Lucisel — Selpercatinib 40 mg, 120 Capsules

Lucisel is formulated as hard gelatin capsules for oral administration. Each capsule contains a precisely controlled therapeutic dose:

• Active Ingredient: Selpercatinib — 40 mg per capsule.
• Excipients: Microcrystalline cellulose (binder and filler), colloidal anhydrous silica (disintegrant and glidant), magnesium stearate (lubricant for uniform drug release).
• Capsule Shell: Pharmaceutical grade gelatin, titanium dioxide (opacifying agent and pigment protecting active ingredients from photo-degradation).

Pharmacodynamics: Selpercatinib is a potent, ATP-competitive selective inhibitor of the RET receptor tyrosine kinase. RET receptor kinases play a pivotal role in intracellular signaling pathways that govern cell division and survival. Chromosomal rearrangements generate fusion proteins (e.g., KIF5B-RET, CCDC6-RET), whereas activating point mutations (e.g., RET M918T) yield constitutively active kinase domains, driving malignant cell transformation. Selpercatinib binds directly to the catalytic domain of RET, preventing autophosphorylation and shutting down downstream RAS/MAPK, PI3K/AKT, and STAT3 signaling cascades. This inhibits tumor cell proliferation and induces cell apoptosis. The compound exhibits potent activity against both wild-type RET and a wide spectrum of mutant RET isoforms.

Pharmacokinetics: Following oral administration, selpercatinib is rapidly absorbed from the gastrointestinal tract. Peak plasma concentration (Cmax) is achieved at a median time of 2 hours (range 1.5 to 4 hours). Absolute oral bioavailability is approximately 73%. Co-administration with a high-fat meal increases AUC (area under the plasma concentration-time curve) by only 9%, which is clinically insignificant; thus, the drug can be taken with or without food. Plasma protein binding is approximately 96%. Selpercatinib undergoes extensive hepatic metabolism, primarily mediated by the CYP3A4 isoenzyme. The elimination half-life (T1/2) is approximately 32 hours, maintaining therapeutic steady-state concentrations with twice-daily administration. Excretion occurs predominantly via feces (67%, 14% unchanged) and kidneys (24%, 11% unchanged).

Lucisel 40 mg is indicated as monotherapy for adult and pediatric patients aged 12 years and older with confirmed RET-driven malignant neoplasms following validated molecular diagnostic testing (NGS, PCR, or FISH):

• 🔹 Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC): Treatment of adult patients with RET fusion-positive NSCLC, both as first-line therapy or following prior platinum-based chemotherapy or immune checkpoint inhibitor therapy.
• 🔹 Advanced or Metastatic Medullary Thyroid Cancer (MTC): Treatment of adult and pediatric patients aged 12 years and older with RET-mutant MTC requiring systemic therapy, who have disease progression following prior therapy or where no satisfactory alternative options exist.
• 🔹 Advanced or Metastatic Thyroid Cancer (Other Histotypes): Treatment of adult and pediatric patients aged 12 years and older with RET fusion-positive thyroid cancer (papillary, follicular, or anaplastic) who are radioactive iodine-refractory (if radioactive iodine is appropriate) and whose disease has progressed.

Treatment with Lucisel should be initiated and supervised by a qualified physician experienced in the administration of targeted anticancer therapies. Capsules must be swallowed whole with water, without chewing, opening, or crushing. Administration occurs orally twice daily (approximately every 12 hours at the same times each day), with or without food.

• Recommended Dose for Body Weight Less than 50 kg: 120 mg (three 40 mg capsules) twice daily (total daily dose 240 mg).
• Recommended Dose for Body Weight 50 kg or Greater: 160 mg (four 40 mg capsules) twice daily (total daily dose 320 mg).
• Dose Reductions for Adverse Reactions: If Grade 3 or Grade 4 CTCAE toxicities develop, or in patients with severe hepatic impairment, treatment should be temporarily withheld until toxicity resolves. Dosing is then resumed at reduced levels: First reduction level — 120 mg twice daily; Second reduction level — 80 mg twice daily; Third reduction level — 40 mg twice daily. Discontinue Lucisel permanently if patients cannot tolerate 40 mg twice daily.
• Missed Dose: If a dose is missed and more than 6 hours remain before the next scheduled dose, the missed dose should be taken immediately. Otherwise, skip the missed dose and resume the normal schedule. Do not take two doses at once. If vomiting occurs after taking a dose, do not take an additional dose.

Lucisel administration is strictly contraindicated in the presence of the following medical conditions:

• ⛔ Hypersensitivity: Severe hypersensitivity to selpercatinib or any excipient present in the capsule formulation.
• ⛔ Pregnancy and Lactation: Strictly contraindicated. Selpercatinib causes severe embryo-fetal lethality, congenital malformations, and teratogenicity.
• ⛔ Age Restrictions: Pediatric patients under 12 years of age (safety and efficacy have not been established in this population).
• ⛔ Uncontrolled Severe Hypertension or QT Prolongation: Baseline QTc interval > 470 ms or severe uncorrected cardiac arrhythmias require clinical stabilization prior to therapy initiation.

