Elacestrant - Indications, Side Effects, Contraindications, and Precautions

Overview

Elacestrant is a highly effective cancer medicine that can treat estrogen receptor (ER)-positive, estrogen receptor 1 gene-mutated, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer that has progressed after undergoing at least one line of endocrine therapy. The biological targets of endogenous estrogens, such as estradiol, are the estrogen receptors, and Elacestrant is an antiestrogen or estrogen receptor antagonist.

Musculoskeletal pain, nausea, elevated liver enzymes, elevated triglycerides, fatigue, decreased hemoglobin, vomiting, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), decreased sodium, increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flashes, and upset stomach are among the most frequent Elacestrant side effects.

Elacestrant received US FDA (United States Food and Drug Administration) approval on January 27, 2023, and EU (European Union) approval in September 2023, bringing an important orally administered treatment for patients with metastatic ER-positive, HER2-negative breast cancer, replacing the injectable Fulvestrant treatment.

In the EU, Elacestrant is now undergoing a regulatory evaluation for the treatment of advanced or metastatic ER-positive, HER2-negative breast cancer. It has been decided to stop development of elacestrant for the treatment of vasomotor symptoms.

Is Elacestrant Chemotherapy?

No, Elacestrant is not chemotherapy. It is a targeted endocrine therapy designed to block the estrogen receptor, thereby stopping estrogen from helping HR-positive breast cancer cells to grow, which differentiates it from traditional chemotherapy drugs that attack all rapidly dividing cells.

Drug Group: Elacetrant is a member of the class of estrogen receptor antagonists.

For Patients:

Why Is Elacestrant Medication Prescribed?

Elacestrant is prescribed for adults with breast cancer that has hormone receptors. However, it is not the first-line treatment for such cases. Elacestrant is prescribed only when the illness has advanced, even after treatment with at least one or more hormone therapies. It works by blocking estrogen's ability to bind to estrogen receptors. As a result, the cancer cells, which are dependent on estrogen, as in the case of estrogen receptor (ER)-positive breast cancer, will stop growing.

How Should Elacestrant Be Used?

• Elacestrant is available as oral tablets. It is typically taken once daily with food. Take Elacestrant at approximately the same time each day.

• It is important to carefully review the details on the prescription label. You can reach out to the doctor or chemist to explain any part that you cannot understand. Pay close attention to the Elacestrant instructions. Never take it more often or in larger doses than prescribed by the physician.

• Swallow the pills whole; do not chew, break, or crush them.

• The doctor may need to change the dosage or suggest stopping Elacetrant based on its side effects in you. Any side effects one has while taking the drug should be reported to the doctor. Take the medication as directed by the doctor until they tell you otherwise.

• Ask the doctor or chemist for more details on whether this drug can be taken while the patient has other illnesses.

What Elacestrant Precautions Should I Follow?

• If you are allergic to Elacestrant, any other medications, or any of the substances in Elacestrant tablets, let your doctor and chemist know before using Elacestrant. A chemist can help you with the ingredient list if you are unable to understand from the medicine label.

• While using Elacestrant, be sure to let the doctor and pharmacist know which prescription and over-the-counter drugs, vitamins, herbal products, and nutritional supplements you are currently taking or intend to use soon. Elacestrant should not be taken with certain medications, and the doctor may need to adjust the prescription's dosage or closely monitor it for potential adverse effects.

• Inform your physician if you have high cholesterol or liver problems.

• Inform the doctor as soon as possible if one is pregnant, plans to become pregnant, or intends to father a child. It is not recommended to become pregnant while taking Elacestrant. It may be necessary to obtain a negative pregnancy test before starting this medication.

• During Elacestrant therapy and for one week after the last dosage, use a trustworthy method of birth control.

Dietary Recommendations:

Follow a balanced, healthy diet unless the doctor instructs otherwise.

Missed Dose:

If one misses a dosage, take it as soon as they recall. If more than six hours have passed since the missed dose, or if they have puked, the missed dose can be excused. Taking an extra dose to make up for the missed dose can have adverse outcomes.

What Are the Side Effects of Elacestrant?

Elacetrant might not be tolerated by some individuals. Notify the doctor straight away if any of these symptoms are severe or persist:

• Joint and muscle aches.

• Weakness or fatigue.

• Vomiting.

• Reduction in appetite.

• Diarrhea and constipation.

• Abdomen aches.

• Heartburn or indigestion with a hot flush.

Some adverse effects can be very harmful. Call the doctor right away if any of these symptoms occur:

• Black urine.

• Yellowing of the skin or eyes.

• Lower abdomen pain.

• Nausea.

• Headache.

• Exhaustion.

Other negative effects of Elacestrant may also develop in some. If a person experiences any unusual side effects while taking this medicine, contact the doctor right away.

Drug Handling and Disposal:

• Keep this medication out of children's reach and properly close the container.

• Keep it at normal temperature and away from extreme moisture and heat.

• Many of the containers (such as weekly pill minders and those for eye drops, lotions, patches, and inhalers) are easily opened by little children and are not child-resistant. Consequently, it is essential to keep all medications out of children's sight and reach. To prevent medicine poisoning, always lock safety caps and store medication up high and out of young children's reach.

• Prescriptions that are not utilized must be disposed of properly to keep animals, children, and other people from consuming them.

• However, this drug should not be flushed down the toilet. Instead, the best way to get rid of the medications is to use a medication take-back program. Speak with the city's recycling or garbage department or the pharmacist to learn about take-back initiatives in the region if a take-back program is not available to you.

What Additional Details Should One Be Aware Of?

Keep all of the appointments with the physician and the lab. To monitor the body's reaction to Elacestrant, the doctor will request specific lab tests.

