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Vero-Tamoxifen

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Vero-Tamoxifen uses


INDICATIONS AND USAGE

Metastatic Breast Cancer

Vero-Tamoxifen tablets are effective in the treatment of metastatic breast cancer in women and men. In premenopausal women with metastatic breast cancer, tamoxifen is an alternative to oophorectomy or ovarian irradiation. Available evidence indicates that patients whose tumors are estrogen receptor positive are more likely to benefit from tamoxifen therapy.

Adjuvant Treatment of Breast Cancer

Vero-Tamoxifen tablets are indicated for the treatment of node-positive breast cancer in women following total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation. In some tamoxifen adjuvant studies, most of the benefit to date has been in the subgroup with four or more positive axillary nodes.

Vero-Tamoxifen tablets are indicated for the treatment of axillary node-negative breast cancer in women following total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation.

The estrogen and progesterone receptor values may help to predict whether adjuvant tamoxifen therapy is likely to be beneficial.

Tamoxifen reduces the occurrence of contralateral breast cancer in patients receiving adjuvant tamoxifen therapy for breast cancer.

Ductal Carcinoma in Situ

In women with DCIS, following breast surgery and radiation, Vero-Tamoxifen tablets are indicated to reduce the risk of invasive breast cancer (see BOXED WARNING at the beginning of the label). The decision regarding therapy with tamoxifen for the reduction in breast cancer incidence should be based upon an individual assessment of the benefits and risks of tamoxifen therapy.

Current data from clinical trials support 5 years of adjuvant tamoxifen therapy for patients with breast cancer.

Reduction in Breast Cancer Incidence in High Risk Women

Vero-Tamoxifen tablets are indicated to reduce the incidence of breast cancer in women at high risk for breast cancer. This effect was shown in a study of 5 years planned duration with a median follow-up of 4.2 years. Twenty-five percent of the participants received drug for 5 years. The longer-term effects are not known. In this study, there was no impact of tamoxifen on overall or breast cancer-related mortality (see BOXED WARNING at the beginning of the label).

Vero-Tamoxifen tablets are indicated only for high-risk women. “High risk” is defined as women at least 35 years of age with a 5 year predicted risk of breast cancer ≥ 1.67%, as calculated by the Gail Model.

Examples of combinations of factors predicting a 5 year risk ≥ 1.67% are:

Age 35 or older and any of the following combination of factors:


Age 40 or older and any of the following combination of factors:


Age 45 or older and any of the following combination of factors:


Age 50 or older and any of the following combination of factors:


Age 55 or older and any of the following combination of factors:


Age 60 or older and:


For women whose risk factors are not described in the above examples, the Gail Model is necessary to estimate absolute breast cancer risk. Health Care Professionals can obtain a Gail Model Risk Assessment Tool by dialing 1-888-838-2872.

There are insufficient data available regarding the effect of tamoxifen on breast cancer incidence in women with inherited mutations (BRCA1, BRCA2) to be able to make specific recommendations on the effectiveness of tamoxifen in these patients.

After an assessment of the risk of developing breast cancer, the decision regarding therapy with tamoxifen for the reduction in breast cancer incidence should be based upon an individual assessment of the benefits and risks of tamoxifen therapy. In the NSABP P-1 trial, tamoxifen treatment lowered the risk of developing breast cancer during the follow-up period of the trial, but did not eliminate breast cancer risk (see Table 3 in CLINICAL PHARMACOLOGY).

CONTRAINDICATIONS

Vero-Tamoxifen tablets are 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

Vero-Tamoxifen tablets are contraindicated in women who require concomitant coumarin-type anticoagulant therapy or in women with a history of deep-vein thrombosis or pulmonary embolus.

WARNINGS

Effects in Metastatic Breast Cancer Patients

As with other additive hormonal therapy, hypercalcemia has been reported in some breast cancer patients with bone metastases within a few weeks of starting treatment with tamoxifen. If hypercalcemia does occur, appropriate measures should be taken and, if severe, tamoxifen should be discontinued.

Effects on the Uterus-Endometrial Cancer and Uterine Sarcoma

An increased incidence of uterine malignancies has been reported in association with tamoxifen treatment. The underlying mechanism is unknown, but may be related to the estrogen-like effect of tamoxifen. Most uterine malignancies seen in association with tamoxifen are classified as adenocarcinoma of the endometrium. However, rare uterine sarcomas, including malignant mixed mullerian tumors (MMMT), have also been reported. Uterine sarcoma is generally associated with a higher FIGO stage (III/IV) at diagnosis, poorer prognosis, and shorter survival. Uterine sarcoma has been reported to occur more frequently among long-term users (≥ 2 years) of tamoxifen than non-users. Some of the uterine malignancies (endometrial carcinoma or uterine sarcoma) have been fatal.

In the NSABP P-1 trial, among participants randomized to tamoxifen there was a statistically significant increase in the incidence of endometrial cancer (33 cases of invasive endometrial cancer, compared to 14 cases among participants randomized to placebo (RR = 2.48, 95% CI: 1.27 to 4.92). The 33 cases in participants receiving tamoxifen were FIGO Stage I, including 20 IA, 12 IB, and 1 IC endometrial adenocarcinomas. In participants randomized to placebo, 13 were FIGO Stage I (8 IA and 5 IB) and 1 was FIGO Stage IV. Five women on tamoxifen and 1 on placebo received postoperative radiation therapy in addition to surgery. This increase was primarily observed among women at least 50 years of age at the time of randomization (26 cases of invasive endometrial cancer, compared to 6 cases among participants randomized to placebo (RR = 4.50, 95% CI: 1.78 to 13.16). Among women ≤ 49 years of age at the time of randomization there were 7 cases of invasive endometrial cancer, compared to 8 cases among participants randomized to placebo (RR = 0.94, 95% CI: 0.28 to 2.89). If age at the time of diagnosis is considered, there were 4 cases of endometrial cancer among participants ≤ 49 randomized to tamoxifen compared to 2 among participants randomized to placebo (RR = 2.21, 95% CI: 0.4 to 12.0). For women ≥ 50 at the time of diagnosis, there were 29 cases among participants randomized to tamoxifen compared to 12 among women on placebo (RR = 2.5, 95% CI: 1.3 to 4.9). The risk ratios were similar in the two groups, although fewer events occurred in younger women. Most (29 of 33 cases in the tamoxifen group) endometrial cancers were diagnosed in symptomatic women, although 5 of 33 cases in the tamoxifen group occurred in asymptomatic women. Among women receiving tamoxifen the events appeared between 1 and 61 months (average = 32 months) from the start of treatment.

