Enzalutamide is a medication used in the treatment of prostate cancer. It belongs to a class of drugs known as androgen receptor inhibitors. Enzalutamide works by blocking the effects of androgens (male hormones), such as testosterone, on prostate cancer cells.
Prostate cancer is often dependent on androgens for growth and progression. Enzalutamide helps to inhibit the binding of androgens to the androgen receptors in the prostate cancer cells, thereby reducing their growth and spread.
Enzalutamide is typically prescribed for patients with metastatic castration-resistant prostate cancer (mCRPC). It may be used as a standalone treatment or in combination with other therapies.
Enzalutamide (Xtandi) Uses:
- Prostate cancer:
- It is used for castration resistant Prostatic carcinoma.
Enzalutamide (Xtandi) Dose in Adults
Note: If you are taking enzalutamide for prostate cancer, it is recommended that you also receive a medication called a gonadotropin-releasing hormone analog or have undergone a surgical procedure called bilateral orchiectomy. These additional treatments help to lower the levels of male hormones in your body, which can further improve the effectiveness of enzalutamide in treating your cancer.
Enzalutamide (Xtandi) Dose in the treatment of Prostate cancer, castration-resistant:
- When using enzalutamide to treat castration-resistant prostate cancer, the recommended dose is 160 mg taken orally once a day.
- This information is based on medical studies and expert recommendations.
Dosage adjustment for concomitant strong CYP2C8 inhibitors:
- If you need to take a medication that is a strong inhibitor of CYP2C8 enzyme while also taking Enzalutamide, it's best to avoid taking them together if possible.
- However, if co-administration is necessary, the Enzalutamide dose should be reduced to 80 mg taken orally once a day.
- This is because CYP2C8 inhibitors can increase the concentration of Enzalutamide in the body, leading to potentially harmful side effects.
- If you stop taking the strong CYP2C8 inhibitor, the Enzalutamide dose can be adjusted back up to the dose you were taking before starting the inhibitor.
Dosage adjustment for concomitant strong CYP3A4 inducers:
- If you are taking a strong CYP3A4 inducer alongside Enzalutamide, it is generally recommended to avoid using them together if possible.
- However, if you need to take them concurrently, the Enzalutamide dose should be increased to 240 mg taken orally once a day.
- This is because CYP3A4 inducers can decrease the concentration of Enzalutamide in the body, which may reduce its effectiveness.
- If you stop taking the strong CYP3A4 inducer, the Enzalutamide dose should be adjusted back to the dose you were taking before starting the inducer.
Use in Children:
Not indicated.
Pregnancy Risk Category: X
- Enzalutamide should not be used by females.
- Studies on animals and the way enzalutamide works suggest that it can cause harm to unborn babies and lead to pregnancy loss.
- If you are a male patient with a female partner who could become pregnant, it's important to use effective contraception during enzalutamide treatment and for three months after the last dose.
- Females who are pregnant or may become pregnant should avoid handling enzalutamide.
- Additionally, enzalutamide may affect sperm production and male fertility.
Use of Enzalutamide while breastfeeding
- It is not known whether enzalutamide is found in breast milk.
- However, it's important to note that enzalutamide is not recommended for use in females.
Enzalutamide (Xtandi) Dose in Kidney disease:
- If your baseline creatinine clearance (CrCl) is between 30 to 89 mL/minute, no initial dosage adjustment is typically required when starting enzalutamide.
- If your baseline CrCl is less than 30 mL/minute or if you have end-stage renal disease (ESRD) at baseline, there are no specific dosage adjustments provided in the manufacturer's labeling for enzalutamide. This means that the effect of enzalutamide in patients with these kidney function conditions has not been extensively studied, and specific dosage recommendations have not been established.
Enzalutamide (Xtandi) Dose in Liver disease:
- If patient had already liver impairment, such as mild, moderate, or severe impairment (known as Child-Pugh class A, B, or C), no initial dosage adjustment is typically required when starting enzalutamide. This means that the standard recommended dosage can be used in individuals with liver impairment.
