ven malformations were reported in 5 viable infants and in 2 cases of fetal loss. Twenty-eight percent of the infants were small for gestational age. Neonatal complications occurred in 27%. Therefore, the risks and benefits of using Gengraf during pregnancy should be carefully weighed.
A limited number of observations in children exposed to cyclosporine in utero is available, up to an age of approximately 7 years. Renal function and blood pressure in these children were normal.
Because of the possible disruption of maternal-fetal interaction, the risk/benefit ratio of using Gengraf in psoriasis patients during pregnancy should carefully be weighed with serious consideration for discontinuation of Gengraf.
Nursing Mothers
Cyclosporine passes into breast milk. Mothers receiving treatment with Gengraf should not breast feed.
Pediatric Use
Although no adequate and well-controlled studies have been completed in children, transplant recipients as young as one year of age have received cyclosporine (MODIFIED) with no unusual adverse effects. The safety and efficacy of cyclosporine (MODIFIED) treatment in pediatric patients with juvenile rheumatoid arthritis or psoriasis below the age of 18 have not been established.
Geriatric Use
In rheumatoid arthritis clinical trials with cyclosporine, 17.5% of patients were age 65 or older. These patients were more likely to develop systolic hypertension on therapy, and more likely to show serum creatinine rises ≥ 50% above the baseline after 3-4 months of therapy.
Clinical studies of cyclosporine oral solution (MODIFIED) in transplant and psoriasis patients did not include a sufficient number of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experiences have not identified differences in response between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
ADVERSE REACTIONS
Kidney, Liver, and Heart Transplantation
The principal adverse reactions of cyclosporine therapy are renal dysfunction, tremor, hirsutism, hypertension, and gum hyperplasia.
Hypertension, which is usually mild to moderate, may occur in approximately 50% of patients following renal transplantation and in most cardiac transplant patients.
Glomerular capillary thrombosis has been found in patients treated with cyclosporine and may progress to graft failure. The pathologic changes resembled those seen in the hemolytic-uremic syndrome and include thrombosis of the renal microvasculature, with platelet-fibrin thrombi occluding glomerular capillaries and afferent arterioles, microangiopathic hemolytic anemia, thrombocytopenia, and decreased renal function. Similar findings have been observed when other immunosuppressives have been employed post-transplantation.
Hypomagnesemia has been reported in some, but not all, patients exhibiting convulsions while on cyclosporine therapy. Although magnesium-depletion studies in normal subjects suggest that hypomagnesemia is associated with neurologic disorders, multiple factors, including hypertension, high dose methylprednisolone, hypocholesterolemia, and ne
