What Is Lapatinib (Tykerb)? FDA Approval, Licensing in Turkey, and Reimbursement
In this article
Tykerb (Lapatinib) is a small-molecule tyrosine kinase inhibitor that blocks both the HER2 and EGFR pathways. It is a cornerstone of combination treatments, particularly in advanced HER2-positive breast cancer.
FDA Approval History
- 13 March 2007: Approval in previously treated advanced/metastatic breast cancer in combination with Xeloda (capecitabine).
- 1 February 2010: For first-line combination treatment in metastatic breast cancer, accelerated approval.
What Is Tykerb, Which Contains Lapatinib?
Tykerb is a cancer medicine that potently and selectively inhibits tyrosine kinases associated with the epidermal growth factor receptor (EGFR) and HER2. It is classified as a targeted agent and belongs to the signal transduction inhibitor group.
Distribution in Turkey: Novartis
How Does It Work?
Lapatinib blocks intracellular signaling pathways by binding to the tyrosine kinase regions on the inner portion of cell-surface receptors:
- Dual Blockade: It inhibits both EGFR (ErbB1) and HER2 (ErbB2) receptors, stopping ErbB phosphorylation.
- Cell Arrest: It suppresses growth-promoting (mitogenic) and cell-death-preventing (anti-apoptotic) signals.
- Antitumor Effect: It prevents cancer cell proliferation and metastasis, reduces angiogenesis (blood vessel formation), and increases treatment sensitivity.
Comparison of the mechanisms of action of cancer medicines targeting HER2.
Licensing and Reimbursement in Turkey
Indications Licensed in Turkey
Licensing in Turkey
The conditions/therapeutic indications for which Tykerb is licensed in Turkey are listed as follows:
Therapeutic Indications:
Teykerb is used in combination with capecitabine to treat patients with metastatic breast cancer who have previously received anthracycline, taxane, and trastuzumab treatment but still show disease progression, and whose c-erb B2 immunohistochemistry result is 3+ or FISH+. These are the patients for whom the combination is used.
SGK Reimbursement Coverage
In addition to the criteria for its licensed indication, reimbursement is available under specified off-label conditions. It is prescribed with a medical oncology specialist's report.
Price as of March 2026:
Selling price of Tykerb 250 mg, 70 Tablets: 26449.57 ₺
Uses Permitted Without Additional TİTCK Approval
- Stage IV Breast Cancer: Combination with capecitabine regardless of anthracycline use.
- Stage IV Colorectal Cancer: For treatment line 2 and beyond in HER2-positive (IHC3+ or FISH+), RAS wild-type disease.
Mechanisms of Resistance
Main factors limiting lapatinib's effectiveness:
- Receptor Mutations: Reduced drug-binding affinity due to EGFR and HER2 mutations.
- Alternative Pathways: HER3 activation, increased c-Met and AXL expression, and increased RON protein.
- Signaling Bypasses: Heregulin-driven PI3K signaling activation and PTEN loss.
- Hormonal Effects: Increased ERα transcription and estrogen signaling.
Pharmacological Properties
Absorption and Distribution
Absorption increases with food. Plasma protein binding is 99%. Steady state is reached in 6–7 days.
Metabolism
It is metabolized primarily in the liver by the enzymes CYP3A4 and CYP3A5. These enzymes account for its principal metabolism.
Elimination
The main route of elimination is hepatic (fecal). Renal excretion is <2% (safe use in patients with kidney disease).
The terminal half-life is 14 hours; with accumulation during continued use, the effective half-life increases to 24 hours.
Dosage and Administration
- Recommended Dose: 1250 mg (5 tablets) orally as a single daily dose.
- Combination (Capecitabine): 1000 mg/m² (every other day for 14 days in 21-day cycles).
Important Drug Interactions
CYP3A4 Inducers (Phenytoin, Rifampin, St. John's Wort): Reduce the medicine's effect.
CYP3A4 Inhibitors (Ketoconazole, Clarithromycin): Increase the risk of toxicity.
Warfarin: INR parameters should be monitored closely.
Side Effects and Monitoring
Common Side Effects
- Diarrhea (65%): The most common dose-limiting side effect.
- Skin Reactions: Hand-foot syndrome and rashes.
- General: Fatigue, loss of appetite, and mild nausea/vomiting.
- Blood Counts: Anemia (common) and thrombocytopenia.
Precautions and Monitoring
- Heart: LVEF and ECG monitoring (risk of QT prolongation) are essential.
- Liver: Increases in transaminases and bilirubin should be monitored.
- Administration: Take 1 hour before or 2 hours after meals.
References
- FDA Prescribing Information: Tykerb (lapatinib) - 2007 & 2010 Update.
- Novartis Türkiye - Tykerb Kısa Ürün Bilgisi (KÜB).
- TİTCK Ek Onay Alınmadan Kullanılabilecek İlaçlar Listesi.
- SGK Bedeli Ödenecek İlaçlar Listesi (March 2026 Update).
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