Exemestane - Uses, Efficacy, Side Effects, Pharmacology, and Warnings

Overview

Exemestane is an oral medication used for the treatment of breast cancer. It sorts with the class of drugs called anti-estrogens, also known as aromatase inhibitors (AIs). This drug is specifically indicated for the adjuvant (alternative) treatment of breast cancer in postmenopausal women who have already received two to three consecutive years of Tamoxifen. It is also indicated for breast cancer treatment in postmenopausal women whose cancerous condition has been aggravated while treated with Tamoxifen. The drug Exemestane received its approval from the Food and Drug Administration (FDA) in October 1999.

How Does Exemestane Work?

Exemestane drug is used to treat several types of breast cancer, particularly hormone-receptor-positive breast cancers in postmenopausal women. Certain breast cancers require estrogen hormone for tumor cell growth. Such cancers are considered to have estrogen receptors (ERs) and are referred to as ER-positive. They might also be called hormonally responsive, estrogen-responsive, or hormone-receptor-positive. Aromatase is an enzyme that is accountable for the synthesis of estrogen in the body by the process of conversion of adrenal hormones to estrogen. Exemestane is an aromatase inhibitor, so it blocks the synthesis of estrogen. When estrogen level is lowered, the growth of the cancer is either slowed down or prevented.

Drug Form and Strength:

• Exemestane tablets are round, biconvex, white to off-white, and bevel-edged tablets.

• Each medication contains 25 mg of Exemestane.

Prescriptions and Drug Dosage

Breast Cancer Treatment

1. Advanced Stage:

• Exemestane is paramountly indicated for the treatment of advanced stages of breast cancer, specifically in postmenopausal women whose cancer disease has progressed even after Tamoxifen therapy.

• The recommended dosage is 25 mg (orally) with a frequency of once daily for days.

2. Adjuvant Treatment:

• Exemestane is indicated as an adjuvant or alternative treatment in postmenopausal women with estrogen receptor and early breast cancer to those who have received Tamoxifen treatment for two to three years and have swapped to Exemestane.

• The recommended dosage of Exemestane for adjuvant treatment is 25 mg once daily.

Breast Cancer Prevention (OFF-LABEL)

• The American Society of Clinical Oncology (ASCO) and other guidelines recommend Exemestane as an alternative treatment to Tamoxifen or Raloxifene for invasive breast cancer prevention in the case of women who have higher risks.

• The recommended dosage for breast cancer prevention is 25 mg once daily for up to a period of five years.

For Patients

What Can Cause Breast Cancer?

Breast cancer is a cancerous disease that involves the cells of the breasts. Breast cancer is the most prevailing cancer to be diagnosed in women, next to skin cancer in the United States. Breast cancer can commonly occur in women while rarely in men. Here, the normal cells of the breast turn out into tumor cells and grow out of control. There are different types of breast cancers based on the location and name of the cells involved. Moreover, breast cancer can form in different parts of the breast, including milk-producing glands called lobules, ducts carrying milk, and the connective tissue that holds every part. Breast cancer could metastasize (spread) to other parts than the breast by means of blood vessels and lymph vessels.

There is no absolute cause for breast cancer. Though, certain factors could increase the risk of breast cancer in women.

• Getting older.

• Having dense breasts or more connective tissue.

• Inherited genetic mutations to specific genes.

• Past history of breast cancer or severe non-cancerous breast diseases.

• Exposure to the drug, particularly Diethylstilbestrol.

• Previous radiation therapy was treated to the breast or chest.

• Family history of cancers, particularly breast and ovarian cancer.

• Reproductive history.

What Are the Common Warning Signs of Breast Cancer?

The symptoms vary from individual to individual based on the type of breast cancer. Several women do not experience any symptoms, while some have distressing symptoms. The common symptoms of breast cancer include:

• Lump formation in the breast or armpit.

• Irritation of the breast skin.

• Bloody discharge from the nipple.

• Changes detected in the size, shape, and texture of the breast and nipple.

• Pulling in the nipple.

• Redness or flaky skin in the breast.

• Pain in any specific part or all parts of the breast.

How Is Breast Cancer Treated?

The treatment of breast cancer typically depends on its stages, such as early, metastasizing, and advanced. The treatment consists of surgical procedures, chemotherapy, radiation therapy, hormone-based chemotherapy, teletherapy, and estrogen modulator. The hormone-based chemotherapy treats those hormone-sensitive cancerous conditions. Estrogen modulators mimic estrogen and its effects, treating various tissues like breasts, reproductive organs, and bones.

