اگزمستان
Exemestane (Aromasin)
اگزمستان

نام ژنریک

Exemestane

شکل دارویی

اشكال دارويي:


Tablet: 25 mg

موارد مصرف

موارد و مقدار مصرف


الف) سرطان سينه پيشرفته در خانمهاي يائسه‌اي كه بيماري آنها بعداز درمان با تاموكسي‌فن پيشرفت كرده است.


بزرگسالان: 25 ميلي‌گرم خوراكي روزانه بعداز غذا مصرف شود.


ب) درمان كمكي مراحل اوليه سرطان سينه استروژن مثبت، 3-2 سال بعداز درمان با تاموكسي‌فن، جهت تكميل دوره 5 ساله درمان كمكي هورمونال


بزرگسالان: 25 ميلي‌گرم خوراكي روزانه بعداز غذا مصرف شود.


تنظيم دوز: در كساني كه داروهاي قوي القاء كنندة آنزيم CYP3A4 مانند فني‌توئين يا ريفامپين، دريافت مي‌كنند. دوز دارو به 50 ميلي‌گرم روزانه افزايش يابد.

موارد منع مصرف

موارد منع مصرف و احتياط


موارد منع مصرف: حساسيت به دارو يا ديگر تركيبات فرمولاسيون؛ حاملگي.


موارد احتياط: دارو نبايد همراه با داروهاي حاوي استروژن استفاده شود. استفاده در دوران قبل از يائسگي هم توصيه نمي‌شود.

عوارض جانبی دارو

عوارض جانبي


اعصاب مرکزي: اضطراب، ضعف، كانفيوژن، افسردگي، گيجي، خستگي، تب، ضعف عمومي، سردرد، هايپواستزي، بي‌خوابي، درد، پاراستزي.


قلبي- عروقي: درد قفسه سينه، ادم، افزايش فشار خون.


چشم، گوش، حلق و بيني: فارنژيت، رينيت، سينوزيت.


دستگاه گوارش: دردهاي شكمي، بي‌اشتهايي، يبوست، اسهال، سوء‌هاضمه، افزايش اشتها، تهوع، استفراغ.


عضلاني ـ اسكلتي: آرترالژي، آرتريت، درد پشت، شكستگي‌‌هاي پاتولوژيك، دردهاي اسكلتي.


تنفسي: برونشيت، سرفه، تنگي نفس، عفونت فوقاني تنفس.


پوست: آلوپسي، افزايش تعريق، خارش، راش، درماتيت.


ساير عوارض: سندرم شبه آنفلونزا، فلاشينگ، عفونت، لنفادم، UTI.


مسموميت و درمان


هيچ آنتي‌دوت اختصاصي ندارد. درمان حمايتي و شامل مانيتورينگ دقيق علائم حياتي و بيمار است.

موارد قابل توجه

-

تداخل دارویی

تداخل دارويي


مصرف همزمان با القاء‌كننده‌هاي CYP3A4 (مثل كاربامازپين، فنوباربيتال، فني‌توئين، ريفامپين) باعث كاهش اثر درماني اين دارو مي‌شود. دوز دارو را به 50 ميلي‌گرم در روز افزايش دهيد.


داروهاي حاوي استروژن، اگزمستان را غيرفعال مي‌كنند. همزمان با هم استفاده نشوند.

مکانیزم اثر

تداخل دارويي


مصرف همزمان با القاء‌كننده‌هاي CYP3A4 (مثل كاربامازپين، فنوباربيتال، فني‌توئين، ريفامپين) باعث كاهش اثر درماني اين دارو مي‌شود. دوز دارو را به 50 ميلي‌گرم در روز افزايش دهيد.


داروهاي حاوي استروژن، اگزمستان را غيرفعال مي‌كنند. همزمان با هم استفاده نشوند.

فارماكوكینتیك

فارماكوكينتيك


جذب: جذب سريعي دارد، حدود 42% دارو بعداز مصرف خوراكي جذب مي‌شود.


پخش: توزيع وسيعي در بافتهاي بدن دارد. 90% به پروتئينهاي پلاسما متصل مي‌شود. مدت اثر دارو 24 ساعت دارد.


متابوليسم: به‌طور وسيعي در كبد توسط آنزيم CYP3A4 متابوليزه مي‌شود.


دفع: به طور مساوي در ادرار و مدفوع دفع مي‌شود. كمتر از 1% دارو
به صورت تغيير نيافته در ادرار دفع مي‌شود. نيمه‌ عمر دفع دارو، حدود 24 ساعت است.

سایر اطلاعات

طبقه‌بندي فارماكولوژيك: غيرفعال كننده آروماتاز.


طبقه‌بندي درماني: ضد نئوپلاسم.


طبقه‌بندي مصرف در بارداري: رده D


نام‌هاي تجاري: Aromasin


ملاحظات اختصاصي


1- دارو تنها در خانمهاي يائسه استفاده شود.


2- بيماران با سرطان سينه پيشرفته بهتر است دارو را ادامه دهند. مگر اينكه بيماري آنها پيشرفت كند.


3- بيماران در مراحل اوليه سرطان سينه كه تاموكسي‌فن را براي 2 تا 3 سال دريافت كرده‌اند. بهتر است جهت تكميل دوره 5 ساله اگزمستان را دريافت كنند. مگر اينكه سرطان عود كند يا در سينه مقابل ظاهر شود.


4- عملكرد كبد و كليه را قبل از شروع درمان و سپس به صورت دوره‌اي چك كنيد.


5- CBC را به طور دوره‌اي بررسي كنيد.


نكات قابل توصيه به بيمار


1- بهتر است دارو را بعد از غذا مصرف شود.


2- ممكن است جهت كنترل بيمار، مصرف طولاني مدت اين دارو لازم باشد.


3- هرگونه عارضه جانبي را گزارش كنيد.


مصرف در كودكان: ايمني و اثربخشي دارو در كودكان اثبات نشده است.


مصرف در شيردهي: به دليل اينكه دارو در شير ترشح مي‌شود، از مصرف دارو در اين دوران خودداري شود.


اثر بر آزمايشهاي تشخيصي


دارو باعث افزايش سطح بيلي‌روبين، آلكالين فسفاتاز و كراتينين مي‌شود.

Exemestane (Aromasin)

AROMASIN®
(exemestane)

DRUG DESCRIPTION

AROMASIN (exemestane) ® Tablets for oral administration contain 25 mg of exemestane, an irreversible, steroidal aromatase inactivator. Exemestane is chemically described as 6-methylenandrosta-1,4-diene-3,17-dione. Its molecular formula is C20H24O2 and its structural formula is as follows:

AROMASIN® (exemestane) Structural Formula Illustration

The active ingredient is a white to slightly yellow crystalline powder with a molecular weight of 296.41. Exemestane is freely soluble in N, N-dimethylformamide, soluble in methanol, and practically insoluble in water.

