Lastet — Etoposide 50 mg Cold chain · Storage +2…+8 °C

Lastet-50 is supplied as hard gelatin capsules for oral administration. The plastic container packaging contains:

• Active Compound (per capsule): Etoposide (Etoposide IP) — 50 mg.
• Inactive Ingredients: Citric acid anhydrous, glycerin, macrogol 400, purified water.
• Capsule Shell Composition: Gelatin, titanium dioxide, purified water, and permitted colors.
• Appearance: Hard gelatin capsules filled with a homogenous paste or liquid formulation of the active ingredient. Supplied in a plastic container containing 8 capsules, enclosed in an outer cardboard carton with an official package leaflet.

Pharmacodynamics: Etoposide exerts a potent cytotoxic effect by damaging cellular DNA during active cell division phases. The drug is cell-cycle phase-specific, acting primarily in the S and G2 phases of cell development to prevent cells from entering mitosis.

Pharmacokinetics: Following oral administration of the capsules, gastrointestinal absorption averages approximately 50% (with individual variations ranging from 25% to 75%). Peak plasma concentration (Cmax) is achieved within 1 to 1.5 hours. Plasma protein binding (mainly to albumin) is high, at approximately 94–97%. Etoposide is partially metabolized in the liver to form inactive metabolites. Excretion occurs primarily through the kidneys, with about 40–50% of the administered dose excreted unchanged in urine within 48 hours. Fecal excretion accounts for 2% to 16% of the drug. The terminal elimination half-life (T1/2) in adults ranges from 4 to 11 hours.

Lastet-50 (50 mg) is indicated for use either as monotherapy or as part of established multi-agent polychemotherapy protocols for the management of the following malignancies:

• 🔹 Small Cell Lung Cancer (SCLC): Utilized in first-line and second-line combination chemotherapy regimens.
• 🔹 Germ Cell Tumors: Malignant testicular carcinomas in men and ovarian malignancies in women.
• 🔹 Hematological Malignancies: Acute myeloid leukemia (AML), Hodgkin's lymphoma, and non-Hodgkin's lymphomas.
• 🔹 Other Solid Tumors: Bladder carcinoma, neuroblastoma, and Kaposi's sarcoma when standard treatments fail.

The dosage regimen, schedule, and duration of Lastet-50 therapy must be individualized by a qualified oncologist based on the patient's clinical diagnosis, body surface area (BSA), and hematological tolerance:

• Recommended Dosage: When administered orally, the standard dose of etoposide ranges from 100 mg to 200 mg per square meter of body surface area (mg/m²) daily. The capsules are taken consecutively for 3 to 5 days, followed by a mandatory treatment-free interval of 2 to 3 weeks.
• Alternative Regimen: Some continuous low-dose protocols mandate 50 mg/m² taken daily for 21 consecutive days, followed by a 1-week rest period.
• Administration Rules: Capsules must be taken on an empty stomach or between meals, swallowed whole with a sufficient amount of water. Do not chew, open, or crush the capsules.
• Dose Adjustments: For patients with renal impairment (creatinine clearance 15–50 ml/min) or hepatic dysfunction, reduce the initial dose by 25–30%. If the white blood cell count falls below 3,000/µL or platelets drop below 100,000/µL, delay therapy until hematological recovery.

The administration of Lastet-50 capsules is strictly contraindicated in the presence of the following clinical factors:

• ⛔ Hypersensitivity: Known individual hypersensitivity or intolerance to etoposide, podophyllotoxin derivatives, or any capsule excipients.
• ⛔ Severe Bone Marrow Suppression: Severe baseline myelosuppression (absolute neutrophil count < 1,500/µL or platelet count < 75,000/µL).
• ⛔ Acute Pathologies: Severe uncontrolled acute infections (bacterial, viral, or fungal), and severe hepatic impairment.
• ⛔ Special Categories: Pregnancy, breastfeeding periods, and pediatric use (safety and efficacy of oral etoposide capsules in children have not been established).

