Cyclosporine
Mechanism :
Cyclosporine is a potent immunosuppressive agent which in animals prolongs survival of allogenic transplants involving skin, heart, kidney, pancreas, bone marrow, small intestine and lung. Cyclosporine has been demonstrated to suppress some humoral immunity and to a greater extent, cell-mediated reactions such as allograft rejection, delayed hypersensitivity and graft vs. host disease.
Indication :
- Psoriasis
- Juvenile idiopathic arthritis
- Atopic dermatitis
- Collagen vascular disorders
- Uveitis
- Vasculitis
- Ulcerative colitis
- Crohn’s disease
- Graft versus host disease
- Organ transplant (off-label)
Contraindications :
Cyclosporine is contraindicated in patients with a hypersensitivity to cyclosporine, abnormal renal function, uncontrolled hypertension, uncontrolled infections and malignancy.
Dosing :
Oral
Juvenile idiopathic arthritis, collagen disease, vasculitis, uveitis:
1-2 mg/kg/dose BDS; increased gradually upto 3 mg/kg/dose BDS.
Organ transplant:
5-7 mg/kg/dose BDS starting 12 hours before transplant and continued for 1-2 weeks postoperatively, gradually reducing to maintenance dose of 1-3 mg/kg/dose BDS.
Bone marrow transplant:
6-7.5 mg/kg/dose BDS starting one day prior to transplant.
Psoriasis/atopic dermatitis:
1.25 mg/kg/dose BDS increased, if no response, after 2 weeks for dermatitis and 4 weeks for psoriasis till 2.5 mg/kg/dose BDS.
Severe ulcerative colitis:
3-4 mg/kg/dose BDS.
Crohn’s disease:
2.5-4.5 mg/kg/dose BDS.
Adverse Effect :
Renal dysfunction, tremor, hirsutism, hypertension, and gum hyperplasia. Others: Hepatic impairment, fatigue, gingival hypertrophy, abdominal pain, nausea, vomiting and diarrhea, headache, rash and hyperkalemia.
Interaction :
Drugs that potentiate renal dysfunction: Antibiotics, antineoplastics, antifungals, anti-inflammatory drugs, immunosuppressive.
Drugs that increase cyclosporin concentrations: CCBs, antifungals, glucocorticoids.
Drugs that decrease cyclosporin levels: Nafcillin, rifampicin, anti-convulsants.
Nonsteroidal Anti-inflammatory Drug (NSAID) Interactions: Serum creatinine should be closely monitored when cyclosporine is used with nonsteroidal anti-inflammatory agents in rheumatoid arthritis patients.
Methotrexate Interaction: When methotrexate and cyclosporine were coadministered to rheumatoid arthritis patients, methotrexate concentrations were increased.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in normal renal function; adjust according to levels |
| HD | Not dialysed. Dose as in normal renal function; adjust according to levels |
| HDF/High flux | Unknown dialysability. Dose as in normal renal function; adjust according to levels |
| CAV/VVHD | Not dialysed. Dose as in normal renal function; adjust according to levels |
Hepatic Dose :
Reduction in dose may be required. Monitor serum cyclosporine levels.