Tamoxifen citrate
1. NAME |
1.1 Substance |
1.2 Group |
1.3 Synonyms |
1.4 Identification numbers |
1.4.1 CAS number |
1.4.2 Other numbers |
1.5 Brand names, Trade names |
1.6 Manufacturers, Importers |
2. SUMMARY |
2.1 Main risks and target organs |
2.2 Summary of clinical effects |
2.3 Diagnosis |
2.4 First aid measures and management principles |
3. PHYSICO-CHEMICAL PROPERTIES |
3.1 Origin of the substance |
3.2 Chemical structure |
3.3 Physical properties |
3.3.1 Properties of the substance |
3.3.2 Properties of the locally available formulation |
3.4 Other characteristics |
3.4.1 Shelf-life of the substance |
3.4.2 Shelf-life of the locally available formulation |
3.4.3 Storage conditions |
3.4.4 Bioavailability |
3.4.5 Specific properties and composition |
4. USES |
4.1 Indications |
4.2 Therapeutic dosage |
4.2.1 Adults |
4.2.2 Children |
4.3 Contraindications |
5. ROUTES OF ENTRY |
5.1 Oral |
5.2 Inhalation |
5.3 Dermal |
5.4 Eye |
5.5 Parenteral |
5.6 Other |
6. KINETICS |
6.1 Absorption by route of exposure |
6.2 Distribution by route of exposure |
6.3 Biological half-life by route of exposure |
6.4 Metabolism |
6.5 Elimination by route of exposure |
7. PHARMACOLOGY AND TOXICOLOGY |
7.1 Mode of action |
7.1.1 Toxicodynamics |
7.1.2 Pharmacodynamics |
7.2 Toxicity |
7.2.1 Human data |
7.2.1.1 Adults |
7.2.1.2 Children |
7.2.2 Relevant animal data |
7.2.3 Relevant in vitro data |
7.3 Carcinogenicity |
7.4 Teratogenicity |
7.5 Mutagenicity |
7.6 Interactions |
7.7 Main adverse effects |
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS |
8.1 Material sampling plan |
8.1.1 Sampling and specimen collection |
8.1.1.1 Toxicological analyses |
8.1.1.2 Biomedical analyses |
8.1.1.3 Arterial blood gas analysis |
8.1.1.4 Haematological analyses |
8.1.1.5 Other (unspecified) analyses |
8.1.2 Storage of laboratory samples and specimens |
8.1.2.1 Toxicological analyses |
8.1.2.2 Biomedical analyses |
8.1.2.3 Arterial blood gas analysis |
8.1.2.4 Haematological analyses |
8.1.2.5 Other (unspecified) analyses |
8.1.3 Transport of laboratory samples and specimens |
8.1.3.1 Toxicological analyses |
8.1.3.2 Biomedical analyses |
8.1.3.3 Arterial blood gas analysis |
8.1.3.4 Haematological analyses |
8.1.3.5 Other (unspecified) analyses |
8.2 Toxicological Analyses and Their Interpretation |
8.2.1 Tests on toxic ingredient(s) of material |
8.2.1.1 Simple Qualitative Test(s) |
8.2.1.2 Advanced Qualitative Confirmation Test(s) |
8.2.1.3 Simple Quantitative Method(s) |
8.2.1.4 Advanced Quantitative Method(s) |
8.2.2 Tests for biological specimens |
8.2.2.1 Simple Qualitative Test(s) |
8.2.2.2 Advanced Qualitative Confirmation Test(s) |
8.2.2.3 Simple Quantitative Method(s) |
8.2.2.4 Advanced Quantitative Method(s) |
8.2.2.5 Other Dedicated Method(s) |
8.2.3 Interpretation of toxicological analyses |
8.3 Biomedical investigations and their interpretation |
8.3.1 Biochemical analysis |
8.3.1.1 Blood, plasma or serum |
8.3.1.2 Urine |
8.3.1.3 Other fluids |
8.3.2 Arterial blood gas analyses |
8.3.3 Haematological analyses |
8.3.4 Interpretation of biomedical investigations |
8.4 Other biomedical (diagnostic) investigations and their interpretation |
8.5 Overall Interpretation of all toxicological analyses and toxicological investigations |
8.6 References |
9. CLINICAL EFFECTS |
9.1 Acute poisoning |
9.1.1 Ingestion |
9.1.2 Inhalation |
9.1.3 Skin exposure |
9.1.4 Eye contact |
9.1.5 Parenteral exposure |
9.1.6 Other |
9.2 Chronic poisoning |
9.2.1 Ingestion |
9.2.2 Inhalation |
9.2.3 Skin exposure |
9.2.4 Eye contact |
9.2.5 Parenteral exposure |
