Certican Adverse Reactions

The frequencies of adverse reactions listed below are derived from analysis of the 12-month incidences of events reported in multicentre, randomised, controlled trials investigating Certican in combination with calcineurin inhibitors (CNI) and corticosteroids in transplant recipients. All but two of the trials (in renal transplant) included non-Certican, CNI-based standard-therapy arms.
Certican combined with ciclosporin, was studied in five trials in renal transplant recipients totalising 2497 patients, and three trials in heart transplant recipients totalising 1531 patients (intent to treat (ITT) populations, see Pharmacology: Pharmacodynamics under Actions).
Certican, combined with tacrolimus, was studied in one trial which included 719 liver transplant recipients (ITT population, see Pharmacology: Pharmacodynamics under Actions).
Table 16 contains adverse drug reactions possibly or probably related to Certican seen in phase III clinical trials. Unless noted as otherwise, these disorders have been identified by an increased incidence in the phase III studies comparing patients on a Certican treated patients with patients on a non-Certican, standard therapy regimen (see Pharmacology: Pharmacodynamics under Actions). Except where noted otherwise, the adverse reaction profile is relatively consistent across all transplant indications. It is compiled according to MedDRA standard organ classes: Adverse reactions are listed according to their frequency which are defined as: very common > 1/10, common > 1/100 and < 1/10, uncommon > 1/1,000 and < 1/100, rare > 1/10,000 and < 1/1,000, very rare < 1/10,000. (See Table 16.)


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In controlled clinical trials in which a total of 3256 patients receiving Certican in combination with other immunosuppressants were monitored, a total of 3.1% developed malignancies, with 1.0% developing skin malignancies and 0.6% developing lymphoma or lymphoproliferative disorder.
The occurrence of the adverse events may depend on the degree and duration of the immunosuppressive regimen. In the studies combining Certican with ciclosporin, elevated serum creatinine was observed more frequently in patients given Certican in combination with full dose ciclosporin for microemulsion than in control patients. The overall incidence of adverse events was lower with reduced dose ciclosporin for microemulsion (see Pharmacology: Pharmacodynamics: Clinical studies under Actions).
The safety profile of Certican in the trials in which it was administered with reduced-dose ciclosporin was similar to that described in the 3 pivotal studies in which full dose of ciclosporin was administered, except that elevation of serum creatinine was less frequent, and mean and median serum creatinine values were lower, than in the other phase III studies.
Cases of interstitial lung disease, implying lung intraparenchymal inflammation (pneumonitis) and/or fibrosis of non-infectious etiology, some fatal, have occurred in patients receiving rapamycins and their derivatives, including Certican. Mostly, the condition resolves after discontinuation of Certican and/or addition of glucocorticoids. However, fatal cases have also occurred.