Adverse Drug Reaction Classification System

Pharmaceutical Information
Drug Name Sirolimus
Drug ID BADD_D02028
Description Sirolimus, also known as rapamycin, is a macrocyclic lactone antibiotic produced by bacteria _Streptomyces hygroscopicus_, which was isolated from the soil of the Vai Atari region of Rapa Nui (Easter Island).[A242412] It was first isolated and identified as an antifungal agent with potent anticandida activity; however, after its potent antitumor and immunosuppressive activities were later discovered, it was extensively investigated as an immunosuppressive and antitumour agent.[A13448] Its primary mechanism of action is the inhibition of the mammalian target of rapamycin (mTOR), which is a serine/threonine-specific protein kinase that regulates cell growth, proliferation, and survival. mTOR is an important therapeutic target for various diseases, as it was shown to regulate longevity and maintain normal glucose homeostasis.[A242417] Targeting mTOR received more attention especially in cancer, as mTOR signalling pathways are constitutively activated in many types of human cancer.[A1320] Sirolimus was first approved by the FDA in 1999 for the prophylaxis of organ rejection in patients aged 13 years and older receiving renal transplants.[A242372] In November 2000, the drug was recognized by the European Agency as an alternative to calcineurin antagonists for maintenance therapy with corticosteroids.[A242412] In May 2015, the FDA approved sirolimus for the treatment of patients with lymphangioleiomyomatosis.[L39292] In November 2021, albumin-bound sirolimus for intravenous injection was approved by the FDA for the treatment of adults with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumour (PEComa).[L39267] Sirolimus was also investigated in other cancers such as skin cancer, Kaposi’s Sarcoma, cutaneous T-cell lymphomas, and tuberous sclerosis.[A242372]
Indications and Usage Sirolimus is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving renal transplants. In patients at low-to moderate-immunologic risk, it is recommended that sirolimus be used initially in a regimen with [cyclosporine] and corticosteroids; cyclosporine should be withdrawn two to four months after transplantation. In patients at high-immunologic risk (defined as Black recipients and/or repeat renal transplant recipients who lost a previous allograft for immunologic reason and/or patients with high panel-reactive antibodies [PRA; peak PRA level > 80%]), it is recommended that sirolimus be used in combination with cyclosporine and corticosteroids for the first year following transplantation.[L19809] It is also used to treat lymphangioleiomyomatosis.[L19809] In the US, albumin-bound sirolimus for intravenous injection is indicated for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumour (PEComa).[L39267] In Europe, it is recommended that sirolimus for the prophylaxis of organ rejection in renal transplants is used in combination with cyclosporin microemulsion and corticosteroids for two to three months. Sirolimus may be continued as maintenance therapy with corticosteroids only if cyclosporin microemulsion can be progressively discontinued.[L7021]
Marketing Status approved; investigational
ATC Code L01EG04; L04AA10; S01XA23
DrugBank ID DB00877
KEGG ID D00753
MeSH ID D020123
PubChem ID 5284616
TTD Drug ID D03LJR
NDC Product Code 42816-1041; 55500-0011; 16714-188; 68382-520; 69238-1594; 59573-0004; 16714-189; 50268-718; 59762-1205; 60505-6197; 65841-772; 68382-352; 68462-683; 68462-684; 42816-1040; 0008-1030; 59762-1001; 65841-771; 70518-3546; 59762-1002; 67877-747; 68462-682; 70518-3547; 73683-101; 42816-1042; 57885-0014; 62991-3184; 68254-1006; 71052-202; 67877-748; 72205-099; 51187-0010; 65727-013; 73212-019; 16714-187; 0008-1040; 68084-915; 68382-351; 0008-1041; 0008-1042; 65841-773; 66689-347; 51552-1608; 73377-024; 42513-0013; 55111-654; 59762-1003; 80803-153; 0904-7248; 55486-1571; 56125-800; 67877-746; 55111-653
UNII W36ZG6FT64
Synonyms Sirolimus | Rapamycin | I-2190A | I 2190A | I2190A | AY 22-989 | AY 22 989 | AY 22989 | Rapamune
Chemical Information
Molecular Formula C51H79NO13
CAS Registry Number 53123-88-9
SMILES CC1CCC2CC(C(=CC=CC=CC(CC(C(=O)C(C(C(=CC(C(=O)CC(OC(=O)C3CCCCN3C(=O)C(=O)C1(O2)O) C(C)CC4CCC(C(C4)OC)O)C)C)O)OC)C)C)C)OC
Chemical Structure
ADRs Induced by Drug
*The priority for ADR severity classification is based on FAERS assessment, followed by the most severe level in CTCAE rating. If neither is available, it will be displayed as 'Not available'.
**The 'Not Available' level is hidden by default and can be restored by clicking on the legend twice..
ADR Term ADReCS ID ADR Frequency (FAERS) ADR Severity Grade (FAERS) ADR Severity Grade (CTCAE)
Graft versus host disease12.02.09.001; 10.02.01.0270.001233%Not Available
Haematochezia24.07.02.012; 07.12.02.0030.000335%Not Available
Haematuria21.10.01.018; 24.07.01.047; 20.02.01.006--
Haemoglobin13.01.05.018--Not Available
Haemolytic uraemic syndrome01.06.02.001; 20.01.03.0110.000268%
Haemoptysis02.11.04.009; 24.07.01.006; 22.02.03.0040.000268%Not Available
Hallucination19.10.04.003--
Headache17.14.01.001--
Hepatic artery thrombosis24.01.03.002; 09.01.06.005--Not Available
Hepatic cirrhosis09.01.04.0010.000134%Not Available
Hepatic failure09.01.03.0020.000402%
Hepatic necrosis09.01.07.002--
Hepatitis09.01.07.0040.000134%Not Available
Hepatocellular injury09.01.07.008--Not Available
Hepatotoxicity12.03.01.008; 09.01.07.009--Not Available
Hernia08.01.04.0010.000201%Not Available
Herpes simplex23.11.05.004; 11.05.02.001--Not Available
Herpes zoster23.11.05.005; 17.09.03.026; 11.05.02.003--
Hiccups22.12.01.001; 07.01.06.009--
Hirsutism05.05.01.005; 23.02.04.001--
Hydronephrosis20.01.05.001--Not Available
Hyperammonaemia09.01.02.002; 14.10.01.0010.000134%Not Available
Hyperbilirubinaemia14.11.01.010; 09.01.01.003; 01.06.04.003--Not Available
Hypercalcaemia05.04.01.002; 14.04.01.003--
Hypercholesterolaemia14.08.01.0010.001742%Not Available
Hyperglycaemia14.06.02.002; 05.06.02.002--
Hyperhidrosis23.02.03.004; 08.01.03.028--
Hyperkalaemia14.05.03.0010.000201%
Hyperlactacidaemia14.01.01.006--Not Available
Hyperphosphataemia14.04.03.007--
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ADReCS-Target
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