Tamoxifen Citrate
(British Approved Name Modified, US Adopted Name, rINNM)
Drug Nomenclature
INNs in main languages (French, Latin, Russian, and Spanish):
Pharmacopoeias. In China, Europe, International, and US.
European Pharmacopoeia, 6th ed., 2008 and Supplements 6.1 and 6.2 (Tamoxifen Citrate). A white or almost white, polymorphic, crystalline powder. Slightly soluble in water and in acetone; soluble in methyl alcohol.
The United States Pharmacopeia 31, 2008 (Tamoxifen Citrate). A white, fine, crystalline powder. Very slightly soluble in water, in alcohol, in acetone, and in chloroform; soluble in methyl alcohol. Protect from light.
Adverse Effects
The most frequent adverse effects of tamoxifen are hot flushes. Other adverse effects include fluid retention, nausea, gastrointestinal intolerance, vaginal bleeding or discharge, pruritus vulvae, rashes, dry skin, and alopecia. There have also been reports of dizziness, headache, depression, confusion, fatigue, and muscle cramps. There may be an increased tendency to thromboembolism, and pulmonary embolism has occurred. Tumour pain and flare may be a sign of response, but hypercalcaemia, sometimes severe, has developed in patients with bony metastases. Transient thrombocyto-penia and leucopenia have been reported. Blurred vision and loss of visual acuity, corneal opacities, retinopathies, and cataracts have occurred rarely. Tamoxifen has been associated with increased liver enzymes, and rarely with cholestasis and hepatitis. Hypertriglyceridaemia has occurred. Uterine fibroids and endometrial changes including hyperplasia and polyps may occur, and an increased incidence of endometrial carcinoma, and rarely uterine sarcoma, has been reported. Suppression of menstruation may occur in premenopausal women and cystic ovarian swellings have occasionally occurred. Very rare cases of interstitial pneumonitis have been reported.
Carcinogenicity. Tamoxifen has a stimulant effect on the endometrium (probably by acting as a partial oestrogen agonist) and its use has been associated with the development of endometrial polyps and endometriosis, and an increased risk of endometrial cancer. The risk, which increases with duration of therapy, is generally agreed to be modest, and the clinical benefit in women with breast cancer outweighs any increased risk of endometrial neoplasm. Women taking tamoxifen to prevent breast cancer have been estimated to have a 2.53-fold greater risk of developing endometrial carcinoma than untreated women. The risk may increase with more prolonged use and a case-control study has reported that long-term (over 2 years) users may have a worse prognosis if endometrial cancer develops, due to less favourable history and stage. Another case-control study showed that the relative risk of endometrial cancer increased with duration of tamoxifen treatment, up to at least 10 years. Risk was not associated with the daily dose of tamoxifen, and was comparable in pre- and postmenopausal women.
It has been recommended that women with breast cancer taking tamoxifen should have annual gynaecological examinations, and any unusual symptoms, including abnormal bleeding or spotting should be investigated promptly. Women taking tamoxifen for prophylaxis of breast cancer should be monitored carefully for endometrial hyperplasia. If atypical hyperplasia develops, tamoxifen should be stopped while the condition is treated and a hysterectomy should be considered before tamoxifen is re-started. However, up to 39% of postmenopausal women taking tamoxifen show endometrial changes and as these seldom progress to cancer, the value of routine endometrial biopsies has been questioned. Transvaginal ultrasonography has been used as a noninvasive method of endometrial screening, but has a high rate of false-positive results. It has been suggested that colour doppler ultrasonography, which distinguishes vascular-ised lesions such as polyps and carcinomas from avascular atrophic lesions, may be a useful alternative. There is some evidence that a levonorgestrel-releasing intra-uterine device can protect against the uterine changes induced by tamoxifen.
Although rare, there is an increase in the risk of uterine sarcoma in women receiving tamoxifen. Between 1978, when tamoxifen was first marketed in the USA, and April 2001, the FDA was aware of 43 cases in women who had been receiving tamoxifen; there had also been reports in 116 women in other countries. Although less than the expected rate in this population, this was considered to be due to underreporting. An evaluation of data from 39 451 breast cancer patients initially treated with tamoxifen found that the overall risk of uterine corpus cancer was more than doubled with the use of tamoxifen; the risk of rare but aggressive forms of uterine tumours, notably malignant mixed mullerian tumours, was increased more than fourfold.
