Aromasin

Name: Aromasin

What special precautions should I follow?

Before taking exemestane,

  • tell your doctor and pharmacist if you are allergic to exemestane or any other medications.
  • tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: carbamazepine (Carbatrol, Epitol, Tegretol); medications that contain estrogen such as hormone replacement therapy and hormonal contraceptives (birth control pills, patches, rings, and injections); phenobarbital; phenytoin (Dilantin); and rifampin (Rifadin, in Rifater, in Rifamate). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
  • tell your doctor what herbal products you are taking, especially St John's wort.
  • tell your doctor if you have or have ever had osteoporosis (condition in which the bones are fragile and break easily), liver or kidney disease.
  • tell your doctor if you are pregnant or plan to become pregnant. You will need to have a negative pregnancy test within 7 days before you begin to take exemestane. You should use birth control to avoid pregnancy during your treatment with exemestane and for 1 month after your final dose. If you become pregnant while taking exemestane, call your doctor immediately. Exemestane may harm the fetus.
  • tell your doctor if you are breastfeeding. You should not breastfeed during your treatment with exemestane and for 1 month after your final dose.

What special dietary instructions should I follow?

Unless your doctor tells you otherwise, continue your normal diet.

What should I know about storage and disposal of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Before taking exemestane

Some medicines are not suitable for people with certain conditions, and sometimes a medicine can only be used if extra care is taken. For these reasons, before you start taking exemestane it is important that your doctor knows:

  • If you have not yet gone through the menopause, or if there is a possibility you could be pregnant.
  • If you have any problems with the way your liver works, or any problems with the way your kidneys work.
  • If you have a loss of bone density, or 'brittle bones' - a condition known as osteoporosis.
  • If you have ever had an allergic reaction to a medicine.
  • If you are taking any other medicines. This includes any medicines you are taking which are available to buy without a prescription, as well as herbal and complementary medicines.

Aromasin Overview

Aromasin is a prescription medication used in the treatment of advanced breast cancer in postmenopausal women previously treated with tamoxifen. Aromasin belongs to a group of drugs called aromatase inhibitors. These medications work by lowering estrogen levels which may slow or stop the growth of certain types of breast cancer. 

Aromasin comes in tablet form and is taken once a day, after a meal.  Common side effects of Aromasin include hot flashes, headache, tiredness and difficulty sleeping. 

Aromasin Dosage

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. The dose your doctor recommends may be based on the following:

  • the condition being treated
  • other medical conditions you have
  • other medications you are taking
  • how you respond to this medication
  • your weight
  • your height
  • your age
  • your gender

The recommended dose of Aromasin in postmenopausal women is 25 mg once daily. The dose your doctor recommends may be higher if you take certain medications.

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What is exemestane?

Exemestane lowers estrogen levels in postmenopausal women, which may slow the growth of certain types of breast tumors that need estrogen to grow in the body.

Exemestane is used to treat breast cancer in postmenopausal women. It is often given to women whose cancer has progressed even after surgery, radiation, or other cancer medications have been tried without success.

Exemestane may also be used for purposes not listed in this medication guide.

Advice to Patients

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.1 Importance of not taking estrogenic agents concomitantly.1

  • Warn of potential hazard to the fetus in cases of inadvertent exposure of pregnant women to exemestane.1 Advise patients that exemestane is indicated for use only in postmenopausal women.1

  • Risk of osteoporosis.1 12 Life-style changes (e.g., weight-bearing exercise, abstinence from smoking, moderation of alcohol consumption) and dietary supplementation with calcium and vitamin D advised.12 13 14 15 Importance of BMD monitoring.1 12 13 15 71 73