In an updated review of long-term data (median length of total follow-up is 6.9 years, including blinded follow-up) on 8,306 women with an intact uterus at randomization in the NSABP P-1 risk reduction trial, the incidence of both adenocarcinomas and rare uterine sarcomas was increased in women taking tamoxifen. During blinded follow-up, there were 36 cases of FIGO Stage I endometrial adenocarcinoma (22 were FIGO Stage IA, 13 IB, and 1 IC) in women receiving tamoxifen and 15 cases in women receiving placebo [14 were FIGO Stage I (9 IA and 5 IB), and 1 case was FIGO Stage IV]. Of the patients receiving tamoxifen who developed endometrial cancer, one with Stage IA and 4 with Stage IB cancers received radiation therapy. In the placebo group, one patient with FIGO Stage IB cancer received radiation therapy and the patient with FIGO Stage IVB cancer received chemotherapy and hormonal therapy. During total follow-up, endometrial adenocarcinoma was reported in 53 women randomized to tamoxifen (30 cases of FIGO Stage IA, 20 were Stage IB, 1 was Stage IC, and 2 were Stage IIIC), and 17 women randomized to placebo (9 cases were FIGO Stage IA, 6 were Stage IB, 1 was Stage IIIC, and 1 was Stage IVB) (incidence per 1,000 women-years of 2.20 and 0.71, respectively). Some patients received postoperative radiation therapy in addition to surgery. Uterine sarcomas were reported in 4 women randomized to tamoxifen (1 was FIGO IA, 1 was FIGO IB, 1 was FIGO IIA, and 1 was FIGO IIIC) and 1 patient randomized to placebo (FIGO 1A); incidence per 1,000 women-years of 0.17 and 0.04, respectively. Of the patients randomized to tamoxifen, the FIGO IA and IB cases were a MMMT and sarcoma, respectively; the FIGO II was a MMMT; and the FIGO III was a sarcoma; and the 1 patient randomized to placebo had a MMMT. A similar increased incidence in endometrial adenocarcinoma and uterine sarcoma was observed among women receiving tamoxifen in 5 other NSABP clinical trials.

Any patient receiving or who has previously received tamoxifen who reports abnormal vaginal bleeding should be promptly evaluated. Patients receiving or who have previously received tamoxifen should have annual gynecological examinations and they should promptly inform their physicians if they experience any abnormal gynecological symptoms, e.g., menstrual irregularities, abnormal vaginal bleeding, changes in vaginal discharge, or pelvic pain or pressure.

In the P-1 trial, endometrial sampling did not alter the endometrial cancer detection rate compared to women who did not undergo endometrial sampling (0.6% with sampling, 0.5% without sampling) for women with an intact uterus. There are no data to suggest that routine endometrial sampling in asymptomatic women taking tamoxifen to reduce the incidence of breast cancer would be beneficial.

Non-Malignant Effects on the Uterus

An increased incidence of endometrial changes including hyperplasia and polyps has been reported in association with tamoxifen treatment. The incidence and pattern of this increase suggest that the underlying mechanism is related to the estrogenic properties of tamoxifen.

There have been a few reports of endometriosis and uterine fibroids in women receiving tamoxifen. The underlying mechanism may be due to the partial estrogenic effect of tamoxifen. Ovarian cysts have also been observed in a small number of premenopausal patients with advanced breast cancer who have been treated with tamoxifen.

Tamoxifen has been reported to cause menstrual irregularity or amenorrhea.

Thromboembolic Effects of Tamoxifen

There is evidence of an increased incidence of thromboembolic events, including deep-vein thrombosis and pulmonary embolism, during tamoxifen therapy. When tamoxifen is coadministered with chemotherapy, there may be a further increase in the incidence of thromboembolic effects. For treatment of breast cancer, the risks and benefits of tamoxifen should be carefully considered in women with a history of thromboembolic events. In a small substudy of the NSABP-1 trial, there appeared to be no benefit to screening women for Factor V Leiden and Prothrombin mutations G20210A as a means to identify those who may not be appropriate candidates for tamoxifen therapy.

Data from the NSABP P-1 trial show that participants receiving tamoxifen without a history of pulmonary emboli (PE) had a statistically significant increase in pulmonary emboli (18 tamoxifen, 6 placebo; RR = 3.01, 95% CI: 1.15 to 9.27). Three of the pulmonary emboli, all in the tamoxifen arm, were fatal. Eighty-seven percent of the cases of pulmonary embolism occurred in women at least 50 years of age at randomization. Among women receiving tamoxifen, the events appeared between 2 and 60 months (average = 27 months) from the start of treatment.

In this same population, a non-statistically significant increase in deep-vein thrombosis (DVT) was seen in the tamoxifen group (30-tamoxifen, 19-placebo; RR = 1.59, 95% CI: 0.86 to 2.98). The same increase in relative risk was seen in women ≤ 49 and in women ≥ 50, although fewer events occurred in younger women. Women with thromboembolic events were at risk for a second related event (7 out of 25 women on placebo, 5 out of 48 women on tamoxifen) and were at risk for complications of the event and its treatment (0/25 on placebo, 4/48 on tamoxifen). Among women receiving tamoxifen, deep-vein thrombosis events occurred between 2 and 57 months (average = 19 months) from the start of treatment.

There was a non-statistically significant increase in stroke among patients randomized to tamoxifen (24 placebo; 34 tamoxifen; RR = 1.42, 95% CI: 0.82 to 2.51). Six of the 24 strokes in the placebo group were considered hemorrhagic in origin and 10 of the 34 strokes in the tamoxifen group were categorized as hemorrhagic. Seventeen of the 34 strokes in the tamoxifen group were considered occlusive and 7 were considered to be of unknown etiology. Fourteen of the 24 strokes on the placebo arm were reported to be occlusive and 4 of unknown etiology. Among these strokes 3 strokes in the placebo group and 4 strokes in the tamoxifen group were fatal. Eighty-eight percent of the strokes occurred in women at least 50 years of age at the time of randomization. Among women receiving tamoxifen, the events occurred between 1 and 63 months (average = 30 months) from the start of treatment.

Effects on the Liver: Liver Cancer

In the Swedish trial using adjuvant tamoxifen 40 mg/day for 2 to 5 years, 3 cases of liver cancer have been reported in the tamoxifen-treated group vs. 1 case in the observation group (see PRECAUTIONS, Carcinogenesis). In other clinical trials evaluating tamoxifen, no cases of liver cancer have been reported to date.

One case of liver cancer was reported in NSABP P-1 in a participant randomized to tamoxifen.

Effects on the Liver: Non-Malignant Effects

Tamoxifen has been associated with changes in liver enzyme levels, and on rare occasions, a spectrum of more severe liver abnormalities including fatty liver, cholestasis, hepatitis and hepatic necrosis. A few of these serious cases included fatalities. In most reported cases the relationship to tamoxifen is uncertain. However, some positive rechallenges and dechallenges have been reported.

In the NSABP P-1 trial, few grade 3 to 4 changes in liver function were observed (10 on placebo and 6 on tamoxifen). Serum lipids were not systematically collected.

Other Cancers

A number of second primary tumors, occurring at sites other than the endometrium, have been reported following the treatment of breast cancer with tamoxifen in clinical trials. Data from the NSABP B-14 and P-1 studies show no increase in other (non-uterine) cancers among patients receiving tamoxifen. Whether an increased risk for other (non-uterine) cancers is associated with tamoxifen is still uncertain and continues to be evaluated.

