ciclosporin indications/contra

Stem definitionDrug idCAS RN
760 59865-13-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • ciclosporin
  • cyclosporine
  • cyclosporin
  • ciclosporine
  • cyclosporin A
A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).
  • Molecular weight: 1202.64
  • Formula: C62H111N11O12
  • CLOGP: 14.36
  • LIPINSKI: 3
  • HAC: 23
  • HDO: 5
  • TPSA: 278.80
  • ALOGS: -5.10
  • ROTB: 15

Drug dosage:

DoseUnitRoute
0.25 g O
0.25 g P

Approvals:

DateAgencyCompanyOrphan
Nov. 14, 1983 FDA NOVARTIS

FDA Adverse Event Reporting System

scroll-->
MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Cytomegalovirus infection 4073.03 26.10 915 19422 3592 3361930
Pyrexia 3228.87 26.10 1520 18817 79595 3285927
Blood creatinine increased 2971.68 26.10 998 19339 20820 3344702
Eye irritation 2828.17 26.10 672 19665 3527 3361995
Graft versus host disease 2811.11 26.10 610 19727 1937 3363585
Renal impairment 2542.48 26.10 850 19487 17411 3348111
Acute graft versus host disease 2422.31 26.10 508 19829 1294 3364228
Kidney transplant rejection 2126.41 26.10 449 19888 1194 3364328
Transplant rejection 1943.07 26.10 436 19901 1675 3363847
Sepsis 1778.47 26.10 764 19573 31609 3333913
Drug ineffective 1697.29 26.10 1130 19207 114960 3250562
Chronic graft versus host disease 1680.05 26.10 349 19988 829 3364693
Posterior reversible encephalopathy syndrome 1600.61 26.10 405 19932 2849 3362673
Nephropathy toxic 1561.64 26.10 393 19944 2696 3362826
Multiple organ dysfunction syndrome 1519.13 26.10 546 19791 13864 3351658
Acute graft versus host disease in skin 1467.54 26.10 298 20039 601 3364921
Epstein-Barr virus infection 1466.02 26.10 333 20004 1365 3364157
Hypertension 1300.75 26.10 649 19688 37817 3327705
Acute kidney injury 1290.28 26.10 702 19635 48981 3316541
Immunosuppressant drug level increased 1194.08 26.10 249 20088 605 3364917
Renal failure 1131.22 26.10 562 19775 32378 3333144
Post transplant lymphoproliferative disorder 1114.82 26.10 231 20106 537 3364985
Thrombotic microangiopathy 1053.53 26.10 268 20069 1924 3363598
Graft versus host disease in gastrointestinal tract 1038.15 26.10 198 20139 235 3365287
Eye pain 1022.14 26.10 327 20010 5720 3359802
Pneumonia 978.80 26.10 666 19671 69477 3296045
Aspergillus infection 945.62 26.10 236 20101 1551 3363971
Graft versus host disease in skin 939.64 26.10 183 20154 263 3365259
Complications of transplanted kidney 938.49 26.10 202 20135 602 3364920
Acute graft versus host disease in intestine 932.39 26.10 187 20150 342 3365180

Pharmacologic Action:

scroll-->
SourceCodeDescription
ATC L04AD01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
IMMUNOSUPPRESSANTS
IMMUNOSUPPRESSANTS
Calcineurin inhibitors
ATC S01XA18 SENSORY ORGANS
OPHTHALMOLOGICALS
OTHER OPHTHALMOLOGICALS
Other ophthalmologicals
MeSH PA D000890 Anti-Infective Agents
MeSH PA D000935 Antifungal Agents
MeSH PA D018501 Antirheumatic Agents
MeSH PA D065095 Calcineurin Inhibitors
MeSH PA D003879 Dermatologic Agents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D007155 Immunologic Factors
MeSH PA D007166 Immunosuppressive Agents
CHEBI has role CHEBI:35842 antirheumatic drug
CHEBI has role CHEBI:50177 dermatologic drug
CHEBI has role CHEBI:35705 immunosuppressive agent
CHEBI has role CHEBI:49167 anti-asthmatic drug
FDA EPC N0000175457 Calcineurin Inhibitor Immunosuppressant
FDA MoA N0000182141 Cytochrome P450 3A4 Inhibitors
FDA MoA N0000185503 P-Glycoprotein Inhibitors

