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| Trade names | Arimidex, Aremed, others[1] |
| Other names | Anastrazole; anastrozol; ICI-D1033; ZD-1033 |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a696018 |
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| Routes of administration | By mouth |
| Drug class | Aromatase inhibitor;Antiestrogen |
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| Pharmacokinetic data | |
| Bioavailability | Unknown (but well-absorbed in animals)[3] |
| Protein binding | 40%[4][5] |
| Metabolism | Liver (~85%) (N-dealkylation,hydroxylation,glucuronidation)[4][3][5] |
| Eliminationhalf-life | 40–50 hours[4][3][5] |
| Excretion | Urine (11%)[4][3][5] |
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| ECHA InfoCard | 100.129.723 |
| Chemical and physical data | |
| Formula | C17H19N5 |
| Molar mass | 293.374 g·mol−1 |
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Anastrozole, sold under the brand nameArimidex among others, is anantiestrogenic medication used in addition to other treatments forbreast cancer.[7][8] Specifically it is used forhormone receptor-positive breast cancer.[8] It has also been used to prevent breast cancer in those at high risk.[8] It is takenby mouth.[8]
Common side effects of anastrozole includehot flashes,altered mood,joint pain, andnausea.[8][7] Severe side effects include an increased risk ofheart disease andosteoporosis.[8] Use duringpregnancy may harm the baby.[8] Anastrozole is in thearomatase-inhibiting family of medications.[8] It works by blocking theproduction ofestrogens in the body, and hence hasantiestrogenic effects.[8]
Anastrozole was patented in 1987 and was approved for medical use in 1995.[9][10] It is on theWorld Health Organization's List of Essential Medicines.[11] Anastrozole is available as ageneric medication.[8] In 2022, it was the 179th most commonly prescribed medication in the United States, with more than 2 million prescriptions.[12][13]
Anastrozole is used in the treatment and prevention ofbreast cancer in women.[8] TheArimidex,Tamoxifen,Alone or inCombination (ATAC) trial was oflocalized breast cancer and women received either anastrozole, theselective estrogen receptor modulatortamoxifen, or both for five years, followed by five years of follow-up.[14] After more than 5 years the group that received anastrozole had better results than the tamoxifen group.[14] The trial suggested that anastrozole is the preferred medical therapy forpostmenopausal women with localizedestrogen receptor-positive breast cancer.[14]
Anastrozole is used at a dosage of 0.5 to 1 mg/day in combination with theantiandrogenbicalutamide in the treatment ofperipheral precocious puberty, for instance due tofamilial male-limited precocious puberty (testotoxicosis) andMcCune–Albright syndrome, in boys.[15][16][17][18][19][20][21][22][23][24]
Anastrozole is available in the form of 1 mgoraltablets.[7][25] No alternativeforms orroutes are available.[25]
Contraindications of anastrozole includehypersensitivity to anastrozole or any other component of anastrozole formulations,pregnancy, andbreastfeeding.[7] Hypersensitivity reactions to anastrozole includinganaphylaxis,angioedema, andurticaria have been observed.[7]
Commonside effects of anastrozole (≥10% incidence) includehot flashes,asthenia,arthritis,pain,arthralgia,hypertension,depression,nausea andvomiting,rash,osteoporosis,bone fractures,back pain,insomnia,headache,bone pain,peripheral edema,coughing,dyspnea,pharyngitis, andlymphedema.[7] Serious but rare adverse effects (<0.1% incidence) includeskin reactions such aslesions,ulcers, orblisters;allergic reactions withswelling of theface,lips,tongue, and/orthroat that may cause difficultyswallowing orbreathing; andabnormal liver function tests as well ashepatitis.[7]
Anastrozole is thought to have clinically negligible inhibitory effects on thecytochrome P450enzymesCYP1A2,CYP2A6,CYP2D6,CYP2C8,CYP2C9, andCYP2C19.[4][3][5][7] As a result, it is thought thatdrug interactions of anastrozole with cytochrome P450substrates are unlikely.[5] No clinically significantdrug interactions have been reported with anastrozole as of 2003.[4]
Anastrozole does not affect circulating levels oftamoxifen or its majormetaboliteN-desmethyltamoxifen.[4][3] However, tamoxifen has been found to decreasesteady-statearea-under-the-curve levels of anastrozole by 27%.[4][3] But estradiol levels were not significantly different in the group that received both anastrozole and tamoxifen compared to the anastrozole alone group, so the decrease in anastrozole levels is not thought to be clinically important.[5]
Anastrozole works byreversibly binding to thearomataseenzyme, and throughcompetitive inhibition blocks the conversion ofandrogens toestrogens in peripheral (extragonadal)tissues.[26] The medication has been found to achieve 96.7% to 97.3% inhibition of aromatase at a dosage of 1 mg/day and 98.1% inhibition of aromatase at a dosage of 10 mg/day in humans.[4][3] As such, 1 mg/day is considered to be the minimal dosage required to achieve maximal suppression of aromatase with anastrozole.[4] This decrease in aromatase activity results in an at least 85% decrease in estradiol levels in postmenopausal women.[4] Levels ofcorticosteroids and otheradrenal steroids are unaffected by anastrozole.[4]
