Soltamox (tamoxifen citrate)

Dosage of tamoxifen citrate is expressed in terms of tamoxifen.

Tamoxifen citrate is commercially available as oral tablets containing 10 mg or 20 mg of tamoxifen, equivalent to 15.2 or 30.4 mg of tamoxifen citrate, respectively. Tamoxifen citrate is also commercially available as an oral solution with each 10 mL containing 20 mg of tamoxifen (equivalent to 30.4 mg tamoxifen citrate).

Tamoxifen is administered orally without regard to meals. Dosages exceeding 20 mg daily should be given in divided doses (morning and evening).

Commercially available tamoxifen tablets should be protected from light and stored in well-closed containers at controlled room temperature (20-25degreesC).

Commercially available tamoxifen oral solution should be protected from light and stored in the original packaging at 20-25degreesC (excursions permitted between 15-30degreesC). Do not freeze or refrigerate the oral solution. Discard any unused portions of the oral solution 3 months after first opening the bottle.

No dosing information is available for this tab.

No dosing information is available for this tab.

Tamoxifen is extensively metabolized by multiple cytochrome P-450 (CYP) isoenzymes, including 2B6, 2C9, 2C19, 2D6, and 3A. The metabolism of tamoxifen to form N-desmethyltamoxifen (major metabolite found in plasma) is mediated mainly by CYP3A. Polymorphic CYP2D6 is involved in the formation of endoxifen and 4-hydroxytamoxifen (minor metabolites) and is the primary enzyme responsible for catalyzing the conversion of N-desmethyltamoxifen to endoxifen.

Phase II metabolizing enzymes, including sulfotransferase family 1A member 1 (SULT1A1), uridine diphosphate-glucuronosyltransferase (UGT) 2B7, and UGT1A4, are involved in the clearance of tamoxifen from plasma. Tamoxifen inhibits P-glycoprotein.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Known hypersensitivity to tamoxifen or other ingredients in the formulation.

*When used in women with ductal carcinoma in situ (DCIS) and women at high risk for breast cancer, history of deep-vein thrombosis (DVT) or pulmonary embolism (PE).

*When used in women with DCIS and women at high risk for breast cancer, concurrent anticoagulant therapy with a warfarin derivative.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Common adverse effects of tamoxifen include hot flushes (flashes), mood disturbances, vaginal discharge, vaginal bleeding, nausea, and fluid retention.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

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The safety and effectiveness of tamoxifen have not been established in pediatric patients.

Tamoxifen has been used for the treatment of Albright syndrome+ (also known as McCune-Albright syndrome) and precocious puberty in girls 2-10 years of age; however, the manufacturer of tamoxifen oral solution states that the safety and effectiveness of the drug for the treatment of girls with McCune-Albright syndrome, including long-term effects, have not been established. In a noncomparative study, 28 girls 2-10 years of age with Albright syndrome and precocious puberty (manifested by physical signs of pubertal development, episodes of vaginal bleeding, and/or advanced bone age) received tamoxifen 20 mg once daily for up to 12 months. Tamoxifen therapy was associated with a 50% reduction in frequency of vaginal bleeding episodes and reductions in bone age maturation and linear growth velocity. An increase in mean uterine volume was observed following 6 months of therapy, with doubling of uterine volume observed after one year of therapy; however, a causal relationship to the drug has not been established. Because tamoxifen has been associated with an increased incidence of endometrial and uterine malignancies in adults, the manufacturer recommends continued monitoring for long-term uterine effects in pediatric patients receiving tamoxifen for the treatment of Albright syndrome. The manufacturer of tamoxifen tablets state that the effects of tamoxifen beyond one year of treatment in girls with McCune-Albright syndrome have not been established.

In animal studies, direct exposure of neonatal mice and rats to tamoxifen resulted in lesions in the female reproductive tract (similar to those observed with DES in humans) and functional defects of the male reproductive tract (e.g., testicular atrophy, arrest of spermatogenesis).

Tamoxifen can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies using tamoxifen in pregnant women. There have been reports of spontaneous abortions, birth defects, fetal deaths, and vaginal bleeding in the postmarketing setting.

In nonhuman primate studies, administration of tamoxifen at doses approximately twice the maximum recommended human dosage was associated with spontaneous abortion. In reproductive toxicity studies in rats and rabbits, tamoxifen administered at doses at or below human doses resulted in increased embryotoxicity, abortions, and alterations in learning behavior in offspring. Furthermore, studies in rodent models demonstrated reproductive tract abnormalities in male and female offspring, resembling changes historically associated with in utero exposure to DES.

Advise women not to become pregnant while receiving tamoxifen or within 2 months after discontinuance of therapy with the drug. When tamoxifen is administered during pregnancy or if the patient becomes pregnant while receiving the drug or within approximately 2 months after discontinuance of therapy with tamoxifen, advise the patient of the potential hazard to the fetus, including the possible long-term risk of a DES-like syndrome.

It is not known if tamoxifen is distributed into human milk. The effects of tamoxifen on the breast-fed infant are unknown; however, data from juvenile animal studies suggest a potential for serious long-term adverse effects for breast-fed infants exposed to tamoxifen through breast milk. Direct exposure (not via breast milk) of neonatal mice and rat pups to tamoxifen has resulted in adverse reproductive tract effects (i.e., lesions in female pups that are similar to those observed in humans after intrauterine DES exposure; functional defects of the reproductive tract, including testicular atrophy and arrested spermatogenesis, in male pups).

Tamoxifen inhibits lactation. In 2 placebo-controlled trials, inhibition of early postpartum milk production was observed in women who received tamoxifen within 24 hours of delivery for a duration of 5-18 days. The effect of tamoxifen on established milk production is not known.

Because of the potential for serious adverse reactions to tamoxifen in nursing infants, advise women not to breast-feed during tamoxifen therapy and for 3 months after the last dose.

The manufacturers make no specific dosage recommendations for geriatric patients.

In the BCPT, 16% of the study participants were 65 years of age or older and 6% were at least 70 years of age. Reductions in the incidence of breast cancer were observed in women receiving tamoxifen across all age groups. Across all other outcomes, the results in the subset of women 65 years of age or older reflect the results observed in the subset of women at least 50 years of age. In this study, no overall differences in safety were observed between geriatric patients and younger adults.

In the NSABP B-24 study evaluating tamoxifen in patients with DCIS, 23% of the study participants were 65 years of age or older and 10% were at least 70 years of age. Because invasive breast cancer occurred in relatively few tamoxifen- or placebo-treated women 65 years of age or older, the results were insufficient to determine whether geriatric patients respond differently than younger adults for this outcome. Across all other outcomes, no overall differences were observed between geriatric patients and younger adults. In this study, no overall differences in safety were observed between geriatric patients and younger adults.