TAMOXIFEN CITRATE (tamoxifen citrate)

There are 2 contraindications. Absolute contraindication.

Contraindication List
Deep venous thrombosis
Lactation

There are 5 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Cerebrovascular accident
Pregnancy
Pulmonary thromboembolism
Thrombocytopenic disorder
Thromboembolic disorder

There are 6 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Cataracts
Congenital long QT syndrome
Disease of liver
Hypercalcemia
Leukopenia
Prolonged QT interval

There are 31 severe adverse reactions.

More Frequent	Less Frequent
General weakness	Cataracts Osteoporosis Tumor flare reaction

Rare/Very Rare

Abnormal hepatic function tests Acute pancreatitis Anemia Angioedema Bullous pemphigoid Cerebrovascular accident Cholestasis Deep venous thrombosis Disorder of cornea Endometrial carcinoma Endometrial hyperplasia Endometrial polyps Erythema multiforme Hepatic necrosis Hepatitis Hypercalcemia Hypersensitivity drug reaction Interstitial pneumonitis Leukopenia Pulmonary thromboembolism Retinal disorder Retinal thrombosis Steatosis of liver Stevens-johnson syndrome Thrombocytopenic disorder Thromboembolic disorder Thrombotic disorder

There are 27 less severe adverse reactions.

More Frequent	Less Frequent
Mood changes Peripheral edema Vaginal discharge Vaginal dryness	Alopecia Bone pain Cough Genital organ pruritus Headache disorder Irregular menstrual periods Menstrual disorder Oligomenorrhea Skin rash Vomiting Weight gain Weight loss

Rare/Very Rare
Abnormal vaginal bleeding Amenorrhea Body fluid retention Depression Dizziness Drug-induced hot flash Dysgeusia Erectile dysfunction Hypertriglyceridemia Libido changes Nausea

Tamoxifen may cause fetal harm when administered to pregnant women. Effects on reproductive function are expected from the antiestrogenic properties of the drug. In reproduction studies in rats using tamoxifen dosages equal to or less than the human dosage, nonteratogenic developmental skeletal changes were observed and were found to be reversible.

In fertility studies in rats and teratology studies in rabbits using dosages at or below those used in humans, a lower incidence of egg implantation and a higher incidence of fetal death or retarded in utero growth were observed, reportedly with slower learning behavior in some rat offspring compared with historical controls, although this latter effect is not clearly established. No teratogenic effects were observed in monkeys receiving tamoxifen during the period of organogenesis or the last half of pregnancy; although the dosage employed was high enough to terminate pregnancy in some of the animals, those that maintained pregnancy delivered offspring without evidence of teratogenicity. In reproduction studies in rats using tamoxifen dosages 0.002-2.4

times the maximum recommended dosages in humans on a mg/m2 basis, changes in both male and female similar to those caused by estradiol, ethynylestradiol, and diethylstilbestrol (DES) (no longer commercially available in the US) were observed. Although the clinical importance of these changes is unknown, some of these changes, especially vaginal adenosis, are similar to those observed in young women who were exposed to DES in utero; such women have a greater risk (1 in 1000) 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; of these, a smaller number have been followed long enough (15-20 years) to determine whether vaginal or cervical neoplasia could occur as a result of exposure to tamoxifen. There are no adequate and well-controlled studies using tamoxifen in pregnant women. There have been reports of spontaneous abortions, birth defects, fetal deaths, and vaginal bleeding.

Women should not become pregnant while receiving tamoxifen or within 2 months after discontinuance of therapy with the drug, and those of childbearing potential should use an effective barrier or other nonhormonal method of contraception during tamoxifen therapy and for approximately 2 months after the drug has been discontinued. When tamoxifen is administered during pregnancy or if the patient becomes pregnant while receiving the drug or within approximately 2 months after discontinuance of therapy with tamoxifen, the patient should be informed of the potential hazard to the fetus, including the possible long-term risk of a DES-like syndrome. Pregnancy testing should be performed prior to initiation of tamoxifen therapy in women of childbearing potential.

Alternatively, for sexually active women of childbearing potential who are receiving tamoxifen for reduction in the incidence of breast cancer, therapy with the drug should be initiated during menstruation. In women with menstrual irregularity, pregnancy testing with a negative beta-human chorionic gonadotropin (beta-HCG) test result should be confirmed immediately prior to the initiation of tamoxifen therapy.

It is not known if tamoxifen is distributed into milk. Direct exposure (not via breast milk) of neonatal mice and rat pups to tamoxifen has resulted in adverse reproductive tract effects (i.e., lesions in female pups that are similar to those observed in humans after intrauterine DES exposure; functional defects, including testicular atrophy and arrested spermatogenesis, in male pups). Because of the potential for serious adverse reactions to tamoxifen in nursing infants, a decision should be made whether to discontinue nursing during tamoxifen therapy and for 3 months after the last dose or to discontinue the drug, taking into account the importance of the drug to the woman.

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

No enhanced Geriatric Use information available for this drug.