Action And Clinical Pharmacology: Pentoxifylline is a xanthine derivative. It belongs to a group of vasoactive drugs which improve peripheral blood flow and thus enhance peripheral tissue oxygenation. The mechanism by which pentoxifylline achieves this effect has not been determined, but it is likely that the following factors are involved: Pentoxifylline, as other xanthine derivatives, relaxes certain smooth muscles including those of the peripheral vessels, thus causing vasodilatation or preventing spasm. This action, however, may have a limited role in patients with chronic obstructive arterial disease when peripheral vessels are already maximally dilated.
Pentoxifylline improves flexibility of red blood cells. This increase in the flexibility of red blood cells probably contributes to the improvement of the ability of blood to flow through peripheral vessels (hemorheologic action). This property was seen during in vitro and in vivo experiments with pentoxifylline but the correlation between it and the clinical improvement of patients with peripheral vascular diseases has not been determined.
Pentoxifylline promotes platelet deaggregation.
Improvement of red blood cell flexibility and platelet deaggregation contribute to the decrease in blood viscosity.
Pentoxifylline is almost completely absorbed after oral administration. The pentoxifylline 400 mg sustained-release tablet showed an initial peak plasma pentoxifylline concentration 2 to 3 hours postadministration. The drug is extensively metabolized. Biotransformation products are almost exclusively eliminated by the kidneys.
Food intake before the administration of pentoxifylline delayed the absorption but did not decrease it.
Indications And Clinical Uses: For the symptomatic treatment of patients with chronic occlusive peripheral vascular disorders of the extremities. In such patients pentoxifylline may give relief of signs and symptoms of impaired blood flow, such as intermittent claudication or trophic ulcers.
Contra-Indications: In patients with acute myocardial infarction, patients with severe coronary artery disease when, in the physician’s judgement, myocardial stimulation might prove harmful, patients with hemorrhage, patients who have previously exhibited intolerance to pentoxifylline or other xanthines such as caffeine, theophylline and theobromine and in patients with peptic ulcers or recent history thereof.
Manufacturers’ Warnings In Clinical States: Since pentoxifylline is extensively metabolized in the liver and eliminated through the kidneys, the use of this drug is not recommended in patients with marked impairment of kidney or liver function. Patients with less severe impairment of the liver and patients with impaired renal function (creatine clearance below 30 mL/min) should be closely monitored during pentoxifylline therapy and they may require lower doses.
The administration of pentoxifylline has been associated with bleeding and/or prolonged prothrombin time (see Precautions, Drug Interactions). The risk of bleeding may be increased by combined treatment with anticoagulant agents. Therefore, in patients on anticoagulant therapy, pentoxifylline should be used with caution and only when in the physician’s judgment the potential benefit outweighs the risk.
Children: The use of pentoxifylline in patients below the age of 18 years is not recommended as safety and effectiveness have not been established in this age group.
Precautions: Low, Labile Blood Pressure: Caution should be exercised when administering pentoxifylline to patients with low or labile blood pressure. In such patients any dose increase should be done gradually.
Geriatrics: Pentoxifylline should be used with caution in elderly patients as peak plasma levels of pentoxifylline and its metabolites are moderately higher in this age group. Elderly patients had a slight increase in the incidence of some adverse effects. Careful dose adjustment is therefore recommended.
Pregnancy : Reproduction studies have been performed in rats, mice and rabbits at doses up to 23, 2 and 11 times the maximum recommended daily human dose and have revealed no evidence of impaired fertility or harm to the fetus due to pentoxifylline. The drug has been shown to cross the blood-placenta barrier in mice. There is no adequate experience in pregnant women. Therefore, pentoxifylline is not recommended for women who are, or may become, pregnant unless the expected benefits for the mother outweigh the potential risk to the fetus.
Lactation: Pentoxifylline and its major metabolites are excreted in human milk, following a 400 mg single oral dose of pentoxifylline. The patient should be advised to discontinue nursing or to discontinue taking the drug depending on the importance of the drug to the mother.
