Indenza — Enzalutamide 40 mg

Indenza is supplied in the form of soft gelatin capsules for oral administration. Each unit contains a fixed therapeutic dose:

• Active Compound: Enzalutamide — 40 mg per capsule.
• Excipients: Caprylocaproyl macrogolglycerides, butylhydroxyanisole, butylhydroxytoluene; soft capsule shell composition: gelatin, sorbitol sorbitan solution, glycerol, titanium dioxide, purified water, black edible ink for printing.
• Appearance: Oblong soft gelatin capsules. Provided in blister packs. The original cardboard package contains 112 capsules (4 blisters containing 28 capsules each) and a comprehensive patient information leaflet.

Pharmacodynamics: Enzalutamide is a pure androgen receptor antagonist completely devoid of any agonist activity. It reduces the proliferation and induces death of prostate cancer cells, resulting in a reduction of tumor volume. It exhibits extremely low affinity for progesterone, estrogen, or glucocorticoid receptors, which accounts for its highly selective antitumor profile.

Pharmacokinetics: Following oral administration, enzalutamide is rapidly absorbed, reaching peak serum concentrations within 1–2 hours. The pharmacokinetic profile is stable and unaffected by food intake. Plasma steady-state is achieved by day 14 of therapy. Plasma protein binding (primarily to albumin) is high, at approximately 97–98%. It is metabolized in the liver via CYP2C8 and CYP3A4 isoenzymes to form an active metabolite. Excretion occurs mainly via the kidneys as metabolites (71%) and through the intestinal tract in feces (14%).

Indenza 40 mg capsules are indicated as monotherapy or as part of combined oncological protocols for the following conditions:

• 🔹 Metastatic Castration-Resistant Prostate Cancer (mCRPC): Treatment of adult men whose disease has progressed during androgen deprivation therapy, including both patients who have previously received docetaxel chemotherapy and chemotherapy-naive individuals.
• 🔹 Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC): Therapy for adult patients at high risk of developing distant metastases, defined by a short PSA doubling time.
• 🔹 Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Treatment of adult men in combination with androgen deprivation therapy (ADT) to achieve maximal androgen blockade.

The dosing regimen, assessment of therapeutic response, and tolerability monitoring must be managed exclusively by a qualified oncologist:

• Recommended Dosage: The standard daily dose of the medication is 160 mg, taken as four 40 mg capsules together once daily.
• Method of Administration: Capsules are taken orally, once a day, at the same time each day, regardless of food intake. Capsules must be swallowed whole with clean water. Do not chew, crush, dissolve, or split the capsule shell prior to ingestion.
• Missed Dose: If a dose is missed, it should be taken as soon as possible if the next scheduled dose is more than 12 hours away. If the next dose is less than 12 hours away, the missed dose should be skipped, and the regimen resumed at the next regular time. Do not take a double dose.
• Duration of Treatment: Treatment with Indenza should be continued until clinical progression (signs of radiological or biochemical advancement) or the development of unacceptable toxicities. Patients who have not undergone surgical castration must continue medical castration with GnRH analogs throughout therapy.

The initiation and administration of Indenza capsules are strictly restricted in the presence of the following contraindications:

• ⛔ Hypersensitivity: Individual hypersensitivity or known allergy to enzalutamide or any of the excipients contained within the formulation.
• ⛔ Female Sex: Enzalutamide is not indicated for use in women; it is absolutely contraindicated in women who are pregnant or who may become pregnant due to high teratogenic risks.
• ⛔ Severe Hepatic or Renal Impairment: Safety and efficacy have not been established in patients with severe hepatic impairment (Child-Pugh Class C) or end-stage renal disease.

Enzalutamide is a strong enzyme inducer, requiring careful evaluation of concomitant medications:

• ❌ CYP2C8 Inhibitors and Inducers: Strong CYP2C8 inhibitors (e.g., gemfibrozil) can increase enzalutamide plasma exposure, requiring a dose reduction of Indenza to 80 mg once daily. Strong CYP2C8 inducers (e.g., rifampicin) may decrease its clinical efficacy.
• ❌ CYP3A4, CYP2C9, and CYP2C19 Substrates: Enzalutamide decreases the plasma concentration of drugs metabolized by these enzymes (including oral anticoagulants, statins, and calcium channel blockers), potentially lowering their therapeutic effects.
• ❌ Seizure-Threshold Lowering Drugs: Caution is warranted when co-administering enzalutamide with other medicinal products known to lower the seizure threshold (e.g., aminophylline, neuroleptics, antidepressants).

Indenza is intended strictly for male patients; however, its specific reproductive toxicity profile requires rigorous precautionary measures:

• Fetal Risks: Enzalutamide can cause fetal harm, embryotoxic effects, or spontaneous abortion when a pregnant woman is exposed to the drug.
• Male Contraception: If the patient engages in sexual activity with a pregnant woman, a condom must be used during treatment and for 3 months after stopping the medication. If the female partner is of childbearing potential, a condom must be used along with another highly effective method of contraception during and for 3 months post-therapy.
• Fertility Impact: Clinical data indicate that enzalutamide therapy may lead to a reversible or irreversible reduction in male fertility and suppression of spermatogenesis.

Antineoplastic therapy may be accompanied by adverse drug reactions that require close monitoring by your treating oncologist:

• 🟢 General Symptoms (Very Common): Severe fatigue, general weakness, asthenia, hot flushes (sudden feeling of warmth), flushing, hyperhidrosis.
• 🟡 Musculoskeletal System: Joint pain (arthralgia), muscle pain (myalgia), muscular weakness, increased risk of osteoporosis, and pathological bone fractures.
• 🟡 Cardiovascular System: Development or worsening of arterial hypertension, ischemic heart disease events.
• 🟠 Nervous System: Headache, memory impairment, cognitive disorders, anxiety; rarely (less than 1%), seizures may occur.
• ⚠️ Urgent Medical Attention: If a seizure occurs, or if the patient experiences severe persistent headache, confusion, vision loss, or a sharp sudden spike in blood pressure, discontinue the medication immediately and seek urgent emergency medical care. These symptoms can be indicative of Posterior Reversible Encephalopathy Syndrome (PRES).

Experience with acute clinical overdose of enzalutamide is very limited, as the drug is distributed and taken under close oncology supervision:

• Main Manifestations: Ingesting doses significantly above the prescribed therapeutic range is expected to cause an exacerbation of known toxicities, primarily severe fatigue, advanced cognitive impairment, and a heightened risk of generalized seizures.
• First Aid: In case of accidental ingestion of an excessive capsule quantity, immediate gastric lavage should be initiated (if the patient is conscious), followed by the administration of activated charcoal or other absorbents.
• Treatment: There is no specific antidote for enzalutamide. Supportive and symptomatic management should be implemented. Due to the long half-life of enzalutamide (more than 5 days) and its extensive plasma protein binding, forced diuresis or hemodialysis will be completely ineffective.

Adherence to specified storage criteria ensures the structural integrity and stability of the soft capsules:

• 🌡️ Temperature Regimen: Store capsules in their original packaging in a dry place at an ambient temperature not exceeding 30°C. Do not freeze.
• 📦 Environmental Protection: Keep the blisters inside the original outer cardboard carton to protect the medication from high humidity and direct ultraviolet light exposure.
• 👶 Accessibility: As a potent cytotoxic agent, this medicinal product must be stored in a highly secure area that is completely out of reach of children and domestic animals.
• ⏳ Special Instructions: Do not use the capsules after the expiration date (24 months) printed by Aprazer on the box edge and the blisters. Expired medications must be disposed of in accordance with hazardous medical waste regulations.