Drug Use (View source of the data)

scroll-->
DiseaseRelationSNOMED_IDDOID
Tear film insufficiency indication 46152009 DOID:10140
Rheumatoid arthritis indication 69896004 DOID:7148
Keratoconjunctivitis sicca indication 302896008 DOID:12895
Prevention of Cardiac Transplant Rejection indication
Prevention of Liver Transplant Rejection indication
Severe Recalcitrant Psoriasis indication
Prevention of Kidney Transplant Rejection indication
Hypercholesterolemia contraindication 13644009
Hyperkalemia contraindication 14140009
Hyperbilirubinemia contraindication 14783006 DOID:2741
Metabolic acidosis, normal anion gap, acidifying salts contraindication 18104000
Hyperuricemia contraindication 35885006 DOID:1920
Hypertensive disorder contraindication 38341003 DOID:10763
Infectious disease contraindication 40733004
Benign intracranial hypertension contraindication 68267002 DOID:11459
Thrombotic thrombocytopenic purpura contraindication 78129009 DOID:10772
Disorder of brain contraindication 81308009 DOID:936
Kidney disease contraindication 90708001 DOID:2527
Neoplasm contraindication 108369006
Malignant lymphoma contraindication 118600007 DOID:0060058
Eye infection contraindication 128351009
Seizure disorder contraindication 128613002 DOID:1826
Liver function tests abnormal contraindication 166603001
Hypomagnesemia contraindication 190855004
Disease of liver contraindication 235856003 DOID:409
Toxic nephropathy contraindication 236514003
Hypertriglyceridemia contraindication 302870006
Primary malignant neoplasm contraindication 372087000
Breastfeeding (mother) contraindication 413712001
Hypertensive urgency contraindication 443482000
BK Polyomavirus Reactivation Nephropathy contraindication
Cyclosporine Toxicity contraindication
Graft-versus-host disease off-label use 234646005
Prevention of Lung Transplant Rejection off-label use
Prevention of Graft Versus Host Disease off-label use
Pure Red Cell Aplasia associated with Chronic Lymphocytic Leukemia off-label use

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

scroll-->
Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
0.05% RESTASIS ALLERGAN N050790 Dec. 23, 2002 RX EMULSION OPHTHALMIC 8633162 Aug. 27, 2024 INCREASE TEAR PRODUCTION TO TREAT PATIENTS WITH KERATOCONJUNCTIVITIS SICCA (DRY EYE).
0.05% RESTASIS MULTIDOSE ALLERGAN N050790 Oct. 27, 2016 RX EMULSION OPHTHALMIC 8633162 Aug. 27, 2024 INCREASE TEAR PRODUCTION TO TREAT PATIENTS WITH KERATOCONJUNCTIVITIS SICCA (DRY EYE).
0.05% RESTASIS ALLERGAN N050790 Dec. 23, 2002 RX EMULSION OPHTHALMIC 8648048 Aug. 27, 2024 INCREASE TEAR PRODUCTION IN PATIENTS WITH KERATOCONJUNCTIVITIS SICCA (DRY EYE).
0.05% RESTASIS MULTIDOSE ALLERGAN N050790 Oct. 27, 2016 RX EMULSION OPHTHALMIC 8648048 Aug. 27, 2024 INCREASE TEAR PRODUCTION IN PATIENTS WITH KERATOCONJUNCTIVITIS SICCA (DRY EYE).
0.05% RESTASIS ALLERGAN N050790 Dec. 23, 2002 RX EMULSION OPHTHALMIC 9248191 Aug. 27, 2024 INCREASE TEAR PRODUCTION TO TREAT PATIENTS WITH KERATOCONJUNCTIVITIS SICCA (DRY EYE).
0.05% RESTASIS MULTIDOSE ALLERGAN N050790 Oct. 27, 2016 RX EMULSION OPHTHALMIC 9248191 Aug. 27, 2024 INCREASE TEAR PRODUCTION TO TREAT PATIENTS WITH KERATOCONJUNCTIVITIS SICCA (DRY EYE).

