Disopyramide dosing

Transferring to mexiletine When transferring from other Class I oral antiarrhythmics to mexiletine, based on theoretical considerations, initiate with a 200 mg dose, and titrate to response as described above, 6 to 12 hours after the last dose of quinidine sulfate, 3 to 6 hours after the last dose of procainamide, 6 to 12 hours after the last disopyramide dose or 8 to 12 hours after the last tocainide dose. 

Disopyr mide. Disopyramide phosphate, a phenylacetamide analogue, is a racemic mixture. The dmg can be adininistered po or iv and is useful in the treatment of ventricular and supraventricular arrhythmias (1,2). After po administration, absorption is rapid and nearly complete (83%). Binding to plasma protein is concentration-dependent (35—95%), but at therapeutic concentrations of 2—4 lg/mL, about 50% is protein-bound. Peak plasma concentrations are achieved in 0.5—3 h. The dmg is metabolized in the fiver to a mono-AJ-dealkylated product that has antiarrhythmic activity. The elimination half-life of the dmg is 4—10 h. About 80% of the dose is excreted by the kidneys, 50% is unchanged and 50% as metabolites 15% is excreted into the bile (1,2). 

ADM INI STERI NG DISOPYRAMID E Disopyramide is administered to tiie patient with a full glass of water either 1 hour before or 2 hours after meals. If patients are receiving procainamide or quinidine tiie manufacturer suggests that disopyramide therapy not be started for 6 to 12 hours after tiie last dose of quinidine and 3 to 6 hours after tiie last dose of procainamide When tiie patient is to switch from taking tiie regular capsules to taking extended-release capsules, 6 hours should lapse after tiie last capsule before therapy is begun with tiie extended-release capsules. 

In the event of increased anticholinergic side effects, plasma levels of disopyramide should be monitored and the dose of the drug adjusted accordingly. A reduction of the dose by one third, from the recommended 600 mg/day to 400 mg/day, would be... 

Metabolism/Excretion - About 50% is excreted in the urine as the unchanged drug and 30% as metabolites (20% mono-N-dealkyIdisopyramide [MND]). The plasma concentration of MND is approximately one-tenth that of disopyramide. The mean plasma half-life is 6.7 hours (range, 4 to 10 hours). In impaired renal function, half-life values ranged from 8 to 18 hours. Therefore, decrease the dose in renal failure to avoid drug accumulation. 

Disopyramide directly depresses myocardial contractility. The negative inotropic effect may be detrimental in patients with compromised cardiac function. Some patients develop overt congestive heart failure. At usual therapeutic doses, depression of myocardial function is not a problem in most patients with normal ventricular function. 

UnUke quinidine, disopyramide does not increase the plasma concentration of digoxin in patients receiving a maintenance dose of the cardiac glycoside. Hypoglycemia has been reported with the use of disopyramide, particularly in conjunction with moderate or excessive alcohol intake. 

In the USA, disopyramide is only available for oral use. The typical oral dosage of disopyramide is 150 mg three times a day, but up to 1 g/d has been used. In patients with renal impairment, dosage must be reduced. Because of the danger of precipitating heart failure, loading doses are not recommended. 

Figure 6.17 The classification of 42 drugs in the (solubility-dose ratio, apparent permeability) plane of the QBCS. The intersection of the dashed lines drawn at the cutoff points form the region of the borderline drugs. Key 1 acetyl salicylic acid 2 atenolol 3 caffeine 4 carbamazepine 5 chlorpheniramine 6 chlorothiazide 7 cimetidine 8 clonidine 9 corticosterone 10 desipramine 11 dexamethasone 12 diazepam 13 digoxin 14 diltiazem 15 disopyramide 16 furosemide 17 gancidovir 18 glycine 19 grizeofulvin 20 hydrochlorothiazide 21 hydrocortisone 22 ibuprofen 23 indomethacine 24 ketoprofen 25 mannitol 26 metoprolol 27 naproxen 28 panadiplon 29 phenytoin 30 piroxicam 31 propanolol 32 quinidine 33 ranitidine 34 salicylic acid 35 saquinavir 36 scopolamine 37 sulfasalazine 38 sulpiride 39 testosterone 40 theophylline 41 verapamil HC1 42 zidovudine.

DISOPYRAMIDE ANALGESICS Disopyramide may slow the onset of action of intermittent dose paracetamol These drugs have anticholinergic effects that include delayed gastric emptying. This will delay absorption Warn patients that the action of paracetamol may be delayed. This will not be the case when paracetamol is taken regularly... 

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