sirolimus 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
immunosuppressants, rapamycin derivatives	2446	53123-88-9

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: sirolimus rapamycin rapammune rapamune supralimus rapalimus AY22989 AY-22989	A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. Limited data describing efficacy in patients with COVID-19 is available. However, its efficacy and safety in the treatment of COVID-19 was not established. Molecular weight: 914.19 Formula: C51H79NO13 CLOGP: 7.04 LIPINSKI: 3 HAC: 14 HDO: 3 TPSA: 195.43 ALOGS: -5.72 ROTB: 6 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

sirolimus
rapamycin
rapammune
rapamune
supralimus
rapalimus
AY22989
AY-22989

A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. Limited data describing efficacy in patients with COVID-19 is available. However, its efficacy and safety in the treatment of COVID-19 was not established.

Molecular weight: 914.19
Formula: C51H79NO13
CLOGP: 7.04
LIPINSKI: 3
HAC: 14
HDO: 3
TPSA: 195.43
ALOGS: -5.72
ROTB: 6

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
3	mg	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	2	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	2 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.15 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	15 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
S (Water solubility)	0.00 mg/mL	Bocci G, Oprea TI, Benet LZ

Approvals:

Date	Agency	Company
Sept. 15, 1999	FDA	PF PRISM CV
July 4, 2014	PMDA	NOBELPHARMA CO., LTD
March 13, 2001	EMA	Pfizer Europe MA EEIG

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Transplant dysfunction	2119.59	18.08	445	18051	4427	63466099
Transplant rejection	2050.09	18.08	501	17995	10279	63460247
Ovarian cyst	1445.06	18.08	412	18084	15533	63454993
Acne	1295.14	18.08	413	18083	22880	63447646
Alopecia	345.40	18.08	456	18040	337080	63133446
Epstein-Barr virus infection	266.66	18.08	97	18399	7953	63462573
Sleep disorder due to general medical condition, insomnia type	246.55	18.08	166	18330	52051	63418475
Liver function test abnormal	236.68	18.08	157	18339	48024	63422502
Product use in unapproved indication	222.37	18.08	267	18229	178813	63291713
Post transplant lymphoproliferative disorder	209.99	18.08	72	18424	4959	63465567
Off label use	208.75	18.08	543	17953	673919	62796607
Thrombotic microangiopathy	203.69	18.08	86	18410	10475	63460051
Kidney transplant rejection	201.43	18.08	67	18429	4204	63466322
Kidney fibrosis	145.19	18.08	43	18453	1838	63468688
Immunosuppressant drug level increased	132.34	18.08	47	18449	3591	63466935
Pneumonia	119.91	18.08	347	18149	456420	63014106
Polyomavirus-associated nephropathy	115.87	18.08	36	18460	1812	63468714
Smooth muscle cell neoplasm	114.50	18.08	30	18466	811	63469715
Graft versus host disease in gastrointestinal tract	99.71	18.08	37	18459	3204	63467322
Chronic allograft nephropathy	99.26	18.08	26	18470	702	63469824
Graft versus host disease	94.68	18.08	44	18452	6719	63463807
Graft versus host disease in skin	92.45	18.08	34	18462	2871	63467655
Epstein-Barr virus associated lymphoproliferative disorder	90.45	18.08	30	18466	1864	63468662
Cytomegalovirus infection	90.25	18.08	63	18433	20889	63449637
Human herpesvirus 6 infection	88.20	18.08	33	18463	2924	63467602
Hypertriglyceridaemia	82.31	18.08	39	18457	6220	63464306
Acute graft versus host disease	81.85	18.08	35	18461	4393	63466133
Liver transplant rejection	77.71	18.08	25	18471	1410	63469116
Condition aggravated	77.46	18.08	275	18221	401942	63068584
Arthralgia	76.96	18.08	35	18461	569675	62900851
Product use issue	76.38	18.08	186	18310	220334	63250192
Alveolar proteinosis	74.48	18.08	18	18478	347	63470179
JC virus infection	68.96	18.08	25	18471	2026	63468500
Drug level increased	68.11	18.08	55	18441	22681	63447845
MELAS syndrome	67.69	18.08	14	18482	127	63470399
Posterior reversible encephalopathy syndrome	67.43	18.08	49	18447	17296	63453230
Cryptosporidiosis infection	61.36	18.08	15	18481	304	63470222
BK virus infection	60.87	18.08	26	18470	3253	63467273
Infusion related reaction	59.14	18.08	3	18493	245518	63225008
Adenovirus infection	58.74	18.08	26	18470	3545	63466981
Fatigue	57.87	18.08	107	18389	887921	62582605
Rash	56.96	18.08	48	18448	560823	62909703
Heart transplant rejection	56.06	18.08	16	18480	599	63469927
Hypersensitivity	53.99	18.08	10	18486	292675	63177851
Renal graft infection	53.87	18.08	13	18483	249	63470277
Arthropathy	53.16	18.08	4	18492	234788	63235738
Joint swelling	51.05	18.08	16	18480	327650	63142876
Skin squamous cell carcinoma metastatic	49.81	18.08	8	18488	12	63470514
Incorrect route of product administration	49.69	18.08	50	18446	27402	63443124
Loss of personal independence in daily activities	49.58	18.08	96	18400	97194	63373332
Chronic graft versus host disease	49.15	18.08	22	18474	3080	63467446
Pseudomonas infection	48.94	18.08	34	18462	11179	63459347
Blood creatinine increased	48.88	18.08	90	18406	87754	63382772
Renal impairment	48.51	18.08	90	18406	88265	63382261
Rheumatoid arthritis	48.26	18.08	173	18323	253646	63216880
Multiple organ dysfunction syndrome	47.63	18.08	70	18426	56682	63413844
Drug interaction	46.86	18.08	160	18336	228971	63241555
Nephropathy toxic	46.75	18.08	31	18465	9448	63461078
Pneumocystis jirovecii pneumonia	46.64	18.08	39	18457	16875	63453651
Dizziness	45.85	18.08	35	18461	429890	63040636
Drug ineffective for unapproved indication	45.77	18.08	53	18443	34010	63436516
Plasmablastic lymphoma	45.62	18.08	11	18485	210	63470316
Morphoea	45.36	18.08	12	18484	337	63470189
Fall	44.36	18.08	30	18466	392304	63078222
Cytomegalovirus infection reactivation	44.01	18.08	22	18474	3941	63466585
Lymphocele	43.29	18.08	14	18482	803	63469723
Septic shock	43.19	18.08	73	18423	66556	63403970
Drug level below therapeutic	42.52	18.08	23	18473	4843	63465683
Mouth ulceration	42.12	18.08	50	18446	32934	63437592
Hypogammaglobulinaemia	41.71	18.08	26	18470	7129	63463397
Respiratory failure	40.75	18.08	91	18405	101767	63368759
Complications of transplanted kidney	40.57	18.08	18	18478	2468	63468058
Avian influenza	39.57	18.08	8	18488	64	63470462
Pancreas transplant rejection	38.82	18.08	9	18487	144	63470382
Proteinuria	38.62	18.08	37	18459	19108	63451418
Globulins decreased	38.57	18.08	10	18486	259	63470267
Neurofibrosarcoma	38.20	18.08	9	18487	155	63470371
Immunosuppressant drug level decreased	37.15	18.08	13	18483	950	63469576
Abdominal discomfort	36.98	18.08	24	18472	320861	63149665
Swelling	36.96	18.08	17	18479	275361	63195165
Polyomavirus viraemia	36.55	18.08	12	18484	722	63469804
Pneumonitis	36.36	18.08	48	18448	35174	63435352
Lymphopenia	36.17	18.08	35	18461	18292	63452234
Sinusitis	35.40	18.08	11	18485	226642	63243884
Focal segmental glomerulosclerosis	35.27	18.08	14	18482	1454	63469072
Therapeutic product effect decreased	34.76	18.08	7	18489	193180	63277346
Pneumothorax	33.89	18.08	32	18464	16229	63454297
Dysplasia	33.76	18.08	12	18484	918	63469608
Drug hypersensitivity	33.46	18.08	25	18471	310662	63159864
Somnolence	33.15	18.08	6	18490	178679	63291847
Chronic graft versus host disease in skin	32.29	18.08	11	18485	742	63469784
Hepatitis E	32.03	18.08	13	18483	1431	63469095
Adjusted calcium decreased	31.85	18.08	8	18488	182	63470344
Pain in extremity	31.62	18.08	30	18466	331456	63139070
Constipation	31.58	18.08	13	18483	224930	63245596
Trichodysplasia spinulosa	31.03	18.08	10	18486	567	63469959
Transplant failure	30.86	18.08	13	18483	1572	63468954
Bacillary angiomatosis	30.80	18.08	7	18489	102	63470424
Jejunal perforation	30.55	18.08	7	18489	106	63470420
Alopecia scarring	30.43	18.08	7	18489	108	63470418
Babesiosis	30.36	18.08	8	18488	221	63470305
Feeling abnormal	29.75	18.08	4	18492	148388	63322138
Dyspnoea	29.35	18.08	97	18399	661216	62809310
Trichostasis spinulosa	29.31	18.08	5	18491	13	63470513
Acute graft versus host disease in skin	29.28	18.08	16	18480	3436	63467090
Bronchiolitis obliterans syndrome	28.96	18.08	7	18489	135	63470391
Overdose	28.62	18.08	86	18410	114992	63355534
Renal-limited thrombotic microangiopathy	28.48	18.08	6	18490	60	63470466
Klebsiella infection	28.39	18.08	22	18474	8544	63461982
Endocarditis Q fever	28.30	18.08	5	18491	17	63470509
Weight increased	28.05	18.08	21	18475	260771	63209755
Graft thrombosis	27.92	18.08	7	18489	158	63470368
Skin graft rejection	27.87	18.08	5	18491	19	63470507
Insomnia	27.78	18.08	14	18482	215238	63255288
Blastomycosis	27.64	18.08	8	18488	315	63470211
Haemodialysis	27.54	18.08	22	18474	8925	63461601
Escherichia bacteraemia	27.53	18.08	16	18480	3867	63466659
Back pain	27.49	18.08	22	18474	264123	63206403
Blister	27.25	18.08	3	18493	129811	63340715
Jarisch-Herxheimer reaction	26.42	18.08	8	18488	369	63470157
Fibrosarcoma	26.33	18.08	4	18492	3	63470523
Squamous cell carcinoma	26.09	18.08	21	18475	8611	63461915
Hypoalbuminaemia	26.08	18.08	24	18472	11781	63458745
Maternal exposure during pregnancy	25.96	18.08	16	18480	220046	63250480
Hepatic fibrosis	25.76	18.08	15	18481	3637	63466889
Renal failure	25.64	18.08	84	18412	117568	63352958
Lower respiratory tract infection	25.52	18.08	4	18492	132303	63338223
Muscle spasms	25.43	18.08	7	18489	156143	63314383
Musculoskeletal stiffness	25.38	18.08	11	18485	184607	63285919
Wound	25.34	18.08	8	18488	163255	63307271
Rhinovirus infection	25.25	18.08	16	18480	4513	63466013
Haemolytic uraemic syndrome	25.18	18.08	13	18483	2490	63468036
Gait disturbance	25.04	18.08	11	18485	183167	63287359
Pulmonary haemorrhage	25.02	18.08	19	18477	7162	63463364
Scleroderma	24.87	18.08	17	18479	5445	63465081
Injection site pain	24.86	18.08	4	18492	129796	63340730
Hypoaesthesia	24.84	18.08	9	18487	168384	63302142
Pruritus	24.81	18.08	42	18454	361411	63109115
Drug level fluctuating	24.75	18.08	8	18488	458	63470068
Obliterative bronchiolitis	24.36	18.08	12	18484	2083	63468443
Drug effective for unapproved indication	24.21	18.08	14	18482	3350	63467176
Anxiety	24.06	18.08	17	18479	217524	63253002
Renal tubular necrosis	24.04	18.08	23	18473	11855	63458671
Human polyomavirus infection	23.11	18.08	7	18489	323	63470203
Viraemia	23.00	18.08	10	18486	1306	63469220
Discomfort	22.96	18.08	10	18486	167364	63303162
Acute kidney injury	22.87	18.08	143	18353	263272	63207254
Lung transplant rejection	22.83	18.08	9	18487	918	63469608
Headache	22.83	18.08	101	18395	633140	62837386
Product dose omission issue	22.57	18.08	21	18475	234292	63236234
Pulmonary alveolar haemorrhage	22.37	18.08	15	18481	4653	63465873
Moyamoya disease	22.06	18.08	5	18491	72	63470454
Bacterial colitis	22.06	18.08	5	18491	72	63470454
Enterovirus infection	22.05	18.08	9	18487	1005	63469521
Hepatic angiosarcoma	21.94	18.08	4	18492	17	63470509
Pterygium	21.84	18.08	6	18490	195	63470331
Pleural effusion	21.62	18.08	68	18428	93142	63377384
Acute hepatitis C	21.51	18.08	5	18491	81	63470445
Nausea	21.22	18.08	154	18342	854317	62616209
Chest pain	21.22	18.08	19	18477	215940	63254586
Interstitial lung disease	21.13	18.08	52	18444	61856	63408670
Urticaria	21.07	18.08	11	18485	165791	63304735
Cat scratch disease	20.99	18.08	6	18490	226	63470300
Aspergillus infection	20.95	18.08	18	18478	8075	63462451
Salivary gland mass	20.86	18.08	5	18491	93	63470433
Bacterial translocation	20.59	18.08	6	18490	242	63470284
Malaise	20.55	18.08	58	18438	415896	63054630
Mobility decreased	20.55	18.08	5	18491	121154	63349372
Pulmonary artery atresia	20.51	18.08	4	18492	26	63470500
Kussmaul respiration	20.45	18.08	6	18490	248	63470278
Haemophagocytic lymphohistiocytosis	20.42	18.08	20	18476	10607	63459919
Therapy partial responder	20.37	18.08	20	18476	10638	63459888
Human herpesvirus 8 infection	20.36	18.08	6	18490	252	63470274
Diabetes mellitus	20.25	18.08	48	18448	55762	63414764
Urinary tract infection pseudomonal	20.02	18.08	8	18488	845	63469681
Drug ineffective	19.98	18.08	420	18076	1044345	62426181
Thymus enlargement	19.65	18.08	5	18491	120	63470406
Syncope	19.61	18.08	5	18491	117380	63353146
Visceral leishmaniasis	19.44	18.08	7	18489	556	63469970
Renal transplant	19.38	18.08	9	18487	1371	63469155
Disseminated mycobacterium avium complex infection	19.27	18.08	5	18491	130	63470396
Cardiac murmur functional	18.99	18.08	4	18492	40	63470486
Magnetic resonance imaging head abnormal	18.95	18.08	10	18486	2003	63468523
Varicella zoster virus infection	18.85	18.08	11	18485	2678	63467848
Intussusception	18.81	18.08	7	18489	611	63469915
Microangiopathic haemolytic anaemia	18.75	18.08	7	18489	616	63469910
Epstein-Barr viraemia	18.72	18.08	8	18488	1002	63469524
Biopsy kidney abnormal	18.64	18.08	4	18492	44	63470482
Chronic kidney disease	18.64	18.08	41	18455	45357	63425169
Graft ischaemia	18.56	18.08	4	18492	45	63470481
Disease recurrence	18.54	18.08	31	18465	27999	63442527
Q fever	18.52	18.08	5	18491	152	63470374
Asthma	18.50	18.08	7	18489	127554	63342972
Craniocerebral injury	18.32	18.08	11	18485	2821	63467705
Acinetobacter infection	18.20	18.08	9	18487	1574	63468952
Wheezing	18.18	18.08	3	18493	95592	63374934
Viral oesophagitis	18.13	18.08	3	18493	6	63470520

