Tamoxifen Citrate

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Overview

What is Tamoxifen Citrate?

Tamoxifen citrate tablets USP, a nonsteroidal antiestrogen, are for oral administration. Tamoxifen citrate tablets are available as:

10 mg Tablets.

20 mg Tablets.

Each tablet contains the following inactive ingredients: carboxymethylcellulose calcium, magnesium stearate, mannitol and starch.

Chemically, tamoxifen is the trans-isomer of a triphenylethylene derivative. The chemical name is (Z)2-[4-(1,2-diphenyl-1-butenyl) phenoxy]-N, N-dimethylethanamine 2-hydroxy-1,2,3- propanetricarboxylate (1:1). The structural and molecular formulas are:

Tamoxifen citrate has a molecular weight of 563.62, the pKa' is 8.85, the equilibrium solubility in water at 37°C is 0.5 mg/mL and in 0.02 N HCl at 37°C, it is 0.2 mg/mL.

What does Tamoxifen Citrate look like?

What are the available doses of Tamoxifen Citrate?

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What should I talk to my health care provider before I take Tamoxifen Citrate?

Sorry No records found

How should I use Tamoxifen Citrate?

Metastatic Breast Cancer:

For patients with breast cancer, the recommended daily dose is 20-40 mg. Dosages greater than 20 mg per day should be given in divided doses (morning and evening).

In three single agent adjuvant studies in women, one 10 mg tamoxifen citrate 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 tamoxifen citrate tablet was given twice a day for at least five years. Results of the B-14 study suggest that continuation of therapy beyond five years does not provide additional benefit (see ). 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 five years of adjuvant tamoxifen therapy for patients with breast cancer.

What interacts with Tamoxifen Citrate?

Tamoxifen citrate 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:

What are the warnings of Tamoxifen Citrate?

Effects in Metastatic Breast Cancer Patients:

Effects on the Uterus-Endometrial Cancer and Uterine Sarcoma:

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: 1.27-4.92). 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: 1.78-13.16). 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: 0.28-2.89). 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: 0.4-12.0). 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: 1.3-4.9). 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 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 post-operative radiation therapy in addition to surgery. Uterine sarcomas were reported in 4 women randomized to tamoxifen (1 FIGO IA, 1 FIGO IB, 1 FIGO IIA, and 1 FIGO IIIC) and one 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 one patient randomized to placebo had a MMMT. A similar incidence in endometrial adenocarcinoma and uterine sarcoma was observed among women receiving tamoxifen in five 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, eg, 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:

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:

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: 1.15-9.27). 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: 0.86-2.98). 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: 0.82-2.51). 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:

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

Effects on the liver: Non-malignant effects:

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

Other cancers:

Effects on the Eye:

In the NSABP P-1 trial, an increased risk of borderline significance of developing cataracts among those women without cataracts at baseline (540- tamoxifen; 483-placebo; RR=1.13, 95% CI: 1.00-1.28) 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: 1.17-2.25) (See in ). 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=1.51, 95% CI: 1.21-1.89). Eye examinations were not required during the study. No other conclusions regarding non-cataract ophthalmic events can be made.

Pregnancy Category D:

or within

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/m 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 15-20) 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:

What are the precautions of Tamoxifen Citrate?

General:

In the NSABP P-1 trial, 6 women on tamoxifen and 2 on placebo experienced grade 3-4 drops in platelet counts (≤50,000/mm).

Information for Patients:

Reduction in Invasive Breast Cancer and DCIS in Women with DCIS:

Array

CLINICAL PHARMACOLOGY

Array

Women who are pregnant or who plan to become pregnant should not take tamoxifen to reduce her 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 ).

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 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:

Drug Interactions:

In the NSABP P-1 trial, women who required coumarin-type anticoagulants for any reason were ineligible for participation in the trial (See ).

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 (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:

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 pre-existing hyperlipidemias (See section).

Carcinogenesis:

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

Mutagenesis:

in vivo

in vitro

in vitro

Impairment of Fertility:

Pregnancy: Teratogenic Effect: Pregnancy Category D:

Nursing Mothers:

Pediatric Use:

Geriatric Use:

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.

What are the side effects of Tamoxifen Citrate?

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:

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, light-headedness, headache, hair thinning and/or partial hair loss, and vaginal dryness.

Premenopausal Women:

Male Breast Cancer:

Adjuvant Breast Cancer:

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.

* Some women had more than one adverse reaction.
	Tamoxifen	Ovarian		Tamoxifen	Ovarian
	All Effects	Ablation		All Effects	Ablation

	% of Women	All Effects		All Effects
		% of Women			% of Women
Adverse Reactions *	n=104	n=100	Adverse Reactions	n=104	n=100
Flush	33	46	Edema	4	1
Amenorrhea	16	69	Fatigue	4	1
Altered Menses	13	5	Musculoskeletal Pain	3	0
Oligomenorrhea	9	1	Pain	3	4
Bone Pair	6	6	Ovarian Cyst(s)	3	2
Menstrual Disorder	6	4	Depression	2	2
Nausea	5	4	Abdominal Cramps	1	2
Cough/Coughing	4	1	Anorexia	1	2
*Defined as a platelet count of <100,000/mm
	% of Women		% of Women
	Tamoxifen	Placebo		Tamoxifen	Placebo
Adverse Effect	(N-1422)	(N=1437)	Adverse Effects	(N=1422)	(N=1437)
Hot Flashes	64	48	Increased Bilirubin	2	1
Fluid Retention	32	30	Increased Creatinine	2	1
Vaginal Discharge	30	15	Thrombocytopenia *	2	1
Nausea	26	24	Thrombotic Events
Irregular Menses	25	19	Deep Vein Thrombosis	0.8	0.2
Weight Loss (>5%)	23	18	Pulmonary Embolism	0.5	0.2
Skin Changes	19	15	Superficial Phlebitis	0.4	0.0
Increased SGOT	5	3

Ductal Carcinoma in Situ (DCIS):

Reduction in Breast Cancer Incidence in High Risk Women:

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.

