Cyclosporine is a potent immunosuppressive agent used to prevent rejection of transplanted organs.
23 cases of hypersensitivity have been reported (17 in patients, 5 in normal volunteers).
General: anaphylactic shock.
Respiratory: dyspnea, bronchospasm.
Cutaneous: erythematous skin rash (generalized or mainly on face and trunk), urticaria, pruritus, periorbital edema. In the 17 patients reported: 5/17 no previous exposure, 12/17 previous exposure to cyclosporine or cremophor EL (15 intravenous route, 2 oral route).
Cutaneous testing is seldom performed: 2/17 patients had positive skin-tests.
Provocation challenge: oral or intravenous.
The organic solvent (cremophor E.L.) contained in the intravenous solution (not in oral form) has been implicated.
IgE-mediated hypersensitivity (positive skin-tests, no specific IgE found).
Direct histamine release.
Use alternative formulations of cyclosporine:
- oral solution (cyclosporine 100 mg/ ml): Sandimmune (diluent: polyoxyethylated oleic glycerides).
- oral soft gelatin capsule: Sandimmune (diluent: polyoxyethylated glycolysed glycerides)
- oral solution microemulsion: Neoral (diluent: polyoxyl 40 hydrogenated castor oil)
- oral soft gelatin capsule microemulsion: Neoral (diluent: polyoxyl 40 hydrogenated castor oil).
The soft, corn oil-based gelatin capsule appears to be the safest formulation of cyclosporine.
If high-dose intravenous cyclosporine is used:
- cyclosporine solutions are incompatible with polyvinyl chloride (PVC) plastics and must be prepared in non-PVC plastic bags, glass bottles or polypropylene syringes. Tubing used for the infusion must not contain PVC.
- cyclosporine should be diluted to 0.5 to 2.5 mg/ ml with 5% dextrose or 0.9% sodium chloride. After adding cyclosporine to the carrier fluid, the infusion must be mixed thoroughly by shaking or swirling the bottle. The infusion fluid must appear homogenous.
- the tubing system must be primed with 0.9% saline or 5% dextrose.
- high-dose cyclosporine should not be administered to the patient unless the patient has received appropriate corticosteroid and antihistamine premedication.
- During the first ten minutes of the first and second cyclosporine infusions, supervision by medical personnel with proper resuscitation skills is advisable.