethyl methyl carbonate.
790:
662:
The most common side effects of baloxavir marboxil include
426:
1712:"New flu drug drives drug resistance in influenza viruses"
848:, as the hydrolysis of baloxavir marboxil is catalyzed by
632:
strategy, with its metabolism releasing the active agent,
2281:"One-dose flu drug Xofluza gets nod from health ministry"
308:)-12-thiepin-11-yl]-6,8-dioxo-3,4,6,8,12,12a-hexahydro-1
312:-oxazinopyrido triazin-7-yl}oxy)methyl methyl carbonate
1631:
3309:
1787:"At the centre: influenza A virus ribonucleoproteins"
1784:
2411:"Baloxavir: game-changer or much ado about nothing?"
2038:
1292:
1290:
1288:
1247:
1245:
1243:
1091:
1089:
1087:
1085:
1083:
1081:
1079:
1077:
1075:
1073:
889:Baloxavir marboxil was developed for the market by
2215:
2182:
1982:. U.S. National Library of Medicine. CID 124081876
1426:
1424:
1422:
1420:
1418:
1416:
1414:
1412:
1410:
701:Baloxavir marboxil is an influenza medication, an
1999:
1997:
1785:Eisfeld AJ, Neumann G, Kawaoka Y (January 2015).
1202:
1200:
1198:
1196:
1194:
1192:
1190:
1097:"Xofluza- baloxavir marboxil tablet, film coated"
3345:
2039:Yoshino R, Yasuo N, Sekijima M (November 2019).
1836:
1522:"Baloxavir Marboxil Monograph for Professionals"
1285:
1240:
1070:
659:complex, a process essential to its life-cycle.
354:
1555:
1553:
1551:
1549:
1547:
1407:
977:
975:
973:
329:
1994:
1955:
1832:
1830:
1187:
1130:
1128:
1126:
1124:
1122:
837:Baloxavir acid (BXA) or simply baloxavir, the
613:, is an antiviral medication for treatment of
141:
2502:
1560:Food and Drug Administration (23 July 2019).
1046:"Summary Basis of Decision (SBD) for Xofluza"
708:In October 2019, the FDA approved an updated
2138:
1604:(Press release). Genentech. 11 August 2022.
1544:
970:
128:
1827:
1516:
1514:
1512:
1510:
1119:
785:, by which the virus derives short, capped
689:(FDA) considers baloxavir marboxil to be a
280:In general: ℞ (Prescription only)
2509:
2495:
2006:Organic Process Research & Development
1298:"FDA Approval Package for 210854Orig1s001"
1208:"FDA approves new drug to treat influenza"
465:
394:
2426:
2391:
2213:
2115:
2074:
2064:
1810:
1649:
1390:
414:
1507:
832:
636:(BXA). Baloxavir acid then functions as
2408:
2141:Expert Opinion on Investigational Drugs
1627:
1625:
1623:
461:
374:
84:
3346:
2003:
1485:from the original on 17 September 2020
923:Ministry of Health, Labour and Welfare
911:
764:
628:Baloxavir marboxil was developed as a
272:
102:
3299:US influenza statistics by flu season
2490:
2278:
1692:from the original on 25 November 2020
1572:from the original on 12 December 2019
1442:from the original on 23 November 2020
1354:from the original on 24 February 2021
260:
136:
119:
70:
3379:Drugs developed by Hoffmann-La Roche
2458:. U.S. National Library of Medicine.
2351:from the original on 24 October 2019
2321:from the original on 20 January 2021
2291:from the original on 2 November 2021
2260:from the original on 21 January 2022
2230:from the original on 20 October 2020
2207:
1722:from the original on 16 January 2021
1620:
1218:from the original on 24 October 2019
1174:Union Register of medicinal products
1149:from the original on 30 January 2021
1107:from the original on 28 October 2020
817:Baloxavir marboxil is a substituted
746:
209:
1608:from the original on 12 August 2022
1532:from the original on 7 October 2019
1026:from the original on 12 August 2022
434:
345:
13:
3294:2017–2018 United States flu season
2367:
996:from the original on 13 March 2020
725:
14:
3430:
3033:Live attenuated influenza vaccine
2468:SPS - Specialist Pharmacy Service
2444:
2195:from the original on 26 July 2020
1314:from the original on 9 April 2021
1263:from the original on 26 July 2020
640:, targeting the influenza virus'
236:
168:
3331:
3319:
1582:
1495:
1452:
1324:
1273:
1228:
1058:from the original on 31 May 2022
988:Therapeutic Goods Administration
506:
500:
494:
29:
2333:
2303:
2272:
2242:
2175:
2132:
2091:
2032:
1968:
1949:
1930:
1911:
1892:
1873:
1778:
1734:
1704:
1674:
1594:
1472:New Drug Therapy Approvals 2018
1464:
1392:10.1016/j.antiviral.2018.10.008
1366:
1336:
946:an individual who has the flu.