Each AROMASIN (exemestane) Tablet contains the following inactive ingredients: mannitol, crospovidone, polysorbate 80, hypromellose, colloidal silicon dioxide, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, simethicone, polyethylene glycol 6000, sucrose, magnesium carbonate, titanium dioxide, methylparaben, and polyvinyl alcohol.

What are the possible side effects of exemestane (Aromasin)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • new or unusual bone pain;
  • vision problems;
  • swelling in your hands or feet;
  • feeling short of breath, even with mild exertion; or
  • chest pain, sudden numbness or weakness, sudden headache, confusion, problems with vision, speech, or balance.

Less serious side effects may include:

  • hot...

Read All Potential Side Effects and See Pictures of Aromasin »

What are the precautions when taking exemestane (Aromasin)?

Before taking exemestane, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: high blood fats (cholesterol), bone problems (such as osteopenia, osteoporosis), stroke or blood clots, heart disease (such as chest pain, heart attack, heart failure), high blood pressure, kidney problems, liver problems.

This drug may make you dizzy and tired. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic...

Read All Potential Precautions of Aromasin »

Last reviewed on RxList: 5/11/2011
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Adjuvant Treatment of Postmenopausal Women

AROMASIN (exemestane) is indicated for 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 (exemestane) for completion of a total of five consecutive years of adjuvant hormonal therapy.

Advanced Breast Cancer in Postmenopausal Women

AROMASIN (exemestane) is indicated for the treatment of advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.

DOSAGE AND ADMINISTRATION

Recommended Dose

The recommended dose of AROMASIN (exemestane) 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 (exemestane) 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

For patients receiving AROMASIN (exemestane) with a potent CYP 3A4 inducer such as rifampicin or phenytoin, the recommended dose of AROMASIN (exemestane) is 50 mg once daily after a meal.

The safety of chronic dosing in patients with moderate or severe hepatic or renal impairment has not been studied. Based on experience with exemestane at repeated doses up to 200 mg daily that demonstrated a moderate increase in non life-threatening adverse events, dosage adjustment does not appear to be necessary [see Use In Specific Populations].

HOW SUPPLIED

Dosage Forms And Strengths

AROMASIN (exemestane) 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.

Storage And Handling

AROMASIN (exemestane) 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.

AROMASIN (exemestane) is packaged in HDPE bottles with a child-resistant screw cap, supplied in packs of 30 tablets.

30-tablet HDPE bottle NDC 0009-7663-04

Store at 25°C (77°F); excursion s permitted to 15°–30°C (59°–86°F) [see USP Controlled Room Temperature].

Distributed by : Pharmacia & Upjohn Company, Division of Pfizer Inc, NY, NY 10017. Revised: 03/2011

Last reviewed on RxList: 5/11/2011
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

AROMASIN (exemestane) was generally well tolerated and adverse events were usually mild to moderate.

In the adjuvant treatment of early breast cancer, adverse events occurring in ≥ 10% of patients in any treatment group (AROMASIN (exemestane) vs tamoxifen) were 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 (exemestane) and tamoxifen (6.3% vs 5.1%). Incidence of cardiac ischemic events (myocardial infarction, angina, and myocardial ischemia) were AROMASIN (exemestane) 1.6%, tamoxifen 0.6%. Incidence of cardiac failure: AROMASIN (exemestane) 0.4%, tamoxifen 0.3%.

In the treatment of advanced breast cancer, the most common adverse events 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 (exemestane) and megestrol acetate, respectively.

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 practice.

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 nd may not reflect the rates observed in clinical practice.

Adjuvant Therapy

The data described below reflect exposure to AROMASIN (exemestane) in 2325 postmenopausal women with early breast cancer. AROMASIN (exemestane) tolerability in postmenopausal women with early breast cancer was evaluated in two well-controlled trials: the IES study (14.1) 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 (exemestane) or tamoxifen, respectively, within the IES study and 23.9 months for patients receiving AROMASIN (exemestane) or placebo within the 027 study. Median duration of observation after randomization for AROMASIN (exemestane) 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 events, 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.

AROMASIN (exemestane) was generally well tolerated and adverse events were usually mild to moderate. Within the IES study, discontinuations due to adverse events occurred in 6.3% and 5.1% of patients receiving AROMASIN (exemestane) 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 events 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 Events 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 Event 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 sweating 3 11.8 10.4
Vascular
  Hot flushes 3 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 (exemestane) 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 (exemestane) group compared to tamoxifen (0.7% vs. < 0.1%). The majority of patients on AROMASIN (exemestane) 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 events occurring in study 027 are described in Table 3.

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

Adverse Event 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
Anxiety 4.1 5.5
* 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 events, mainly within the first 10 weeks of treatment; late discontinuations because of adverse events were uncommon (0.3%).

In the comparative study, adverse reactions were assessed for 358 patients treated with AROMASIN (exemestane) and 400 patients treated with megestrol acetate. Fewer patients receiving AROMASIN (exemestane) discontinued treatment because of adverse events than those treated with megestrol acetate (2% vs. 5%). Adverse events 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 (exemestane) 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 (exemestane) (17% vs. 8%). Table 4 shows the adverse events of all CTC grades, regardless of causality, reported in 5% or greater of patients in the study treated either with AROMASIN (exemestane) or megestrol acetate.

Table 4: Incidence (%) of Adverse Events 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 Event 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 events of any cause (from 2% to 5%) reported in the comparative study for patients receiving AROMASIN (exemestane) 25 mg once daily were fever, generalized weakness, paresthesia, pathological fracture, bronchitis, sinusitis, rash, itching, urinary tract infection, and lymphedema.

Additional adverse events 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 events 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 (exemestane) . 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.

Cases of hepatitis including cholestatic hepatitis have been observed in clinical trials and reported through post-marketing surveillance.

Read the Aromasin (exemestane) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

Drugs That Induce CYP 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.

Significant pharmacokinetic interactions mediated by inhibition of CYP isoenzymes therefore appear unlikely. Comedications 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 potent CYP 3A4 inducer [see DOSAGE AND ADMINISTRATION].

Drugs That Inhibit CYP 3A4

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 have been conducted, significant effects on exemestane clearance by CYP isoenzyme inhibitors appear unlikely.

Last reviewed on RxList: 5/11/2011
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Administration with Estrogen-Containing Agents

AROMASIN (exemestane) should not be coadministered with estrogen-containing agents as these could interfere with its pharmacologic action.

