After oral administration, Nolvadex is absorbed rapidly with maximum serum concentrations attained within 4 - 7 hours. Steady state concentrations (about 300 ng/ml) are achieved after four weeks treatment with 40 mg daily. The drug is highly protein bound to serum albumin (>99%). Metabolism is by hydroxylation, demethylation and conjugation, giving rise to several metabolites which have a similar pharmacological profile to the parent compound and thus contribute to the therapeutic effect. Excretion occurs primarily via the faeces and an elimination half - life of approximately seven days has been calculated for the drug itself, whereas that for N-desmethyltamoxifen, the principal circulating metabolite, is 14 days.
The risks of Nolvadex therapy include endometrial cancer, DVT, PE, stroke, cataract formation and cataract surgery (See Table 3 ). In the NSABP P-1 trial, 33 cases of endometrial cancer were observed in the Nolvadex group vs. 14 in the placebo group (RR=, 95% CI: -). Deep vein thrombosis was observed in 30 women receiving Nolvadex vs. 19 in women receiving placebo (RR=, 95% CI: -). Eighteen cases of pulmonary embolism were observed in the Nolvadex group vs. 6 in the placebo group (RR=, 95% CI: -). There were 34 strokes on the Nolvadex arm and 24 on the placebo arm (RR=; 95% CI: -). Cataract formation in women without cataracts at baseline was observed in 540 women taking Nolvadex vs. 483 women receiving placebo (RR=, 95% CI: -). Cataract surgery (with or without cataracts at baseline) was performed in 201 women taking Nolvadex vs. 129 women receiving placebo (RR=, 95% CI: -) (See WARNINGS ).