Pentoxifylline

Description

DESCRIPTION Pentoxifylline extended-release tablets, USP for oral administration contain 400 mg of the active drug and the following inactive ingredients: D&C Red No. 30 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, FD&C Yellow No. 6 Aluminum Lake, hydroxyethylcellulose, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, povidone, titanium dioxide and triacetin in an extended-release formulation. Pentoxifylline USP is a tri-substituted xanthine derivative designated chemically as 1-(5-oxohexyl)-3,7-dimethylxanthine that, unlike theophylline, is a hemorrheologic agent, i.e., an agent that affects blood viscosity. Pentoxifylline USP is soluble in water and ethanol, and sparingly soluble in toluene. The CAS Registry Number is 6493-05-6. The chemical structure is: Meets USP Dissolution Test 6. pentoxifyllinestruct

What Is Pentoxifylline Used For?

INDICATIONS & 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.

Dosage and Administration

DOSAGE & ADMINISTRATION The usual dosage of pentoxifylline in extended-release tablet form is one tablet (400 mg) three times a day with meals. While the effect of pentoxifylline extended-release tablets 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 pentoxifylline extended-release tablets should be discontinued. In patients with severe renal impairment (creatinine clearance below 30 mL/min) reduce dose to 400 mg once a day. Dosing information cannot be provided for patients with hepatic impairment.

Side Effects (Adverse Reactions)

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 mg 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 Pentoxifylline extended-release 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 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 Rising Pharma Holdings, Inc. at 1-844-874-7464 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. pentoxifyllinetable

Drug Interactions

DRUG INTERACTIONS Bleeding has been reported in patients treated with pentoxifylline extended-release tablets with or without concomitant NSAIDs, anticoagulants, or platelet aggregation inhibitors. Increased prothrombin time has been reported in patients concomitantly treated with pentoxifylline and vitamin K antagonists. Monitoring of anticoagulant activity in these patients is recommended when pentoxifylline is introduced or the dose is changed. Concomitant administration of pentoxifylline extended-release tablets and theophylline-containing drugs leads to increased theophylline levels and theophylline toxicity in some individuals. Monitor theophylline levels when starting pentoxifylline extended-release tablets or changing dose. Concomitant administration of strong CYP1A2 inhibitors (including e.g., ciprofloxacin or fluvoxamine) may increase the exposure to pentoxifylline (see ADVERSE REACTIONS). Pentoxifylline extended-release tablets have been used concurrently with antihypertensive drugs, beta blockers, digitalis, diuretics, and antiarrhythmics, without observed problems. Small decreases in blood pressure have been observed in some patients treated with pentoxifylline extended-release tablets; periodic systemic blood pressure monitoring is recommended for patients receiving concomitant antihypertensive therapy. If indicated, dosage of the antihypertensive agents should be reduced. Postmarketing cases of increased anticoagulant activity have been reported in patients concomitantly treated with pentoxifylline and vitamin K antagonists. Monitoring of anticoagulant activity in these patients is recommended when pentoxifylline is introduced or the dose is changed. Concomitant administration with cimetidine is reported to increase the average steady state plasma concentration of pentoxifylline (~25%) and the Metabolite I (~30%).

Contraindications

CONTRAINDICATIONS Pentoxifylline extended-release tablets 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.

Pregnancy and Breastfeeding

Pregnancy: Category C: Teratogenicity studies have been performed in rats and rabbits using oral doses up to 576 mg/kg and 264 mg/kg, respectively. On a weight basis, these doses are 24 and 11 times the maximum recommended human daily dose (MRHD); on a body-surface-area basis, they are 4.2 and 3.5 times the MRHD. No evidence of fetal malformation was observed. Increased resorption was seen in rats of the 576 mg/kg group. There are no adequate and well controlled studies in pregnant women. Pentoxifylline extended-release tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

NURSING MOTHERS Pentoxifylline and its metabolites are excreted in human milk. Because of the potential for tumorigenicity shown for pentoxifylline in rats, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Overdosage

OVERDOSAGE Overdosage with pentoxifylline extended-release tablets 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 extended-release tablets noted that symptoms usually occurred 4 to 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.

How Supplied

HOW SUPPLIED Pentoxifylline Extended-Release Tablets, USP are available containing 400 mg of pentoxifylline, USP. The 400 mg tablet is a lavender, film-coated, modified capsule-shaped, biconvex tablet debossed with R856 on one side of the tablet and plain on the other side. It is available as follows: NDC 16571-856-01 bottles of 100 tablets NDC 16571-856-50 bottles of 500 tablets NDC 16571-856-90 blister pack of 1 x 10 tablets Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from light. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Manufactured for: Rising Pharma Holdings, Inc. East Brunswick, NJ 08816 Made in India. Code No. GUJ/DRUGS/G-1430 Revised: 03/2025 PIR85601-01 141368 image description