916:
773:targeting the influenza virus'
755:
696:
596:Key:RZVPBGBYGMDSBG-GGAORHGYSA-N
2470:. 29 June 2018. Archived from
1562:"Drug Trial Snapshot: Xofluza"
1162:
1038:
1008:
518:
512:
488:
249:
56:BXM (S-033188), BXA (S-033447)
1:
3091:Russian flu (1889–1890)
2516:
2428:10.1016/S2213-2600(18)30469-7
2153:10.1080/13543784.2019.1606210
1170:"Xofluza Product information"
1016:"Xofluza Product information"
963:
733:
3384:Drugs developed by Genentech
2279:Otake T (24 February 2018).
2214:Branswell H (27 June 2018).
1851:10.1016/j.coviro.2019.01.006
1791:Nature Reviews. Microbiology
1566:Food and Drug Administration
1479:Food and Drug Administration
1436:Food and Drug Administration
1305:Food and Drug Administration
1257:Food and Drug Administration
1212:Food and Drug Administration
927:Food and Drug Administration
812:
687:Food and Drug Administration
609:, sold under the brand name
7:
2409:Mushtaq A (December 2018).
2104:Clinical Drug Investigation
1839:Current Opinion in Virology
10:
3435:
2866:Transmission and infection
2359:– via Business Wire.
2329:– via publicnow.com.
2066:10.1038/s41598-019-53945-1
1616:– via Business Wire.
871:
858:United States Adopted Name
478:Chemical and physical data
3281:
3228:
3203:
3165:
3158:
3146:Central Luzon H5N6 (2017)
3124:
3086:Influenza pandemic (1557)
3081:Influenza pandemic (1510)
3071:
3060:
3023:
2948:
2939:
2919:
2910:
2853:
2817:
2808:
2788:
2760:
2751:
2606:
2570:
2524:
2189:Pharmaceutical Substances
2117:10.1007/s40261-018-0697-2
1756:10.1038/s41564-019-0609-0
1438:(FDA). 23 November 2020.
1141:European Medicines Agency
691:first-in-class medication
579:
559:
537:
524:
482:
477:
445:
425:
405:
385:
365:
340:
320:
292:
287:
226:
221:
196:
182:
156:
92:
78:
60:
52:
42:
37:
28:
3188:2007 Australian outbreak
2315:Shionogi & Co., Ltd.
2018:10.1021/acs.oprd.9b00144
1307:(FDA). 16 October 2019.
1259:(FDA). 7 December 2018.
1214:(FDA). 24 October 2018.
799:neuraminidase inhibitors
2975:Neuraminidase inhibitor
2456:Drug Information Portal
3289:Influenza-like illness
2958:Adamantane derivatives
1434:(Press release). U.S.
1210:(Press release). U.S.
841:
3394:Nitrogen heterocycles
3359:Anti-influenza agents
3139:1989–1990 UK outbreak
3101:Asian flu (1957-1958)
2393:10.1056/NEJMoa1915341
1651:10.1056/NEJMoa1716197
1481:(FDA). January 2019.
836:
3354:Anti–RNA virus drugs
3106:Hong Kong flu (1968)
2898:Pandemic preparation
2464:"Baloxavir marboxil"
2452:"Baloxavir marboxil"
2184:"Baloxavir Marboxil"
1688:. 26 November 2019.
16:Antiviral medication
3409:Sulfur heterocycles
3389:Japanese inventions
2347:. 17 October 2019.
2256:. 3 November 2016.
2057:2019NatSR...917464Y
1803:10.1038/nrmicro3367
1744:Nature Microbiology
1145:. 9 November 2020.
1103:. 28 October 2019.
1054:. 23 October 2014.
925:(JMHLW) and the US
912:Society and culture
862:carbonic acid ester
765:Mechanism of action
740:acquired resistance
648:activity, used in "
245:(Prescription only)
25:
3096:Spanish flu (1918)
3015:Baloxavir marboxil
2840:West Bengal (2008)
2775:1977 (Russian flu)
2770:1918 (Spanish flu)
2317:23 February 2018.
2285:Japan Times Online
2254:ClinicalTrials.gov
2045:Scientific Reports
842:
607:Baloxavir marboxil
130:Baloxavir_marboxil
23:Baloxavir marboxil
21:
3307:
3306:
3224:
3223:
3154:
3153:
3134:Fujian flu (H3N2)
3056:
3055:
2935:
2934:
2906:
2905:
2861:Genetic structure
2804:
2803:
2608:Influenza A virus
2547:Genome sequencing
2415:Lancet Respir Med
2343:(Press release).
2313:(Press release).
2110:(11): 1053–1060.
1718:(Press release).