Tamoxifen has been shown to form DNA adducts in rat livers, and there has been speculation that it may cause liver cancer in humans. However, there is considerable interspecies variation in the metabolism of tamoxifen and several large-scale clinical trials did not find an increase in liver carcinogenicity in humans. There is also little evidence of an increased relative risk of other secondary malignancies such as gastrointestinal or ovarian cancers.
Effects on the blood. Pancytopenia developed shortly after beginning tamoxifen therapy in an elderly woman, and persisted for some years; the patient eventually developed very severe leucopenia and died of infection. Thrombocytopenia has also been reported.
Effects on blood lipids. Tamoxifen has been reported to have a generally favourable effect on serum lipid profiles. Patients with breast cancer and subsequent chemotherapy-induced ovarian failure developed marked increases in total cholesterol and low-density lipoprotein levels; adjuvant tamoxifen was found to decrease these serum lipid concentrations to below baseline concentrations. No significant changes in high-density lipoprotein or serum triglyceride concentrations were observed. However, some cases of increased serum triglycerides in women with preexisting hypertriglyceridaemia have been reported. Pancreatitis has also resulted. It has been suggested that tamoxifen should be used with caution in patients with hypertriglyceridaemia.
Effects on the cardiovascular system. ISCHAEMIC HEART DISEASE. For discussion of whether the effects of tamoxifen on lipid profiles can alter the incidence of ischaemic heart disease, see Cardiovascular Disorders under Uses and Administration, below.
STROKE. An excess risk of stroke was seen in tamoxifen compared with placebo recipients (5 cases versus 1) in a study of adjuvant tamoxifen. A statistically non-significant increase in stroke was also seen in a study on the use of tamoxifen for breast cancer prevention (0.5 excess cases per 1000 women per year). A meta-analysis of 9 trials for prevention or treatment of breast cancer, involved data from 39 601 women, of whom 19 954 received tamoxifen. It concluded that use of tamoxifen increased the risk of ischaemic stroke by 82%, and the risk of any stroke by 29%; however, the absolute increase in risk was small.
In contrast, a case-control study of 11 045 women with breast cancer, found that tamoxifen use was not associated with an increased risk of first stroke.
THROMBOEMBOLISM. A case control study, involving 25 cases of deep-vein thrombosis or pulmonary embolism among more than 10 000 women with breast cancer, suggested that current use of tamoxifen was associated with an estimated relative risk of developing idiopathic venous thromboembolism of 7.1 (95% confidence interval 1.5 to 33). Past use of tamoxifen was not associated with a materially increased risk. In a randomised placebo-controlled study, there was an increase in pulmonary emboli in women receiving tamoxifen for cancer prevention (excess of 0.46 cases per 1000 women per year). The fatality rate from pulmonary emboli in tamoxifen recipients was about 17%. In this study, there was also a trend towards more deep-vein thrombosis in tamoxifen recipients. In another controlled study of breast cancer prevention, tamoxifen approximately doubled the risk of developing a major thromboembolic event such as pulmonary embolism, deep-vein thrombosis, or retinal thrombosis. Cerebral sinus thrombosis has also been reported. An analysis of 4 tamoxifen prevention studies also found that venous thromboembolic events were increased in all studies, with a relative risk of 1.9 for those taking tamoxifen compared with placebo. However, another randomised study found only a borderline significantly higher risk of developing venous thromboem-bolic events in those women allocated to tamoxifen; most of these events were superficial thrombophlebitis. Furthermore, women already at risk for atherosclerosis had a higher risk of venous thrombo embolism. While the authors could not exclude a selection bias for healthier subjects in the study, they commented that the prothrombotic effect of tamoxifen may depend on the patient’s existing endocrine status, and may be attenuated in those women taking HRT, especially when it is used transdermally.
Effects on the eyes. Tamoxifen has been reported to be associated with decreased visual acuity, corneal opacities and cataract, and retinopafhy. The latter is sometimes progressive although in most cases it has shown improvement once the drug was stopped. A prospective study in 63 patients taking tamoxifen 20 mg daily found evidence of decreased visual acuity, macular oedema, and retinal opacities in 4, occurring after 10 to 35 months of therapy. A small excess risk of developing cataracts (3.1 extra per year per 1000 women) and of requiring cataract surgery (1.7 per year per 1000 women) was found in women taking tamoxifen for up to 5 years to reduce the risk of breast cancer. Studies in vitro have suggested that cataract formation may be due to inhibition of chloride channels in the lens by tamoxifen or its hydroxy metabolite. Retinopafhy after high-dose tamoxifen treatment may be associated with crystalline deposition of the drug in the retina.
