When NOLVADEX is used in combination with coumarin-type anticoagulants, a significant increase in anticoagulant
effect may occur. Where such coadministration exists, careful monitoring of the patientís prothrombin time is
In the NSABP P-1 trial, women who required coumarin-type anticoagulants for any reason were ineligible for
participation in the trial.
There is an increased risk of thromboembolic events occurring when cytotoxic agents are used in combination with
Nolvadex reduced letrozole plasma concentrations by 37%. The effect of tamoxifen on metabolism and excretion of
other antineoplastic drugs, such as cyclophosphamide and other drugs that require mixed function oxidases for
activation, is not known. Nolvadex and N-desmethyl tamoxifen plasma concentrations have been shown to be reduced
when coadministered with rifampin or aminoglutethimide. Induction of CYP3A4-mediated metabolism is considered to be
the mechanism by which these reductions occur; other CYP3A4 inducing agents have not been studied to confirm this
One patient receiving NOLVADEX with concomitant phenobarbital exhibited a steady state serum level of tamoxifen
lower than that observed for other patients (ie, 26 ng/mL vs. mean value of 122 ng/mL). However, the clinical
significance of this finding is not known. Rifampin induced the metabolism of tamoxifen and significantly reduced the
plasma concentrations of tamoxifen in 10 patients. Aminoglutethimide reduces tamoxifen and N desmethyl tamoxifen
plasma concentrations. Medroxyprogesterone reduces plasma concentrations of N-desmethyl, but not tamoxifen.
Concomitant bromocriptine therapy has been shown to elevate serum tamoxifen and N-desmethyl tamoxifen.
Drug/Laboratory Testing Interactions:
During postmarketing surveillance, T4 elevations were reported for a few postmenopausal patients which may be
explained by increases in thyroid-binding globulin. These elevations were not accompanied by clinical
Variations in the karyopyknotic index on vaginal smears and various degrees of estrogen effect on Pap smears have
been infrequently seen in postmenopausal patients given NOLVADEX.
In the postmarketing experience with NOLVADEX, infrequent cases of hyperlipidemias have been reported. Periodic
monitoring of plasma triglycerides and cholesterol may be indicated in patients with pre-existing hyperlipidemias