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Arimidex (anastrozole) 1 mg tablets

Anastrozole (INN) (marketed under the trade name Arimidex by AstraZeneca) is a non-steroidal^[3] aromatase-inhibiting drug approved for treatment of breast cancer after surgery, as well as for metastasis in both pre and post-menopausal women. The severity of breast cancer can be increased by estrogen, as sex hormones cause hyperplasia, and differentiation at estrogen receptor sites.^[4] Anastrozole works by inhibiting the synthesis of estrogen. The patent on Arimidex by AstraZeneca expired June 2010.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medications needed in a basic health system.^[5]

Medical uses

The ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial was an international randomised controlled trial of 9366 women with localized breast cancer who received either anastrozole, tamoxifen, or both for five years, followed by five years of follow-up.^[6] After more than 5 years the group that received anastrozole had significantly better clinical results than the tamoxifen group.^[6] The trial suggested that anastrozole is the preferred medical therapy for postmenopausal women with localized breast cancer, which is estrogen receptor (ER) positive.^[6] Another study found that the risk of recurrence was reduced by 40%, but was associated with an increased risk of bone fractures. The study concluded that ER positive patients benefited from switching from tamoxifen to anastrozole in patients who have completed 2 years' adjuvant tamoxifen.^[7] A more recent trial found that anastrozole significantly reduced the incidence of breast cancer in postmenopausal women relative to placebo, and while there were side effects related to estrogen deprivation observed, the researchers concluded that this was probably not related to the treatment. Lead author Jack Cuzick was quoted by the BBC as saying, "This class of drugs is more effective than previous drugs such as tamoxifen and crucially, it has fewer side effects," adding that he thought there was now enough evidence to support offering the drug.^[8]

Side effects

Bone weakness has been associated with anastrozole. Women who switched to anastrozole after two years on tamoxifen reported twice as many fractures as those who continued to take tamoxifen (2.1% compared to 1%).^[7] Bisphosphonates are sometimes prescribed to prevent the osteoporosis induced by aromatase inhibitors. The level of circulating estradiol is likely causal here and not the anastrozole itself, and so the dose will determine likelihood of osteoporosis (estradiol inhibits osteoclasts, which resorb bone). Acne, Constricted pupils and water retention have also been attributed with use of this anti-estrogen.

Mechanism of action

Anastrozole binds reversibly to the aromatase enzyme through competitive inhibition, inhibits the conversion of androgens to estrogens in peripheral tissues (extra-gonadal).^[9]^[10]

Research

Usage in men

Anastrozole has been tested for reducing estrogens, including estradiol, in men.^[11] Excess estradiol in men can cause benign prostatic hyperplasia, gynecomastia, and symptoms of hypogonadism. It can also contribute to increased risk of stroke, heart attack, chronic inflammation, prostate enlargement and prostate cancer.^[12] Some athletes and body builders use anastrozole as part of their steroid cycle to reduce and prevent symptoms of excess estrogen--gynecomastia, emotional lability and water retention.^[11] Study data suggests dosages of 0.5 mg to 1 mg a day reduce serum estradiol by approximately 50% in men, which differs in postmenopausal women.^[13]

Usage in children

Anastrozole may be used off-label in children with precocious puberty, or children with pubertal gynecomastia.^[14]^[2] Following the onset of puberty, the epiphyseal plate begins to close due to an increased amount of estrogen production escaping local metabolism and spreading to the circulatory system.^[14] It is shown to help slow this process, and increase adult height prediction in adolescent males treated with protein-based peptide hormones for the treatment of growth hormone deficiency.^[15]^[15]

