PENTOXIL^®
(Pentoxifylline Extended-release Tablets, USP) 400 mg

Rx only

Pentoxil^® (Pentoxifylline Extended-release Tablets, USP) for oral administration contain 400 mg of the active drug and the following inactive ingredients: D&C Red No. 27 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake, hypromellose USP, magnesium stearate NF, polyethylene glycol NF, polysorbate 80 NF, povidone USP, silicon dioxide NF and titanium dioxide USP, in an extended-release formulation. Pentoxifylline is a tri-substituted xanthine derivative designated chemically as 3,7-Dihydro-3,7-dimethyl-1-(5-oxohexyl)-1H-purine-2,6-dione that, unlike theophylline, is a hemorrheologic agent, i.e., an agent that affects blood viscosity. Pentoxifylline is soluble in water and ethanol, and sparingly soluble in toluene. The structural formula is:

Meets USP Dissolution Test 3.

Pentoxil^® (Pentoxifylline Extended-release Tablets, USP) is indicated for the treatment of patients with intermittent claudication on the basis of chronic occlusive arterial disease of the limbs. Pentoxil^® 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.

Pentoxil^® (Pentoxifylline Extended-release Tablets, USP) 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.

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, 200-400 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.

Pentoxifylline tablets have 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 uled to serve as information for physicians. Cardiovascular—angina, arrhythmia, tachycardia, anaphylactoid reactions. Digestive— hepatitis, jaundice, increased liver enzymes; and Hemic and Lymphatic—decreased serum fibrinogen, pancytopenia, aplastic anemia, leukemia, purpura, thrombocytopenia.

Overdosage with pentoxifylline has been reported in pediatric patients and adults. Symptoms appear to be dose related. A report from a poison control center on 44 patients taking overdoses of enteric-coated pentoxifylline tablets noted that symptoms usually occurred 4-5 hours after ingestion and lasted about 12 hours. The highest amount ingested was 80 mg/kg; flushing, hypotension, convulsions, somnolence, loss of consciousness, fever, and agitation occurred. All patients recovered.

In addition to symptomatic treatment and gastric lavage, special attention must be given to supporting respiration, maintaining systemic blood pressure, and controlling convulsions. Activated charcoal has been used to absorb pentoxifylline in patients who have overdosed.

The usual dosage of Pentoxil^® (Pentoxifylline Extended-release Tablets, USP) in extended-release tablet form is one tablet (400 mg) three times a day with meals.

While the effect of Pentoxil^® (Pentoxifylline Extended-release Tablets, USP) may be seen within 2 to 4 weeks, it is recommended that treatment be continued for at least 8 weeks. Efficacy has been demonstrated in double-blind clinical studies of 6 months duration.

Digestive and central nervous system side effects are dose related. If patients develop these effects it is recommended that the dosage be lowered to one tablet twice a day (800 mg/day). If side effects persist at this lower dosage, the administration of Pentoxil^® (Pentoxifylline Extended-release Tablets, USP) should be discontinued.

Pentoxil^® (Pentoxifylline Extended-release Tablets, USP) is available for oral administration as 400 mg light-pink, unscored, film-coated, capsule-shaped tablets imprinted U-S 027; supplied in bottles of 100 (NDC 0245-0027-11); bottles of 270 (NDC 0245-0027-27); bottles of 500 (NDC 0245-0027-15); bottles of 5000 (NDC 0245-0027-55) and Unit Dose Packs of 100 (NDC 0245-0027-01).

Store at 20-25°C (68-77°F). Excursions permitted to 15-30°C (59-86°F). [See USP Controlled Room Temperature.]

Dispense in well-closed, light-resistant containers.

Protect bulers from light.

Manufactured by
UPSHER-SMITH
UPSHER-SMITH LABORATORIES, INC.
Minneapolis, MN 55447

Rev 0405