Drug Interactions: Antihypertensive Agents: Pentoxifylline may potentiate the action of antihypertensive agents. Patients receiving these agents require blood pressure monitoring and possibly a dose reduction of the antihypertensive agents.
Sympathomimetics: Combined use with other xanthines or with sympathomimetics may cause excessive CNS stimulation.
Theophylline: Although causality has not been established, concurrent use of pentoxifylline with theophylline has resulted in elevated theophylline plasma levels, which may enhance the possibility of adverse effects.
Erythromycin: No data are available on the possible interaction of pentoxifylline and erythromycin. However concurrent administration of erythromycin and theophylline has resulted in significant elevation of serum theophylline levels with toxic reactions.
Hypoglycemic Agents: In patients treated with hypoglycemic agents, a moderate adjustment in the dose of these agents may be required when pentoxifylline is prescribed.
Anticoagulants: There have been reports of bleeding and/or prolonged prothrombin time in patients treated with pentoxifylline with and without anticoagulants or platelet aggregation inhibitors. Patients on warfarin should have more frequent monitoring of prothrombin time, while patients with other risk factors complicated by hemorrhage (e.g., recent surgery) should have periodic examinations for signs of bleeding, including hematocrit and hemoglobin.
Antacids: In patients with digestive side effects, antacids may be administered with pentoxifylline. In a comparative bioavailability study, no interference with absorption of pentoxifylline by antacids was observed.
Cimetidine: During concurrent use of cimetidine and pentoxifylline, cimetidine has been shown to significantly increase the steady-state plasma concentration of pentoxifylline, which may enhance the possibility of adverse effects.
Adverse Reactions: The most frequent adverse effect reported with pentoxifylline is nausea (14%). Individual signs/symptoms not marked with an asterisk occurred at an incidence below 1% (*=incidence between 1 and 3%).
Cardiovascular: flushing*, chest pain, arrhythmia, hypertension, dyspnea, edema, hypotension, angina, tachycardia.
CNS: dizziness/lightheadedness (9.4%), headache (4.9%), drowsiness/sleepiness, tremor, agitation, anxiety, confusion, insomnia, restlessness.
Gastrointestinal: nausea (14%), vomiting (3.4%), abdominal discomfort*, bloating*, diarrhea*, dyspepsia*, abdominal burning, abdominal pain, anorexia, flatus, constipation, hemorrhage, heartburn, salivation, dry mouth/throat, hepatitis, jaundice, increased liver enzymes.
Hemic and Lymphatic: decreased serum fibrinogen, pancytopenia, purpura, thrombocytopenia, leukopenia, anemia, aplastic anemia.
Hypersensitivity: pruritus, rash, urticaria, angioedema.
Organs of Special Sense: blurred vision, scotoma, lacrimation, epistaxis.
Miscellaneous: malaise*, muscle aches/spasms, weight change, backache, bad taste in mouth, leg cramps, fever, weakness, sweating.
Symptoms And Treatment Of Overdose: Overdosage with pentoxifylline has been reported in children and adults.Symptoms: Symptoms appear to be dose related and 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.
Treatment: In addition to symptomatic treatment and gastric lavage, special attention must be given to supporting respiration, maintaining systemic blood pressure, and controlling convulsions with i.v. diazepam. Activated charcoal has been used to adsorb pentoxifylline in patients who have overdosed.
Dosage And Administration: The recommended starting dosage of pentoxifylline is 400 mg twice daily after meals. The usual maintenance dose is 400 mg 2 or 3 times daily. A maximum dose of 400 mg 3 times daily should not be exceeded.
It may take up to 2 months to obtain full results.
Tablets must be swallowed whole.
Availability And Storage: Each pink, oblong, film-coated, sustained-release tablet contains: pentoxifylline 400 mg. Nonmedicinal ingredients: FD&C Red No. 3, hydroxyethyl cellulose, hydroxypropyl methylcellulose, magnesium stearate, polyethylene glycol, povidone, talc and titanium dioxide. Unit pack boxes of 60 (6´10 blister-packed). Plastic bottles of 500 and 100. Store between 15 and 30°C.
ALBERT® PENTOXIFYLLINE Albert Pharma Pentoxifylline Vasoactive Agent