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Transplant rejection	464.54	14.32	187	19979	10124	34926641
Off label use	350.33	14.32	753	19413	418771	34517994
Product use in unapproved indication	348.77	14.32	382	19784	117117	34819648
Kidney transplant rejection	310.32	14.32	128	20038	7369	34929396
Cytomegalovirus infection	167.64	14.32	131	20035	26004	34910761
Adenovirus infection	159.19	14.32	72	20094	5185	34931580
Immunosuppressant drug level increased	152.51	14.32	73	20093	5982	34930783
Post transplant lymphoproliferative disorder	150.27	14.32	74	20092	6454	34930311
Liver transplant rejection	140.57	14.32	51	20115	2068	34934697
Thrombotic microangiopathy	139.52	14.32	83	20083	10547	34926218
Transplant failure	138.01	14.32	58	20108	3495	34933270
Epstein-Barr virus infection	130.96	14.32	71	20095	7557	34929208
Acute graft versus host disease	112.95	14.32	61	20105	6442	34930323
BK virus infection	102.95	14.32	55	20111	5683	34931082
Product use issue	101.77	14.32	152	20014	63064	34873701
Nephropathy toxic	100.54	14.32	72	20094	12516	34924249
Cytomegalovirus viraemia	100.07	14.32	59	20107	7371	34929394
Cytomegalovirus infection reactivation	94.48	14.32	50	20116	5068	34931697
Graft versus host disease in skin	88.85	14.32	44	20122	3881	34932884
Squamous cell carcinoma	85.64	14.32	63	20103	11412	34925353
Chronic graft versus host disease	81.51	14.32	43	20123	4330	34932435
Squamous cell carcinoma of skin	79.54	14.32	59	20107	10822	34925943
Polyomavirus-associated nephropathy	77.95	14.32	40	20126	3804	34932961
Lymphocele	76.56	14.32	29	20137	1328	34935437
Blood creatinine increased	72.00	14.32	165	20001	94811	34841954
Complications of transplanted kidney	68.43	14.32	39	20127	4570	34932195
Nocardiosis	68.43	14.32	37	20129	3914	34932851
Chronic allograft nephropathy	67.81	14.32	26	20140	1231	34935534
Skin squamous cell carcinoma recurrent	65.24	14.32	13	20153	42	34936723
Graft versus host disease in gastrointestinal tract	65.21	14.32	35	20131	3648	34933117
Smooth muscle cell neoplasm	64.28	14.32	16	20150	169	34936596
Proteinuria	62.77	14.32	65	20101	18577	34918188
Graft versus host disease in liver	60.23	14.32	24	20142	1260	34935505
Heart transplant rejection	57.71	14.32	23	20143	1208	34935557
Renal impairment	57.57	14.32	151	20015	94362	34842403
Transplant dysfunction	54.97	14.32	28	20138	2621	34934144
Acute graft versus host disease in skin	54.01	14.32	35	20131	5166	34931599
Propionibacterium infection	53.90	14.32	15	20151	251	34936514
Meningitis viral	53.40	14.32	20	20146	887	34935878
Multiple organ dysfunction syndrome	52.54	14.32	128	20038	76438	34860327
Skin squamous cell carcinoma metastatic	51.71	14.32	11	20155	53	34936712
Pneumonia cytomegaloviral	51.22	14.32	28	20138	3026	34933739
Kidney fibrosis	50.50	14.32	25	20141	2203	34934562
Epidermodysplasia verruciformis	49.93	14.32	14	20152	241	34936524
Diarrhoea haemorrhagic	47.92	14.32	36	20130	6728	34930037
Brain abscess	47.90	14.32	27	20139	3098	34933667
Bronchopulmonary aspergillosis	47.35	14.32	50	20116	14609	34922156
Pneumatosis intestinalis	47.25	14.32	29	20137	3894	34932871
Scleroderma	45.91	14.32	21	20145	1551	34935214
Fatigue	45.46	14.32	91	20075	370562	34566203
Dizziness	45.15	14.32	36	20130	218485	34718280
Constipation	42.67	14.32	13	20153	136969	34799796
Herpes zoster meningoencephalitis	42.38	14.32	13	20153	310	34936455
Interstitial lung disease	41.47	14.32	106	20060	65176	34871589
Acute graft versus host disease in intestine	40.43	14.32	23	20143	2685	34934080
Hypotension	40.42	14.32	41	20125	221608	34715157
Diaphragmatic hernia	40.29	14.32	12	20154	258	34936507
Abdominal wall abscess	39.77	14.32	14	20152	519	34936246
Cow pox	39.22	14.32	8	20158	30	34936735
Impaired healing	38.72	14.32	46	20120	15288	34921477
Retinal scar	38.36	14.32	12	20154	306	34936459
Human herpesvirus 8 infection	38.14	14.32	16	20150	959	34935806
Graft versus host disease	37.65	14.32	38	20128	10531	34926234
Staphylococcal mediastinitis	35.99	14.32	8	20158	49	34936716
Escherichia infection	35.70	14.32	33	20133	8212	34928553
Pleocytosis	35.54	14.32	13	20153	539	34936226
Renal tubular atrophy	35.31	14.32	16	20150	1156	34935609
Cytomegalovirus chorioretinitis	34.46	14.32	23	20143	3566	34933199
Hyperlipidaemia	34.10	14.32	42	20124	14487	34922278
Central nervous system lymphoma	34.06	14.32	15	20151	1013	34935752
Hepatic cancer recurrent	34.05	14.32	11	20155	312	34936453
Malacoplakia	33.96	14.32	12	20154	450	34936315
Mouth ulceration	33.89	14.32	38	20128	11872	34924893
Drug ineffective for unapproved indication	33.86	14.32	54	20112	23661	34913104
Transitional cell carcinoma	33.78	14.32	19	20147	2170	34934595
Pericardial effusion	33.64	14.32	55	20111	24607	34912158
Nephrogenic diabetes insipidus	33.48	14.32	16	20150	1305	34935460
Haemolytic uraemic syndrome	33.01	14.32	19	20147	2267	34934498
Venoocclusive liver disease	32.79	14.32	31	20135	7935	34928830
Protothecosis	32.69	14.32	7	20159	35	34936730
Human herpesvirus 6 infection	31.95	14.32	18	20148	2063	34934702
Renal tubular necrosis	31.56	14.32	42	20124	15638	34921127
Gastroenteritis norovirus	31.29	14.32	16	20150	1510	34935255
Drug interaction	31.21	14.32	230	19936	225716	34711049
Acute graft versus host disease in liver	30.90	14.32	16	20150	1550	34935215
Tularaemia	30.69	14.32	8	20158	103	34936662
Metastases to lung	30.47	14.32	32	20134	9288	34927477
Bradycardia	30.00	14.32	4	20162	75414	34861351
Anxiety	29.95	14.32	10	20156	99418	34837347
Hypogammaglobulinaemia	29.74	14.32	29	20137	7711	34929054
Focal segmental glomerulosclerosis	29.70	14.32	17	20149	2008	34934757
Scedosporium infection	29.64	14.32	13	20153	869	34935896
Alveolar proteinosis	29.63	14.32	11	20155	476	34936289
Malignant fibrous histiocytoma	29.28	14.32	9	20157	216	34936549
Pruritus	28.53	14.32	24	20142	141957	34794808
Right ventricular diastolic collapse	28.47	14.32	7	20159	70	34936695
Drug level increased	28.42	14.32	48	20118	22048	34914717
Chronic graft versus host disease in skin	28.40	14.32	13	20153	961	34935804
Nausea	28.31	14.32	101	20065	339807	34596958
Drug effective for unapproved indication	28.22	14.32	18	20148	2584	34934181
Hydronephrosis	27.72	14.32	32	20134	10314	34926451
Epstein-Barr viraemia	27.61	14.32	14	20152	1298	34935467
Drug level decreased	27.57	14.32	28	20138	7818	34928947
Pharyngitis	27.27	14.32	28	20138	7916	34928849
Varicella	27.09	14.32	15	20151	1662	34935103
Renal-limited thrombotic microangiopathy	26.79	14.32	7	20159	91	34936674
Chronic graft versus host disease in liver	26.58	14.32	10	20156	449	34936316
Complications of transplanted heart	26.28	14.32	9	20157	307	34936458
Fall	25.49	14.32	49	20117	202836	34733929
Diffuse large B-cell lymphoma	25.34	14.32	26	20140	7344	34929421
Renal tubular injury	25.20	14.32	12	20154	971	34935794
Back pain	25.19	14.32	20	20146	121769	34814996
Arthralgia	25.11	14.32	37	20129	170004	34766761
Philadelphia positive chronic myeloid leukaemia	24.67	14.32	7	20159	126	34936639
Lung transplant rejection	24.45	14.32	11	20155	781	34935984
Venoocclusive disease	24.27	14.32	17	20149	2850	34933915
Drug resistance	24.13	14.32	49	20117	25878	34910887
Depression	24.07	14.32	13	20153	97085	34839680
Muscle spasms	23.55	14.32	7	20159	74994	34861771
Ileal ulcer	23.51	14.32	10	20156	620	34936145
Enteritis	23.20	14.32	26	20140	8116	34928649
Syncope	23.03	14.32	12	20154	91439	34845326
Ophthalmic herpes zoster	23.02	14.32	11	20155	897	34935868
Insomnia	22.86	14.32	16	20150	103891	34832874
Obliterative bronchiolitis	22.44	14.32	12	20154	1241	34935524
Disseminated varicella zoster virus infection	22.31	14.32	8	20158	313	34936452
Somnolence	22.05	14.32	19	20147	111097	34825668
Aspergillus infection	21.91	14.32	31	20135	12223	34924542
Basal cell carcinoma	21.78	14.32	40	20126	19618	34917147
Neuroendocrine carcinoma of the skin	21.33	14.32	10	20156	781	34935984
Inappropriate schedule of product administration	21.10	14.32	5	20161	62291	34874474
Mycobacterium chelonae infection	21.05	14.32	10	20156	805	34935960
Posterior reversible encephalopathy syndrome	20.55	14.32	27	20139	9927	34926838
Hyperhidrosis	20.48	14.32	9	20157	75683	34861082
Hepatitis B	20.38	14.32	21	20145	5962	34930803
Ureteric stenosis	20.33	14.32	11	20155	1165	34935600
Wound dehiscence	19.92	14.32	16	20150	3295	34933470
Viraemia	19.80	14.32	11	20155	1227	34935538
Encephalitis eastern equine	19.38	14.32	3	20163	0	34936765
Rash	19.30	14.32	65	20101	222687	34714078
Periorbital infection	19.25	14.32	6	20160	151	34936614
Spirochaetal infection	19.21	14.32	4	20162	17	34936748
Toxoplasmosis	19.17	14.32	11	20155	1305	34935460
Splenic neoplasm malignancy unspecified	19.03	14.32	4	20162	18	34936747
Nail discolouration	19.00	14.32	10	20156	1001	34935764
Escherichia urinary tract infection	18.96	14.32	16	20150	3530	34933235
Histology abnormal	18.94	14.32	7	20159	299	34936466
Alveolitis	18.84	14.32	12	20154	1718	34935047
Cytomegalovirus oesophagitis	18.78	14.32	8	20158	498	34936267
Atypical haemolytic uraemic syndrome	18.53	14.32	7	20159	318	34936447
Lip haemorrhage	18.52	14.32	9	20157	761	34936004
Varicella zoster virus infection	18.37	14.32	12	20154	1794	34934971
Perinephric collection	18.35	14.32	6	20160	177	34936588
Acne	18.33	14.32	27	20139	11039	34925726
Livedo reticularis	18.26	14.32	13	20153	2236	34934529
Dyspnoea	18.23	14.32	135	20031	376647	34560118
Kaposi sarcoma inflammatory cytokine syndrome	18.21	14.32	4	20162	23	34936742
Pulmonary toxicity	18.15	14.32	20	20146	6127	34930638
Joint swelling	18.07	14.32	6	20160	59884	34876881
Cytomegalovirus colitis	17.92	14.32	14	20152	2770	34933995
Aphthous ulcer	17.86	14.32	18	20148	4977	34931788
Normocytic anaemia	17.78	14.32	13	20153	2331	34934434
Osmotic demyelination syndrome	17.63	14.32	9	20157	846	34935919
Parvovirus B19 infection	17.63	14.32	9	20157	846	34935919
Pericarditis constrictive	17.63	14.32	7	20159	364	34936401
Hypertriglyceridaemia	17.57	14.32	23	20143	8425	34928340
Pneumonia pseudomonal	17.57	14.32	16	20150	3906	34932859
Inferior vena cava stenosis	17.53	14.32	4	20162	28	34936737
Pneumonitis	17.49	14.32	51	20115	33827	34902938
Pseudomonas infection	17.40	14.32	28	20138	12354	34924411
Pain in extremity	17.27	14.32	29	20137	126484	34810281
Cerebellar stroke	17.21	14.32	6	20160	216	34936549
SARS-CoV-2 RNA	17.18	14.32	4	20162	31	34936734
Bacterial sepsis	17.12	14.32	18	20148	5232	34931533
Candida infection	17.10	14.32	34	20132	17681	34919084
Alternaria infection	17.07	14.32	7	20159	396	34936369
Macroglossia	16.94	14.32	7	20159	404	34936361
Septic shock	16.84	14.32	84	20082	71750	34865015
Skin erosion	16.81	14.32	12	20154	2073	34934692
Staphylococcal infection	16.61	14.32	49	20117	32711	34904054
Chronic obstructive pulmonary disease	16.42	14.32	4	20162	48914	34887851
Overdose	16.38	14.32	17	20149	91042	34845723
Reticulocyte count decreased	16.32	14.32	8	20158	690	34936075
Peritoneal hernia	16.08	14.32	3	20163	6	34936759
Product administered to patient of inappropriate age	15.87	14.32	14	20152	3277	34933488
Haemorrhagic pneumonia	15.85	14.32	5	20161	131	34936634
Human polyomavirus infection	15.83	14.32	8	20158	736	34936029
Blood pressure decreased	15.82	14.32	5	20161	51510	34885255
Stomatitis	15.62	14.32	57	20109	42457	34894308
Herpes virus infection	15.56	14.32	13	20153	2829	34933936
Red blood cell burr cells present	15.53	14.32	4	20162	49	34936716
Confusional state	15.45	14.32	38	20128	144122	34792643
Musculoskeletal stiffness	15.31	14.32	4	20162	46676	34890089
Paraesthesia	15.31	14.32	9	20157	64163	34872602
Anuria	15.31	14.32	24	20142	10361	34926404
Osteomyelitis chronic	15.24	14.32	6	20160	305	34936460
Ovarian cyst	15.22	14.32	3	20163	9	34936756
Urinary tract infection neonatal	15.22	14.32	3	20163	9	34936756
Cryptococcosis	15.22	14.32	12	20154	2407	34934358
Enterobacter infection	15.17	14.32	12	20154	2418	34934347
Hepatic neoplasm	15.07	14.32	11	20155	1966	34934799
Fusarium infection	15.06	14.32	9	20157	1151	34935614
Viral haemorrhagic cystitis	14.92	14.32	9	20157	1171	34935594
Necrotising retinitis	14.90	14.32	8	20158	834	34935931
Myocarditis toxoplasmal	14.78	14.32	4	20162	60	34936705
Metastatic malignant melanoma	14.69	14.32	11	20155	2044	34934721
Wheezing	14.67	14.32	3	20163	41399	34895366
Pelvic fluid collection	14.67	14.32	5	20161	168	34936597
Rabies	14.55	14.32	3	20163	12	34936753
Urticaria	14.53	14.32	9	20157	62368	34874397
Anogenital warts	14.43	14.32	7	20159	590	34936175
Immunosuppressant drug level decreased	14.41	14.32	9	20157	1245	34935520

