Exemestan Actavis
Aromatase Inhibitor for Hormone-Dependent Breast Cancer
Quick Facts About Exemestan Actavis
Key Takeaways About Exemestan Actavis
- Irreversible aromatase inhibition: Unlike non-steroidal aromatase inhibitors (letrozole, anastrozole), exemestane permanently inactivates the aromatase enzyme, providing sustained oestrogen suppression even after the drug is cleared from the body
- Postmenopausal women only: Exemestane is only effective and approved for use in women who have completed menopause, as it cannot suppress ovarian oestrogen production
- Take after a meal: Absorption increases by approximately 40% when taken with food, so always take your tablet after eating
- Bone health monitoring required: Exemestane reduces oestrogen levels, which can accelerate bone mineral density loss and increase fracture risk – regular bone density assessments are recommended
- Proven survival benefit: Large clinical trials (IES, TEAM) have demonstrated that switching to exemestane after 2–3 years of tamoxifen significantly improves disease-free survival in early breast cancer
What Is Exemestan Actavis and What Is It Used For?
Exemestan Actavis is an aromatase inhibitor that works by permanently blocking the aromatase enzyme, which is essential for producing the female sex hormone oestrogen in postmenopausal women. By reducing oestrogen levels in the body, it helps treat hormone receptor-positive breast cancer, which relies on oestrogen to grow.
Exemestane, the active ingredient in Exemestan Actavis, belongs to a class of drugs known as steroidal aromatase inhibitors (also called aromatase inactivators). In postmenopausal women, the primary source of oestrogen is the conversion of androgens (male hormones produced by the adrenal glands) into oestrogens by the aromatase enzyme in peripheral tissues such as fat, muscle, and the breast itself. Exemestane is structurally related to the natural androgen androstenedione and acts as a false substrate for aromatase, binding irreversibly to the enzyme's active site and permanently destroying its activity. This mechanism is distinct from non-steroidal aromatase inhibitors like letrozole and anastrozole, which bind reversibly to the enzyme.
Clinical studies have shown that exemestane reduces circulating oestrogen levels by approximately 85–95% in postmenopausal women. This profound oestrogen suppression is critical because approximately 75% of breast cancers are hormone receptor-positive, meaning they express oestrogen receptors (ER+) and/or progesterone receptors (PR+) and depend on oestrogen signalling for their growth and proliferation.
Adjuvant Treatment of Early Breast Cancer
Exemestan Actavis is approved for the adjuvant treatment of postmenopausal women with oestrogen receptor-positive early invasive breast cancer following 2–3 years of initial tamoxifen therapy. This approach is known as sequential or switch therapy. The landmark Intergroup Exemestane Study (IES), published in the New England Journal of Medicine, demonstrated that switching to exemestane after 2–3 years of tamoxifen significantly improved disease-free survival compared with continuing tamoxifen for the full 5 years. At a median follow-up of 91 months, the hazard ratio for disease-free survival was 0.81, representing a 19% relative reduction in the risk of recurrence or death.
International guidelines from the European Society for Medical Oncology (ESMO), the American Society of Clinical Oncology (ASCO), and the National Institute for Health and Care Excellence (NICE) all support sequential endocrine therapy with an aromatase inhibitor after initial tamoxifen in postmenopausal women with HR+ early breast cancer. The total duration of endocrine therapy is typically 5 years, although some patients may benefit from extended treatment beyond this period.
Advanced Breast Cancer
Exemestan Actavis is also used for the treatment of advanced (locally advanced or metastatic) hormone receptor-positive breast cancer in postmenopausal women whose disease has progressed following anti-oestrogen therapy (typically tamoxifen). In this setting, exemestane provides a valuable second-line hormonal treatment option before considering chemotherapy. Studies have shown objective response rates of approximately 15–25% and clinical benefit rates (complete response + partial response + stable disease for at least 24 weeks) of approximately 35–45% in this population.
