Polfilin® prolongatum: composition and dosage form
One prolonged-release tablet contains 400 mg of pentoxifylline. The prolonged-release form sets the dosing pattern: not four to six times a day, as an ordinary tablet would require, but two to three.
The rules for taking it are short and all three are compulsory. The tablet is taken whole — not split and not chewed, because the rate of release depends on the form staying intact. It is taken after meals. And it is washed down with a sufficient amount of liquid.
How Polfilin® prolongatum works
Pentoxifylline is a synthetic xanthine derivative, and that kinship explains two things that come up later: the contraindication in hypersensitivity to methylxanthines — caffeine, theophylline, theobromine — and the interaction with theophylline. The point of the treatment, though, lies elsewhere: pentoxifylline and its metabolites improve blood flow by reducing its viscosity. In patients with chronic arterial changes this increases the blood supply to the pathologically altered areas and improves the oxygenation of the tissues.
- increases the elasticity of red blood cells;
- inhibits the aggregation of red blood cells;
- inhibits platelet aggregation by enhancing prostacyclin synthesis;
- reduces the pathologically raised fibrinogen concentration;
- inhibits the adhesion of leucocytes to the endothelium;
- reduces leucocyte activation and the endothelial damage that follows from it.
To this are added two effects that the product information mentions with a qualifier: a slight vasodilating action and a slight positive inotropic action. The word "slight" is essential here. Pentoxifylline replaces neither vasodilators nor agents that strengthen the work of the heart: it works above all through rheology — through how easily the blood passes along the small vessels.
Indications
There are four indications and all of them say the same thing in different organs: there is flow, but not enough of it. Two are large and well known. Intermittent claudication is the pain in the legs on walking that forces a person to stop and wait it out. States of cerebral ischaemia cover both the period after a stroke and disorders of brain function of vascular origin, which make themselves known through lack of concentration, dizziness and memory disturbances.
The other two indications concern the sense organs, and there the count runs in days. In the eye the medicine is used when the circulation in the eyeball suffers, both acutely and chronically, with the retina and the choroid involved. In the inner ear, when circulatory changes disturb its function and a person hears worse or loses hearing suddenly. What all four have in common is that it is not the vessel disease being treated here but its consequences. Hence the silence of the product information about time limits: the duration of treatment depends on the type of disease and is set by the doctor individually.
Method of administration and dosage
Adults are given one prolonged-release tablet, that is 400 mg of pentoxifylline, 2–3 times a day. In patients with severe circulatory disturbances the effect of the preparation may be hastened by giving pentoxifylline at the same time as an intravenous infusion. The dose and the duration are set by the doctor according to the severity of the symptoms and the tolerance of the medicine.
Three situations call for the dose to be reconsidered. With low or variable blood pressure the dosing schedule may have to be modified. With impaired kidney function and a creatinine clearance below 30 ml/min the dose is reduced to 50–70% of the standard one depending on individual tolerance — for instance 2 tablets a day instead of 3. With severe impairment of liver function a dose reduction is essential. Children and adolescents are not given the medicine: the safety and efficacy of use in children have not been established to date.
Contraindications
There are seven prohibitions and they fall into three groups of meaning — by the active substance, by recent vascular events and by bleeding.
- hypersensitivity to the active substance or to any of the excipients;
- hypersensitivity to methylxanthines: caffeine, theophylline, theobromine;
- a recently sustained myocardial infarction;
- a recently sustained cerebral stroke;
- bleeding of considerable severity;
- conditions with a high risk of haemorrhage;
- retinal haemorrhage.
The last point deserves careful reading, because it looks like a contradiction: circulatory disturbance in the retina is an indication, while retinal haemorrhage is a contraindication. There is no contradiction. The medicine helps when blood reaches the retina poorly, and is forbidden when a vessel there has already sprung a leak: everything pentoxifylline does to platelets and fibrinogen works against the patient in that situation.
Special warnings and precautions
The first rule concerns allergy and brooks no delay: at the first signs of an anaphylactic or anaphylactoid reaction pentoxifylline is stopped at once and the doctor is informed. The second concerns blood pressure. In patients with hypotension or severe coronary artery disease the medicine is used with caution, because transient hypotension is possible and it can occasionally reduce the flow in the coronary vessels themselves. That is why in hypotension, in unstable circulation and wherever a fall in blood pressure carries a particular risk — in severe coronary disease or significant narrowing of the vessels supplying the brain — treatment begins with small doses and they are raised gradually.
The groups that are watched especially closely are listed separately. These are patients with impaired kidney function and with severe impairment of liver function: at a creatinine clearance below 30 ml/min the daily dose is reduced to prevent accumulation of the drug. These are patients with severe cardiac rhythm disorders, those who have had a myocardial infarction, and patients with hypotension. These are all with an increased tendency to bleed — because of clotting disorders, for instance — and all who are simultaneously receiving vitamin K antagonists or other anticoagulants. And finally these are patients on antidiabetic drugs: the blood-sugar-lowering effect of insulin and of oral agents may be enhanced. One more warning concerns everyday life: pentoxifylline can cause dizziness, and that affects the ability to drive and to operate machinery.