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Transplant rejection	2160.01	14.69	641	33384	18796	79691567
Transplant dysfunction	1899.21	14.69	470	33555	6751	79703612
Ovarian cyst	1338.39	14.69	402	33623	12253	79698110
Acne	1141.26	14.69	431	33594	26759	79683604
Product use in unapproved indication	577.48	14.69	618	33407	249741	79460622
Off label use	527.21	14.69	1176	32849	906039	78804324
Alopecia	357.92	14.69	466	33559	230889	79479474
Kidney transplant rejection	353.43	14.69	141	33884	10105	79700258
Epstein-Barr virus infection	335.56	14.69	150	33875	14266	79696097
Post transplant lymphoproliferative disorder	324.70	14.69	137	33888	11327	79699036
Thrombotic microangiopathy	299.14	14.69	154	33871	20015	79690348
Adenovirus infection	259.57	14.69	107	33918	8340	79702023
Acute graft versus host disease	243.69	14.69	108	33917	10059	79700304
Cytomegalovirus infection	235.17	14.69	173	33852	42471	79667892
Immunosuppressant drug level increased	229.66	14.69	100	33925	8927	79701436
Sleep disorder due to general medical condition, insomnia type	220.79	14.69	168	33857	43388	79666975
Product use issue	193.52	14.69	332	33693	209490	79500873
BK virus infection	174.67	14.69	82	33943	8722	79701641
Polyomavirus-associated nephropathy	171.94	14.69	71	33954	5556	79704807
Liver function test abnormal	161.97	14.69	167	33858	64308	79646055
Cytomegalovirus infection reactivation	160.14	14.69	77	33948	8639	79701724
Graft versus host disease in skin	153.57	14.69	67	33958	6006	79704357
Transplant failure	146.70	14.69	60	33965	4581	79705782
Nephropathy toxic	145.60	14.69	97	33928	20322	79690041
Chronic allograft nephropathy	145.35	14.69	46	33979	1665	79708698
Graft versus host disease in gastrointestinal tract	144.26	14.69	65	33960	6291	79704072
Chronic graft versus host disease	130.96	14.69	62	33963	6719	79703644
Graft versus host disease	130.94	14.69	81	33944	14945	79695418
Smooth muscle cell neoplasm	129.98	14.69	37	33988	925	79709438
Liver transplant rejection	127.13	14.69	49	33976	3199	79707164
Human herpesvirus 6 infection	115.81	14.69	53	33972	5317	79705046
Squamous cell carcinoma	106.07	14.69	72	33953	15550	79694813
Arthralgia	103.16	14.69	58	33967	571745	79138618
Blood creatinine increased	96.72	14.69	208	33817	154849	79555514
Multiple organ dysfunction syndrome	96.22	14.69	179	33846	120067	79590296
Renal impairment	93.12	14.69	207	33818	157576	79552787
Acute graft versus host disease in skin	92.44	14.69	51	33974	7607	79702756
Nocardiosis	86.01	14.69	44	33981	5635	79704728
Cytomegalovirus viraemia	84.45	14.69	58	33967	12763	79697600
Skin squamous cell carcinoma metastatic	84.34	14.69	16	34009	55	79710308
Fatigue	83.40	14.69	170	33855	929557	78780806
Alveolar proteinosis	83.04	14.69	25	34000	764	79709599
Dizziness	81.92	14.69	63	33962	526378	79183985
Complications of transplanted kidney	81.28	14.69	44	33981	6322	79704041
Proteinuria	77.66	14.69	82	33943	32420	79677943
Pneumonia	77.60	14.69	514	33511	659732	79050631
Epstein-Barr virus associated lymphoproliferative disorder	76.61	14.69	35	33990	3497	79706866
Drug level increased	75.76	14.69	89	33936	39562	79670801
Lymphocele	75.34	14.69	28	33997	1653	79708710
Fall	75.03	14.69	59	33966	487570	79222793
Joint swelling	74.67	14.69	16	34009	288630	79421733
Heart transplant rejection	74.51	14.69	27	33998	1483	79708880
Drug interaction	71.50	14.69	358	33667	414825	79295538
Mouth ulceration	71.40	14.69	85	33940	38309	79672054
Squamous cell carcinoma of skin	70.78	14.69	54	33971	13979	79696384
Kidney fibrosis	70.35	14.69	33	33992	3502	79706861
Chronic graft versus host disease in skin	66.11	14.69	25	34000	1549	79708814
Posterior reversible encephalopathy syndrome	65.82	14.69	68	33957	26213	79684150
Infusion related reaction	65.50	14.69	10	34015	230227	79480136
Rash	65.35	14.69	91	33934	578267	79132096
Bronchopulmonary aspergillosis	63.78	14.69	62	33963	22232	79688131
Constipation	63.18	14.69	21	34004	283029	79427334
Human herpesvirus 8 infection	60.89	14.69	22	34003	1198	79709165
Drug ineffective for unapproved indication	60.71	14.69	91	33934	51147	79659216
Hypertriglyceridaemia	59.85	14.69	47	33978	12693	79697670
JC virus infection	58.57	14.69	30	33995	3851	79706512
Epidermodysplasia verruciformis	57.64	14.69	16	34009	364	79709999
Acute graft versus host disease in intestine	57.43	14.69	30	33995	4011	79706352
Pneumatosis intestinalis	57.04	14.69	35	33990	6362	79704001
MELAS syndrome	56.95	14.69	14	34011	194	79710169
Skin squamous cell carcinoma recurrent	56.88	14.69	11	34014	43	79710320
Interstitial lung disease	56.83	14.69	139	33886	112461	79597902
Plasmablastic lymphoma	56.76	14.69	17	34008	510	79709853
Nausea	56.67	14.69	214	33811	956982	78753381
Hypersensitivity	55.88	14.69	21	34004	262218	79448145
Propionibacterium infection	55.31	14.69	15	34010	312	79710051
Renal tubular atrophy	55.28	14.69	23	34002	1833	79708530
Pruritus	54.32	14.69	53	33972	394595	79315768
Back pain	53.12	14.69	32	33993	304148	79406215
Pseudomonas infection	52.19	14.69	54	33971	20849	79689514
Pain in extremity	51.28	14.69	48	33977	364490	79345873
Septic shock	51.09	14.69	141	33884	122660	79587703
Focal segmental glomerulosclerosis	51.07	14.69	26	33999	3295	79707068
Haemolytic uraemic syndrome	49.26	14.69	28	33997	4421	79705942
Syncope	48.37	14.69	9	34016	179440	79530923
Somnolence	47.88	14.69	21	34004	238960	79471403
Renal tubular necrosis	47.49	14.69	56	33969	24983	79685380
Cryptosporidiosis infection	47.06	14.69	16	34009	727	79709636
Therapeutic product effect decreased	46.87	14.69	7	34018	163856	79546507
Pneumocystis jirovecii pneumonia	46.25	14.69	63	33962	32445	79677918
Arthropathy	45.41	14.69	10	34015	177101	79533262
Dyspnoea	45.40	14.69	200	33825	856825	78853538
Transitional cell carcinoma	45.32	14.69	22	34003	2519	79707844
Anxiety	45.01	14.69	25	34000	248487	79461876
Pericardial effusion	44.93	14.69	75	33950	46162	79664201
Respiratory failure	44.75	14.69	174	33851	180737	79529626
Renal-limited thrombotic microangiopathy	44.70	14.69	11	34014	153	79710210
Staphylococcal mediastinitis	44.09	14.69	9	34016	49	79710314
Meningitis viral	44.06	14.69	20	34005	1968	79708395
Varicella zoster virus infection	44.00	14.69	26	33999	4415	79705948
Pneumonia cytomegaloviral	43.83	14.69	27	33998	4942	79705421
Aspergillus infection	43.40	14.69	47	33978	19114	79691249
Condition aggravated	43.28	14.69	363	33662	500761	79209602
Hypotension	42.37	14.69	77	33948	440240	79270123
Varicella	42.33	14.69	22	34003	2910	79707453
Epstein-Barr viraemia	42.08	14.69	20	34005	2185	79708178
Pancreas transplant rejection	41.67	14.69	12	34013	313	79710050
Cow pox	41.63	14.69	8	34017	30	79710333
Drug effective for unapproved indication	41.55	14.69	28	33997	5973	79704390
Brain abscess	41.46	14.69	26	33999	4910	79705453
Scleroderma	41.27	14.69	27	33998	5483	79704880
Drug level decreased	41.09	14.69	40	33985	14362	79696001
Hyperlipidaemia	40.86	14.69	53	33972	26040	79684323
Escherichia infection	40.47	14.69	44	33981	17973	79692390
Drug hypersensitivity	40.12	14.69	41	33984	298875	79411488
Graft versus host disease in liver	40.00	14.69	18	34007	1736	79708627
Klebsiella infection	39.95	14.69	41	33984	15679	79694684
Venoocclusive liver disease	39.94	14.69	36	33989	11735	79698628
Insomnia	39.79	14.69	28	33997	245142	79465221
Sinusitis	39.44	14.69	17	34008	195484	79514879
Diaphragmatic hernia	39.30	14.69	12	34013	385	79709978
Urticaria	39.16	14.69	15	34010	185186	79525177
Herpes zoster meningoencephalitis	39.02	14.69	14	34011	747	79709616
Musculoskeletal stiffness	39.00	14.69	13	34012	174995	79535368
Muscle spasms	38.90	14.69	13	34012	174717	79535646
Maternal exposure during pregnancy	38.66	14.69	6	34019	136532	79573831
Venoocclusive disease	38.19	14.69	24	34001	4549	79705814
Malignant fibrous histiocytoma	37.38	14.69	10	34015	197	79710166
Haemodialysis	36.74	14.69	42	33983	18126	79692237
Drug resistance	36.46	14.69	65	33960	42148	79668215
Diarrhoea haemorrhagic	36.35	14.69	36	33989	13198	79697165
Injection site pain	36.10	14.69	6	34019	129832	79580531
Asthma	35.92	14.69	7	34018	135088	79575275
Mobility decreased	35.44	14.69	5	34020	122170	79588193
Acute graft versus host disease in liver	35.25	14.69	17	34008	1918	79708445
Diffuse large B-cell lymphoma	35.15	14.69	34	33991	12115	79698248
Blood triglycerides increased	34.93	14.69	44	33981	20996	79689367
Immunosuppressant drug level decreased	34.69	14.69	17	34008	1987	79708376
Drug ineffective	34.43	14.69	649	33376	1080264	78630099
Viraemia	34.33	14.69	19	34006	2850	79707513
Avian influenza	34.32	14.69	8	34017	87	79710276
Retinal scar	34.27	14.69	11	34014	417	79709946
Hyperhidrosis	34.20	14.69	11	34014	151481	79558882
Pneumonitis	33.80	14.69	78	33947	60782	79649581
Malacoplakia	33.74	14.69	12	34013	624	79709739
Wheezing	33.32	14.69	5	34020	116659	79593704
Chronic graft versus host disease in liver	33.19	14.69	12	34013	655	79709708
Rheumatoid arthritis	33.17	14.69	176	33849	208294	79502069
Tularaemia	32.94	14.69	8	34017	105	79710258
Gastroenteritis norovirus	32.92	14.69	19	34006	3087	79707276
Abdominal wall abscess	32.80	14.69	14	34011	1189	79709174
Protothecosis	32.79	14.69	7	34018	49	79710314
Lung transplant rejection	32.66	14.69	15	34010	1516	79708847
Dyspepsia	32.60	14.69	4	34021	108683	79601680
Malaise	32.58	14.69	104	33921	489765	79220598
Central nervous system lymphoma	32.55	14.69	17	34008	2272	79708091
Neurofibrosarcoma	32.00	14.69	9	34016	215	79710148
Weight increased	31.90	14.69	43	33982	277343	79433020
Drug level below therapeutic	31.43	14.69	29	33996	9741	79700622
Nephrogenic diabetes insipidus	30.78	14.69	16	34009	2118	79708245
Glossodynia	30.52	14.69	4	34021	103333	79607030
Cytomegalovirus colitis	30.39	14.69	21	34004	4664	79705699
Bradycardia	30.32	14.69	10	34015	135547	79574816
Confusional state	30.22	14.69	56	33969	317941	79392422
Blister	30.11	14.69	7	34018	119469	79590894
Depression	29.92	14.69	29	33996	216761	79493602
Contusion	29.90	14.69	13	34012	148763	79561600
