Active substance: Pentoxifylline 100 mg in 5 ml. 

For a full list of excipients, see section 6.1.

Solution for injection 

Description of the preparation: clear, colourless solution. 

Peripheral arterial and arteriovenous disturbances of blood supply on the bases of atherosclerotic, diabetic and inflammatory background, dystrophic disorders (postthrombotic syndrome, gangrene, frostbite), angio-neuropathy (paraesthesia, acrocyanosis, Morbus Raynaud).  Disorders of blood supply to the brain caused by atherosclerosis, ischemic and  postapoplectic states.  Disorders of blood supply to the eye (acute and chronic insufficiency of blood supply to the retina and choroid). Acute functional disorders of the inner ear.

a) Dosage for children 

There are not sufficient experiences with pentoxifylline application in children. 

b) Dosage for adults 

The dosage is based on the type and severity of circulatory difficulties and according to the individual tolerance of the patient. It is necessary to ascertain the individual tolerance by application of a half volume of the ampoule, diluted with sodium chloride isotonic solution (2.5 ml to 10 ml), at beginning of the treatment. One ampoule (100 mg of pentoxifylline) is usually applied very slowly (5 minutes) intravenously or intraarterially to a recumbent patient 1-2 times daily. More advantageous is to apply an infusion of 200 or 300 mg of pentoxifylline in 250 or 500 ml of infusion solution two times daily. It is recommended to apply only one infusion and the dose complement with the oral form, when the infusion is not tolerated by the patient. 

A 24 hours intravenous droplet infusion is recommended in patients with great pains, gangrene or ulcers. 

Calculation of a single dose is based on the relation: 0.6 mg/kg/hour. The maximal daily dose is 1200 mg of pentoxifylline. 

In patients with renal function disorders (creatinine clearance below 30 ml/min), it is necessary to reduce the dose by 30 to 50%, however the dose depends also on the individual tolerance. 

Reduction of the doses is also necessary in patients with severe liver function impairment. 

In hypotensive patients with labile circulation or when the fall of blood pressure is a great risk for the patients,•it is necessary to start the treatment with low doses and increase them gradually. 

Hypersensitivity to pentoxifylline or methylxantine derivatives or to any excipient, fresh cardiac infarction, severe bleeding, haemorrhages. 

Great care is necessary in patients with severe coronary and cerebral sclerosis and also with serious cardiac arrhythmias. In patients with labile blood circulation or hypotension, the blood pressure after pentoxifylline administration can suddenly drop up to collapse or stenocardiac complaints may occur. It is suitable to monitor the blood pressure also during the infusion. In patients with cardiac insufficiency, sufficient doses of cardiac glycosides should be administered. In patients with renal insufficiency, it is necessary to reduce the dose (at creatinine clearance below 30 ml/min). In patients with diabetes mellitus, it is necessary to adjust the insulin dosage, in order to prevent hypoglycaemia. 

This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e. essentially ‘sodium free’.

Patients with severe renal insufficiency require a dose modification and especially careful medical supervision.  Because of sporadically occurring hematologic changes it is advisable to monitor the blood count during the long-term therapy.

The risk: benefit ratio of the treatment should be considered:

• in coagulation disorders 

• in severe coronary or cerebral arteriosclerosis, 

• in serious arrhythmias, 

• in hypotension, 

• in patients with diabetes mellitus. 

Pentoxifylline can potentiate the effect of antihypertensives. A fall of blood pressure may occur when combined with sympatholytics, ganglioplegics and vasodilators. High doses, administered in diabetics, potentiate the effect of insulin and oral antidiabetics (risk of hypoglycaemia), Theophylline plasma level may increase (risk of adverse effects of theophylline) in simultaneous administration with theophylline preparations. 

It is not recommended to administer pentoxifylline in pregnancy, because of insufficient experiences with its administration in this period. Pentoxifylline passes into breast milk in small quantities. It is necessary to consider the risks and benefit before pentoxifylline application in breast-feeding mothers. 

