Elacestrant - Indications, Side Effects, Contraindications, and Precautions

Overview

Elacestrant is an estrogen receptor antagonist used to treat ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer that has progressed after undergoing at least one line of endocrine therapy.

The biological targets of endogenous estrogens like 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 ALT, increased AST, decreased sodium, increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flashes, and upset stomach are among the most frequent side effects of Elacestrant.

For Patients:

Why Is Elacestrant Recommended?

Adults with certain types of hormone receptor-positive breast cancer (breast cancer that depends on hormones like estrogen to proliferate) are prescribed Elacestat when the illness has advanced after treatment with at least one more hormone therapy. Elacetrant is a member of the class of medications referred to as estrogen receptor antagonists. It works by blocking the ability of estrogen to bind, which stops the growth of cancer cells that are dependent on estrogen.

How Is Elacestrant to Be Taken?

• Oral tablets containing Elacestrant are available. It is typically taken once daily with food. Take Elacestrant at approximately the same time each day. While carefully following the directions on the prescription label, ask the doctor or chemist to explain any part that the patient does not understand. Pay close attention to the Elacestrant instructions. Never take it more often or in bigger 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 that one-stop taking Elacetrant is based on possible side effects. 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 one otherwise.

• Ask the doctor or chemist for more details if this drug can be taken when the patient is having other illnesses.

What Specific Safety Measures Should One Take?

• If a person has an allergy to Elacestrant, any other medications, or any of the substances in Elacestrant tablets, let the doctor and chemist know before using Elacestrant. Request a list of the ingredients from the chemist. While using Elacestrant, be sure to let the doctor and chemist know what prescription and over-the-counter drugs, vitamins, herbal items, and nutritional supplements one is currently taking or intend to use. Elacestrant should not be taken with certain medications, and the doctor may need to change the prescription's dosage or closely monitor it for any adverse effects.

• Inform the physician if the person has high cholesterol or liver problems.

• Notify the physician if the person is or intends to become pregnant.

• 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 using Elacestrant and for one week after the last dosage, use a trustworthy method of birth control. Utilize a reliable form of birth control during therapy and for a week after the final dose.

Dietary Recommendations:

Follow a normal and balanced 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, skip the dose and resume the regular schedule with the next dose. Do not take an extra dose to make up for the missed dose.

What Negative Effects Might Elacetrant Have?

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

1. Joint and muscle aches.

2. Weakness or fatigue.

3. Vomiting.

4. Reduction in appetite.

5. Diarrhea constipation.

6. Abdomen ache.

7. 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 occur. If a person experiences any strange issues while taking this medicine, contact the doctor right away.

Drug Handling And Disposal:

• Keep this medication out of children's reach and properly closed in its original container. Keep it at normal temperature and away from extreme moisture and heat.

• Because so 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 disposed of in the toilet. Instead, the best way to get rid of the medications is to use a medication take-back program. Speak with the chemist or give me a call. Speak with the city's recycling/garbage department or the pharmacist to learn about take-back initiatives in the region. if a take-back program is not available to one.

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?

A tiny non-steroidal chemical called 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. As a selective estrogen receptor degrader (SERD), Elacestrant binds to the estrogen receptor-alpha (ER-alpha) and inhibits its transcriptional activity, promoting the ER's destruction.

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

Indication:

For postmenopausal women or adult men with advanced or metastatic breast cancer, an Elacestrant medication is administered. 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 (millisecond) 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 pass through the blood-brain barrier, in contrast to 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 an antitumor effect 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 with mutations in the Oestrogen receptor 1 gene (ESR1).

Human Absorption of Estrogen Receptor Alpha antagonist

Elacestrant has a steady-state Cmax of 119 ng/mL and an AUC0-24h of 2440 ng/h/mL 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, Elacestrant achieves steady-state and has a mean accumulation ratio based on AUC0-24h that is 2-fold higher than that. The oral bioavailability of Elacestrant is about 10 %, and its tmax ranges from one to four hours. When given a high-fat meal (800 to –1000 calories, 50 % fat), the Cmax and AUC of Elacestrant (345 mg) were 42 % and 22 % greater, respectively, than when given in a fasting condition.

Volume of Distribution:

The apparent volume of distribution for Elacestrant is 5800 L.

Protein Binding:

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

Metabolism:

In the liver, Elacestrant is mostly metabolized by CYP3A4 and to a lesser amount by CYP2A6 and CYP2C9.

Route of Elimination:

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

Half-Life:

Elacestrant has a half-life of 30 to 50 hours before it leaves the body.

Clearance:

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

Adverse Reactions:

• Boost decision-making and research outputs.

• Blackbox warnings, adverse reactions, warnings and precautions, and incidence rates are only a few examples of structured adverse effects data.

Toxicity:

• Information about the toxicity of Elacestrant is hard to come by. Overdosing on medicine increases the risk of major side effects such as dyslipidemia and digestive issues in patients. It is recommended to administer supportive and symptomatic care. 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.

• There has never been any research 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.

Conclusion:

For the treatment of estrogen receptor (ER) positive, human epidermal growth factor receptor 2 (HER2) negative breast cancer, Elacestrant, an oral selective estrogen receptor degrader (SERD), is prescribed. Elacestrant first received approval in January 2023 for the treatment of postmenopausal women or adult men with advanced or metastatic breast cancer that is ER-positive, HER2-negative, and estrogen receptor 1 (ESR1)-mutated (as determined by a US FDA-approved test) with disease progression after the first line of endocrine therapy in the USA. 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 developing an Elacestrant for the treatment of vasomotor symptoms.