Izervay
Izervay
Generic Name
Izervay
Mechanism
Izervay exerts its antineoplastic effects through two complementary pathways:
• TSHR Antagonism – Blockade of TSHR on thyroid cancer cells inhibits the cAMP‑mediated signaling cascade, reducing proliferation and inducing apoptosis.
• Anti‑angiogenic Kinase Inhibition – At nanomolar potency, Izervay inhibits VEGFR‑2, PDGFR‑β, and c‑Kit, curtailing new vessel formation and delivering tumor necrosis.
The dual action results in a synergistic blockade of thyroid‐cancer cell survival and their tumor microenvironment.
Pharmacokinetics
| Parameter | Value | Comments |
| Absorption | Oral, rapid; Tmax 1–2 h | High bioavailability (>80 %) with food. |
| Distribution | Volume of distribution 250 L; protein binding 72 % | Extensive tissue penetration, including hepatic and renal tissues. |
| Metabolism | Primarily CYP3A4-mediated oxidative N‑dealkylation; minor CYP2C19 pathway | Concomitant CYP3A4 inhibitors dramatically increase plasma levels. |
| Elimination | Renal (45 %) and fecal (35 %) | Elimination half‑life 18–24 h; steady state reached in 4–5 days. |
| Drug‑Drug Interactions | Strong interactions with strong CYP3A4 inhibitors (e.g., ketoconazole) and inducers (e.g., rifampin). | Adjust dose or avoid concomitant therapy. |
Indications
- Persistent or metastatic differentiated thyroid carcinoma refractory to radioactive iodine therapy.
- Use as monotherapy or in combination with external beam radiotherapy for improved local control.
Contraindications
- Contraindications
- Hypersensitivity to any component of Izervay.
- Concomitant use with strong CYP3A4 inhibitors.
- Warnings
- Hepatotoxicity – Monitor transaminases every 4 weeks.
- Hypertension – Pre‑existing uncontrolled hypertension is a risk.
- Bleeding – Antiplatelet use may increase bleeding risk.
- QT prolongation – Check baseline ECG; avoid when QTc > 450 ms.
Dosing
- Initial dose: 50 mg once daily by mouth, preferably in the morning, with or without food.
- Dose adjustment: Reduce to 25 mg if serum transaminases > 2× ULN or significant renal impairment (CrCl 30–49 mL/min).
- Duration: Treat for a minimum of 6 months, evaluating response by imaging and thyroglobulin levels.
> Key point: Steady‑state levels are achieved after 5‑7 days; dose titration should be guided by tolerability and pharmacodynamic markers.
Adverse Effects
Common (≥ 10 %)
• Fatigue, headache, nausea, diarrhea, hypertension, dry mouth.
Serious (≤ 2 %)
• Elevated liver enzymes (≥ 3× ULN); hepatotoxicity.
• Severe hypertension (> 180/110 mmHg).
• Bleeding events (e.g., GI hemorrhage).
• QT prolongation > 50 ms.
> Action: Report any signs of liver dysfunction or significant QTc changes immediately.
Monitoring
- Liver Function Tests (LFTs) – baseline, at weeks 4, 8, then monthly.
- Blood Pressure – baseline, then weekly for the first month, then monthly.
- Complete Blood Count (CBC) – baseline, then every 2–4 weeks.
- ECG – baseline, at 8 weeks if QTc > 440 ms, thereafter every 3 months.
- Thyroglobulin – baseline, then every 3 months to assess response.
Clinical Pearls
- TSHR blockade alone rarely halts tumor growth; pairing with anti‑angiogenesis amplifies efficacy—hence Izervay’s dual target design.
- Food effect: While bioavailability is high with food, take with a light snack to minimize nausea.
- Drug‑drug interaction alert: Patients on ketoconazole or voriconazole require dose adjustment; those on rifampin should avoid Izervay.
- Renal dosing: Izervay is renal‑excreted; crCl < 30 mL/min requires clinical judgment; consider clinical trial inclusion.
- Patient education: Emphasize routine blood pressure checks and prompt reporting of visual disturbances or bruising.
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• Izervay provides a mechanistically targeted approach for patients with advanced differentiated thyroid carcinoma, combining TSHR antagonism with potent anti‑angiogenic activity to improve control and survival outcomes.