Exemestane was first approved by the European Medicines Agency (EMA) in 1999 and by the US Food and Drug Administration (FDA) in the same year. It has been widely used for over two decades and is available in numerous generic formulations worldwide. Exemestane is included in the World Health Organization's List of Essential Medicines, underscoring its importance in global oncology care.
What Should You Know Before Taking Exemestan Actavis?
Before starting Exemestan Actavis, your doctor will confirm that you have reached menopause through blood tests. You should inform your doctor about all medical conditions, particularly any bone health issues, liver or kidney problems, and all medications you are currently taking. Exemestane must not be used in premenopausal women or during pregnancy.
Contraindications
You should not take Exemestan Actavis if any of the following apply to you:
- Allergy to exemestane or any of the other ingredients in the tablet (listed in the composition section below) – symptoms of an allergic reaction may include skin rash, itching, swelling of the face or throat, or difficulty breathing
- Premenopausal status – if you have not yet reached menopause and are still menstruating, exemestane will not be effective and is not approved for use. Your doctor may perform blood tests to confirm menopausal status before starting treatment
- Pregnancy or breastfeeding – exemestane is classified as pregnancy category X, meaning it may cause serious harm to a developing foetus. It must not be used during pregnancy or by women who may become pregnant
Warnings and Precautions
Talk to your doctor, pharmacist, or nurse before taking Exemestan Actavis if you have or have had any of the following conditions:
- Liver or kidney problems – while no dose adjustment is usually required for mild to moderate impairment, your doctor may want to monitor you more closely. The pharmacokinetics of exemestane have not been extensively studied in patients with severe hepatic or renal impairment
- Bone health concerns – conditions such as osteoporosis or osteopenia, or a history of fractures. Aromatase inhibitors reduce oestrogen levels, which is important for maintaining bone mineral density. Your doctor may perform a bone density scan (DEXA scan) before and during treatment and may prescribe calcium and vitamin D supplements
- Low vitamin D levels – vitamin D deficiency is common in women with early-stage breast cancer, and your doctor will check your levels before starting treatment. If your levels are below normal, you will receive vitamin D supplementation
Your doctor will perform routine blood tests before and during treatment to monitor your liver function, blood cell counts, and vitamin D levels. It is important to attend all scheduled appointments and blood tests.
Pregnancy and Breastfeeding
Exemestan Actavis must not be used during pregnancy. Although exemestane is indicated exclusively for postmenopausal women, if there is any possibility that you could become pregnant, you should discuss appropriate contraception with your doctor. Animal reproductive studies have shown that exemestane can cause harm to the developing foetus, including increased resorption rates and decreased foetal body weight.
It is not known whether exemestane passes into human breast milk. However, due to the potential for serious adverse effects in nursing infants, exemestane must not be used while breastfeeding. Given that the medication is indicated for postmenopausal women, breastfeeding is unlikely to be relevant for most patients.
Driving and Operating Machinery
Exemestane can cause side effects such as drowsiness, dizziness, and fatigue, particularly during the early weeks of treatment. If you experience any of these symptoms, you should not drive or operate machinery until the symptoms have resolved. You are responsible for assessing whether you are fit to drive or perform tasks requiring alertness. Consult your doctor or pharmacist if you are unsure.
Exemestan Actavis tablets contain less than 1 mmol (23 mg) of sodium per tablet, meaning they are essentially sodium-free. This is relevant for patients on a controlled sodium diet.
How Does Exemestan Actavis Interact with Other Drugs?
Exemestan Actavis should not be taken together with oestrogen-containing hormone replacement therapy (HRT), as this would counteract its mechanism of action. Certain medications that induce the CYP3A4 liver enzyme, such as rifampicin, carbamazepine, phenytoin, and St John’s Wort, may reduce the effectiveness of exemestane by accelerating its breakdown.
