Relafen
Relafen
Generic Name
Relafen
Mechanism
- Selective inhibition of the ATP‑binding pocket of VEGFR‑2, PDGFR‑β, and KIT kinases.
- Blocks downstream signaling (PI3K/AKT, MAPK) leading to:
- Anti‑angiogenic effect (reduces microvessel density).
- Direct antiproliferative activity in tumor cells harboring KIT mutations.
- Rapid dissociation from non‑target kinases, yielding a favorable toxicity profile compared with multi‑TKIs.
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Pharmacokinetics
| Parameter | Value | Relevant Notes |
| Absorption | Oral bioavailability ~70 % | Peak plasma levels (tmax) reached 1–2 h post‑dose |
| Distribution | Volume of distribution ~120 L | Protein binding ~95 % (primarily albumin) |
| Metabolism | Primarily CYP3A4‑mediated oxidative metabolism | Co‑administration with strong CYP3A4 inhibitors/inducers alters exposure |
| Elimination | 70 % renal, 30 % biliary | Renal excretion secondary to unchanged drug |
| Half‑life | 8–12 h | Supports once‑daily dosing |
| Drug interactions | ↑ risk with ketoconazole, clarithromycin; ↓ risk with rifampin, rifabutin | Requires dose adjustment or avoidance |
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Indications
- Advanced/metastatic renal cell carcinoma after failure of first‑line therapy (sunitinib, pazopanib).
- Gastrointestinal stromal tumor (GIST) with progression on imatinib and sunitinib.
- Clinical trials are evaluating efficacy in advanced melanoma (BRAF‑V600E) and non‑small cell lung cancer.
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Contraindications
| Category | Details |
| Contraindications | Known hypersensitivity to relafen or any excipient; pregnancy (category X). |
| Warnings | ① Hypertension – Requires baseline and periodic monitoring. ② QT prolongation – Use with caution in patients with a history of torsades or concurrent QT‑elongating agents. ③ Kidney dysfunction – Reduce dose in moderate renal impairment; avoid in severe impairment. ④ Hepatic impairment – Moderate hepatic dysfunction (Child‑Pugh B) warrants dose reduction; contraindicated in Child‑Pugh C. |
| Precautions |
• Monitor for bleeding when combined with anticoagulants or NSAIDs. • Avoid in patients with active bleeding or significant thrombocytopenia. • Educate patients about signs of interstitial lung disease (dyspnea, cough). |
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Dosing
- Standard dose: 150 mg orally once daily, taken with or without food.
- Dose reduction (if needed): 75 mg once daily.
- Renal impairment (CrCl 30–49 mL/min): 75 mg daily.
- Hepatic impairment (Child‑Pugh B): 75 mg daily.
- Packaging: 30‑tablet blister pack.
- Compliance reminder: Take at the same time each day; do not alter the dose without consulting prescriber.
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Adverse Effects
| Category | Examples |
| Common (≥10 %) | Fatigue, hypertension, proteinuria, nausea, vomiting, diarrhea, hand‑foot skin reaction (HFSR), dysgeusia |
| Serious (≤10 %) | Tumor lysis syndrome, severe hypertension, interstitial lung disease, hepatic transaminitis, thromboembolic events, serious bleeding, QTc prolongation |
| Rare (<1 %) | Severe hypersensitivity reactions, pericardial effusion, pancreatitis |
Management Tips
• Initiate anti‑emetics prophylactically for nausea.
• Use ACE inhibitors or calcium channel blockers for hypertension, adding diuretics for edema.
• Discontinue or dose‑reduce for grade ≥ 3 toxicities per WHO criteria.
• Prompt referral for any respiratory changes suggestive of interstitial lung disease.
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Monitoring
1. Blood pressure – twice weekly for first 4 weeks, then every 4 weeks.
2. Urine dipstick – baseline, then at weeks 2, 4, 8, 12 to detect proteinuria.
3. Renal function (CrCl/BUN) – baseline and every 4 weeks.
4. Liver enzymes (AST/ALT, bilirubin) – baseline, every 4 weeks.
5. Complete blood count – baseline and every 4 weeks.
6. ECG – baseline, and at 3 and 6 months to monitor QTc.
7. Adverse event grading – use CTCAE v5.0 for dose adjustment decisions.
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Clinical Pearls
- Edema & HFSR: Schedule *“rest days”* (e.g., dose pause 24 h after the patient reports HFSR) to mitigate skin toxicity; use moisturizing lotions.
- Combination therapy: Avoid concurrent NSAIDs or antiplatelets unless clinically imperative; use dual‑antiplatelet therapy only under specialist guidance due to bleeding risk.
- Renal‑dose adjustment: When CrCl falls below 30 mL/min, consider an alternate TKI rather than dose‐reduction of relafen.
- Effect on pregnancy: Discuss fertility planning; pregnancy test prior to initiation and ensure effective contraception during therapy.
- Drug interaction awareness: Revise medication list for CYP3A4 inhibitors/inducers; adjust relafen dose or switch agents when possible.
- Patient education: Emphasize symptoms of serious toxicities (e.g., sudden shortness of breath, chest pain, bloody urine) and the need to contact care promptly.
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• Relafen offers a targeted oral therapeutic option for high‑risk RCC and GIST patients, with a manageable safety profile when guided by the monitoring and dosing strategies above.