Swelling	29.90	14.69	29	33996	216682	79493681
Morphoea	29.74	14.69	10	34015	439	79709924
Renal tubular injury	29.67	14.69	14	34011	1505	79708858
Inappropriate schedule of product administration	29.64	14.69	10	34015	133618	79576745
Right ventricular diastolic collapse	29.64	14.69	7	34018	81	79710282
Cytomegalovirus chorioretinitis	29.63	14.69	22	34003	5468	79704895
Reticulocyte count decreased	29.51	14.69	12	34013	902	79709461
Pulmonary alveolar haemorrhage	29.33	14.69	30	33995	11427	79698936
Globulins decreased	29.28	14.69	10	34015	461	79709902
Feeling abnormal	28.83	14.69	16	34009	159183	79551180
Alopecia scarring	28.41	14.69	7	34018	98	79710265
Gait disturbance	28.36	14.69	28	33997	207478	79502885
Drug intolerance	28.34	14.69	43	33982	264076	79446287
Rhinovirus infection	28.33	14.69	25	34000	7928	79702435
Loss of personal independence in daily activities	28.12	14.69	102	33923	102478	79607885
Polyomavirus viraemia	28.12	14.69	14	34011	1693	79708670
Obliterative bronchiolitis	28.11	14.69	17	34008	3011	79707352
Hypogammaglobulinaemia	28.00	14.69	31	33994	12920	79697443
Incorrect route of product administration	27.91	14.69	52	33973	34877	79675486
Musculoskeletal pain	27.86	14.69	5	34020	102349	79608014
Trichodysplasia spinulosa	27.65	14.69	11	34014	781	79709582
Adjusted calcium decreased	27.48	14.69	8	34017	217	79710146
Trichostasis spinulosa	27.40	14.69	5	34020	13	79710350
Human polyomavirus infection	27.31	14.69	12	34013	1094	79709269
Pleocytosis	27.30	14.69	13	34012	1426	79708937
PIK3CA related overgrowth spectrum	27.04	14.69	4	34021	0	79710363
Wound	27.01	14.69	8	34017	116171	79594192
Headache	26.98	14.69	166	33859	653606	79056757
Scedosporium infection	26.97	14.69	13	34012	1465	79708898
Abdominal pain upper	26.44	14.69	34	33991	223785	79486578
Bacillary angiomatosis	26.37	14.69	8	34017	251	79710112
Pleural effusion	26.15	14.69	127	33898	145135	79565228
Hypoaesthesia	25.92	14.69	23	34002	179329	79531034
Bacterial sepsis	25.73	14.69	24	34001	8174	79702189
Neuroendocrine carcinoma of the skin	25.34	14.69	12	34013	1300	79709063
Anaphylactic reaction	25.32	14.69	3	34022	83740	79626623
Therapy partial responder	25.17	14.69	34	33991	17363	79693000
Blastomycosis	25.15	14.69	10	34015	709	79709654
Mucormycosis	25.06	14.69	24	34001	8445	79701918
Paraesthesia	25.02	14.69	23	34002	176300	79534063
Stem cell transplant	24.97	14.69	17	34008	3687	79706676
Loss of consciousness	24.92	14.69	21	34004	167922	79542441
Arthritis	24.79	14.69	9	34016	114871	79595492
Stomatitis	24.78	14.69	126	33899	146631	79563732
Philadelphia positive chronic myeloid leukaemia	24.70	14.69	7	34018	172	79710191
Biopsy kidney abnormal	24.40	14.69	7	34018	180	79710183
Acute kidney injury	24.40	14.69	333	33692	519071	79191292
Drug level fluctuating	24.37	14.69	10	34015	769	79709594
Skin graft rejection	24.23	14.69	5	34020	29	79710334
Escherichia bacteraemia	24.12	14.69	21	34004	6541	79703822
Renal graft infection	24.06	14.69	9	34016	541	79709822
Chest pain	24.01	14.69	53	33972	282251	79428112
Glomerulosclerosis	23.96	14.69	11	34014	1111	79709252
Babesiosis	23.71	14.69	8	34017	355	79710008
Perinephric collection	23.58	14.69	8	34017	361	79710002
Hydronephrosis	23.58	14.69	33	33992	17421	79692942
Lower respiratory tract infection	23.38	14.69	13	34012	129207	79581156
Bacterial colitis	23.37	14.69	6	34019	100	79710263
Pulmonary haemorrhage	23.21	14.69	30	33995	14687	79695676
Injection site erythema	23.15	14.69	3	34022	78194	79632169
Herpes simplex	22.68	14.69	27	33998	12160	79698203
Periorbital infection	22.63	14.69	6	34019	114	79710249
Dry mouth	22.49	14.69	5	34020	88014	79622349
Diabetes mellitus	22.38	14.69	79	33946	78311	79632052
Product dose omission issue	22.28	14.69	45	33980	247492	79462871
Osteoarthritis	22.23	14.69	5	34020	87304	79623059
Abdominal discomfort	22.21	14.69	46	33979	250681	79459682
Ophthalmic herpes zoster	22.20	14.69	14	34011	2670	79707693
Toxoplasmosis	22.13	14.69	14	34011	2683	79707680
Blood pressure increased	22.10	14.69	35	33990	211325	79499038
Hyponatraemia	22.07	14.69	26	33999	177822	79532541
Heart rate increased	22.05	14.69	12	34013	120712	79589651
Enteritis	21.87	14.69	29	33996	14554	79695809
Dysplasia	21.75	14.69	11	34014	1375	79708988
Ureteric stenosis	21.70	14.69	11	34014	1381	79708982
Vomiting	21.66	14.69	181	33844	665647	79044716
Cystitis viral	21.61	14.69	9	34016	719	79709644
Metastases to lung	21.14	14.69	32	33993	18131	79692232
Psoriasis	21.13	14.69	6	34019	89581	79620782
Renal transplant failure	21.11	14.69	12	34013	1895	79708468
Product administered to patient of inappropriate age	20.87	14.69	18	34007	5535	79704828
Haemophagocytic lymphohistiocytosis	20.65	14.69	35	33990	21802	79688561
Pneumonia haemophilus	20.46	14.69	10	34015	1162	79709201
Salivary gland mass	20.42	14.69	5	34020	68	79710295
Peripheral swelling	20.25	14.69	54	33971	269563	79440800
Spirochaetal infection	20.23	14.69	4	34021	18	79710345
Lymphopenia	20.18	14.69	42	33983	30515	79679848
Exposure during pregnancy	20.06	14.69	9	34016	101123	79609240
Asthenia	20.02	14.69	132	33893	511557	79198806
Pulmonary cavitation	19.91	14.69	11	34014	1645	79708718
Hepatitis B	19.86	14.69	21	34004	8311	79702052
Disease recurrence	19.69	14.69	52	33973	44057	79666306
Chronic obstructive pulmonary disease	19.64	14.69	6	34019	85413	79624950
Jejunal perforation	19.59	14.69	7	34018	369	79709994
Discomfort	19.52	14.69	15	34010	125602	79584761
Kaposi sarcoma inflammatory cytokine syndrome	19.41	14.69	4	34021	23	79710340
Disseminated varicella zoster virus infection	19.38	14.69	8	34017	625	79709738
Adenovirus reactivation	19.36	14.69	7	34018	382	79709981
Balance disorder	19.29	14.69	9	34016	98848	79611515
Pneumocystis jirovecii infection	18.84	14.69	13	34012	2881	79707482
Clostridium difficile infection	18.72	14.69	50	33975	42635	79667728
Skin mass	18.65	14.69	20	34005	8043	79702320
Lymphangioma	18.61	14.69	4	34021	29	79710334
Respiratory distress	18.59	14.69	61	33964	58278	79652085
Graft loss	18.51	14.69	9	34016	1034	79709329
Chest discomfort	18.43	14.69	19	34006	138025	79572338
SARS-CoV-2 RNA	18.38	14.69	4	34021	31	79710332
Graft thrombosis	18.37	14.69	7	34018	443	79709920
Pulmonary toxicity	18.32	14.69	25	34000	12889	79697474
Encephalitis eastern equine	18.20	14.69	3	34022	3	79710360
Lung infiltration	18.16	14.69	34	33991	22878	79687485
Fibrosarcoma	18.16	14.69	4	34021	33	79710330
Cardio-respiratory arrest	18.11	14.69	12	34013	108498	79601865
Hepatic angiosarcoma	18.05	14.69	4	34021	34	79710329
Cytomegalovirus oesophagitis	17.97	14.69	8	34017	752	79709611
Pneumonia pseudomonal	17.96	14.69	17	34008	5894	79704469
Microangiopathic haemolytic anaemia	17.96	14.69	10	34015	1517	79708846
Ileal ulcer	17.82	14.69	9	34016	1121	79709242
Memory impairment	17.80	14.69	13	34012	111721	79598642
Staphylococcal infection	17.73	14.69	60	33965	58235	79652128
Actinic keratosis	17.65	14.69	17	34008	6025	79704338
Lymphoedema	17.57	14.69	24	34001	12389	79697974
Cardiac murmur functional	17.56	14.69	4	34021	39	79710324
Intussusception	17.53	14.69	9	34016	1161	79709202
Bladder transitional cell carcinoma	17.48	14.69	12	34013	2638	79707725
Chronic kidney disease	17.47	14.69	65	33960	66089	79644274
Thymus enlargement	17.45	14.69	5	34020	128	79710235
Bronchitis	17.42	14.69	18	34007	130626	79579737
Aplasia pure red cell	17.41	14.69	19	34006	7791	79702572
Graft ischaemia	17.38	14.69	4	34021	41	79710322
Therapeutic product effect incomplete	17.26	14.69	21	34004	141624	79568739
Urine protein/creatinine ratio increased	17.08	14.69	9	34016	1225	79709138
Renal vessel disorder	16.91	14.69	6	34019	310	79710053
Livedo reticularis	16.86	14.69	14	34011	4089	79706274
Papilloma viral infection	16.78	14.69	10	34015	1724	79708639
Nasopharyngitis	16.78	14.69	54	33971	253827	79456536
Gastrooesophageal reflux disease	16.77	14.69	12	34013	104234	79606129
Viral oesophagitis	16.67	14.69	3	34022	7	79710356
Splenic neoplasm malignancy unspecified	16.51	14.69	4	34021	52	79710311
Adverse drug reaction	16.51	14.69	4	34021	66388	79643975
Pterygium	16.46	14.69	6	34019	335	79710028
Renal failure	16.45	14.69	144	33881	200824	79509539
Inferior vena cava stenosis	16.44	14.69	4	34021	53	79710310
Suicidal ideation	16.43	14.69	6	34019	76334	79634029
Post transplant distal limb syndrome	16.42	14.69	7	34018	593	79709770
Opportunistic infection	16.32	14.69	12	34013	2938	79707425
Palpitations	16.26	14.69	18	34007	126592	79583771
Red blood cell burr cells present	16.23	14.69	4	34021	56	79710307
Decreased appetite	16.23	14.69	83	33942	342335	79368028
Jarisch-Herxheimer reaction	16.21	14.69	8	34017	949	79709414
Hepatitis E	16.19	14.69	12	34013	2974	79707389
Acquired mitochondrial DNA mutation	16.13	14.69	3	34022	9	79710354
Complications of transplanted heart	15.99	14.69	6	34019	364	79709999
ABO incompatibility	15.89	14.69	3	34022	10	79710353
Endocarditis	15.78	14.69	21	34004	10576	79699787
Depressed level of consciousness	15.72	14.69	11	34014	96641	79613722
Myocarditis toxoplasmal	15.68	14.69	4	34021	65	79710298
Alternaria infection	15.55	14.69	7	34018	675	79709688
Parvovirus B19 infection	15.55	14.69	9	34016	1471	79708892
Cat scratch disease	15.52	14.69	6	34019	395	79709968
Pyrexia	15.24	14.69	388	33637	678321	79032042
Injury	15.21	14.69	7	34018	77489	79632874
Kussmaul respiration	15.15	14.69	6	34019	421	79709942
Orbital apex syndrome	15.14	14.69	4	34021	75	79710288
COVID-19	15.06	14.69	117	33908	157557	79552806
Cachexia	15.04	14.69	21	34004	11062	79699301
Disseminated mycobacterium avium complex infection	15.04	14.69	5	34020	212	79710151
Hallucination	14.98	14.69	9	34016	85736	79624627
HIV infection	14.98	14.69	8	34017	1119	79709244
Incorrect dose administered	14.92	14.69	7	34018	76623	79633740
Blood pressure systolic increased	14.87	14.69	5	34020	66981	79643382
Acute hepatitis C	14.86	14.69	5	34020	220	79710143
Kaposi's sarcoma	14.84	14.69	7	34018	752	79709611
Rabies	14.75	14.69	3	34022	16	79710347
Acinetobacter infection	14.70	14.69	11	34014	2766	79707597