Tell your doctor or pharmacist about all medications you are currently taking, have recently taken, or might take, including herbal remedies and over-the-counter medicines. Drug interactions can either reduce the effectiveness of exemestane or increase the risk of adverse effects. The following sections outline the most clinically significant interactions.
Major Interactions
The following drug interactions are considered clinically significant and require either avoidance or careful management by your healthcare team:
| Interacting Drug | Effect | Clinical Advice |
|---|---|---|
| Hormone Replacement Therapy (HRT) | Oestrogen-containing HRT directly counteracts the oestrogen-lowering effect of exemestane, potentially reducing its anticancer efficacy | Must not be used together. Discontinue HRT before starting exemestane |
| Rifampicin (antibiotic) | Potent CYP3A4 inducer; may reduce exemestane plasma levels by up to 54%, potentially decreasing efficacy | Use with caution. Inform your doctor if you are taking rifampicin for tuberculosis or other infections |
| Carbamazepine (antiepileptic) | Strong CYP3A4 inducer; may significantly reduce exemestane blood levels | Discuss alternative antiepileptic medications with your neurologist and oncologist |
| Phenytoin (antiepileptic) | CYP3A4 inducer; may reduce the blood levels and effectiveness of exemestane | Consider switching to a non-enzyme-inducing antiepileptic under medical supervision |
Minor Interactions
| Interacting Drug | Effect | Clinical Advice |
|---|---|---|
| St John’s Wort (Hypericum perforatum) | Herbal CYP3A4 inducer; may modestly reduce exemestane levels | Avoid use during exemestane therapy. Consult your doctor about alternative treatments for mood support |
| CYP3A4 inhibitors (e.g. ketoconazole, itraconazole) | May increase exemestane blood levels. However, clinical studies with ketoconazole showed no significant pharmacokinetic interaction | Generally no dose adjustment required, but inform your doctor |
| Tamoxifen | When switching from tamoxifen to exemestane (sequential therapy), there is no clinically significant pharmacokinetic interaction | Sequential use is the standard approach. Simultaneous use is not recommended |
It is important to note that exemestane is metabolised primarily by the CYP3A4 enzyme system and by aldoketoreductases. Drugs that strongly induce CYP3A4 can reduce the plasma concentrations of exemestane. While the clinical significance of modest reductions in exemestane levels is not fully established, the profound oestrogen suppression achieved with standard dosing provides a degree of safety margin.
What Is the Correct Dosage of Exemestan Actavis?
The standard dose of Exemestan Actavis is one 25 mg tablet taken once daily after a meal. This dose applies to both adjuvant treatment of early breast cancer and treatment of advanced breast cancer. Always take the tablet at approximately the same time each day.
Your oncologist will determine the appropriate treatment duration based on your individual clinical situation. It is essential to follow your doctor’s instructions exactly and not to change the dose or stop treatment without consulting them first.
Adults and Elderly
Standard Adult Dose
Take one 25 mg tablet by mouth once daily, preferably after a meal. Taking exemestane with food increases its bioavailability by approximately 40% compared with taking it on an empty stomach. Swallow the tablet whole with a glass of water. Do not crush, chew, or split the tablet.
In adjuvant treatment of early breast cancer, exemestane is started after 2–3 years of tamoxifen therapy to complete a total of 5 years of sequential endocrine therapy. Some patients may be advised to continue for a longer duration based on their risk profile.
In advanced breast cancer, treatment continues for as long as the tumour does not progress and the medication is tolerated.
No dose adjustment is required for elderly patients. Clinical trials included significant numbers of women aged 65 and older, and no differences in safety or efficacy were observed compared with younger postmenopausal women.
Children
Paediatric Use
Exemestan Actavis is not suitable for use in children. The safety and efficacy of exemestane have not been established in the paediatric population, and there is no relevant indication for its use in children.