How Does Exemestane Help Treat Breast Cancer?

Exemestane is used chiefly for the treatment of early stage of breast cancer in individuals who have passed menopause (end of menstrual periods) and women who have undergone previous treatment with Tamoxifen (medication) treatment for about two to three years. Subsequently, Exemestane is also prescribed for treating breast cancer in women who have passed menopause and whose breast cancer condition has aggravated during Tamoxifen treatment. Exemestane sorts with a class of drugs called aromatase inhibitors (AIs). It works by reducing the estrogen concentration in the body. This results in slowing down or ending the growth of certain breast tumors that require estrogen for their growth.

How Can Exemestane Be Administered?

Exemestane comes as oral tablets. The medical healthcare professionals will prescribe the appropriate dosage of Exemestane based on age, the stage of cancer to be treated, the severity of the cancer, and underlying medical illnesses. The drug could influence individuals in a contrary fashion, presenting certain effects. Therefore, one should take the drug Exemestane according to the instructions and directions of doctors to get its full effects while reducing the risks of adverse reactions associated with Exemestane. One should not take less or more of the medication than the prescribed dosage. For more information, read the manufacturer’s information labeled on the prescription leaflet.

Things to Inform the Doctor Before Commencement:

• Tell the doctor if one has any allergic reaction to Exemestane or any other ingredient constituted in the prescribed medication. In such cases, the doctors advise not to take this medication.

• Inform the doctor about the medical conditions one has ever had in the past years.

• One should inform the doctor about the medications one takes, such as prescription drugs, over-the-counter medications, vitamins, herbal products, and nutritional supplements. Specifically, tell the doctor if one takes medication containing estrogen and other birth control aids and hormone replacement therapy. The doctors might advise not to take Exemestane medicine since the drugs containing estrogen would affect the efficacy of Exemestane.

• Inform the doctor if one still has menstrual periods or has not passed menopause since Exemestane medication is only for postmenopausal women.

• Convey the doctor if one has or has ever had bone concerns like osteoporosis (weak or brittle bones).

• Subsequently, inform the doctor if one has any liver or kidney problems.

• The doctor should know if one is pregnant or has any further plans for pregnancy. The doctors consider the potential risk and benefits since taking Exemestane during pregnancy time or within one month of becoming pregnant could harm the unborn child.

• Tell the doctor if one is breastfeeding or has a plan to breastfeed. The clinical findings do not demonstrate that Exemestane could pass into the breast milk. But, the doctors generally advise not to breastfeed during Exemestane treatment and for about one month following the last dose.

Important Considerations:

• Females who are about to or able to become pregnant should do a pregnancy test within a period of seven days before Exemestane treatment initiation.

• Addedly, females with the ability to become pregnant should use appropriate and effective birth control aids during the treatment of Exemestane medication and for about one month after the final dose.

• One should inform the doctor straight away if one becomes pregnant during the treatment.

Directions to Take Exemestane Medication:

• Exemestane medication is to be taken orally.

• Take an Exemestane tablet once daily after a meal.

• Swallow the tablet wholly only with a glass of water. So, one should not chew or break them.

• Take the doses as per the physicians’ directions, such as the number of capsules, frequency of doses, and length of duration.

• One should not bring to stop taking Exemestane unless the doctor says so.

• Complete the number of drugs as prescribed, though with an improvement.

• Moreover, call and inform the doctor if there prevails no improvement or worsening of the condition.

Dietetic Consideration:

One can follow the routine diet schedule and the usual eating method until the doctor utters any dietetic restrictions. Nevertheless, a well-balanced and healthy diet clears the way for good physical and emotional states.

Storage and Disposal of Exemestane

Storage:

• Store Exemestane at a constant room temperature, aside from the heat, sunlight, and moisture.

• The Medication should be stored between 20 and 25 degrees Celsius (68 to 77 degrees Fahrenheit)

• Keep Exemestane and other medications away from the sight and reach of the children.

Disposal:

• It is recommended to safely dispose of unused or expired Exemestane medication so that the companions and little children could not reach it.

• Exemestane or any medication should not be flushed in the toilet or just thrown in the community garbage.

• A good way of disposing of the medication is with the local recycling technique or by other safe recycling ways in the community.

How Effective Is Exemestane?