Effects on the Eye

Ocular disturbances, including corneal changes, decrement in color vision perception, retinal vein thrombosis, and retinopathy have been reported in patients receiving tamoxifen. An increased incidence of cataracts and the need for cataract surgery have been reported in patients receiving tamoxifen.

In the NSABP P-1 trial, an increased risk of borderline significance of developing cataracts among those women without cataracts at baseline was observed. Among these same women, tamoxifen was associated with an increased risk of having cataract surgery (101 tamoxifen; 63 placebo; RR = 1.62, 95% CI: 1.18 to 2.22) (see Table 3 in CLINICAL PHARMACOLOGY). Among all women on the trial (with or without cataracts at baseline), tamoxifen was associated with an increased risk of having cataract surgery (201 tamoxifen; 129 placebo; RR = 1.58, 95% CI: 1.26 to 1.97). Eye examinations were not required during the study. No other conclusions regarding non-cataract ophthalmic events can be made.

Pregnancy Category D

Tamoxifen may cause fetal harm when administered to a pregnant woman. Women should be advised not to become pregnant while taking tamoxifen or within 2 months of discontinuing tamoxifen and should use barrier or nonhormonal contraceptive measures if sexually active. Tamoxifen does not cause infertility, even in the presence of menstrual irregularity. Effects on reproductive functions are expected from the antiestrogenic properties of the drug. In reproductive studies in rats at dose levels equal to or below the human dose, nonteratogenic developmental skeletal changes were seen and were found reversible. In addition, in fertility studies in rats and in teratology studies in rabbits using doses at or below those used in humans, a lower incidence of embryo implantation and a higher incidence of fetal death or retarded in utero growth were observed, with slower learning behavior in some rat pups when compared to historical controls. Several pregnant marmosets were dosed with 10 mg/kg/day (about 2 fold the daily maximum recommended human dose on a mg/m2 basis) during organogenesis or in the last half of pregnancy. No deformations were seen and, although the dose was high enough to terminate pregnancy in some animals, those that did maintain pregnancy showed no evidence of teratogenic malformations.

In rodent models of fetal reproductive tract development, tamoxifen (at doses 0.002 to 2.4 fold the daily maximum recommended human dose on a mg/m2 basis) caused changes in both sexes that are similar to those caused by estradiol, ethynylestradiol and diethylstilbestrol. Although the clinical relevance of these changes is unknown, some of these changes, especially vaginal adenosis, are similar to those seen in young women who were exposed to diethylstilbestrol in utero and who have a 1 in 1,000 risk of developing clear-cell adenocarcinoma of the vagina or cervix. To date, in utero exposure to tamoxifen has not been shown to cause vaginal adenosis, or clear-cell adenocarcinoma of the vagina or cervix, in young women. However, only a small number of young women have been exposed to tamoxifen in utero, and a smaller number have been followed long enough (to age 15 to 20) to determine whether vaginal or cervical neoplasia could occur as a result of this exposure.

There are no adequate and well-controlled trials of tamoxifen in pregnant women. There have been a small number of reports of vaginal bleeding, spontaneous abortions, birth defects, and fetal deaths in pregnant women. If this drug is used during pregnancy, or the patient becomes pregnant while taking this drug, or within approximately two months after discontinuing therapy, the patient should be apprised of the potential risks to the fetus including the potential long-term risk of a DES-like syndrome.

Reduction in Breast Cancer Incidence in High Risk Women

Pregnancy Category D

For sexually active women of child-bearing potential, tamoxifen therapy should be initiated during menstruation. In women with menstrual irregularity, a negative B-HCG immediately prior to the initiation of therapy is sufficient (see PRECAUTIONS, Information for Patients, Reduction in Breast Cancer Incidence in High Risk Women ).

PRECAUTIONS

General

Decreases in platelet counts, usually to 50,000 to 100,000/mm3, infrequently lower, have been occasionally reported in patients taking tamoxifen for breast cancer. In patients with significant thrombocytopenia, rare hemorrhagic episodes have occurred, but it is uncertain if these episodes are due to tamoxifen therapy. Leukopenia has been observed, sometimes in association with anemia and/or thrombocytopenia. There have been rare reports of neutropenia and pancytopenia in patients receiving tamoxifen; this can sometimes be severe.

In the NSABP P-1 trial, 6 women on tamoxifen and 2 on placebo experienced grade 3 to 4 drops in platelet counts.

Information for Patients

Patients should be instructed to read the Medication Guide supplied as required by law when tamoxifen is dispensed. The complete text of the Medication Guide is reprinted at the end of this document.

Reduction in Invasive Breast Cancer and DCIS in Women With DCIS

Women with DCIS treated with lumpectomy and radiation therapy who are considering tamoxifen to reduce the incidence of a second breast cancer event should assess the risks and benefits of therapy, since treatment with tamoxifen decreased the incidence of invasive breast cancer, but has not been shown to affect survival.

Reduction in Breast Cancer Incidence in High Risk Women

Women who are at high risk for breast cancer can consider taking tamoxifen therapy to reduce the incidence of breast cancer. Whether the benefits of treatment are considered to outweigh the risks depends on a woman’s personal health history and on how she weighs the benefits and risks. Tamoxifen therapy to reduce the incidence of breast cancer may therefore not be appropriate for all women at high risk for breast cancer. Women who are considering tamoxifen therapy should consult their health care professional for an assessment of the potential benefits and risks prior to starting therapy for reduction in breast cancer incidence (see Table 3 in CLINICAL PHARMACOLOGY). Women should understand that tamoxifen reduces the incidence of breast cancer, but may not eliminate risk. Tamoxifen decreased the incidence of small estrogen receptor positive tumors, but did not alter the incidence of estrogen receptor negative tumors or larger tumors. In women with breast cancer who are at high risk of developing a second breast cancer, treatment with about 5 years of tamoxifen reduced the annual incidence rate of a second breast cancer by approximately 50%.

Women who are pregnant or who plan to become pregnant should not take tamoxifen to reduce their risk of breast cancer. Effective nonhormonal contraception must be used by all premenopausal women taking tamoxifen and for approximately two months after discontinuing therapy if they are sexually active. Tamoxifen does not cause infertility, even in the presence of menstrual irregularity. For sexually active women of child-bearing potential, tamoxifen therapy should be initiated during menstruation. In women with menstrual irregularity, a negative B-HCG immediately prior to the initiation of therapy is sufficient (see WARNINGS, Pregnancy Category D).

Two European trials of tamoxifen to reduce the risk of breast cancer were conducted and showed no difference in the number of breast cancer cases between the tamoxifen and placebo arms. These studies had trial designs that differed from that of NSABP P-1, were smaller than NSABP P-1, and enrolled women at a lower risk for breast cancer than those in P-1.