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Exemestane

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

25 mg*

Aromasin

Pfizer

Exemestane Tablets

Aromasin Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common
  • Cough or hoarseness
  • difficult or labored breathing
  • fever or chills
  • lower back or side pain
  • mental depression
  • swelling of the hands, ankles, feet, or lower legs
  • tightness in the chest
Less common
  • Chest pain
  • difficult, burning, or painful urination
  • frequent urge to urinate
  • headache
  • sore throat
  • unexplained broken bones
Incidence not known
  • Abdominal or stomach pain
  • clay-colored stools
  • confusion
  • dark urine
  • decreased urine output
  • diarrhea
  • difficulty with speaking
  • dilated neck veins
  • dizziness
  • double vision
  • inability to move the arms, legs, or facial muscles
  • inability to speak
  • irregular breathing
  • irregular heartbeat
  • itching or rash
  • loss of appetite
  • nausea
  • slow speech
  • unpleasant breath odor
  • unusual tiredness or weakness
  • vomiting of blood
  • weight gain
  • yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Anxiety
  • constipation
  • general feeling of discomfort or illness
  • general feeling of tiredness or weakness
  • hot flashes
  • increased sweating
  • pain
  • trouble sleeping
Less common
  • Back pain
  • bone pain
  • burning, tingling, or prickly sensations
  • decreased sense of touch
  • increased appetite
  • joint pain
  • loss of hair
  • runny nose
  • stomach upset
  • weakness, generalized

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Aromasin Dosage and Administration

Recommended Dose

The recommended dose of Aromasin in early and advanced breast cancer is one 25 mg tablet once daily after a meal.

  • adjuvant treatment of postmenopausal women with estrogen-receptor positive early breast cancer who have received two to three years of tamoxifen and are switched to Aromasin for completion of a total of five consecutive years of adjuvant hormonal therapy.
  • the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.

Dose Modifications

Concomitant use of strong CYP 3A4 inducers decreases exemestane exposure, For patients receiving Aromasin with a strong CYP 3A4 inducer such as rifampicin or phenytoin, the recommended dose of Aromasin is 50 mg once daily after a meal [see Drug Interactions (7) and Clinical Pharmacology (12.3)].

Dosage Forms and Strengths

Aromasin Tablets are round, biconvex, and off-white to slightly gray. Each tablet contains 25 mg of exemestane. The tablets are printed on one side with the number "7663" in black.

Drug Interactions

Drugs That Induce CYP 3A4

Co-medications that induce CYP 3A4 (e.g., rifampicin, phenytoin, carbamazepine, phenobarbital, or St. John's wort) may significantly decrease exposure to exemestane. Dose modification is recommended for patients who are also receiving a strong CYP 3A4 inducer [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].

Overdosage

Clinical trials have been conducted with exemestane given as a single dose to healthy female volunteers at doses as high as 800 mg and daily for 12 weeks to postmenopausal women with advanced breast cancer at doses as high as 600 mg. These dosages were well tolerated. There is no specific antidote to overdosage and treatment must be symptomatic. General supportive care, including frequent monitoring of vital signs and close observation of the patient, is indicated.

A male child (age unknown) accidentally ingested a 25-mg tablet of exemestane. The initial physical examination was normal, but blood tests performed 1 hour after ingestion indicated leucocytosis (WBC 25000/mm3 with 90% neutrophils). Blood tests were repeated 4 days after the incident and were normal. No treatment was given.

In mice, mortality was observed after a single oral dose of exemestane of 3200 mg/kg, the lowest dose tested (about 640 times the recommended human dose on a mg/m2 basis). In rats and dogs, mortality was observed after single oral doses of exemestane of 5000 mg/kg (about 2000 times the recommended human dose on a mg/m2 basis) and of 3000 mg/kg (about 4000 times the recommended human dose on a mg/m2 basis), respectively.

Convulsions were observed after single doses of exemestane of 400 mg/kg and 3000 mg/kg in mice and dogs (approximately 80 and 4000 times the recommended human dose on a mg/m2 basis), respectively.

Aromasin - Clinical Pharmacology

Mechanism of Action

Breast cancer cell growth may be estrogen-dependent. Aromatase is the principal enzyme that converts androgens to estrogens both in pre- and postmenopausal women. While the main source of estrogen (primarily estradiol) is the ovary in premenopausal women, the principal source of circulating estrogens in postmenopausal women is from conversion of adrenal and ovarian androgens (androstenedione and testosterone) to estrogens (estrone and estradiol) by the aromatase enzyme in peripheral tissues.

