Usage
- Anastrozole is prescribed for the treatment of hormone receptor-positive breast cancer in postmenopausal women. This includes:
- Early breast cancer: To reduce the risk of recurrence after surgery or other primary treatments.
- Advanced breast cancer: As a first-line treatment for locally advanced or metastatic breast cancer that has not been previously treated with hormonal therapy.
- Advanced breast cancer (second-line): For breast cancer that has progressed after tamoxifen therapy.
- Primary prevention: In postmenopausal women at moderate to high risk of developing breast cancer.
- Pharmacological Classification: Anastrozole is classified as an aromatase inhibitor, specifically a non-steroidal aromatase inhibitor.
- Mechanism of Action: Anastrozole works by blocking the enzyme aromatase, which is responsible for the conversion of androgens to estrogens in postmenopausal women. By reducing estrogen production, anastrozole slows or stops the growth of estrogen-dependent breast cancers.
Alternate Names
- Generic Name: Anastrozole
- Brand Name: Arimidex
- Other Names: There are no widely used international or regional variations of the name.
How It Works
- Pharmacodynamics: Anastrozole significantly reduces circulating estrogen levels in postmenopausal women. This estrogen deprivation inhibits the growth of hormone-receptor-positive breast cancer cells.
- Pharmacokinetics:
- Absorption: Anastrozole is well-absorbed orally, with peak plasma concentrations reached within two hours.
- Metabolism: Anastrozole is extensively metabolized in the liver primarily by CYP3A4 and to a lesser extent by CYP1A2, 2C8/9, and 2C19.
- Elimination: Anastrozole is primarily excreted in the urine, with a small portion eliminated in feces. The elimination half-life is approximately 40-50 hours.
- Mode of Action: Anastrozole competitively binds to the heme group of the aromatase enzyme, inhibiting its activity. This blocks the synthesis of estrogen from androgens, effectively lowering estrogen levels.
- Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Anastrozole acts through competitive inhibition of the aromatase enzyme. It does not directly interact with estrogen receptors or neurotransmitters.
- Elimination Pathways: Primarily renal excretion of metabolites. Some metabolites are eliminated in feces.
Dosage
Standard Dosage
Adults:
- 1 mg orally once daily.
- The recommended duration of adjuvant treatment for early breast cancer is 5 years. For advanced breast cancer, treatment continues until disease progression. For primary prevention, the treatment duration is 5 years.
Children:
- Anastrozole is not recommended for use in children and adolescents due to insufficient data on safety and efficacy.
Special Cases:
- Elderly Patients: No dose adjustments are necessary for elderly patients.
- Patients with Renal Impairment: No dose adjustment is necessary for mild or moderate renal impairment. Caution is advised in patients with severe renal impairment.
- Patients with Hepatic Dysfunction: No dose adjustment is necessary for mild hepatic impairment. Caution is advised in patients with moderate to severe hepatic impairment.
- Patients with Comorbid Conditions: Patients with pre-existing ischemic heart disease should be carefully monitored, as anastrozole may increase the risk of cardiovascular events. Patients with osteoporosis or at risk for osteoporosis should have their bone mineral density monitored.
Clinical Use Cases
Anastrozole’s primary use is in the outpatient setting for the treatment and prevention of breast cancer. It does not have a role in acute clinical situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations such as status epilepticus or cardiac arrest.
Dosage Adjustments
Dose adjustments may be considered for patients with severe renal or hepatic impairment based on clinical assessment and monitoring.
Side Effects
Common Side Effects
- Hot flashes
- Joint pain
- Muscle pain
- Headache
- Weakness/fatigue
- Nausea
- Vomiting
- Back pain
- Skin rash
- Bone pain
- Vaginal dryness or bleeding
- Difficulty sleeping
Rare but Serious Side Effects
- Allergic reactions (rash, shortness of breath, swelling of the face, dizziness)
- Ischemic cardiovascular events (chest pain, shortness of breath, leg swelling)
- Osteoporosis and fractures
- Hypercholesterolemia
Long-Term Effects
- Increased risk of osteoporosis and fractures with prolonged use.