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.

1
2
3
NSABP P-1 Trial: All Adverse Events
	% of Women		% of Women
	Tamoxifen	Placebo		Tamoxifen	Placebo
	N=6681	N=6707		N=6681	N=6707
Self Reported Symptoms	N=6441	1	N=6469	1	Adverse Effects	N=6492	3	N=6484	3
Hot Flashes	80	68	Other Toxicities
Vaginal Discharges	55	35	Mood	11.6	10.8
Vaginal Bleeding	23	22	Infection/Sepsis	6.0	5.1
			Constipation	4.4	3.2
Laboratory Abnormalities	N=6520	2	N=6535	2	Alopecia	5.2	4.4
Platelets decreased	0.7	0.3	Skin	5.6	4.7
			Allergy	2.5	2.1

Postmarketing experience:

Pediatric Patients – McCune-Albright Syndrome:

What should I look out for while using Tamoxifen Citrate?

Tamoxifen citrate 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:

What might happen if I take too much Tamoxifen Citrate?

Signs observed at the highest doses following studies to determine LD 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 3-5 days of beginning tamoxifen and cleared within 2-5 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/m loading dose, followed by maintenance doses of 150 mg/m 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/m loading dose, followed by maintenance doses of 80 mg/m of tamoxifen given twice a day. For a woman with a body surface area of 1.5 m 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.

How should I store and handle Tamoxifen Citrate?

Store below 30°C (86°F).Manufactured by:DANBURY PHARMACAL, INC.Danbury, CT 06810Store below 30°C (86°F).Manufactured by:DANBURY PHARMACAL, INC.Danbury, CT 0681010 mg Tablets:20 mg Tablets:Store at controlled room temperature, 20-25°C (68-77°F) [see USP]. Dispense in a well-closed, light-resistant container.Manufactured by:Ft. Lauderdale, FL 33314Toll Free 1-866-292-6719Rev. date: 02/03A722710 mg Tablets:20 mg Tablets:Store at controlled room temperature, 20-25°C (68-77°F) [see USP]. Dispense in a well-closed, light-resistant container.Manufactured by:Ft. Lauderdale, FL 33314Toll Free 1-866-292-6719Rev. date: 02/03A722710 mg Tablets:20 mg Tablets:Store at controlled room temperature, 20-25°C (68-77°F) [see USP]. Dispense in a well-closed, light-resistant container.Manufactured by:Ft. Lauderdale, FL 33314Toll Free 1-866-292-6719Rev. date: 02/03A722710 mg Tablets:20 mg Tablets:Store at controlled room temperature, 20-25°C (68-77°F) [see USP]. Dispense in a well-closed, light-resistant container.Manufactured by:Ft. Lauderdale, FL 33314Toll Free 1-866-292-6719Rev. date: 02/03A722710 mg Tablets:20 mg Tablets:Store at controlled room temperature, 20-25°C (68-77°F) [see USP]. Dispense in a well-closed, light-resistant container.Manufactured by:Ft. Lauderdale, FL 33314Toll Free 1-866-292-6719Rev. date: 02/03A7227

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Clinical Information

Chemical Structure

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Clinical Pharmacology

Absorption and Distribution:

Non-Clinical Toxicology

Tamoxifen citrate 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:

Drug Interactions:

In the NSABP P-1 trial, women who required coumarin-type anticoagulants for any reason were ineligible for participation in the trial (See ).

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 (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.

General:

In the NSABP P-1 trial, 6 women on tamoxifen and 2 on placebo experienced grade 3-4 drops in platelet counts (≤50,000/mm).

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:

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, light-headedness, headache, hair thinning and/or partial hair loss, and vaginal dryness.

Premenopausal Women:

Male Breast Cancer:

Adjuvant Breast Cancer:

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.

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Reference

This information is obtained from the National Institute of Health's Standard Packaging Label drug database.
"https://dailymed.nlm.nih.gov/dailymed/"

While we update our database periodically, we cannot guarantee it is always updated to the latest version.

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Clonazepam Description Each single-scored tablet, for oral administration, contains 0.5 mg, 1 mg, or 2 mg Clonazepam, USP, a benzodiazepine. Each tablet also contains corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Clonazepam tablets USP 0.5 mg contain Yellow D&C No. 10 Aluminum Lake. Clonazepam tablets USP 1 mg contain Yellow D&C No. 10 Aluminum Lake, as well as FD&C Blue No. 1 Aluminum Lake. Chemically, Clonazepam, USP is 5-(o-chlorophenyl)-1,3-dihydro-7-nitro-2H-1,4-benzodiazepin-2-one. It is a light yellow crystalline powder. It has the following structural formula: C15H10ClN3O3 M.W. 315.72

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