Exemestane is considered a safe and effective medication for the early and advanced stages of breast cancer. It works efficiently by blocking the process of aromatization. So, it reduces the concentration of estrogen in the body. In the early stage of breast cancer, taking Exemestane medication helps in preventing breast cancer recurrence. In advanced cases of breast cancer, Exemestane either reduces or halts the growth of tumor cells. The clinical data shows that women who take the drug Exemestane had 65 percent fewer possibilities of having breast cancer when related to women who took a placebo.

What Are the Side Effects of Exemestane?

Exemestane can induce certain undesirable effects, though it is safe and effective to use. But, it is not sure that every individual would experience side effects. The most prevalent side effects of the drug Exemestane include the following. These side effects are less serious and can be resolved over time. However, inform the doctor if these effects are distressing and not going away.

• Headache.

• Hot flashes.

• Joint pain.

• Tiredness.

• Nausea.

• Diarrhea.

• Dizziness.

• Upset stomach.

• Increased appetite.

• Excessive sweating.

• Hair loss.

• Pain with the joint, muscle, or bone.

• Anxiety.

• Depression.

• Sleep problems or altered sleep patterns.

Exemestane might cause certain serious side effects. In such a case, one should get professional help right away before it becomes serious, requiring emergency medical attention. The potentially serious side effects associated with Exemestane include the following:

• Unusual bone pain.

• Bone fractures.

• Mood changes.

• Vaginal bleeding.

• Dark urine.

• Yellowish discoloration of eyes or skin.

• Shortness of breath.

• Persistent nausea and vomiting.

• Swelling in the upper and lower extremities.

• Chest pain or discomfort.

• Sudden headache episodes.

• Numbness or weakness.

• Confusion.

• Vision, hearing, and speech problems.

• Problems with balance.

Bone Loss:

Exemestane can cause serious bone loss concerns. This drug can reduce the amount of estrogen in the system, culminating in the reduction of bone mineral density (BMD) with time. So, this might raise the risk of osteoporosis (weak and brittle bones) or bone fractures. Hence, the doctors perform certain assessments and tests for the bones during the treatment with Exemestane in case one has osteoporosis or is at high risk for osteoporosis.

For Doctors

Clinical Data of Exemestane:

Drug Name: Exemestane.

Generic Name: Exemestane.

Other Names: FCE- 24304.

Drug Class: Antiestrogen or Aromatase inhibitor.

Route of Administration: Oral.

Chemical Formula: C20H24O2.

Molar Mass: 296.410 g.mol-1

Pharmacology of Exemestane

Indications:

Exemestane is generally indicated for breast cancer treatment in postmenopausal women in whom the cancer disease has progressed following Tamoxifen therapy.

Associated Conditions

• Stage one breast cancer.

• Refractory and advanced breast cancer.

Pharmacodynamics:

There is an enzyme known as aromatase which converts hormones to estrogen in the adrenal glands of the body. The aromatase inhibitors (AI) drugs decrease the levels of estrogen by blocking the enzyme aromatase and Irma’s action in the adrenal glands. Moreover, selective aromatase inhibitors, or SAIs selectively decrease the levels of estrogen even without influencing the levels of other significant steroid hormones of the adrenal gland. Exemestane sorts in a class of drugs called selective aromatase inhibitors.

Mechanism of Action

In breast cancer, the tumor cell growth can be estrogen-dependent. Aromatase is the predominant enzyme involved in the conversion of androgens to estrogen in women with both premenopausal and postmenopausal phases. Since the principal source is the ovary for estrogen in premenopausal women, the chief source of encircling estrogens in the case of postmenopausal women is obtained from the conversion of ovarian and adrenal androgen like testosterone and androstenedione to estrogens. This results from an enzyme called Aromatase.

Exemestane is a steroidal aromatase inactivator. It has a structure parallel to the natural substrate or hormone called androstenedione. So, it serves as a false substrate for the enzyme aromatase and can be processed to an intermediate binding irreversibly with the active portion of the enzyme resulting in inactivation or suicide inhibition effect. As a result, Exemestane markedly reduces the encircling estrogen levels in postmenopausal women but with no discernible impact on the adrenal biosynthesis process of aldosterone or corticosteroids. The clinical findings show that Exemestane shows no effect on other enzymes attributed to steroidogenic pathways up until a level of a minimum of 600.

Absorption:

• Following an oral administration, Exemestane shows rapid absorption in women with breast cancer when compared to healthy individuals.

• So, the mean time to peak drug concentration (Tmax) is about 1.2 hours in breast cancer women and about 2.9 hours in the case of healthy women.

• It is estimated about 42 percent of the radiolabeled dose of Exemestane is absorbed from the gastrointestinal tract.