Effects on the genito-urinary system. Persistent nocturnal priapism was reported in a man receiving tamoxifen 20 mg daily. Symptoms abated within 24 hours of withdrawing the drug. Impotence has been reported in men receiving tamoxifen, and has been attributed to a paradoxical oestrogenic effect.
Effects on the liver. Cholestasis and increased liver enzyme values have been reported on use of tamoxifen in a 75-year-old patient. Enzyme activity rose again on rechallenge with tamoxifen. Fatal hepatocellular necrosis and agranulocytosis, possibly exacerbated by continuing to take the drug once jaundice developed, has also been reported; the authors noted that 4 cases of hepatic failure (3 fatal) and 5 cases of hepatitis (1 fatal) had been reported to the UK CSM. Patients taking tamoxifen may also develop steatohepatitis, which must be distinguished from alcohol-induced liver disease. Steatohepatitis is reversible on withdrawal of tamoxifen. A study in healthy women who had had hysterectomies found the risk of steatohepatitis to be particularly high among obese women, moderately high among overweight women, and similar to that with placebo in women of normal weight. Bezafibrate has been tried to prevent progression of steatohepatitis and permit continued use of tamoxifen. For a report of peliosis hepatis and liver haemorrhage in a patient receiving tamoxifen and warfarin, see under Interactions, below.
For reference to studies in animals suggesting that tamoxifen has the potential to cause liver cancer, see Carcinogenicity, above.
Effects on the ovaries. Ovarian cysts are relatively common as an adverse effect in women receiving adjuvant tamoxifen: a study in 95 such women reported the development of ovarian cysts in 6 of 16 (37.5%) who were premenopausal and in 5 of 79 postmenopausal women (6.3%). In 2 of the premenopausal women the cysts were complex. Two women underwent laparot-omy for persistent cysts that were found to be benign, and 1 for leiomyoma; the cysts in the other 8 women resolved after withdrawal of tamoxifen. A study of 142 breast cancer patients receiving tamoxifen found ovarian cysts in 24 patients after treatment. Cyst development was more common in pre-menopausal women, patients with high oestrogen levels, and patients who did not receive high-dose chemotherapy. There is little evidence that tamoxifen increases the risk of ovarian cancer (see Carcinogenicity, above).
Effects on the skin and hair. Vasculitis has been reported in patients given tamoxifen.,t Withdrawal of the drug resulted in complete clearance of the lesions; in one case, on re-introduction, purpura developed again within a few days. The results suggest that tamoxifen can produce immune-mediated vascular damage.
In another report a patient with white hair developed darkening and repigmentation of the hair after about 2 / years of tamoxifen therapy. Alopecia has also been reported in women given tamoxifen, and in older patients the follicle may not recover.
Precautions
All patients being considered for treatment with tamoxifen should be assessed for any increased risk of thromboembolism. Tamoxifen should not be used for treatment of infertility or the prophylaxis of breast cancer in women with a history of thromboembolic events. When used to treat breast cancer in such women, the risks and benefits should be considered; in some patients, especially those given cytotoxic drugs, prophylactic anticoagulation may be justified. Care is also needed during or immediately after major surgery or prolonged immobility; all patients should be given prophylaxis against thrombosis. In patients being treated for infertility, tamoxifen should be stopped at least 6 weeks before surgery or long-term immobility and only restarted when the patient is fully mobile. Patients should be made aware of the symptoms of thromboembolism and advised to report sudden breathlessness or any pain in the calf of one leg. Tamoxifen should be withdrawn immediately in any patient developing thromboembolism and appropriate treatment given. Treatment should not usually be restarted for infertility therapy but resumption of tamoxifen with prophylactic anticoagulation may be justified in selected patients with breast cancer.
Women treated with tamoxifen should have routine gynaecological monitoring, and any abnormal symptoms such as menstrual irregularities, abnormal vaginal bleeding or discharge, or pelvic pain should be investigated (see also under Carcinogenicity, above). Periodic complete blood counts and liver function tests have been suggested.