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

scroll-->
TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Peptidyl-prolyl cis-trans isomerase A Enzyme MODULATOR IC50 8.05 WOMBAT-PK CHEMBL
Dihydroorotate dehydrogenase (quinone), mitochondrial Enzyme IC50 6.70 WOMBAT-PK
Peptidyl-prolyl cis-trans isomerase FKBP1A Enzyme IC50 7.80 WOMBAT-PK
Substance-K receptor GPCR Ki 5.86 DRUG MATRIX
Multidrug resistance protein 1 Transporter EC50 6.30 WOMBAT-PK
Cytochrome P450 3A4 Enzyme Ki 5.31 WOMBAT-PK
Sodium/bile acid cotransporter Transporter INHIBITOR IC50 6 IUPHAR
Solute carrier organic anion transporter family member 1B3 Transporter INHIBITOR IC50 6.10 IUPHAR
fMet-Leu-Phe receptor GPCR ANTAGONIST EC50 6.30 IUPHAR
Canalicular multispecific organic anion transporter 1 Transporter IC50 4.87 CHEMBL
Multidrug resistance-associated protein 1 Transporter IC50 5.57 CHEMBL
Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform Enzyme Kd 8.40 CHEMBL
Peptidyl-prolyl cis-trans isomerase D Enzyme Ki 8.15 CHEMBL
Peptidyl-prolyl cis-trans isomerase B Enzyme Kd 8.01 CHEMBL
Peptidyl-prolyl cis-trans isomerase FKBP1B Enzyme Ki 8.22 CHEMBL
Peptidyl-prolyl cis-trans isomerase FKBP4 Enzyme IC50 7.80 CHEMBL
ATP-binding cassette sub-family G member 2 Transporter IC50 4.20 CHEMBL
Bile salt export pump Transporter IC50 6.30 CHEMBL
Solute carrier organic anion transporter family member 1B1 Transporter INHIBITOR Ki 7.29 IUPHAR
Reverse transcriptase/RNaseH Enzyme IC50 6.34 CHEMBL
Bile salt export pump Unclassified IC50 6.22 CHEMBL

External reference:

scroll-->
IDSource
DB00091 DRUGBANK_ID
4018761 VUID
N0000147064 NUI
C0010592 UMLSCUI
1024 IUPHAR_LIGAND_ID
D00184 KEGG_DRUG
CHEMBL160 ChEMBL_ID
3008 RXNORM
80906007 SNOMEDCT_US
4521 MMSL
d00079 MMSL
4018761 VANDF
31626 MMSL
72396 MMSL
N0000147064 NDFRT
N0000007346 NDFRT
003420 NDDF
387467008 SNOMEDCT_US
83HN0GTJ6D UNII
5086 INN_ID
5284373 PUBCHEM_CID
D016572 MESH_DESCRIPTOR_UI
CHEBI:4031 CHEBI

Pharmaceutical products:

