Anastrozole

The standard, FDA-recommended dosage for Anastrozole in the treatment of all approved indications—including adjuvant treatment of early breast cancer and treatment of advanced breast cancer—is 1 mg taken once daily.

Clinical trials, most notably the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial, compared 1 mg and 10 mg doses and found that the 1 mg dose was highly effective at suppressing estrogen levels and providing clinical benefit with a lower risk of side effects. Therefore, increasing the dose beyond 1 mg is not typically recommended as it does not provide additional therapeutic efficacy but may increase toxicity.

Anastrozole is not approved for use in pediatric patients. Its safety and effectiveness in children have not been established. While it has been studied off-label for conditions such as McCune-Albright syndrome and growth hormone deficiency to delay bone age maturation, the FDA has not granted approval for these uses, and clinical trials in these areas have shown inconsistent results.

Renal Impairment

No dosage adjustment is required for patients with mild to moderate renal (kidney) impairment. For patients with severe renal impairment (creatinine clearance less than 30 mL/min), the drug should be used with caution, although specific dose reductions are not standardized in the labeling. Monitoring of kidney function is recommended.

Hepatic Impairment

No dosage adjustment is necessary for patients with mild to moderate hepatic (liver) impairment, such as stable cirrhosis. However, Anastrozole has not been extensively studied in patients with severe hepatic impairment. Because the drug is primarily metabolized by the liver, healthcare providers should closely monitor patients with significant liver disease for potential side effects.

Elderly Patients

No dosage adjustment is required for elderly patients. In clinical trials, the efficacy and safety profiles in patients over the age of 65 were similar to those in younger postmenopausal adults.

To ensure the medication works effectively and to maintain consistent blood levels, follow these guidelines:

• Consistency: Take Anastrozole at the same time every day. This helps you remember the dose and keeps the level of medication in your body steady.
• With or Without Food: You may take the tablet with or without food. If you find that the medication causes an upset stomach, taking it with a meal may help.
• Swallow Whole: The tablet should be swallowed whole with a glass of water. Do not crush, chew, or break the tablet unless specifically instructed by your doctor.
• Duration: For early breast cancer, Anastrozole is typically taken for 5 years, though some recent guidelines suggest that 10 years of therapy may be beneficial for certain high-risk patients. Do not stop taking the medication without consulting your oncologist (cancer specialist).
• Storage: Store the medication at room temperature, between 68°F and 77°F (20°C to 25°C). Keep the container tightly closed and away from moisture and direct sunlight.

If you miss a dose of Anastrozole, take it as soon as you remember. However, if it is almost time for your next scheduled dose (within 12 hours), skip the missed dose and return to your regular dosing schedule. Do not take two doses at once to make up for a missed one, as this increases the risk of side effects.

Clinical experience with Anastrozole overdose is limited. There is no specific antidote for an Anastrozole overdose. In the event of an accidental overdose, symptoms may include severe nausea, vomiting, or dizziness.

Emergency Measures: If an overdose is suspected, contact your local poison control center or seek emergency medical attention immediately. Treatment is generally supportive, involving monitoring of vital signs and managing symptoms as they arise.

> Important: Follow your healthcare provider's dosing instructions exactly. Do not adjust your dose or stop the medication without medical guidance, as this could impact the effectiveness of your cancer treatment.

Because Anastrozole significantly lowers estrogen levels, many of its side effects mimic the symptoms of menopause. The most frequently reported side effects include:

• Hot Flashes (Vasomotor Symptoms): Sudden feelings of warmth, often most intense over the face, neck, and chest. These can occur frequently throughout the day and night.
• Joint Pain and Stiffness (Arthralgia): This is a hallmark side effect of aromatase inhibitors. Patients often report aching in the hands, knees, hips, or back, particularly upon waking in the morning. This is sometimes referred to as AI-induced musculoskeletal syndrome (AIMSS).
• Asthenia (Weakness and Fatigue): A general feeling of tiredness or lack of energy that does not always improve with rest.
• Mood Changes: Including increased anxiety or mild depression.
• Nausea: Mild stomach upset, which usually subsides as the body adjusts to the medication.

• Bone Thinning (Osteoporosis/Osteopenia): Reduced estrogen leads to a decrease in bone mineral density, increasing the risk of fractures.
• Carpal Tunnel Syndrome: Numbness, tingling, or weakness in the hand and wrist due to fluid retention or tissue changes pressing on the median nerve.
• Hypercholesterolemia: An increase in total cholesterol levels. Your doctor may monitor your lipid profile periodically.
• Thinning of Hair: Some women notice a slight decrease in hair density, similar to the thinning seen after menopause.
• Vaginal Dryness: Due to the lack of estrogen, which can lead to discomfort during intercourse.
• Peripheral Edema: Swelling in the hands, ankles, or feet caused by fluid retention.

