Propafenone dosage

An established and clinically relevant metabolic drug interaction. The dosage of oral propafenone will need increasing during concurrent use of ri-fampicin. Alternatively, if possible, the authors of the case report advise the use of another antibacterial, where possible, because of the probable difficulty in adjusting the propafenone dosage. 

Propafenone is administered orally every 8 hours. Any previously given antiarrhythmic drug should be discontinued before propafenone therapy is started. Dosage changes are done 3 to 4 days apart because of the length of time the drug remains active in the body. 

During die initiation of therapy, patients taking propafenone must be monitored carefully. To minimize adverse reactions, dosage is increased slowly at a minimum of 3- to 4-day intervals. Periodic ECG monitoringis necessary to evaluate the effects on cardiac conduction. 

Absorption/Distribution - Propafenone is nearly completely absorbed after oral administration with peak plasma levels occurring approximately 3.5 hours after administration. It exhibits extensive first-pass metabolism resulting in a dose-dependent and dosage-form-dependent absolute bioavailability. Propafenone follows a nonlinear pharmacokinetic disposition presumably due to saturation of first-pass hepatic metabolism as the liver is exposed to higher concentrations of propafenone and shows a very high degree of interindividual variability. 

As propafenone exerts both beta blockade and a (dose-related) negative inotropic effect on cardiac muscle, fully compensate patients with CHF before receiving propafenone. If CHF worsens, discontinue propafenone unless CHF is due to the cardiac arrhythmia and, if indicated, restart at a lower dosage only after adequate cardiac compensation has been established. 

Propafenone has some structural similarities to propranolol and possesses weak 3-blocking activity. Its spectrum of action is very similar to that of quinidine, but it does not prolong the action potential. Its sodium channel-blocking kinetics are similar to that of flecainide. Propafenone is metabolized in the liver, with an average half-life of 5-7 hours. The usual daily dosage of propafenone is 450-900 mg in three divided doses. The drug is used primarily for supraventricular arrhythmias. The most common adverse effects are a metallic taste and constipation arrhythmia exacerbation can also occur. 

When a pregnant woman was given propafenone from the fifth month to term in a dosage of 300 mg tds her dysrhythmias responded satisfactorily and the neonate was healthy (37). 

Information seems to be limited to these reports but they suggest that anticoagulant control should be well monitored if propafenone is given to patients taking warfarin, and probably also phenprocoumon and the indanedione fluindione. The anticoagulant dosage should be reduced where necessary. It would be prudent to apply the same precautions with any other coumarin or indanedione anticoagulant. 

Information is limited but the interaetion would seem to be established. Concurrent use need not be avoided but antieipate the need to reduce the dosage of metoprolol and propranolol. Monitor closely because some patients may experience adverse effects. If the suggested mechanism of interaction is correct it is possible (but not confirmed) that other beta blockers that undergo liver metabolism will interact similarly but not those largely excreted unchanged in the urine. See Table 22.1 , (p.833) for the metabolism of some commonly used beta blockers. Also note that propafenone and the beta blockers have negative inotropic effects, which could be additive and result in unwanted cardiodepression. 

A very well established interaetion of clinical importance. Monitor the ef-feets ofeoneurrent use and reduce the digoxin dosage appropriately in order to avoid toxieity. Most patients appear to be affected and dosage reductions in the range 15 to 70% were found necessary in one of the studies cited. The data available suggest that the extent of the rise may possibly depend on the propafenone serum concentration rather than on its dose. ... 

In a 71-year-old man, propafenone 150 mg daily raised the levels of sustained-release theophylline 300 mg twice daily from a range of 10.2 to 12.8 mg/L to 19 mg/L, and signs of theophylline toxieity developed. The day after propafenone was withdrawn the level fell to 10.8 mg/L. When the propafenone was later restarted the theophylline levels rose again to 17.7 mg/L within one week, but fell when the theophylline dosage was re-dueed by one-third. ... 

The raised desipramine levels are thought to result from decreased metabolism and clearance, caused by propafenone. The general importance of this case is uncertain, but be alert for signs of desipramine toxicity in any patient given propafenone concurrently. Adjust the desipramine dosage appropriately. 

A 46-year-old man developed syncope, a widen QRS interval, and depressed left ventricular systolic function while taking propafenone 425 bd for atrial fibrillation. This may have been due to an increased dosage of propafenone combined with heavy alcohol consumption, possibly associated with genetic susceptibility to inhibition of propafenone metabolism by alcohol. 

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