scroll-->
ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
Restasis MultiDose HUMAN PRESCRIPTION DRUG LABEL 1 0023-5301 EMULSION 0.50 mg OPHTHALMIC NDA 15 sections
RESTASIS HUMAN PRESCRIPTION DRUG LABEL 1 0023-9163 EMULSION 0.50 mg OPHTHALMIC NDA 14 sections
Gengraf HUMAN PRESCRIPTION DRUG LABEL 1 0074-0541 CAPSULE 50 mg ORAL ANDA 13 sections
Gengraf HUMAN PRESCRIPTION DRUG LABEL 1 0074-3108 CAPSULE 25 mg ORAL ANDA 13 sections
Gengraf HUMAN PRESCRIPTION DRUG LABEL 1 0074-3109 CAPSULE 100 mg ORAL ANDA 13 sections
Gengraf HUMAN PRESCRIPTION DRUG LABEL 1 0074-6463 CAPSULE 25 mg ORAL ANDA 13 sections
Gengraf HUMAN PRESCRIPTION DRUG LABEL 1 0074-6479 CAPSULE 100 mg ORAL ANDA 13 sections
Gengraf HUMAN PRESCRIPTION DRUG LABEL 1 0074-7269 SOLUTION 100 mg ORAL ANDA 13 sections
Sandimmune HUMAN PRESCRIPTION DRUG LABEL 1 0078-0109 INJECTION 50 mg INTRAVENOUS NDA 20 sections
Sandimmune HUMAN PRESCRIPTION DRUG LABEL 1 0078-0110 SOLUTION 100 mg ORAL NDA 20 sections
Sandimmune HUMAN PRESCRIPTION DRUG LABEL 1 0078-0240 CAPSULE, LIQUID FILLED 25 mg ORAL NDA 20 sections
Sandimmune HUMAN PRESCRIPTION DRUG LABEL 1 0078-0241 CAPSULE, LIQUID FILLED 100 mg ORAL NDA 20 sections
Neoral HUMAN PRESCRIPTION DRUG LABEL 1 0078-0246 CAPSULE, LIQUID FILLED 25 mg ORAL NDA 20 sections
Neoral HUMAN PRESCRIPTION DRUG LABEL 1 0078-0248 CAPSULE, LIQUID FILLED 100 mg ORAL NDA 20 sections
Neoral HUMAN PRESCRIPTION DRUG LABEL 1 0078-0274 SOLUTION 100 mg ORAL NDA 20 sections
Cyclosporine HUMAN PRESCRIPTION DRUG LABEL 1 0093-5740 CAPSULE, LIQUID FILLED 25 mg ORAL ANDA 12 sections
Cyclosporine HUMAN PRESCRIPTION DRUG LABEL 1 0093-5741 CAPSULE, LIQUID FILLED 50 mg ORAL ANDA 12 sections
Cyclosporine HUMAN PRESCRIPTION DRUG LABEL 1 0093-5742 CAPSULE, LIQUID FILLED 100 mg ORAL ANDA 12 sections
Cyclosporine HUMAN PRESCRIPTION DRUG LABEL 1 0172-7313 SOLUTION 100 mg ORAL ANDA 12 sections
Cyclosporine HUMAN PRESCRIPTION DRUG LABEL 1 0185-0932 CAPSULE 25 mg ORAL ANDA 13 sections
Cyclosporine HUMAN PRESCRIPTION DRUG LABEL 1 0185-0933 CAPSULE 100 mg ORAL ANDA 13 sections
Cyclosporine HUMAN PRESCRIPTION DRUG LABEL 1 0574-0866 INJECTION, SOLUTION 50 mg INTRAVENOUS ANDA 13 sections
CycloSPORINE HUMAN PRESCRIPTION DRUG LABEL 1 0591-2222 CAPSULE, LIQUID FILLED 25 mg ORAL ANDA 13 sections
CycloSPORINE HUMAN PRESCRIPTION DRUG LABEL 1 0591-2223 CAPSULE, LIQUID FILLED 100 mg ORAL ANDA 13 sections
CycloSPORINE HUMAN PRESCRIPTION DRUG LABEL 1 0591-2224 SOLUTION 100 mg ORAL ANDA 13 sections
RESTASIS HUMAN PRESCRIPTION DRUG LABEL 1 50090-1242 EMULSION 0.50 mg OPHTHALMIC NDA 14 sections
Cyclosporine HUMAN PRESCRIPTION DRUG LABEL 1 51862-458 CAPSULE, LIQUID FILLED 25 mg ORAL ANDA 14 sections
Cyclosporine HUMAN PRESCRIPTION DRUG LABEL 1 51862-460 CAPSULE, LIQUID FILLED 100 mg ORAL ANDA 14 sections
RESTASIS HUMAN PRESCRIPTION DRUG LABEL 1 54868-4793 EMULSION 0.50 mg OPHTHALMIC NDA 11 sections
Cyclosporine HUMAN PRESCRIPTION DRUG LABEL 1 54868-5522 CAPSULE, LIQUID FILLED 100 mg ORAL ANDA 12 sections