Polfenon: composition and presentation
One film-coated tablet contains 150 mg or 300 mg of propafenone hydrochloride. It is taken after a meal, washed down with a little liquid.
The composition includes lactose, so the medicine is unsuitable for people with the rare hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption syndrome. One unusual item among the contraindications is worth noting separately: the medicine must not be used where there is hypersensitivity not only to the active substance but also to soya and peanuts.
How Polfenon works
Propafenone is an antiarrhythmic that stabilises cell membranes and blocks the sodium channel; in the Vaughan-Williams classification it belongs to group IC. It inhibits the fast sodium current, which slows the upstroke of phase zero of the action potential. The duration of the action potential in heart muscle cells it lengthens slightly, and in Purkinje fibres it shortens.
The practical point lies elsewhere: by reducing the rate at which the action potential arises, propafenone lowers the speed of impulse conduction — that is the negative dromotropic effect. The refractory period is lengthened in the atrium, the atrioventricular node and the ventricles, and in patients with Wolff-Parkinson-White syndrome also in the accessory conduction pathways. Propafenone also has weak beta-blocking properties, and they have to be remembered twice: in asthma, and when it is combined with other medicines that slow the heart rate.
Indications
The first group of indications is symptomatic supraventricular tachyarrhythmias: nodal tachycardia, supraventricular tachycardia in patients with Wolff-Parkinson-White syndrome, and paroxysmal atrial fibrillation.
The second is life-threatening, severe, symptomatic ventricular tachyarrhythmia. The difference between the two groups is not only one of severity: treatment of ventricular tachyarrhythmias must take place in hospital conditions, and that is written directly into the dosing section. What both groups share is the word "symptomatic" — the medicine is prescribed when the rhythm disturbance is felt and gets in the way, not when it has been found by chance on a trace.
Method of use and dosage
The dose is set individually, according to the patient's needs and response to treatment, and the lowest effective one is used. For a patient of around 70 kilograms the recommended daily dose is 450 to 600 mg, given in two or three divided doses. With lower body weight, lower doses are used.
| Situation | What is done |
| Increasing the dose | sometimes the daily dose has to be brought up to 900 mg, but no more often than every 3–4 days and only under strict cardiological supervision |
| The sign that the dose is too high | marked widening of the QRS complex or atrioventricular block of grade II or III — grounds for considering a reduction |
| Setting the maintenance dose | done under cardiological supervision, with ECG monitoring and repeated measurement of blood pressure |
| Elderly patients, left ventricular ejection fraction below 35%, damaged heart muscle | treatment starts at low doses, and they may be raised only after 5–8 days and with extreme caution |
| Liver failure | bioavailability and half-life increase, so the dose is chosen carefully |
| Impaired kidney function | caution is needed here too: the dose is matched to the capacity for elimination |
| Children and adolescents under 18 | efficacy and safety have not been determined; because of the medicine's strength it is not given to children |
Note the logic behind these rules: propafenone is dosed not by a schedule but by the electrocardiogram. Widening of the QRS and the appearance of block are not a separate complication but a feedback signal on which the dose is taken back down.
Contraindications
Besides hypersensitivity to the active substance, to soya, to peanuts or to any excipient, diagnosed Brugada syndrome is named separately. Then comes clinically significant structural heart disease, and the list of it is specific.
- myocardial infarction within the last 3 months;
- decompensated congestive heart failure with a left ventricular ejection fraction below 35%;
- cardiogenic shock, except shock caused by the arrhythmia itself;
- symptomatic severe bradycardia, sinus node dysfunction, disorders of atrial conduction;
- atrioventricular block of grade II and above, bundle branch block or distal block in patients without a pacemaker;
- severe arterial hypotension, signs of disturbed water and electrolyte balance, for example of potassium metabolism;
- severe obstructive lung disease, myasthenia, and concurrent use of ritonavir.
The list is best read as the description of a single idea: propafenone slows conduction of the impulse, so it is forbidden everywhere that conduction is already disturbed, or where the heart would not withstand additional depression of contractility. There is one exception to that rule and it is stated separately — cardiogenic shock caused by the arrhythmia itself is not a contraindication.
Special warnings and precautions
Before treatment starts and during it, every patient has an electrocardiogram, a blood pressure measurement and an assessment of their clinical state — in order to establish whether the response to propafenone confirms the need to use it. The wording is unusual but precise: here continuation of treatment has to be justified, not assumed.
- taking propafenone may unmask Brugada syndrome or produce Brugada-like changes on the electrocardiogram in carriers of the syndrome in whom no symptoms had been seen before; that is why, once treatment has begun, an ECG is done specifically to rule such changes out;
- treatment may affect the pacing threshold and sensitivity of an implanted pacemaker, so its function is checked during therapy and reprogrammed if necessary;
- paroxysmal atrial fibrillation may turn into atrial flutter with conduction block in a 2:1 or 1:1 ratio — the rhythm can thus become slower yet more dangerous;
- because of the beta-blocking action, caution is needed in patients with asthma;
- in patients with clinically significant structural heart disease severe adverse reactions may occur, and that is precisely why the medicine is contraindicated for them.