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01EG04	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PROTEIN KINASE INHIBITORS Mammalian target of rapamycin (mTOR) kinase inhibitors
ATC	L04AA10	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS IMMUNOSUPPRESSANTS IMMUNOSUPPRESSANTS Selective immunosuppressants
ATC	S01XA23	SENSORY ORGANS OPHTHALMOLOGICALS OTHER OPHTHALMOLOGICALS Other ophthalmologicals
FDA MoA	N0000175076	Protein Kinase Inhibitors
FDA PE	N0000175550	Decreased Immunologic Activity
CHEBI has role	CHEBI:35610	antineoplastic agents
CHEBI has role	CHEBI:35705	immunosuppressive agents
CHEBI has role	CHEBI:36047	antibacterial drugs
CHEBI has role	CHEBI:68481	mTOR inhibitors
CHEBI has role	CHEBI:149553	anticoronaviral drug
CHEBI has role	CHEBI:176497	geroprotectors
FDA EPC	N0000175605	Kinase Inhibitor
FDA MoA	N0000175624	mTOR Inhibitors
FDA EPC	N0000175625	mTOR Inhibitor Immunosuppressant
MeSH PA	D000900	Anti-Bacterial Agents
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D000903	Antibiotics, Antineoplastic
MeSH PA	D000935	Antifungal Agents
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D007155	Immunologic Factors
MeSH PA	D007166	Immunosuppressive Agents