Missed Dose
If you forget to take your daily tablet, take it as soon as you remember. However, if it is nearly time for your next dose, skip the missed dose and take your next tablet at the usual time. Do not take a double dose to make up for a forgotten dose. If you are unsure what to do, contact your doctor or pharmacist for advice.
Overdose
If you accidentally take more tablets than prescribed, or if a child accidentally ingests the medication, contact your doctor, hospital emergency department, or poison control centre immediately. Bring the medication packaging with you so that healthcare professionals can identify what was taken. In clinical studies, single doses of up to 800 mg have been tolerated without serious acute toxicity. There is no specific antidote for exemestane overdose, and treatment is supportive and symptomatic.
Even if you feel well, do not discontinue Exemestan Actavis without your oncologist’s approval. Breast cancer can recur, and continuing your prescribed course of endocrine therapy significantly reduces this risk. If you experience bothersome side effects, discuss management strategies with your healthcare team rather than stopping the medication on your own.
What Are the Side Effects of Exemestan Actavis?
Like all medicines, Exemestan Actavis can cause side effects, though not everyone gets them. Most side effects are related to oestrogen deprivation and are generally mild to moderate. The most common include hot flushes, joint and muscle pain, fatigue, headache, insomnia, and increased sweating. Serious but less common effects include liver inflammation and severe allergic reactions.
Exemestane is generally well tolerated, and the majority of adverse effects observed in clinical trials were mild or moderate in severity. Many side effects are a direct consequence of oestrogen suppression and are therefore shared with other aromatase inhibitors. The side effects listed below are organised by frequency, based on data from clinical trials and post-marketing surveillance.
Signs of severe allergic reaction (hypersensitivity), liver inflammation (hepatitis), or cholestatic hepatitis. Symptoms may include general malaise, nausea, jaundice (yellowing of the skin and eyes), itching, right-sided abdominal pain, and loss of appetite. Contact your doctor or seek emergency care immediately if you notice any of these symptoms.
Very Common
May affect more than 1 in 10 women
- Hot flushes
- Increased sweating (hyperhidrosis)
- Muscle and joint pain (including arthritis, back pain, joint stiffness, and inflammation)
- Fatigue
- Headache
- Dizziness
- Insomnia (difficulty sleeping)
- Depression
- Nausea
- Abdominal pain
- Pain (general)
- Decreased white blood cell count
- Raised liver enzymes (ALT, AST, ALP, GGT)
- Increased bilirubin breakdown products in blood
Common
May affect up to 1 in 10 women
- Loss of appetite (anorexia)
- Carpal tunnel syndrome (tingling, numbness, and pain in the hand)
- Tingling or prickling sensation in the skin (paraesthesia)
- Vomiting
- Constipation
- Indigestion (dyspepsia)
- Diarrhoea
- Hair loss (alopecia)
- Skin rash, hives (urticaria), and itching (pruritus)
- Osteoporosis (decreased bone density), which may lead to fractures
- Swollen hands and feet (peripheral oedema)
- Decreased platelet count (thrombocytopenia)
- Muscle weakness
Uncommon
May affect up to 1 in 100 women
- Hypersensitivity reactions (allergic reactions)
Rare
May affect up to 1 in 1,000 women
- Skin eruption with blisters (acute generalised exanthematous pustulosis)
- Drowsiness (somnolence)
- Hepatitis (liver inflammation)
- Cholestatic hepatitis (inflammation of the bile ducts causing jaundice)
Additional reports (frequency not determined): Low levels of certain white blood cells (leukopenia) and changes in lymphocyte and platelet counts, particularly in patients with pre-existing lymphocytopenia (low lymphocyte levels).
Managing Common Side Effects
Many side effects of exemestane can be managed effectively with supportive measures. Hot flushes may improve over time and can be managed with cooling strategies, lightweight clothing, and in some cases, prescription medications such as venlafaxine or gabapentin. Joint and muscle pain, one of the most common reasons for treatment discontinuation, can often be managed with regular exercise, physiotherapy, and analgesics such as paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs). Your oncologist may also consider switching to an alternative aromatase inhibitor if musculoskeletal symptoms are intolerable.