Exemestane is an irreversible, steroidal aromatase inactivator, structurally related to the natural substrate androstenedione. It acts as a false substrate for the aromatase enzyme, and is processed to an intermediate that binds irreversibly to the active site of the enzyme, causing its inactivation, an effect also known as "suicide inhibition." Exemestane significantly lowers circulating estrogen concentrations in postmenopausal women, but has no detectable effect on adrenal biosynthesis of corticosteroids or aldosterone. Exemestane has no effect on other enzymes involved in the steroidogenic pathway up to a concentration at least 600 times higher than that inhibiting the aromatase enzyme.

Pharmacodynamics

Effect on Estrogens: Multiple doses of exemestane ranging from 0.5 to 600 mg/day were administered to postmenopausal women with advanced breast cancer. Plasma estrogen (estradiol, estrone, and estrone sulfate) suppression was seen starting at a 5-mg daily dose of exemestane, with a maximum suppression of at least 85% to 95% achieved at a 25-mg dose. Exemestane 25 mg daily reduced whole body aromatization (as measured by injecting radiolabeled androstenedione) by 98% in postmenopausal women with breast cancer. After a single dose of exemestane 25 mg, the maximal suppression of circulating estrogens occurred 2 to 3 days after dosing and persisted for 4 to 5 days.

Effect on Corticosteroids: In multiple-dose trials of doses up to 200 mg daily, exemestane selectivity was assessed by examining its effect on adrenal steroids. Exemestane did not affect cortisol or aldosterone secretion at baseline or in response to ACTH at any dose. Thus, no glucocorticoid or mineralocorticoid replacement therapy is necessary with exemestane treatment.

Other Endocrine Effects: Exemestane does not bind significantly to steroidal receptors, except for a slight affinity for the androgen receptor (0.28% relative to dihydrotestosterone). The binding affinity of its 17-dihydrometabolite for the androgen receptor, however, is 100 times that of the parent compound. Daily doses of exemestane up to 25 mg had no significant effect on circulating levels of androstenedione, dehydroepiandrosterone sulfate, or 17-hydroxyprogesterone, and were associated with small decreases in circulating levels of testosterone. Increases in testosterone and androstenedione levels have been observed at daily doses of 200 mg or more. A dose-dependent decrease in sex hormone binding globulin (SHBG) has been observed with daily exemestane doses of 2.5 mg or higher. Slight, nondose-dependent increases in serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels have been observed even at low doses as a consequence of feedback at the pituitary level. Exemestane 25 mg daily had no significant effect on thyroid function [free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH)].

Coagulation and Lipid Effects: In study 027 of postmenopausal women with early breast cancer treated with exemestane (N=73) or placebo (N=73), there was no change in the coagulation parameters activated partial thromboplastin time [APTT], prothrombin time [PT], and fibrinogen. Plasma HDL cholesterol was decreased 6–9% in exemestane treated patients; total cholesterol, LDL cholesterol, triglycerides, apolipoprotein-A1, apolipoprotein-B, and lipoprotein-a were unchanged. An 18% increase in homocysteine levels was also observed in exemestane treated patients compared with a 12% increase seen with placebo.

Pharmacokinetics

Following oral administration to healthy postmenopausal women, plasma concentrations of exemestane decline polyexponentially with a mean terminal half-life of about 24 hours. The pharmacokinetics of exemestane are dose proportional after single (10 to 200 mg) or repeated oral doses (0.5 to 50 mg). Following repeated daily doses of exemestane 25 mg, plasma concentrations of unchanged drug are similar to levels measured after a single dose. Pharmacokinetic parameters in postmenopausal women with advanced breast cancer following single or repeated doses have been compared with those in healthy, postmenopausal women. After repeated dosing, the average oral clearance in women with advanced breast cancer was 45% lower than the oral clearance in healthy postmenopausal women, with corresponding higher systemic exposure. Mean AUC values following repeated doses in women with breast cancer (75.4 ng∙h/mL) were about twice those in healthy women (41.4 ng∙h/mL).

