Apalutamide - A brief overview.

Overview

In February 2018, the non-steroidal anti-androgen (NSAA) drug was approved to be used in the treatment of prostate cancer (malignant growth in the prostate). It was first described in 2007 and has since been actively used. Apalutamide is utilized in the management of both NM-CRPC and mCSPC. It was among the first drugs to be reserved for treating NM-CRPC. Sold as tablets, Apalutamide is a medicine that can be purchased only with a prescription from a physician.

Drug Group:

It is an androgen receptor inhibitor used to treat prostate cancer. It works by blocking the action of androgens (like testosterone) that stimulate cancer growth. It is used primarily for non-metastatic castration-resistant prostate cancer (nmCRPC) or advanced prostate cancer.

Dosage:

1. For Adults: The recommended adult dose is 240 mg (four 60 mg tablets) daily once. It can be taken with our without food

2. For Pediatric Patients: Children should not take Apalutamide since there is insufficient information on its safety and effectiveness.

For Patients:

Indication: Apalutamide is indicated for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) in adult men.

Contraindication: None.

Limitations of Apalutamide: Apalutamide is approved for the treatment of both nmCRPC and metastatic castration-sensitive prostate cancer (mCSPC). So it can be used to treat metastatic diseases(cancer that has spread to other parts of the body). It should not be used in patients with severe liver disorders, as it may exacerbate liver dysfunction or interfere with the drug's metabolism, potentially leading to harmful side effects.

What Is Apalutamide and How Does It Work for Prostate Cancer?

Apalutamide is an anti-androgenic drug. It is a class of drugs that is used in hormone therapy in patients diagnosed with prostate cancer. It works by blocking or impeding the formation of androgens (hormones responsible for male sex characteristics). Hormone therapy is a type of cancer treatment that works by stopping or removing hormones, thereby inhibiting the growth of cancer cells. In the case of prostate cancer, androgen, the male sex hormone, exacerbates cancer. This form of therapy is also known as androgen deprivation therapy or ADT. This medication can affect men's fertility.

How Should Apalutamide Be Used?

Apalutamide is manufactured as tablets and is taken as a single oral dose of 240 milligrams, with or without food. Each tablet contains 60 milligrams. Instead of breaking or chewing, the tablet should be swallowed whole.

If the patient cannot swallow the tablet without crushing or chewing it, then the patient can administer the medicine in the following way:

• Take a tablet (60 milligrams, or mg) of Apalutamide, place it in a container with 120 milliliters (4 ounces) of applesauce, and allow it to dissolve without crushing it.

• Repeat the process for all four tablets (240 milligrams of Apalutamide) with a 15-minute interval between each tablet.

• Once all the tablets have been dissolved, drink the concentrate immediately.

• Pour about 60 milliliters (2 ounces) of water into the container to rinse its sides, then drink it immediately. This ensures that no medicine is left behind.

What Are the Side Effects of Apalutamide?

Patients taking Apalutamide may experience several side effects, mild and severe.

Common side effects include:

• Decreased appetite.

• Hyperlipidaemia is a high level of cholesterol in the blood.

• Hypertriglyceridemia or high triglyceride level.

• Dysgeusia (altered taste).

• Ischemic heart disease (reduced blood flow).

• Hypertension (high blood pressure).

• Skin rash.

• Blurred vision.

• Headache.

• Tachycardia (increased heart rate).

• Pruritus (itching).

• Alopecia (hair loss).

• Fractures.

• Arthralgia (joint pain).

• Diarrhea.

• Muscle spasms.

• Fatigue.

• Weight loss.

• Nausea.

• Weakness.

• Hot flushes.

Severe and less common side effects that require immediate medical attention include:

• Seizures.

• Arrhythmias, also known as irregular heartbeats, are abnormal heart rhythms.

• Chest pain, especially if sharp or shooting, may be in the shoulder, arm, jaw, or back.

• Loss of consciousness.

• Swelling of the extremities.

• Angina.

• Dyspnea (shortness of breath).

• Blistering of the skin.

• Steven-Johnson syndrome (severe skin reaction).

What Are the Things to Inform the Doctor Before Taking Apalutamide Capsules?

Inform your doctor if you have any history of heart problems, liver disease, or seizures. Also, inform them if you have diabetes, any allergies to other medications, foods, or other substances, if you are pregnant or planning to become pregnant, or if you are breastfeeding. Also, disclose if you are taking other medications, including over-the-counter (OTC) drugs, herbal supplements, or vitamins.

Overdose:

Get emergency medical attention or call a poison control center as soon as you suspect an overdose. Avoid trying to handle the matter yourself. You should take apalutamide exactly as directed by your physician and never give it to anybody else.

Missing Dose:

If you miss a dose of Apalutamide, take it as soon as you remember unless it is close to your next scheduled dose. In this case, skip the missed dose and take your next dose at the regular time. Do not double-dose to make up for a missed dose.