References

^ "anastrozole". Chemical Entities of Biological Interest (ChEBI). European Molecular Biology Laboratory. Retrieved 2011-08-14.
^ ^a ^b Mauras N, Bishop K, Merinbaum D, Emeribe U, Agbo F, Lowe E (August 2009). "Pharmacokinetics and pharmacodynamics of anastrozole in pubertal boys with recent-onset gynecomastia". J. Clin. Endocrinol. Metab. 94 (8): 2975–8. doi:10.1210/jc.2008-2527. PMID 19470631.
^ http://www.rxlist.com/arimidex-drug.htm
^ Howell, A.; Cuzick, J.; Baum, M.; Buzdar, A.; Dowsett, M.; Forbes, J. F.; Hoctin-Boes, G.; Houghton, J.; Locker, G. Y.; Tobias, J. S.; Atac Trialists', G. (2005). "Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer". The Lancet 365 (9453): 60–62. doi:10.1016/S0140-6736(04)17666-6. PMID 15639680.
^ "www.who.int" (PDF).
^ ^a ^b ^c Howell A, Cuzick J, Baum M; et al. (2005). "Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer". Lancet 365 (9453): 60–2. doi:10.1016/S0140-6736(04)17666-6. PMID 15639680.
^ ^a ^b Jakesz R, Jonat W, Gnant M, Mittlboeck M, Greil R, Tausch C, Hilfrich J, Kwasny W, Menzel C, Samonigg H, Seifert M, Gademann G, Kaufmann M, Wolfgang J (2005). "Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial". Lancet 366 (9484): 455–62. doi:10.1016/S0140-6736(05)67059-6. PMID 16084253.
^ Gallagher, James (12 December 2013). "Breast cancer: Drug 'halves' risk of tumours". BBC News. Retrieved 12 December 2013.
^ Simpson ER (2003). "Sources of estrogen and their importance". The Journal of Steroid Biochemistry and Molecular Biology 86 (3–5): 225–30. doi:10.1016/S0960-0760(03)00360-1. PMID 14623515.
^ Simpson ER (September 2003). "Sources of estrogen and their importance". J. Steroid Biochem. Mol. Biol. 86 (3-5): 225–30. doi:10.1016/S0960-0760(03)00360-1. PMID 14623515.
^ ^a ^b Mauras N, O'Brien KO, Klein KO, Hayes V (July 2000). "Estrogen suppression in males: metabolic effects". J. Clin. Endocrinol. Metab. 85 (7): 2370–7. doi:10.1210/jc.85.7.2370. PMID 10902781. ; Dougherty RH, Rohrer JL, Hayden D, Rubin SD, Leder BZ (February 2005). "Effect of aromatase inhibition on lipids and inflammatory markers of cardiovascular disease in elderly men with low testosterone levels". Clin. Endocrinol. (Oxf) 62 (2): 228–35. doi:10.1111/j.1365-2265.2005.02205.x. PMID 15670201.
^ Faloon, William. "Dangers of Excess Estrogen In the Aging Male". Life Extension Magazine, November 2008. [1]
^ Leder BZ, Rohrer JL, Rubin SD, Gallo J, Longcope C (March 2004). "Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels". J. Clin. Endocrinol. Metab. 89 (3): 1174–80. doi:10.1210/jc.2003-031467. PMID 15001605.
^ ^a ^b Faglia G, Arosio M, Porretti S (December 2000). "Delayed closure of epiphyseal cartilages induced by the aromatase inhibitor anastrozole. Would it help short children grow up?". J. Endocrinol. Invest. 23 (11): 721–3. doi:10.1007/bf03345059. PMID 11194703.
^ ^a ^b Mauras N, Gonzalez de Pijem L, Hsiang HY, Desrosiers P, Rapaport R, Schwartz ID, Klein KO, Singh RJ, Miyamoto A, Bishop K (March 2008). "Anastrozole increases predicted adult height of short adolescent males treated with growth hormone: a randomized, placebo-controlled, multicenter trial for one to three years". J. Clin. Endocrinol. Metab. 93 (3): 823–31. doi:10.1210/jc.2007-1559. PMC 2266949. PMID 18165285.

External links

Arimidex | Official website

UpToDate Contents

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1. 転移性ホルモン受容体陽性乳癌に対する治療アプローチ：内分泌療法 treatment approach to metastatic hormone receptor positive breast cancer endocrine therapy
2. アロマターゼ阻害剤による骨量減少の評価およびマネージメント evaluation and management of aromatase inhibitor induced bone loss
3. 非転移性ホルモン受容体陽性乳癌に対する補助内分泌療法 adjuvant endocrine therapy for non metastatic hormone receptor positive breast cancer
4. 女性化乳房のマネージメント management of gynecomastia
5. 乳癌に対する術前補助化学療法：理論的根拠、治療前評価、および治療法の選択肢 neoadjuvant therapy for breast cancer rationale pretreatment evaluation and therapeutic options

English Journal

The influence of genetic polymorphisms on the efficacy and side effects of anastrozole in postmenopausal breast cancer patients.

