Anastrozole

Anastrozole is an antineoplastic agent belonging to the pharmacological class of non-steroidal aromatase inhibitors.

The FDA has approved anastrozole for the treatment of breast cancer in postmenopausal women.

Once administered, anastrozole is rapidly and completely absorbed from the gastrointestinal with a slight decrease in absorption rate when taken with food, exhibiting 40% plasma protein binding. It undergoes extensive liver metabolism, producing the primary inactive metabolite, triazole. Anastrozole is mainly eliminated through faeces along with urine-containing metabolites.

The most common side effects of anastrozole are hot flashes, nausea, rashes, joint pain, osteoporosis, and weakness.

Anastrozole is available in the form of oral tablets.

The molecule is available in India, the United States, Canada, the United Kingdom, Italy, Australia, Germany, France, Japan and Spain.

Anastrozole is an antineoplastic agent belonging to the pharmacological class of non-steroidal aromatase inhibitors.

The enzyme aromatase, primarily located in the liver, adipose tissues, and adrenal glands, is selectively and competitively inhibited by anastrozole to produce its anti-estrogenic effects. A large number of breast cancers are hormone receptor-positive, which means that hormones like progesterone or estrogen either drive or sustain the growth of the tumour. Estrogen in postmenopausal women is mainly obtained from the aromatase enzyme, which converts androgens produced by the adrenal gland into estrogens. Anastrozole effectively suppresses circulating estrogen levels and, consequently, the growth of hormone receptor-positive tumours by competitively inhibiting estrogen biosynthesis at these enzymes.

Peak plasma concentration occurs at 2 hours when taken without food and 5 hours when taken with food.

Estradiol reduction reaches 70% within 24 hours and increases to 80% after two weeks of treatment onset.

Steady-state levels are achieved within seven days of continuous treatment.

Anastrozole is available in the form of an oral tablet.

Tablet: To be swallowed whole with water/liquid. Do not chew, crush or break it.

As the physician recommends, take the medication orally once daily, preferably after meals as directed.

Anastrozole can be used in the Treatment of Breast cancer.

Treatment of Breast Cancer: By preventing the production of estrogen, anastrozole is helpful in the treatment of breast cancer. It lowers estrogen levels and inhibits tumour growth because it is a non-steroidal aromatase inhibitor that prevents androgens from converting to estrogen. Anastrozole is an adjuvant treatment that effectively prevents cancer recurrence and improves overall survival in postmenopausal women with hormone receptor-positive breast cancer. It shows better tolerance than tamoxifen and reduces the incidence of contralateral breast cancer. By managing issues related to estrogen deficiency, the medication supports cardiovascular and bone health. Anastrozole is a beneficial treatment option with a well-established role in breast cancer therapy. Its beneficial effect on long-term outcomes and quality of life for postmenopausal women is emphasized.

• Indicated as an adjuvant treatment for postmenopausal women who have early breast cancer that is hormone receptor-positive.
• Indicated as the initial line of treatment for postmenopausal women with locally progressed or metastatic breast cancer that is hormone receptor-positive or hormone receptor-unknown.
• Indicated for postmenopausal women whose breast cancer has progressed after using tamoxifen for treatment.

Orally: Anastrozole, administered orally, is typically prescribed as a once-daily tablet. Patients are advised to take the medication simultaneously daily, usually after meals. The tablets should be swallowed whole with a glass of water, avoiding crushing or breaking them. Individuals must adhere strictly to the prescribed dosage and administration schedule. Patients are also advised to consult their healthcare provider about the medication's benefits and potential side effects.

The dosage and duration of treatment should be as per the treating physician's clinical judgment.

Anastrozole is available in the form of oral tablets.

Dose Adjustment in Adult Patients:

Breast Cancer

Adjuvant therapy for early-stage breast cancer

In postmenopausal women with early-stage breast cancer that is hormone receptor-positive

1 mg PO qDay x 5 years.