Selpercatinib is extensively metabolized by CYP3A4 and serves as a substrate for P-gp and BCRP transporters, requiring careful evaluation of concomitant drugs:

• ⚠️ Strong and Moderate CYP3A4 Inducers: Co-administration with rifampin, carbamazepine, phenytoin, or St. John's wort significantly decreases selpercatinib plasma exposure (AUC reduced by >70%), leading to targeted therapy failure. Concurrent use must be avoided.
• ⚠️ Strong and Moderate CYP3A4 Inhibitors: Co-administration with ketoconazole, itraconazole, clarithromycin, or grapefruit juice increases selpercatinib plasma concentrations and elevates toxicity risks. If co-administration cannot be avoided, reduce the Lucisel dose (e.g., from 160 mg to 80 mg twice daily).
• ⚠️ Acid-Reducing Agents: Selpercatinib solubility is pH-dependent. When co-administered with proton pump inhibitors (omeprazole, esomeprazole), Lucisel must be taken with food. When combined with H2-receptor antagonists, take Lucisel 2 hours before or 10 hours after the H2-receptor antagonist. Antacids should be taken 2 hours before or 2 hours after Lucisel.
• ⚠️ QT-Prolonging Medications: Concomitant use with antiarrhythmic drugs (amiodarone, sotalol) necessitates frequent ECG monitoring and regular serum electrolyte assessments (potassium, magnesium).

The use of Lucisel during pregnancy and lactation is strictly prohibited due to direct risks of embryo-fetal toxicity:

• Females of Reproductive Potential: A negative pregnancy test must be verified prior to initiating treatment. Female patients must utilize highly effective contraceptive methods (including barrier and hormonal methods) during treatment with Lucisel and for at least 1 week after the final dose.
• Male Patients: Male patients with female partners of reproductive potential must use effective contraception during treatment and for at least 2 weeks after receiving the final dose.
• Lactation: It is unknown whether selpercatinib is excreted in human milk. Due to potential serious adverse reactions in nursing infants, breastfeeding must be discontinued during treatment and for 1 week following the last dose.

During clinical trials and real-world oncology practice, the most frequent and clinically significant adverse reactions associated with Lucisel were:

• 🔴 Hepatotoxicity and Laboratory Alterations: Elevated ALT and AST liver enzymes (may require dose hold or reduction), increased serum creatinine, elevated alkaline phosphatase, lymphopenia, hyponatremia, and hypocalcemia.
• 🟡 Cardiovascular System: Hypertension (blood pressure elevation requiring antihypertensive intervention), electrocardiogram QT interval prolongation, and rare hemorrhagic events.
• 🟠 Gastrointestinal Tract: Dry mouth (xerostomia), diarrhea, nausea, vomiting, constipation, decreased appetite, and dysgeusia (taste disturbance).
• 🟢 General and Dermatological Effects: Fatigue, asthenia, peripheral edema (swelling of legs, hands, or face), skin rash, maculopapular rash, pruritus, arthralgia, myalgia, and headache.

No specific antidote exists for selpercatinib overdose. Clinical experience with acute overdose remains limited:

• Symptoms: Accidental or intentional ingestion of doses higher than recommended leads to severe exacerbation of known toxicities: marked hypertension, severe hepatotoxicity (marked ALT/AST spikes), cardiac arrhythmias secondary to QTc prolongation, severe diarrhea, and dehydration.
• Management: In case of suspected overdose, immediately discontinue Lucisel. Institute supportive and symptomatic treatment. Conduct continuous monitoring of blood pressure, frequent ECG recordings, and regular liver function, renal function, and serum electrolyte evaluations. Due to high plasma protein binding, hemodialysis is ineffective.

Storage instructions to maintain chemical integrity and product potency:

• 🌡️ Temperature Control: Store in the original tightly sealed container in a dry, dark place protected from direct sunlight and moisture at temperatures not exceeding 25 °C.
• 👶 Safety Precautions: Keep out of reach and sight of children and pets.
• ⏳ Expiration Date: Stamped on the outer carton and bottle label. Do not use after the expiration date (Exp. Date). Unused medication must be disposed of in accordance with local medical waste regulations.

Authentic Lucisel 40 mg (120 Capsules) manufactured by Lucius Pharmaceuticals is supplied in security-protected packaging featuring multiple anti-counterfeiting measures:

• 🛡️ Holographic Security Seal with QR Code: The top flap of the outer carton is sealed with a custom iridescent holographic sticker. The seal displays a scannable QR code and an individual serial verification number (e.g., 150205) for immediate digital authentication on the manufacturer's official portal.
• 🔒 Brand Logo and Typography: The upper right corner of the box features a bright green «LUCIUS PHARMACEUTICALS» logo with a stylized flower emblem. The product name «LUCISEL» is printed in prominent gradient lettering transitioning smoothly from deep blue to green.
• 🔍 Geometric Artwork and Color Band: The lower left quadrant displays an abstract geometric design composed of overlapping blue and green triangles. A solid dark blue horizontal band extends across the box, displaying the dosage «40mg» in clear white font.
• 🔢 Product Labels and Batch Information: The bottom blue panel displays the total package count «120 Capsules». Directly beneath the brand name, mandatory descriptors «Selpercatinib Capsules» and «Rx only» (prescription drug) are present. Side panels feature embossed or crisp printed details for Batch No., Manufacturing Date (Mfg. Date), and Expiration Date (Exp. Date).