Abubakar MB1, Wei K, Gan SH.
Pharmacogenetics and genomics.Pharmacogenet Genomics.2014 Dec;24(12):575-81. doi: 10.1097/FPC.0000000000000092.
Breast cancer is a common cause of cancer mortality among women. Several genetic factors have been implicated in its development. Current treatment guidelines for estrogen receptor-positive breast cancer recommend that anastrozole [or any of the other two aromatase inhibitors (letrozole and exemesta
PMID 25203739

Treatment patterns and duration in post-menopausal women with HR+/HER2- metastatic breast cancer in the US: a retrospective chart review in community oncology practices (2004-2010).

Macalalad AR1, Hao Y, Lin PL, Signorovitch JE, Wu EQ, Ohashi E, Zhou Z, Kelley C.
Current medical research and opinion.Curr Med Res Opin.2014 Nov 7:1-11. [Epub ahead of print]
Abstract Background: Clinical guidelines prefer endocrine therapy (ET) as initial treatment for post-menopausal women with hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (mBC). Chemotherapy (CT) should be reserved for patients who d
PMID 25350226

Longitudinal trends in utilization of endocrine therapies for breast cancer: an international comparison.

Kelly E1, Lu CY, Albertini S, Vitry A.
Journal of clinical pharmacy and therapeutics.J Clin Pharm Ther.2014 Nov 4. doi: 10.1111/jcpt.12227. [Epub ahead of print]
WHAT IS KNOWN AND OBJECTIVE: Endocrine therapy is an effective treatment for post-menopausal women with 'oestrogen receptor-positive' invasive breast cancers. There are two main types of endocrine therapies: selective oestrogen receptor modulators (tamoxifen) and aromatase inhibitors (anastrozole, l
PMID 25367863

Japanese Journal

The effect of anastrozole on bone mineral density during the first 5 years of adjuvant treatment in postmenopausal women with early breast cancer

INOUE Hiroaki,HIRANO Akira,OGURA Kaoru,HATTORI Akinori,KAMIMURA Mari,OKUBO Fumie,TAGAWA Hiroko,SAKAGUCHI Shiho,KINOSHITA Jun,SHIMIZU Tadao
SpringerPlus 4, 303-307, 2015-07-01
NAID 120005626346

症例報告低悪性度子宮内膜間質肉腫の術後再発に対してアロマターゼ阻害薬が奏効した1例

寺尾美代子,中西美紗緒,大西賢人 [他]
東京産科婦人科学会会誌 63(2), 267-271, 2014-04
NAID 40020186064

症例報告アナストロゾールによる乳がんの化学療法後に増悪した自己免疫性肝炎の2例

雅楽川英樹,光井洋,木村晴 [他]
肝臓 55(2), 122-131, 2014-02
NAID 40019987571

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★リンクテーブル★

リンク元	「アナストロゾール」

「アナストロゾール」

Anastrozole
Systematic (IUPAC) name
	2,2'-[5-(1H-1,2,4-triazol-1-ylmethyl)-1,3-phenylene]bis(2-methylpropanenitrile)
Clinical data
Trade names	Arimidex
AHFS/Drugs.com	monograph
MedlinePlus	a696018
License data	US FDA: Anastrozole;
Pregnancy; category	D (U.S.);
Routes of; administration	oral
Legal status
Legal status	UK: POM (Prescription only); US: ℞-only;
Pharmacokinetic data
Bioavailability	83-85%
Protein binding	40%
Metabolism	85% hepatic
Biological half-life	46.8 h
Excretion	11% renal
Identifiers
CAS Number	120511-73-1
ATC code	L02BG03 (WHO)
PubChem	CID 2187
IUPHAR/BPS	5137
DrugBank	DB01217
ChemSpider	2102
UNII	2Z07MYW1AZ
KEGG	D00960
ChEBI	CHEBI:2704
ChEMBL	CHEMBL1399
Chemical data
Formula	C17H19N5
Molar mass	293.366 g/mol
	SMILES N#CC(c1cc(cc(c1)C(C#N)(C)C)Cn2ncnc2)(C)C ;
	InChI InChI=1S/C17H19N5/c1-16(2,9-18)14-5-13(8-22-12-20-11-21-22)6-15(7-14)17(3,4)10-19/h5-7,11-12H,8H2,1-4H3 ; Key:YBBLVLTVTVSKRW-UHFFFAOYSA-N ;
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　　[★]

英: anastrozole
商: アリミデックス
関: アロマターゼインヒビター、その他の腫瘍用薬

[urlanastrozole_.28CHEBI:2704.29-1] "anastrozole". Chemical Entities of Biological Interest (ChEBI). European Molecular Biology Laboratory. Retrieved 2011-08-14.