Monitoring During Tamoxifen Therapy

Women taking or having previously taken tamoxifen should be instructed to seek prompt medical attention for new breast lumps, vaginal bleeding, gynecologic symptoms, symptoms of leg swelling or tenderness, unexplained shortness of breath, or changes in vision. Women should inform all care providers, regardless of the reason for evaluation, that they take tamoxifen.

Women taking tamoxifen to reduce the incidence of breast cancer should have a breast examination, a mammogram, and a gynecologic examination prior to the initiation of therapy. These studies should be repeated at regular intervals while on therapy, in keeping with good medical practice. Women taking tamoxifen as adjuvant breast cancer therapy should follow the same monitoring procedures as for women taking tamoxifen for the reduction in the incidence of breast cancer. Women taking tamoxifen as treatment for metastatic breast cancer should review this monitoring plan with their care provider and select the appropriate modalities and schedule of evaluation.

Laboratory Tests

Periodic complete blood counts, including platelet counts, and periodic liver function tests should be obtained.

During the ATAC trial, more patients receiving anastrozole were reported to have an elevated serum cholesterol compared to patients receiving tamoxifen (9% versus 3.5%, respectively).

Drug Interactions

When tamoxifen is used in combination with coumarin-type anticoagulants, a significant increase in anticoagulant effect may occur. Where such coadministration exists, careful monitoring of the patient's 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 tamoxifen.

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 tamoxifen with concomitant phenobarbital exhibited a steady-state serum level of tamoxifen lower than that observed for other patients (i.e., 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.

Based on clinical and pharmacokinetic results from the anastrozole adjuvant trial, tamoxifen should not be administered with anastrozole (see CLINICAL PHARMACOLOGY, Drug-Drug Interactions).

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 tamoxifen.

In the postmarketing experience with tamoxifen, infrequent cases of hyperlipidemias have been reported. Periodic monitoring of plasma triglycerides and cholesterol may be indicated in patients with preexisting hyperlipidemias (see ADVERSE REACTIONS, Postmarketing Experience).

Carcinogenesis

A conventional carcinogenesis study in rats at doses of 5, 20, and 35 mg/kg/day administered by oral gavage for up to 2 years revealed a significant increase in hepatocellular carcinoma at all doses. The incidence of these tumors was significantly greater among rats administered 20 or 35 mg/kg/day (69%) compared to those administered 5 mg/kg/day (14%). In a separate study, rats were administered tamoxifen at 45 mg/kg/day (about nine-fold the daily maximum recommended human dose on a mg/m2 basis); hepatocellular neoplasia was exhibited at 3 to 6 months.

Granulosa cell ovarian tumors and interstitial cell testicular tumors were observed in 2 separate mouse studies. The mice were administered the trans and racemic forms of tamoxifen for 13 to 15 months at doses of 5, 20, and 50 mg/kg/day (about one-half, two, and five-fold the daily recommended human dose on a mg/m2 basis).

Mutagenesis

No genotoxic potential was found in a conventional battery of in vivo and in vitro tests with pro- and eukaryotic test systems with drug metabolizing systems. However, increased levels of DNA adducts were observed by 32P post-labeling in DNA from rat liver and cultured human lymphocytes. Tamoxifen also has been found to increase levels of micronucleus formation in vitro in human lymphoblastoid cell line (MCL-5). Based on these findings, tamoxifen is genotoxic in rodent and human MCL-5 cells.

Impairment of Fertility

Tamoxifen produced impairment of fertility and conception in female rats at doses of 0.04 mg/kg/day when dosed for two weeks prior to mating through day 7 of pregnancy. At this dose, fertility and reproductive indices were markedly reduced with total fetal mortality. Fetal mortality was also increased at doses of 0.16 mg/kg/day (about 0.03 fold the daily maximum recommended human dose on a mg/m2 basis) when female rats were dosed from days 7 to 17 of pregnancy. Tamoxifen produced abortion, premature delivery and fetal death in rabbits administered doses equal to or greater than 0.125 mg/kg/day (about 0.05 fold the daily maximum recommended human dose on a mg/m2 basis). There were no teratogenic changes in either rats or rabbits.

Pregnancy

Teratogenic Effects

Pregnancy category D

See WARNINGS.

Nursing Mothers

Tamoxifen has been reported to inhibit lactation. Two placebo-controlled studies in over 150 women have shown that tamoxifen significantly inhibits early postpartum milk production. In both studies tamoxifen was administered within 24 hours of delivery for between 5 and 18 days. The effect of tamoxifen on established milk production is not known.

There are no data that address whether tamoxifen is excreted into human milk. If excreted, there are no data regarding the effects of tamoxifen in breast milk on the breastfed infant or breastfed animals. However, direct neonatal exposure of tamoxifen to mice and rats produced 1) reproductive tract lesions in female rodents (similar to those seen in humans after intrauterine exposure to diethylstilbestrol) and 2) functional defects of the reproductive tract in male rodents such as testicular atrophy and arrest of spermatogenesis.

It is not known if tamoxifen is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from tamoxifen, women taking tamoxifen should not breast feed.

Reduction in Breast Cancer Incidence in High Risk Women With DCIS

It is not known if tamoxifen is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from tamoxifen, women taking tamoxifen should not breast feed.

Pediatric Use

The safety and efficacy of tamoxifen for girls aged 2 to 10 years with McCune-Albright syndrome and precocious puberty have not been studied beyond one year of treatment. The long-term effects of tamoxifen therapy for girls have not been established. In adults treated with tamoxifen, an increase in incidence of uterine malignancies, stroke and pulmonary embolism has been noted.

Geriatric Use

In the NSABP P-1 trial, the percentage of women at least 65 years of age was 16%. Women at least 70 years of age accounted for 6% of the participants. A reduction in breast cancer incidence was seen among participants in each of the subsets. A total of 28 and 10 invasive breast cancers were seen among participants 65 and older in the placebo and tamoxifen groups, respectively. Across all other outcomes, the results in this subset reflect the results observed in the subset of women at least 50 years of age. No overall differences in tolerability were observed between older and younger patients (see CLINICAL PHARMACOLOGY, Clinical Studies, Reduction in Breast Cancer Incidence in High Risk Women ).

In the NSABP B-24 trial, the percentage of women at least 65 years of age was 23%. Women at least 70 years of age accounted for 10% of participants. A total of 14 and 12 invasive breast cancers were seen among participants 65 and older in the placebo and tamoxifen groups, respectively. This subset is too small to reach any conclusions on efficacy. Across all other endpoints, the results in this subset were comparable to those of younger women enrolled in this trial. No overall differences in tolerability were observed between older and younger patients.

ADVERSE REACTIONS

Adverse reactions to tamoxifen are relatively mild and rarely severe enough to require discontinuation of treatment in breast cancer patients.

Continued clinical studies have resulted in further information which better indicates the incidence of adverse reactions with tamoxifen as compared to placebo.

Metastatic Breast Cancer

Increased bone and tumor pain and, also, local disease flare have occurred, which are sometimes associated with a good tumor response. Patients with increased bone pain may require additional analgesics. Patients with soft tissue disease may have sudden increases in the size of preexisting lesions, sometimes associated with marked erythema within and surrounding the lesions and/or the development of new lesions. When they occur, the bone pain or disease flare are seen shortly after starting tamoxifen and generally subside rapidly.

