Trental 400 mg

Interactions with food have not been established.

Combined use with other xanthines or with sympathomimetics may cause excessive CNS stimulation.

Interactions with laboratory tests have not been established.

Interactions with herbal product have not been established.

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.

Interactions with lifestyles have 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 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 haemoglobin.

The blood-sugar lowering effect of insulin or oral antidiabetic agents may be potentiated. In patients treated with hypoglycemic agents, a moderate adjustment in the dose of these agents may be required when Trental is prescribed.

In patients with digestive side effects, antacids may be administered with Trental. In comparative bioavailability study, no interference with absorption of Trental by antacids was observed.

Trental (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.

No data are available on the possible interaction of Trental and erythromycin. However concurrent administration of erythromycin and theomycin has resulted in significant elevation of serum theophylline levels with toxic reactions.

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.

The recommended starting dosage of Trental (pentoxifylline) is 400 mg twice daily after meals. The usual dose is 400 mg twice or three times daily. A maximum of 400 mg three times daily should not be exceeded.

It may take up to two months to obtain full results.

Trental 400 mg sustained release tablets must be swallowed whole.

abdominal burning, abdominal pain, anorexia flatus, constipation, haemorrhage, heartburn, salivation, dry mouth/throat, hepatitis, jaundice, increased liver enzymes.

blurred vision, scotoma, lacrimation, epistaxis.

muscle aches/spasm, weight change, backache, bad taste in mouth, leg cramps, fever, weakness, sweating.

reddening of skin.

aseptic meningitis.

sleep disturbances.

intrahepatic cholestasis.

pruritus, rash, urticaria, angioedema.

drowsiness/sleepiness, tremor, agitation anxiety, confusion, insomnia, restlessness.

transaminase elevation.

severe anaphylactic/anaphylactoid reaction with, for example, angioneurotic edema, bronchospasms, sometimes shock.

decreased serum fibrinogen, pancytopenia, purpura, thrombocytopenia, leucopenia, anemia, aplastic anemia.

chest pain, arrhythmia, hypertension, dyspnea, edema, hypotension, angina, tachycardia.

Trental 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.

The administration of Trental has been associated with bleeding and/or prolonged prothrombin time (see Drug Interactions). The risk of bleeding may be increased by combined treatment with anticoagulant agents or use in coagulation disorders. Therefore, in patients with coagulation disorders or being treated with anticoagulant therapy, Trental should be used with caution and only when, in the physician’s judgement, the potential benefit outweighs the risk.

Caution should be exercised when administering Trental (pentoxifylline) to patients with low or labile blood pressure. In such patients any dose increase should be done gradually.

Patients with hepatic impairment should be closely monitored during Trental therapy and may require lower doses. Since Trental (pentoxifylline) is extensively metabolized in the liver, the use of this drug is not recommended in patients with severe hepatic impairment of liver function (Child-Pugh class C, score >9).

Patients with renal impairment (creatinine clearance below 80 mL/min) should be closely monitored during Trental therapy and may require lower doses. Since Trental (pentoxifylline) is eliminated through the kidneys, the use of this drug is not recommended in patients with severe renal impairment (creatinine clearance below 30 mL/min).

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, Trental is not recommended for women who are, or may become, pregnant unless the expected benefits for the mothers outweigh the potential risk to the fetus.

The use of Trental in patients below the age of 18 years is not recommended as safety and effectiveness have not been established in this age group.

Pentoxifylline and its major metabolites are excreted in human milk, following a 400 mg single oral dose of Trental. The patient should be advised to discontinue nursing or to discontinue taking the drug depending on the importance of the drug to the mother.

Pentoxifylline is almost completely absorbed after oral administration. The Trental 400 mg sustained release tablet showed an initial peak plasma pentoxifylline concentration 2 to 3 hours post-administration. The drug is extensively metabolized. Biotransformation products are almost exclusively eliminated by the kidneys.

Food intake before the administration of Trental delayed the absorption but did not decrease it.

Trental (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 Trental achieves this effect has not been determined, but it is likely that the following factors are involved:

• Trental, as with 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.

  
  

• Trental 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 (haemorheologic action). This property was seen during in vitro and in vivo experiments with Trental but the correlation between it and the clinical improvement of patients with peripheral vascular diseases has not been determined.

  
  

• Trental promotes platelet deaggregation.

  
  

Improvement of red blood cell flexibility and platelet deaggregation contribute to the decrease in blood viscosity.