Absorption: Following oral administration, exemestane appeared to be absorbed more rapidly in women with breast cancer than in the healthy women, with a mean -tmax of 1.2 hours in the women with breast cancer and 2.9 hours in healthy women. Approximately 42% of radiolabeled exemestane was absorbed from the gastrointestinal tract. A high-fat breakfast increased AUC and Cmax of exemestane by 59% and 39%, respectively, compared to fasted state.

Distribution: Exemestane is distributed extensively into tissues. Exemestane is 90% bound to plasma proteins and the fraction bound is independent of the total concentration. Albumin and α11-acid glycoprotein both contribute to the binding. The distribution of exemestane and its metabolites into blood cells is negligible.

Metabolism: Exemestane is extensively metabolized, with levels of the unchanged drug in plasma accounting for less than 10% of the total radioactivity. The initial steps in the metabolism of exemestane are oxidation of the methylene group in position 6 and reduction of the 17-keto group with subsequent formation of many secondary metabolites. Each metabolite accounts only for a limited amount of drug-related material. The metabolites are inactive or inhibit aromatase with decreased potency compared with the parent drug. One metabolite may have androgenic activity [see Clinical Pharmacology (12.2)]. Studies using human liver preparations indicate that cytochrome P 450 3A4 (CYP 3A4) is the principal isoenzyme involved in the oxidation of exemestane. Exemestane is metabolized also by aldoketoreductases.

Elimination: Following administration of radiolabeled exemestane to healthy postmenopausal women, the cumulative amounts of radioactivity excreted in urine and feces were similar (42 ± 3% in urine and 42 ± 6% in feces over a 1-week collection period). The amount of drug excreted unchanged in urine was less than 1% of the dose.

Specific Populations

Geriatric: Healthy postmenopausal women aged 43 to 68 years were studied in the pharmacokinetic trials. Age-related alterations in exemestane pharmacokinetics were not seen over this age range.

Gender: The pharmacokinetics of exemestane following administration of a single, 25-mg tablet to fasted healthy males (mean age 32 years) were similar to the pharmacokinetics of exemestane in fasted healthy postmenopausal women (mean age 55 years).

Race: The influence of race on exemestane pharmacokinetics has not been evaluated.

Hepatic Impairment: The pharmacokinetics of exemestane have been investigated in subjects with moderate or severe hepatic impairment (Childs-Pugh B or C). Following a single 25-mg oral dose, the AUC of exemestane was approximately 3 times higher than that observed in healthy volunteers.

Renal Impairment: The AUC of exemestane after a single 25-mg dose was approximately 3 times higher in subjects with moderate or severe renal insufficiency (creatinine clearance <35 mL/min/1.73 m2) compared with the AUC in healthy volunteers.

Pediatric: The pharmacokinetics of exemestane have not been studied in pediatric patients.

Drug Interactions

Exemestane does not inhibit any of the major CYP isoenzymes, including CYP 1A2, 2C9, 2D6, 2E1, and 3A4.

In a pharmacokinetic interaction study of 10 healthy postmenopausal volunteers pretreated with potent CYP 3A4 inducer rifampicin 600 mg daily for 14 days followed by a single dose of exemestane 25 mg, the mean plasma Cmax and AUC 0–∞ of exemestane were decreased by 41% and 54%, respectively [see Dosage and Administration (2.2) and Drug Interactions (7)].

In a clinical pharmacokinetic study, coadministration of ketoconazole, a potent inhibitor of CYP 3A4, has no significant effect on exemestane pharmacokinetics. Although no other formal drug-drug interaction studies with inhibitors have been conducted, significant effects on exemestane clearance by CYP isoenzyme inhibitors appear unlikely.

What is exemestane (aromasin)?

Exemestane lowers estrogen levels in postmenopausal women, which may slow the growth of certain types of breast tumors that need estrogen to grow in the body.

Exemestane is used to treat breast cancer in postmenopausal women. It is often given to women whose cancer has progressed even after taking tamoxifen (Nolvadex, Soltamox) for 2 to 3 years.