Laboratory Tests

In patients with early breast cancer, the incidence of hematological abnormalities of Common Toxicity Criteria (CTC) grade ≥ 1 was lower in the exemestane treatment group, compared with tamoxifen. Incidence of CTC grade 3 or 4 abnormalities was low (approximately 0.1%) in both treatment groups. Approximately 20% of patients receiving exemestane in clinical studies in advanced breast cancer experienced CTC grade 3 or 4 lymphocytopenia. Of these patients, 89% had a pre-existing lower grade lymphopenia. Forty percent of patients either recovered or improved to a lesser severity while on treatment. Patients did not have a significant increase in viral infections, and no opportunistic infections were observed. Elevations of serum levels of AST, ALT, alkaline phosphatase, and gamma glutamyl transferase > 5 times the upper value of the normal range (i.e., ≥ CTC grade 3) have been rarely reported in patients treated for advanced breast cancer but appear mostly attributable to the underlying presence of liver and/or bone metastases. In the comparative study in advanced breast cancer patients, CTC grade 3 or 4 elevation of gamma glutamyl transferase without documented evidence of liver metastasis was reported in 2.7% of patients treated with AROMASIN (exemestane) and in 1.8% of patients treated with megestrol acetate.

In patients with early breast cancer, elevations in bilirubin, alkaline phosphatase, and creatinine were more common in those receiving exemestane than either tamoxifen or placebo. Treatment-emergent bilirubin elevations (any CTC grade) occurred in 5.3% of exemestane patients and 0.8% of tamoxifen patients on the Intergroup Exemestane Study (IES), and in 6.9% of exemestane treated patients vs. 0% of placebo treated patients in the 027 study. CTC grade 3–4 increases in bilirubin occurred in 0.9% of exemestane treated patients compared to 0.1% of tamoxifen treated patients. Alkaline phosphatase elevations of any CTC grade occurred in 15.0% of exemestane treated patients on the IES compared to 2.6% of tamoxifen treated patients, and in 13.7% of exemestane treated patients compared to 6.9% of placebo treated patients in study 027. Creatinine elevations occurred in 5.8% of exemestane treated patients and 4.3% of tamoxifen treated patients on the IES and in 5.5% of exemestane treated patients and 0% of placebo treated patients in study 027.

Reductions in Bone Mineral Density (BMD)

Reductions in bone mineral density (BMD) over time are seen with exemestane use. Table 1 describes changes in BMD from baseline to 24 months in patients receiving exemestane compared to patients receiving tamoxifen (IES) or placebo (027). Concomitant use of bisphosphonates, vitamin D supplementation, and calcium was not allowed.

Table 1: Percent Change in BMD from Baseline to 24 months, Exemestane vs. Control1

BMD IES 027
Exemestane N=29 Tamoxifen N=38 Exemestane N=59 Placebo N=65
Lumbar spine (%) -3.14 -0.18 -3.51 -2.35
Femoral neck (%) -4.15 -0.33 -4.57 -2.59

Patient Counseling Information

See FDA-Approved Patient Labeling

Premenopausal Women

Patients should be advised that AROMASIN (exemestane) is not for use in premenopausal women.

Other Estrogen-Containing Agents

Patients should be informed that they should not take estrogen-containing agents while they are taking AROMASIN (exemestane) as these could interfere with its pharmacologic action.

Bone Effects

Patients should be informed that AROMASIN (exemestane) lowers the level of estrogen in the body. This may lead to reduction in bone mineral density (BMD) over time. The lower the BMD, the greater the risk of osteoporosis and fracture.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

A 2-year carcinogenicity study in mice at doses of 50, 150, and 450 mg/kg/day exemestane (gavage), resulted in an increased incidence of hepatocellular adenomas and/or carcinomas in both genders at the high dose level. Plasma AUC (0–24hr) at the high dose were 2575 ± 386 and 5667 ± 1833 ng.hr/mL in males and females (approx. 34 and 75 fold the AUC in postmenopausal patients at the recommended clinical dose). An increased incidence of renal tubular adenomas was observed in male mice at the high dose of 450 mg/kg/day. Since the doses tested in mice did not achieve an MTD, neoplastic findings in organs other than liver and kidneys remain unknown.

A separate carcinogenicity study was conducted in rats at the doses of 30, 100, and 315 mg/kg/day exemestane (gavage) for 92 weeks in males and 2 years in females. No evidence of carcinogenic activity up to the highest dose tested of 315 mg/kg/day was observed in females. The male rat study was inconclusive since it was terminated prematurely at Week 92. At the highest dose, plasma AUC(0–24hr) levels in male (1418 ± 287 ng.hr/mL) and female (2318 ± 1067 ng.hr/mL) rats were 19 and 31 fold higher than those measured in postmenopausal cancer patients receiving the recommended clinical dose.

Exemestane was not mutagenic in vitro in bacteria (Ames test) or mammalian cells (V79 Chinese hamster lung cells). Exemestane was clastogenic in human lymphocytes in vitro without metabolic activation but was not clastogenic in vivo (micronucleus assay in mouse bone marrow). Exemestane did not increase unscheduled DNA synthesis in rat hepatocytes when tested in vitro .

In a pilot reproductive study in rats, male rats were treated with doses of 125–1000 mg/kg/day exemestane, beginning 63 days prior to and during cohabitation. Untreated female rats showed reduced fertility when mated to males treated with ≥ 500 mg/kg/day exemestane ( ≥ 200 times the recommended human dose on a mg/m² basis). In a separate study, exemestane was given to female rats at 4–100 mg/kg/day beginning 14 days prior to mating and through day 15 or 20 of gestation. Exemestane increased the placental weights at ≥ 4 mg/kg/day ( ≥ 1.5 times the human dose on a mg/m² basis). Exemestane showed no effects on ovarian function, mating behavior, and conception rate in rats given doses up to 20 mg/kg/day (approximately 8 times the recommended human dose on a mg/m² basis); however, decreases in mean litter size and fetal body weight, along with delayed ossification were evidenced at ≥ 20 mg/kg/day. In general toxicology studies, changes in the ovary, including hyperplasia, an increase in the incidence of ovarian cysts, and a decrease in corpora lutea were observed with variable frequency in mice, rats, and dogs at doses that ranged from 3–20 times the human dose on a mg/m² basis.

Use In Specific Populations

Pregnancy

Pregnancy Category X. See “CONTRAINDICATIONS” section.

AROMASIN (exemestane) can cause fetal harm when administered to a pregnant woman and the clinical benefit to premenopausal women with breast cancer has not been demonstrated. AROMASIN (exemestane) is contraindicated in women who are or may become pregnant. There are no adequate and well-controlled studies of AROMASIN (exemestane) in pregnant women.

In non-clinical studies in rats and rabbits, exemestane was embryotoxic, fetotoxic, and abortifacient. Radioactivity related to 14C-exemestane crossed the placenta of rats following oral administration of 1 mg/kg exemestane. The concentration of exemestane and its metabolites was approximately equivalent in maternal and fetal blood. When rats were administered exemestane from 14 days prior to mating until either days 15 or 20 of gestation, and resuming for the 21 days of lactation, an increase in placental weight was seen at 4 mg/kg/day (approximately 1.5 times the recommended human daily dose on a mg/m² basis). Prolonged gestation and abnormal or difficult labor was observed at doses equal to or greater than 20 mg/kg/day. Increased resorption, reduced number of live fetuses, decreased fetal weight, and retarded ossification were also observed at these doses. No malformations were noted when exemestane was administered to pregnant rats during the organogenesis period at doses up to 810 mg/kg/day (approximately 320 times the recommended human dose on a mg/m² basis). Daily doses of exemestane, given to rabbits during organogenesis, caused a decrease in placental weight at 90 mg/kg/day (approximately 70 times the recommended human daily dose on a mg/m² basis). Abortions, an increase in resorptions, and a reduction in fetal body weight were seen at 270 mg/kg/day. There was no increase in the incidence of malformations in rabbits at doses up to 270 mg/kg/day (approximately 210 times the recommended human dose on a mg/m² basis).

