Exemestane (Aromasin) is an irreversible steroidal aromatase inhibitor that is used in the treatment of breast cancer in postmenopausal women.

Exemestane (Aromasin) Uses:

• Breast cancer:

  • It is used for the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy;
  • adjuvant treatment of postmenopausal women with estrogen receptor-positive early breast cancer following 2 to 3 years of tamoxifen (for a total of 5 consecutive years of adjuvant therapy).

• Off Label Use of Exemestane in Adults:

  • Used for the first-line adjuvant treatment of estrogen receptor-positive early breast cancer in postmenopausal women.
  • Used in postmenopausal women for Risk reduction for invasive breast cancer.

Exemestane (Aromasin) Dose in Adults

Exemestane (Aromasin) Dose in the treatment of advanced Breast cancer:

• Postmenopausal females:

  • Oral: 25 mg once in a day; continue until tumor progression

Exemestane (Aromasin) Dose in the treatment of Early-stage Breast cancer (adjuvant treatment):

• Postmenopausal females:

  • Oral: 25 mg once in a day (continue 2 to 3 years of tamoxifen therapy) for a total time period of 5 years of endocrine therapy (in the absence of recurrence or contralateral breast cancer).

• Duration of therapy:

  • Required a maximum Time period of 5 years of aromatase inhibitor (AI) therapy for postmenopausal women, American Society of Clinical Oncology (ASCO) guidelines for Adjuvant Endocrine Therapy of Hormone Receptor-Positive Breast Cancer (Focused Update)
  • AIs may be combined with tamoxifen for a total duration of up to 10 years of endocrine therapy.
  • Refer to the guidelines for specific recommendations based on menopausal status and tolerability.
  • In a phase III study with another AI (letrozole), treatment with an additional 5 years of AI therapy (for a total of 10 years of aromatase inhibitor therapy) demonstrated a significantly improved rate of disease-free survival and a decreased risk of disease recurrence and contralateral breast cancer (when compared to placebo), although overall survival was not significantly different between groups and bone-related adverse events occurred more frequently with letrozole versus placebo.

Exemestane (Aromasin) Dose in the treatment of Early-stage Breast cancer, (first-line adjuvant treatment; off-label):

• Postmenopausal females:

• Oral: 25 mg for 5 years once in a day.

• Duration of therapy:

  • For postmenopausal women, ASCO guidelines for Adjuvant Endocrine Therapy of Hormone Receptor-Positive Breast Cancer (Focused Update) recommend a maximum Time period of 5 years of aromatase inhibitor (AI) therapy.
  • AIs may be combined with tamoxifen for a total Time period of up to 10 years of endocrine therapy.
  • Refer to the guidelines for specific recommendations based on menopausal status and tolerability.
  • In a phase III study with another AI (letrozole), treatment with an additional Time period of 5 years of AI therapy ( Total of 10 years of aromatase inhibitor therapy) demonstrated a significantly improved rate of disease-free survival and a decreased risk of disease recurrence and contralateral breast cancer (when compared to placebo), although overall survival was not significantly different between groups and bone-related adverse events occurred more frequently with letrozole versus placebo.

Exemestane (Aromasin) Dose in the treatment of Breast cancer, risk reduction (off-label):

• Postmenopausal females ≥35 years:

  • Oral: 25 mg for 5 years once in a day.
  • Dosage adjustment with strong CYP3A4 inducers:
    • 50 mg once in a day when used with potent inducers (eg, rifampin, phenytoin)

Use in Children:

Not indicated.

Exemestane (Aromasin) Pregnancy Risk Category: X

• Premenopausal women should not use it.
• Exemestane can cause fetal harm depending on its Phenomenon and animal data. It is likely to cause fetal harm to pregnant women if it is administered.
• Effective contraception should be used by women with reproductive potential during treatment, and for one month after the last dose.
• Pregnancy testing is highly recommended for females with reproductive potential within 7 days of therapy initiation.

Breastfeeding:

• It is only used in women who are postmenopausal.
• Breast-feeding is recommended for 1 month following the last dose. This is because of the risk of serious adverse reactions in breast-feeding infants.

Exemestane (Aromasin) Dose in Kidney Disease:

No adjustment required (although the safety of chronic doses in patients with moderate-to-severe renal impairment has not been studied, dosage adjustment does not appear necessary).

Exemestane (Aromasin) Dose in Liver disease:

No adjustment required (although the safety of chronic doses in patients with moderate-to-severe renal impairment has not been studied, dosage adjustment does not appear necessary).

