Xtrant — Estramustine Phosphate 140 mg Capsules, 100 Caps

X-trant is supplied as oral hard capsules. Each capsule contains the active ingredient Estramustine Phosphate equivalent to estramustine phosphate disodium in accordance with British Pharmacopoeia (BP) specifications. The capsule contents and shell incorporate pharmaceutical-grade excipients (including magnesium stearate, colloidal silicon dioxide, talc, gelatin, and approved colorants) to ensure stability and reliable drug release in the digestive tract.

The medication is packaged in original white high-density polyethylene (HDPE) bottles containing 100 capsules per bottle. The bottle neck features a sealed tamper-evident foil membrane and a child-resistant cap. A desiccant canister/sachet is placed inside to protect capsules from moisture. Each bottle, along with an official package leaflet, is enclosed in a branded cardboard box bearing a security hologram and factory-printed batch details.

Pharmacodynamics: Estramustine Phosphate acts through a dual mechanism. It selectively binds to microtubule-associated proteins (MAPs) and tubulin within prostate carcinoma cells, leading to spindle disruption during the M-phase of mitosis and subsequent cell apoptosis. Concurrently, the estrogenic metabolite suppresses the hypothalamic-pituitary-gonadal axis, reducing serum testosterone levels to castration levels and providing an additional antiandrogenic effect.

Pharmacokinetics: Following oral intake, estramustine phosphate is dephosphorylated in the gastrointestinal tract and liver into estramustine, estromustine, and estradiol. Peak plasma concentrations of active metabolites are reached within 2 to 3 hours. The drug and its metabolites are extensively bound to plasma proteins. Elimination occurs predominantly via the biliary/fecal route (approx. 80%) and to a lesser extent through renal excretion. The elimination half-life of key active metabolites ranges from 10 to 20 hours, supporting steady therapeutic levels with daily dosing.

X-trant is indicated for adult male patients for the following conditions:

• • Advanced, progressive carcinoma of the prostate;
• • Hormone-refractory (castration-resistant) metastatic prostate cancer;
• • Initial treatment of prostate cancer in patients with poor prognostic factors (as primary therapy or in combination with other cytotoxic agents).

Treatment with X-trant should be initiated and monitored under the supervision of an experienced oncologist or urologist.

• Method of Administration: Capsules should be swallowed whole with a glass of water. Capsules must not be chewed, split, or opened.
• Administration Timing & Diet: Take capsules at least 1 hour before or 2 hours after meals. Important: Do not take X-trant with milk, dairy products, or calcium/magnesium/aluminum-containing antacids, as these cations form insoluble complexes with estramustine and severely impair absorption.
• Recommended Dosage: The daily dose is calculated based on body weight, typically ranging from 7 to 14 mg per kg of body weight per day (usually 4 to 8 capsules daily) divided into 2 or 3 doses.
• Monitoring & Precautions: Regular evaluation of hepatic function, blood pressure, coagulation profiles, and glycemic control (in diabetic patients) is essential. Therapy must be discontinued immediately if severe thromboembolic events occur.

The use of X-trant is strictly contraindicated in the presence of:

• • Known hypersensitivity to estramustine, estradiol, or any inactive ingredients of the capsule;
• • Severe hepatic impairment;
• • Severe cardiovascular disease (ischemic heart disease, uncompensated cardiac failure);
• • Active thrombophlebitis or history of thromboembolic disorders (including PE and DVT) associated with estrogen therapy;
• • Use in women and pediatric patients (indicated exclusively for adult males).

• Calcium, Magnesium, Aluminum & Dairy Products: Form insoluble chelates with estramustine in the gastrointestinal tract, drastically reducing oral bioavailability. Administration of dairy or mineral-containing drugs must be separated by at least 2 hours.
• Anticoagulants: Estramustine may enhance the hypoprothrombinemic response to oral anticoagulants (e.g., warfarin), requiring close monitoring of INR levels.
• Antihypertensives & Tricyclic Antidepressants: Estrogen-induced fluid retention may decrease the efficacy of antihypertensive agents and alter the metabolism of certain psychotropic drugs.

X-trant is indicated exclusively for male patients and is strictly contraindicated in female patients, including pregnant or lactating women.

Estramustine exhibits mutagenic and genotoxic potential on spermatogenesis. Male patients undergoing treatment with X-trant must utilize effective barrier contraception during therapy and for at least 3 months following the final dose to prevent potential adverse effects on embryonic development during conception.

Treatment with X-trant may be accompanied by the following adverse drug reactions:

• • Cardiovascular System: Fluid retention/edema, elevated blood pressure, thromboembolic events, thrombophlebitis.
• • Endocrine System: Gynecomastia (breast enlargement and tenderness), decreased libido, erectile dysfunction, weight gain.
• • Gastrointestinal Tract: Nausea, vomiting (especially during initial therapy days), diarrhea, flatulence, anorexia.
• • Hepatobiliary System: Transient elevations in hepatic transaminases (ALT, AST), hyperbilirubinemia, impaired liver function.
• • Hematologic System: Rarely, anemia, leukopenia, or thrombocytopenia.
• • CNS & General: Headache, lethargy, fatigue, allergic skin reactions.

Overdose with X-trant leads to an exaggeration of its pharmacological and toxic effects, presenting as severe nausea, persistent vomiting, pronounced fluid retention/edema, and hyperestrogenic manifestations.

There is no known specific antidote for estramustine overdose. Management consists of immediate gastric lavage (if presented early) and supportive symptomatic treatment. Monitoring of liver function, coagulation parameters, and cardiovascular status for at least 2 weeks post-ingestion is recommended.

Store X-trant in its original container in a dry place protected from light at a temperature between 2 °C and 8 °C (in a refrigerator). Short-term storage below 25 °C is permissible according to manufacturer guidance, but refrigerated storage is preferred. Do not freeze. Keep out of reach of children. Shelf life is 24 months (2 years) from the manufacturing date. Do not use after the expiration date. Prescription status: Prescription only (Rx-only).

To ensure protection against counterfeit products, Natco Pharma Ltd. incorporates multiple security features on X-trant packaging:

• ✅ Two-Layer QR Code Sticker: A peel-off two-layer security sticker is placed on the box's top flap. Removing the top layer reveals a QR code and hidden verification code for authentication on the official Natco portal.
• ✅ Security Hologram: High-resolution multi-angle Natco hologram applied to the cardboard carton.
• ✅ Tamper-Evident Packaging: Bottle features an intact foil seal under the cap and a child-resistant mechanism.
• ✅ Matching Batch Details: The Batch Number, Manufacturing Date, and Expiration Date printed on the carton must fully match the details on the bottle label.