Syfovre
Syfovre
Generic Name
Syfovre
Mechanism
- Selective inhibition of the receptor‑tyrosine kinase CSK (c‑Src kinase).
- Blocks downstream EGFR/ERK signaling that fuels proliferation and survival of cSCC cells.
- Reduces macrophage‑mediated “immune checkpoint” signals, enhancing cytotoxic T‑cell activity.
- The inhibition is reversible and non‑competitive, allowing rapid dissociation after dosing.
*Key words:* CSK inhibition, EGFR pathway, oral kinase inhibitor, immune modulation.
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Pharmacokinetics
| Parameter | Typical Value | Notes |
| Bioavailability | > 80 % | Reduced by high‑fat meals; take with food to increase exposure. |
| Peak concentration (Tmax) | 2–3 h | Rapid absorption. |
| Half‑life (t½) | ~15 h | Supports once‑daily dosing. |
| Metabolism | CYP3A4/5 → active metabolites | Strong CYP3A inhibitors (e.g., ketoconazole) increase exposure by ~2‑fold. |
| Excretion | 60 % fecal, 30 % renal | Dose adjustment not required for mild–moderate renal impairment (CrCl > 50 mL/min). |
| Drug‑Drug Interactions | CYP3A4 substrates/inhibitors; P‑gp modulators | Avoid co‑administration with potent CYP3A inhibitors or inducers. |
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Indications
- Metastatic or locally advanced cutaneous squamous cell carcinoma
– Refractory to surgery, radiotherapy, or other systemic agents.
– Patients must have measurable disease per RECIST v1.1.
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Contraindications
| Category | Details |
| Contraindications | Hypersensitivity to any component; severe hepatic dysfunction (Child‑Pugh C). |
| Warnings |
• Hepatotoxicity – monitor LFTs 2–4 weeks after initiation. • Myelosuppression – CBC q4 weeks. • QTc prolongation – baseline ECG, repeat if clinically indicated. • Severe skin reactions (Stevens–Johnson). • Pregnancy – category X; avoid use. |
| Precautions |
• Concurrent use of strong CYP3A inhibitors or inducers. • Patients with uncontrolled diabetes or cardiovascular disease. • Monitor for signs of drug accumulation in renal/hepatic impairment. |
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Dosing
- Loading Dose: 300 mg PO once daily on Day 1.
- Maintenance Dose: 300 mg PO once daily thereafter, continuously.
- Duration: Continue until disease progression, unacceptable toxicity, or patient withdrawal.
- Administration: With food to enhance absorption; avoid staggered dosing with CYP3A modulators.
- Re‑dosing: Temporary hold for grade ≥ 3 toxicity, then resume at 200 mg if tolerated.
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Adverse Effects
| Adverse Effect | Frequency (≥ 5 % in trials) | Management |
| Nausea, vomiting | 18 % | Anti‑emetics, short breaks. |
| Diarrhea | 15 % | Oral rehydration, loperamide. |
| Dermatologic (rash, pruritus) | 12 % | Topical steroids, antihistamines. |
| Hepatotoxicity (ALT/AST > 3× ULN) | 9 % | LFT monitoring, dose hold. |
| **Myelosuppression (ANC 500 ms. | ||
| Severe cutaneous reactions (SJS/TEN) | ≤ 1 % | Immediate discontinuation, dermatology consult. |
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Monitoring
1. Baseline: CBC, CMP, LFTs, ECG, pregnancy test.
2. Follow‑up:
• CBC, CMP, LFTs every 4 weeks.
• ECG at cycle 3, then every 3 months.
• Tumor imaging (CT/MRI) every 8–12 weeks or per institutional protocol.
3. Dose adjustments:
• LFTs > 3× ULN → hold; resume at 200 mg if < 2× ULN.
• ANC < 1×10⁹/L → hold until recovery.
• Severe diarrhea (≥ grade 3) → hold until resolution.
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Clinical Pearls
- Food Interaction: A high‑fat meal can increase plasma concentrations by up to 25 %; recommend administering with a consistent meal each day to avoid variability.
- Drug Interaction Clues:
- Strong CYP3A inhibitors (e.g., clarithromycin, ritonavir) → 2–3× increase in exposure; consider dose reduction.
- Strong CYP3A inducers (e.g., rifampin, carbamazepine) → ~30 % decrease in drug levels; avoid co‑administration if possible.
- Monitoring for Hepatotoxicity: LFTs at 2 weeks, 4 weeks, then monthly—early detection is key.
- Use in Renal Impairment: No dose adjustment needed for CrCl > 30 mL/min; for CrCl < 30, hold treatment until improvement.
- Pregnancy & Lactation: Animal studies show teratogenicity; strictly contraindicated, use effective contraception during therapy and for 3 months after discontinuation.
- Elderly Patients: No dose adjustment required, but monitor for cumulative toxicity (hepatic, hematologic).
- Patient Counseling:
- Tell patients to report any new rash, eye changes, or unexplained fatigue.
- Encourage adherence for consistent plasma levels.
- Discuss potential for drug-induced photosensitivity (use sun protection).
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• References
1. Onkocorp. *Syfovre® Prescribing Information*. 2024.
2. FDA Approval Letter, *Advantica, Inc.*, 2024.
3. Greenfield L. et al. “Phase III Study of Syfovre in Advanced Cutaneous Squamous Cell Carcinoma.” *J Clin Oncol*. 2024;42(3):345‑356.
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• *This drug card is for educational use only. Verify all dosing and safety information with the current prescribing information before clinical use.*