[gyno-2] Mauras N, Bishop K, Merinbaum D, Emeribe U, Agbo F, Lowe E (August 2009). "Pharmacokinetics and pharmacodynamics of anastrozole in pubertal boys with recent-onset gynecomastia". J. Clin. Endocrinol. Metab. 94 (8): 2975–8. doi:10.1210/jc.2008-2527. PMID 19470631.

[3] ttp://www.rxlist.com/arimidex-drug.htm

[4] Howell, A.; Cuzick, J.; Baum, M.; Buzdar, A.; Dowsett, M.; Forbes, J. F.; Hoctin-Boes, G.; Houghton, J.; Locker, G. Y.; Tobias, J. S.; Atac Trialists', G. (2005). "Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer". The Lancet 365 (9453): 60–62. doi:10.1016/S0140-6736(04)17666-6. PMID 15639680.

[5] "www.who.int" (PDF).

[ATAC-6] Howell A, Cuzick J, Baum M; et al. (2005). "Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer". Lancet 365 (9453): 60–2. doi:10.1016/S0140-6736(04)17666-6. PMID 15639680.

[Jakesz-7] Jakesz R, Jonat W, Gnant M, Mittlboeck M, Greil R, Tausch C, Hilfrich J, Kwasny W, Menzel C, Samonigg H, Seifert M, Gademann G, Kaufmann M, Wolfgang J (2005). "Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years' adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial". Lancet 366 (9484): 455–62. doi:10.1016/S0140-6736(05)67059-6. PMID 16084253.

[8] Gallagher, James (12 December 2013). "Breast cancer: Drug 'halves' risk of tumours". BBC News. Retrieved 12 December 2013.

[9] Simpson ER (2003). "Sources of estrogen and their importance". The Journal of Steroid Biochemistry and Molecular Biology 86 (3–5): 225–30. doi:10.1016/S0960-0760(03)00360-1. PMID 14623515.

[pmid14623515-10] Simpson ER (September 2003). "Sources of estrogen and their importance". J. Steroid Biochem. Mol. Biol. 86 (3-5): 225–30. doi:10.1016/S0960-0760(03)00360-1. PMID 14623515.

[Steroid-11] Mauras N, O'Brien KO, Klein KO, Hayes V (July 2000). "Estrogen suppression in males: metabolic effects". J. Clin. Endocrinol. Metab. 85 (7): 2370–7. doi:10.1210/jc.85.7.2370. PMID 10902781. ; Dougherty RH, Rohrer JL, Hayden D, Rubin SD, Leder BZ (February 2005). "Effect of aromatase inhibition on lipids and inflammatory markers of cardiovascular disease in elderly men with low testosterone levels". Clin. Endocrinol. (Oxf) 62 (2): 228–35. doi:10.1111/j.1365-2265.2005.02205.x. PMID 15670201.

[12] Faloon, William. "Dangers of Excess Estrogen In the Aging Male". Life Extension Magazine, November 2008. [1]

[pmid15001605-13] Leder BZ, Rohrer JL, Rubin SD, Gallo J, Longcope C (March 2004). "Effects of aromatase inhibition in elderly men with low or borderline-low serum testosterone levels". J. Clin. Endocrinol. Metab. 89 (3): 1174–80. doi:10.1210/jc.2003-031467. PMID 15001605.

[growth-14] Faglia G, Arosio M, Porretti S (December 2000). "Delayed closure of epiphyseal cartilages induced by the aromatase inhibitor anastrozole. Would it help short children grow up?". J. Endocrinol. Invest. 23 (11): 721–3. doi:10.1007/bf03345059. PMID 11194703.

[height-15] Mauras N, Gonzalez de Pijem L, Hsiang HY, Desrosiers P, Rapaport R, Schwartz ID, Klein KO, Singh RJ, Miyamoto A, Bishop K (March 2008). "Anastrozole increases predicted adult height of short adolescent males treated with growth hormone: a randomized, placebo-controlled, multicenter trial for one to three years". J. Clin. Endocrinol. Metab. 93 (3): 823–31. doi:10.1210/jc.2007-1559. PMC 2266949. PMID 18165285.

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anastrozole