Abuse. Although the supervised use of tamoxifen for the treatment of gynaecomastia resulting from the abuse of anabolic steroids has been reported it also appears to be widely used without medical supervision. Tamoxifen can be used to treat idiopathic gynaecomastia and gynaecomastia resulting as an adverse effect of nonsteroidal anti-androgens used to treat prostate cancer (see under Breast Disorders, Non-malignant, below).
Breast feeding. Tamoxifen was shown to inhibit lactation in 60 puerperal women. Licensed product information recommends that it should not be given to lactating women.
Porphyria. Tamoxifen has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients.
Pregnancy. Tamoxifen is contra-indicated in pregnancy. Ambiguous genitalia have been reported in an infant exposed to tamoxifen in utero, although no causal link was demonstrated. Another infant was born with Goldenhar’s syndrome (oculoau-riculovertebral dysplasia) after exposure to tamoxifen throughout a 26-week pregnancy. The mother had also taken cocaine and marijuana during the first 6 weeks of pregnancy, and a bone scan using technetium Tc99m medronate had been performed. The US manufacturer of tamoxifen (Zeneca, USA) was aware of 50 pregnancies in patients taking tamoxifen, resulting in 19 normal births, 8 terminations, 13 unknown outcomes and 10 infants with fetal or neonatal abnormalities.
Tamoxifen has also been used to stimulate ovulation in women with luteal phase dysfunction. In one study tamoxifen was given to 40 women, resulting in 14 pregnancies. Although 9 infants were born with no congenital abnormalities, there were 5 spontaneous abortions, which the authors felt was unacceptably high. Another study, using lower doses of tamoxifen (in some cases sequentially with clomifene), reported 32 pregnancies and only 3 spontaneous abortions in 65 treated patients.
Radiotherapy. There are reports of radiation recall, with erythema at the site of previous radiotherapy, in patients receiving tamoxifen.
Interactions
There is a risk of increased anticoagulant effect if tamoxifen is given with coumarin anticoagulants. Conversely, use with cytotoxic drugs may increase the risk of thromboembolic events; prophylactic anticoagulation should be considered. Tamoxifen increases the dopaminergic effect of bromocriptine. Use with inhibitors of cytochrome P450 isoenzyme CYP2D6 has been shown to reduce plasma concentrations of en-doxifen, a tamoxifen metabolite (see Pharmacokinetics, below); the clinical relevance is unclear.
Allopurinol. For reference to exacerbation of hepatotoxicity when tamoxifen was given with allopurinol.
Antibacterials. Rifampicin was found to decrease plasma concentrations of tamoxifen in 10 healthy subjects. This was thought to be due to induction of cytochrome P450 isoenzyme CYP3A4 by rifampicin.
Anticoagulants. Cases of a potentially life-threatening interaction between tamoxifen and warfarin, with marked prolongation of prothrombin times, haematuria, and haematoma, have been reported. It has been suggested that in addition to enhancement of the effects of warfarin, competition for the same metabolic enzyme systems might reduce the activity of tamoxifen against tumours, but this remains speculative.
Peliosis hepatis and fatal liver haemorrhage have been reported in a patient who was receiving tamoxifen with warfarin and a liothyronine-levothyroxine preparation.
Antidepressants. The metabolism of tamoxifen to an active metabolite, 4-hydroxy-N-desmethyltamoxifen (endoxifen), may be inhibited by paroxetine, a potent inhibitor of the cytochrome P450 isoenzyme CYP2D6. However, the clinical consequences of this are, as yet, unclear. In addition, a case-control study found that patients taking tamoxifen with known inhibitors of CYP isoenzymes, including CYP2D6, were no more likely to relapse than those not receiving a CYP inhibitor.
Antineoplastics. Aminoglutethimide reduces serum tamoxifen concentrations, possibly by increasing its metabolism. For mention of an increased risk of haemolytic-uraemic syndrome in patients who received therapy with tamoxifen and mitomycin see Effects on the Kidneys, under Mitomycin. Tamoxifen is reported to reduce plasma concentrations of letrozole.
Immunosuppressants. For the results of a study in vitro suggesting that tamoxifen might inhibit the metabolism of tacrolimus by inhibiting the cytochrome P450 isoenzyme system, see under Interactions of Tacrolimus.