Interaction with other medicines
Pentoxifylline's interactions are best sorted not by drug group but by what they end in: hypoglycaemia, bleeding, or the accumulation of another xanthine.
| With what | What happens | What to do |
| Insulin and oral antidiabetic drugs | large injected doses of pentoxifylline in rare cases enhanced their hypoglycaemic effect; no effect on insulin release after oral administration has been shown | observe patients being treated for diabetes carefully |
| Antihypertensives and other agents able to lower blood pressure | pentoxifylline enhances their action | take into account when adjusting doses |
| Vitamin K antagonists | cases of enhanced anticoagulant effect have been recorded | monitor the anticoagulant effect at the start of treatment and on a dose change |
| Anticoagulants and antiplatelet agents, including aspirin | bleeding is possible | especially careful observation |
| Ketorolac | the risk of bleeding and of a prolonged prothrombin time increases | they are not given together |
| Theophylline | in some patients the theophylline concentration in the blood rises and its unwanted effects are intensified | take into account when giving them together |
The last row takes us back to the beginning: both pentoxifylline and theophylline are xanthine derivatives, and the body handles them in a similar way. The practical conclusion is simple: if you take theophylline for your lungs, adding pentoxifylline is not a neutral event that can go unmentioned.
Pregnancy and breastfeeding
The wording here is cautious, and this is the case where caution means not a ban but an absence of knowledge. There are no sufficient data on the use of pentoxifylline in pregnant women, and the product is therefore not recommended during pregnancy.
With breastfeeding the position is a little softer. Pentoxifylline passes into human milk in small amounts that should not affect the infant. But here too the data are insufficient, so use during breastfeeding is limited to particularly justified cases. The difference between the two paragraphs is practical: pregnancy is an argument against prescribing, breastfeeding an argument for weighing up whether there is sufficient reason.
Adverse effects
It is worth starting with the most dangerous, even though it is also the rarest. In isolated cases, in the first minutes after the dose, very severe hypersensitivity reactions may develop: angioedema, bronchospasm, anaphylactic shock. That is precisely why the first signs of an allergic reaction call for immediate withdrawal.
- rare: anaphylactic and anaphylactoid reactions, hypersensitivity reactions — itching, erythema, urticaria with weals and itching; dizziness and headache; arrhythmia and tachycardia;
- very rare: thrombocytopenia; agitation and sleep disturbances; symptoms of angina pectoris, occurring above all with large doses; bleeding episodes — into the skin, mucous membranes, stomach, intestine; intrahepatic cholestasis; a rise in liver enzyme activity, aminotransferases and alkaline phosphatase;
- unknown frequency: aseptic meningitis; hot flushes with facial reddening; a fall in blood pressure; digestive complaints — nausea, vomiting, bloating, a feeling of fullness and diarrhoea.
Two points on that list carry explanations. Aseptic meningitis was noted mainly in patients with connective tissue disorders. Cases of bleeding — from the skin and mucous membranes — were reported in patients treated with pentoxifylline both with and without anticoagulant or antiplatelet drugs; in severe cases this means bleeding from the digestive tract, the genitourinary system and from areas of the body with multiple wounds, including surgical ones, where risk factors for bleeding are present. The causal relationship between pentoxifylline therapy and the occurrence of bleeding has not been established, and thrombocytopenia occurred in only a few cases.
Overdose
The picture of an overdose is recognisable and unfolds in an escalating sequence: dizziness, nausea, coffee-ground vomiting, a fall in blood pressure, tachycardia, cardiac rhythm disturbances, sudden facial flushing, tonic-clonic convulsions, loss of consciousness, fever, agitation, absence of reflexes. Coffee-ground vomiting in that list is a sign of gastric bleeding and is directly connected with the way the drug acts on clotting.
If the medicine was taken relatively recently, gastric lavage may be performed or activated charcoal given to prevent further absorption of pentoxifylline. The medicine has no specific antidote. After that, symptomatic treatment is given, breathing and circulation are supported and convulsive states are controlled.
How to get a prescription for Polfilin® prolongatum online
Pentoxifylline has an unusual set of prohibitions: three of the seven contraindications concern bleeding, and two more groups of patients from the precautions section are those taking anticoagulants or antiplatelet agents. The main question when prescribing is therefore not "does the medicine fit the indication" but "do you have an increased risk of bleeding". On e-zdrowie.com you fill in a medical questionnaire, the doctor reviews the answers and, if the medicine is suitable, issues an electronic prescription: the code arrives by message, and any Polish pharmacy will dispense the tablets against it.
Begin the questionnaire with blood clotting: list every agent that affects it — warfarin and other vitamin K antagonists, anticoagulants, aspirin and other antiplatelet drugs, ketorolac — and state whether you have had bleeding and whether you have a clotting disorder. Report separately any recent heart attack or stroke and any retinal haemorrhage: these are direct contraindications. Write down what your blood pressure is and whether it is ever low or unstable, whether there is severe coronary disease or narrowing of the cerebral vessels — the starting dose depends on it. Give your creatinine or creatinine clearance and any liver disease: below a clearance of 30 ml/min and with severe liver impairment the dose is reduced. And name the rest of your medicines — above all insulin and antidiabetic tablets, theophylline and blood pressure drugs, as well as any allergy to caffeine and other methylxanthines.
