Ositag — Osimertinib 80 mg Tablets, 30 Tabs

Ositag is supplied as film-coated tablets with a precisely measured active and inactive ingredient profile:

• Presentation and Packaging: 1 original cardboard box contains blister strips holding tablets. Total count is 30 film-coated tablets (designed for a full 30-day treatment cycle). The package includes manufacturer security features and a comprehensive package insert.
• Active Ingredient:
  • Osimertinib Mesylate INN — equivalent to 80 mg of free osimertinib per tablet.
• Excipients: Mannitol, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, sodium stearyl fumarate, hypromellose, titanium dioxide, macrogol, polyvinyl alcohol, talc, black iron oxide, red iron oxide, yellow iron oxide.

Pharmacodynamics: Osimertinib is an irreversible tyrosine kinase inhibitor (TKI). It forms a covalent bond with the C797 residue in the ATP-binding pocket of the EGFR receptor. The drug selectively inhibits EGFR autophosphorylation, blocking downstream signaling cascades (RAS/RAF/MEK/ERK and PI3K/AKT/mTOR) responsible for uncontrolled tumor cell proliferation, survival, and metastasis. Osimertinib exhibits high affinity for T790M, L858R, and exon 19 deletion mutant EGFR, with minimal activity against wild-type EGFR.

Pharmacokinetics: Following oral administration, osimertinib is absorbed through the GI tract, reaching peak plasma concentration (Cmax) in approximately 6 hours (range 3–24 hours). Steady-state plasma levels are achieved after approximately 15 days of once-daily dosing. Plasma protein binding is exceptionally high (~94.7%). Metabolism occurs primarily in the liver via CYP3A4 and CYP3A5 enzymes, producing two active metabolites (AZ5104 and AZ7550). Elimination occurs predominantly via feces (68%) and to a lesser extent via urine (14%). The elimination half-life (T1/2) is approximately 48 hours.

Ositag is indicated for the treatment of adult patients with the following oncological conditions:

• 🔹 First-Line NSCLC Treatment: First-line treatment of patients with locally advanced or metastatic non-small cell lung cancer whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations.
• 🔹 Second-Line & Subsequent Lines (T790M+): Treatment of patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC whose disease has progressed on or after EGFR TKI therapy.
• 🔹 Adjuvant Therapy: Adjuvant treatment following complete tumor resection in patients with early-stage (IB–IIIA) EGFR-mutated NSCLC.
• 🔹 CNS Metastases Management: Treatment of NSCLC patients with confirmed brain metastases or leptomeningeal disease.

Administration of Ositag must be initiated and supervised by an experienced medical oncologist:

• 👨‍⚕️ Recommended Dosing:
  • The standard recommended dose is 80 mg (1 tablet) taken once daily.
• 👨‍⚕️ Duration of Treatment: Treatment should continue until disease progression or unacceptable toxicity occurs. In the adjuvant setting, treatment is recommended for up to 3 years.
• 🥤 Administration Rules: Tablets should be swallowed whole with water, with or without food, at approximately the same time every day. Do not crush, break, or chew the tablet. For patients with swallowing difficulties, the tablet can be dispersed in 50 mL of non-carbonated drinking water (without crushing), stirred until dispersed, and swallowed immediately.

The use of Ositag is strictly contraindicated in the presence of the following conditions:

• ❌ Hypersensitivity or known severe allergic reaction to osimertinib or any excipient of the tablet.
• ❌ Concomitant use with strong CYP3A4 inducers (such as St. John's Wort, rifampicin, phenytoin, carbamazepine).
• ❌ Pregnancy and the entire period of breastfeeding.
• ❌ Pediatric population under 18 years of age (safety and efficacy have not been established).
• ❌ Severe hepatic impairment or end-stage renal disease (creatinine clearance less than 15 mL/min).

When prescribing Ositag, potential pharmacokinetic interactions with concomitant medications must be evaluated:

• ⚠️ CYP3A4 Inducers: Co-administration with strong CYP3A4 inducers (rifampicin, carbamazepine, phenobarbital, St. John's wort) significantly decreases osimertinib AUC. Concomitant use is contraindicated. Moderate inducers should be avoided.
• ⚠️ CYP3A4 & P-gp Inhibitors: Strong inhibitors (ketoconazole, itraconazole, erythromycin) may slightly increase plasma concentrations of osimertinib.
• ⚠️ BCRP & P-gp Substrates: Osimertinib may increase exposure to BCRP substrates (e.g., rosuvastatin) and P-glycoprotein substrates (digoxin), requiring monitoring for substrate-related toxicities.
• ⚠️ QTc Prolonging Drugs: Caution is required when combined with antiarrhythmic agents or other drugs known to prolong the QTc interval.

The use of Ositag during pregnancy and lactation is prohibited due to serious fetal harm:

• 🤰 Embryo-Fetal Toxicity: Osimertinib causes embryo-fetal lethality and structural malformations. Female patients of reproductive potential must undergo pregnancy testing prior to initiating therapy.
• 🛡️ Contraception: Females of reproductive potential must use effective contraception during treatment and for at least 2 months after the final dose. Male patients with female partners of reproductive potential must use effective contraception for 4 months after treatment completion.
• 🤱 Lactation: It is unknown whether osimertinib is excreted in human milk. Breastfeeding is contraindicated during treatment and for 2 weeks after the last dose.

During Ositag therapy, the following adverse drug reactions may be encountered:

• 🔴 Dermatologic Reactions: Rash, pruritus, dry skin, paronychia (nail bed inflammation), alopecia.
• 🟡 Gastrointestinal Disorders: Diarrhea, nausea, stomatitis, decreased appetite, abdominal pain.
• 🟠 Hematologic Abnormalities: Lymphopenia, thrombocytopenia, neutropenia, anemia.
• 🟢 Respiratory Disorders: Interstitial lung disease (ILD) / pneumonitis (requires immediate permanent discontinuation if confirmed).
• 🟣 Cardiovascular Effects: Electrocardiogram QTc interval prolongation, reduction in left ventricular ejection fraction (LVEF).

Clinical manifestations and management in case of accidental ingestion of excessive doses:

• Symptoms: Doses up to 240 mg daily in clinical trials did not reveal specific dose-limiting toxicities, but an increased frequency and severity of standard adverse reactions (diarrhea, skin rash) may occur.
• Therapeutic Measures: There is no specific antidote for osimertinib overdose. In case of overdose, discontinue Ositag, initiate symptomatic and supportive treatment, perform ECG monitoring, and closely monitor vital functions.

Rules for storage and transport of Ositag:

• Temperature Range: Store in a dry place at a temperature not exceeding 30 °C.
• Environmental Protection: Keep in the original packaging to protect from moisture and direct sunlight.
• Safety: Keep out of reach of children and unauthorized personnel.
• Shelf Life: 3 years (36 months) from the manufacturing date. Do not use after the expiration date printed on the carton and blister foil.

Criteria for verifying the authenticity of Ositag manufactured by Beacon Pharmaceuticals:

• Packaging & Typography: The carton box is made of high-quality white cardboard. The name Ositag and dosage 80 mg are printed with sharp, high-precision lettering. The front panel features the stylized lung logo.
• Factory Markings: The side panel displays laser/inkjet printed batch data: Batch Number (BATCH), Manufacturing Date (MFG), Expiry Date (EXP), and Maximum Retail Price (IP/PRICE).
• Blister Foil: Blister strips are made of durable aluminum foil clearly printed with the Ositag 80mg logo, Beacon branding, and batch details along the edge. The box displays the official company name Beacon Pharmaceuticals Limited.