Naftidrofuryl Oxalate

• Peripheral Arterial Disease (PAD): Treatment of intermittent claudication to improve walking distance and reduce symptoms of pain caused by insufficient blood flow.
• Cerebral Vascular Insufficiency: Used to alleviate symptoms related to chronic cerebral ischemia, such as dizziness, vertigo, and cognitive disturbances.
• Raynaud’s Phenomenon: Management of symptoms caused by vasospasm in small arteries of fingers and toes.
• Tinnitus and Vertigo: Sometimes used off-label to relieve vascular-related inner ear symptoms.
• Diabetic Microangiopathy: Occasionally prescribed off-label to improve microcirculation and reduce complications related to diabetic vascular disease.

Adults:

• Oral administration of 100 mg three times daily (TID), preferably 30 minutes before meals.
• Duration: Generally 2 to 3 months; treatment may be extended based on clinical response.

Elderly:

• Same dosage as adults; monitor for tolerance and adverse effects.

Pediatrics:

• Safety and efficacy have not been established; use not recommended.

Renal Impairment:

• Use with caution; no specific dose adjustments established, but monitoring is advised.

Hepatic Impairment:

• Caution recommended; dose adjustments may be necessary in severe liver dysfunction.

Route of Administration:

• Oral tablets, swallowed whole with water.

Naftidrofuryl oxalate is a selective peripheral vasodilator that antagonizes serotonin (5-HT2) receptors on vascular smooth muscle cells. By blocking serotonin-induced vasoconstriction, it promotes dilation of small arteries and arterioles, leading to improved peripheral and cerebral blood flow. Additionally, it enhances tissue oxygenation by increasing oxygen affinity of hemoglobin and favoring anaerobic metabolic pathways, which together reduce ischemic symptoms and improve functional capacity in affected tissues.

• Absorption: Rapidly absorbed after oral administration; peak plasma levels within 1 to 2 hours.
• Bioavailability: Moderate due to first-pass hepatic metabolism.
• Distribution: Widely distributed; moderate plasma protein binding.
• Metabolism: Primarily hepatic metabolism via oxidation and conjugation.
• Half-life: Approximately 1 to 2 hours.
• Excretion: Mainly renal as metabolites; minor fecal elimination.

• Pregnancy: Classified as FDA Pregnancy Category C. Animal studies have shown potential risks at high doses, but human data are limited. Use only if clearly needed and benefits outweigh risks.
• Lactation: Drug is excreted in breast milk in small amounts; use with caution. Monitor breastfed infants for any adverse effects.
• General: Insufficient data; avoid unless necessary.

• Primary Class: Peripheral vasodilator.
• Subclass: Serotonin (5-HT2) receptor antagonist.

• Hypersensitivity to naftidrofuryl or any components of the formulation.
• Severe hepatic impairment.
• Acute or chronic heart failure.
• Pregnancy and lactation unless benefit outweighs risk.
• Severe renal impairment (relative contraindication).

• Use cautiously in patients with heart conditions or arrhythmias.
• Monitor for hypersensitivity reactions (e.g., rash, anaphylaxis).
• Exercise caution in severe hepatic or renal impairment; monitor liver and kidney function.
• May worsen angina symptoms in coronary artery disease patients.
• Elderly patients may be more sensitive to central nervous system side effects.
• Discontinue treatment immediately if severe adverse reactions occur.

Common:

• Gastrointestinal: Nausea, abdominal pain, diarrhea.
• Nervous System: Headache, dizziness, fatigue.
• Skin: Rash, itching.

Serious but Rare:

• Hypersensitivity reactions including angioedema and anaphylaxis.
• Hepatotoxicity (very rare).
• Cardiovascular: Palpitations, tachycardia.

Notes:

• Side effects are generally mild and occur early in treatment.
• Gastrointestinal discomfort is dose-dependent and often transient.

• May increase hypotensive effects when combined with other vasodilators or antihypertensive agents.
• Caution with concomitant serotonergic drugs due to potential additive vascular effects.
• No significant CYP450 enzyme interactions reported, but caution advised with drugs metabolized hepatically.
• Alcohol may increase vasodilatory and central nervous system adverse effects.

• No significant recent changes in indications or dosing by FDA, EMA, or WHO.
• Recommended as a second-line treatment option for intermittent claudication when non-pharmacologic therapies are insufficient.
• Ongoing studies investigating its benefits in diabetic microangiopathy and cerebrovascular insufficiency.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and direct sunlight.
• Keep in a tightly closed container.
• Do not freeze.
• Keep out of reach of children.