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Gorham's disease	indication	1515008
Tuberous sclerosis syndrome	indication	7199000	DOID:13515
Lymphangiectasis	indication	48087001
Pulmonary lymphangioleiomyomatosis	indication	277844007	DOID:3319
Lymphangioma	indication	400178008	DOID:1475
Lymphangiomatosis	indication	403546006
Renal cell carcinoma	indication	702391001	DOID:4450
Prevention of Kidney Transplant Rejection	indication
Coronavirus infection	off-label use	186747009
Prevention of Cardiac Transplant Rejection	off-label use
Hypercholesterolemia	contraindication	13644009
Hyperbilirubinemia	contraindication	14783006	DOID:2741
Transplantation of liver	contraindication	18027006
Progressive multifocal leukoencephalopathy	contraindication	22255007	DOID:643
Cytomegalovirus infection	contraindication	28944009
Proteinuria	contraindication	29738008	DOID:576
Hypertensive disorder	contraindication	38341003	DOID:10763
Infectious disease	contraindication	40733004
Body fluid retention	contraindication	43498006
Gastrointestinal perforation	contraindication	51875005
Hyperlipidemia	contraindication	55822004	DOID:1168
Acute infectious disease	contraindication	63171007
Interstitial pneumonia	contraindication	64667001
Diabetes mellitus	contraindication	73211009	DOID:9351
Hyperglycemia	contraindication	80394007	DOID:4195
Transplant of lung	contraindication	88039007
Kidney disease	contraindication	90708001	DOID:557
Secondary malignant neoplasm of cerebrum	contraindication	94248000
Malignant lymphoma	contraindication	118600007	DOID:0060058
Perioperative care	contraindication	133897009
Cerebrovascular accident	contraindication	230690007
Interstitial lung disease	contraindication	233703007	DOID:3082
Lymphedema	contraindication	234097001	DOID:4977
Disease of liver	contraindication	235856003	DOID:409
Impaired wound healing	contraindication	271618001
Peripheral edema	contraindication	271809000
Pregnancy, function	contraindication	289908002
Hypertriglyceridemia	contraindication	302870006
Primary malignant neoplasm	contraindication	372087000
Malignant neoplasm of skin	contraindication	372130007	DOID:4159
Pericardial effusion	contraindication	373945007	DOID:118
Surgical procedure	contraindication	387713003
Ascites	contraindication	389026000
Breastfeeding (mother)	contraindication	413712001
Pneumocystosis jiroveci pneumonia	contraindication	415125002	DOID:11339
Malignant neoplasm of brain	contraindication	428061005	DOID:1319
Bronchial Anastomotic Dehiscence in Lung Transplant	contraindication
Pleural Effusions	contraindication
Sirolimus Toxicity	contraindication
Hepatic Artery Thrombosis in Liver Transplant	contraindication
BK Polyomavirus Reactivation Nephropathy	contraindication