If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus and the potential risk for pregnancy loss.

Nursing Mothers

AROMASIN (exemestane) is only indicated in postmenopausal women. However, radioactivity related to exemestane appeared in rat milk within 15 minutes of oral administration of radiolabeled exemestane. Concentrations of exemestane and its metabolites were approximately equivalent in the milk and plasma of rats for 24 hours after a single oral dose of 1 mg/kg 14Cexemestane. It is not known whether exemestane is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reaction in nursing infants from AROMASIN (exemestane) , a decision should be made whether to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

The use of AROMASIN (exemestane) in geriatric patients does not require special precautions.

Hepatic Insufficiency

The pharmacokinetics of exemestane have been investigated in subjects with moderate or severe hepatic insufficiency (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.

The safety of chronic dosing in patients with moderate or severe hepatic impairment has not been studied. Based on experience with exemestane at repeated doses up to 200 mg daily that demonstrated a moderate increase in non life-threatening adverse events, dosage adjustment does not appear to be necessary.

Renal Insufficiency

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. The safety of chronic dosing in patients with moderate or severe renal impairment has not been studied. Based on experience with exemestane at repeated doses up to 200 mg daily that demonstrated a moderate increase in non life- threatening adverse events, dosage adjustment does not appear to be necessary.

Last reviewed on RxList: 5/11/2011
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

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.

CONTRAINDICATIONS

Hypersensitivity

AROMASIN (exemestane) Tablets are contraindicated in patients with a known hypersensitivity to the drug or to any of the excipients.

Pregnancy

AROMASIN (exemestane) can cause fetal harm when administered to a pregnant woman. Based on its mechanism of action AROMASIN (exemestane) is expected to result in adverse reproductive effects. In non-clinical studies in rats and rabbits, exemestane was embryotoxic, fetotoxic, and abortifacient.

AROMASIN (exemestane) is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.

AROMASIN (exemestane) Tablets should not be administered to premenopausal women [see Use in Specific Populations].

Last reviewed on RxList: 5/11/2011
This monograph has been modified to include the generic and brand name in many instances.

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. Estrogen deprivation through aromatase inhibition is an effective and selective treatment for some postmenopausal patients with hormone-dependent breast cancer.

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 25mg 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, exemestane is rapidly absorbed. After maximum plasma concentration is reached, levels decline polyexponentially with a mean terminal half-life of about 24 hours. Exemestane is extensively distributed and is cleared from the systemic circulation primarily by metabolism. 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. Exemestane appeared to be more rapidly absorbed in the 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 the healthy 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 of radiolabeled exemestane, at least 42% of radioactivity was absorbed from the gastrointestinal tract. Exemestane plasma levels increased by approximately 40% after a high-fat breakfast.

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/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. 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 17keto 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 Pharmacodynamics). 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 by cytochrome P 450 3A4 (CYP 3A4) and aldoketoreductases. It does not inhibit any of the major CYP isoenzymes, including CYP 1A2, 2C9, 2D6, 2E1, and 3A4.

Special 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 Insufficiency: The pharmacokinetics of exemestane have been investigated in subjects with moderate or severe hepatic insufficiency (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 Insufficiency: 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.

Clinical Studies

Adjuvant Treatment in Early Breast Cancer

The Intergroup Exemestane Study 031 (IES) was a randomized, double-blind, multicenter, multinational study comparing exemestane (25 mg/day) vs. tamoxifen (20 or 30 mg/day) in postmenopausal women with early breast cancer. Patients who remained disease-free after receiving adjuvant tamoxifen therapy for 2 to 3 years were randomized to receive an additional 3 or 2 years of AROMASIN (exemestane) or tamoxifen to complete a total of 5 years of hormonal therapy.

The primary objective of the study was to determine whether, in terms of disease-free survival, it was more effective to switch to AROMASIN (exemestane) rather than continuing tamoxifen therapy for the remainder of five years. Disease-free survival was defined as the time from randomization to time of local or distant recurrence of breast cancer, contralateral invasive breast cancer, or death from any cause.

The secondary objectives were to compare the two regimens in terms of overall survival and long-term tolerability. Time to contralateral invasive breast cancer and distant recurrence-free survival were also evaluated.

A total of 4724 patients in the intent-to-treat (ITT) analysis were randomized to AROMASIN (exemestane tablets) 25 mg once daily (N = 2352) or to continue to receive tamoxifen once daily at the same dose received before randomization (N = 2372). Demographics and baseline tumor characteristics are presented in Table 5. Prior breast cancer therapy is summarized in Table 6.

Table 5: Demographic and Baseline Tumor Characteristics from the IES Study of Postmenopausal Women with Early Breast Cancer (ITT Population)

Parameter Exemestane
(N =2352)
Tamoxifen
(N =2372)
Age (years):
Median age (range) 63.0 (38.0– 96.0) 63.0 (31.0– 90.0)
Race, n (%):
Caucasian 2315 (98.4) 2333 (98.4)
Hispanic 13 (0.6) 13(0.5)
Asian 10(0.4) 9 (0.4)
Black 7 (0.3) 10 (0.4)
Other/not reported 7 (0.3) 7 (0.3)
Nodal status, n (%):
Negative 1217 (51.7) 1228 (51.8)
Positive 1051 (44.7) 1044 (44.0)
  1–3 Positive nodes 721 (30.7) 708 (29.8)
  4–9 Positive nodes 239(10.2) 244 (10.3)
   > 9 Positive nodes 88 (3.7) 86(3.6)
  Not reported 3 (0.1) 6 (0.3)
Unknown or missing 84 (3.6) 100 (4.2)
Histologic type, n (%):
Infiltrating ductal 1777 (75.6) 1830 (77.2)
Infiltrating lobular 341 (14.5) 321 (13.5)
Other 231 (9.8) 213 (9.0)
Unknown or missing 3 (0.1) 8 (0.3)
Receptor status*, n (%):
ER and PgR Positive 1331 (56.6) 1319 (55.6)
ER Positive and PgR Negative/Unknown 677 (28.8) 692 (29.2)
ER Unknown and PgR Positive**/Unknown 288 (12.2) 291 (12.3)
ER Negative and PgR Positive 6 (0.3) 7 (0.3)
ER Negative and PgR Negative/Unknown (none positive) 48 (2.0) 58 (2.4)
Missing 2 (0.1) 5 (0.2)
Tumor Size, n (%):
≤ 0.5 cm 58 (2.5) 46 (1.9)
> 0.5 – 1.0 cm 315 (13.4) 302 (12.7)
> 1.0 – 2 cm 1031 (43.8) 1033 (43.5)
> 2.0 – 5.0 cm 833 (35.4) 883 (37.2)
> 5.0 cm 62 (2.6) 59 (2.5)
Not reported 53 (2.3) 49 (2.1)
Tumor Grade, n (%):
G1 397 (16.9) 393 (16.6)
G2 977 (41.5) 1007 (42.5)
G3 454 (19.3) 428 (18.0)
G4 23 (1.0) 19 (0.8)
Unknown/Not Assessed/Not reported 501 (21.3) 525 (22.1)
* Results for receptor status include the results of the post-randomization testing of specimens from subjects for whom receptor status was unknown at randomization.
**Only one subject in the exemestane group had unknown ER status and positive PgR status.

