4.3 Addition of of "Known hypersensitivity to propafenone or to any of the other ingredients"
4.4 Addition of " THere is a potnetial for conversion of paroxysmal atrial fibrillation to atrial flutter with accompanying 2:1 or 1:1 conduction block."
4.5 Replacement of " Concomitant administration of propafenone and quinidine may result in decreased oral clearance with an increase in sterady state plasma concentrations of propafenone" with "Coadministration of propafenone hydrochloride with drugs metabolised by CYP2D6 (such as venlafaxine) might lead to increased levels of these drugs.
Drugs that inhibit CYP2D6, CYP1A2 and CYP3A4, e.g. ketoconazole, cimetidine, quinidine, tropisetron, dolasetron, mizolastine, erythromycin and grapefruit juice may lead to increased levels of propafenone hydrochloride. When propafenone hydrochloride is administered with inhibitors of these enzymes, the patients should be closely monitored and the dose adjusted accordingly.
Due to the potential for increased plasma concentrations, co-administration of 800-1200mg/day doses of ritonavir and propafenone hydrochloride is contraindicated.
Combination therapy of amiodarone and propafenone hydrochloride can affect conduction and repolarisation and lead to abnormalities that have the potential to be proarrhythmic. Dose adjustments of both compounds based on therapeutic response may be required.
No significant effects on the pharmacokinetics of propafenone or lidocaine have been seen following their concomitant use in patients. However, concomitant use of propafenone hydrochloride and intravenous lidocaine have been reported to increase the risks of central nervous system side effects of lidocaine. Phenobarbital is a known inducer of CYP3A4. Response to propafenone hydrochloride therapy should be monitored during concomitant chronic phenobarbital use." and also "Concomitant administration of propafenone hydrochloride and fluoxetine in extensive metabolisers increased the S propafenone Cmax and AUC by 39 and 50% and the R propafenone Cmax and AUC by 71 and 50%. Elevated levels of plasma propafenone may occur when propafenone hydrochloride is used concomitantly with paroxetine. Lower doses of propafenone may be sufficient to achieve the desired therapeutic response."
4.8 Addition of the following side effects : fainting, abdominal pain, ataxia, chest pain, rash and "Liver abnormalities, including hepatocellular injury, jaundice and hepatitis, elevated liver enzymes (serum transaminases and alkaline phosphatase). "
4.9 The following sentence has been added "The effects of propafenoone hydrochloride overdose in the myocardium manifest as impilse generation and conduction disordres such as PQ prolongation, QRS widening, supression of sinus node automaticity, AV block, ventricular tachycardia, ventricular flutter and ventricular fibrillation. Hypotensiopn may also occur. Convulsions somnolence and death may occur.
