Apo-Tamox - General Information
One of the selective estrogen receptor modulators with tissue-specific activities. Apo-Tamox acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the endometrium.
Pharmacology of Apo-Tamox
Apo-Tamox belongs to a class of drugs called selective estrogen receptor modulators (SERMs), which have both estrogenic and antiestrogenic effects. Apo-Tamox has the same nucleus as diethylstilbestrol but possesses an additional side chain (trans isomer) which accounts for its antiestrogenic activity.
Apo-Tamox for patients
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 recommended.
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.
Tamoxifen 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. Tamoxifen 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 effect.
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 hyperthyroidism.
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.
NOLVADEX is contraindicated in patients with known hypersensitivity to the drug or any of its ingredients.
Reduction in Breast Cancer Incidence in High Risk Women and Women with DCIS:
NOLVADEX is contraindicated in women who require concomitant coumarin-type anticoagulant therapy or in women with a history of deep vein thrombosis or pulmonary embolus.
Additional information about Apo-Tamox
Apo-Tamox Indication: for the treatment of breast cancer
Mechanism Of Action: Apo-Tamox binds to estrogen receptors (ER), inducing a conformational change in the receptor. This results in a blockage or change in the expression of estrogen dependent genes. The prolonged binding of tamoxifen to the nuclear chromatin of these results in reduced DNA polymerase activity, impaired thymidine utilization, blockade of estradiol uptake, and decreased estrogen response. It is likely that tamoxifen interacts with other coactivators or corepressors in the tissue and binds with different estrogen receptors, ER-alpha or ER-beta, producing both estrogenic and antiestrogenic effects.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Tamoxifen
Synonyms: Tamoxifenum [Inn-Latin]; Tamoxifeno [Inn-Spanish]; Tamoxifene [Inn-French]; Trans-Tamoxifen; Tamoxifen Citrate
Drug Category: Antineoplastic Agents, Hormonal; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators
Drug Type: Small Molecule; Approved
Other Brand Names containing Tamoxifen: Apo-Tamox; Citofen; Crisafeno; Diemon; Gen-Tamoxifen; Istubol; Kessar; Noltam; Nolvadex; Nolvadex-D; Nourytam; Novo-Tamoxifen; Oncomox; PMS-Tamoxifen; Retaxim; Tamizam; Tamofen; Tamone; Tamoxasta; Tamoxen; Valodex; Zemide;
Absorption: Not Available
Toxicity (Overdose): Signs observed at the highest doses following studies to determine LD50 in animals were respiratory difficulties and convulsions.
Protein Binding: Not Available
Biotransformation: Hepatic. Tamoxifen is extensively metabolized after oral administration. N-desmethyl tamoxifen is the major metabolite found in plasma. N-desmethyl tamoxifen activity is similar to tamoxifen. 4-Hydroxytamoxifen and a side chain primary alcohol derivative of tamoxifen have been identified as minor metabolites in plasma. Tamoxifen is a substrate of cytochrome P450 CYP3A4, CYP2C9 and CYP2D6, and an inhibitor of P-glycoprotein.
Half Life: Distribution: 7 to 14 hours; Elimination: 5 to 7 days
Dosage Forms of Apo-Tamox: Tablet Oral
Chemical IUPAC Name: 2-[4-[(Z)-1,2-di(phenyl)but-1-enyl]phenoxy]-N,N-dimethylethanamine
Chemical Formula: C26H29NO
Tamoxifen on Wikipedia: http://en.wikipedia.org/wiki/Tamoxifen
Organisms Affected: Humans and other mammals