Table 6: Prior Breast Cancer Therapy of Patients in the IES Study of Postmenopausal Women with Early Breast Cancer (ITT Population)

Parameter Exemestane
(N=2352)
Tamoxifen
(N =2372)
Type of surgery, n (%):
Mastectomy 1232 (52.4) 1242 (52.4)
Breast-conserving 1116 (47.4) 1123 (47.3)
Unknown or missing 4 (0.2) 7 (0.3)
Radiotherapy to the breast, n (%):
Yes 1524 (64.8) 1523 (64.2)
No 824 (35.5) 843 (35.5)
Not reported 4 (0.2) 6 (0.3)
Prior therapy, n (%):
Chemotherapy 774 (32.9) 769 (32.4)
Hormone replacement therapy 567(24.1) 561 (23.7)
Bisphosphonates 43 (1.8) 34(1.4)
Duration of tamoxifen therapy at randomization (months):
Median (range) 28.5 (15.8– 52.2) 28.4 (15.6– 63.0)
Tamoxifen dose, n (%):
20 mg 2270 (96.5) 2287 (96.4)
30 mg* 78 (3.3) 75 (3.2)
Not reported 4 (0.2) 10 (0.4)
*The 30 mg dose was used only in Denmark, where this dose was the standard of care.

After a median duration of therapy of 27 months and with a median follow-up of 34.5 months, 520 events were reported, 213 in the AROMASIN (exemestane) group and 307 in the tamoxifen group (Table 7).

Table 7: Primary Endpoint Events (ITT Population)

Event First Events N (%)
Exemestane (N= 2352) Tamoxifen (N= 2372)
Loco-regional recurrence 34 (1.45) 45 (1.90)
Distant recurrence 126 (5.36) 183(7.72)
Second primary –contralateral breast cancer 7 (0.30) 25 (1.05)
Death – breast cancer 1(0.04) 6 (0.25)
Death – other reason 41 (1.74) 43 (1.81)
Death – missing/unknown 3 (0.13) 5 (0.21)
Ipsilateral breast cancer 1 (0.04) 0
Total number of events 213 (9.06) 307 (12.94)

Disease-free survival in the intent-to-treat population was statistically significantly improved [Hazard Ratio (HR) = 0.69, 95% CI: 0.58, 0.82, P = 0.00003, Table 8, Figure 1] in the AROMASIN (exemestane) arm compared to the tamoxifen arm. In the hormone receptor-positive subpopulation representing about 85% of the trial patients, disease-free survival was also statistically significantly improved (HR = 0.65, 95% CI: 0.53, 0.79, P = 0.00001) in the AROMASIN (exemestane) arm compared to the tamoxifen arm. Consistent results were observed in the subgroups of patients with node negative or positive disease, and patients who had or had not received prior chemotherapy. Overall survival was not significantly different in the two groups, with 116 deaths occurring in the AROMASIN (exemestane) group and 137 in the tamoxifen group.

Table 8: Efficacy Results from the IES Study in Postmenopausal Women with Early Breast Cancer

ITT Population Hazard Ratio (95% CI) p-value (log-rank test)
Disease-free survival 0.69 (0.58–0.82) 0.00003
Time to contralateral breast cancer 0.32 (0.15–0.72) 0.00340
Distant recurrence-free survival 0.74 (0.62–0.90) 0.00207
Overall survival 0.86 (0.67–1.10) 0.22962
ER and/or PgR positive
Disease-free survival 0.65 (0.53–0.79) 0.00001
Time to contralateral breast cancer 0.22 (0.08–0.57) 0.00069
Distant recurrence-free survival 0.73 (0.59–0.90) 0.00367
Overall survival 0.88 (0.67–1.17) 0.37460

 

Figure 1: Disease-Free Survival in the IES Study of Postmenopausal Women with Early Breast Cancer (ITT Population)

Disease-Free Survival in the IES Study of Postmenopausal Women with Early Breast Cancer - Illustration

Treatment of Advanced Breast Cancer

Exemestane 25 mg administered once daily was evaluated in a randomized double-blind, multicenter, multinational comparative study and in two multicenter single-arm studies of postmenopausal women with advanced breast cancer who had disease progression after treatment with tamoxifen for metastatic disease or as adjuvant therapy. Some patients also have received prior cytotoxic therapy, either as adjuvant treatment or for metastatic disease.

The primary purpose of the three studies was evaluation of objective response rate (complete response [CR] and partial response [PR]). Time to tumor progression and overall survival were also assessed in the comparative trial. Response rates were assessed based on World Health Organization (WHO) criteria, and in the comparative study, were submitted to an external review committee that was blinded to patient treatment. In the comparative study, 769 patients were randomized to receive AROMASIN (exemestane tablets) 25 mg once daily (N = 366) or megestrol acetate 40 mg four times daily (N = 403). Demographics and baseline characteristics are presented in Table 9.

Table 9: Demographics and Baseline Characteristics from the Comparative Study of Postmenopausal Women with Advanced Breast Cancer Whose Disease Had Progressed after Tamoxifen Therapy

Parameter AROMASIN (N = 366) Megestrol Acetate (N = 403)
Median Age (range) 65 (35–89) 65 (30–91)
ECOG Performance Status    
  0 167 (46%) 187 (46%)
  1 162 (44%) 172 (43%)
  2 34 (9%) 42 (10%)
Receptor Status    
  ER and/or PgR + 246 (67%) 274 (68%)
  ER and PgR unknown 116 (32%) 128 (32%)
    Responders to prior tamoxifen 68 (19%) 85 (21%)
    NE for response to prior tamoxifen 46 (13%) 41 (10%)
Site of Metastasis    
  Visceral ± other sites 207 (57%) 239 (59%)
  Bone only 61 (17%) 73 (18%)
  Soft tissue only 54 (15%) 51 (13%)
  Bone & soft tissue 43 (12%) 38 (9%)
Measurable Disease 287 (78%) 314 (78%)
Prior Tamoxifen Therapy    
  Adjuvant or Neoadjuvant 145 (40%) 152 (38%)
  Advanced Disease, Outcome    
    CR, PR, or SD > 6 months 179 (49%) 210 (52%)
    SD < 6 months, PD or NE 42 (12%) 41 (10%)
Prior Chemotherapy    
   For advanced disease ± adjuvant 58 (16%) 67 (17%)
  Adjuvant only 104 (28%) 108 (27%)
  No chemotherapy 203 (56%) 226 (56%)

The efficacy results from the comparative study are shown in Table 10. The objective response rates observed in the two treatment arms showed that AROMASIN (exemestane) was not different from megestrol acetate. Response rates for AROMASIN (exemestane) from the two single-arm trials were 23.4% and 28.1%.

