Hormone Therapy Drug

What Is Exemestane?

Exemestane is a type of hormone therapy used to treat certain kinds of breast cancer. It works by lowering estrogen levels in the body, which helps slow or stop the growth of hormone-sensitive cancer cells. It is most often given to postmenopausal women (women who have completed menopause - no periods for more than a year), but is also prescribed to premenopausal women (before menopause) when their ovaries are suppressed. While Exemestane is used rarely in men, it is prescribed for treating breast cancer in males. However, Tamoxifen is usually the first-choice treatment for male breast cancer due to its reported success rate and is known to work well.

What Is Exemestane Used For?

Exemestane is mainly used to treat certain types of breast cancer in postmenopausal women. It is especially helpful for cancers that grow in response to estrogen by lowering estrogen levels in the body. Exemestane helps slow down or stop the growth of these tumors.

Doctors often prescribe Exemestane for early-stage breast cancer in women who have gone through menopause and have already taken Tamoxifen for two to three years. It is also used for advanced breast cancer if the cancer continues to grow or returns while a woman is taking Tamoxifen.

Who Should Not Use Exemestane?

• Exemestane may not be right for everyone. You should not take Exemestane if you are allergic to it or any of its ingredients.

• It is not safe during pregnancy, as it can harm an unborn baby. If there is any chance you could become pregnant, it is important to use effective birth control while taking this medication.

• Breastfeeding is also not recommended during treatment with Exemestane because it is not clear whether the drug passes into breast milk and affects the baby.

How Does Exemestane Work?

Exemestane is a drug used to treat several types of breast cancer, particularly hormone-receptor-positive breast cancers in postmenopausal women. Certain breast cancers require the 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 responsible for the synthesis of estrogen in the body by the process of converting adrenal hormones to estrogen. Exemestane is an aromatase inhibitor, so it blocks the synthesis of estrogen. When estrogen levels are lowered, the growth of the cancer is either slowed or prevented. It is one of the medications included in the aromatase inhibitor list, commonly used in hormone-related cancer treatments.

For Patients

How Should I Use Exemestane?

Exemestane comes as oral tablets. Your doctor will prescribe the right dosage of Exemestane based on your age, the stage of cancer to be treated, the severity of the cancer, and underlying medical illnesses. The drug could influence people in opposite ways, producing certain effects. Therefore, you should take the Exemestane tablet as directed by your doctor to achieve its full effects while reducing the risk of adverse reactions.

You should not take less or more of the medication than the dosage prescribed by your doctor. For more information, read the manufacturer’s information labeled on the prescription leaflet.

What Exemestane Precautions Should I Follow?

Precautions you should take while taking Exemestane are:

Warning and Precautions:

You must pay attention to the Exemestane warnings, as they can cause serious side effects if not used with caution. Therefore, you should inform the doctor of the following things before starting Exemestane therapy:

• Tell the doctor if you have any allergic reaction to Exemestane or any other ingredient contained in the prescribed medication. In such cases, doctors advise against taking this medication.

• Inform your treating doctor about the medical conditions you have ever had in the past.

• You should inform your doctor about all medications you take, including prescription drugs, over-the-counter medications, vitamins, herbal products, and nutritional supplements. Specifically, tell the doctor if you are on medication containing estrogen, other birth control aids, or hormone replacement therapy. The doctors might advise against taking Exemestane medicine since drugs containing estrogen would affect the efficacy of Exemestane.

• Inform your doctor if you still have menstrual periods or have not passed menopause, since Exemestane medication is only for postmenopausal women.

• Tell your doctor if you have had, or ever had, bone concerns such as osteoporosis (weak or brittle bones) or bone marrow disease, such as lymphocytopenia.

• Subsequently, inform your doctor if you have any liver or kidney problems.

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

• Also, if you are breastfeeding or have a plan to breastfeed, you must tell your doctor. The clinical findings do not indicate that Exemestane could be excreted into breast milk. But the doctors generally advise not to breastfeed during Exemestane treatment and for about one month following the last dose.

Important Considerations:

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

• Additionally, women 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.

• You should inform the doctor straight away if you become pregnant during the treatment.