Drug Interactions:

Apalutamide can interact with certain medicines, including Warfarin, anti-seizure drugs such as Carbamazepine, and other medications that influence the CYP3A4 enzyme. These are only examples, not a complete list. Because of this, it is essential to tell your doctor about all the medicines you use, including your prescription drugs, over-the-counter products, herbal remedies, and vitamin supplements. You should also let your healthcare provider know if you smoke or drink alcohol, as these habits may change how apalutamide works in your body.

Storage and Disposal:

Store Apalutamide at room temperature in a dry place, away from light and moisture. Keep it out of reach of children. For disposal, follow local regulations and either place unused medication in the trash or return it to the pharmacy. Do not flush the medication down the toilet or pour it down a drain.

For Doctors:

Clinical Pharmacology:

• Chemical Name: N-[3-(4-Cyano-3-(trifluoromethyl)phenyl)-2-hydroxypropyl]-2-(4-trifluoromethylphenyl)-5-fluoro-1,2-dihydro-3H-pyrrolo[3,4-b]quinolin-3-yl]-N-(4-fluorophenyl).

• Chemical Formula: C21H17F4N3.

• Appearance: White to off-white crystalline powder.

• Inactive Ingredients: Cellulose microcrystalline, hydroxypropyl cellulose, iron oxide, magnesium stearate, polyethylene glycol, and sodium starch glycolate.

Mechanism of Action

Apalutamide expressly inhibits the androgen receptor (AR) and interacts with its ligand-binding site. By doing so, it intercepts and inhibits nuclear translocation, DNA binding, and transcription mediated by the AR. The drug increases anti-tumor drug activity by reducing cell proliferation and increasing apoptosis of cancerous cells.

Pharmacodynamics

Apalutamide inhibits the androgen receptor, blocking the effects of testosterone and other androgens on prostate cancer cells.

Pharmacokinetics

• Absorption - Peak plasma concentration is achieved after two hours of oral administration, as the oral absorption is high.

• Distribution - The mean volume of distribution following oral administration, at a steady state, is 276 L (liters). This volume exceeds the total body water, thus indicating extensive extravascular distribution.

• Metabolism - Apalutamide is metabolized to form N-desmethyl Apalutamide with the help of CYP2C8 and CYP3A4 enzymes. It is further metabolized to form inactive carboxylic metabolites.

• Elimination - Apalutamide is primarily excreted in urine as metabolites.

Apalutamide Warnings and Precautions

There are several important considerations and side effects of Apalutamide to be aware of:

• Seizures: Any use of Apalutamide ought to be accompanied by a warning; the drug is not recommended for patients who have had seizures (abnormal electrical brain activity), a brain injury, a stroke, or a brain tumor in the last year. If status epilepticus or other seizures happen during therapy, the drug should be stopped.

• Renal Impairment: It is equally important that any patient receiving the medicine should be closely monitored, especially one with a history of renal impairment.

• Liver Disease: This drug is contraindicated in patients with hepatic problems as it is primarily metabolized in the liver.

• Falls and Fractures: There is evidence that Apalutamide may increase the risk of falls and fractures; the patient’s bone health must be evaluated before treatment. It could be reduced by using bone-targeted medications.

• Cardiovascular Concerns: Apalutamide may cause life-threatening events of ischemic heart disease or ischemic cerebrovascular disorders. Any patient with a history of cardiac issues should be monitored for blood pressure, cholesterol, and blood sugar.

• Steven-Johnson Syndrome: The use of Apalutamide should be avoided in patients with this condition, an autoimmune reaction that has severe side effects and can cause skin reactions.

• Conduction disorder: Apalutamide may bring about QT interval prolongation and, as such, should be used cautiously in patients with cardiac conditions that make them prone to this ailment.

Use in Specific Populations:

• Pregnancy: Apalutamide is contraindicated during pregnancy due to potential harm to the fetus.

• Lactation: There are potential risks; the decision to use Apalutamide during lactation should be made after careful consideration of the benefits to the mother and the possible risks to the infant.

• Pediatric Population: Apalutamide is contraindicated in the pediatric population. It is not recommended for use in individuals under 18 years of age.

• Renal and Hepatic Impairment: Caution is recommended for patients with mild, moderate, or severe renal impairment. For patients with hepatic impairment, including those with mild, moderate, or severe liver dysfunction (Child-Pugh Class A, B, or C).

• Geriatric Population: Clinical studies have not precisely assessed Apalutamide's safety and efficacy in persons aged 65 years and older. However, current research indicates that older patients do not need their doses adjusted.

Clinical Studies:

Men with non-metastatic castration-resistant prostate cancer (nmCRPC) were the primary participants in apalutamide clinical trials. Treatment with apalutamide significantly increased metastasis-free survival in a phase 3 trial. Fatigue, skin rash, and elevated blood pressure were the most often reported side effects.

It is crucial to remember that the safety and effectiveness data that are now available are based on research conducted on adult male patients and do not specifically assess their use in metastatic prostate cancer or other disease situations.