Ematra — Tretinoin 100 Soft Gelatin Capsules

Ematra is manufactured in the form of soft gelatin capsules for oral use, containing a strictly calibrated dose of components:

• Active Compound: Tretinoin (all-trans retinoic acid) — 10 mg in each capsule.
• Excipients: Beeswax, soybean oil, partially hydrogenated soybean oil (components of the oil core); gelatin, glycerin, titanium dioxide, colorants (components of the capsule shell).
• Appearance: Oval soft gelatin capsules, contained in a plastic bottle containing 100 capsules, packed in an original cardboard box.

Pharmacodynamics: Tretinoin is a retinoid that induces cell differentiation. By binding to nuclear RAR receptors, it cleaves the abnormal chimeric PML-RARa protein characteristic of APL, restoring the transcription of genes responsible for the normal maturation of myeloid progenitor cells.

Pharmacokinetics: Following oral administration, tretinoin is well absorbed in the GI tract. Peak plasma concentrations are reached in approximately 90–120 minutes. Plasma protein binding (predominantly to albumin) is greater than 95%. It is metabolized in the liver by cytochrome P450 isoenzymes. The elimination half-life is about 30–120 minutes, excreted via kidneys and feces.

Ematra is used strictly as prescribed by a specialized professional (oncohematologist or oncologist) for the therapy of the following conditions:

• 🔹 Acute Promyelocytic Leukemia (APL): Induction of remission in patients with previously untreated disease course, as well as in patients with relapses or resistance to standard chemotherapy (including anthracyclines).
• 🔹 Combination Therapy: Used in conjunction with standard chemotherapy regimens or arsenic trioxide to maximize therapeutic response and prevent relapses.

Dose calculation and monitoring of therapy are carried out by medical personnel in a specialized hospital setting. Alteration of treatment regimens without an oncologist is strictly prohibited:

• Recommended Dosage: The standard daily dose is calculated based on body surface area and is 45 milligrams per square meter (45 mg/m2) per day.
• Method of Administration: Capsules are taken orally whole during or immediately after meals, swallowed with a sufficient amount of water. Capsules must not be chewed or divided.
• Dosing Regimen: The total daily dose is divided into two absolutely equal administrations at equal intervals (morning and evening). For children, the standard dose is similar but may be adjusted upon toxicity.
• Duration of Treatment: Therapy is continued for 30–90 days until complete molecular-genetic remission is achieved, or up to a maximum of 30 days after achieving hematological remission.

The use of Ematra capsules is strictly prohibited in the presence of the following contraindications or physiological conditions:

• ⛔ Hypersensitivity: Individual intolerance to tretinoin, other retinoids, soy, peanuts, or any excipient component.
• ⛔ Pregnancy and Lactation: The drug possesses extremely high teratogenic toxicity, causing severe fetal developmental defects; breastfeeding must be discontinued.
• ⛔ Combination with Vitamin A: Concomitant intake of vitamin A or other systemic retinoids (due to the risk of developing severe hypervitaminosis).
• ⛔ Combination with Tetracyclines: Concomitant use with tetracycline-class antibiotics (causes a risk of developing benign intracranial hypertension).

Tretinoin undergoes intensive metabolism in the liver, requiring careful monitoring when concomitantly administering other medications:

• ❌ Tetracyclines: Concomitant intake increases intracranial pressure, causing severe headaches, papilledema, and nausea.
• ❌ Antifibrinolytic Agents: Drugs such as aminocaproic or tranexamic acid, when co-administered, increase the risk of developing dangerous thrombotic complications.
• ⚠️ CYP450 Inducers and Inhibitors: Rifampicin, glucocorticoids, and phenobarbital lower tretinoin concentrations, whereas ketoconazole, cimetidine, and erythromycin increase them, enhancing toxicity.

The drug possesses pronounced genotoxic and teratogenic actions, potentially hazardous to the reproductive system:

• Risks to the Fetus: The use of tretinoin causes severe, life-incompatible developmental defects of the fetal skull, CNS, heart, and skeleton. Pregnancy is an absolute contraindication.
• Contraception for Women: Female patients of childbearing potential must use two independent effective methods of contraception for at least 1 month prior to starting therapy, during treatment, and for 1 month following its completion.
• Testing: A double negative pregnancy test is mandatory prior to initiating therapy, which is then repeated monthly during treatment.

Therapy with Ematra is associated with a risk of developing systemic adverse reactions requiring timely management by the treating medical staff:

• 🟢 APL Differentiation Syndrome (Extremely Dangerous): Characterized by fever, dyspnea, fluid retention, pleural effusion, edema, and requires immediate administration of high-dose dexamethasone.
• 🟡 Dermatological Reactions (Very Common): Marked dryness of skin and mucous membranes, cheilitis (cracked lips), peeling, pruritus, dry mouth, and dry nose.
• 🟡 Central Nervous System: Severe headache, benign intracranial hypertension, dizziness, increased anxiety, insomnia.
• 🟠 Laboratory Parameters: Hypercholesterolemia, hypertriglyceridemia, transient increase in liver transaminase activity (ALT, AST).
• ⚠️ Urgent Medical Attention: Upon first occurrence of dyspnea, unexplained cough, severe headache not relieved by analgesics, or chest pain, a doctor must be called immediately.

Exceeding the calculated dosages of tretinoin poses a direct threat to health and is characterized by manifestations of acute hypervitaminosis A:

• Main Manifestations: Acute overdose leads to the development of severe headache, vomiting, pronounced skin peeling, facial flushing, abdominal pain, and marked dizziness.
• First Aid: Immediate discontinuation of the drug, performing gastric lavage (if capsules were ingested recently).
• Treatment: No specific antidote exists. Symptomatic and supportive therapy is provided in a hospital setting with mandatory monitoring of liver functions and intracranial pressure.

Adherence to the regulated storage conditions of the capsules guarantees the preservation of its chemical stability:

• 🌡️ Temperature Regimen: Store in the original tightly closed bottle in a dry, light-protected place at a temperature strictly not exceeding 30°C. Do not expose to heat.
• 📦 Environmental Protection: The bottle is sensitive to light and moisture, so it must always be kept tightly sealed and inside the factory cardboard pack.
• 👶 Accessibility: The medicinal product must be stored in a secure, locked cabinet, completely excluding access by children or pets.
• ⏳ Special Instructions: Do not use the medication after the expiration date printed on the pack. Any unused capsules must be disposed of in accordance with dangerous medical waste regulations.