Pharmacokinetic data from pediatric patients administered Neoral® or Sandimmune® are very limited. In 15 renal transplant patients aged 3-16 years, cyclosporine whole blood clearance after IV administration of Sandimmune® was 10.6±3.7 mL/min/kg (assay: Cyclo-trac specific RIA). In a study of 7 renal transplant patients aged 2-16, the cyclosporine clearance ranged from 9.8-15.5 mL/min/kg. In 9 liver transplant patients aged 0.6-5.6 years, clearance was 9.3±5.4 mL/min/kg (assay: HPLC).
In the pediatric population, Neoral® also demonstrates an increased bioavailability as compared to Sandimmune®. In 7 liver de novo transplant patients aged 1.4-10 years, the absolute bioavailability of Neoral® was 43% (range 30%-68%) and for Sandimmune® in the same individuals absolute bioavailability was 28% (range 17%-42%).
| Pediatric Pharmacokinetic Parameters (mean±SD) |
| Dose/day || Dose/weight || AUC 1 || Cmax || CL/F || CL/F |
| Patient Population || (mg/d) || (mg/kg/d) || (ng·hr/mL) || (ng/mL) || (mL/min) || (mL/min/kg) |
|Stable liver transplant2|
|Age 2-8, Dosed TID (N=9)||101±25||5.95±1.32||2163±801||629±219||285±94||16.6±4.3|
|Age 8-15, Dosed BID (N=8)||188±55||4.96±2.09||4272±1462||975±281||378±80||10.2±4.0|
|Stable liver transplant3|
|Age 3, Dosed BID (N=1)||120||8.33||5832||1050||171||11.9|
|Age 8-15, Dosed BID (N=5)||158±55||5.51±1.91||4452±2475||1013±635||328±121||11.0±1.9|
|Stable renal transplant3|
|Age 7-15, Dosed BID (N=5)||328±83||7.37±4.11||6922±1988||1827±487||418±143||8.7±2.9|
1AUC was measured over one dosing interval
2Assay: Cyclo-trac specific monoclonal radioimmunoassay
3Assay: TDx specific monoclonal fluorescence polarization immunoassay
Comparison of single dose data from both normal elderly volunteers (N=18, mean age 69 years) and elderly rheumatoid arthritis patients (N=16, mean age 68 years) to single dose data in young adult volunteers (N=16, mean age 26 years) showed no significant difference in the pharmacokinetic parameters.
There is a minimal experience with cyclosporine overdosage. Forced emesis can be of value up to 2 hours after administration of Neoral®. Transient hepatotoxicity and nephrotoxicity may occur which should resolve following drug withdrawal. General supportive measures and symptomatic treatment should be followed in all cases of overdosage. Cyclosporine is not dialyzable to any great extent, nor is it cleared well by charcoal hemoperfusion. The oral dosage at which half of experimental animals are estimated to die is 31 times, 39 times, and >54 times the human maintenance dose for transplant patients (6mg/kg; corrections based on body surface area) in mice, rats, and rabbits.
Neoral® is contraindicated in patients with a hypersensitivity to cyclosporine or to any of the ingredients of the formulation.
Rheumatoid arthritis patients with abnormal renal function, uncontrolled hypertension, or malignancies should not receive Neoral®.
Psoriasis patients who are treated with Neoral® should not receive concomitant PUVA or UVB therapy, methotrexate or other immunosuppressive agents, coal tar or radiation therapy. Psoriasis patients with abnormal renal function, uncontrolled hypertension, or malignancies should not receive Neoral®.