Bicalutamide - Indications, Uses, Adverse Effects, Drug Interactions, and Clinical Pharmacology

Overview

Bicalutamide is a medicine used mainly to treat advanced (metastatic) prostate cancer. It is often given along with other hormone treatments such as Leuprolide or Goserelin (gonadotropin-releasing hormone). This medicine works by blocking the action of male hormones like testosterone, which prostate cancer cells need to grow. By stopping these hormones from working, Bicalutamide helps slow down or stop the growth and spread of cancer cells. It is available as a tablet for oral administration and is used alongside LHRH (luteinizing hormone-releasing hormone) analogs. Bicalutamide was approved by the FDA (Food and Drug Administration) on December 19, 2008.

Drug Group

Bicalutamide is categorized as a non-steroidal antiandrogen. It works by inhibiting the effects of androgens, including male hormones such as testosterone, in the body. While it does not cure prostate cancer, it effectively controls its progression.

Indications

• Bicalutamide 50 mg is used for stage D2 metastatic carcinoma of the prostate. This is an advanced-stage prostate cancer that spreads beyond the confines of the prostate gland and can reach other areas of the body, such as the bones and lymph nodes. It has been associated with poor prognosis and would require aggressive therapy to control it. It can be administered concurrently with LHRH analogs, including Leuprolide and Goserelin.

• It can also be used as monotherapy (150 mg) for stage 3 prostate cancer (locally advanced). However, further research is needed.

Dosage Forms and Available Strengths

Bicalutamide is available in 50 mg (milligrams) tablets for oral administration.

For Patients

How Does Bicalutamide Work For Metastatic Prostate Cancer?

Bicalutamide blocks androgens, especially testosterone. Prostate cancer cells need testosterone to grow. By stopping testosterone from reaching cancer cells, Bicalutamide slows down the disease. It may even shrink tumors.

What Are the Clinical Uses of Bicalutamide?

Bicalutamide uses are:

Bicalutamide is used alongside LHRH analogs to treat advanced prostate cancer. It is typically prescribed for metastatic prostate cancer. The goal is to block testosterone from reaching and fueling cancer cells.

What Is the Dosage of Bicalutamide?

The recommended dosage is 50 mg daily. It is essential to start Bicalutamide treatment at the same time as the LHRH analog.

How Is Bicalutamide Administered?

Bicalutamide is administered orally, taken orally with or without food. It should be taken at the same time every day. It is typically taken as a 50 mg tablet once daily, in combination with LHRH analogs.

What Are the Side Effects of Bicalutamide?

Bicalutamide side effects are:

• Hot flashes or flushing.

• Bone, back, or pelvic pain.

• Muscle weakness.

• Muscle or joint pain.

• Headache.

• Shortness of breath.

• Increased blood pressure.

• Swelling of the hands, feet, ankles, or lower legs.

• Cough.

• Constipation.

• Nausea.

• Vomiting.

• Abdominal pain.

• Diarrhea.

• Gas.

• Weight change (loss or gain).

• Loss of appetite.

• Dizziness.

• Pain, burning, or tingling in the hands or feet.

• Difficulty sleeping.

• A feeling of uneasiness or dread.

• Rash.

• Sweating.

• Inability to get or keep an erection.

• Need to urinate frequently during the night.

• Bloody urine.

• Painful or difficult urination.

• Frequent and urgent need to urinate.

• Difficulty emptying the bladder.

• Painful or swollen breasts.

Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:

• Yellowing of the skin or eyes (jaundice).

• Pain in the upper right part of the stomach.

• Extreme tiredness.

• Unusual bleeding or bruising.

• Lack of energy.

• Upset stomach.

• Loss of appetite.

• Flu-like symptoms.

• Dull or sharp side pain.

• Chest pain.

What Are the Things to Inform the Doctor Before Taking Bicalutamide?

Patients should inform their doctor if they have:

• A history of liver problems or hepatitis (inflammation of the liver).

• Inform the doctor if you are taking anticoagulants (such as Coumadin) or have a history of bleeding.

• Have diabetes (high blood sugar levels) or prediabetes (precursor to diabetes).

Dietary Considerations

No specific dietary restrictions are mentioned, but it is important to maintain a balanced diet and monitor blood glucose levels during treatment.

Missed Dose

If a dose is missed, take the next planned dose at its usual time. Do not double the dose to make up for a missed dose.

