Cerator 400

Pentoxifylline.

Pharmacotherapeutic group: Peripheral vasodilator.
Pharmacology: Leukocyte properties of hemorrheologic importance have been modified in animal and in vitro human studies. Pentoxifylline has been shown to increase leukocyte deformability and to inhibit neutrophil adhesion and activation.
Pharmacokinetics: The half life of absorption of Pentoxifylline 400 is 4-6 hours. Pentoxifylline is extensively metabolized, mainly in the liver. Sixty percent of a single dose of Pentoxifylline 400 is eliminated via the kidney over 24 hours.

Cerebral circulatory disorders (sequelae of cerebral arteriosclerosis, e .g. lack/difficulty in concentration, vertigo, forgetfulness/impairment of memory), ischemic and postapopletic conditions.
Peripheral occlusive arterial disease and arteriovenous disorders of an arteriosclerotic or diabetic nature (e.g. intermittent claudication or rest pain) and trophic disturbances (e.g. leg ulcers and gangrene).

In principle, dosage and mode of administration is based on the type of severity of the circulatory disorder and on how the individual patient tolerates the drug. Dosage is generally based on the following guidelines and is determined by the physician in accordance with individual requirements.
Usual dose: 1 tab 2 or 3 times daily. The tablets are to be swallowed whole during or shortly after a meal with sufficient amounts of liquid (approximately 1/2 glass).
In patients with marked impairment of renal function (creatinine clearance < 10 mL/ min), it may be necessary to reduce the dose to 2 or 1 tablet daily.
The precise reduction implemented will vary depending o n how the patient tolerates the drug.
A dose reduction, guided by individual tolerance is necessary in patients with severely impaired liver function.
Treatment must be started with low doses in hypotensive patients or patients whose circulation is unstable as well as in patients who would be at particular risk from a reduction in blood pressure (e.g. patients with severe coronary heart disease or relevant stenoses of blood vessels supplying the brain): in such cases, the dose must be increased only gradually.

The signs of overdose include flushing, loss of consciousness, "coffee -ground" vomitus, absent reflexes, tonic-clonic convulsions. In addition to the general measures for treatment of over-intake of drugs, special attention is to be paid to the blood pressure where a pronounced lowering should be managed with judicious use of plasma expander. Convulsions are to be controlled with Diazepam.

Contraindicated in cases where there is known hypersensitivity to the active constituent Pentoxifylline, other methyl xanthines or any of the excipients. Also in patients with cerebral hemorrhage, extensive retinal hemorrhage, acute myocardial infarction and severe cardiac arrhythmias.

In patients with hypotension or severe coronary artery disease, Pentoxifylline should be used with caution, as a transient hypotensive effect is possible and, in isolated cases, might result in a reduction in coronary artery perfusion.
Particularly careful monitoring is required in patients with impaired renal function. In patients with a creatinine clearance of less than 30 mL/min, it may be necessary to reduce the daily dose of Pentoxifylline to one or two tablets to avoid accumulation. In patients with severely impaired liver function, the dosage may need to be reduced.
Effects on Ability to Drive and Use Machines: No effect known.

There is no information on the use of' Cerator in pregnancy but no untoward effects have been found in animal studies. Cerator should not be administered during pregnancy.
Pentoxifylline passes into breast milk in minute quantities. Because insufficient experience has been gained, the possible risks and benefits must be weighed before administration of Cerator to breast feeding mothers.

Gastrointestinal side effects (e.g. nausea, vomiting, diarrhea), may occur which, in individual cases, could necessitate discontinuation of treatment. Headache, dizziness, agitation and sleep disorders may occasionally occur as well as, in isolated cases intrahepatic cholestasis and transaminase elevation. There have been reports of flushing, occasionally tachycardia and rarely angina pectoris and hypotension, particularly if using high doses of Pentoxifylline. In such cases, discontinuation of the medication or a reduction of the daily dosage is required.
Hypersensitivity reactions such as pruritus, rash, urticaria, anaphylactic or anaphylactoid reactions with angioneurotic edema or bronchospasm may occur in isolated cases and usually disappear rapidly after discontinuation of the drug treatment.
A few very rare events of' bleeding (e.g. skin, mucosa) have been reported in patients treated with Pentoxifylline with and without anticoagulants or platelet aggregation inhibitors. The serious cases are predominantly concentrated in the gastrointestinal, genitourinary, multiple site and surgical wound areas and are associated with bleeding risk factors. A causal relationship between Pentoxifylline therapy and bleeding has not been established.
Thrombocytopenia has occurred in isolated cases.

Pentoxifylline may potentiate the effect of' anti-hypertensive agents and the dosage of the latter may need to be reduced.
Pentoxifylline should not be given concomitantly with Ketorolac as there is increased risk of bleeding and/or prolongation of prothrombin time.
Concomitant administration of Pentoxifylline and Theophylline may increase Theophylline levels in some patients. Therefore there may be an increase in and intensification of adverse effects of Theophylline.

Store at temperature of not more than 30°C.

Haemorrheologicals

C04AD03 - pentoxifylline ; Belongs to the class of purine derivative agents. Used as peripheral vasodilators.

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