Adverse Drug Reactions (ADR)
- Severe allergic reactions requiring immediate medical attention.
- Ischemic cardiovascular events.
Contraindications
- Pregnancy and breastfeeding
- Premenopausal women
- Known hypersensitivity to anastrozole or any of its components
Drug Interactions
- Estrogen-containing therapies: Co-administration should be avoided as this may diminish the effectiveness of anastrozole.
- Tamoxifen: Co-administration showed no efficacy benefit compared to tamoxifen alone.
- CYP3A4 inducers and inhibitors: May alter the metabolism of anastrozole. Close monitoring is required when co-administered with strong CYP3A4 inducers or inhibitors.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: X (Contraindicated)
- Fetal risks: Anastrozole is contraindicated during pregnancy as it can cause fetal harm and pregnancy loss.
- Breastfeeding: Anastrozole is not recommended during breastfeeding. It is unknown if anastrozole passes into breast milk, but it is likely to be present in high amounts, potentially causing adverse effects in the nursing infant.
Drug Profile Summary
- Mechanism of Action: Aromatase inhibitor, reduces estrogen production.
- Side Effects: Hot flashes, joint pain, muscle pain, headache, weakness, nausea, osteoporosis risk.
- Contraindications: Pregnancy, breastfeeding, premenopausal women, hypersensitivity.
- Drug Interactions: Estrogen-containing therapies, tamoxifen, CYP3A4 inducers/inhibitors.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 1 mg orally once daily.
- Monitoring Parameters: Bone mineral density, cholesterol levels, cardiovascular health.
Popular Combinations
Anastrozole is generally used as monotherapy. Combined hormonal therapy is not recommended with Anastrozole.
Precautions
- General Precautions: Assess bone mineral density and cardiovascular risk factors before and during treatment. Monitor cholesterol levels.
- Specific Populations: Contraindicated in pregnancy and breastfeeding. Not recommended for premenopausal women or children.
- Lifestyle Considerations: Encourage weight-bearing exercise and a calcium-rich diet to mitigate the risk of osteoporosis.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Anastrozole?
A: The standard dosage for adults is 1 mg orally once daily.
Q2: How does Anastrozole differ from Tamoxifen?
A: While both are hormonal therapies for breast cancer, tamoxifen is a selective estrogen receptor modulator (SERM), while anastrozole is an aromatase inhibitor. Tamoxifen blocks estrogen’s effects on breast tissue, while anastrozole reduces the body’s estrogen production.
Q3: Can Anastrozole be used in premenopausal women?
A: No, Anastrozole is contraindicated in premenopausal women because it is not effective in reducing estrogen levels in these women.
Q4: What are the most common side effects of Anastrozole?
A: Common side effects include hot flashes, joint pain, muscle aches, headache, and fatigue.
Q5: Are there any serious side effects associated with Anastrozole?
A: Yes, although rare, serious side effects can include increased risk of cardiovascular events, osteoporosis and fractures, and allergic reactions.
Q6: What should patients do if they miss a dose of Anastrozole?
A: If a dose is missed, the patient should take it as soon as they remember, unless it is almost time for the next dose. They should not double the dose to catch up.
Q7: How long should patients take Anastrozole?
A: The treatment duration depends on the indication. For adjuvant treatment of early breast cancer and primary prevention, it is typically 5 years. For advanced breast cancer, it continues until disease progression.
Q8: What are the key drug interactions to be aware of with Anastrozole?
A: Co-administration of estrogen-containing therapies and tamoxifen should be avoided. Close monitoring is necessary when using strong CYP3A4 inhibitors or inducers.
Q9: Can Anastrozole be taken with food?
A: Yes, anastrozole can be taken with or without food.
Q10: How does anastrozole affect bone health?
A: Anastrozole can decrease bone mineral density and increase the risk of osteoporosis and fractures. Regular bone density monitoring is recommended for patients on long-term therapy.