9.2.6 Other |
9.3 Course, prognosis, cause of death |
9.4 Systematic description of clinical effects |
9.4.1 Cardiovascular |
9.4.2 Respiratory |
9.4.3 Neurological |
9.4.3.1 CNS |
9.4.3.2 Peripheral nervous system |
9.4.3.3 Autonomic nervous system |
9.4.3.4 Skeletal and smooth muscle |
9.4.4 Gastrointestinal |
9.4.5 Hepatic |
9.4.6 Urinary |
9.4.6.1 Renal |
9.4.6.2 Other |
9.4.7 Endocrine and reproductive systems |
9.4.8 Dermatological |
9.4.9 Eye, ear, nose, throat: local effects |
9.4.10 Haematological |
9.4.11 Immunological |
9.4.12 Metabolic |
9.4.12.1 Acid-base disturbances |
9.4.12.2 Fluid and electrolyte disturbances |
9.4.12.3 Others |
9.4.13 Allergic reactions |
9.4.14 Other clinical effects |
9.4.15 Special risks |
9.5 Other |
9.6 Summary |
10. MANAGEMENT |
10.1 General principles |
10.2 Relevant laboratory analyses |
10.2.1 Sample collection |
10.2.2 Biomedical analysis |
10.2.3 Toxicological analysis |
10.2.4 Other investigations |
10.3 Life supportive procedures and symptomatic/specific treatment |
10.4 Decontamination |
10.5 Elimination |
10.6 Antidote treatment |
10.6.1 Adults |
10.6.2 Children |
10.7 Management discussion |
11. ILLUSTRATIVE CASES |
11.1 Case reports from literature |
11.2 Internally extracted data on cases |
11.3 Internal cases |
12. Additional information |
12.1 Availability of antidotes |
12.2 Specific preventive measures |
12.3 Other |
13. REFERENCES |
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES) |
PHARMACEUTICALS
1. NAME
1.1 Substance
Tamoxifen
1.2 Group
Anti-oestrogen, non-steroidal derivative of triphenyl ethylene
ATC: L02B A01
1.3 Synonyms
(Z)-2-[4-(1,2-Diphenylbut-1-enyl)phenoxy]-N,N-dimethylethylamine citrate
ICI 46 474
[trans-1-(4-beta-dimethylaminoethoxyphenyl)-1,2-diphenylbut-1-ene]
1.4 Identification numbers
1.4.1 CAS number
10540
1.4.2 Other numbers
Tamoxifen citrate: 54965-24-1
1.5 Brand names, Trade names
Emblon (Berk)
Noltam (Lederle)
Nolvadex (ICI)
Nolvadex-D (ICI)
Nolvadex forte(ICI)
Tamofen (Tillotts)
1.6 Manufacturers, Importers
Berk Pharmaceuticals Ltd., ICI Pharmaceuticals (UK).,
Lederle Laboratories., Tillotts Laboratories.
2. SUMMARY
2.1 Main risks and target organs
There is no record of serious effects from tamoxifen after
acute overdosage.
Adverse effects in therapeutic use are usually mild. They
include effects caused by antagonism of endogenous oestrogens:
hot flushes, non-specific gastrointestinal effects (nausea and
vomiting), central nervous system effects, and rare ocular
effects. Adverse haematological effects have been reported,
also isolated cases of death from peliosis hepatis and from
hyperlipidaemia.
In the treatment of breast cancer, hypercalcaemia and tumour
flare can occur.
2.2 Summary of clinical effects
Anti-oestrogenic effects in women treated with tamoxifen
include vasomotor symptoms (hot flushes), vaginal bleeding and
(in premenopausal women) irregular menses, and pruritus
vulvae. Nausea and vomiting can occur.
Dizziness, lethargy, depression, irritability and cerebellar
dysfunction have been described.
Reversible retinopathy with macular oedema has been reported
after high cumulative doses (>7g), and corneal changes can
occur.
Thrombocytopenia or leukopenia have been associated with
tamoxifen treatment. Thromboembolism, which may be due to the
disease rather than the treatment, has been recorded in women
given tamoxifen for breast cancer.
2.3 Diagnosis
Based on history of exposure and occurrence of adverse effects
such as hot flushes, nausea, vomiting, ocular disorders,
tumour flare, hypercalcemia, vaginal bleeding and CNS signs
and symptoms.