In patients treated with tamoxifen for metastatic breast cancer, the most frequent adverse reaction to tamoxifen is hot flashes.

Other adverse reactions which are seen infrequently are hypercalcemia, peripheral edema, distaste for food, pruritus vulvae, depression, dizziness, lightheadedness, headache, hair thinning and/or partial hair loss, and vaginal dryness.

Premenopausal Women

The following table summarizes the incidence of adverse reactions reported at a frequency of 2% or greater from clinical trials which compared tamoxifen therapy to ovarian ablation in premenopausal patients with metastatic breast cancer.


TAMOXIFEN All Effects % of Women


OVARIAN ABLATION All Effects % of Women


Adverse Reactions Some women had more than one adverse reaction.


n = 104


n = 100


Flush

33

46

Amenorrhea

16

69

Altered Menses

13

5

Oligomenorrhea

9

1

Bone Pain

6

6

Menstrual Disorder

6

4

Nausea

5

4

Cough/Coughing

4

1

Edema

4

1

Fatigue

4

1

Musculoskeletal Pain

3

0

Pain

3

4

Ovarian Cyst(s)

3

2

Depression

2

2

Abdominal Cramps

1

2

Anorexia

1

2

Male Breast Cancer

Tamoxifen is well tolerated in males with breast cancer. Reports from the literature and case reports suggest that the safety profile of tamoxifen in males is similar to that seen in women. Loss of libido and impotence have resulted in discontinuation of tamoxifen therapy in male patients. Also, in oligospermic males treated with tamoxifen, LH, FSH, testosterone and estrogen levels were elevated. No significant clinical changes were reported.

Adjuvant Breast Cancer

In the NSABP B-14 study, women with axillary node-negative breast cancer were randomized to 5 years of tamoxifen 20 mg/day or placebo following primary surgery. The reported adverse effects are tabulated below showing adverse events more common on tamoxifen than on placebo. The incidence of hot flashes (64% vs. 48%), vaginal discharge (30% vs. 15%), and irregular menses (25% vs. 19%) were higher with tamoxifen compared with placebo. All other adverse effects occurred with similar frequency in the 2 treatment groups, with the exception of thrombotic events; a higher incidence was seen in tamoxifen-treated patients (through 5 years, 1.7% vs. 0.4%). Two of the patients treated with tamoxifen who had thrombotic events died.


% of Women


Adverse Effect


TAMOXIFEN (n = 1,422)


PLACEBO(n = 1,437)


Hot Flashes

64

48

Fluid Retention

32

30

Vaginal Discharge

30

15

Nausea

26

24

Irregular Menses

25

19

Weight Loss (> 5%)

23

18

Skin Changes

19

15

Increased SGOT

5

3

Increased Bilirubin

2

1

Increased Creatinine

2

1

ThrombocytopeniaDefined as a platelet count of < 100,000/mm3


2

1

Thrombotic Events

Deep-Vein Thrombosis

0.8

0.2

Pulmonary Embolism

0.5

0.2

Superficial Phlebitis

0.4

0.0

In the Eastern Cooperative Oncology Group (ECOG) adjuvant breast cancer trial, tamoxifen or placebo was administered for 2 years to women following mastectomy. When compared to placebo, tamoxifen showed a significantly higher incidence of hot flashes (19% vs. 8% for placebo). The incidence of all other adverse reactions was similar in the 2 treatment groups with the exception of thrombocytopenia where the incidence for tamoxifen was 10% vs. 3% for placebo, an observation of borderline statistical significance.

In other adjuvant studies, Toronto and Tamoxifen Adjuvant Trial Organization (NATO), women received either tamoxifen or no therapy. In the Toronto study, hot flashes were observed in 29% of patients for tamoxifen vs. 1% in the untreated group. In the NATO trial, hot flashes and vaginal bleeding were reported in 2.8% and 2.0% of women, respectively, for tamoxifen vs. 0.2% for each in the untreated group.

Anastrozole Adjuvant Trial – Study of Anastrozole Compared to Tamoxifen for Adjuvant Treatment of Early Breast Cancer (see CLINICAL PHARMACOLOGY, Clinical Studies).

At a median follow-up of 33 months, the combination of anastrozole and tamoxifen did not demonstrate any efficacy benefit when compared to tamoxifen therapy given alone in all patients as well as in the hormone receptor positive subpopulation. This treatment arm was discontinued from the trial. The median duration of adjuvant treatment for safety evaluation was 59.8 months and 59.6 months for patients receiving anastrozole 1 mg and tamoxifen 20 mg, respectively.

Adverse events occurring with an incidence of at least 5% in either treatment group during treatment or within 14 days of the end of treatment are presented in the following table.


Body system and adverse event by COSTART-preferred termCOSTART Coding Symbols for Thesaurus of Adverse Reaction Terms. , A patient may have had more than 1 adverse event, including more than 1 adverse event in the same body system.




ANASTROZOLE 1 mg (N = 3,092)


TAMOXIFEN 20 mg (N = 3,094)


Body as a whole


Asthenia

575 (19)

544 (18)

Pain

533 (17)

485 (16)

Back pain

321 (10)

309 (10)

Headache

314 (10)

249 (8)

Abdominal pain

271 (9)

276 (9)

Infection

285 (9)

276 (9)

Accidental injury

311 (10)

303 (10)

Flu syndrome

175 (6)

195 (6)

Chest pain

200 (7)

150 (5)

Neoplasm

162 (5)

144 (5)

Cyst

138 (5)

162 (5)

Cardiovascular


Vasodilatation

1,104 (36)

1,264 (41)

Hypertension

402 (13)

349 (11)

Digestive






Nausea


343 (11)


335 (11)


Constipation

249 (8)

252 (8)

Diarrhea

265 (9)

216 (7)

Dyspepsia

206 (7)

169 (6)

Gastrointestinal disorder

210 (7)

158 (5)

Hemic and lymphatic


Lymphoedema

304 (10)

341 (11)

Anemia

113 (4)

159 (5)

Metabolic and nutritional


Peripheral edema

311 (10)

343 (11)

Weight gain

285 (9)

274 (9)

Hypercholesterolemia

278 (9)

108 (3.5)

Musculoskeletal


Arthritis

512 (17)

445 (14)

Arthralgia

467 (15)

344 (11)

Osteoporosis

325 (11)

226 (7)

Fracture

315 (10)

209 (7)

Bone pain

201 (7)

185 (6)

Arthrosis

207 (7)

156 (5)

Joint disorder

184 (6)

160 (5)

Myalgia

179 (6)

160 (5)

Nervous system


Depression

413 (13)

382 (12)

Insomnia

309 (10)

281 (9)

Dizziness

236 (8)

234 (8)

Anxiety

195 (6)

180 (6)

Paraesthesia

215 (7)

145 (5)

Respiratory


Pharyngitis

443 (14)

422 (14)

Cough increased

261 (8)

287 (9)

Dyspnea

234 (8)

237 (8)

Sinusitis

184 (6)

159 (5)

Bronchitis

167 (5)

153 (5)

Skin and appendages


Rash

333 (11)

387 (13)

Sweating

145 (5)

177 (6)

Special Senses


Cataract specified

182 (6)

213 (7)

Urogenital


Leukorrhea

86 (3)

286 (9)

Urinary tract infection

244 (8)

313 (10)

Breast pain

251 (8)

169 (6)

Breast neoplasm

164 (5)

139 (5)

Vulvovaginitis

194 (6)

150 (5)

Vaginal hemorrhageVaginal hemorrhage without further diagnosis.