First-line treatment

1 mg PO qDay; continue until tumour progression

Second-line treatment.

1 mg PO qDay; continue until tumour progression

When taking anastrozole, adhere to dietary recommendations and safety guidelines for optimal well-being. Maintaining a healthy diet rich in essential nutrients and incorporating leafy vegetables, fruits, fatty fish, and dairy is necessary. Limit intake of processed foods, refined carbs, and added sugars. Encourage regular exercise to support overall health and weight management. Refrain from smoking and excessive alcohol consumption.

The dietary restriction should be individualized as per patient requirements.

Anastrozole may be contraindicated in the following conditions:-

•Anyone who has previously experienced hypersensitivity to any of the product's constituents.

•Women of premenopausal endocrine status, including pregnant women.

• Use anastrozole with caution in women with preexisting ischemic heart disease due to an increased incidence of ischemic cardiovascular events; only use if the benefits significantly outweigh the risks.

• Monitor closely for decreased lumbar spine and total hip bone mineral density, which increases the risk of fractures and osteoporosis. Concurrent use with bisphosphonates may be beneficial in patients at risk for fractures. Follow available guidelines for bone mineral density management in postmenopausal women, especially those with preexisting osteopenia at a higher risk of developing osteoporosis.

• Elevated serum cholesterol has been reported; monitor and manage cholesterol levels cautiously, especially in patients with hyperlipidemias, following current guidelines for patients with LDL elevations.

• Anastrozole provides no clinical benefit to premenopausal women with breast cancer.

• Patients with preexisting ischemic cardiac disease face an increased risk of ischemic cardiovascular events when using anastrozole. Consider the potential risks and benefits carefully in such cases. Regular monitoring and prompt management are essential for patient safety.

It is unsafe to consume Anastrozole with alcohol.

It is not recommended for use during breastfeeding.

It is not recommended for use during pregnancy.

Limit intake of saturated fats for safety and consume nutrient-rich foods.

The adverse reactions related to Anastrozole can be categorized as

•Common Adverse Effects: Hot flashes, vasodilation, fatigue, mood disturbances, nausea and vomiting, weakness, arthritis, pain, arthralgia, pharyngitis, depression, hypertension, bone pain, increased cough, osteoporosis, and rash.

•Less Common Adverse Effects: Accidental injury, back pain, fractures, headache, insomnia, peripheral oedema, dyspnea, abdominal pain, infection, lymphedema, diarrhoea, constipation, breast pain, dizziness, urinary tract infection, chest pain, dyspepsia, paresthesia, anxiety, cataracts, flu syndrome, sinusitis, vulvovaginitis, xerostomia, breast neoplasm, bronchitis, cyst, diaphoresis, neoplasm, vaginal bleeding, fractures of the spine, hip, or wrist, ischemic cardiovascular disease, vaginal bleeding, vaginitis, leukorrhea, deep vein thrombosis, endometrial cancer (intact uterus at baseline), ischemic cerebrovascular event, weight gain, lethargy.

•Rare Adverse Effects: Severe allergic reactions, hepatotoxicity, musculoskeletal events, ocular effects like cataracts, hematologic and dermatologic reactions.

Reports on Postmarketing

Hepatitis: high bilirubin, aminotransferases, gamma-glutamyl transferase, and alkaline phosphatase

Allergic responses, such as anaphylaxis, urticaria, and oedema rash, including conditions of the mucosa, such as Stevens-Johnson syndrome and erythema multiforme

Trigger finger, myalgia, and hypercalcemia (with or without parathyroid hormone rise).

The clinically relevant drug interactions of anastrozole are briefly summarized here.

• Drug-Drug Interactions: Taking Anastrozole with thalidomide (an immunomodulatory drug) can raise the risk of life-threatening blood clots.
• There were no drug-food interactions discovered.
• Drug-Disease Interactions: High cholesterol, osteoporosis (thinning of the bone), heart disease, and liver disease are among the diseases that Anastrozole may interact with.