• Trigger Finger: A condition where a finger gets stuck in a bent position.
• Hepatitis: Inflammation of the liver, which may manifest as yellowing of the skin or eyes (jaundice).
• Erythema Multiforme: A skin reaction that can look like targets (bullseye) on the skin.
• Hypercalcemia: High levels of calcium in the blood, particularly in patients with bone metastases.

> Warning: Stop taking Anastrozole and call your doctor immediately if you experience any of the following:

• Signs of a Stroke: Sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech, or vision problems.
• Chest Pain (Ischemic Heart Disease): Anastrozole may increase the risk of heart-related events in women with pre-existing heart disease. Seek help for chest pressure, shortness of breath, or pain radiating to the jaw or arm.
• Severe Allergic Reactions (Anaphylaxis): Swelling of the face, lips, tongue, or throat; difficulty breathing; or severe hives.
• Severe Skin Reactions: Blistering, peeling, or painful rashes (Stevens-Johnson Syndrome).
• Bone Fractures: Sudden, intense pain in the hip, wrist, or spine, which may indicate a fracture due to bone loss.

The most significant long-term concern with Anastrozole use is the impact on Bone Mineral Density (BMD). Estrogen plays a critical role in maintaining bone strength; by nearly eliminating estrogen, Anastrozole accelerates bone loss. Long-term users are at a higher risk for osteoporosis and clinical fractures. To manage this, doctors often recommend baseline and periodic DEXA (Dual-Energy X-ray Absorptiometry) scans, along with Vitamin D and Calcium supplementation or bone-strengthening medications like bisphosphonates.

Another long-term consideration is Cardiovascular Health. Some data suggest a slightly higher rate of cardiovascular events compared to other treatments like tamoxifen, particularly in women with pre-existing heart conditions. Regular monitoring of blood pressure and cholesterol is essential.

No FDA black box warnings for Anastrozole. Unlike some other hormonal therapies, Anastrozole does not carry a black box warning for uterine cancer or blood clots, which are risks more commonly associated with tamoxifen.

Report any unusual symptoms, especially persistent joint pain or signs of heart trouble, to your healthcare provider immediately.

Anastrozole is a powerful medication that significantly alters the hormonal environment of the body. It is intended only for women who are confirmed to be postmenopausal. Using this drug in women who are still ovulating is ineffective and may lead to unintended hormonal complications. Before starting treatment, your doctor may perform a blood test to check your FSH (follicle-stimulating hormone) and estradiol levels to confirm your menopausal status.

No FDA black box warnings for Anastrozole. While it is a potent medication, it does not currently meet the FDA criteria for a boxed warning. However, this does not mean the drug is without risk; the precautions listed below are clinically significant.

• Allergic Reactions / Anaphylaxis Risk: While rare, serious hypersensitivity reactions, including angioedema (swelling under the skin) and anaphylaxis, have been reported. If you have a known allergy to Anastrozole or any of its inactive ingredients (like lactose), you must not take this medication.
• Bone Health (Osteoporosis): Because Anastrozole lowers estrogen levels, it causes a reduction in bone mineral density. Patients with pre-existing osteoporosis or those at high risk for fractures must be managed carefully. Your healthcare provider will likely recommend a bone density test before and during treatment.
• Ischemic Heart Disease: In women with pre-existing ischemic heart disease (clogged arteries), there is an increased risk of cardiovascular events (like angina or heart attack) when taking Anastrozole. The risks and benefits must be weighed carefully in these patients.
• Cholesterol Levels: Anastrozole can cause an increase in blood cholesterol. High cholesterol is a risk factor for heart disease. Regular blood tests to monitor lipid levels are often required.
• Liver Function: Although rare, Anastrozole can cause changes in liver function tests. Patients with existing liver disease should be monitored closely for signs of hepatotoxicity (liver damage).

To ensure safety while taking Anastrozole, your healthcare provider will likely schedule the following tests:

• DEXA Scans: To monitor bone mineral density every 1–2 years.
• Lipid Panels: To check cholesterol and triglyceride levels.
• Liver Function Tests (LFTs): Periodic blood work to ensure the liver is processing the drug correctly.
• Clinical Breast Exams and Mammograms: To monitor the effectiveness of the treatment and check for any changes in breast tissue.

Anastrozole generally does not interfere with the ability to drive or operate machinery. However, some patients report asthenia (weakness) and somnolence (drowsiness) during the initial weeks of treatment. If you feel dizzy or unusually tired, avoid these activities until you know how the medication affects you.

There is no direct contraindication between alcohol and Anastrozole. However, alcohol can exacerbate certain side effects like hot flashes and may contribute to bone loss over time. Furthermore, both alcohol and Anastrozole are processed by the liver. Moderate to heavy alcohol consumption should be discussed with your doctor to avoid unnecessary liver strain.