2.4 First aid measures and management principles
General measures such as inducing emesis or gastric lavage may
be indicated in massive overdosage.
Treatment is symptomatic.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Synthetic.
3.2 Chemical structure
(Z)-2-[4-(1,2-Diphenylbut-1-enyl)phenoxy]-N,N-
dimethylethylamine citrate
C26H29NO, C6H8O7
[trans-1-(4-beta-dimethylaminoethoxyphenyl)-1, 2-diphenylbut-1-ene]
Molecular weight = 563.6
pKa = 8.85
3.3 Physical properties
3.3.1 Properties of the substance
Solubility in water at 37 °C = 0.05 g/100 ml.
3.3.2 Properties of the locally available formulation
No data available.
3.4 Other characteristics
3.4.1 Shelf-life of the substance
Assumed to be at least 5 years.
3.4.2 Shelf-life of the locally available formulation
Assumed to be at least 5 years.
3.4.3 Storage conditions
Store between 15 and 30 °C
Protect from light
3.4.4 Bioavailability
(to be added)
3.4.5 Specific properties and composition
(to be added by centre).
4. USES
4.1 Indications
Treatment of advanced breast cancer and adjuvant
treatment of early breast cancer.
Treatment of anovulatory infertility.
4.2 Therapeutic dosage
4.2.1 Adults
Breast cancer: initial dose 10 mg twice daily;
if no response after 1 month, 20 mg twice daily.
Infertility: regular menstruation, 10 mg twice daily on
days 2,3,4 and 5 of cycle, increasing to 20 mg twice
daily and 40 mg twice daily in successive cycles if
ovulation does not occur.
Amenorrhoea: 10 mg twice daily on 4 successive days,
increasing to 20 mg twice daily and 40 mg twice daily
after intervals of 45 and 90 days if ovulation does not
occur.
4.2.2 Children
No data available.
4.3 Contraindications
Pregnancy is an absolute contraindication because of the anti-
oestrogenic effects.
5. ROUTES OF ENTRY
5.1 Oral
Usual route of entry
5.2 Inhalation
Not relevant.
5.3 Dermal
Not relevant.
5.4 Eye
Not relevant.
5.5 Parenteral
Not relevant.
5.6 Other
Not relevant.
6. KINETICS
6.1 Absorption by route of exposure
Peak concentrations occur 4-7 h after oral dosing. Peak
concentrations after single oral doses of 20 mg are about 40
µ/l. There is no information on absolute bioavailability.
(Martindale, 1989; Buckley & Goa, 1989; Lien et al., 1989)
6.2 Distribution by route of exposure
Tamoxifen is more than 99% protein-bound in serum,
predominantly to albumin. In patients with breast cancer,
concentrations of tamoxifen and its metabolites in pleural,
pericardial and peritoneal effusion fluid are between 20 and
100% of those in serum, but only trace amounts enter the
cerebrospinal fluid. Concentrations in breast cancer tissue
exceed those in serum.
The volume of distribution is 50-60 l/kg (Martindale, 1989;
Buckley & Goa, 1989; Lien et al., 1989)
6.3 Biological half-life by route of exposure
The elimination is biphasic, with an initial half-life of
around 7 h and a terminal half-life of 7-11 days. (Martindale,
1989; Buckley & Goa, 1989; Lien et al., 1989)
6.4 Metabolism
Tamoxifen citrate undergoes extensive hepatic metabolism to:
1-(4-ethanolyloxyphenyl)-1,2-diphenylbut-1-ene (the primary
alcohol)
N-desmethyl tamoxifen
4-hydroxy tamoxifen
4-hydroxy-N-desmethyl tamoxifen
N-desdimethyl tamoxifen
(Martindale, 1989; Buckley & Goa, 1989; Lien et al., 1989)
6.5 Elimination by route of exposure
The major excretory route is via the bile as metabolites and
enterohepatic recirculation occurs. Less than 1% is excreted
in the urine. (Martindale, 1989; Buckley & Goa, 1989; Lien et
al., 1989).
7. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
7.1.1 Toxicodynamics
The adverse effects observed are due mainly to its anti-
oestrogen effect, as Tamoxifen and certain of its
metabolites antagonise the effects of oestrogens in
oestrogen-sensitive tissues.
7.1.2 Pharmacodynamics
Tamoxifen and several of its metabolites (particularly 4-
hydroxytamoxifen) bind to nuclear oestrogen receptors in
oestrogen-sensitive tissues, and also to a microsomal
protein termed the 'anti-oestrogen binding site'.
