Ciclosporin
L04A - Immunosuppressants
ATC L04AA01
Protein
approved 1983
Oral
Parenteral
Topical
Natural product
Orphan
Narrow therapeutic index
Black-box warning
JFDA label: SANDIMMUN NEORAL SOL
⚠ Black-Box Warning
- carcinogenicity — ChEMBL drug_warning (Black Box Warning) | United States
- immune system toxicity — ChEMBL drug_warning (Black Box Warning) | United States
- nephrotoxicity — ChEMBL drug_warning (Black Box Warning) | United States
- vascular toxicity — ChEMBL drug_warning (Black Box Warning) | United States
- infectious disease — ChEMBL drug_warning (Black Box Warning) | United States
Mechanism of Action
Modulator of Peptidyl-prolyl cis-trans isomerase A — Cyclophilin A modulator
| Target | Action | Gene / class |
|---|---|---|
| Peptidyl-prolyl cis-trans isomerase A efficacy | MODULATOR | PPIA |
Indications
Approved
- Arthritis, Rheumatoid — rheumatoid arthritis
- Conjunctivitis — conjunctivitis
- Corneal Diseases — corneal disease
- Eye Diseases — eye disease
- Immune System Diseases — immune system disease
- Inflammation — inflammation
- Keratitis — keratitis
- Keratoconjunctivitis — keratoconjunctivitis
- Psoriasis — psoriasis
Off-label
- Acute Kidney Injury
- Anemia, Aplastic
- Anemia, Hemolytic, Autoimmune
- Aortic Aneurysm, Abdominal
- Behcet Syndrome
- Brain Injuries
- Breast Neoplasms
- Bronchiolitis Obliterans
- Bronchiolitis Obliterans Syndrome
- Burkitt Lymphoma
- Carcinoma, Hepatocellular
- Colorectal Neoplasms
- Conjunctivitis, Allergic
- Cystitis, Interstitial
- Dermatitis, Atopic
- Dermatomyositis
- Diabetes Mellitus
- Diabetes Mellitus, Type 1
- Dry Eye Syndromes
- Eczema
- Endocardial Cushion Defects
- Fallopian Tube Neoplasms
- Glaucoma
- Glomerulonephritis, Membranoproliferative
- Glomerulonephritis, Membranous
- Glomerulosclerosis, Focal Segmental
- Graft vs Host Disease
- Granulomatous Disease, Chronic
- HIV Infections
- Heart Arrest
- Heart Diseases
- Hematologic Neoplasms
- Hepatitis C
- Hepatitis C, Chronic
- Hepatitis, Autoimmune
- Hodgkin Disease
- Hyperlipoproteinemia Type I
- Infections
- Kidney Diseases
- Kidney Failure, Chronic
- Kidney Neoplasms
- Lacrimal Apparatus Diseases
- Leprosy
- Leukemia
- Leukemia, Large Granular Lymphocytic
- Leukemia, Lymphocytic, Chronic, B-Cell
- Leukemia, Mast-Cell
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Leukemia, Myeloid, Acute
- Leukemia, Prolymphocytic, B-Cell
- Leukemia, Prolymphocytic, T-Cell
- Liver Diseases
- Lung Diseases
- Lupus Nephritis
- Lymphohistiocytosis, Hemophagocytic
- Lymphoma
- Lymphoma, AIDS-Related
- Lymphoma, Follicular
- Lymphoma, Large B-Cell, Diffuse
- Lymphoma, Mantle-Cell
- Lymphoma, Non-Hodgkin
- Melanoma
- Multiple Myeloma
- Myelodysplastic Syndromes
- Myelodysplastic-Myeloproliferative Diseases
- Myocardial Infarction
- Myocarditis
- Myositis
- Neoplasm Metastasis
- Neoplasms
- Neoplasms, Plasma Cell
- Neuroblastoma
- Optic Atrophy, Hereditary, Leber
- Ovarian Neoplasms
- Paraparesis, Tropical Spastic
- Periodontitis
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Prostatic Neoplasms, Castration-Resistant
- Pterygium
- Purpura, Thrombocytopenic, Idiopathic
- Purpura, Thrombotic Thrombocytopenic
- Red-Cell Aplasia, Pure
- Renal Artery Obstruction
- Renal Insufficiency
- Renal Insufficiency, Chronic
- Reperfusion Injury
- Retinal Vasculitis
- Retinoblastoma
- Sarcoma
- Severe Acute Respiratory Syndrome
- Skin Neoplasms
- Stevens-Johnson Syndrome
- Systemic Inflammatory Response Syndrome
- Takotsubo Cardiomyopathy
- Waldenstrom Macroglobulinemia
Contraindications
Source: Curated
- Malignancies (except specific psoriasis/RA indications) Absolute
Pregnancy & Lactation
Pregnancy
FDA category C
Caution
Continue in transplant patients. TDM essential. BP control critical (CsA causes hypertension — switch to nifedipine, methyldopa, or hydralazine for hypertension management)
Lactation
Caution
Hale L3
RID 1.7%
No reports of adverse effects on infants’ growth, development or kidney function
Chemistry & Properties
| Formula | C62H111N11O12 |
|---|---|
| Molecular weight | 1202.63 g/mol |
