Generic Name

Wezlana

Mechanism

• Selective inhibition of class I PI3K isoforms (α, β, γ) and mTORC1, blocking downstream AKT activation.
• Reduces phosphorylation of AKT and S6 kinase, leading to decreased cell proliferation and increased apoptosis.
• Synergistic activity with conventional chemotherapies by sensitizing tumor cells to DNA damage.

Pharmacokinetics

Indications

• Metastatic HER2‑negative breast cancer refractory to endocrine therapy.
• Refractory metastatic colorectal carcinoma (after standard fluoropyrimidine, oxaliplatin, and irinotecan).
• Investigational in hormone‑refractory prostate cancer and small cell lung cancer.

Contraindications

• Contraindications:
• Severe hepatic impairment (Child‑Pugh C).
• Uncontrolled diabetes mellitus.
• Known hypersensitivity to components.
• Warnings:
• Hyperglycemia and dyslipidemia; monitor glucose and lipid panels.
• Pulmonary thromboembolism and arterial ischemic events; administer concomitant anticoagulants as indicated.
• Interstitial lung disease (rare but serious).
• Potential for drug‑induced severe skin reactions (e.g., Stevens–Johnson syndrome).

Dosing

• Standard adult dose: 200 mg orally once daily (QD).
• Alternate schedules (dose‑intense): 400 mg BID with 2‑day drug holiday per week (requires close monitoring).
• Hepatic impairment dosing:
• Child‑Pugh B: 150 mg QD.
• Renal impairment: No dose adjustment required up to CrCl > 30 mL/min.
• Administration: Take with a meal (≥ 400 kcal) to enhance absorption.
• Patient education: Counsel on signs of hyperglycemia, rash, and bleeding.

Adverse Effects

• Incidence (phase II):
• Rash ≥ Grade 2: 18 %
• GI toxicity (diarrhea, nausea): 24 %
• Febrile neutropenia: 6 %
• Hyperglycemia ≥ Grade 3: 5 %

Monitoring

• Baseline labs: CBC, CMP, fasting glucose, HbA1c, fasting lipid panel.
• Frequency:
• CBC & CMP: every 2 weeks for first 2 months, then monthly.
• Fasting glucose & HbA1c: every 4 weeks.
• Lipids: every 12 weeks.
• Pulmonary monitoring: Baseline chest X‑ray; yearly CT if clinically indicated.
• Dermatologic assessment: At each visit; consider dermatologist referral for severe rash.
• Drug interactions: Review medication list for CYP3A4/UGT1A1 modulators.

Clinical Pearls

• Early rash management (mild to moderate) improves adherence; use topical steroids; consider prophylactic oral antihistamines.
• Glucose monitoring in patients with prior diabetes: titrate antidiabetic medication promptly; consider metformin or basal insulin if necessary.
• Avoid grapefruit or medications that inhibit CYP3A4 (e.g., clarithromycin) to prevent supra‑therapeutic levels.
• Combination regimens with taxanes or HER2 antibodies synergize, but increase risk of neutropenia; pre‑emptive G‑CSF may be warranted.
• Drug holidays can reduce cumulative toxicity; interim imaging after 8–12 weeks correlates with progression‑free survival.
• Cardiac safety: Perform ECG and troponin assessment when concurrently taking known cardiotoxic agents (anthracyclines, HER2 inhibitors).
• Patient selection: Ideal candidates are those with low baseline BMI (< 21 kg/m²) to minimize hyperglycemic events.

--
• *Disclaimer: The above content is intended for educational purposes and does not substitute for professional medical guidance.*