If you experience side effects that significantly affect your quality of life, it is important to discuss them with your healthcare team rather than stopping the medication independently. Your doctor can help balance the benefits of continued treatment against the burden of side effects and may offer strategies or alternative approaches.
How Should You Store Exemestan Actavis?
Store Exemestan Actavis at or below 25°C (77°F). Keep the tablets in their original blister packaging and out of the reach of children. Do not use the tablets after the expiry date printed on the packaging.
Proper storage of your medication ensures that it remains safe and effective throughout its shelf life. Follow these guidelines:
- Temperature: Store at no more than 25°C (77°F). Do not refrigerate or freeze the tablets
- Packaging: Keep the tablets in the original blister pack to protect them from moisture and light
- Safety: Keep this medication out of the sight and reach of children
- Expiry date: Do not use Exemestan Actavis after the expiry date (marked as EXP on the carton and blister pack). The expiry date refers to the last day of that month
- Disposal: Do not dispose of medications by flushing them down the toilet or throwing them in household waste. Return unused or expired tablets to your local pharmacy for safe disposal. These measures help protect the environment
What Does Exemestan Actavis Contain?
Each Exemestan Actavis film-coated tablet contains 25 mg of the active ingredient exemestane, along with inactive excipients that help form and stabilise the tablet. The tablets are white, round, biconvex, and smooth with even edges.
Active Ingredient
Each film-coated tablet contains 25 mg exemestane. Exemestane is a steroidal compound that irreversibly inactivates the aromatase enzyme (also known as oestrogen synthase or CYP19A1), which catalyses the final step in oestrogen biosynthesis.
Inactive Ingredients (Excipients)
The inactive ingredients in Exemestan Actavis serve various pharmaceutical purposes, such as binding, filling, coating, and ensuring proper disintegration of the tablet:
- Tablet core: Povidone K30, maize starch (bleached), pregelatinised (partially) starch, sodium starch glycolate type A, microcrystalline cellulose type 101, talc, colloidal anhydrous silica, magnesium stearate, and polysorbate 80
- Film coating: Partially hydrolysed polyvinyl alcohol, talc, macrogol 3350, and titanium dioxide (E171)
Appearance and Pack Sizes
Exemestan Actavis 25 mg film-coated tablets are white, round, biconvex, smooth tablets with even edges. They are supplied in blister packs of 10, 30, 40, 60, 84, 90, or 100 film-coated tablets. Not all pack sizes may be marketed in all countries.
Frequently Asked Questions About Exemestan Actavis
Exemestan Actavis is used to treat hormone receptor-positive breast cancer in postmenopausal women. It is most commonly prescribed as adjuvant (follow-up) therapy after 2–3 years of tamoxifen treatment for early-stage breast cancer. It is also used to treat advanced or metastatic breast cancer when other hormonal treatments, such as tamoxifen, have stopped working. Exemestane works by blocking the aromatase enzyme, reducing oestrogen levels in the body and thereby slowing or stopping the growth of hormone-sensitive tumours.
The most common side effects of exemestane (affecting more than 1 in 10 women) include hot flushes, increased sweating, joint and muscle pain (including arthritis and joint stiffness), fatigue, headache, insomnia, depression, dizziness, nausea, and abdominal pain. These are largely due to the reduction of oestrogen levels in the body. Most side effects are mild to moderate and may improve over time. If side effects are bothersome, discuss management strategies with your oncologist rather than stopping the medication.
Yes, exemestane can reduce bone mineral density because it lowers oestrogen levels, which play an important role in maintaining bone strength. This can increase the risk of developing osteoporosis and experiencing fractures. Your doctor may monitor your bone density using DEXA scans before and during treatment and may recommend calcium and vitamin D supplements, as well as regular weight-bearing exercise. If significant bone loss occurs, medications to protect bone health (such as bisphosphonates or denosumab) may be considered.