Exemestane may also be used for purposes not listed in this medication guide.

Side effects

In the adjuvant treatment of early breast cancer, the most common adverse reactions occurring in ≥10% of patients in any treatment group (AROMASIN vs. tamoxifen) were mild to moderate hot flushes (21.2% vs. 19.9%), fatigue (16.1% vs. 14.7%), arthralgia (14.6% vs. 8.6%), headache (13.1% vs. 10.8%), insomnia (12.4% vs. 8.9%), and increased sweating (11.8% vs. 10.4%). Discontinuation rates due to AEs were similar between AROMASIN and tamoxifen (6.3% vs. 5.1%). Incidences of cardiac ischemic events (myocardial infarction, angina, and myocardial ischemia) were AROMASIN 1.6%, tamoxifen 0.6%. Incidence of cardiac failure: AROMASIN 0.4%, tamoxifen 0.3%.

In the treatment of advanced breast cancer, the most common adverse reactions were mild to moderate and included hot flushes (13% vs. 5%), nausea (9% vs. 5%), fatigue (8% vs. 10%), increased sweating (4% vs. 8%), and increased appetite (3% vs. 6%) for AROMASIN and megestrol acetate, respectively.

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Adjuvant Therapy

The data described below reflect exposure to AROMASIN in 2325 postmenopausal women with early breast cancer. AROMASIN tolerability in postmenopausal women with early breast cancer was evaluated in two well-controlled trials: the IES study and the 027 study (a randomized, placebo-controlled, double-blind, parallel group study specifically designed to assess the effects of exemestane on bone metabolism, hormones, lipids, and coagulation factors over 2 years of treatment).

The median duration of adjuvant treatment was 27.4 months and 27.3 months for patients receiving AROMASIN or tamoxifen, respectively, within the IES study and 23.9 months for patients receiving AROMASIN or placebo within the 027 study. Median duration of observation after randomization for AROMASIN was 34.5 months and for tamoxifen was 34.6 months. Median duration of observation was 30 months for both groups in the 027 study.

Certain adverse reactions, which were expected based on the known pharmacological properties and side effect profiles of test drugs, were actively sought through a positive checklist. Signs and symptoms were graded for severity using CTC in both studies. Within the IES study, the presence of some illnesses/conditions was monitored through a positive checklist without assessment of severity. These included myocardial infarction, other cardiovascular disorders, gynecological disorders, osteoporosis, osteoporotic fractures, other primary cancer, and hospitalizations.

Within the IES study, discontinuations due to adverse reactions occurred in 6.3% and 5.1% of patients receiving AROMASIN and tamoxifen, respectively, and in 12.3% and 4.1% of patients receiving exemestane or placebo respectively within study 027.

Deaths due to any cause were reported for 1.3% of the exemestane treated patients and 1.4% of the tamoxifen treated patients within the IES study. There were 6 deaths due to stroke on the exemestane arm compared to 2 on tamoxifen. There were 5 deaths due to cardiac failure on the exemestane arm compared to 2 on tamoxifen.

The incidence of cardiac ischemic events (myocardial infarction, angina, and myocardial ischemia) was 1.6% in exemestane treated patients and 0.6% in tamoxifen treated patients in the IES study. Cardiac failure was observed in 0.4% of exemestane treated patients and 0.3% of tamoxifen treated patients.

Treatment-emergent adverse reactions and illnesses including all causalities and occurring with an incidence of ≥5% in either treatment group of the IES study during or within one month of the end of treatment are shown in Table 2.