Table 10: Efficacy Results from the Comparative Study of Postmenopausal Women with Advanced Breast Cancer Whose Disease Had Progressed after Tamoxifen Therapy

Response Characteristics AROMASIN (N=366) Megestrol Acetate (N=403)
Objective Response Rate = CR + PR (%) 15.0 12.4
  Difference in Response Rate (AR-MA) 2.6
  95% C.I. 7.5, -2.3
CR (%) 2.2 1.2
PR (%) 12.8 11.2
  SD ≥ 24 Weeks (%) 21.3 21.1
Median Duration of Response (weeks) 76.1 71.0
Median TTP (weeks) 20.3 16.6
  Hazard Ratio (AR-MA) 0.84
Abbreviations: CR = complete response, PR = partial response, SD = stable disease (no change), TTP = time to tumor progression, C.I. = confidence interval, MA = megestrol acetate, AR = AROMASIN

There were too few deaths occurring across treatment groups to draw conclusions on overall survival differences. The Kaplan-Meier curve for time to tumor progression in the comparative study is shown in Figure 2.

Figure 2: Time to Tumor Progression in the Comparative Study of Postmenopausal Women With Advanced Breast Cancer Whose Disease Had Progressed After Tamoxifen Therapy

Time to Tumor Progression in the Comparative Study - Illustration

Last reviewed on RxList: 5/11/2011
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

AROMASIN®
(ah ROME ah sin)
(exemestane tablets)

Read the patient information leaflet that comes with AROMASIN (exemestane) before you start taking it. Read the leaflet each time you get a refill. There may be new information. This leaflet does not replace talking with your doctor about your condition or treatment. If you have any questions about AROMASIN (exemestane) , ask your nurse, doctor, or pharmacist.

1. What is AROMASIN (exemestane) ?

AROMASIN (exemestane) is used in women who are past menopause. It is used in:

  • Early breast cancer (cancer that has not spread outside the breast). AROMASIN (exemestane) lowers the risk the cancer will come back. It is for women who:
    • Have cancer that needs the female hormone estrogen to grow and
    • Had surgery for breast cancer, and possibly other treatments for breast cancer including radiation or chemotherapy and
    • Have taken tamoxifen for 2 to 3 years and
    • Are switching to AROMASIN (exemestane) to finish 5 years in a row of hormonal therapy.
  • Advanced breast cancer (cancer that has spread), to treat cancer that came back after treatment with tamoxifen.

Certain breast cancers need the female hormone estrogen to grow (estrogen receptor-positive cancer).

While you are taking AROMASIN (exemestane) , your body stops making estrogen. AROMASIN (exemestane) may slow or stop the growth of the cancer.

AROMASIN (exemestane) is hormone therapy. It is not chemotherapy. It is not hormone replacement therapy (HRT).

2. Who should not take AROMASIN (exemestane) ?

Do not take AROMASIN (exemestane) if:

  • You are allergic to AROMASIN or anything in it. The active ingredient is exemestane. There is a list of what is in AROMASIN (exemestane) at the end of this leaflet.

3. What should I tell my doctor before taking AROMASIN (exemestane) ?

Tell your doctor about all your medical conditions. Be sure to tell your doctor if you:

  • Are still having menstrual periods (are not past menopause). AROMASIN (exemestane) is only for women who are past menopause.
  • Are pregnant or could be pregnant. Taking AROMASIN (exemestane) during pregnancy may cause birth defects or miscarriage.
  • Are breast-feeding. Do not breast-feed while you are being treated with AROMASIN (exemestane) .
  • Have liver or kidney problems.

Tell your doctor about all the medicines you take. Include prescription and nonprescription medicines, herbal remedies, and vitamins. AROMASIN (exemestane) and other medicines may affect how each other work.

Be sure to tell your doctor if you take:

  • Medicines with estrogen, such as Premarin®, other hormone replacement therapy, or birth control pills or patches. AROMASIN (exemestane) should not be taken with these medicines as they could affect how well AROMASIN (exemestane) works.
  • Rifadin® (rifampin)
  • Dilantin® (phenytoin), Tegretol® (carbamazepine), or Luminal® (phenobarbital)
  • St. John's wort

Know what medicines you take. Keep a list of them with you. Show it to your doctor or pharmacist each time you get a new prescription.

4. What are the possible side effects of AROMASIN (exemestane) ?

Serious Side Effects

  • Bone loss. AROMASIN (exemestane) may reduce your bone mineral density (BMD) over time. This may raise your risk for bone fractures.
  • Chest pain, heart failure, or stroke. A small number of women had chest pain, heart failure, or a stroke while taking AROMASIN (exemestane) .

Common Side Effects

  • hot flashes
  • headache
  • depression
  • difficulty
  • feeling tired
  • trouble sleeping
  • feeling anxious
  • in breathing
  • joint pain
  • increased sweating
  • upset stomach

Your doctor may do blood tests to check your liver and kidney function during treatment.

These are not all the side effects with AROMASIN (exemestane) . Ask your cancer nurse or doctor for a more complete list.

5. How Should I take AROMASIN (exemestane) ?

  • Take your dose of AROMASIN (exemestane) once a day, every day, after a meal. AROMASIN (exemestane) comes in 25mg tablets you take by mouth. Your doctor will tell you how many AROMASIN (exemestane) tablets to take for your dose.
  • Try to take your treatment at the same time each day.
  • Take your medicine for as long as your doctor tells you.
  • Tell your doctor if you do not feel well after starting AROMASIN (exemestane) .
  • If you miss a dose of AROMASIN (exemestane) , take it as soon as you remember. If it is close to your next dose, just take your next dose at your regular time.
  • Don't take more than one dose of AROMASIN (exemestane) at a time.
  • Make a note of when your prescription will run out. That way, you can get it refilled on time.

6. How Should I Store AROMASIN (exemestane) ?

  • Keep AROMASIN (exemestane) and all medicines out of the reach of children.
  • Store AROMASIN (exemestane) at room temperature, 77°F (25°C), in its original container.

7. General information about AROMASIN (exemestane)

Doctors can prescribe medicines for conditions that are not in the patient information leaflet. Use AROMASIN (exemestane) only for what your doctor prescribed. Do not give it to other people, even if they have the same conditions you have. It may harm them.

