No dose adjustment is necessary when Simulect is added to triple-immunosuppression regimens, including cyclosporine, corticosteroids, and either azathioprine or mycophenolate mofetil. Three clinical trials have investigated Simulect use in combination with triple-therapy regimens. Pharmacokinetics were assessed in two of these trials. Total body clearance of Simulect was reduced by an average 22% and 51% when azathioprine and mycophenolate mofetil, respectively, were added to a regimen consisting of cyclosporine, USP (MODIFIED) and corticosteroids. Nonetheless, the range of individual Simulect clearance values in the presence of azathioprine (12-57 mL/h) or mycophenolate mofetil (7-54 mL/h) did not extend outside the range observed with dual therapy (10-78 mL/h). The following medications have been administered in clinical trials with Simulect with no increase in adverse reactions: ATG/ALG, azathioprine, corticosteroids, cyclosporine, mycophenolate mofetil, and muromonab-CD3.

###  Carcinogenesis/Mutagenesis/Impairment of Fertility

No mutagenic potential of Simulect was observed in the in vitro assays with Salmonella (Ames) and V79 Chinese hamster cells. No long-term or fertility studies in laboratory animals have been performed to evaluate the potential of Simulect to produce carcinogenicity or fertility impairment, respectively.

There are no adequate and well-controlled studies in pregnant women. No maternal toxicity, embryotoxicity, or teratogenicity was observed in cynomolgus monkeys 100 days post coitum following dosing with basiliximab during the organogenesis period; blood levels in pregnant monkeys were 13-fold higher than those seen in human patients. Immunotoxicology studies have not been performed in the offspring. Because IgG molecules are known to cross the placental barrier, because the IL-2 receptor may play an important role in development of the immune system, and because animal reproduction studies are not always predictive of human response, Simulect should only be used in pregnant women when the potential benefit justifies the potential risk to the fetus. Women of childbearing potential should use effective contraception before beginning Simulect therapy, during therapy, and for 4 months after completion of Simulect therapy.

###  Nursing Mothers

It is not known whether Simulect is excreted in human milk. Because many drugs, including human antibodies are excreted in human milk, and because of the potential for adverse reactions, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

###  Pediatric Use

No randomized, placebo-controlled studies have been completed in pediatric patients. In a safety and pharmacokinetic study, 41 pediatric patients (1-11 years of age [n = 27], 12-16 years of age [n = 14], median age 8.1 years) were treated with Simulect via intravenous bolus injection in addition to standard immunosuppressive agents, including cyclosporine, USP (MODIFIED), corticosteroids, azathioprine, and mycophenolate mofetil. The acute rejection rate at 6 months was comparable to that in adults in the triple-therapy trials. The most frequently reported adverse events were hypertension, hypertrichosis, and rhinitis (49% each), urinary tract infections (46%), and fever (39%). Overall, the adverse event profile was consistent with general clinical experience in the pediatric renal transplantation population and with the profile in the controlled adult renal transplantation studies. The available pharmacokinetic data in children and adolescents are described in CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION.

It is not known whether the immune response to vaccines, infection, and other antigenic stimuli administered or encountered during Simulect therapy is impaired or whether such response will remain impaired after Simulect therapy.

###  Geriatric Use

Controlled clinical studies of Simulect have included a small number of patients 65 years and older (Simulect 28; placebo 32). From the available data comparing Simulect and placebo-treated patients, the adverse event profile in patients ≥ 65 years of age is not different from patients < 65 years of age and no age-related dosing adjustment is required. Caution must be used in giving immunosuppressive drugs to elderly patients.