| Generation | Medication | Dosage | % inhibitiona | Classb | IC50c |
|---|---|---|---|---|---|
| First | Testolactone | 250 mg 4x/dayp.o. | ? | Type I | ? |
| 100 mg 3x/weeki.m. | ? | ||||
| Rogletimide | 200 mg 2x/dayp.o. 400 mg 2x/dayp.o. 800 mg 2x/dayp.o. | 50.6% 63.5% 73.8% | Type II | ? | |
| Aminoglutethimide | 250 mg mg 4x/dayp.o. | 90.6% | Type II | 4,500 nM | |
| Second | Formestane | 125 mg 1x/dayp.o. 125 mg 2x/dayp.o. 250 mg 1x/dayp.o. | 72.3% 70.0% 57.3% | Type I | 30 nM |
| 250 mg 1x/2 weeksi.m. 500 mg 1x/2 weeksi.m. 500 mg 1x/1 weeki.m. | 84.8% 91.9% 92.5% | ||||
| Fadrozole | 1 mg 1x/dayp.o. 2 mg 2x/dayp.o. | 82.4% 92.6% | Type II | ? | |
| Third | Exemestane | 25 mg 1x/dayp.o. | 97.9% | Type I | 15 nM |
| Anastrozole | 1 mg 1x/dayp.o. 10 mg 1x/dayp.o. | 96.7–97.3% 98.1% | Type II | 10 nM | |
| Letrozole | 0.5 mg 1x/dayp.o. 2.5 mg 1x/dayp.o. | 98.4% 98.9%–>99.1% | Type II | 2.5 nM | |
| Footnotes:a = Inpostmenopausal women.b = Type I:Steroidal,irreversible (substrate-binding site). Type II:Nonsteroidal,reversible (binding to and interference with thecytochrome P450hememoiety).c = Inbreast cancerhomogenates.Sources: See template. | |||||
Thebioavailability of anastrozole in humans is unknown, but it was found to bewell-absorbed in animals.[3][7] Absorption of anastrozole is linear over a dosage range of 1 to 20 mg/day in humans and does not change with repeated administration.[4][5][7]Food does not significantly influence the extent of absorption of anastrozole.[5][7]Peak levels of anastrozole occur a median 3 hours after administration, but with a wide range of 2 to 12 hours.[3][5]Steady-state levels of anastrozole are achieved within 7 to 10 days of continuous administration, with 3.5-fold accumulation.[4][3][5] However, maximal suppression of estradiol levels occurs within 3 or 4 days of therapy.[4]
Activeefflux of anastrozole byP-glycoprotein at theblood–brain barrier has been found to limit thecentral nervous system penetration of anastrozole in rodents, whereas this was not the case withletrozole andvorozole.[27][28][29] As such, anastrozole may haveperipheral selectivity in humans, although this has yet to be confirmed.[29] In any case, estradiol is synthesized peripherally and readily crosses the blood–brain barrier, so anastrozole would still expected to reduce estradiol levels in the central nervous system to a certain degree. Theplasma protein binding of anastrozole is 40%.[4][5]
Themetabolism of anastrozole is byN-dealkylation,hydroxylation, andglucuronidation.[4] Inhibition of aromatase is due to anastrozole itself rather than tometabolites, with the major circulating metabolite being inactive.[7] Theelimination half-life of anastrozole is 40 to 50 hours (1.7 to 2.1 days).[4][3][5] This allows for convenient once-daily administration.[5] The medication iseliminated predominantly by metabolism in theliver (83 to 85%) but also by residualexcretion by thekidneys unchanged (11%).[4][3][5] Anastrozole is excreted primarily inurine but also to a lesser extent infeces.[5]
Anastrozole is anonsteroidalbenzyltriazole.[4][5] It is also known as α,α,α',α'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-m-benzenediacetonitrile.[1] Anastrozole is structurally related toletrozole,fadrozole, andvorozole, with all being classified asazoles.[30][31][32][33]
Anastrozole was patented byImperial Chemical Industries (ICI) in 1987 and was approved for medical use, specifically the treatment of breast cancer, in 1995.[9][10]
Anastrozole is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name,USANTooltip United States Adopted Name,BANTooltip British Approved Name, andJANTooltip Japanese Accepted Name.[1]
Anastrozole is primarily sold under the brand name Arimidex.[1] However, it is also marketed under a variety of other brand names throughout the world.[1]
Anastrozole is available widely throughout the world.[1]
Anastrozole is surprisingly ineffective at treatinggynecomastia, in contrast toselective estrogen receptor modulators liketamoxifen.[34][35]
Anastrozole was under development for the treatment offemale infertility but did not complete development and hence was never approved for this indication.[36]
An anastrozole andlevonorgestrelvaginal ring (developmental code name BAY 98–7196) was under development for use as ahormonal contraceptive and treatment forendometriosis, but development was discontinued in November 2018 and the formulation was never marketed.[37]
Anastrozole increasestestosterone levels in males and has been studied as an alternative method ofandrogen replacement therapy in men withhypogonadism.[38][39] However, there are concerns about its long-term influence onbone mineral density in this patient population, as well as other adverse effects.[38]