Neuromuscular blockers. For reference to prolonged neuromuscular blockade in a patient given atracurium while receiving tamoxifen.
Pharmacokinetics
Peak plasma concentrations of tamoxifen occur 4 to 7 hours after an oral dose. It is extensively protein bound. Plasma clearance is reported to be biphasic and the terminal half-life may be up to 7 days. It is extensively metabolised by the cytochrome P450 isoenzymes CYP3A4, CYP2C9, and CYP2D6. The major serum metabolite, N-desmethyltamoxifen, has a half-life at steady state of about 14 days. 4-Hydroxytamoxifen is a minor metabolite. In-vitro studies suggest that both these metabolites are further metabolised to 4-hydroxy-N-desmethyltamoxifen (endoxifen). Several of the metabolites are stated to have similar pharmacological activity to the parent compound. Tamoxifen is excreted slowly in the faeces, mainly as conjugates. Small amounts are excreted in urine. Tamoxifen appears to undergo enterohepatic circulation.
Genetic factors. Tamoxifen is metabolised by the cytochrome P450 isoenzymes, and its metabolites may play a role in its anti-neoplastic effect. Studies have suggested that patients with low or absent CYP2D6 activity or who are being treated with CYP2D6 inhibitors have lower concentrations of endoxifen. Patients with CYP2D6*3, *4, *5, and *6 alleles are designated as poor metabolisers, those with *9, *10, *17, *29, and *41 as intermediate metabolisers, and those with *1, *2, and *35 as extensive metabolisers. Genetic polymorphism in the enzymes responsible for tamoxifen biotransformation has the potential to affect clinical outcomes. While a small study showed a decreased risk of breast cancer recurrence in patients with the CYP2D6*4 allele when treated with tamoxifen, another found that this allele was an independent predictor of a higher risk of disease relapse and a lower incidence of hot flashes in postmenopausal women with breast cancer. A further study found that carriers of CYP2D6 alleles *4 or *5 showed a greater risk for breast cancer relapse. Furthermore, carriers of the CYP2C19*17 genotype had a more favourable clinical outcome. These results prompted the Clinical Pharmacology Subcommittee of the US FDA Advisory Committee for Pharmaceutical Science to advise that availability of genotypic testing be included in licensed product information for tamoxifen. Some have commented that it would seem reasonable to confine CYP2D6 testing to situations where it might guide the choice between tamoxifen and an alternative.
Metabolism. Tamoxifen is extensively metabolised by cytochrome P450 isoenzymes, to active metabolites that include N-desmethyltamoxifen, 4-hydroxytamoxifen, and 4-hydroxy-N-desmethyltamoxifen (endoxifen). In-vitro studies suggest that both N-desmethyltamoxifen and 4-hydroxytamoxifen are further metabolised to endoxifen. However, the biotransformation of tamoxifen has not been fully elucidated, and there is growing interest in how genetic polymorphism might influence the efficacy and toxicity of tamoxifen and its metabolites (see Genetic Factors, above).
Uses and Administration
Tamoxifen is an oestrogen antagonist with actions similar to those of clomifene citrate. It may also inhibit the production or release of cellular growth factors and induce apoptosis. It is used in the adjuvant endocrine therapy of node-positive breast cancer, in the treatment of metastatic disease, and for prophylaxis in women at increased risk including those with ductal carcinoma in situ. It has been tried in some other malignancies including tumours of the ovary and in malignant melanoma. Tamoxifen is also used to stimulate ovulation in women with anovulatory infertility. See also the cross-references below. Tamoxifen is given orally as the citrate but doses are calculated in terms of the base; tamoxifen citrate 15.2 mg is equivalent to about 10 mg of tamoxifen. In the treatment of breast cancer, usual doses are tamoxifen 20 mg daily, in 2 divided doses or as a single daily dose. Doses of up to 40 mg daily may be given butno additional benefit has been demonstrated. Adjuvant therapy is normally continued for up to 5 years, although the optimum duration is still uncertain. To reduce breast cancer incidence in women at high risk of the disease, the licensed dose of tamoxifen is 20 mg daily for 5 years.
