After taking phenobarbital 100mg daily for 21 days, half-life and AUC of a single 200mg dose of disopyramide were reduced by about 35%. The apparent metabolic clearance more than doubled, and fraction recovered in urine as metabolite increased. Sixteen healthy subjects took part in study and no significant differences were seen between those who smoked and those who did not (See reference number 1).
It seems probable that phenobarbital (a known enzyme inducer) increases metabolism of disopyramide by liver, and thereby increases its loss from body.
This interaction appears to be established,but its clinical importance is uncertain. The extent to which it would reduce control of arrhythmias by disopyramide is unknown, but monitor effects and serum levels of disopyramide if phenobarbital is added or withdrawn. The manufacturer of disopyramide(See reference number 2) recommends avoiding using it in combination with inducers of cytochrome P450 isoenzyme CYP3A, such as phenobarbital. Other barbiturates would be expected to interact similarly.
Kapil RP,Axelson JE, Mansfield IL, Edwards DJ, McErlane B, Mason MA, Lalka D, Kerr CR.Disopyramide pharmacokinetics and metabolism: effect of inducers. Br J Clin Pharmacol (1987) 24, 781–91.
Rythmodan Capsules (Disopyramide). Sanofi-Aventis. UK Summary of product characteristics,November 2005.