1022:. 25 April 2012.
747:Contraindications
604:
603:
550:Interactive image
447:CompTox Dashboard
276:
264:
252:
240:
172:
139:
122:
105:
3426:
3369:Carbonate esters
3336:
3335:
3324:
3323:
3322:
3315:
3238:Acute bronchitis
3163:
3162:
3116:Swine flu (2009)
3111:1977 Russian flu
3069:
3068:
3005:
2946:
2945:
2917:
2916:
2815:
2814:
2780:2009 (Swine flu)
2758:
2757:
2578:Orthomyxoviridae
2511:
2504:
2497:
2488:
2487:
2483:
2481:
2479:
2459:
2440:
2430:
2405:
2395:
2361:
2360:
2358:
2356:
2337:
2331:
2330:
2328:
2326:
2307:
2301:
2300:
2298:
2296:
2276:
2270:
2269:
2267:
2265:
2246:
2240:
2239:
2237:
2235:
2219:
2211:
2205:
2204:
2202:
2200:
2186:
2179:
2173:
2172:
2136:
2130:
2129:
2119:
2095:
2089:
2088:
2078:
2068:
2036:
2030:
2029:
2012:(7): 1298–1307.
2001:
1992:
1991:
1989:
1987:
1972:
1966:
1965:
1964:
1960:
1953:
1947:
1946:
1945:
1941:
1934:
1928:
1927:
1926:
1922:
1915:
1909:
1908:
1907:
1903:
1896:
1890:
1889:
1888:
1884:
1877:
1871:
1870:
1834:
1825:
1824:
1814:
1782:
1776:
1775:
1738:
1732:
1731:
1729:
1727:
1708:
1702:
1701:
1699:
1697:
1678:
1672:
1671:
1653:
1629:
1618:
1617:
1615:
1613:
1598:
1592:
1586:
1585:
1581:
1579:
1577:
1557:
1542:
1541:
1539:
1537:
1518:
1505:
1499:
1498:
1494:
1492:
1490:
1476:
1468:
1462:
1456:
1455:
1451:
1449:
1447:
1428:
1405:
1404:
1394:
1370:
1364:
1363:
1361:
1359:
1340:
1334:
1328:
1327:
1323:
1321:
1319:
1313:
1302:
1294:
1283:
1277:
1276:
1272:
1270:
1268:
1249:
1238:
1232:
1231:
1227:
1225:
1223:
1204:
1185:
1184:
1182:
1180:
1166:
1160:
1158:
1156:
1154:
1132:
1117:
1116:
1114:
1112:
1093:
1068:
1067:
1065:
1063:
1042:
1036:
1035:
1033:
1031:
1012:
1006:
1005:
1003:
1001:
992:. 2 March 2020.
979:
821:derivative of a
771:enzyme inhibitor
638:enzyme inhibitor
552:
532:
520:
514:
508:
502:
496:
490:
470:
469:
455:
453:
438:
418:
398:
378:
358:
348:
347:
333:
274:
271:
262:
259:
251:
248:
238:
235:
213:
170:
167:
149:
138:
135:
132:
121:
118:
115:
104:
101:
88:
74:
33:
26:
24:
20:
3434:
3433:
3429:
3428:
3427:
3425:
3424:
3423:
3364:Antiviral drugs
3344:
3343:
3342:
3330:
3320:
3318:
3310:
3308:
3303:
3277:
3220:
3199:
3150:
3120:
3065:
3063:
3052:
3019:
3003:
2950:Antiviral drugs
2931:
2902:
2888:Human mortality
2881:clinical trials
2849:
2800:
2784:
2747:
2611:
2609:
2602:
2566:
2520:
2515:
2477:
2475:
2474:on 26 July 2020
2462:
2450:
2447:
2421:(12): 903–904.
2380:N. Engl. J. Med
2370:
2368:Further reading
2365:
2364:
2354:
2352:
2339:
2338:
2334:
2324:
2322:
2309:
2308:
2304:
2294:
2292:
2277:
2273:
2263:
2261:
2248:
2247:
2243:
2233:
2231:
2212:
2208:
2198:
2196:
2181:
2180:
2176:
2137:
2133:
2096:
2092:
2037:
2033:
2002:
1995:
1985:
1983:
1974:
1973:
1969:
1962:
1954:
1950:
1943:
1938:JPWO 2016175224
1935:
1931:
1924:
1919:JPWO 2017221869
1916:
1912:
1905:
1900:JPWO 2018030463
1897:
1893:
1886:
1878:
1874:
1835:
1828:
1783:
1779:
1739:
1735:
1725:
1723:
1710:
1709:
1705:
1695:
1693:
1680:
1679:
1675:
1644:(10): 913–923.
