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When NOLVADEX is used in combination with coumarin-type anticoagulants, a significant increase in anticoagulant effect may occur. Where such co-administration is initiated, careful monitoring of the patient is recommended.
When NOLVADEX is used in combination with cytotoxic agents, for the treatment of breast cancer, there is an increased risk of thromboembolic events occurring (see Precautions and Adverse Reactions). Because of this increase in risk of VTE, thrombosis prophylaxis should be considered for these patients for the period of concomitant chemotherapy.
The use of tamoxifen in combination with an aromatase inhibitor as adjuvant therapy has not shown improved efficacy compared with tamoxifen alone.
As NOLVADEX is metabolised by cytochrome P450 3A4, care is required when co-administering with drugs, such as rifampicin, known to induce this enzyme as tamoxifen levels may be reduced. The clinical relevance of this reduction is unknown.
Pharmacokinetic interaction with CYP2D6 inhibitors, showing a reduction in plasma level of an active tamoxifen metabolite, 4-hydroxy-N-desmethyltamoxifen (endoxifen), has been reported in the literature.
Pharmacokinetic interaction with CYP2D6 inhibitors, showing a 65-75% reduction in plasma levels of one of the more active forms of the drug, i.e. endoxifen, has been reported in the literature. Reduced efficacy of tamoxifen has been reported with concomitant usage of some SSRI antidepressants (e.g. paroxetine) in some studies. As a reduced effect of tamoxifen cannot be excluded, co-administration with potent CYP2D6 inhibitors (e.g. paroxetine, fluoxetine, quinidine, cinacalcet or bupropion) should whenever possible be avoided (see Precautions and Interactions).