Table 2. Incidence (%) of Adverse Reactions of all Grades1 and Illnesses Occurring in (≥5%) of Patients in Any Treatment Group in Study IES in Postmenopausal Women with Early Breast Cancer

Body system and Adverse Reaction by MedDRA dictionary % of patients
AROMASIN 25 mg daily (N=2252) Tamoxifen 20 mg daily2 (N=2280)
Eye
  Visual disturbances3 5.0 3.8
Gastrointestinal
  Nausea3 8.5 8.7
General Disorders
  Fatigue3 16.1 14.7
Musculoskeletal
  Arthralgia 14.6 8.6
  Pain in limb 9.0 6.4
  Back pain 8.6 7.2
  Osteoarthritis 5.9 4.5
Nervous System
  Headache3 13.1 10.8
  Dizziness3 9.7 8.4
Psychiatric
  Insomnia3 12.4 8.9
  Depression 6.2 5.6
Skin & Subcutaneous Tissue
  Increased sweating3 11.8 10.4
Vascular
  Hot flushes3 21.2 19.9
  Hypertension 9.8 8.4
1 Graded according to Common Toxicity Criteria;
2 75 patients received tamoxifen 30 mg daily;
3 Event actively sought.

In the IES study, as compared to tamoxifen, AROMASIN was associated with a higher incidence of events in musculoskeletal disorders and in nervous system disorders, including the following events occurring with frequency lower than 5% (osteoporosis [4.6% vs. 2.8%], osteochondrosis and trigger finger [0.3% vs. 0 for both events], paresthesia [2.6% vs. 0.9%], carpal tunnel syndrome [2.4% vs. 0.2%], and neuropathy [0.6% vs. 0.1%]). Diarrhea was also more frequent in the exemestane group (4.2% vs. 2.2%). Clinical fractures were reported in 94 patients receiving exemestane (4.2%) and 71 patients receiving tamoxifen (3.1%). After a median duration of therapy of about 30 months and a median follow-up of about 52 months, gastric ulcer was observed at a slightly higher frequency in the AROMASIN group compared to tamoxifen (0.7% vs. <0.1%). The majority of patients on AROMASIN with gastric ulcer received concomitant treatment with non-steroidal anti-inflammatory agents and/or had a prior history.

Tamoxifen was associated with a higher incidence of muscle cramps [3.1% vs. 1.5%], thromboembolism [2.0% vs. 0.9%], endometrial hyperplasia [1.7% vs. 0.6%], and uterine polyps [2.4% vs. 0.4%].

Common adverse reactions occurring in study 027 are described in Table 3.

Table 3. Incidence of Selected Treatment-Emergent Adverse Reactions of all CTC Grades* Occurring in ≥ 5% of Patients in Either Arm in Study 027

Adverse Reaction Exemestane
N=73
(% incidence)
Placebo
N=73
(% incidence)
Hot flushes 32.9 24.7
Arthralgia 28.8 28.8
Increased sweating 17.8 20.6
Alopecia 15.1 4.1
Hypertension 15.1 6.9
Insomnia 13.7 15.1
Nausea 12.3 16.4
Fatigue 11.0 19.2
Abdominal pain 11.0 13.7
Depression 9.6 6.9
Diarrhea 9.6 1.4
Dizziness 9.6 9.6
Dermatitis 8.2 1.4
Headache 6.9 4.1
Myalgia 5.5 4.1
Edema 5.5 6.9
* Most events were CTC grade 1–2

Treatment Of Advanced Breast Cancer

A total of 1058 patients were treated with exemestane 25 mg once daily in the clinical trials program. Only one death was considered possibly related to treatment with exemestane; an 80-year-old woman with known coronary artery disease had a myocardial infarction with multiple organ failure after 9 weeks on study treatment. In the clinical trials program, only 3% of the patients discontinued treatment with exemestane because of adverse reactions, mainly within the first 10 weeks of treatment; late discontinuations because of adverse reactions were uncommon (0.3%).

In the comparative study, adverse reactions were assessed for 358 patients treated with AROMASIN and 400 patients treated with megestrol acetate. Fewer patients receiving AROMASIN discontinued treatment because of adverse reactions than those treated with megestrol acetate (2% vs. 5%). Adverse reactions that were considered drug related or of indeterminate cause included hot flashes (13% vs. 5%), nausea (9% vs. 5%), fatigue (8% vs. 10%), increased sweating (4% vs. 8%), and increased appetite (3% vs. 6%) for AROMASIN and megestrol acetate, respectively. The proportion of patients experiencing an excessive weight gain (>10% of their baseline weight) was significantly higher with megestrol acetate than with AROMASIN (17% vs. 8%). Table 4 shows the adverse reactions of all CTC grades, regardless of causality, reported in 5% or greater of patients in the study treated either with AROMASIN or megestrol acetate.