| IUPAC name | (3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-30-ethyl-33-[(E,1R,2R)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,17,20,23,26,29,32-undecone |
| CAS | 59865-13-3 |
| PubChem CID | 5284373 |
| InChIKey | PMATZTZNYRCHOR-CGLBZJNRSA-N |
SMILES
C/C=C/C[C@@H](C)[C@@H](O)[C@H]1C(=O)N[C@@H](CC)C(=O)N(C)CC(=O)N(C)[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@H](C)C(=O)N(C)[C@@H](CC(C)C)C(=O)N(C)[C@@H](CC(C)C)C(=O)N(C)[C@@H](C(C)C)C(=O)N1CBiology & Pharmacokinetics
Pharmacokinetics
| BBB penetrant | Yes (logBB 0.52) |
|---|
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP2C19 | Inhibitor | IC₅₀ 7.000000000000002 µM |
| CYP2C19 | Substrate | — |
| CYP2C9 | Inhibitor | IC₅₀ 38.79999999999996 µM |
| CYP3A4 | Inhibitor | Ki 1.3028766461882177 µM |
| CYP3A4 | Substrate | — |
Receptor binding (top 8)
| Target | Action | Affinity |
|---|---|---|
| peptidylprolyl isomerase A (PPIA) | Inhibitor | pIC50 8.3 |
| peptidylprolyl isomerase D (PPID) | Inhibitor | pIC50 8.0 |
| peptidylprolyl isomerase A (PPIA) | Inhibitor | pKi 7.8 |
| OATP1B1 (SLCO1B1) | Inhibitor | pKi 7.3 |
| ABCG2 (ABCG2) | Inhibitor | pKi 6.3 |
| OATP1B3 (SLCO1B3) | Inhibitor | pIC50 6.1 |
| Sodium/bile acid and sulphated solute cotransporter 1 (SLC10A1) | Inhibitor | pIC50 6.0 |
| Sodium/bile acid and sulphated solute cotransporter 1 (SLC10A1) | Inhibitor | pKi 5.1 |
Transporters
BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MATE1 (Inhibitor)MDR1 (Inhibitor)MRP (Inhibitor)MRP1 (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)MRP7 (Inhibitor)NTCP (Inhibitor)OAT (Inhibitor)OAT1 (Inhibitor)OAT3 (Inhibitor)OATP (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OATP1C1 (Inhibitor)OATP2B1 (Inhibitor)OATP3A1 (Inhibitor)OATP4C1 (Inhibitor)OATP5A1 (Inhibitor)OATP6A1 (Inhibitor)OCT(unspecified) (Inhibitor)OCT1 (Inhibitor)OCT3 (Inhibitor)OCTN1 (Inhibitor)OCTN2 (Inhibitor)P-gp (Inhibitor)PEPT (Inhibitor)PEPT1 (Inhibitor)Transporter(unspecified) (Inhibitor)MDR1 (Substrate)MRP2 (Substrate)OCT(unspecified) (Substrate)P-gp (Substrate)
Drug–drug interactions (100+, DDInter)
| Interacting drug | Severity | Management |
|---|---|---|
| Adalimumab | major | |
| Aliskiren | major | |
| Ambrisentan | major | |
| Amprenavir | major | |
| Atazanavir | major | |
| Atorvastatin | major | |
| Bacillus calmette-guerin substrain tice live antigen | major | |
| Baricitinib | major | |
| Berotralstat | major | |
| Betrixaban | major | |
| Boceprevir | major | |
| Bosentan | major | |
| Carbamazepine | major | |
| Ceritinib | major | |
| Cerivastatin | major | |
| Certolizumab pegol | major | |
| Cidofovir | major | |
| Cisapride | major | |
| Cladribine | major | |
| Clarithromycin | major | |
| Cobicistat | major | |
| Colchicine | major | |
| Conivaptan | major | |
| Darunavir | major | |
| Deferasirox | major | |
| Delavirdine | major | |
| Diatrizoate | major | |
| Docetaxel | major | |
| Dronedarone | major | |
| Edoxaban | major | |
| Elagolix | major | |
| Eluxadoline | major | |
| Erythromycin | major | |
| Etanercept | major | |
| Everolimus | major | |
| Fingolimod | major | |
| Fosamprenavir | major | |
| Foscarnet | major | |
| Glecaprevir | major | |
| Golimumab | major |
Showing 40 of 100+.
Registered Products (8)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| Restasis Ophthalmic emulsion | Ophthalmic Emulsion 0.05 % | 0.4 ml | Arab Company for Medical & Agricultural Products | 23.570 |
| ClasGen | Ophthalmic Emulsion 0.05 % | 0.4 ml | Amman Pharmaceutical Indusries | 26.950 |
| SANDIMMUN NEORAL Cap | Capsule 25 mg | 50 cap | The Jordan Drugstore Co | 35.410 |
| SANDIMMUN NEORAL Cap | Capsule 50 mg | 50 cap | The Jordan Drugstore Co | 70.010 |
| SANDIMMUN NEORAL Cap | Capsule 100 mg | 50 cap | The Jordan Drugstore Co | 98.980 |
| Cyclorine Oral Solution | Solution 100 mg/ml | 50 ml | UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN | 119.490 |
| SANDIMMUN NEORAL SOL | Solution 100 mg/ml | 50 ml | The Jordan Drugstore Co | 141.140 |
| Sandimmun Con for Inf | Ampoule 50 mg/ml | 10 amp | The Jordan Drugstore Co | — |