Anastrozole

Anastrozole is a selective, reversible, nonsteroidal triazole aromatase inhibitor. It is FDA-approved as Arimidex 1 mg tablets and generic equivalents. Lake Hills Pharmacy compounds low-strength oral capsules for prescriber-directed use, chiefly in men receiving testosterone therapy.

Arimidex is labeled for postmenopausal women with breast cancer: adjuvant treatment of hormone receptor-positive early breast cancer; first-line treatment of hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer; and advanced breast cancer with disease progression after tamoxifen.

No FDA-labeled indication exists in men. Prescribers use anastrozole off-label in men receiving testosterone therapy to limit estradiol, and in some cases of male hypogonadism and gynecomastia.

Anastrozole competitively inhibits aromatase (CYP19A1), the enzyme that converts androstenedione to estrone and testosterone to estradiol in peripheral tissues such as adipose tissue, muscle and liver. This is the main source of estrogen in postmenopausal women and in men. It lowers serum estradiol without a meaningful effect on adrenal corticosteroid or aldosterone synthesis. In men, reduced estrogen feedback at the hypothalamus and pituitary can raise LH, FSH and endogenous testosterone.

Anastrozole is well absorbed, with peak plasma levels about 2 hours after a fasting dose; food slows the rate but not the extent of absorption. It is about 40% protein bound. Elimination is mainly hepatic (N-dealkylation, hydroxylation and glucuronidation) to inactive metabolites, with about 10% excreted unchanged in the urine. The terminal half-life is about 50 hours, so steady state is reached in about 7 days of daily dosing. No dose adjustment is labeled for renal or mild to moderate hepatic impairment.

• Hypersensitivity to anastrozole or any excipient (reactions have included anaphylaxis, angioedema and urticaria). This is the only contraindication in current Arimidex labeling; embryo-fetal toxicity is a warning (below).

• Ischemic cardiovascular events: in women with pre-existing ischemic heart disease, more ischemic events occurred with anastrozole than with tamoxifen in adjuvant trials.
• Bone effects: anastrozole decreases bone mineral density; consider bone density assessment in long-term use.
• Cholesterol: increases in total and LDL cholesterol have been reported.
• Embryo-fetal toxicity: anastrozole can cause fetal harm. Verify pregnancy status in females of reproductive potential before starting and advise effective contraception (see Pregnancy & Lactation).
• Men: estradiol over-suppression can cause loss of bone mineral density, reduced libido, erectile dysfunction, joint pain, fatigue, depressed mood and unfavorable lipid changes. Fixed dosing without laboratory monitoring increases this risk.
• Hepatic: elevated liver enzymes and, rarely, hepatitis have been reported.

• Tamoxifen: lowers anastrozole concentrations; the two should not be combined.
• Estrogen-containing therapies: oppose the pharmacologic action of anastrozole.
• Anastrozole has no clinically significant effect on CYP-mediated metabolism at therapeutic doses and does not alter the anticoagulant effect of warfarin.

Hot flashes, asthenia, arthralgia and arthritis, joint stiffness, back pain, pain, pharyngitis, hypertension, depression, nausea and vomiting, rash, insomnia, headache, peripheral edema, lymphedema, osteoporosis and fractures, carpal tunnel syndrome, trigger finger and hypercholesterolemia. Rare: Stevens-Johnson syndrome, angioedema, anaphylaxis and hepatitis. In women: vaginal dryness and bleeding.

Anastrozole can cause fetal harm. Females of reproductive potential should have a pregnancy test before starting and use reliable contraception during treatment and for 3 weeks after the last dose. Breastfeeding is not advised during treatment and for 2 weeks after the last dose. Animal data suggest anastrozole may impair fertility in females and males.

In men: serum estradiol by a sensitive assay, total testosterone, symptoms of estrogen deficiency or excess, lipid panel, and bone mineral density with long-term use or other risk factors. In women: bone mineral density and lipids. Liver tests if symptoms suggest hepatic injury.

• Arimidex (anastrozole) Tablets Prescribing Information, ANI Pharmaceuticals (originally AstraZeneca).
• Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline (2018).
• Evaluation and Management of Testosterone Deficiency: AUA Guideline (2018), American Urological Association.