Caution is also required in liver and kidney failure. And one more practical circumstance: blurred vision, dizziness, fatigue and orthostatic hypotension can slow reactions, so they affect the ability to drive and to operate machinery.
Interactions with other medicines
The first direction is substances that raise the concentration of propafenone. Medicines that inhibit the isoenzymes CYP2D6, CYP1A2 and CYP3A4 — cimetidine, ketoconazole, quinidine, erythromycin — and grapefruit juice as well can increase it. With such a combination the circulatory system is monitored and the dose changed if necessary.
- selective serotonin reuptake inhibitors, for example fluoxetine and paroxetine, raise the plasma concentration of propafenone: in fast metabolisers fluoxetine increased the peak concentration and the area under the curve of S-propafenone by 39% and 50%, and of R-propafenone by 71% and 50%, so a smaller dose may prove sufficient;
- amiodarone together with propafenone affects conduction and repolarisation and can cause disturbances leading to arrhythmia; the doses of both may have to be chosen afresh;
- lidocaine has no appreciable effect on the pharmacokinetics of propafenone, but in those taking propafenone the risk of central nervous system adverse effects rises;
- the risk of adverse effects grows when it is combined with local anaesthetics — for example during pacemaker implantation or a surgical or dental procedure — and with other medicines that slow the rhythm or reduce contractility: beta-blockers and tricyclic antidepressants;
- substances metabolised by the CYP2D6 isoenzyme, such as venlafaxine, may accumulate when taken together with it.
Ritonavir deserves a separate reminder: taking it at the same time as propafenone is outright contraindicated, not merely a matter for caution.
Pregnancy and breastfeeding
There are no adequate controlled studies in pregnant women. Propafenone hydrochloride is used in pregnancy only where the benefit to the mother outweighs the possible risk to the fetus.
Propafenone is known to cross the placental barrier: its concentration in cord blood has been reported at about 30% of the concentration in the mother's blood. Passage into human milk has not been studied, and limited data indicate that propafenone may pass into milk, so it is prescribed to breastfeeding women with caution. There is no outright prohibition in the leaflet, but no assertion of safety either — the decision rests with the doctor, who weighs the need for antiarrhythmic treatment in the particular woman.
Adverse reactions
The adverse reactions of propafenone fall into two directions — cardiac and general — the first calling for observation of the electrocardiogram, the second noticeable to the patient.
On the cardiac side these are disturbances of the conduction system visible on the trace: lengthening of the PQ interval, widening of the QRS complex, suppression of sinus node automaticity, atrioventricular blocks. From the rest of the body the commonest are headache, dizziness, blurred vision, paraesthesia, tremor, nausea, constipation and a dry mouth; fatigue and orthostatic hypotension belong here too, and through them the medicine affects the ability to drive. The negative inotropic effect deserves a separate mention: reduced contractility may lead to a fall in blood pressure. That is exactly why watching blood pressure is part of the dose-setting plan on a par with the electrocardiogram, rather than being ordered separately on symptoms.
Overdose
In overdose it is above all the heart's conduction system that suffers: the PQ interval lengthens, the QRS complex widens, sinus node automaticity is suppressed, and atrioventricular blocks, ventricular tachycardia and ventricular flutter and fibrillation appear. Reduced contractility can cause hypotension and, in severe cases, cardiogenic shock. Headache, dizziness, blurred vision, paraesthesia, tremor, nausea, constipation and a dry mouth are common; convulsions were observed very rarely, and a fatal outcome has also been recorded. In severe poisoning tonic-clonic convulsions, paraesthesia, drowsiness, coma and respiratory arrest are possible.
Treatment is carried out in an intensive care unit: vital functions are monitored and, where necessary, brought back to normal. Defibrillation and infusions of dopamine and isoprenaline proved effective in controlling rhythm and blood pressure, and convulsions could be stopped with intravenous diazepam. General support of vital functions may also be needed — mechanical ventilation and external cardiac massage. Attempts to remove the substance by haemoperfusion are of limited effectiveness, and haemodialysis is useless altogether: propafenone is 95% protein-bound and has a large volume of distribution.
How to get a Polfenon prescription online
The medicine is available on prescription, and prescribing it without information about the heart is impossible: the dose is set by the electrocardiogram and blood pressure, and with ventricular rhythm disturbances treatment begins in hospital in the first place. The doctor therefore needs a recent electrocardiogram, information about the left ventricular ejection fraction if it has been measured, and the exact name of your arrhythmia.
For the online consultation prepare information about any heart attack and when it happened, about heart failure, bradycardia and blocks, about an implanted pacemaker, about Brugada syndrome in yourself or your family, about lung disease, myasthenia, liver and kidney disease, and also about allergy to soya and peanuts. List the medicines you take: other antiarrhythmics, beta-blockers, antidepressants, anti-HIV drugs, antibiotics and antifungals. The doctor will assess these circumstances and, if there are no contraindications, will issue an electronic prescription.
