Torinat 10 — Everolimus 10 mg Tablets, 28 Tablets

Torinat 10 is supplied as tablets containing 10 mg of everolimus.

Qualitative and Quantitative Composition per Tablet:

• Active Ingredient: Everolimus — 10 mg.
• Excipients: Anhydrous lactose, crospovidone, hypromellose, butylated hydroxytoluene, magnesium stearate.

Packaging and Presentation: White to slightly yellowish, round, flat-faced beveled-edge tablets with debossing. 7 tablets per aluminum blister strip. 4 blister strips (total 28 tablets) are packaged in an outer carton displaying Torinat 10 (Everolimus Tablets) along with Natco Pharma corporate graphics and official prescribing information.

Pharmacodynamics:
Everolimus is an inhibitor of mammalian target of rapamycin (mTOR). mTOR is a key serine/threonine kinase whose activity is upregulated in many tumors. Inhibition of mTOR by everolimus prevents protein translation and transcription by reducing the activity of ribosomal protein S6 kinase (S6K1) and eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). This leads to cell cycle arrest, decreased cell proliferation, apoptosis, and reduced angiogenesis.

Pharmacokinetics:

• Absorption: Following oral administration, peak plasma concentrations ($C_{max}$) are reached within 1 to 2 hours. Bioavailability is high with moderate-fat meals, though food affects the rate and extent of absorption (consistent administration with or without food is recommended).
• Distribution: Plasma protein binding is approximately 74% (primarily albumin). Volume of distribution is large.
• Metabolism: Metabolized in the liver primarily via the cytochrome P450 isoenzyme CYP3A4 and serves as a substrate for P-glycoprotein (P-gp).
• Elimination: Excreted predominantly via feces (~80%) as metabolites and renally (~5%). Terminal elimination half-life ($T_{1/2}$) averages approximately 30 hours.

Torinat 10 is indicated in adult patients for:

• Advanced Renal Cell Carcinoma: Treatment of patients with advanced renal cell carcinoma following failure of prior VEGF-receptor tyrosine kinase inhibitor therapy (sunitinib or sorafenib).
• Neuroendocrine Tumors: Treatment of unresectable or metastatic neuroendocrine tumors of gastrointestinal, lung, or pancreatic origin with progressive disease.
• Hormone-Dependent Breast Cancer: Treatment of advanced hormone-positive HER2-negative breast cancer in combination with exemestane in postmenopausal women following prior non-steroidal aromatase inhibitor therapy.
• Renal Angiomyolipoma: Associated with tuberous sclerosis complex not requiring immediate surgery.

Torinat 10 is administered orally once daily at the same time each day (in the morning) with a glass of water.

Administration Instructions:
Tablets must be swallowed whole without chewing, crushing, or dividing. Take consistently either always with food (low-fat) or always on an empty stomach.

Dosing Regimen:
The standard therapeutic daily dose for oncology indications is 10 mg once daily. Dose interruptions or reductions may be required to manage toxicity.

Administration of Torinat 10 is contraindicated in:

• Hypersensitivity: Known hypersensitivity to everolimus, other rapamycin derivatives (sirolimus, temsirolimus), or any excipient.
• Severe Hepatic Impairment: Child-Pugh Class C.
• Pregnancy and Lactation: Strictly contraindicated in pregnant or breastfeeding women.
• Pediatric Population: The 10 mg strength is not intended for pediatric use (except under strict specialized indications).

Everolimus is metabolized via CYP3A4 and is a P-gp substrate:

• Strong CYP3A4 and P-gp Inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice): Significantly increase everolimus blood concentrations. Concomitant use should be avoided.
• Strong CYP3A4 Inducers (rifampicin, carbamazepine, phenobarbital, St. John's wort): Significantly decrease everolimus concentrations, reducing efficacy. Concomitant use should be avoided.

Pregnancy:
Torinat 10 is contraindicated during pregnancy due to embryo-fetal toxicity and teratogenic risks. Women of childbearing potential must use effective contraception during treatment and for 8 weeks post-therapy.

Lactation:
Excretion into human breast milk is unknown. Breastfeeding is strictly prohibited during treatment.

The most frequent and clinically significant adverse reactions associated with everolimus include:

• Stomatitis and Oral Ulceration (Very Common): Inflammation of the oral mucosa requiring proper hygiene and rinses.
• Infections: Increased risk of bacterial, fungal, and viral infections, including pneumonia.
• Respiratory System: Non-infectious pneumonitis (interstitial lung disease), cough, dyspnea.
• Gastrointestinal Tract: Diarrhea, nausea, vomiting, abdominal pain, decreased appetite.
• Hematologic Toxicity: Anemia, leukopenia, thrombocytopenia, neutropenia.
• Metabolic Disorders: Hyperglycemia, hypercholesterolemia, hypertriglyceridemia, elevated serum creatinine and liver enzymes.
• Skin & Appendages: Rash, dry skin, pruritus, acne, stomatitis.

Symptoms:
Clinical experience with everolimus overdose in humans is limited. Single doses up to 70 mg showed toxicity profiles consistent with known adverse events (stomatitis, rash, fatigue, laboratory abnormalities).

Treatment:
No specific antidote exists. Supportive and symptomatic management should be administered under close medical supervision.

Storage Requirements for Torinat 10:

• 🌡️ Temperature Range: Store protected from light at temperatures below 25–30 °C.
• 💧 Moisture Protection: Keep in original blister packaging to protect tablets from moisture.
• 👶 Safety Precautions: Keep strictly out of reach of children.
• ⏳ Shelf Life: Stated on carton and blisters. Do not use past expiration date. Prescription-only hospital medicine.

To verify the authenticity of genuine Torinat 10 manufactured by Natco Pharma, inspect the following features:

• ✅ Corporate Logo: Distinctive blue-green Natco Pharma corporate logo printed on the outer carton and blister foil.
• ✅ Packaging Markings: Clear factory printing displaying Batch No., Mfg. Date, Exp. Date, and product designation Torinat 10 (Everolimus Tablets).
• ✅ Blister Quantity: Standard box contains exactly 4 blister strips of 7 tablets each (total 28 tablets).
• ✅ Print Quality: High-grade packaging artwork without color fading or typography errors.