INDICATIONS AND USAGE Pentoxifylline Extended-Release Tablets are indicated for the treatment of patients with intermittent claudication on the basis of chronic occlusive arterial disease of the limbs.

Pentoxifylline Extended-Release Tablets 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.

ADVERSE REACTIONS Clinical trials were conducted using either extended-release pentoxifylline tablets for up to 60 weeks or immediate-release pentoxifylline capsules for up to 24 weeks.

Dosage ranges in the tablet studies were 400 mg bid to tid and in the capsule studies, 200 to 400 mg tid.

The table summarizes the incidence (in percent) of adverse reactions considered drug related, as well as the numbers of patients who received extended-release pentoxifylline tablets, immediate-release pentoxifylline capsules, or the corresponding placebos.

The incidence of adverse reactions was higher in the capsule studies (where dose related increases were seen in digestive and nervous system side effects) than in the tablet studies.

Studies with the capsule include domestic experience, whereas studies with the extended-release tablets were conducted outside the U.S.

The table indicates that in the tablet studies few patients discontinued because of adverse effects.

INCIDENCE (%) OF SIDE EFFECTS Extended-Release Tablets Immediate-Release Capsules Commercially Available Used only for Controlled Clinical Trials Pentoxifylline Placebo Pentoxifylline Placebo (Numbers of Patients at Risk) (321) (128) (177) (138) Discontinued for Side Effect 3.1 0 9.6 7.2 CARDIOVASCULAR SYSTEM Angina/Chest Pain 0.3 - 1.1 2.2 Arrhythmia/Palpitation - - 1.7 0.7 Flushing - - 2.3 0.7 DIGESTIVE SYSTEM Abdominal Discomfort - - 4.0 1.4 Belching/Flatus/Bloating 0.6 - 9.0 3.6 Diarrhea - - 3.4 2.9 Dyspepsia 2.8 4.7 9.6 2.9 Nausea 2.2 0.8 28.8 8.7 Vomiting 1.2 - 4.5 0.7 NERVOUS SYSTEM Agitation/Nervousness - - 1.7 0.7 Dizziness 1.9 3.1 11.9 4.3 Drowsiness - - 1.1 5.8 Headache 1.2 1.6 6.2 5.8 Insomnia - - 2.3 2.2 Tremor 0.3 0.8 - ‑ Blurred Vision - - 2.3 1.4 Pentoxifylline has been marketed in Europe and elsewhere since 1972.

In addition to the above symptoms, the following have been reported spontaneously since marketing or occurred in other clinical trials with an incidence of less than 1%; the causal relationship was uncertain: Cardiovascular - dyspnea, edema, hypotension.

Digestive - anorexia, cholecystitis, constipation, dry mouth/thirst.

Nervous - anxiety, confusion, depression, seizures, aseptic meningitis.

Respiratory - epistaxis, flu-like symptoms, laryngitis, nasal congestion.

Skin and Appendages - brittle fingernails, pruritus, rash, urticaria, angioedema.

Special Senses - blurred vision, conjunctivitis, earache, scotoma.

Miscellaneous - bad taste, excessive salivation, leukopenia, malaise, sore throat/swollen neck glands, weight change.

A few rare events have been reported spontaneously worldwide since marketing in 1972.

Although they occurred under circumstances in which a causal relationship with pentoxifylline could not be established, they are listed to serve as information for physicians.

Cardiovascular — angina, arrhythmia, tachycardia.

Digestive — hepatitis, jaundice, cholestasis, increased liver enzymes; and Hemic and Lymphatic — decreased serum fibrinogen, pancytopenia, aplastic anemia, leukemia, purpura, thrombocytopenia.

Immune system disorders — anaphylactic reaction, anaphylactoid reaction, anaphylactic shock.

To report SUSPECTED ADVERSE REACTIONS, contact ANI Pharmaceuticals, Inc.

at 1-800-308-6755 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.