Anastrozole does not require a tapering schedule (gradually reducing the dose) and does not typically cause a withdrawal syndrome. However, stopping the medication early significantly increases the risk of breast cancer recurrence. You should only discontinue Anastrozole under the direct supervision of your oncologist. If you are stopping due to side effects, your doctor may suggest alternative treatments such as Letrozole or Exemestane.

> Important: Discuss all your medical conditions, especially heart disease, liver problems, and osteoporosis, with your healthcare provider before starting Anastrozole.

Certain medications can completely negate the benefits of Anastrozole or lead to dangerous outcomes. These should be avoided:

• Estrogen-Containing Therapies: This includes Hormone Replacement Therapy (HRT), estrogen creams, and birth control pills. Since Anastrozole’s entire mechanism is to lower estrogen, taking estrogen supplements directly contradicts the therapy and may allow the cancer to grow.
• Tamoxifen: Clinical data from the ATAC trial showed that combining Anastrozole with Tamoxifen did not provide any additional benefit over Tamoxifen alone and actually reduced the blood levels of Anastrozole by about 27%. Therefore, they are not used together.

• Warfarin: While not a direct metabolic interaction, changes in hormonal status can sometimes affect blood clotting factors. Patients on anticoagulants (blood thinners) should have their INR monitored closely when starting or stopping Anastrozole.
• Thalidomide: There is a potential increased risk of blood clots when used in combination with certain cancer therapies, though this is more relevant in specific chemotherapy regimens.

• CYP3A4 Inducers (e.g., Rifampin, Phenytoin): These medications can speed up the metabolism of Anastrozole, potentially lowering its concentration in the blood and reducing its effectiveness. Your doctor may need to monitor your response to therapy more closely.
• CYP3A4 Inhibitors (e.g., Ketoconazole, Clarithromycin): These can slow the breakdown of Anastrozole, potentially increasing the risk of side effects. However, because Anastrozole has a wide safety margin, this is usually manageable without dose changes.

• Grapefruit and Grapefruit Juice: Grapefruit contains compounds that inhibit the CYP3A4 enzyme. While the effect on Anastrozole is not as dramatic as with other drugs (like statins), it is generally recommended to avoid large amounts of grapefruit to maintain consistent drug levels.
• Soy and Isoflavones: Large amounts of soy contain phytoestrogens (plant-based estrogens). While dietary soy in moderation is usually fine, concentrated soy supplements should be avoided as they may interfere with the estrogen-lowering goals of Anastrozole.
• Dairy: There are no known interactions with dairy products.

• St. John’s Wort: This herbal supplement is a potent inducer of liver enzymes and can significantly reduce the effectiveness of Anastrozole. It should be avoided by patients undergoing cancer treatment.
• Red Clover / Black Cohosh: These are often used for menopausal symptoms but contain estrogen-like compounds. They may interfere with Anastrozole’s efficacy and should not be used without consulting an oncologist.
• Vitamin D and Calcium: These are actually recommended interactions. Most patients on Anastrozole should take these supplements to help mitigate the risk of bone loss.

Anastrozole may affect the results of certain laboratory tests:

• Thyroid Function Tests: Some changes in thyroid-binding globulin have been noted, though clinical thyroid disease is rare.
• Liver Enzymes: Elevations in ALT, AST, and alkaline phosphatase may occur and do not always indicate permanent liver damage but require monitoring.
• Cholesterol Tests: As mentioned, expect potential increases in total cholesterol and LDL (bad cholesterol).

For each major interaction, the primary concern is either the reduction of efficacy (the cancer is not being treated effectively) or an increase in toxicity (side effects become unbearable).

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter pain relievers and vitamins.

Anastrozole must NEVER be used in the following situations:

1. 1Pregnancy: Anastrozole is classified as Pregnancy Category X (or equivalent under newer labeling). It can cause significant fetal harm, including birth defects and pregnancy loss. Because it is used in postmenopausal women, this is rarely an issue, but it is strictly forbidden in any woman who is or could become pregnant.
2. 2Premenopausal Status: The drug is not effective in women with functioning ovaries. In premenopausal women, the drop in estrogen caused by the drug triggers the brain (hypothalamus/pituitary) to signal the ovaries to produce even more estrogen, which can stimulate tumor growth.
3. 3Known Hypersensitivity: If a patient has had a previous severe allergic reaction to Anastrozole or any component of the tablet (such as lactose or magnesium stearate), the drug is strictly contraindicated.

These are conditions where the drug should be used only if the benefits clearly outweigh the risks, and with extreme caution:

• Severe Renal Impairment: Due to the lack of clinical data in patients with a CrCl below 30 mL/min, use requires intense monitoring.
• Severe Hepatic Disease: Patients with end-stage liver disease may not be able to metabolize the drug, leading to toxic accumulation.
• Pre-existing Osteoporosis: While not a reason to avoid the drug entirely (as the cancer benefit is high), it requires aggressive concurrent bone-protective therapy.
• Ischemic Heart Disease: Patients with a history of heart attacks or unstable angina need careful cardiovascular monitoring.