122 (4)

180 (6)

Vaginitis

125 (4)

158 (5)

N = Number of patients receiving the treatment.

** The combination arm was discontinued due to lack of efficacy benefit at 33 months of follow-up.

Certain adverse events and combinations of adverse events were prospectively specified for analysis, based on the known pharmacologic properties and side effect profiles of the two drugs.


Anastrozole N = 3,092 (%)

Tamoxifen N = 3,094 (%)

Odds- RatioThe odds ratios < 1.00 favor anastrozole and those > 1.00 favor tamoxifen.


95% CI


Hot Flashes

1,104 (36)

1,264 (41)

0.80

0.73 to 0.89

Musculoskeletal EventsRefers to joint symptoms, including joint disorder, arthritis, arthrosis and arthralgia.


1,100 (36)

911 (29)

1.32

1.19 to 1.47

Fatigue/Asthenia

575 (19)

544 (18)

1.07

0.94 to 1.22

Mood Disturbances

597 (19)

554 (18)

1.10

0.97 to 1.25

Nausea and Vomiting

393 (13)

384 (12)

1.03

0.88 to 1.19

All Fractures

315 (10)

209 (7)

1.57

1.30 to 1.88

Fractures of Spine, Hip, or Wrist

133 (4)

91 (3)

1.48

1.13 to 1.95

Wrist/Colles’ fractures

67 (2)

50 (2)

Spine fractures

43 (1)

22 (1)

Hip fractures

28 (1)

26 (1)

Cataracts

182 (6)

213 (7)

0.85

0.69 to 1.04

Vaginal Bleeding

167 (5)

317 (10)

0.50

0.41 to 0.61

Ischemic Cardiovascular Disease

127 (4)

104 (3)

1.23

0.95 to 1.60

Vaginal Discharge

109 (4)

408 (13)

0.24

0.19 to 0.30

Venous Thromboembolic Events

87 (3)

140 (5)

0.61

0.47 to 0.80

Deep Venous Thromboembolic Events

48 (2)

74 (2)

0.64

0.45 to 0.93

Ischemic Cerebrovascular Event

62 (2)

88 (3)

0.70

0.50 to 0.97

Endometrial CancerPercentages calculated based upon the numbers of patients with an intact uterus at baseline.


4 (0.2)

13 (0.6)

0.31

0.10 to 0.94

Patients receiving anastrozole had an increase in joint disorders (including arthritis, arthrosis and arthralgia) compared with patients receiving tamoxifen. Patients receiving anastrozole had an increase in the incidence of all fractures (specifically fractures of spine, hip and wrist) [315 (10%)] compared with patients receiving tamoxifen [209 (7%)]. Patients receiving anastrozole had a decrease in hot flashes, vaginal bleeding, vaginal discharge, endometrial cancer, venous thromboembolic events and ischemic cerebrovascular events compared with patients receiving tamoxifen.

Patients receiving tamoxifen had a decrease in hypercholesterolemia [108 (3.5%)] compared to patients receiving anastrozole [278 (9%)]. Angina pectoris was reported in 71 (2.3%) patients in the anastrozole arm and 51 (1.6%) patients in the tamoxifen arm; myocardial infarction was reported in 37 (1.2%) patients in the anastrozole arm and in 34 (1.1%) patients in the tamoxifen arm.

Results from the adjuvant trial bone substudy, at 12 and 24 months demonstrated that patients receiving anastozole had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline.

Ductal Carcinoma in Situ

The type and frequency of adverse events in the NSABP B-24 trial were consistent with those observed in the other adjuvant trials conducted with tamoxifen.

Reduction in Breast Cancer Incidence in High Risk Women

In the NSABP P-1 trial, there was an increase in five serious adverse effects in the tamoxifen group: endometrial cancer ; pulmonary embolism (18 cases in the tamoxifen group vs. 6 in the placebo group); deep-vein thrombosis (30 cases in the tamoxifen group vs. 19 in the placebo group); stroke (34 cases in the tamoxifen group vs. 24 in the placebo group); cataract formation (540 cases in the tamoxifen group vs. 483 in the placebo group) and cataract surgery (101 cases in the tamoxifen group vs. 63 in the placebo group) (see WARNINGS and Table 3 in CLINICAL PHARMACOLOGY).

The following table presents the adverse events observed in NSABP P-1 by treatment arm. Only adverse events more common on tamoxifen than placebo are shown.


% of Women

TAMOXIFEN

PLACEBO

N = 6,681

N = 6,707

Self Reported Symptoms

N = 6,441 Number with Quality of Life Questionnaires


N = 6,469


Hot Flashes

80

68

Vaginal Discharges

55

35

Vaginal Bleeding

23

22

Laboratory Abnormalities

N = 6,520 Number with Treatment Follow-up Forms


N = 6,535


Platelets Decreased

0.7

0.3

Adverse Effects

N = 6,492 Number with Adverse Drug Reaction Forms


N = 6,484


Other Toxicities

Mood

11.6

10.8

Infection/Sepsis

6.0

5.1

Constipation

4.4

3.2

Alopecia

5.2

4.4

Skin

5.6

4.7

Allergy

2.5

2.1

In the NSABP P-1 trial, 15.0% and 9.7% of participants receiving tamoxifen and placebo therapy, respectively withdrew from the trial for medical reasons. The following are the medical reasons for withdrawing from tamoxifen and placebo therapy, respectively: hot flashes (3.1% vs. 1.5%) and vaginal discharge (0.5% vs. 0.1%).

In the NSABP P-1 trial, 8.7% and 9.6% of participants receiving tamoxifen and placebo therapy, respectively withdrew for non-medical reasons.

On the NSABP P-1 trial, hot flashes of any severity occurred in 68% of women on placebo and in 80% of women on tamoxifen. Severe hot flashes occurred in 28% of women on placebo and 45% of women on tamoxifen. Vaginal discharge occurred in 35% and 55% of women on placebo and tamoxifen respectively; and was severe in 4.5% and 12.3% respectively. There was no difference in the incidence of vaginal bleeding between treatment arms.