1638:N. Engl. J. Med
1630:
1621:
1611:
1609:
1600:
1599:
1595:
1583:
1575:
1573:
1558:
1545:
1535:
1533:
1520:
1519:
1508:
1496:
1488:
1486:
1477:(Report). U.S.
1474:
1470:
1469:
1465:
1453:
1445:
1443:
1430:
1429:
1408:
1371:
1367:
1357:
1355:
1342:
1341:
1337:
1325:
1317:
1315:
1311:
1300:
1296:
1295:
1286:
1274:
1266:
1264:
1251:
1250:
1241:
1229:
1221:
1219:
1206:
1205:
1188:
1178:
1176:
1168:
1167:
1163:
1152:
1150:
1134:
1133:
1120:
1110:
1108:
1095:
1094:
1071:
1061:
1059:
1044:
1043:
1039:
1029:
1027:
1014:
1013:
1009:
999:
997:
981:
980:
971:
966:
935:priority review
919:
914:
874:
815:
767:
758:
749:
736:
728:
726:Available forms
699:
600:
597:
592:
587:
586:
575:
572:
567:
566:
555:
530:
517:
511:
505:
499:
493:
473:
463:DTXSID601027758
449:
441:
421:
401:
381:
361:
344:
336:
316:
313:
300:
299:
283:
217:
185:
178:
159:
152:
17:
12:
11:
5:
3432:
3422:
3421:
3416:
3411:
3406:
3401:
3396:
3391:
3386:
3381:
3376:
3371:
3366:
3361:
3356:
3341:
3340:
3328:
3305:
3304:
3302:
3301:
3296:
3291:
3285:
3283:
3282:Related topics
3279:
3278:
3276:
3275:
3270:
3265:
3260:
3255:
3250:
3245:
3240:
3234:
3232:
3226:
3225:
3222:
3221:
3219:
3218:
3213:
3207:
3205:
3201:
3200:
3198:
3197:
3192:
3191:
3190:
3180:
3175:
3169:
3167:
3160:
3156:
3155:
3152:
3151:
3149:
3148:
3143:
3142:
3141:
3130:
3128:
3122:
3121:
3119:
3118:
3113:
3108:
3103:
3098:
3093:
3088:
3083:
3077:
3075:
3066:
3061:
3058:
3057:
3054:
3053:
3051:
3050:
3045:
3040:
3035:
3029:
3027:
3021:
3020:
3018:
3017:
3012:
3007:
3004:(experimental)
2999:
2998:
2997:
2992:
2987:
2982:
2972:
2971:
2970:
2965:
2954:
2952:
2943:
2937:
2936:
2933:
2932:
2930:
2929:
2923:
2921:
2914:
2908:
2907:
2904:
2903:
2901:
2900:
2895:
2890:
2885:
2884:
2883:
2873:
2868:
2863:
2857:
2855:
2851:
2850:
2848:
2847:
2845:2020s outbreak
2842:
2837:
2832:
2827:
2825:Croatia (2005)
2821:
2819:
2812:
2806:
2805:
2802:
2801:
2799:
2798:
2792:
2790:
2786:
2785:
2783:
2782:
2777:
2772:
2766:
2764:
2755:
2749:
2748:
2746:
2745:
2740:
2735:
2730:
2725:
2720:
2715:
2710:
2705:
2700:
2695:
2690:
2685:
2680:
2675:
2670:
2665:
2660:
2655:
2650:
2645:
2640:
2635:
2630:
2625:
2620:
2614:
2612:
2607:
2604:
2603:
2601:
2600:
2595:
2590:
2585:
2580:
2574:
2572:
2568:
2567:
2565:
2564:
2559:
2557:Superinfection
2554:
2549:
2544:
2539:
2534:
2528:
2526:
2525:General topics
2522:
2521:
2514:
2513:
2506:
2499:
2491:
2485:
2484:
2460:
2446:
2445:External links
2443:
2442:
2441:
2406:
2386:(4): 309–320.
2369:
2366:
2363:
2362:
2332:
2302:
2271:
2241:
2206:
2174:
2147:(5): 481–488.
