Lucivos — Ivosidenib 250 mg Tablets, 60 Tablets

Lucivos 250 mg is supplied as film-coated tablets for oral administration. The tablets feature a protective film coating that guards the active substance against environmental degradation.

Qualitative and Quantitative Composition per Tablet:

• • Active Ingredient: Ivosidenib — 250 mg.
• • Tablet Core Excipients: Microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, hypromellose, colloidal silicon dioxide.
• • Film Coating Excipients: Hypromellose, titanium dioxide, lactose monohydrate, triacetin, colorants.

Packaging Configuration: 250 mg tablets are supplied as 60 pieces per HDPE bottle equipped with a child-resistant cap and desiccant, or in blister packs. The box contains exactly 60 tablets, corresponding to a 30-day supply of standard continuous daily therapy (2 tablets once daily). The bottle is enclosed in an official Lucius Pharmaceuticals carton featuring a security hologram and prescribing insert.

Pharmacodynamics and Molecular Action:
Ivosidenib is an oral, small-molecule inhibitor targeting the mutant isocitrate dehydrogenase-1 (IDH1) enzyme. Mutant IDH1 (primarily R132 mutations) acquires a neomorphic activity, catalyzing the reduction of alpha-ketoglutarate to the oncometabolite R-2-hydroxyglutarate (2-HG).

High concentrations of 2-HG induce global DNA and histone hypermethylation, arresting cellular differentiation. Ivosidenib inhibits mutant IDH1 at much lower concentrations than wild-type IDH1. Inhibition reduces intracellular 2-HG levels, promoting differentiation of leukemic blasts in AML and suppressing proliferation in IDH1-mutated cholangiocarcinoma cells.

Pharmacokinetics:

• • Absorption: Rapidly absorbed following oral administration. Peak plasma concentration ($T_{max}$) is reached within 2 to 4 hours. High-fat meals increase ivosidenib exposure ($C_{max}$ by ~1.5-fold, AUC by ~1.25-fold).
• • Distribution: Extensively bound to human plasma proteins (92% to 96%). Apparent volume of distribution at steady state is approximately 234 L.
• • Metabolism: Extensively metabolized in the liver mainly via CYP3A4-mediated oxidation and glucuronidation pathways.
• • Elimination: Terminal elimination half-life ($T_{1/2}$) is approximately 72–129 hours at steady state. Approximately 77% is excreted in feces (mostly unchanged) and 17% in urine.

Lucivos 250 mg is indicated for:

• • Acute Myeloid Leukemia (AML): Treatment of adult patients with relapsed or refractory AML with a susceptible IDH1 R132 mutation.
• • Newly Diagnosed AML: As monotherapy or in combination with azacitidine for newly diagnosed AML in adult patients aged ≥75 years or who have comorbidities precluding intensive induction chemotherapy.
• • Cholangiocarcinoma: Treatment of adult patients with previously treated, locally advanced or metastatic cholangiocarcinoma with an IDH1 R132 mutation.

Treatment with Lucivos 250 mg must be initiated and supervised by a physician experienced in the administration of antineoplastic agents.

Method of Administration:
For oral use. Swallow tablets whole with a glass of water at approximately the same time every day. Do not chew, crush, or split the tablets. Avoid taking the medication with a high-fat meal to prevent erratic systemic exposure.

Standard Dosing Regimen:

• • Recommended Dose: 500 mg (two 250 mg tablets) once daily continuously.
• • Treatment Duration: Continued until disease progression or unacceptable toxicity. For AML, treatment is recommended for at least 6 months to allow adequate time for clinical response.

Missed Dose or Vomiting Instructions:

• • If a dose is missed by more than 12 hours: Take the missed dose (2 tablets) as soon as remembered.
• • If less than 12 hours remain before the next scheduled dose: Skip the missed dose and resume the regular dosing schedule.
• • If vomiting occurs after taking a dose: Do not take an additional dose; take the next dose as scheduled the following day.

Dose Modifications: In cases of QTc prolongation (>500 ms) or severe Differentiation Syndrome, treatment interruption or dose reduction to 250 mg (1 tablet) daily may be required as directed by the oncologist.