• A high-fat-containing meal can increase the area under the curve (AUC) and the maximum serum concentration (Cmax) of Exemestane by 59 % and 39 % correspondingly when compared to fasting states.

Distribution:

• Exemestane is well and extensively distributed to the tissues.

• The plasma protein binding capacity of Exemestane is about 90 percent, and the fraction bound is completely independent of the total concentration.

• The two significant components contributing to binding are albumin and alpha 1-acid glycoprotein.

• The distribution of Exemestane and its metabolites into the blood cells is inappreciable.

Metabolism:

• Exemestane undergoes hepatic metabolism.

• It is well and extensively metabolized in the liver, with unchanged drug levels in the plasma counting for less than ten percent of the total radioactivity.

• Oxidation of the methylene group takes place in position six while with the reduction of group 17-keto together with the formation of certain secondary metabolites. This step makes up the very first step in metabolism.

• Every metabolite formed counts for a minimal amount of the drug-related substance.

• But the metabolites tend to be inactive or possess less potency for the inhibition of aromatase when compared to the parent drug.

• Clinical studies specifying live preparation say that cytochrome P 450 3A4 is the significant and primary isoenzyme contributing to the oxidation process of Exemestane.

• The metabolism of Exemestane also proceeds by aldo-keto reductases.

Elimination:

• The route of elimination is through urine and feces.

• The incremental amount of radioactivity traced in urine and feces were much similar following an oral administration of radiolabeled Exemestane in the case of healthy postmenopausal women.

• The amount of Exemestane excreted in unchanged form in urine was less than one percent of the administered dose.

Half-Life and Clearance:

• The mean half-life of Exemestane was estimated to be about 24 hours.

Contraindications:

• Exemestane is strictly contraindicated for individuals who have or ever had hypersensitivity reactions to the drug.

• This medicine is contraindicated in premenopausal women, including pregnant and lactating women.

Dosage Modification:

The Dosage modification is considered only during coadministration with strong CYP3A4 inducers. This is because concomitant administration of potent CYP 3A4 tends to decrease the exposure of Exemestane. So, the dosage recommendation of Exemestane is 50 mg once daily for individuals receiving concomitant use of Exemestane oral medication with a potent CYP 3A4 inducer like Phenytoin and Rifampicin.

Important Cautions:

• Exemestane therapy is not recommended to use in conjugation with estrogen-containing drugs or agents since these agents could influence the pharmacological action of Exemestane.

• It is recommended to perform a routine assessment of the levels of 25- hydroxy vitamin D before the initiation of aromatase inhibitor treatment. This is because clinical studies show a greater prevalence of vitamin D deficiency problems in women with early-stage breast cancer. Moreover, make sure those women with vitamin D deficiency receive appropriate supplements.

• Reductions in bone mineral density have been reported largely with this therapy, particularly during adjuvant treatment with Exemestane. So, it is essential to assess formal bone mineral density by bone densitometry tool at the initiation of treatment for women having osteoporosis or at a higher risk of osteoporosis. Monitor women for bone mineral density loss, and if suspected, treat accordingly.

• Exemestane is not indicated for breast cancer treatment in premenopausal women.

• Advise use of effective contraceptive aids for those women with reproductive potential during the whole treatment and for the one month following the final dose.

• Certain animal-based studies and findings describe fertility impairments in males and females by Exemestane treatment.

Specific Populations and Considerations:

• Geriatric: The pharmacokinetic trials also include the study of the drug in healthy postmenopausal women between the ages of 43 and 68 years. Age-related changes or effects in pharmacokinetics were not noticed for this age range. So, no dosage adjustment should be significantly necessary.

• Pediatric: The safety and pharmacokinetics of Exemestane have not been established in the pediatric population.

• Gender: The clinical studies demonstrate that the pharmacokinetics of the drug Exemestane following a single dose of 25 mg oral administration in healthy males were much similar to those detected in healthy postmenopausal females after intermittent fasting.

• Hepatic Impairment: The pharmacokinetics of Exemestane had inspected in individuals with moderate to severe forms of hepatic impairment. The area under the curve (AUC) was nearly three times greater than the observations in healthy individuals following a single dose of 25 mg tablet.

• Renal Impairment: Following a single 25 mg Exemestane dose, the area under the curve (AUC) was nearly three times higher than in individuals with moderate to severe renal impairments (creatinine clearance less than 35 mL/min/1.73 m2) when compared to the AUC in healthy individuals.