2131:
2090:
2031:
1993:
1967:
1948:
1929:
1910:
1891:
1872:
1826:
1777:
1733:
1703:
1673:
1619:
1593:
1543:
1506:
1463:
1406:
1365:
1348:Huateng Pharma
1335:
1284:
1239:
1186:
1161:
1136:"Xofluza EPAR"
1118:
1069:
1037:
1007:
968:
967:
965:
962:
918:
915:
913:
910:
898:pharmaceutical
873:
870:
814:
811:
766:
763:
757:
754:
748:
745:
735:
732:
727:
724:
698:
695:
634:baloxavir acid
602:
601:
599:
598:
595:
593:
590:
582:
581:
580:
577:
576:
574:
573:
570:
562:
561:
560:
557:
556:
554:
553:
545:
543:
535:
534:
528:
522:
521:
515:
509:
503:
497:
491:
486:
480:
479:
475:
474:
472:
471:
458:
456:
443:
442:
440:
439:
431:
429:
423:
422:
420:
419:
411:
409:
403:
402:
400:
399:
391:
389:
383:
382:
380:
379:
371:
369:
363:
362:
360:
359:
351:
349:
338:
337:
335:
334:
326:
324:
318:
317:
315:
314:
303:
295:
294:
293:
290:
289:
285:
284:
282:
281:
278:
269:
257:
246:
232:
230:
224:
223:
219:
218:
216:
215:
202:
200:
194:
193:
188:
186:administration
180:
179:
177:
176:
174:
164:
162:
154:
153:
151:
150:
133:
116:
98:
96:
90:
89:
82:
76:
75:
68:
58:
57:
54:
50:
49:
46:
40:
39:
35:
34:
15:
9:
6:
4:
3:
2:
3431:
3420:
3417:
3415:
3412:
3410:
3407:
3405:
3402:
3400:
3397:
3395:
3392:
3390:
3387:
3385:
3382:
3380:
3377:
3375:
3372:
3370:
3367:
3365:
3362:
3360:
3357:
3355:
3352:
3351:
3349:
3339:
3334:
3329:
3327:
3317:
3316:
3313:
3300:
3297:
3295:
3292:
3290:
3287:
3286:
3284:
3280:
3274:
3271:
3269:
3266:
3264:
3261:
3259:
3256:
3254:
3251:
3249:
3246:
3244:
3243:Bronchiolitis
3241:
3239:
3236:
3235:
3233:
3231:
3230:Complications
3227:
3217:
3216:Fujian (H5N1)
3214:
3212:
3209:
3208:
3206:
3202:
3196:
3193:
3189:
3186:
3185:
3184:
3181:
3179:
3176:
3174:
3171:
3170:
3168:
3164:
3161:
3157:
3147:
3144:
3140:
3137:
3136:
3135:
3132:
3131:
3129:
3127:
3123:
3117:
3114:
3112:
3109:
3107:
3104:
3102:
3099:
3097:
3094:
3092:
3089:
3087:
3084:
3082:
3079:
3078:
3076:
3074:
3070:
3067:
3062:Pandemics and
3059:
3049:
3046:
3044:
3041:
3039:
3036:
3034:
3031:
3030:
3028:
3026:
3022:
3016:
3013:
3011:
3008:
3006:
3000:
2996:
2993:
2991:
2988:
2986:
2983:
2981:
2978:
2977:
2976:
2973:
2969:
2966:
2964:
2961:
2960:
2959:
2956:
2955:
2953:
2951:
2947:
2944:
2942:
2938:
2928:
2925:
2924:
2922:
2918:
2915:
2913:
2909:
2899:
2896:
2894:
2893:Social impact
2891:
2889:
2886:
2882:
2879:
2878:
2877:
2874:
2872:
2871:Global spread
2869:
2867:
2864:
2862:
2859:
2858:
2856:
2852:
2846:
2843:
2841:
2838:
2836:
2833:
2831:
2828:
2826:
2823:
2822:
2820:
2816:
2813:
2811:
2807:
2797:
2794:
2793:
2791:
2787:
2781:
2778:
2776:
2773:
2771:
2768:
2767:
2765:
2763:
2759:
2756:
2754:
2750:
2744:
2741:
2739:
2736:
2734:
2731:
2729:
2726:
2724:
2721:
2719:
2716:
2714:
2711:
2709:
2706:
2704:
2701:
2699:
2696:
2694:
2691:
2689:
2686:
2684:
2681:
2679:
2676:
2674:
2671:
2669:
2666:
2664:
2661:
2659:
2656:
2654:
2651:
2649:
2646:
2644:
2641:
2639:
2636:
2634:
2631:
2629:
2626:
2624:
2621:
2619:
2616:
2615:
2613:
2605:
2599:
2596:
2594:
2591:
2589:
2586:
2584:
2581:
2579:
2576:
2575:
2573:
2569:
2563:
2560:
2558:
2555:
2553:
2550:
2548:
2545:
2543:
2540:
2538:
2535:
2533:
2530:
2529:
2527:
2523:
2519:
2512:
2507:
2505:
2500:
2498:
2493:
2492:
2489:
2473:
2469:
2465:
2461:
2457:
2453:
2449:
2448:
2438:
2434:
2429:
2424:
2420:
2416:
2412:
2407:
2403:
2399:
2394:
2389:
2385:
2381:
2377:
2372:
2371:
2350:
2346:
2342:
2336:
2320:
2316:
2312:
2306:
2290:
2286:
2282:
2275:
2259:
2255:
2251:
2245:
2229:
2225:
2224:
2218:
2210:
2194:
2190:
2185:
2178:
2170:
2166:
2162:
2158:
2154:
2150:
2146:
2142:
2135:
2127:
2123:
2118:
2113:
2109:
2105:
2101:
2094:
2086:
2082:
2077:
2072:
2067:
2062:
2058:
2054:
2050:
2046:
2042:
2035:
2027:
2023:
2019:
2015:
2011:
2007:
2000:
1998:
1981:
1977:
1971:
1958:
1952:
1939:
1933:
1920:
1914:
1901:
1895:
1882:
1881:WO 2019070059
1876:
1868:
1864:
1860:
1856:
1852:
1848:
1844:
1840:
1833:
1831:
1822:
1818:
1813:
1808:
1804:
1800:
1796:
1792:
1788:
1781:
1773:
1769:
1765:
1761:
1757:
1753:
1749:
1745:
1737:
1721:
1717:
1713:
1707:
1691:
1687:
1683:
1677:
1669:
1665:
1661:
1657:
1652:
1647:
1643:
1639:
1635:
1628:
1626:
1624:
1607:
1603:
1597:
1590:
1589:public domain
1571:
1567:
1563:
1556:
1554:
1552:
1550:
1548:
1531:
1527:
1523:
1517:
1515:
1513:
1511:
1503:
1502:public domain
1484:
1480:
1473:
1467:
1460:
1459:public domain
1441:
1437:
1433:
1427:
1425:
1423:
1421:
1419:
1417:
1415:
1413:
1411:
1402:
1398:
1393:
1388:
1384:
1380:
1379:Antiviral Res
1376:
1369:
1353:
1349:
1345:
1339:
1332:
1331:public domain
1310:
1306:
1299:
1293:
1291:
1289:
1281:
1280:public domain
1262:
1258:
1254:
1248:
1246:
1244:
1236:
1235:public domain
1217:
1213:
1209:
1203:
1201:
1199:
1197:
1195:
1193:
1191:
1175:
1171:
1165:
1148:
1144:
1142:
1137:
1131:
1129:
1127:
1125:
1123:
1106:
1102:
1098:
1092:
1090:
1088:
1086:
1084:
1082:
1080:
1078:
1076:
1074:
1057:
1053:
1052:
1051:Health Canada
1047:
1041:
1025:
1021:
1020:Health Canada
1017:
1011:
995:
991:
989:
984:
978:
976:
974:
969:
961:
958:
954:
950:
947:
944:
940:
936:
930:
928:
924:
909:
907:
903:
900:company, and
899:
896:
892:
887:
884:
880:
869:
867:
863:
859:
854:
851:
850:arylacetamide
847:
840:
839:active moiety
835:
831:
828:
824:
820:
810:
808:
804:
800:
796:
792:
788:
784:
783:cap snatching
780:
776:
772:
762:
753:
744:
741:
731:
723:
720:
717:
713:
711:
706:
704:
694:
692:
688:
683:
681:
677:
673:
669:
665:
660:
658:
655:
651:
650:cap snatching
647:
643:
639:
635:
631:
626:
624:
620:
616:
612:
608:
594:
589:
588:
585:
578:
569:
568:
565:
558:
551:
547:
546:
544:
541:
536:
529:
527:
523:
487:
485:
481:
476:
468:
464:
460:
459:
457:
448:
444:
437:
433:
432:
430:
428:
424:
417:
413:
412:
410:
408:
404:
397:
393:
392:
390:
388:
384:
377:
373:
372:
370:
368:
364:
357:
353:
352:
350:
343:
339:
332:
328:
327:
325:
323:
319:
311:
307:
302:
301:
298:
291:
286:
279:
277: Rx-only
270:
268:
258:
256:
247:
244:
234:
233:
231:
229:
225:
220:
212:
207:
204:
203:
201:
199:
195:
192:
189:
187:
181:
175:
166:
165:
163:
161:
155:
148:
144:
134:
131:
126:
117:
114:
109:
100:
99:
97:
95:
91:
87:
83:
81:
77:
73:
69:
67:
63:
59:
55:
51:
47:
45:
41:
38:Clinical data
36:
32:
27:
19:
3419:Orphan drugs
3374:Fluoroarenes
3273:Strep throat
3253:Otitis media
3014:
2830:India (2006)
2552:Reassortment
2476:. Retrieved
2472:the original
2467:
2455:
2418:
2414:
2383:
2379:
2353:. Retrieved
2335:
2323:. Retrieved
2305:
2293:. Retrieved
2284:
2274:
2262:. Retrieved
2253:
2244:
2232:. Retrieved
2221:
2209:
2197:. Retrieved
2188:
2177:
2144:
2140:
2134:
2107:
2103:
2093:
2051:(1): 17464.