Tamoxifen interferes with the physiological sequence by
which oestrogen binds to its receptor, is translocated
in the nucleus and then activates messenger RNA
synthesis. Although the tamoxifen-receptor complex is
transported in the nucleus in the same way as oestrogen-
receptor complex, it fails to activate synthesis of
mRNA. (Buckley & Goa, 1990)
A meta-analysis of published trials in breast cancer
(Early Breast Cancer Trialists, 1988) demonstrates a
reduction in odds of death of about 20% over the first 5
years from diagnosis in women aged over 50 years.
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
There is no information on the acute toxicity of
tamoxifen in overdosage.
The lowest cumulative dose of tamoxifen known to
have induced retinopathy, an adverse effect
which is recognised to be dose-dependent, is 7.7
g (Griffiths, 1987)
7.2.1.2 Children
No data available.
7.2.2 Relevant animal data
In some animal species, oestrogenic agonist effects
become manifest at dosages equivalent to 10-100 times
the human therapeutic dose (ABPI, 1989).
7.2.3 Relevant in vitro data
No data available.
7.3 Carcinogenicity
A case-control study (Hardell, 1988) showed a significantly
increased relative risk of carcinoma of the uterus in women
previously treated with tamoxifen AND who had previously had
radiotherapy involving the uterus. The study showed an
increase in relative risk with tamoxifen treatment alone which
was NOT statistically significant (see also Section 7.4).
7.4 Teratogenicity
Studies in neonatal male (Taguchi, 1987) and female (Taguchi &
Nishizuka, 1985) mice at relative doses 10 times higher than
those used in humans have shown genital tract abnormalities
similar to those caused by diethylstilboestrol, a known
transplacental carcinogen (diethylstilboestrol causes vaginal
adenosis, which predisposes to clear cell carcinoma).
7.5 Mutagenicity
Tamoxifen is believed not to be mutagenic (Martindale, 1989).
7.6 Interactions
Tamoxifen POTENTIATES the anticoagulant effect of warfarin,
and this interaction can be life-threatening (Tenni et al,
1989; Ritchie & Grant, 1989).
7.7 Main adverse effects
Adverse effects are usually mild. Thrombocytopenia,
leukopenia, thromboembolism, peliosis hepatis and
hyperlipidaemia have been mentioned in case reports.
Severe hypercalcaemia can occur rarely when treatment is
started in patients with metastases to bone.
8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
8.1 Material sampling plan
8.1.1 Sampling and specimen collection
8.1.1.1 Toxicological analyses
8.1.1.2 Biomedical analyses
8.1.1.3 Arterial blood gas analysis
8.1.1.4 Haematological analyses
8.1.1.5 Other (unspecified) analyses
8.1.2 Storage of laboratory samples and specimens
8.1.2.1 Toxicological analyses
8.1.2.2 Biomedical analyses
8.1.2.3 Arterial blood gas analysis
8.1.2.4 Haematological analyses
8.1.2.5 Other (unspecified) analyses
8.1.3 Transport of laboratory samples and specimens
8.1.3.1 Toxicological analyses
8.1.3.2 Biomedical analyses
8.1.3.3 Arterial blood gas analysis
8.1.3.4 Haematological analyses
8.1.3.5 Other (unspecified) analyses
8.2 Toxicological Analyses and Their Interpretation
8.2.1 Tests on toxic ingredient(s) of material
8.2.1.1 Simple Qualitative Test(s)
8.2.1.2 Advanced Qualitative Confirmation Test(s)
8.2.1.3 Simple Quantitative Method(s)
8.2.1.4 Advanced Quantitative Method(s)
8.2.2 Tests for biological specimens
8.2.2.1 Simple Qualitative Test(s)
8.2.2.2 Advanced Qualitative Confirmation Test(s)
8.2.2.3 Simple Quantitative Method(s)
8.2.2.4 Advanced Quantitative Method(s)
8.2.2.5 Other Dedicated Method(s)
8.2.3 Interpretation of toxicological analyses
8.3 Biomedical investigations and their interpretation
8.3.1 Biochemical analysis
8.3.1.1 Blood, plasma or serum
8.3.1.2 Urine
8.3.1.3 Other fluids
8.3.2 Arterial blood gas analyses
8.3.3 Haematological analyses
8.3.4 Interpretation of biomedical investigations
8.4 Other biomedical (diagnostic) investigations and their
interpretation
8.5 Overall Interpretation of all toxicological analyses and
toxicological investigations
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
No data available.
