Pentoxifylline is indicated in:

• Peripheral arterial occlusive disease (PAOD) of arteriosclerotic or diabetic origin (e.g., intermittent claudication and rest pain)
• Trophic lesions (e.g., leg ulcers and gangrene)
• Cerebrovascular diseases
• Circulatory disturbances of the eye associated with degenerative vascular disorders

Pentoxifylline and its metabolites improve blood flow properties by reducing blood viscosity. In patients with chronic peripheral arterial disease, this leads to increased microcirculatory blood flow and improved tissue oxygenation. The exact mechanism of action is not fully understood. However, Pentoxifylline has been shown to produce dose-dependent hemorheological effects, including reduction of blood viscosity and improvement of erythrocyte flexibility. It also affects leukocyte function by increasing leukocyte deformability and inhibiting neutrophil adhesion and activation. In both animal and in vitro human studies, these effects contribute to improved microcirculation. Therapeutic doses have been shown to significantly increase tissue oxygen levels in patients with peripheral arterial disease.

In principle, dosage is based on the type and severity of the circulatory disorders and on how the individual patient tolerates the drug. Usual dosage is 400 mg pentoxifylline 2 to 3 times daily. Tablets are to be swallowed whole during or shortly after a meal with sufficient amounts of liquid (approx. ½ glass).

• Precautions for use: The blood-glucose-lowering effect of insulin and oral antidiabetic drugs may be enhanced. Therefore, diabetic patients should be carefully monitored.
• Post-marketing reports have shown increased anticoagulant activity in patients receiving pentoxifylline with anti-vitamin K drugs. Monitoring of anticoagulant effect is recommended when treatment is started or dose is adjusted.
• The blood-pressure-lowering effect of antihypertensive drugs may be increased by pentoxifylline.
• Concomitant use with theophylline may increase theophylline levels, leading to increased adverse effects.
• Co-administration with ciprofloxacin may increase pentoxifylline serum levels and adverse reactions.
• Additive effect with platelet aggregation inhibitors may increase bleeding risk (e.g. clopidogrel, NSAIDs, aspirin, ticlopidine, dipyridamole and others). Caution is required.
• Cimetidine may increase plasma concentration of pentoxifylline and its active metabolite.

Pentoxifylline must not be used:

• in patients with hypersensitivity to pentoxifylline, other methylxanthines, or any excipients
• in patients with massive bleeding
• in patients with extensive retinal hemorrhage

Reported adverse reactions include:

• Investigations: Increased transaminases, decreased blood pressure
• Cardiac disorders: Arrhythmia, tachycardia, angina pectoris
• Blood disorders: Thrombocytopenia, leukopenia, neutropenia
• Nervous system: Dizziness, headache, aseptic meningitis
• Gastrointestinal: Abdominal discomfort, nausea, vomiting, diarrhea, constipation, bloating, hypersalivation
• Skin: Pruritus, rash, urticaria, erythema
• Vascular disorders: Flushing, hemorrhage
• Immune system: Anaphylactic reaction, anaphylactoid reaction, angioedema, bronchospasm, anaphylactic shock
• Hepatobiliary: Intrahepatic cholestasis
• Psychiatric: Agitation, sleep disturbances

There is insufficient experience with use during pregnancy. Therefore, pentoxifylline is not recommended during pregnancy. Small amounts of pentoxifylline may pass into breast milk. Due to limited data, the benefits and risks should be carefully considered before use in breastfeeding women.

At the first sign of an anaphylactic or anaphylactoid reaction, treatment must be stopped immediately.

• Careful monitoring is required in patients with:
• severe cardiac arrhythmias
• myocardial infarction
• hypotension
• renal impairment (creatinine clearance < 30 mL/min)
• severe liver impairment
• increased bleeding risk
• concomitant use with anticoagulants or platelet inhibitors
• concomitant use with antidiabetic drugs, ciprofloxacin, or theophylline

Hepatic impairment: Dose reduction is required in severe liver disease based on tolerance.

Renal impairment: Dose reduction of about 30–50% may be required in patients with creatinine clearance < 30 mL/min.

Other: Treatment should be started at low doses in patients with low blood pressure or unstable circulation, or in those at risk of hypotension (e.g. severe coronary disease or cerebral vascular stenosis). Dose should be increased gradually.

Symptoms may include nausea, dizziness, tachycardia, hypotension, fever, agitation, flushing, loss of consciousness, convulsions, and gastrointestinal bleeding (coffee-ground vomiting). There is no specific antidote. Management includes supportive care and measures to reduce absorption such as gastric lavage or activated charcoal if taken recently.

Peripheral Vasodilator drugs: Intermittent Claudication

Store in a cool and dry place, away from light. Do not use after expiry date. Keep out of reach of children. To be used only on the prescription of a registered physician.