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	10.5	acidic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
100MG/VIAL	FYARRO	AADI	N213312	Nov. 22, 2021	RX	POWDER	INTRAVENOUS	8911786	Feb. 14, 2029	TREATMENT OF ADULT PATIENTS WITH LOCALLY ADVANCED UNRESECTABLE OR METASTATIC MALIGNANT PERIVASCULAR EPITHELIOID CELL TUMOR (PECOMA)
100MG/VIAL	FYARRO	AADI	N213312	Nov. 22, 2021	RX	POWDER	INTRAVENOUS	10973806	June 29, 2036	TREATMENT OF ADULT PATIENTS WITH LOCALLY ADVANCED UNRESECTABLE OR METASTATIC MALIGNANT PERIVASCULAR EPITHELIOID CELL TUMOR (PECOMA) WITH A DOSE BETWEEN ABOUT 56 MG/M2 AND ABOUT 100 MG/M2 ADMINISTERED ON DAYS 1 AND 8 OF A 21-DAY CYCLE

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
100MG/VIAL	FYARRO	AADI	N213312	Nov. 22, 2021	RX	POWDER	INTRAVENOUS	Nov. 22, 2024	NEW PRODUCT
0.2%	HYFTOR	NOBELPHARMA	N213478	March 22, 2022	RX	GEL	TOPICAL	March 22, 2025	NEW PRODUCT
100MG/VIAL	FYARRO	AADI	N213312	Nov. 22, 2021	RX	POWDER	INTRAVENOUS	Nov. 22, 2028	FOR THE TREATMENT OF ADULT PATIENTS WITH LOCALLY ADVANCED UNRESECTABLE OR METASTATIC MALIGNANT PERIVASCULAR EPITHELIOID CELL TUMOR (PECOMA)
0.2%	HYFTOR	NOBELPHARMA	N213478	March 22, 2022	RX	GEL	TOPICAL	March 22, 2029	TREATMENT OF FACIAL ANGIOFIBROMA ASSOCIATED WITH TUBEROUS SCLEROSIS IN ADULTS AND PEDIATRIC PATIENTS 6 YEARS OF AGE AND OLDER