Overdose

There have been no reports of life-threatening effects from a single dose of up to 200 mg. Treatment of an overdose is symptomatic. Inducing vomiting may be helpful in conscious patients, but dialysis is not suitable since Bicalutamide is highly protein-bound.

Storage and Handling

Store Bicalutamide at room temperature between 20°C and 25°C (68°F to 77°F), away from moisture and light. Store this medication in its original container, tightly closed and out of reach of children. Keep it at room temperature, away from heat and moisture (not in the bathroom). Medications should be stored out of the reach and sight of children since most containers are not child-resistant. Safety caps should always be locked, and the medication should be placed in a safe location.

Disposal:

Please throw away unused medicines safely. This helps protect children and pets from accidentally taking them. Don’t flush medication down the toilet. The best option is to use a medicine take-back program. You can also ask your pharmacist or local waste service how to dispose of them safely.

For extra guidance, you can check the FDA’s website on the safe disposal of medicines.

For Doctors

Chemical Taxonomy

Bicalutamide is a non-steroidal antiandrogen with the chemical structure:

Propanamide, N [4 cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methyl-,(+−).

Molecular Weight: 430.37 g/mol.

What Are the Pharmacological Actions of Bicalutamide?

Mechanism of Action:

Bicalutamide is a selective androgen receptor antagonist. Testosterone and other androgens bind to androgen receptors on prostate cancer cells. This activates the cells, causing them to grow and divide. Bicalutamide attaches to these same receptors first. It blocks testosterone and other androgens from binding. This disrupts the pathways cancer cells use to grow and survive. With these pathways blocked, tumor activity decreases. Bicalutamide works exceptionally well when combined with other therapies, such as LHRH agonists. Together, they are more effective at treating prostate cancer.

Pharmacodynamics:

Bicalutamide is a hormone-based medicine used to treat prostate cancer. It works by blocking the effects of male hormones, which prostate cancer cells need to grow. The drug binds to androgen receptors and stops hormones produced by the testes and adrenal glands from acting on prostate tissue, including cancer cells. Because most prostate cancers depend on these hormones, bicalutamide is usually given along with other treatments that lower androgen levels, since it is less effective when used alone.

Pharmacokinetics:

Bicalutamide is a selective androgen receptor antagonist. The effects of testosterone and other androgens are mediated by binding to androgen receptors on prostate cancer cells, activating them, and stimulating cell division and growth. Bicalutamide acts by binding to these androgen receptors, thereby preventing testosterone and other androgens from binding.

This inhibits signaling pathways that are usually involved in the growth and survival of prostate cancer cells, thereby reducing tumor activity. Therefore, Bicalutamide is an effective agent for the treatment of prostate cancer, mainly when used in combination with other therapies such as luteinizing hormone-releasing hormone agonists.

Toxicity:

Animal studies showed that Bicalutamide can cause liver damage and changes in liver enzyme levels. Male rats also showed reproductive organ changes, including altered testicular development. These effects happened at doses much higher than what humans take. They have not been seen in human clinical trials at normal therapeutic doses. In humans, Bicalutamide's side effects are generally manageable. Liver function tests are recommended during long-term use, especially for patients with existing liver problems. Reproductive organ issues observed in animals are not a concern for people taking standard doses.

Warnings and Precautions

• Hepatitis: Cases of hospitalization and death have been reported during post-marketing due to the use of Bicalutamide. The reason for the serious instances was a severe liver injury or hepatic failure. Hepatotoxicity was noted within the first three to four months of the start of treatment. In controlled clinical trials, hepatitis or an elevation of the liver enzymes led to the discontinuation of drug use in approximately one percent of patients on Bicalutamide. If signs of liver problems appear, such as nausea, vomiting, stomach pain, loss of appetite, fatigue, dark urine, jaundice, tenderness in the upper right abdomen, or flu-like symptoms, liver enzymes should be checked immediately. The primary test is for serum ALT (alanine transaminase) levels. Liver function should be tested before starting Bicalutamide. Then check regularly during the first four months of treatment. After that, continue periodic testing throughout the treatment phase. The use of Bicalutamide should be stopped immediately in cases where the patients present with symptoms of jaundice or in whom the ALT levels have doubled when compared to the normal upper limit. Also, close follow-up of liver function is recommended.

• Hemorrhage With a Consequent Use of Coumarin Anticoagulant: Cases of elevated prothrombin time (PT) and International Normalized Ratio (INR) days to weeks after introducing Bicalutamide have been used in patients who had previously been stable on coumarin anticoagulant therapy. Patients have reported severe bleeding, including intracranial, retroperitoneal, and gastrointestinal bleeding. They required a blood transfusion or Vitamin K administration. It is advised that PT and INR be closely monitored and that the anticoagulant dose be adjusted as needed.