Etoposide requires careful clinical management when administered concurrently with other pharmacological treatments:

• ❌ Concomitant Cytostatics or Radiotherapy: Concurrent administration exacerbates bone marrow suppression and gastrointestinal mucosal toxicities.
• ❌ High-Dose Cyclosporine Effect: Concomitant administration of high-dose oral cyclosporine can significantly elevate etoposide plasma exposure by inhibiting its clearance, severely increasing myelotoxicity risks.
• ❌ Interaction with Anticoagulants: Etoposide may enhance the anticoagulant effect of warfarin, necessitating frequent international normalized ratio (INR) monitoring.
• ❌ Vaccinations: Due to pronounced drug-induced immunosuppression, live virus vaccines are strictly contraindicated during chemotherapy due to the risk of vaccine-derived systemic infections.

Lastet-50 exhibits documented mutagenic, teratogenic, and embryotoxic properties, requiring strict safety parameters:

• Fetal Risk: Etoposide use is strictly contraindicated in pregnant women. Exposure can induce irreversible congenital anomalies, genetic mutations, or spontaneous miscarriage. If pregnancy occurs during treatment, discontinue therapy immediately.
• Contraceptive Measures: Both male and female patients of reproductive potential must practice highly effective barrier and hormonal contraceptive methods throughout the entire duration of therapy and for at least 6 months following the final dose.
• Lactation: Excretion into human breast milk is not fully quantified; however, because of the high risk of neonatal toxicity, breastfeeding must be discontinued before starting treatment.
• Fertility Impact: Etoposide can cause permanent infertility, leading to amenorrhea in women and azoospermia in men. Patients should seek reproductive counseling and consider sperm or oocyte cryopreservation prior to starting chemotherapy.

Systemic cytostatic treatment with etoposide frequently leads to adverse drug reactions requiring close laboratory and clinical supervision:

• 🟢 Hematological Toxicity (Very Common): Dose-limiting myelosuppression, presenting as leukopenia, neutropenia (nadir typically occurs 7–14 days post-treatment), thrombocytopenia, and anemia.
• 💡 Gastrointestinal Tract: Nausea, vomiting, anorexia, diarrhea, abdominal pain, and stomatitis (mucosal inflammation of the mouth).
• 🟡 Dermatological and General Symptoms: Reversible alopecia (hair loss), fatigue, generalized physical weakness, and asthenia.
• 🟠 Allergic Reactions: Fever, chills, tachycardia, and bronchospasm (more common with intravenous administration but possible with oral intake).
• ⚠️ Urgent Clinical Signals: If a fever exceeding 38°C develops, unexplained bleeding or bruising occurs, black tarry stools appear, or severe mouth sores develop, contact the oncologist immediately for urgent supportive medical intervention.

Exceeding the therapeutic dose range of Lastet-50 capsules results in severe, accelerated multi-system toxicities:

• Overdose Manifestations: The predominant effects include severe bone marrow failure (profound granulocytopenia and thrombocytopenia) presenting within 1–2 weeks, alongside extensive ulcerative mucositis, stomatitis, and severe unmanageable nausea. Hepatotoxicity may also develop.
• Immediate First Aid: Promptly discontinue medication administration and perform gastric lavage if the capsules were ingested recently.
• Management: There is no known specific antidote for etoposide. Treatment is supportive and symptomatic, managed in an inpatient setting. This includes colony-stimulating factors (G-CSF) for hematopoiesis, broad-spectrum prophylactic antibiotics, platelet/red blood cell transfusions, and intravenous fluid replacement. Hemodialysis is ineffective due to high protein binding.

Strict compliance with the storage instructions of Lastet-50 capsules is mandatory to preserve the drug's stability and chemical efficacy:

• 🌡️ Temperature Regimen: The capsule container must be stored in a dry environment at controlled room temperature between 15°C and 25°C. Avoid exposure to high heat and do not freeze.
• 📦 Moisture and Light Protection: Keep the capsules inside the original, tightly closed plastic bottle and within the outer cardboard box to protect the gelatin shell from humidity and ultraviolet breakdown.
• 👶 Safety Precautions: Because etoposide is a hazardous cytotoxic agent, it must be stored in a secure, locked area completely out of reach of children, pets, and unauthorized individuals.
• ⏳ Shelf Life: The shelf life is 24 months from the date of manufacture. Using the capsules past the expiration date printed on the container by Khandelwal Laboratories is strictly prohibited.