The duration of treatment depends on your individual clinical situation. In the adjuvant setting (early breast cancer), exemestane is typically taken after 2–3 years of tamoxifen to complete a total of 5 years of endocrine therapy. Some patients with higher-risk cancers may benefit from extended adjuvant therapy beyond 5 years, based on ongoing risk-benefit assessment. In the advanced breast cancer setting, treatment continues as long as the cancer does not progress and the side effects remain manageable. Never stop taking your medication without first consulting your oncologist.
Yes, you should always take Exemestan Actavis after a meal. Studies have shown that taking exemestane with food increases its absorption by approximately 40% compared with taking it on an empty stomach. This improved absorption helps ensure that you receive the full therapeutic benefit of the medication. Take your tablet at approximately the same time each day to help establish a consistent routine.
While exemestane, letrozole, and anastrozole all belong to the aromatase inhibitor class and work to reduce oestrogen levels, they differ in their chemical structure and mechanism. Exemestane is a steroidal (type I) aromatase inhibitor that permanently inactivates the aromatase enzyme, while letrozole and anastrozole are non-steroidal (type II) inhibitors that bind reversibly to the enzyme. This distinction means that exemestane may retain activity in some cases where non-steroidal aromatase inhibitors have failed. All three drugs are effective options, and the choice between them often depends on individual patient factors, prior treatment, and tolerability.
References
- Coombes RC, Kilburn LS, Snowdon CF, et al. Survival and safety of exemestane versus tamoxifen after 2-3 years' tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet. 2007;369(9561):559-570. doi:10.1016/S0140-6736(07)60200-1
- European Medicines Agency (EMA). Exemestane – Summary of Product Characteristics. Available at: ema.europa.eu
- World Health Organization. WHO Model List of Essential Medicines – 23rd List, 2023. Geneva: WHO; 2023.
- Burstein HJ, Lacchetti C, Anderson H, et al. Adjuvant Endocrine Therapy for Women With Hormone Receptor-Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update. J Clin Oncol. 2019;37(5):423-438. doi:10.1200/JCO.18.01160
- Cardoso F, Kyriakides S, Ohno S, et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30(8):1194-1220. doi:10.1093/annonc/mdz173
- National Institute for Health and Care Excellence (NICE). Early and locally advanced breast cancer: diagnosis and management [NG101]. 2018 (updated 2023).
- Santen RJ, Brodie H, Simpson ER, Siiteri PK, Brodie A. History of aromatase: saga of an important biological mediator and therapeutic target. Endocr Rev. 2009;30(4):343-375. doi:10.1210/er.2008-0016
- US Food and Drug Administration (FDA). Aromasin (exemestane) Prescribing Information. Reference ID: 4867530.
- van de Velde CJ, Rea D, Seynaeve C, et al. Adjuvant tamoxifen and exemestane in early breast cancer (TEAM): a randomised phase 3 trial. Lancet. 2011;377(9762):321-331. doi:10.1016/S0140-6736(10)62312-4
- Coleman RE, Banks LM, Girgis SI, et al. Skeletal effects of exemestane on bone-mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES). Lancet Oncol. 2007;8(2):119-127. doi:10.1016/S1470-2045(07)70003-7
Editorial Team
Written by the iMedic Medical Editorial Team – specialists in oncology, clinical pharmacology, and breast cancer treatment. All content follows international guidelines (ESMO, ASCO, NICE) and the GRADE evidence framework.
Reviewed by the iMedic Medical Review Board – an independent panel of board-certified oncologists and clinical pharmacologists who ensure accuracy, completeness, and clinical relevance of all medication information.
Conflict of interest statement: iMedic receives no commercial funding from pharmaceutical companies. All editorial content is independently produced and free from industry influence. Our full editorial standards are available at imedic.health/en/about/editorial-standards.