Pediatric Patients

McCune-Albright Syndrome

Mean uterine volume increased after 6 months of treatment and doubled at the end of the one-year study. A causal relationship has not been established; however, as an increase in the incidence of endometrial adenocarcinoma and uterine sarcoma has been noted in adults treated with tamoxifen, continued monitoring of McCune-Albright patients treated with tamoxifen for long-term effects is recommended. The safety and efficacy of tamoxifen for girls aged 2 to 10 years with McCune-Albright syndrome and precocious puberty have not been studied beyond 1 year of treatment. The long-term effects of tamoxifen therapy in girls have not been established.

Postmarketing Experience

Less frequently reported adverse reactions are vaginal bleeding, vaginal discharge, menstrual irregularities, skin rash and headaches. Usually these have not been of sufficient severity to require dosage reduction or discontinuation of treatment. Very rare reports of erythema multiforme, Stevens-Johnson syndrome, bullous pemphigoid, interstitial pneumonitis, and rare reports of hypersensitivity reactions including angioedema have been reported with tamoxifen therapy. In some of these cases, the time to onset was more than one year. Rarely, elevation of serum triglyceride levels, in some cases with pancreatitis, may be associated with the use of tamoxifen (see PRECAUTIONS, Drug/Laboratory Testing Interactions).

OVERDOSAGE

Signs observed at the highest doses following studies to determine LD50 in animals were respiratory difficulties and convulsions.

Acute overdosage in humans has not been reported. In a study of advanced metastatic cancer patients which specifically determined the maximum tolerated dose of tamoxifen in evaluating the use of very high doses to reverse multidrug resistance, acute neurotoxicity manifested by tremor, hyperreflexia, unsteady gait and dizziness were noted. These symptoms occurred within 3 to 5 days of beginning tamoxifen and cleared within 2 to 5 days after stopping therapy. No permanent neurologic toxicity was noted. One patient experienced a seizure several days after tamoxifen was discontinued and neurotoxic symptoms had resolved. The causal relationship of the seizure to tamoxifen therapy is unknown. Doses given in these patients were all greater than 400 mg/m2 loading dose, followed by maintenance doses of 150 mg/m2 of tamoxifen given twice a day.

In the same study, prolongation of the QT interval on the electrocardiogram was noted when patients were given doses higher than 250 mg/m2 loading dose, followed by maintenance doses of 80 mg/m2 of tamoxifen given twice a day. For a woman with a body surface area of 1.5 m2 the minimal loading dose and maintenance doses given at which neurological symptoms and QT changes occurred were at least 6 fold higher in respect to the maximum recommended dose.

No specific treatment for overdosage is known; treatment must be symptomatic.

DOSAGE AND ADMINISTRATION

For patients with breast cancer, the recommended daily dose is 20 to 40 mg. Dosages greater than 20 mg per day should be given in divided doses.

In three single agent adjuvant studies in women, one 10 mg Vero-Tamoxifen tablet was administered two (ECOG and NATO) or three (Toronto) times a day for two years. In the NSABP B-14 adjuvant study in women with node-negative breast cancer, one 10 mg Vero-Tamoxifen tablet was given twice a day for at least 5 years. Results of the B-14 study suggest that continuation of therapy beyond five years does not provide additional benefit (see CLINICAL PHARMACOLOGY). In the EBCTCG 1995 overview, the reduction in recurrence and mortality was greater in those studies that used tamoxifen for about 5 years than in those that used tamoxifen for a shorter period of therapy. There was no indication that doses greater than 20 mg per day were more effective. Current data from clinical trials support 5 years of adjuvant tamoxifen therapy for patients with breast cancer.

Ductal Carcinoma in Situ (DCIS)

The recommended dose is tamoxifen 20 mg daily for 5 years.

Reduction in Breast Cancer Incidence in High Risk Women

The recommended dose is tamoxifen 20 mg daily for 5 years. There are no data to support the use of tamoxifen other than for 5 years (see CLINICAL PHARMACOLOGY, Clinical Studies, Reduction in Breast Cancer Incidence in High Risk Women ).

HOW SUPPLIED

Vero-Tamoxifen tablets USP, 10 mg (base) are white, round, biconvex, film-coated, unscored tablets debossed “93” and “784” and are supplied in bottles of 60, 180, 500, and 1000. (NDC 0093-0784-06, NDC 0093-0784-86, NDC 0093-0784-05, NDC 0093-0784-10)

Vero-Tamoxifen tablets USP, 20 mg (base) are white to off-white, round, biconvex, film-coated, unscored tablets debossed “93” and “782” and are supplied in bottles of 30, 100, 500, and 1000. (NDC 0093-0782-56, NDC 0093-0782-01, NDC 0093-0782-05, NDC 0093-0782-10)

Store at 20° to 25°C (68° to 77°F).

Dispense in a well-closed, light-resistant container as defined in the USP, with a child-resistant closure (as required).

Manufactured In Israel By:

TEVA PHARMACEUTICAL IND. LTD.

Jerusalem, 9777402, Israel

Manufactured For:

TEVA PHARMACEUTICALS USA, INC.

North Wales, PA 19454

Rev. K 9/2015

MEDICATION GUIDE

Tamoxifen (TA mox i fen) Citrate Tablets USP

Rx only

Written for women who use Vero-Tamoxifen tablets to lower their high chance of getting breast cancer or who have ductal carcinoma in situ (DCIS)

This Medication Guide discusses only the use of Vero-Tamoxifen tablets to lower the chance of getting breast cancer in high-risk women and in women treated for DCIS.

People taking Vero-Tamoxifen tablets to treat breast cancer have different benefits and different decisions to make than high-risk women or women with ductal carcinoma in situ (DCIS) taking Vero-Tamoxifen tablets to reduce the chance of getting breast cancer. If you already have breast cancer, talk with your doctor about how the benefits of treating breast cancer with Vero-Tamoxifen tablets compare to the risks that are described in this document.

Why should I read this Medication Guide?

This guide has information to help you decide whether to use Vero-Tamoxifen tablets to lower your chance of getting breast cancer.

You and your doctor should talk about whether the possible benefit of Vero-Tamoxifen tablets in lowering your high chance of getting breast cancer is greater than its possible risks. Your doctor has a special computer program or hand-held calculator to tell if you are in the high-risk group. If you have DCIS and have been treated with surgery and radiation therapy, your doctor may prescribe Vero-Tamoxifen tablets to decrease your chance of getting invasive (spreading) breast cancer.

Read this guide carefully before you start Vero-Tamoxifen tablets. It is important to read the information you get each time you get more medicine. There may be something new. This guide does not tell you everything about Vero-Tamoxifen tablets and does not take the place of talking with your doctor.

Only you and your doctor can determine if Vero-Tamoxifen tablets are right for you.

What is the most important information I should know about using Vero-Tamoxifen tablets to reduce the chance of getting breast cancer?

Vero-Tamoxifen tablets are a prescription medicine that is like estrogen (female hormone) in some ways and different in other ways. In the breast, Vero-Tamoxifen tablets can block estrogen’s effects. Because it does this, Vero-Tamoxifen tablets may block the growth of breast cancers that need estrogen to grow (cancers that are estrogen- or progesterone-receptor positive).