2048:
2044:
2034:
2009:
2005:
1984:. Retrieved
1979:
1970:
1957:CN 108440564
1951:
1932:
1913:
1894:
1875:
1842:
1838:
1797:(1): 28–41.
1794:
1790:
1780:
1750:(1): 27–33.
1747:
1743:
1736:
1724:. Retrieved
1715:
1706:
1694:. Retrieved
1686:FiercePharma
1685:
1676:
1641:
1637:
1610:. Retrieved
1596:
1574:. Retrieved
1534:. Retrieved
1525:
1489:16 September
1487:. Retrieved
1466:
1444:. Retrieved
1382:
1378:
1368:
1356:. Retrieved
1347:
1338:
1318:30 September
1316:. Retrieved
1265:. Retrieved
1220:. Retrieved
1177:. Retrieved
1173:
1164:
1151:. Retrieved
1139:
1109:. Retrieved
1100:
1060:. Retrieved
1049:
1040:
1028:. Retrieved
1019:
1010:
998:. Retrieved
986:
959:
955:
951:
948:
931:
920:
917:Legal status
888:
875:
853:deacetylases
845:
843:
816:
795:endonuclease
779:endonuclease
768:
759:
756:Side effects
750:
737:
729:
721:
718:
714:
707:
700:
697:Medical uses
684:
661:
646:endonuclease
633:
627:
610:
606:
605:
331:1985606-14-1
309:
305:
228:Legal status
222:Legal status
94:License data
18:
3414:4-Pyridones
3399:Morpholines
3258:Pharyngitis
3204:Non-mammals
2985:Laninamivir
2980:Oseltamivir
2968:Rimantadine
2796:2009 A/H1N1
2598:Influenza D
2593:Influenza C
2588:Influenza B
2583:Influenza A
2325:23 February
1976:"Baloxavir"
1446:23 November
1385:: 109–117.
902:Switzerland
883:viral loads
879:oseltamivir
803:oseltamivir
777:-dependent
644:-dependent
619:influenza B
615:influenza A
533: g·mol
288:Identifiers
80:MedlinePlus
53:Other names
44:Trade names
3348:Categories
3010:Umifenovir
3002:Peramivir
2963:Amantadine
2941:Treatments
2562:Flu season
2355:23 October
1716:EurekAlert
1222:23 October
1153:25 January
964:References
943:indication
866:4-pyridone
823:polycyclic
734:Resistance
710:indication
668:bronchitis
657:polymerase
538:3D model (
526:Molar mass
416:505CXM6OHG
387:ChemSpider
322:CAS Number
297:IUPAC name
3268:Sinusitis
3263:Pneumonia
3159:Non-human
3126:Epidemics
3073:Pandemics
3064:epidemics
3043:Pandemrix
2995:Zanamivir
2990:Peramivir
2927:2020–2022
2920:Outbreaks
2835:UK (2007)
2818:Outbreaks
2762:Pandemics
2542:Treatment
2518:Influenza
2345:Genentech
2295:8 January
2264:11 August
2199:8 January
2169:131775842
2026:197172102
1845:: 14–18.
1772:208279215
1726:8 January
1696:8 January
1612:11 August
1576:7 January
1536:9 January
1526:Drugs.com
1111:9 January
1000:16 August
813:Chemistry
807:zanamivir
703:antiviral
676:sinusitis
652:" by the
356:124081896
184:Routes of
158:Pregnancy
72:Monograph
66:Drugs.com
3404:Prodrugs
3326:Medicine
3025:Vaccines
2610:subtypes
2532:Research
2437:30420246
2402:32640124
2349:Archived
2319:Archived
2289:Archived
2258:Archived
2228:Archived
2193:Archived
2161:31018720
2126:30203386
2085:31767949
1867:73726080
1859:30852344
1821:25417656
1764:31768027
1720:Archived
1690:Archived
1668:52173453
1660:30184455
1606:Archived
1570:Archived
1530:Archived
1483:Archived
1440:Archived
1401:30316915
1352:Archived
1309:Archived
1261:Archived
1216:Archived
1147:Archived
1105:Archived
1101:DailyMed
1056:Archived
1024:Archived
994:Archived
939:Shionogi
933:granted
921:Japan's
906:Roche AG
895:Japanese
891:Shionogi
827:Shionogi
819:pyridone
801:such as
680:headache
664:diarrhea
623:by mouth
396:59718643
367:DrugBank
198:ATC code
191:By mouth
173: B3
160:category
125:DailyMed
3338:Viruses
3312:Portals
3166:Mammals
2876:Vaccine
2854:Science
2789:Science
2571:Viruses
2537:Vaccine
2234:28 June
2076:6877583
2053:Bibcode
1986:28 July
1980:PubChem
1812:5619696
1568:(FDA).
1564:. U.S.
1303:. U.S.
1255:. U.S.