Directions to Take Exemestane Medication:

• Exemestane medication is to be taken by mouth (orally).

• Take an Exemestane tablet once daily after a meal.

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

• Take the doses as directed by your physician, including the number of capsules, dose frequency, and duration.

• You should not 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 is no improvement or worsening of the condition.

Dietetic Consideration:

Follow a routine diet plan and the usual eating method until the doctor advises any dietary restrictions. Nevertheless, a well-balanced, healthy diet lays the foundation for good physical and emotional health.

What Are the Drug Interactions of Exemestane?

Exemestane may interact with certain medications and supplements. It is important to inform doctors about all prescription and over-the-counter medications, vitamins, minerals, and herbal supplements being used to avoid potential Exemestane interactions.

Notable Drug Interactions:

• Estrogen-Based Products: Exemestane will be less effective when taken with estrogen-containing medications, such as hormone replacement therapy, certain birth control pills, or estrogen creams, rings, and suppositories.

• Seizure Medications: Drugs like Phenytoin, Carbamazepine, and Phenobarbital, which are commonly used for seizure control or nerve pain, may interfere with the efficacy of Exemestane.

• Antibiotics and Antituberculosis Medications: Rifampin, an antibiotic often used to treat tuberculosis, may affect the blood levels of Exemestane.

• Herbal Supplements: Some herbal medicines that are prescribed and taken for treating depression affect the metabolism of Exemestane, which in turn decreases its efficacy.

• Other Considerations: You must talk to your doctor about any new or ongoing medications, as some medications can alter Exemestane's blood concentration. Additionally, despite no food, beverage, or alcohol interactions being noted, it is best to consult your healthcare providers for proper precautions and instructions.

Storage and Disposal of Exemestane

Storage:

• Aside from heat, sunlight, and moisture, Exemestane should be stored at normal room temperature.

• The medication needs to be kept between 20 and 25 degrees Celsius (68 to 77 degrees Fahrenheit).

• Keep Exemestane and other medications out of sight and reach of children.

Disposal:

• It is recommended that unused or expired Exemestane medication be disposed of safely so that pets and small children cannot reach it.

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

• A good way to dispose of the medication is to use the local recycling program or other safe community recycling methods.

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 aromatization. So, it reduces the body's estrogen concentration. 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 show that women who take the drug Exemestane have 65 percent fewer chances of having breast cancer when compared to women who took a placebo.

What Are the Side Effects of Exemestane?

Exemestane can cause undesirable effects, though it is safe and effective. However, it is not certain that every person will have the same side effects. Exemestane side effects are generally less serious and can resolve over time. However, inform the doctor if these effects are distressing and persist.

The most prevalent side effects of Exemestane include the following.

• Headache.

• Hot flashes.

• Joint pain.

• Tiredness.

• Nausea.

• Diarrhea.

• Dizziness.

• Upset stomach.

• Increased appetite.

• Excessive sweating.

• Hair loss.

• Pain in the joint, muscle, or bone.

• Anxiety.

• Depression.

• Sleep problems or altered sleep patterns.

Exemestane might cause certain serious side effects. In such a case, you should get professional help right away before it becomes serious and requires 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 has serious bone loss concerns. This drug reduces estrogen levels, leading to a gradual reduction in bone mineral density (BMD) over time. So, this might increase the risk of osteoporosis (weak, brittle bones) or bone fractures. Hence, the doctors perform certain bone assessments and tests during treatment with Exemestane if one has osteoporosis or is at high risk for osteoporosis.

What Should I Do if I Miss a Dose?

If a dose of Exemestane is missed, it should be taken as soon as it is remembered. However, if the missed dose is close to the next scheduled dose, skip the missed dose and take only the next dose as planned. Taking a double or extra dose to compensate for a missed dose should be strictly avoided to prevent potential complications.

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 has progressed following Tamoxifen therapy.

Associated Conditions

• Stage one breast cancer.

• Refractory and advanced breast cancer.

Pharmacodynamics:

There is an enzyme called aromatase that converts hormones into estrogen in the adrenal glands. Aromatase inhibitors (AIs) decrease estrogen levels by blocking the aromatase enzyme and its action in the adrenal glands. Moreover, selective aromatase inhibitors (SAIs) decrease estrogen levels without affecting other significant adrenal steroid hormones. Exemestane is a selective aromatase inhibitor.