In the treatment of anovulatory infertility the usual dose is tamoxifen 20 mg daily on days 2 to 5 of the menstrual cycle, increased if necessary in subsequent cycles up to 80 mg daily. In women with irregular menstruation the initial course may be begun on any day, and a second course begun at a higher dose after 45 days if there has been no response. If the patient responds with menstruation, subsequent courses may begin on day 2 of the cycle.
A topical formulation of 4-hydroxytamoxifen, a metabolite of tamoxifen, is under investigation for the treatment of cyclic mastalgia.
Breast disorders, non-malignant. GYNAECOMASTIA. Tamoxifen, usually in doses of 10 mg twice daily, has been reported to be effective in reducing pain, swelling, and breast size in men or pubertal boys with gynaecomastia. Tamoxifen has been recommended as a drug of choice in patients requiring drug therapy, given for 3 months to see if a response occurs. It has also been reported to be effective for the prevention and treatment of gynaecomastia and breast pain caused by the nonsteroidal anti-androgen bicalutamide, which is used in the treatment of prostate cancer (see Gynaecomastia under Adverse Effects and Precautions of Flutamide).
MASTALGIA. Tamoxifen 20 mg daily has been shown to be effective in patients with both cyclic and non-cyclic mastalgia, and improvement has also been reported at a lower dose of 10 mg daily. However, there is concern about the use of tamoxifen in otherwise healthy premenopausal women, particularly since many patients relapse on withdrawal, and it has been recommended that tamoxifen be reserved for patients who fail to respond to other drugs. A topical formulation of 4-hydroxytamoxifen, a metabolite of tamoxifen, is under investigation in the treatment of cyclic mastalgia.
Cardiovascular disorders. Tamoxifen has been reported to have a generally favourable effect on lipid profiles (see Effects on Blood Lipids, under Adverse Effects, above) suggesting it may have cardiovascular benefits. A cohort study of adjuvant tamoxifen found that the drug reduced the incidence of myocardial infarction, and a randomised study of the same therapy also showed a trend towards a decrease in mortality from coronary heart disease. However, in a much larger breast cancer prevention trial, tamoxifen did not reduce the risk of, and mortality from, ischaemic heart disease, neither of which differed between placebo and tamoxifen recipients. This lack of difference was independent of pre-existing cardiovascular disease. A review noted that while the available data suggested an overall benefit, most of them came from studies in women at low absolute risk of myocardial infarction; studies in men at high absolute risk would be needed to determine whether tamoxifen and related drugs were suitable as cardioprotectants.
Disorders related to the menstrual cycle. Apart from cyclic mastalgia (see above) tamoxifen has been used in a number of cases in which disorders were linked to the hormonal changes of the menstrual cycle, including menorrhagia due to myometrial hypertrophy, an auto-immune dermatitis due to post-ovulatory rises in serum progesterone (see Effects on the Skin under Progesterone, p.2125), and premenstrual migraine. However, tamoxifen was thought to be a cause of recurrent migraines in another patient, because of its action at oestrogen receptors.
Infertility. Tamoxifen is reported to be as effective as clomifene in the treatment of anovulatory infertility in women, and may be useful in women in whom abnormal cervical mucus acts as a barrier to spermatozoa. In infertile men, however, results are reportedly contradictory, with some studies reporting increase in sperm density and improved pregnancy rates while others failed to demonstrate any effect The addition of testosterone may improve outcomes, however, and a later study of men with idiopathic oligozoospermia reported that tamoxifen with testosterone improved sperm variables and pregnancy rates compared with a placebo group (there was no comparison with tamoxifen alone).
Malignant neoplasms. For reference to the use of tamoxifen in malignant neoplasms of breast, ovary, and in cutaneous melanoma. The most common use of tamoxifen is for the endocrine therapy of oestrogen-receptor positive early or advanced breast cancer, where there seems to be a clear benefit. How long such therapy should be continued remains uncertain although continuing therapy beyond 5 years may not increase the overall benefit. However, extending therapy by following 5 years of tamoxifen therapy with several years of an aromatase inhibitor such as letrozole does seem to provide additional benefit.
Extension of tamoxifen use to the attempted prophylaxis of breast cancer has proved controversial. Nonetheless, evidence that tamoxifen can reduce short-term incidence of breast cancer in some women at increased risk has been seen, and tamoxifen has been approved for such use in the USA. Despite some positive data, tamoxifen does not appear to be effective in the treatment of hepatocellular carcinoma.