There is a potential for cross-sensitivity between different non-steroidal aromatase inhibitors. If a patient has had a severe skin reaction or angioedema with Letrozole (Femara), they may be at a higher risk for a similar reaction with Anastrozole. However, they may be able to tolerate a steroidal aromatase inhibitor like Exemestane (Aromasin), as its chemical structure is fundamentally different.

> Important: Your healthcare provider will evaluate your complete medical history, including your menopausal status and bone health, before prescribing Anastrozole.

Anastrozole is strictly contraindicated in pregnant women. Based on its mechanism of action (lowering estrogen), it is highly teratogenic (causes birth defects). Animal studies have shown that Anastrozole causes pregnancy loss, low birth weight, and skeletal variations in the fetus. If a woman becomes pregnant while taking this drug, she must be informed of the potential hazard to the fetus. In the context of fertility treatments (off-label), it is used before conception to induce ovulation and is not present in the body during the actual pregnancy.

It is not known whether Anastrozole is excreted in human milk. However, because many drugs are excreted in milk and because of the potential for serious adverse reactions in a nursing infant, women should not breastfeed while taking Anastrozole and for at least two weeks after the final dose.

Anastrozole is not indicated for use in children. Clinical trials in boys with 'testotoxicosis' (precocious puberty) and girls with McCune-Albright syndrome did not demonstrate sufficient efficacy to warrant FDA approval. Furthermore, there are concerns about the long-term impact of estrogen suppression on bone mineral density and growth plate closure in developing children.

In the large ATAC trial, 45% of patients were 65 years of age or older. No overall differences in safety or effectiveness were observed between these patients and younger patients. However, elderly patients are naturally at a higher risk for osteoporosis and cardiovascular disease, so the monitoring of bone density and heart health is particularly critical in this population. No specific dose adjustment is needed based on age alone.

• Mild to Moderate (CrCl 30-89 mL/min): No dose adjustment is necessary.
• Severe (CrCl <30 mL/min): Use with caution. Anastrozole is not significantly removed by hemodialysis because of its distribution and protein binding characteristics.

• Mild to Moderate (Child-Pugh A and B): No dose adjustment is required for patients with stable hepatic cirrhosis.
• Severe (Child-Pugh C): Anastrozole has not been studied in this group. Since the liver is the primary site of metabolism, there is a risk of increased drug exposure. Treatment should be closely monitored by a specialist.

> Important: Special populations require individualized medical assessment to balance the life-saving benefits of cancer therapy against potential physiological risks.

Anastrozole is a potent and highly selective non-steroidal aromatase inhibitor. In postmenopausal women, the enzyme aromatase converts adrenal androgens (primarily androstenedione and testosterone) into estrogens (estrone and estradiol). Anastrozole binds reversibly to the heme group of the cytochrome P450 unit of the aromatase enzyme. This prevents the enzyme from converting androgens into estrogens. By blocking this pathway, Anastrozole reduces serum estrogen concentrations by approximately 80% to 85% from baseline, thereby depriving estrogen-dependent breast cancer cells of the stimulus they need to grow and proliferate.

Anastrozole does not possess any progestogenic, androgenic, or estrogenic activity. At the therapeutic dose of 1 mg, it does not affect the secretion of cortisol or aldosterone from the adrenal glands, meaning it does not disrupt the body's stress response or electrolyte balance. The onset of estrogen suppression occurs within 24 hours of the first dose, and maximum suppression is typically achieved within 2 to 4 days of continuous use.

| Parameter | Value |

|---|---|

| Bioavailability | ~85% (Rapidly absorbed) |

| Protein Binding | ~40% |

| Half-life | ~50 hours |

| Tmax (Time to peak) | ~2 hours (fasting) |

| Metabolism | Hepatic (N-dealkylation, glucuronidation) |

| Excretion | Fecal (~60%), Renal (~10% unchanged) |

• Molecular Formula: C15H17N5
• Molecular Weight: 293.37 g/mol
• Solubility: Moderately soluble in water; freely soluble in methanol, acetone, and ethanol.
• Structure: It is a benzyltriazole derivative. Chemically, it is described as 1,3-Benzenediacetonitrile, a, a, a', a'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl).

Anastrozole is classified as a Third-Generation Aromatase Inhibitor. It is distinct from first-generation (aminoglutethimide) and second-generation (formestane) inhibitors due to its higher potency and selectivity. It is a non-steroidal inhibitor, distinguishing it from steroidal inhibitors like Exemestane, which bind irreversibly to the aromatase enzyme.