This leaflet gives the most important information about AROMASIN (exemestane) . For more information about AROMASIN (exemestane) , talk with your doctor, nurse, or pharmacist. You can visit our Web site at www.AROMASIN (exemestane) .com, or call 1-888-AROMASIN (exemestane) (1-888-276-6274).

8. What is in AROMASIN?

Active ingredient: exemestane

Inactive ingredients: mannitol, crospovidone, polysorbate 80, hypromellose, colloidal silicon dioxide, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, simethicone, polyethylene glycol 6000, sucrose, magnesium carbonate, titanium dioxide, methylparaben, and polyvinyl alcohol.

Last reviewed on RxList: 5/11/2011
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

AROMASIN®
(ah ROME ah sin)
(exemestane tablets)

Read the patient information leaflet that comes with AROMASIN (exemestane) before you start taking it. Read the leaflet each time you get a refill. There may be new information. This leaflet does not replace talking with your doctor about your condition or treatment. If you have any questions about AROMASIN (exemestane) , ask your nurse, doctor, or pharmacist.

1. What is AROMASIN (exemestane) ?

AROMASIN (exemestane) is used in women who are past menopause. It is used in:

  • Early breast cancer (cancer that has not spread outside the breast). AROMASIN (exemestane) lowers the risk the cancer will come back. It is for women who:
    • Have cancer that needs the female hormone estrogen to grow and
    • Had surgery for breast cancer, and possibly other treatments for breast cancer including radiation or chemotherapy and
    • Have taken tamoxifen for 2 to 3 years and
    • Are switching to AROMASIN (exemestane) to finish 5 years in a row of hormonal therapy.
  • Advanced breast cancer (cancer that has spread), to treat cancer that came back after treatment with tamoxifen.

Certain breast cancers need the female hormone estrogen to grow (estrogen receptor-positive cancer).

While you are taking AROMASIN (exemestane) , your body stops making estrogen. AROMASIN (exemestane) may slow or stop the growth of the cancer.

AROMASIN (exemestane) is hormone therapy. It is not chemotherapy. It is not hormone replacement therapy (HRT).

2. Who should not take AROMASIN (exemestane) ?

Do not take AROMASIN (exemestane) if:

  • You are allergic to AROMASIN or anything in it. The active ingredient is exemestane. There is a list of what is in AROMASIN (exemestane) at the end of this leaflet.

3. What should I tell my doctor before taking AROMASIN (exemestane) ?

Tell your doctor about all your medical conditions. Be sure to tell your doctor if you:

  • Are still having menstrual periods (are not past menopause). AROMASIN (exemestane) is only for women who are past menopause.
  • Are pregnant or could be pregnant. Taking AROMASIN (exemestane) during pregnancy may cause birth defects or miscarriage.
  • Are breast-feeding. Do not breast-feed while you are being treated with AROMASIN (exemestane) .
  • Have liver or kidney problems.

Tell your doctor about all the medicines you take. Include prescription and nonprescription medicines, herbal remedies, and vitamins. AROMASIN (exemestane) and other medicines may affect how each other work.

Be sure to tell your doctor if you take:

  • Medicines with estrogen, such as Premarin®, other hormone replacement therapy, or birth control pills or patches. AROMASIN (exemestane) should not be taken with these medicines as they could affect how well AROMASIN (exemestane) works.
  • Rifadin® (rifampin)
  • Dilantin® (phenytoin), Tegretol® (carbamazepine), or Luminal® (phenobarbital)
  • St. John's wort

Know what medicines you take. Keep a list of them with you. Show it to your doctor or pharmacist each time you get a new prescription.

4. What are the possible side effects of AROMASIN (exemestane) ?

Serious Side Effects

  • Bone loss. AROMASIN (exemestane) may reduce your bone mineral density (BMD) over time. This may raise your risk for bone fractures.
  • Chest pain, heart failure, or stroke. A small number of women had chest pain, heart failure, or a stroke while taking AROMASIN (exemestane) .

Common Side Effects

  • hot flashes
  • headache
  • depression
  • difficulty
  • feeling tired
  • trouble sleeping
  • feeling anxious
  • in breathing
  • joint pain
  • increased sweating
  • upset stomach

Your doctor may do blood tests to check your liver and kidney function during treatment.

These are not all the side effects with AROMASIN (exemestane) . Ask your cancer nurse or doctor for a more complete list.

5. How Should I take AROMASIN (exemestane) ?

  • Take your dose of AROMASIN (exemestane) once a day, every day, after a meal. AROMASIN (exemestane) comes in 25mg tablets you take by mouth. Your doctor will tell you how many AROMASIN (exemestane) tablets to take for your dose.
  • Try to take your treatment at the same time each day.
  • Take your medicine for as long as your doctor tells you.
  • Tell your doctor if you do not feel well after starting AROMASIN (exemestane) .
  • If you miss a dose of AROMASIN (exemestane) , take it as soon as you remember. If it is close to your next dose, just take your next dose at your regular time.
  • Don't take more than one dose of AROMASIN (exemestane) at a time.
  • Make a note of when your prescription will run out. That way, you can get it refilled on time.

6. How Should I Store AROMASIN (exemestane) ?

  • Keep AROMASIN (exemestane) and all medicines out of the reach of children.
  • Store AROMASIN (exemestane) at room temperature, 77°F (25°C), in its original container.

7. General information about AROMASIN (exemestane)

Doctors can prescribe medicines for conditions that are not in the patient information leaflet. Use AROMASIN (exemestane) only for what your doctor prescribed. Do not give it to other people, even if they have the same conditions you have. It may harm them.

This leaflet gives the most important information about AROMASIN (exemestane) . For more information about AROMASIN (exemestane) , talk with your doctor, nurse, or pharmacist. You can visit our Web site at www.AROMASIN (exemestane) .com, or call 1-888-AROMASIN (exemestane) (1-888-276-6274).

8. What is in AROMASIN?

Active ingredient: exemestane

Inactive ingredients: mannitol, crospovidone, polysorbate 80, hypromellose, colloidal silicon dioxide, microcrystalline cellulose, sodium starch glycolate, magnesium stearate, simethicone, polyethylene glycol 6000, sucrose, magnesium carbonate, titanium dioxide, methylparaben, and polyvinyl alcohol.

Last reviewed on RxList: 5/11/2011
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Aromasin Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

EXEMESTANE - ORAL

(ex-em-ESS-tain)

COMMON BRAND NAME(S): Aromasin

USES: This medication is used to treat certain types of breast cancer (such as hormone-receptor-positive breast cancer) in women after menopause. Exemestane is also used to help prevent the cancer from returning. Some breast cancers are made to grow faster by a natural hormone called estrogen. Exemestane decreases the amount of estrogen the body makes and helps to slow or reverse the growth of these breast cancers.

Exemestane is usually not used in women of childbearing age.

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start using exemestane and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Take this medication by mouth, usually once daily with food (after a meal), or as directed by your doctor.