9.1.2 Inhalation
No data available.
9.1.3 Skin exposure
No data available.
9.1.4 Eye contact
No data available.
9.1.5 Parenteral exposure
No data available.
9.1.6 Other
No data available.
9.2 Chronic poisoning
9.2.1 Ingestion
Retinal damage and keratitis have been reported in
patients after large cumulative doses of tamoxifen,
generally over 180 mg per day for more than 1 year
(Buckley & Goa, 1989), though sometimes with smaller
doses (Griffiths, 1987). There seems to be correlation
between long-term tamoxifen administration and
endometrical proliferation (Uziely et al, 1993).
9.2.2 Inhalation
No data available.
9.2.3 Skin exposure
No data available.
9.2.4 Eye contact
No data available.
9.2.5 Parenteral exposure
No data available.
9.2.6 Other
No data available.
9.3 Course, prognosis, cause of death
No data available.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
No data available.
9.4.2 Respiratory
No data available.
9.4.3 Neurological
9.4.3.1 CNS
A case of depression, syncope, and
incoordination has been described during therapy
with 10 mg twice daily (Pluss et al., 1984). The
symptoms resolved when tamoxifen was
discontinued and reappeared when treatment was
restarted.
9.4.3.2 Peripheral nervous system
No data available.
9.4.3.3 Autonomic nervous system
No data available.
9.4.3.4 Skeletal and smooth muscle
No data available.
9.4.4 Gastrointestinal
Nausea and vomiting occur with therapeutic doses in some
patients, and are anticipated in overdosage (ABPI, 1989)
9.4.5 Hepatic
A fatal case of peliosis hepatis has been reported in a
woman treated with tamoxifen for 2 years after
mastectomy for carcinoma (Loomus et al., 1983).
9.4.6 Urinary
9.4.6.1 Renal
No data available.
9.4.6.2 Other
A case of persistent nocturnal priapism has been
reported (Fernando & Tobias, 1989).
9.4.7 Endocrine and reproductive systems
The anti-oestrogenic effects of tamoxifen in
premenopausal women receiving therapeutic doses can
cause irregular menses.
Anti-oestrogenic adverse effects in women treated with
tamoxifen include vasomotor symptoms (hot flushes),
vaginal bleeding and pruritus vulvae (Buckley & Goa,
1989).
9.4.8 Dermatological
No data available.
9.4.9 Eye, ear, nose, throat: local effects
Treatment has been associated with retinal and corneal
changes: see para 9.2.
9.4.10 Haematological
Thromboembolism may be more common in patients treated
with tamoxifen, though this is not certain, as patients
with cancer are at increased risk anyway.
A small reduction in antithrombin III concentration was
noted in a study of 11 postmenopausal women treated
with tamoxifen, but it was clinically insignificant,
and no significant reduction was seen in a group of
premenopausal women (Jordan et al., 1987).
Thrombocytopenia and leukopenia can occur during
therapy, but are not usually severe (ABPI, 1989). One
case of severe myelosuppression has been reported
(International Adjuvant Therapy Organisation, 1985).
9.4.11 Immunological
No data available.
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
No data available.
9.4.12.2 Fluid and electrolyte disturbances
Severe hypercalcaemia, associated with
increased bone resorption, has been noted when
patients with bony metastases commenced
therapy (Martindale, 1989).
9.4.12.3 Others
Severe hyperlipidaemia is occasionally seen,
and has been ascribed to an oestrogenic effect
(Noguchi et al., 1987)
9.4.13 Allergic reactions
No data available.
9.4.14 Other clinical effects
No data available.
9.4.15 Special risks
Pregnancy, breast feeding, enzyme deficiencies: no data
available (see sections 7.3 and 7.4)
9.5 Other
No data available.
9.6 Summary
10. MANAGEMENT
10.1 General principles
It is unlikely that serious acute toxicity would occur, and
management is supportive. The stomach should be emptied
after massive overdosage.
10.2 Relevant laboratory analyses
10.2.1 Sample collection
No data available.
10.2.2 Biomedical analysis
Urea, creatinine and electrolytes may be helpful in
the assessment of patients who are vomiting.
10.2.3 Toxicological analysis
Not relevant.
10.2.4 Other investigations
Not relevant.
10.3 Life supportive procedures and symptomatic/specific
treatment
Nausea and vomiting may make intravenous fluid replacement
necessary.
10.4 Decontamination
Gastric lavage may be of value in massive overdosage, but
there are no data on this subject.