The common side effects of anastrozole include:

• Hot flashes
• Nausea
• Headache
• Osteoporosis
• Skin rash
• Musculoskeletal (bone, muscle, or joint) pain
• Weakness

• Pregnancy

Pregnancy Category X (FDA): The risks outweigh the potential benefits. Safer alternatives exist.

When given to a pregnant woman, anastrozole may harm the fetus and has little therapeutic value for breast cancer patients who are premenopausal. Pregnant or potentially pregnant women should not take anastrozole. Anastrozole increased pregnancy loss, resulted in pregnancy failure, and showed symptoms of delayed fetal development in animal trials. Pregnant women's use of anastrozole has not been studied. The patient should be made aware of the possible risks to the fetus and pregnancy loss if they use anastrozole while pregnant or if they fall pregnant while taking this medication.

Animal data

Treatment may reduce the fertility of females capable of bearing children, according to research on female animals. Area under the curve (AUC) measurements show that anastrozole produced embryo-fetal toxicities in rats at maternal exposures nine times greater than human clinical exposure; at doses equivalent to or more than sixteen times the authorized human dose in terms of mg/m2, anastrozole caused pregnancy failure in rabbits.

• Nursing Mothers

Mothers who are nursing are advised not to breastfeed during treatment and for two weeks following the last dose because many drugs are excreted in human milk and because anastrozole is tumorigenic in animal studies. Additionally, there is no information on the presence of drugs or their metabolites in human milk, their effects on breastfed children, or their production of milk.

• Pediatric Use

As per the FDA, it is not recommended for use in the pediatric population.

Dose Adjustment in Kidney Impairment Patients:

The total body clearance of anastrozole remains unaffected by renal impairment because only approximately 10% of the drug is eliminated unaltered by urine. It is not necessary to change the dosage in patients who have renal impairment.

Dose Adjustment in Hepatic Impairment Patients:

Moderate to mild impairment or stable cirrhosis of the liver: No need to change the dose.

Not studied for severe hepatic impairment.

The physician should be vigilant about the knowledge pertaining to identifying and treating overdosage of Anastrozole.

Anastrozole has been used in clinical trials; healthy male volunteers were given up to 60 mg in a single dose, and postmenopausal women with metastatic breast cancer were given up to 10 mg daily; these amounts were well tolerated. It has not been determined if taking an anastrozole dose alone can cause potentially fatal symptoms. Overdosing has no known cure; hence, the only option for therapy is symptomatic. It is essential to keep in mind that more than one agent may have been ingested when managing an overdose. If the patient is awake, it is possible to induce vomiting. Because anastrozole is not firmly protein bound, dialysis might be beneficial. It is recommended to provide general supportive care, which includes regular vital sign monitoring and careful patient observation.

Continuous observation and appropriate, timely medical interventions to address specific symptoms or complications are recommended.

Pharmacodynamics:

Anastrozole inhibits the conversion of adrenal androgens, such as testosterone, to estrogen in peripheral and tumour tissues. Anastrozole helps in the treatment of breast malignancies by lowering circulating estrogen levels, which are known to trigger and support the growth of many breast cancers. Because of its relatively long half-life, anastrozole can be used once daily. Serum estradiol is suppressed for up to six days after the medication is stopped, and it decreases by around 70% within 24 hours of starting at 1 mg once daily.

Pharmacokinetics:

• Absorption: The gastrointestinal tract rapidly and almost wholly absorbs anastrozole. The rate of absorption slightly decreases with food.
• Distribution: Anastrozole exhibits 40% plasma protein binding.
• Metabolism: Extensive liver metabolism occurs through processes of N-dealkylation, hydroxylation, and glucuronidation, resulting in the primary inactive metabolite, triazole.
• Excretion: Anastrozole is primarily excreted via faeces, with urine containing metabolites. The elimination half-life is approximately 40-50 hours.

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