Zyflo
Zyflo
Generic Name
Zyflo
Mechanism
- DNA synthesis inhibition – 5‑FU is metabolized intracellularly to 5‑fluorodeoxyuridine monophosphate (FdUMP).
- Thymidylate synthase (TS) inhibition – FdUMP forms a covalent ternary complex with TS and 5‑dihydrofolate, blocking the conversion of dUMP to dTMP.
- Cell‑cycle arrest (S‑phase) – Depletion of dTMP leads to DNA strand breaks and apoptosis in rapidly dividing keratinocytes.
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Pharmacokinetics
| Parameter | Value/Comment |
| Absorption | Limited systemic absorption; predominant local skin penetration. |
| Distribution | Poor systemic distribution; negligible plasma levels (usually < 1 µg/L). |
| Metabolism | Primarily converted to inactive metabolites locally via cytidine deaminase. |
| Elimination | Renal excretion of metabolites; not dose‑dependent. |
| Bioavailability | Not applicable for oral route. |
*Key point:* Minimal systemic exposure keeps systemic toxicity low.
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Indications
- Actinic keratosis – lesions confined to non‑ulcerated facial skin, scalp, neck, forearm, or hand.
- Superficial basal‑cell carcinoma – lesions ≤ 2 cm, non‑infiltrative, without peri‑oral or periorbital involvement.
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Contraindications
- Contraindications
- Large or ulcerated lesions.
- Periorbital, perineal, or mucosal surfaces (may cause severe irritation).
- Warnings
- Photosensitivity – patients should avoid intense sun exposure.
- Pregnancy/Breastfeeding – use with caution; consult obstetrician.
- Immunosuppressed patients – may experience prolonged skin reactions; monitor closely.
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Dosing
- Typical regimen – Apply a thin, even layer to the target area once or twice daily for 12 weeks.
- Post‑treatment care – Stop application after lesion resolution; apply gentle emollient.
- Missed dose – Apply at next scheduled time; do not double dose.
*Tip:* Use a clean, dry cotton applicator to avoid contamination.
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Adverse Effects
| Adverse Effect | Frequency | Notes |
| Erythema and desquamation | Common | Often the first sign of therapeutic response. |
| Papules, vesicles, ulceration | Common | May persist up to 8 weeks; treat with topical steroids if severe. |
| Dry skin, pruritus | Common | Use barrier moisturizer post‑therapy. |
| Systemic flu‑like symptoms | Rare | Usually transient; monitor if symptomatic. |
| Hypopigmentation / hyperpigmentation | Rare | Possible skin tone changes; counsel patient. |
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Monitoring
- Lesion assessment – baseline and every 4–6 weeks; resolution or change in appearance.
- Skin reaction grading – per Common Terminology Criteria for Adverse Events (CTCAE).
- Patient diary – record application time, skin reaction, and photosensitivity incidents.
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Clinical Pearls
1. Therapeutic Inflammation → Indicator of Response
• Early erythema and scaling are hallmarks of active cellular turnover; do not discontinue prematurely.
2. Patch‑Test First
• Perform a small test area 3–5 days before full‑area application to predict hypersensitivity.
3. Adjunctive Sunscreen
• Mandate broad‑spectrum SPF 30+ daily and reapply every 2 hours while outdoors to prevent phototoxicity.
4. Tolerability in Elderly
• Elderly patients may have heightened sensitivity; consider a reduced frequency (e.g., every other day) for initial weeks.
5. Avoid Steroid‑Co‑Therapy
• Concurrent potent topical steroids may mask skin reactions; avoid unless absolutely necessary.
6. Record Documentation
• Photographic documentation before, during, and after therapy aids in compliance evaluation and medicolegal records.
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• References
1. *American Academy of Dermatology Guidelines for Actinic Keratosis*.
2. *Dermatologic Pharmacology – 5‑Fluorouracil*.
3. FDA Label – Zyflo, 5 % 5‑FU Topical Cream.
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