10.5 Elimination
Therapy to enhance elimination is not likely to be effective,
given the large volume of distribution.
10.6 Antidote treatment
10.6.1 Adults
Not relevant.
10.6.2 Children
Not relevant.
10.7 Management discussion
No data available.
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
No data available.
11.2 Internally extracted data on cases
One manufacturer (ICI) is aware of the case of a woman aged
51 years who claimed to have swallowed 100 x 10 mg tablets
of tamoxifen, and who suffered no ill effects (JI Landles,
personal communication).
11.3 Internal cases
No data available.
12. Additional information
12.1 Availability of antidotes
Not relevant.
12.2 Specific preventive measures
No data available.
12.3 Other
No data available.
13. REFERENCES
ABPI (Association of the British Pharmaceutical Industry) (1989)
Data Sheet Compendium. London.
Buckley M M-T, Goa KL (1989). Tamoxifen: a reappraisal of its
pharmacodynamic and pharmacokinetic properties and therapeutic
use. Drugs, 37: 451-490.
Early Breast Cancer Trialists Collaborative Group (1988).
Effects of adjuvant tamoxifen and of cytotoxic therapy on
mortality in early breast cancer. New Eng. J. Med., 319: 1681-
1692.
Fernando IN, Tobias JS (1989). Priapism in patient on tamoxifen.
Lancet; i:436
Griffiths MFP (1987). Tamoxifen retinopathy at low dosage. Am.
J. Ophthalmol., 104: 185-6.
Hardell L (1988). Pelvic irradiation and tamoxifen as risk
factors for carcinoma of cervix uteri. Lancet, ii: 1432.
International Adjuvant Therapy Group (1985). Myelosuppression
occurring after receiving tamoxifen for breast cancer. Br, J.
Radiol., 58: 1220.
Jordan VC, Fritz NF, Tormey DC (9187). Long-term adjuvant
therapy with tamoxifen: effect on sex hormone binding globulin
and antithrombin III. Cancer Res., 47: 4517-4519.
Lien EA, Solheim E, Lea OA et al (1989). Distribution of 4-
hydroxy-N-desmethyltamoxifen and other tamoxifen metabolites in
human biological fluids during tamoxifen treatment. Cancer Res.,
49: 2175-2183.
Lipton A, Harvey HA, Hamilton RW (1984). Venous thrombosis as a
side effect of tamoxifen treatment. Cancer Treatment Reports, 68:
887-889.
Loomus GN, Aneja P, Bota RA (1983). A case of peliosis hepatis
in association with tamoxifen therapy. Am. J. Clin. Path., 80:
881-882.
Reynolds EF, Ed (1989). Martindale, The Extra Pharmacopoeia. 29th
edition. Pharmaceutical Press, London.
Merck Index (1983). 10th edition. Merck & Co., Inc., Rahaway,
NJ.
Noguchi M, Taniya T, Tajiri K et al (1987). Fatal
hyperlipidaemia in a case of metastatic breast cancer treated by
tamoxifen. Br. J. Surg., 74: 586-487.
Pluss JL, Dibella NJ (1984). Reversible central nervous system
dysfunction due to tamoxifen in a patient with breast cancer.
Ann. Int. Med., 101: 652.
Ritchie LD, Grant SMT (1989). Tamoxifen-warfarin interaction:
the Aberdeen Hospitals file. Br. Med. J., 298: 1253.
Taguchi O (1987). Reproductive tract lesions in male mice
treated neonatally with tamoxifen. Biol. Reproduc., 37: 113-116.
Taguchi O, Noguchi M (1985). Reproductive tract abnormalities in
female mice treated neonatally with tamoxifen. Am. J. Obs.
Gynecol., 151: 675-678.
Tenni P, Lalich DL, Byrne MJ (1989). Life threatening
interaction between tamoxifen and warfarin. Br. Med. J. 298: 93.
Uziely B, Lewin A, Brufman G, Dorembus D, Mor-Josef S- (1993).
The effect of tamoxifen on the endometrium. Breast Cancer Res.
Treat. 26(1): 101-5.
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Author: Dr R.E. Ferner
Northern Drug and Therapeutics Centre
The Wolfson Unit
Royal Victoria Infirmary
Newcastle-upon-Tyne NE1 4LP
United Kingdom
Tel: 44-91-2328511
Fax: 44-91-2323613
Date: 15 April 1990
Peer Review: Strasbourg, France, April 1990
Review: IPCS, May 1994