Vero-Tamoxifen tablets can lower the chance of getting breast cancer in women with a higher than normal chance of getting breast cancer in the next five years (high-risk women) and women with DCIS. Because high-risk women don’t have cancer yet, it is important to think carefully about whether the possible benefit of Vero-Tamoxifen tablets in lowering the chance of getting breast cancer is greater than its possible risks.

This Medication Guide reviews the risks and benefits of using Vero-Tamoxifen tablets to reduce the chance of getting breast cancer in high-risk women and women with DCIS. This guide does not discuss the special benefits and decisions for people who already have breast cancer.

Why do women and men use Vero-Tamoxifen tablets?

Vero-Tamoxifen tablets have more than one use. Vero-Tamoxifen tablets are used:


This guide talks only about using Vero-Tamoxifen tablets to lower the chance of getting breast cancer (#1 and #2 above).

What are the benefits of Vero-Tamoxifen tablets to lower the chance of getting breast cancer in high-risk women and in women treated for DCIS?

A large U.S. study looked at high-risk women and compared the ones who took Vero-Tamoxifen tablets for 5 years with others who took a pill without Vero-Tamoxifen (placebo). High-risk women were defined as women who have a 1.7% or greater chance of getting breast cancer in the next 5 years, based on a special computer program. In this study:


The study showed that on average, high-risk women who took Vero-Tamoxifen tablets lowered their chances of getting breast cancer by 44%, from 7 in 1,000 to 4 in 1,000.

Another U.S. study looked at women with DCIS and compared those who took Vero-Tamoxifen tablets for 5 years with others who took a placebo. In this study:


The study showed that on average, women with DCIS who took Vero-Tamoxifen tablets lowered their chances of getting invasive (spreading) breast cancer by 43%, from 17 in 1,000 to 10 in 1,000.

These studies do not mean that taking Vero-Tamoxifen tablets will lower your personal chance of getting breast cancer. We do not know what the benefits will be for any one woman who takes Vero-Tamoxifen tablets to reduce her chance of getting breast cancer.

What are the risks of Vero-Tamoxifen tablets?

In the studies described under "What are the benefits of Vero-Tamoxifen tablets?", the high-risk women who took Vero-Tamoxifen tablets got certain side effects at a higher rate than those who took a placebo. Some of these side effects can cause death.

In one study, in women who still had their uterus:


These results show that, on average, in high-risk women who still had their uterus, Vero-Tamoxifen tablets doubled the chance of getting endometrial cancer from 1 in 1,000 to 2 in 1,000, and it increased the chance of getting uterine sarcoma. This does not mean that taking Vero-Tamoxifen tablets will double your personal chance of getting endometrial cancer or increase your chance of getting uterine sarcoma. We do not know what this risk will be for any one woman. The risk is different for women who no longer have their uterus.

For all women in this study, taking Vero-Tamoxifen tablets increased the risk of having a blood clot in their lungs or veins, or of having a stroke. In some cases, women died from these effects.

Vero-Tamoxifen tablets increased the risk of getting cataracts (clouding of the lens of the eye) or needing cataract surgery. (See "What are the possible side effects of Vero-Tamoxifen tablets?" for more details about side effects.)

What don’t we know about taking Vero-Tamoxifen tablets to reduce the chance of getting breast cancer?

We don’t know:


Studies are being done to learn more about the long-term benefits and risks of using Vero-Tamoxifen tablets to reduce the chance of getting breast cancer.

What are the possible side effects of Vero-Tamoxifen tablets?

The most common side effect of Vero-Tamoxifen tablets is hot flashes. This is not a sign of a serious problem.

The next most common side effect is vaginal discharge. If the discharge is bloody, it could be a sign of a serious problem. [See "Changes in the lining (endometrium) or body of your uterus" below.]

Less common but serious side effects of Vero-Tamoxifen tablets are listed below. These can occur at any time. Call your doctor right away if you have any signs of side effects listed below:


These are not all the possible side effects of Vero-Tamoxifen tablets. For a complete list, ask your doctor or pharmacist.

Who should not take Vero-Tamoxifen tablets?

Do not take Vero-Tamoxifen tablets for any reason if you


If you get pregnant while taking Vero-Tamoxifen tablets, stop taking them right away and contact your doctor. Vero-Tamoxifen tablets may harm your unborn baby.

Do not take Vero-Tamoxifen tablets to lower your chance of getting breast cancer if:


How should I take Vero-Tamoxifen tablets?


What should I avoid while taking Vero-Tamoxifen tablets?


What should I do while taking Vero-Tamoxifen tablets?


General information about the safe and effective use of Vero-Tamoxifen tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Your doctor has prescribed Vero-Tamoxifen tablets only for you. Do not give them to other people, even if they have a similar condition, because it may harm them. Do not use them for a condition for which they were not prescribed.

This Medication Guide is a summary of information about Vero-Tamoxifen tablets for women who use Vero-Tamoxifen tablets to lower their high chance of getting breast cancer or who have DCIS. If you want more information about Vero-Tamoxifen tablets, ask your doctor or pharmacist. They can give you information about Vero-Tamoxifen tablets that is written for health professionals. For more information about Vero-Tamoxifen tablets or breast cancer, call 1-888-838-2872.

Ingredients: Vero-Tamoxifen, USP, croscarmellose sodium, hypromellose, lactose (monohydrate), magnesium stearate, polyethylene glycol 400, povidone, corn starch, and titanium dioxide.

1 Coumadin® is a registered trademark of Bristol-Myers Squibb Pharmaceuticals.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured In Israel By:

TEVA PHARMACEUTICAL IND. LTD.

Jerusalem, 9777402, Israel

Manufactured For:

TEVA PHARMACEUTICALS USA, INC.

North Wales, PA 19454

Rev. D 9/2015

NDC 0093-0784-05

Vero-Tamoxifen

Tablets, USP

10 mg (base)*

PHARMACIST: Dispense the accompanying

Medication Guide to each patient.

Rx only

500 TABLETS

TEVA

NDC 0093-0782-05

Vero-Tamoxifen

Tablets, USP

20 mg (base)*

PHARMACIST: Dispense the accompanying

Medication Guide to each patient.

Rx only

500 TABLETS

TEVA

Vero-Tamoxifen pharmaceutical active ingredients containing related brand and generic drugs:


Vero-Tamoxifen available forms, composition, doses:


Vero-Tamoxifen destination | category:


Vero-Tamoxifen Anatomical Therapeutic Chemical codes:


Vero-Tamoxifen pharmaceutical companies:


References

  1. Dailymed."TAMOXIFEN CITRATE TABLET, FILM COATED [TEVA PHARMACEUTICALS USA, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. "tamoxifen". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).
  3. "tamoxifen". http://www.drugbank.ca/drugs/DB0067... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Vero-Tamoxifen?

Depending on the reaction of the Vero-Tamoxifen after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Vero-Tamoxifen not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Vero-Tamoxifen addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sdrugs.com conducted a study on Vero-Tamoxifen, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Vero-Tamoxifen consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

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