Common Side Effects of Enzalutamide (Xtandi):
- Cardiovascular:
- Peripheral Edema
- Hypertension
- Central Nervous System:
- Fatigue
- Falling
- Dizziness
- Headache
- Endocrine & Metabolic:
- Hypoglycemia
- Hypomagnesemia
- Hot Flash
- Hyponatremia
- Weight Loss
- Gastrointestinal:
- Constipation
- Diarrhea
- Decreased Appetite
- Nausea
- Hematologic & Oncologic:
- Neutropenia
- Neuromuscular & Skeletal:
- Asthenia
- Back Pain
- Arthralgia
- Musculoskeletal Pain
- Respiratory:
- Upper Respiratory Tract Infection
- Dyspnea
Less Common Side Effects Of Enzalutamide (Xtandi):
- Cardiovascular:
- Ischemic Heart Disease
- Central Nervous System:
- Myasthenia
- Insomnia
- Paresthesia
- Cauda Equina Syndrome
- Spinal Cord Compression
- Anxiety
- Altered Mental Status
- Cognitive Dysfunction
- Hypoesthesia
- Restless Leg Syndrome
- Dermatologic:
- Pruritus
- Xeroderma
- Endocrine & Metabolic:
- Gynecomastia
- Gastrointestinal:
- Dysgeusia
- Genitourinary:
- Hematuria
- Pollakiuria
- Neuromuscular & Skeletal:
- Bone Fracture
- Stiffness
- Respiratory:
- Lower Respiratory Tract Infection
- Epistaxis
Contraindication to Enzalutamide (Xtandi):
- In the manufacturer's US labelling for enzalutamide, no specific contraindications are listed.
- In the Canadian labelling, enzalutamide is contraindicated in individuals who have hypersensitivity to enzalutamide or any component of the formulation. Additionally, enzalutamide is contraindicated in women who are pregnant, may become pregnant, or are lactating.
Warnings and precautions
Cardiovascular effects
- Enzalutamide may increase the risk of ischemic heart disease, including severe events that can be fatal.
- Androgen-deprivation therapy, like enzalutamide, may also increase the risk of cardiovascular disease.
- Enzalutamide has been shown to increase both systolic and diastolic blood pressures, which can worsen pre-existing hypertension.
- Therefore, it's essential to monitor for signs and symptoms of ischemic heart disease and manage cardiovascular risk factors such as hypertension, diabetes, and/or dyslipidemia.
- If you experience grade 3 or 4 ischemic heart disease, enzalutamide should be discontinued.
- It's crucial to consult with your healthcare provider, who can help you manage these risks and determine the most appropriate treatment plan for you.
Fractures
- Patients who receive enzalutamide are at a higher risk of experiencing falls and fractures.
- The incidence of falls and fractures is higher in patients who receive enzalutamide compared to those who receive a placebo, and grades 3/4 fractures have occurred.
- It takes a median time of 337 days for fracture onset (range: 2 days to approximately 3 years).
- It's essential to evaluate fall and fracture risk, monitor it, and manage it according to established treatment guidelines.
- Bone density routine assessment and osteoporosis treatment with bone-modifying agents were not performed in studies.
- Therefore, it's advisable to consider the use of bone-modifying agents to manage fracture risk.
- It's important to consult with your healthcare provider, who can help you manage these risks and determine the most appropriate treatment plan for you.
Hypersensitivity
- Some patients may experience hypersensitivity reactions while taking enzalutamide.
- These reactions can manifest as swelling of the face, tongue, or lips, and pharyngeal edema (swelling in the throat).
- If you notice any symptoms of hypersensitivity, it's important to temporarily stop taking enzalutamide and seek immediate medical attention.
- In cases of serious hypersensitivity reactions, enzalutamide should be permanently discontinued.
- It's crucial to inform your healthcare provider if you experience any signs of hypersensitivity while taking enzalutamide.
- They can provide guidance on appropriate management and determine the best course of action for your treatment.
The posterior reversible syndrome of encephalopathy:
- Enzalutamide has been associated with a neurological disorder called posterior reversible encephalopathy syndrome (PRES).
- Patients who develop PRES may experience symptoms such as headache, seizure, lethargy, confusion, blindness, and other visual or neurological disturbances.
- Some patients may also have high blood pressure.
- PRES can be diagnosed with magnetic resonance imaging (MRI).
- If a patient develops PRES, enzalutamide should be discontinued.
Seizures
- Enzalutamide may cause seizures, which can occur between 13 days and 20 months after starting treatment.
- Patients who have factors that increase the risk of seizures may be more likely to experience them.
- In clinical trials, 2.2% of patients with risk factors experienced a seizure while taking enzalutamide.
- If a patient experiences a seizure while taking enzalutamide, the medication should be stopped permanently.
- It is not known if antiepileptic medications can prevent enzalutamide-related seizures.
- Patients should be advised of the risk of seizures and to avoid activities that could be dangerous if they experience sudden loss of consciousness.