Table 4. Incidence (%) of Adverse Reactions of all Grades* and Causes Occurring in ≥5% of Advanced Breast Cancer Patients In Each Treatment Arm in the Comparative Study

Body system and Adverse Reaction by WHO ART dictionary AROMASIN
25 mg
once daily (N=358)
Megestrol Acetate
40 mg QID
(N=400)
Autonomic Nervous
  Increased sweating 6 9
Body as a Whole
  Fatigue 22 29
  Hot flashes 13 6
  Pain 13 13
  Influenza-like symptoms 6 5
  Edema (includes edema, peripheral edema, leg edema) 7 6
Cardiovascular
  Hypertension 5 6
Nervous
  Depression 13 9
  Insomnia 11 9
  Anxiety 10 11
  Dizziness 8 6
  Headache 8 7
Gastrointestinal
  Nausea 18 12
  Vomiting 7 4
  Abdominal pain 6 11
  Anorexia 6 5
  Constipation 5 8
  Diarrhea 4 5
  Increased appetite 3 6
Respiratory
  Dyspnea 10 15
  Coughing 6 7
* Graded according to Common Toxicity Criteria

Less frequent adverse reactions of any cause (from 2% to 5%) reported in the comparative study for patients receiving AROMASIN 25 mg once daily were fever, generalized weakness, paresthesia, pathological fracture, bronchitis, sinusitis, rash, itching, urinary tract infection, and lymphedema.

Additional adverse reactions of any cause observed in the overall clinical trials program (N = 1058) in 5% or greater of patients treated with exemestane 25 mg once daily but not in the comparative study included pain at tumor sites (8%), asthenia (6%), and fever (5%). Adverse reactions of any cause reported in 2% to 5% of all patients treated with exemestane 25 mg in the overall clinical trials program but not in the comparative study included chest pain, hypoesthesia, confusion, dyspepsia, arthralgia, back pain, skeletal pain, infection, upper respiratory tract infection, pharyngitis, rhinitis, and alopecia.

Post-Marketing Experience

The following adverse reactions have been identified during post approval use of AROMASIN. Because reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune system disorders - hypersensitivity

Hepatobiliary disorders - hepatitis including cholestatic hepatitis

Nervous system disorders - paresthesia

Skin and subcutaneous tissue disorders - acute generalized exanthematous pustulosis, urticaria, pruritus

Read the entire FDA prescribing information for Aromasin (Exemestane)

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Before taking this medicine

You should not use Aromasin if you are allergic to exemestane, or:

  • if you are pregnant or able to become pregnant; or

  • if you have not yet completed menopause, and are still having menstrual periods.

To make sure Aromasin is safe for you, tell your doctor if you have:

  • liver disease; or

  • kidney disease.

Aromasin can decrease bone mineral density, which may increase your risk of developing osteoporosis. Talk to your doctor about your individual risk of bone loss.

Although it is not likely that a postmenopausal woman would be pregnant, exemestane can cause birth defects. Do not take this medicine if you are pregnant or may become pregnant. You may need to have a negative pregnancy test before starting this treatment.

If you are not past menopause, use effective birth control to prevent pregnancy while you are taking Aromasin and for at least 1 month after your last dose. Tell your doctor right away if you become pregnant while taking Aromasin.

It is not known whether exemestane passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

How should I take Aromasin?

Take Aromasin exactly as prescribed by your doctor. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Aromasin is usually taken once per day, after a meal. Try to take the medicine at the same time each day.

Use this medicine regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely. You may need to keep taking take this medication for up to 5 years.

While using Aromasin, you may need frequent blood tests.

Store in the original container at room temperature away from moisture and heat.

What should I avoid?

Exemestane can pass into body fluids (including urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash ands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

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