Osteoporosis. Tamoxifen has been reported to have favourable effects on bone mass, but any general role in the prevention of osteoporosis seems unlikely given concerns about the carcinogenic ity of tamoxifen. The effects are reported to be comparable in magnitude to those of calcium supplementation, and less than those of oestrogens or bisphosphonates. It has been suggested that such an effect on bone would provide an additional benefit in women receiving tamoxifen for the prophylaxis of breast cancer, although others dispute the benefits.
Precocious puberty. Tamoxifen has been reported to be beneficial in the treatment of precocious puberty.
Preparations
British Pharmacopoeia 2008: Tamoxifen Tablets
The United States Pharmacopeia 31, 2008: Tamoxifen Citrate Tablets
Single-ingredient Preparations
The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.
Argentina: Crisafeno; Diemon; Farmifeno¤; Ginarsan; Nolvadex; Rolap; Tamofen¤; Tamoxis; Taxfeno; Trimetrox; Australia: Estroxyn¤; Genox; Kessar¤; Nolvadex; Noxitem¤; Tamosin; Tamoxen; Austria: Ebefen; Kessar; Nolvadex; Tamax; Tamofen; Tamoplex; Belgium: Nolvadex; Tamizam; Brazil: Bioxifeno; Estrocur; Kessar; Nolvadex; Tamofen¤; Tamooex¤; Tamoplex; Tamox; Tamoxin; Taxofen; Tecnotax; Canada: Apo-Tamox; Nolvadex; Tamofen; Tamone¤; Tamoplex¤; Chile: Kessar; Nolvadex; Tamolem¤; Taxus; Czech Republic: Nolvadex; Tamifen; Zitazonium; Denmark: Tamofen¤; Finland: Nolvadex¤; Tadex; Tamexin; Tamofen; France: Kessar; Lesporene¤; Nolvadex; Oncotam; Tamofene¤; Germany: Dignotamoxi¤; duratamoxifen¤; Jenoxifen; Kessar; Mandofen; Nolvadex; Nourytam; Tamobeta¤; Tamofen¤; Tamokadin; Tamopham¤; Tamox; Tamoxasta¤; Tamoxigenat¤; Tamoximerck; Tamoxistad; Zemide¤; Zitazonium¤; Greece: Adifen; Defarol¤; Kessar; Nolvadex; Puretam; Tamoplex; Zymoplex; Hong Kong: Apo-Tamox; Nolvadex; Novofen; Tamifen¤; Tamofen¤; Zitazonium; Hungary: Zitazonium; India: Caditam; Cytotam; Mamofen; Nolvadex; Tamodex; Ireland: Clonoxifen¤; Nolgen; Nolvadex; Tamofen¤; Tamox; Israel: Nolvadex; Tamofen; Tamoplex¤; Tamoxen; Tamoxi; Italy: Kessar; Ledertam; Nolvadex; Nomafen; Tamoxene; Virtamox¤; Malaysia: Genox; Nolvadex; Novofen; Tamoplex; Zitazonium; Mexico: Bilem; Cryoxifeno; Kessar; Nolvadex; Ralsifen-X¤; Tamofen¤; Tamoxan; Taxus; Tecnofen; Netherlands: Nolvadex; Tamoplex¤; Norway: Nolvadex; Tamofen¤; New Zealand: Genox; Nolvadex; Tamofen; Portugal: Nolvadex; Tamoxan; Russia: Bilem (Билем); Tamifen (Тамифен); Zitazonium (Зитазониум); South Africa: Kessar; Neophedan; Nolvadex; Tamoplex; Singapore: Apo-Tamox; Nolvadex; Tamofen; Tamoplex¤; Spain: Nolvadex; Oxeprax¤; Sinmaren¤; Yacesal; Sweden: Ledertam¤; Nolvadex; Tamaxin¤; Switzerland: Kessar; Nolvadex; Tamec; Thailand: Gynatam; Nolvadex; Novofen; Tamofen; Tamoplex; Tuosomin; Zitazonium; United Arab Emirates: Tamophar; United Kingdom: Emblon¤; Fentamox¤; Noltam¤; Nolvadex; Oestrifen¤; Soltamox; Tamofen¤; United States: Nolvadex; Soltamox; Venezuela: Nolvadex; Taxus
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