Dosage is based on your medical condition and response to treatment.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.

Since this drug can be absorbed through the skin and lungs, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets. (See also Precautions section.)

Inform your doctor immediately if your condition worsens (such as you get new breast lumps).

Disclaimer

Aromasin Consumer (continued)

SIDE EFFECTS: Hot flashes, hair loss, joint/bone/muscle pain, tiredness, unusual sweating, nausea, diarrhea, dizziness, and trouble sleeping may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: bone fractures, mental/mood changes (such as depression, anxiety), vaginal bleeding.

This medication (and cancer) may rarely cause serious problems from blood clots (such as heart attack or stroke). Seek immediate medical attention if you experience: sudden shortness of breath, chest/jaw/left arm pain, confusion, coughing up blood, sudden dizziness/fainting, pain/swelling/warmth in the groin/calf, tingling/weakness/numbness in the arms/legs, slurred speech, swelling of arms/legs, weakness on one side of the body, vision changes, sudden/severe headache.

Tell your doctor immediately if any of these rare but very serious side effects occur: persistent nausea/vomiting, unusual tiredness, dark urine, yellowing eyes/skin.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching/swelling (especially of the face/tongue/throat/neck), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

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

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Aromasin (exemestane) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking exemestane, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: high blood fats (cholesterol), bone problems (such as osteopenia, osteoporosis), stroke or blood clots, heart disease (such as chest pain, heart attack, heart failure), high blood pressure, kidney problems, liver problems.

This drug may make you dizzy and tired. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. Limit alcoholic beverages.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

This medication must not be used during pregnancy. It may harm an unborn baby. Exemestane is used mainly in women after menopause. If you are near menopause or have not gone through menopause and your doctor has prescribed this for you, discuss with your doctor whether you need to use reliable forms of birth control. Do not use birth control products containing estrogen. Consult your doctor for more details. If you become pregnant or think you may be pregnant, tell your doctor immediately. (See also How to Use section.)

It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.

Disclaimer

Aromasin Consumer (continued)

DRUG INTERACTIONS: The effects of some drugs can change if you take other drugs or herbal products at the same time. This can increase your risk for serious side effects or may cause your medications not to work correctly. These drug interactions are possible, but do not always occur. Your doctor or pharmacist can often prevent or manage interactions by changing how you use your medications or by close monitoring.

To help your doctor and pharmacist give you the best care, be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products) before starting treatment with this product. While using this product, do not start, stop, or change the dosage of any other medicines you are using without your doctor's approval.

Some products that may interact with this drug include: estrogens (such as ethinyl estradiol, conjugated estrogens), estrogen blockers (such as anastrozole, tamoxifen), raloxifene.

Other medications can increase the removal of exemestane from your body, which may affect how well exemestane works. Examples include drugs used to treat seizures (such as carbamazepine, phenobarbital, phenytoin), rifamycins (such as rifabutin), St. John's wort, among others.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (such as bone density tests, cholesterol levels, liver function tests) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

This medication can increase the risk of bone loss (osteoporosis). Talk with your doctor about your risk, and about available treatments for osteoporosis. Lifestyle changes that reduce the risk of bone loss include doing weight-bearing exercise, getting enough calcium and vitamin D, stopping smoking, and limiting alcohol.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store exemestane tablets at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised March 2011. Copyright(c) 2011 First Databank, Inc.

Aromasin Patient Information Including Side Effects

Brand Names: Aromasin

Generic Name: exemestane (Pronunciation: ex e MES tane)

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.

Aromasin 25 mg

round, gray, imprinted with 7663

What are the possible side effects of exemestane (Aromasin)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • new or unusual bone pain;
  • vision problems;
  • swelling in your hands or feet;
  • feeling short of breath, even with mild exertion; or
  • chest pain, sudden numbness or weakness, sudden headache, confusion, problems with vision, speech, or balance.

Less serious side effects may include:

  • hot flashes;
  • headache, tired feeling;
  • anxiety;
  • joint pain;
  • upset stomach;
  • depressed mood;
  • sleep problems (insomnia); or
  • increased sweating.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Aromasin (exemestane) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about exemestane (Aromasin)?

You may need to take a pregnancy test before using exemestane, to make sure you are not pregnant.

You should not use this medication if you are allergic to exemestane, or if you are breast-feeding a baby.

Before using exemestane, tell your doctor if you have liver or kidney disease, or if you have not yet completed menopause and are still having menstrual periods.

Use exemestane 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. Follow your doctor's instructions.

Exemestane may not work as well if you take it together with hormone replacement medication, or while using birth control pills or patches.

Side Effects Centers

Aromasin Patient Information including How Should I Take

What should I discuss with my healthcare provider before taking exemestane (Aromasin)?

You should not use this medication if you are allergic to exemestane, or if you are breast-feeding a baby.

To make sure you can safely take exemestane, tell your doctor if you have any of these other conditions:

  • liver disease;
  • kidney disease; or
  • if you have not yet completed menopause, and are still having menstrual periods.

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

FDA pregnancy category D. Do not use exemestane if you are pregnant. It could harm the unborn baby or cause a miscarriage. Use effective birth control, and tell your doctor if you become pregnant during treatment.

You may need to take a pregnancy test before using exemestane, to make sure you are not pregnant.

It is not known whether exemestane passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take exemestane (Aromasin)?

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

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

Use exemestane 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. Follow your doctor's instructions.

To be sure this medication is not causing harmful effects, your blood may need to be tested often. Visit your doctor regularly.

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

Side Effects Centers

Aromasin Patient Information including If I Miss a Dose

What happens if I miss a dose (Aromasin)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Aromasin)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking exemestane (Aromasin)?

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

What other drugs will affect exemestane (Aromasin)?

Exemestane may not work as well if you take it together with hormone replacement medication, or while using birth control pills or patches.

Tell your doctor about all other medicines you use, especially:

  • bosentan (Tracleer);
  • dexamethasone (Decadron, Hexadrol);
  • St. John's wort;
  • rifabutin (Mycobutin), rifampin (Rifadin, Rifater, Rifamate), or rifapentine (Priftin);
  • a barbiturate such as butabarbital (Butisol), secobarbital (Seconal), pentobarbital (Nembutal), or phenobarbital (Luminal, Solfoton);
  • HIV medication such as efavirenz (Sustiva, Atripla), etravirine (Intelence), nevirapine (Viramune), or ritonavir (Norvir, Kaletra);
  • medicines to treat narcolepsy, such as armodafanil (Nuvigil) or modafanil (Progivil); or
  • seizure medication such as carbamazepine (Carbatrol, Tegretol), felbamate (Felbatol), oxcarbazepine (Trileptal), phenytoin (Dilantin), or primidone (Mysoline).

This list is not complete and other drugs may interact with exemestane. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about exemestane.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 4.01. Revision date: 5/27/2011.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Healthwise

Side Effects Centers

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