4.7 Effects on ability to drive and use machines 

Pentoxifylline has no influence on the ability to drive and use machines. 

4.8 Undesirable effects 

Nausea, vomiting, stomach ache and tension, vertigo and burning sensation in the face occur in 4-6% of patients (especially at high dose administration or at quick application of an infusion), sudden drop of blood pressure, heart rhythm disturbances, rarely pruritus and urticaria, possibility of anaphylactic reaction occurrence.

Sometimes headache, restlessness, insomnia may appear and in isolated cases intrahepatic cholestasis and transaminase increase may occur. 

Symptoms: Initial symptoms of acute overdose could be nausea, dizziness, tachycardia or drop of blood pressure.  Furthermore, fever, irritability, hot flushes, loss of consciousness, areflexia, tonic-clonic seizures and vomit of color of tea leaves as a manifestation of gastrointestinal bleeding might appear. 

Treatment: It is symptomatic, the specific antidote is not known. In convulsions diazepam may be administered and bradycardia can be managed with atropine. 

Pharmacotherapeutic group: Peripheral vasodilators 

ATC code: C04AD03

Mechanism of action 

Pentoxifylline is a substance of the methylxanthine derivative group. Its effect is based on improving the blood circulation through the vascular bed. Increased blood supply is achieved either by its effect on changed vascular walls, or mainly by changing the rheologie properties of blood, by decrease of its viscosity, increase of erythrocyte flexibility, decrease of thrombocyte aggregation ability and also by decrease of fibrinogen concentration. 

Pentoxifylline removes blood circulation disorders also in sclerotic blood vessels, where the vasodilator effect of other vasodilators can not be of use, due to this disorder. The effect is biphasic. In the first phase, the peripheral resistance decreases in healthy as well as in pathologic vessels. In healthy vessels, it will return to the initial level and even cross it in 10 minutes, while in pathologic vessels, the fall lasts and after one hour it will still deepen. Based on this biphasic effect, so called luxury hyperaemia of healthy vessels to the detriment of pathologic vessels (Steal's syndrome)•does not occur. Pentoxifylline expressively improves the metabolism in affected areas by positive influencing the blood circulation in areas supplied by pathologic vessels. It acts against thrombocyte agglutination, by inhibition of cAMP-phosphodiesterase localized on vascular walls, what causes an increase of cAMP in the thrombocyte inside. 

5.2 Pharmacokinetic properties 

In the case of parenteral administration, pentoxifylline is well and completely absorbed. The therapeutic plasma concentrations are in the range of 2 - 10 µg/ml. The distribution is equable, metabolites are formed at the liver passage, with especially two among them being effective. It is excreted mainly in the urine (about 94%) and stool (4%), About 90% of the total dose will be excreted within 4 hours after its administration. Pentoxifylline and its metabolites do not cumulate in the organism, only their traces are present in the urine after 24 hours. 

5.3. Preclinical safety data 

 Embryotoxic, cytotoxic, teratogenic and carcinogenic effects are not known. 

6. PHARMACEUTICAL PARTICULARS 

6.1 List of excipients 

Sodium chloride

Water for injection 

Sodium hydrogen carbonate (for pH adjustment)

Sodium content: 2.606 mg/ml, what corresponds to 0.113 mMol/ml.

6.2 Incompatibilities 

Not aplicable. 

4 years 

6.4 Special precautions for storage 

Do not store above 25°C. Do not refrigerate or freeze. 

6.5 Nature and contents of container 

Colourless glass ampoule, PVC mould, paper folder, 

Size of the package: 5 ampoules of 5 ml 

6.6 Special precautions for disposal

No special requirements.

7. MARKETING AUTHORISATION HOLDER 

BB Pharma Pod Višňovkou 1662/21, 140 00 Prague 4, Czech Republic 

8. MARKETING AUTHORISATION NUMBER(S) 

83/0759/92-S

December 31^st , 1992/September 2^nd, 1998

February 1^st, 2006