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Peptidyl-prolyl cis-trans isomerase FKBP1A	Enzyme	P62942	FKB1A_HUMAN	INHIBITOR	Kd	8.96	WOMBAT-PK	CHEMBL
Cytochrome P450 3A4	Enzyme	P08684	CP3A4_HUMAN		IC50	5.70	DRUG MATRIX
Multidrug resistance protein 1	Transporter	P08183	MDR1_HUMAN		IC50	6.20	WOMBAT-PK
ATP-binding cassette sub-family G member 2	Transporter	Q9UNQ0	ABCG2_HUMAN		IC50	5.72	CHEMBL
Cytochrome P450 2C9	Enzyme	P11712	CP2C9_HUMAN		IC50	5.70	DRUG MATRIX
Serine/threonine-protein kinase mTOR	Kinase	P42345	MTOR_HUMAN		IC50	10	CHEMBL
Peptidyl-prolyl cis-trans isomerase FKBP3	Enzyme	Q00688	FKBP3_HUMAN		Kd	9.70	WOMBAT-PK
Cytochrome P450 2C19	Enzyme	P33261	CP2CJ_HUMAN		IC50	5.40	DRUG MATRIX
Peptidyl-prolyl cis-trans isomerase FKBP1B	Enzyme	P68106	FKB1B_HUMAN		Kd	9.70	CHEMBL
Peptidyl-prolyl cis-trans isomerase FKBP5	Enzyme	Q13451	FKBP5_HUMAN		Ki	8.52	CHEMBL
Programmed cell death protein 4	Nuclear other	Q53EL6	PDCD4_HUMAN		EC50	7.30	CHEMBL
Eukaryotic translation initiation factor 4E	Nuclear other	P06730	IF4E_HUMAN		Kd	9.30	CHEMBL
Sodium/nucleoside cotransporter 1	Transporter	O00337	S28A1_HUMAN		Ki	6.43	DRUG MATRIX
Peptidyl-prolyl cis-trans isomerase FKBP1A	Enzyme		FKB1A_MOUSE		IC50	9	CHEMBL
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1	Enzyme		AT2A1_RABIT		IC50	4.11	CHEMBL
Serine/threonine-protein kinase mTOR	Kinase		MTOR_MOUSE		IC50	10.30	CHEMBL

External reference:

ID	Source
4021176	VUID
N0000148624	NUI
D00753	KEGG_DRUG
4021176	VANDF
C0072980	UMLSCUI
CHEBI:9168	CHEBI
CHEMBL413	ChEMBL_ID
D020123	MESH_DESCRIPTOR_UI
DB00877	DRUGBANK_ID
6031	IUPHAR_LIGAND_ID
7104	INN_ID
W36ZG6FT64	UNII
5284616	PUBCHEM_CID
258355	RXNORM
210889	MMSL
31418	MMSL
8303	MMSL
d04453	MMSL
007885	NDDF
116109004	SNOMEDCT_US
387014003	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Rapamune	HUMAN PRESCRIPTION DRUG LABEL	1	0008-1030	SOLUTION	1 mg	ORAL	NDA	34 sections
Rapamune	HUMAN PRESCRIPTION DRUG LABEL	1	0008-1030	SOLUTION	1 mg	ORAL	NDA	34 sections
Rapamune	HUMAN PRESCRIPTION DRUG LABEL	1	0008-1030	SOLUTION	1 mg	ORAL	NDA	34 sections
Rapamune	HUMAN PRESCRIPTION DRUG LABEL	1	0008-1040	TABLET, SUGAR COATED	0.50 mg	ORAL	NDA	34 sections
Rapamune	HUMAN PRESCRIPTION DRUG LABEL	1	0008-1040	TABLET, SUGAR COATED	0.50 mg	ORAL	NDA	34 sections
Rapamune	HUMAN PRESCRIPTION DRUG LABEL	1	0008-1040	TABLET, SUGAR COATED	0.50 mg	ORAL	NDA	34 sections
Rapamune	HUMAN PRESCRIPTION DRUG LABEL	1	0008-1041	TABLET, SUGAR COATED	1 mg	ORAL	NDA	34 sections
Rapamune	HUMAN PRESCRIPTION DRUG LABEL	1	0008-1041	TABLET, SUGAR COATED	1 mg	ORAL	NDA	34 sections
Rapamune	HUMAN PRESCRIPTION DRUG LABEL	1	0008-1041	TABLET, SUGAR COATED	1 mg	ORAL	NDA	34 sections
Rapamune	HUMAN PRESCRIPTION DRUG LABEL	1	0008-1042	TABLET, SUGAR COATED	2 mg	ORAL	NDA	34 sections
Rapamune	HUMAN PRESCRIPTION DRUG LABEL	1	0008-1042	TABLET, SUGAR COATED	2 mg	ORAL	NDA	34 sections
Rapamune	HUMAN PRESCRIPTION DRUG LABEL	1	0008-1042	TABLET, SUGAR COATED	2 mg	ORAL	NDA	34 sections
sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	0904-7147	TABLET, FILM COATED	1 mg	ORAL	ANDA	29 sections
sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	0904-7147	TABLET, FILM COATED	1 mg	ORAL	ANDA	29 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	0904-7248	TABLET	1 mg	ORAL	ANDA	29 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	13668-658	SOLUTION	1 mg	ORAL	ANDA	22 sections
sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	16714-187	TABLET, FILM COATED	0.50 mg	ORAL	ANDA	30 sections
sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	16714-187	TABLET, FILM COATED	0.50 mg	ORAL	ANDA	30 sections
sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	16714-188	TABLET, FILM COATED	1 mg	ORAL	ANDA	30 sections
sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	16714-188	TABLET, FILM COATED	1 mg	ORAL	ANDA	30 sections
sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	16714-189	TABLET, FILM COATED	2 mg	ORAL	ANDA	30 sections
sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	16714-189	TABLET, FILM COATED	2 mg	ORAL	ANDA	30 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	50268-718	TABLET	1 mg	ORAL	ANDA	29 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	55111-653	TABLET	1 mg	ORAL	ANDA	28 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	55111-653	TABLET	1 mg	ORAL	ANDA	28 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	55111-654	TABLET	2 mg	ORAL	ANDA	28 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	55111-654	TABLET	2 mg	ORAL	ANDA	28 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	59762-1001	TABLET, SUGAR COATED	0.50 mg	ORAL	NDA AUTHORIZED GENERIC	31 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	59762-1001	TABLET, SUGAR COATED	0.50 mg	ORAL	NDA AUTHORIZED GENERIC	31 sections
Sirolimus	HUMAN PRESCRIPTION DRUG LABEL	1	59762-1002	TABLET, SUGAR COATED	1 mg	ORAL	NDA AUTHORIZED GENERIC	31 sections