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 of estrogen in premenopausal women is the ovary, the chief source of estrogen in postmenopausal women is the conversion of ovarian and adrenal androgens, such as testosterone and androstenedione, to estrogens. This is carried out by an enzyme called aromatase.

Exemestane is a steroidal aromatase inactivator. It has a structure parallel to that of the natural substrate or hormone, androstenedione. So, it serves as a false substrate for the enzyme aromatase and can be processed to an intermediate that binds irreversibly to the enzyme's active site, resulting in inactivation or a suicide inhibition effect. As a result, Exemestane's mechanism of action leads to a marked reduction in circulating estrogen levels in postmenopausal women without a discernible impact on adrenal biosynthesis of aldosterone or corticosteroids. The clinical findings show that Exemestane has no effect on other enzymes associated with steroidogenic pathways at levels up to 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 and about 2.9 hours in the case of healthy women.

• It is estimated that 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%, respectively, compared with fasting conditions.

Distribution:

• Exemestane is well and widely distributed throughout 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 major components contributing to binding are albumin and alpha-1-acid glycoprotein.

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

Metabolism:

• Exemestane undergoes hepatic metabolism.

• It is well and extensively metabolized in the liver, with plasma levels of the unchanged drug accounting for less than 10% of the total radioactivity.

• Oxidation of the methylene group takes place in position six, while the reduction of group 17-keto leads to the formation of certain secondary metabolites. This is the very first step in metabolism.

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

• However, the metabolites tend to be inactive or less potent inhibitors of aromatase than the parent drug.

• Clinical studies using live preparations indicate that cytochrome P450 3A4 is the primary isoenzyme responsible for the oxidation of Exemestane.

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

Elimination:

• The route of elimination is through urine and feces.

• The incremental amounts of radioactivity detected in urine and feces were similar following oral administration of radiolabeled Exemestane in 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 CYP3A4 inhibitors tends to decrease the exposure to Exemestane. The recommended dosage of Exemestane is 50 mg once daily for individuals receiving concomitant use of Exemestane with a potent CYP 3A4 inducer such as Phenytoin or Rifampicin.

Important Cautions:

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

• It is recommended that routine assessments of 25-hydroxy vitamin D levels be performed before initiating 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, ensure that women with vitamin D deficiency receive appropriate supplementation.

• Reductions in bone mineral density have been reported largely with this therapy, particularly during adjuvant treatment with Exemestane. It is essential to assess bone mineral density using a bone densitometry tool at the initiation of treatment for women with osteoporosis or at 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 the use of effective contraceptive aids for those women with reproductive potential during the whole treatment and for one month following the final dose.

• Certain animal-based studies report fertility impairments in males and females following Exemestane treatment.

Specific Populations and Considerations:

• Geriatric: The pharmacokinetic trials also include studies of the drug in healthy postmenopausal women aged 43-68 years. Age-related changes in pharmacokinetics were not observed in 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: Clinical studies demonstrate that the pharmacokinetics of Exemestane following a single 25 mg oral dose in healthy males were similar to those observed in healthy postmenopausal females after intermittent fasting.

• Hepatic Impairment: The pharmacokinetics of Exemestane were examined in individuals with moderate to severe forms of hepatic impairment. The area under the curve (AUC) was nearly three times higher than observed in healthy individuals following a single dose of a 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.

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 primarily indicated for the treatment of advanced stages of breast cancer, specifically in postmenopausal women whose cancer has progressed even after Tamoxifen therapy.

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

2. Adjuvant Treatment:

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

• To help prevent breast cancer, 25 mg is usually taken once a day for five years.

Key Takeaways:

1. Exemestane is a hormone therapy used to treat estrogen-dependent breast cancer, mainly in postmenopausal women.

2. It is commonly started after two to three years of Tamoxifen or when cancer progresses despite Tamoxifen treatment.

3. By lowering estrogen levels in the body, exemestane helps stop the growth of hormone-sensitive breast tumors.