• Gynecomastia and Breast pain: Clinical trials on Bicalutamide 150 mg, which was used as a single therapy for prostate cancer, showed that there were gynecomastia and breast pain in 38 percent and 39 percent of patients, respectively.

• Glucose Tolerance: Reduced glucose tolerance was noted in patients receiving LHRH agonists. This leads to the development of diabetes or a loss of glycemic control in people with prediabetes. Glucose monitoring is therefore necessary for patients receiving Bicalutamide and LHRH agonists.

• Laboratory Tests: Regular testing of serum prostate-specific antigen (PSA) is required to monitor for rising PSA levels. If, during treatment, the PSA levels rise along with the clinical progression of the disease, it is recommended to go on a treatment-free period while continuing only the LHRH analog.

• Somnolence: Patients should be cautious when driving or operating machinery.

• Photosensitivity: Limit sun exposure and use sunscreen.

What Are the Contraindications of Bicalutamide?

• Hypersensitivity to Bicalutamide or its ingredients: Do not use Bicalutamide if there is a known allergy to it or any of its ingredients. Allergic reactions can include rash, itching, swelling, severe dizziness, or trouble breathing. If an allergic reaction happens, stop taking Bicalutamide right away and get medical help.

• Use in Females: Bicalutamide is not meant to be used by women. Its effects in females have not been well studied, and it can disrupt normal hormone balance by blocking the action of male hormones. Because of this, it may be harmful, especially for women who are pregnant or may become pregnant. For these reasons, Bicalutamide should not be used in females.

• Use During Pregnancy: Bicalutamide should not be taken during pregnancy because it may harm the unborn baby. Studies in animals have shown that exposure to this medicine during pregnancy can affect normal development, particularly of male reproductive organs. Although similar studies in humans are limited, the potential risk is serious. Therefore, Bicalutamide is not recommended during pregnancy.

What Are the Drug Interactions of Bicalutamide?

• CYP3A4 Inhibition: Bicalutamide can slow down the activity of the CYP3A4 enzyme, which helps the body break down many medicines. Because of this, drugs such as Midazolam may stay in the body longer and have stronger effects. Extra caution is needed when these medicines are used together.

• Coumarin Anticoagulants: Bicalutamide can increase the risk of bleeding, requiring close monitoring of PT and INR.

Clinical Studies

Bicalutamide has been studied in combination with LHRH analogs in prostate cancer patients, showing efficacy in slowing disease progression. However, 150 mg doses of Bicalutamide are not recommended for certain cancer stages due to an increased risk of mortality.

Use in Specific Populations

Pregnancy: Bicalutamide is not intended for use in females and is contraindicated during pregnancy due to the potential for fetal harm. Animal studies conducted on rats showed that male rats treated with Bicalutamide had abnormal development of the reproductive organs. These rats received doses ranging from 0.7 to 2 times the maximum recommended human dose.

Lactation: There is insufficient data available regarding the presence of Bicalutamide in human breast milk, its effect on milk production, or its potential adverse effects on a breastfed infant. However, traces of Bicalutamide have been detected in rats' milk.

Males of Reproductive Potential: Evidence suggests that antiandrogen therapy, such as Bicalutamide, can affect sperm morphology. Based on animal studies, it is recommended that female partners of male patients use effective contraception during treatment with Bicalutamide and for 130 days after the final dose. The long-term side effects of Bicalutamide on male fertility have not been investigated. However, animal studies have shown that Bicalutamide inhibits spermatogenesis, potentially affecting male fertility.

Pediatric Use: The safety and efficacy of Bicalutamide in pediatric patients have not been investigated.

Geriatric Use: In studies involving patients receiving 50 mg or 150 mg of Bicalutamide, there was no significant correlation between age and steady-state total Bicalutamide levels.

Hepatic Impairment: Bicalutamide is metabolized only by the liver. Use caution in patients with mild to moderate liver impairment; the drug may take longer to leave the body and could build up over time. For long-term treatment, liver function tests should be done regularly in patients with liver problems. The drug behaves similarly in patients with mild to moderate liver impairment compared to those with normal liver function.

Renal Impairment: There is no significant impact on the elimination of Bicalutamide due to creatinine clearance changes in patients with renal impairment.