Administration of Lucivos 250 mg is strictly contraindicated in:

• • Hypersensitivity: Known hypersensitivity to ivosidenib or any inactive ingredient in the tablet formulation.
• • Congenital Long QT Syndrome: Baseline severe QTc prolongation or high risk for torsades de pointes.
• • Pregnancy and Lactation: Contraindicated during pregnancy and breastfeeding.
• • Pediatric Population: Safety and efficacy in children and adolescents under 18 years of age have not been established.
• • Severe Renal/Hepatic Impairment: Limited safety data available.

Ivosidenib is a substrate and inducer of CYP3A4, necessitating careful evaluation of concurrent drug regimens.

Key Drug Interactions:

• • Strong CYP3A4 Inhibitors: Co-administration with strong CYP3A4 inhibitors (ketoconazole, itraconazole, voriconazole, clarithromycin) increases ivosidenib exposure. Reduce Lucivos dose to 250 mg once daily if co-administration is unavoidable.
• • Strong CYP3A4 Inducers: Co-administration with strong CYP3A4 inducers (rifampin, carbamazepine, St. John's Wort) significantly decreases ivosidenib concentration. Avoid concurrent use.
• • QTc Prolonging Drugs: Concomitant use with drugs known to prolong the QTc interval (amiodarone, sotalol, fluoroquinolones) increases arrhythmia risk. Regular ECG monitoring is required.
• • CYP3A4 & P-gp Substrates: Ivosidenib induces CYP3A4, which may decrease concentrations of hormonal contraceptives. Non-hormonal barrier contraception is required.

Pregnancy:
Lucivos is contraindicated during pregnancy due to potential embryo-fetal harm. Females of reproductive potential must undergo pregnancy testing prior to initiating treatment and use effective non-hormonal contraception during therapy and for at least 1 month after the final dose.

Male patients with female partners of reproductive potential must use effective contraception during treatment and for 1 month following the last dose.

Lactation:
It is unknown whether ivosidenib is excreted in human milk. Due to potential adverse reactions in nursing infants, breastfeeding must be discontinued during treatment and for at least 1 month after the final dose.

Lucivos 250 mg can cause significant adverse reactions requiring diligent clinical monitoring.

Key Adverse Reactions:

• • Differentiation Syndrome: A serious, potentially fatal condition characterized by fever, dyspnea, hypoxia, pulmonary infiltrates, pleural/pericardial effusion, rapid weight gain, and peripheral edema. Requires immediate systemic corticosteroid therapy (dexamethasone 10 mg IV b.i.d.).
• • Cardiovascular Disorders: Electrocardiogram QTc interval prolongation, atrial fibrillation, hypotension.
• • Hematologic & Laboratory Abnormalities: Anemia, neutropenia, thrombocytopenia, leukocytosis, hyperbilirubinemia, elevated ALT/AST, hypophosphatemia, hypokalemia.
• • Gastrointestinal Disorders: Nausea, diarrhea, vomiting, constipation, abdominal pain, mucositis, decreased appetite.
• • General Disorders: Fatigue, asthenia, peripheral edema, headache, arthralgia, rash.

Symptoms:
Doses exceeding recommended levels may exacerbate systemic toxicities, causing marked QTc prolongation, severe gastrointestinal distress, and heightened risk of Differentiation Syndrome.

Treatment:
There is no specific antidote for ivosidenib overdose. Treatment consists of immediate drug discontinuation, gastric lavage (if early after ingestion), administration of activated charcoal, continuous ECG monitoring, and supportive care.

Storage Requirements for Lucivos 250 mg:

• 🌡️ Temperature: Store below 30°C in a dry place. Do not freeze.
• ☀️ Light & Moisture Protection: Store in original container, tightly closed, to protect from moisture and light.
• 👶 Safety: Keep out of reach of children.
• ⏳ Shelf Life: 24 months from manufacturing date. Do not use past expiration date. Dispensing status: Prescription only (Rx-only).

To safeguard patients against counterfeit products, Lucius Pharmaceuticals integrates security measures into Lucivos 250 mg packaging:

• ✅ Security Hologram: Top carton flap features a proprietary security hologram label with the "LUCIUS" brand logo and a scratch-off QR verification code.
• ✅ Brand Identification: Distinct "LUCIUS PHARMACEUTICALS" wordmark paired with the corporate crystal logo.
• ✅ Packaging Design: Bold dark-font "LUCIVOS" product title with registered trademark ®, hexagonal molecular graphic patterns, and a green base bar stating "60 Tablets".
• ✅ Batch Identification: Clearly printed Lot No., Mfg Date, and Exp Date stamped on the side panel.