Generic Name

pentoxifylline

Brand Names

for pentoxifylline, a methylxanthine derivative widely used to improve microcirculatory blood flow in peripheral arterial disease (PAD) and related conditions.

Mechanism

• Pentoxifylline exerts a dual action:
• Improves red‑cell deformability and reduces whole‑blood viscosity, enhancing capillary perfusion.
• Inhibits the synthesis of pro‑inflammatory cytokines (TNF‑α, IFN‑γ) and prostaglandin E₂, thereby attenuating local inflammation.
• It also boosts nitric oxide (NO) availability, contributing to vasodilation and endothelial function improvement.

Pharmacokinetics

• Absorption: Rapid oral absorption; peak plasma concentrations reached in 1–2 h.
• Bioavailability: Approximately 20–30 % due to first‑pass hepatic metabolism.
• Half‑life: 1.5–3 h (oral); IV infusion extends exposure to ~1–2 h per dose.
• Metabolism: Hepatic microsomal oxidation (primarily 4‑hydroxylation); main metabolite is 3‑hydroxypentoxifylline.
• Elimination: 10–25 % unchanged drug excreted renally; remaining metabolites eliminated via urine and feces.
• Drug interactions: CYP450 inhibitors (erythromycin, ciprofloxacin) ↑ serum levels; inducers (phenobarbital, rifampicin) ↓ levels.

Indications

• Peripheral arterial disease (intermittent claudication) – to reduce claudication distance and improve exercise tolerance.
• Diabetic foot ulcers – enhances wound perfusion and accelerates healing.
• Chronic limb ischemia – adjunctive treatment for patients unsuitable for revascularization.
• Venous stasis ulcers – off‑label use for improving microcirculation.
• Diabetic peripheral neuropathy – symptomatic relief in select cases.

Contraindications

• Contraindications: Hypersensitivity to pentoxifylline or any component; known allergy to xanthine derivatives.
• Warnings:
• Caution in uncontrolled hypertension and significant arrhythmias due to vasodilatory effects.
• Use with caution in patients with heart failure; monitor for fluid overload.
• Concomitant use with anticoagulants or antiplatelet agents may increase bleeding risk.
• Avoid in patients with severe renal impairment (creatinine clearance <30 mL/min) – dose adjustment or discontinuation may be required.

Dosing

• Initiate therapy gradually; titrate dose over 1–2 weeks if tolerated.
• Ensure proper hydration and monitor blood pressure during IV infusion.

Adverse Effects

Common (≥10 %)
• Nausea, vomiting, abdominal pain
• Diarrhea or constipation
• Headache, dizziness
• Metallic taste, restless leg syndrome

Serious (≤1 %)
• Hypotension or fainting (especially after IV infusion)
• Cardiac arrhythmias (torsades de pointes, bradyarrhythmias)
• GI bleeding when combined with anticoagulants
• Severe rash or anaphylaxis (rare)

Monitoring

• Vital signs: Blood pressure pre‑ and post‑IV infusion; daily during therapy.
• ABIs (ankle‑brachial index): baseline and every 4–6 weeks to assess perfusion improvement.
• Laboratory:
• CBC, liver function tests, renal panel at baseline, then monthly.
• Serum electrolytes if clinically indicated.
• Clinical: Observe for signs of bleeding, allergic reactions, or worsening heart failure.

Clinical Pearls

• Exercise synergy: Combine Extavia with supervised exercise programs; up to a 20 % greater increase in claudication distance compared with exercise alone.
• High‑dose effectiveness: 1,200–1,600 mg/day yields superior outcomes vs. 600 mg/day for PAD; monitor for side effects.
• Inflammation modulation: In diabetic foot ulcers, Extavia lowers systemic TNF‑α, potentially enhancing wound healing; consider adjunctive anti‑inflammatory therapy.
• Medication tapering: In patients on nitrates or calcium‑channel blockers, introduce Extavia cautiously and steadily to avoid additive hypotension.
• Renal excretion: In chronic kidney disease, reduce dosing to 40 % of the standard (e.g., 800 mg/day) and monitor closely.
• Avoid in severe asthma or COPD: Report any respiratory adverse events promptly; caution due to bronchodilator effects of methylxanthines.

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• References: UpToDate™; NCCN Guidelines (Peripheral Vascular Disease); FDA prescribing information (Oct 2022).