No one else should take the medication. Any queries a person may have regarding prescription refills should be directed to the chemist. One should keep a written record of every medication.

For Doctors:

What Is Elacestrant?

Elacestrant is an estrogen receptor antagonist (ER). It was given FDA (Food and Drug Administration) approval in January 2023 for the treatment of advanced or metastatic breast cancer that was ER-positive, HER2-negative, and ESR1 mutant. It is basically a selective estrogen receptor degrader (SERD). Elacestrant can block the activity of estrogen receptor alpha by binding to it. That is how Elacestrant promotes the destruction of the estrogen receptor.

The use of a SERD is a therapeutic strategy for the treatment of endocrine-resistant breast cancers. Other forms of endocrine therapy, such as selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs), may eventually cause drug resistance. Unlike another SERD, Fulvestrant, Elacestrant is orally bioavailable.

Indication:

For postmenopausal women or adult men with advanced or metastatic breast cancer, Elacestrant is considered. It is generally prescribed to ER-positive, HER2-negative, and ESR1-mutant patients whose illness has advanced following at least one session of endocrine therapy.

Clinical Pharmacology

Pharmacodynamics:

Elacestrant's pharmacodynamic time course and exposure-response linkages have not yet been completely characterized. The usage of Elacestrant does not result in QTc interval increases greater than 20 msec (milliseconds) when taken at the approved recommended dose. Patients taking Elacestrant have developed hypercholesterolemia and hypertriglyceridemia, and giving this medication to pregnant women may harm the fetus. Elacestrant can cross the blood-brain barrier, unlike other selective estrogen receptor modulators and degraders.

Mechanism of Action:

Elacestrant is an oral estrogen receptor-alpha (ER-alpha) selective estrogen receptor degrader (SERD). Endocrine treatments that target the estrogen receptor (ER) are frequently utilized in the treatment of breast tumors that express ER, since these tumors rely on estrogen-mediated growth signaling. Elacestrant shows antitumor activity in vitro and in vivo in ER+ HER2-resistant breast cancer models resistant to Fulvestrant and cyclin-dependent kinase 4/6 inhibitors, as well as in cancer models harboring mutations in the estrogen receptor 1 (ESR1) gene.

Human Absorption of Estrogen Receptor Alpha Antagonist:

Elacestrant has a steady-state Cmax (maximum concentration) of 119 ng/mL (nanogram per milliliter) and an AUC0-24h of 2440 ng/h/mL (nanogram per hour per milliliter) at the recommended dosage of 345 mg (milligrams) once daily. Between 43 mg and 862 mg once a day (0.125 to 2.5 times the accepted recommended dosage). By day six, the Elacestrant achieves steady-state and has a mean accumulation ratio based on AUC0-24h that is 2-fold higher than that of. The oral bioavailability of Elacestrant is about 10%, and its tmax ranges from 1 to 4 hours. When given a high-fat meal (800 to 1000 calories, 50 percent fat), the Cmax and AUC of Elacestrant (345 mg) were 42 percent and 22 percent greater, respectively, than when given in a fasting condition.

Volume of Distribution:

The apparent volume of distribution for Elacestrant is 5800 L (liters).

Protein Binding:

Elacestrant's plasma protein binding is greater than 99% and concentration-independent.

Metabolism:

In the liver, Elacestrant is mostly metabolized by CYP3A4 (cytochrome P450 family 3 subfamily A member 4) and, to a lesser amount, by CYP2A6 (Cytochrome P450 family 2 subfamily A member 6) and CYP2C9 (Cytochrome P450 family 2 subfamily C member 9).

Route of Elimination:

The primary methods of Elacestrant elimination are feces and urine. Following a single exposure, almost 82 percent was recovered in feces (34 percent unchanged), and 7.5 percent was retrieved in urine (one percent unchanged).

Half-Life:

Elacestrant has a half-life of 30 to 50 hours.

Clearance:

The estimated renal clearance of Elacestrant is 0.14 L/hour, while the estimated total clearance is 186 L/hr.

Toxicity:

• Information about the toxicity of Elacestrant is hard to come by. Overdosing on Elacestrant increases the risk of major Elacestrant side effects, such as dyslipidemia and digestive issues, in patients. It is recommended that supportive and symptomatic care be administered. The possible carcinogenicity of Elacestrant has not been investigated. The mutagenicity and clonogenicity of Elacestrant were not demonstrated by in vitro chromosome aberration tests, in vivo rat bone marrow micronucleus assays, or the in vitro Ames assay.

• No research has been done on animal Elacestrant fertility. Rats and cynomolgus monkeys showed adverse effects in their female reproductive organs, such as uterine, vaginal, and follicular cysts in the ovary, after being given repeated doses of Elacestrant. Male rat testicular seminiferous epithelium displayed atrophy and decreased Leydig cell cellularity.

Use in Specific Populations:

• During Pregnancy: Elacestrant is not suitable for administration during pregnancy. As per the animal study reports, it can cause serious harm to the fetus. Therefore, it should never be prescribed to a pregnant person.

• During Breastfeeding: Although there is limited evidence on the excretion of Elacestrant through breast milk, it is advised to stop breastfeeding while on Elacestrant.

• Pediatric Population: Elacestrant is not for pediatric patients and should not be advised for them.

• Hepatic Impairment: For those with mild hepatic impairment, the standard Elacestrant dose can be prescribed. But for those with moderate hepatic impairment, proper dose adjustments (reduction) must be made. While Elacestrant therapy is not advisable for those with severe hepatic impairment.

• Geriatric Population: No significant differences in safety or effectiveness were observed with Elacestrant in the elderly population. The outcomes were comparable to those of the adult population.