After administration of the 400 mg extended-release TRENTAL tablet, plasma levels of the parent compound and its metabolites reach their maximum within 2 to 4 hours and remain constant over an extended period of time. Coadministration of TRENTAL tablets with meals resulted in an increase in mean C and AUC by about 28% and 13% for pentoxifylline, respectively. C for Metabolite 1 also increased by about 20%. The extended release of pentoxifylline from the tablet eliminates peaks and troughs in plasma levels for improved gastrointestinal tolerance.

TRENTAL is indicated for the treatment of patients with intermittent claudication on the basis of chronic occlusive arterial disease of the limbs. TRENTAL can improve function and symptoms but is not intended to replace more definitive therapy, such as surgical bypass, or removal of arterial obstructions when treating peripheral vascular disease.

TRENTAL should not be used in patients with recent cerebral and/or retinal hemorrhage or in patients who have previously exhibited intolerance to this product or methylxanthines such as caffeine, theophylline, and theobromine.

Patients with chronic occlusive arterial disease of the limbs frequently show other manifestations of arteriosclerotic disease. TRENTAL has been used safely for treatment of peripheral arterial disease in patients with concurrent coronary artery and cerebrovascular diseases, but there have been occasional reports of angina, hypotension, and arrhythmia. Controlled trials do not show that TRENTAL causes such adverse effects more often than placebo, but, as it is a methylxanthine derivative, it is possible some individuals will experience such responses. Patients on Warfarin should have more frequent monitoring of prothrombin times, while patients with other risk factors complicated by hemorrhage (e.g., recent surgery, peptic ulceration, cerebral and/or retinal bleeding) should have periodic examinations for bleeding including, hematocrit and/or hemoglobin.

Although a causal relationship has not been established, there have been reports of bleeding and/or prolonged prothrombin time in patients treated with TRENTAL with and without anticoagulants or platelet aggregation inhibitors. Patients on Warfarin should have more frequent monitoring of prothrombin times, while patients with other risk factors complicated by hemorrhage (e.g., recent surgery, peptic ulceration) should have periodic examinations for bleeding including hematocrit and/or hemoglobin. Concomitant administration of TRENTAL and theophylline-containing drugs leads to increased theophylline levels and theophylline toxicity in some individuals. Such patients should be closely monitored for signs of toxicity and have their theophylline dosage adjusted as necessary. TRENTAL has been used concurrently with antihypertensive drugs, beta blockers, digitalis, diuretics, antidiabetic agents, and antiarrhythmics, without observed problems. Small decreases in blood pressure have been observed in some patients treated with TRENTAL; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensive therapy. If indicated, dosage of the antihypertensive agents should be reduced.

Long-term studies of the carcinogenic potential of