Enzalutamide: Drug Interaction
Enzalutamide is a moderate inducer of CYP2C9 and a strong inducer of CYP3A4
Note: Drug Interaction Categories:
- Risk Factor C: Monitor When Using Combination
- Risk Factor D: Consider Treatment Modification
- Risk Factor X: Avoid Concomitant Use
Drug Interactions Category C Drugs: Need to monitor the combination treatment:
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Enzalutamide lowers the blood levels of these drugs |
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Enzalutamide increases the blood levels of these drugs |
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These drugs lower the plasma levels of Enzalutamide |
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These drugs raise the plasma levels of Enzalutamide |
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Enzalutamide may diminish the therapeutic effect of these drugs |
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Drug Interactions Category D Drugs
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Risk Category D: Enzalutamide lowers the blood levels of these drugs |
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Enzalutamide increases the blood levels of these drugs |
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Drug Interactions: Risk Category X Drugs (Avoid these combinations)
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Enzalutamide lowers the blood levels of these drugs |
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Enzalutamide reduces the diagnostic efficacy of these drugs |
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Monitoring parameters:
To ensure the safe and effective use of Enzalutamide, several monitoring measures should be implemented. Here are the key areas to monitor:
Blood Tests:
- Complete Blood Count (CBC) with differential: This test helps assess blood cell levels and detect any abnormalities.
- Liver Function Tests: These tests evaluate the functioning of the liver and check for any liver-related issues.
- International Normalized Ratio (INR) Monitoring (if on warfarin): If you are taking warfarin, regular INR monitoring is necessary to ensure proper blood clotting.
Blood Pressure:
- Baseline Measurement: Initial blood pressure measurement is important to establish a reference point.
- Periodic Monitoring: Regularly check and monitor blood pressure levels throughout the treatment period.
Specific Symptom Monitoring:
- Signs/Symptoms of Ischemic Heart Disease: Keep an eye out for any symptoms associated with ischemic heart disease, such as chest pain or shortness of breath. Report them to your healthcare provider.
- Posterior Reversible Encephalopathy Syndrome (PRES): Be aware of symptoms like severe headaches, seizures, confusion, or vision disturbances. If any of these occur, seek medical attention promptly.
- Seizure: Pay attention to seizure-related symptoms, including convulsions or loss of consciousness. Contact your healthcare provider immediately if you experience a seizure.
Fall and Fracture Risk Evaluation:
- Regularly assess the risk of falls and fractures.
- Consider implementing preventive measures, such as modifying the environment to reduce fall hazards or improving bone health through appropriate interventions.
Adherence Monitoring:
- Ensure that you are taking Enzalutamide as prescribed by your healthcare provider.
- Discuss any challenges or concerns you may have regarding adherence with your healthcare provider.
How to administer Enzalutamide (Xtandi)?
To properly administer Enzalutamide, follow these instructions:
- Timing: Take Enzalutamide at the same time every day to maintain a consistent dosage schedule.
- Food: You can take Enzalutamide with or without food. It is not necessary to adjust your meals when taking the medication.
- Swallow Whole: Take the capsules by swallowing them whole. Do not chew, dissolve, or open the capsules before ingestion. This ensures the medication is released properly in your body.
By adhering to these guidelines, you can ensure the appropriate administration of Enzalutamide and maximize its effectiveness.
Mechanism of action of Enzalutamide (Xtandi):
- Enzalutamide is a type of medication called a pure androgen receptor signaling inhibitor.
- Unlike some other antiandrogen therapies, it does not have any known agonistic properties.
- Enzalutamide works by inhibiting the translocation of androgen receptors to the nucleus of cells, preventing them from binding to DNA and recruiting coactivators.
- This disruption of the androgen receptor signaling pathway leads to cellular apoptosis (programmed cell death) and a reduction in the volume of prostate tumors.
- By blocking the actions of androgens, enzalutamide helps to control the growth and spread of prostate cancer.
Absorption:
- Enzalutamide is quickly absorbed into the body after oral administration.
Distribution:
- It is distributed widely throughout the body, with a volume of distribution of approximately 110 liters.
Protein Binding:
- Enzalutamide binds strongly to plasma proteins, particularly albumin. About 97% to 98% of the parent drug and 95% of the active metabolite are bound to plasma proteins.
Metabolism:
- The primary pathway of metabolism for enzalutamide is in the liver, where it is metabolized by enzymes called CYP2C8 and CYP3A4.
- These enzymes are responsible for the formation of the active metabolite called N-desmethyl enzalutamide.
- Another enzyme called carboxylesterase 1 further metabolizes N-desmethyl enzalutamide and enzalutamide itself into an inactive carboxylic acid metabolite.
Half-Life:
- The elimination half-life of the parent drug is approximately 5.8 days, with a range of 2.8 to 10.2 days.
- The active metabolite, N-desmethyl enzalutamide, has a longer elimination half-life ranging from 7.8 to 8.6 days.
Time to Peak:
- Enzalutamide reaches its peak concentration in the blood within approximately 1 hour after administration, with a range of 0.5 to 3 hours.
Excretion:
- The majority of enzalutamide and its metabolites are eliminated from the body through the urine (71%).
- A smaller portion is excreted in the feces (14%).
- The metabolites are primarily inactive.
International Brand Names of Enzalutamide:
- Xtandi
- Xtandi SC
Enzalutamide Brand Names in Pakistan:
Not available.
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