1179:3 March
904:-based
893:Co., a
872:History
846:in vivo
787:primers
685:The US
630:prodrug
611:Xofluza
484:Formula
376:DB13997
342:PubChem
253::
214:)
208: (
206:J05AX25
147:Xofluza
145::
127::
110::
86:a618062
48:Xofluza
3183:Equine
3178:Feline
3173:Canine
3048:Audenz
3038:Brands
2478:10 May
2435:
2400:
2167:
2159:
2124:
2083:
2073:
2024:
1963:
1944:
1925:
1906:
1887:
1865:
1857:
1819:
1809:
1770:
1762:
1666:
1658:
1399:
1358:29 May
1267:10 May
1062:29 May
1030:29 May
678:, and
672:nausea
654:virus'
564:SMILES
531:571.55
436:D11021
304:({(12a
267:℞-only
265:
255:℞-only
241:
140:
123:
113:by INN
106:
3248:Croup
3211:Avian
3195:Swine
2743:H11N9
2738:H11N2
2733:H10N8
2728:H10N7
2723:H10N3
2165:S2CID
2022:S2CID
1863:S2CID
1768:S2CID
1664:S2CID
1475:(PDF)
1312:(PDF)
1301:(PDF)
1143:(EMA)
990:(TGA)
791:mRNAs
584:InChI
540:JSmol
2912:H5N8
2810:H5N1
2753:H1N1
2718:H9N2
2713:H7N9
2708:H7N7
2703:H7N4
2698:H7N3
2693:H7N2
2688:H7N1
2683:H6N1
2678:H5N9
2673:H5N8
2668:H5N6
2663:H5N3
2658:H5N2
2653:H5N1
2648:H3N8
2643:H3N2
2638:H3N1
2633:H2N3
2628:H2N2
2623:H1N2
2618:H1N1
2480:2020
2433:PMID
2398:PMID
2357:2019
2327:2018
2297:2020
2266:2022
2236:2018
2223:Stat
2201:2020
2157:PMID
2122:PMID
2081:PMID
1988:2021
1855:PMID
1817:PMID
1760:PMID
1728:2020
1698:2020
1656:PMID
1614:2022
1578:2020
1538:2020
1491:2020
1448:2020
1397:PMID
1360:2020
1320:2020
1269:2020
1224:2019
1181:2023
1155:2021
1113:2020
1064:2022
1032:2022
1002:2020
805:and
617:and
427:KEGG
407:UNII
62:AHFS
2423:doi
2388:doi
2384:383
2149:doi
2112:doi
2071:PMC
2061:doi
2014:doi
1847:doi
1807:PMC
1799:doi
1752:doi
1646:doi
1642:379
1387:doi
1383:160
775:cap
642:cap
452:EPA
346:CID
211:WHO
143:FDA
108:EMA
3350::
2466:.
2454:.
2431:.
2417:.
2413:.
2396:.
2382:.
2378:.
2287:.
2283:.
2252:.
2226:.
2220:.
2191:.
2187:.
2163:.
2155:.
2145:28
2143:.
2120:.
2108:38
2106:.
2102:.
2079:.
2069:.
2059:.
2047:.
2043:.
2020:.
2010:23
2008:.
1996:^
1978:.
1861:.
1853:.
1843:35
1841:.
1829:^
1815:.
1805:.
1795:13
1793:.
1789:.
1766:.
1758:.
1746:.
1714:.
1684:.
1662:.
1654:.
1640:.
1636:.
1622:^
1546:^
1524:.
1509:^
1409:^
1395:.
1381:.
1377:.
1350:.
1346:.
1287:^
1242:^
1189:^
1172:.
1138:.
1121:^
1099:.
1072:^
1048:.
1018:.
985:.
972:^
809:.
693:.
682:.
674:,
670:,
666:,
498:23
492:27
273:EU
261:US
250:CA
243:S4
237:AU
169:AU
137:US
120:US
103:EU
3314::
2510:e
2503:t
2496:v
2482:.
2439:.
2425::
2419:6
2404:.
2390::
2299:.
2268:.
2238:.
2203:.
2171:.
2151::
2128:.
2114::
2087:.
2063::
2055::
2049:9
2028:.
2016::
1990:.
1869:.
1849::
1823:.
1801::
1774:.
1754::
1748:5
1730:.
1700:.
1670:.
1648::
1591:.
1580:.
1540:.
1504:.
1493:.
1461:.
1450:.
1403:.
1389::
1362:.
1333:.
1322:.
1282:.
1271:.
1237:.
1226:.
1183:.
1157:.
1115:.
1066:.
1034:.
1004:.
542:)
519:S
516:7
513:O
510:3
507:N
504:2
501:F
495:H
489:C
454:)
450:(
310:H
306:R
275::
263::
239::
171::
64:/
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.