Side Effects of Exemestane (Aromasin):

• Cardiovascular:

  • Hypertension
  • Edema
  • Ischemic Heart Disease
  • Chest Pain

• Central Nervous System:

  • Fatigue
  • Insomnia
  • Pain
  • Headache
  • Depression
  • Dizziness
  • Anxiety
  • Paresthesia
  • Carpal Tunnel Syndrome
  • Confusion
  • Hypoesthesia

• Dermatological:

  • Hyperhidrosis
  • Alopecia
  • Dermatitis
  • Pruritus
  • Skin Rash

• Endocrine & Metabolic:

  • Hot Flash
  • Weight Gain
  • Increased Follicle-Stimulating Hormone
  • Increased Luteinizing Hormone
  • Increased Sex Hormone Binding Globulin

• Gastrointestinal:

  • Nausea
  • Abdominal Pain
  • Diarrhea
  • Vomiting
  • Anorexia
  • Constipation
  • Increased Appetite
  • Dyspepsia

• Genitourinary:

  • Urinary Tract Infection

• Hematologic & Oncologic:

  • Lymphedema

• Hepatic:

  • Increased Serum Alkaline Phosphatase
  • Increased Serum Bilirubin

• Infection:

  • Infection

• Neuromuscular & Skeletal:

  • Arthralgia
  • Back Pain
  • Limb Pain
  • Myalgia
  • Osteoarthritis
  • Weakness
  • Osteoporosis
  • Pathological Fracture
  • Muscle Cramps

• Ophthalmic:

  • Visual Disturbance

• Renal:

  • Increased Serum Creatinine

• Respiratory:

  • Dyspnea
  • Cough
  • Flu-Like Symptoms
  • Bronchitis
  • Pharyngitis
  • Rhinitis
  • Sinusitis
  • Upper Respiratory Tract Infection

• Miscellaneous:

  • Fever

Contraindications to Exemestane (Aromasin):

• Hypersensitivity to exemestane and any component of the formulation

Warnings and precautions

• Reduced bone mineral density

  • Exemestane can cause a decrease in bone mineral density due to decreased estrogen levels.
  • In studies that did not allow the simultaneous use of calcium, bisphosphonates and vitamin D, there were decreases in the lumbar spine (from baseline), and in the femoral neck (from placebo).
  • Patients with osteoporosis or at-risk of it should be assessed at baseline.
  • If necessary, exemestane therapy can be used to monitor bone mineral density and start osteoporosis treatment.

• Lymphopenia

  • Exemestane has been shown to cause grade 3 and 4 lymphopenia.
  • However, most patients had lower-grade lymphopenia. Some patients were able to recover or improve while on exemestane.
  • Lymphopenia didn't cause a significant increase of viral infections and there were no opportunistic infection.

• Parameters for the lab

  • Patients with advanced breast cancer may have elevated levels of AST, ALT and alkaline phosphatase.
  • These elevations are rare and could be due to the underlying liver or bone metastases.
  • Patients with early breast cancer had higher levels of bilirubin, alkalinephosphatase and serum creatinine when they received exemestane than those who received Tamoxifen, or placebo.

Exemestane: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• 25-hydroxy vitamin D levels (at baseline);
• bone mineral density

How to administer Exemestane?

Administer after a meal.

Mechanism of action of Exemestane (Aromasin):

• Exemestane acts as an irreversible, steroidal inactivator of the aromatase enzyme. 
• It is structurally similar to androstenedione.
• The intermediate converts it to an inhibitor that irreversibly blocks active site of aromatase enzyme.
• This causes inactivation ("suicide inhibition"), and prevents the conversion of androgens into estrogens in peripheral tissues.
• In breast cancers that are estrogen-dependent, the circulating estrogens are significantly lower in women who have postmenopausal estrogens.

Absorption:

• Rapid and moderate (~42%) following oral administration;
• AUC and C increased by 59% and 39%, respectively, following a high-fat breakfast (compared to fasted state)

Distribution:

• Extensive into tissues

Protein binding:

• 90%, primarily to albumin and α -acid glycoprotein

Metabolism:

• Extensively hepatic; oxidation (CYP3A4) of methylene group, reduction of 17-keto group with formation of many secondary metabolites; metabolites are inactive

Half-life elimination:

• ~24 hours

Time to peak:

• Women with breast cancer: 1.2 hours

Excretion:

• Urine (<1% as unchanged drug, 39% to 45% as metabolites);
• feces (36% to 48%)

International Brand Names of Exemestane:

• Aromasin
• ACT Exemestane
• APO-Exemestane
• MED-Exemestane
• TEVA-Exemestane
• Aromasil
• Aromasin
• Aromasine
• Aromastan
• Emestane
• Escepran
• Exaccord
• Exetas
• Linkotax
• Orapec
• Xtane

Exemestane Brand Names in Pakistan: