Altered pharmacokinetics of quinidine: diltiazem significantly decreases the clearance and increases
the t1/2 of quinidine, but quinidine does not alter the kinetics of diltiazem. Drugs that alkalinize the
urine (carbonic-anhydrase inhibitors, sodium bicarbonate, thiazide diuretics) reduce renal elimination of
By pharmacokinetic mechanisms that are not well understood, quinidine levels are increased by coadministration of
amiodarone or cimetidine. Very rarely, and again by mechanisms not understood, quinidine levels are
decreased by coadministration of nifedipine.
Hepatic elimination of quinidine may be accelerated by coadministration of drugs (phenobarbital, phenytoin,
rifampin) that induce production of cytochrome P450IIIA4.
Perhaps because of competition for the P450IIIA4 metabolic pathway, quinidine levels rise when ketaconazole is
Coadministration of propranolol usually does not affect quinidine pharmacokinetics, but in some studies the
b-blocker appeared to cause increases in the peak serum levels of quinidine, decreases in
quinidines volume of distribution, and decreases in total quinidine clearance. The effects (if any) of
coadministration of other b-blockers on quinidine pharmacokinetics have not been
Hepatic clearance of quinidine is significantly reduced during coadministration of verapamil, with
corresponding increases in serum levels and half-life.
Altered pharmacokinetics of other drugs: Duraquin slows the elimination of digoxin and simultaneously
reduces digoxins apparent volume of distribution. As a result, serum digoxin levels may be as much as doubled. When
quinidine and digoxin are coadministered, digoxin doses usually need to be reduced. Serum levels of digitoxin are
also raised when quinidine is coadministered, although the effect appears to be smaller.
By a mechanism that is not understood, quinidine potentiates the anticoagulatory action of warfarin, and the
anticoagulant dosage may need to be reduced.
Cytochrome P450IID6 is an enzyme critical to the metabolism of many drugs, notably including mexiletine, some
phenothiazines, and most polycyclic antidepressants. Constitutional deficiency of cytochrome P450IID6
is found in less than 1% of Orientals, in about 2% of American blacks, and in about 8% of American whites. Testing
with debrisoquine is sometimes used to distinguish the P450IID6-deficient "poor metabolizers" from the
majority-phenotype "extensive metabolizers".
When drugs whose metabolism is P450IID6-dependent are given to p.o. metabolizers, the serum levels achieved are
higher, sometimes much higher, than the serum levels achieved when identical doses are given to extensive
metabolizers. To obtain similar clinical benefit without toxicity, doses given to poor metabolizers may need to be
greatly reduced. In the case of prodrugs whose actions are actually mediated by P450IID6-produced metabolites (for
example, codeine and hydrocodone, whose analgesic and antitussive effects appear to be mediated by
morphine and hydromorphone, respectively), it may not be possible to achieve the desired clinical benefits in poor
Duraquin is not metabolized by cytochrome P450IID6, but therapeutic serum levels of quinidine inhibit the action of
cytochrome P450IID6, effectively converting extensive metabolizers into p.o. metabolizers. Caution must be exercised
whenever quinidine is prescribed together with drugs metabolized by cytochrome P450IID6.
Perhaps by competing for pathways of renal clearance, coadministration of quinidine causes an increase in serum
levels of procainamide.
Serum levels of haloperidol are increased when quinidine is coadministered.
Presumably because both drugs are metabolized by cytochrome P450IIIA4, coadministration of quinidine causes variable
slowing of the metabolism of nifedipine. Interactions with other dihydropyridine calcium channel blockers have
not been reported, but these agents (including felodipine, nicardipine, and nimodipine) are all
dependent upon P450IIIA4 for metabolism, so similar interactions with quinidine should be anticipated.
Altered pharmacodynamics of other drugs: Duraquins anticholinergic, vasodilating, and negative
inotropic actions may be additive to those of other drugs with these effects, and antagonistic to those of drugs with
cholinergic, vasoconstricting, and positive inotropic effects. For example, when quinidine and verapamil are
coadministered in doses that are each well tolerated as monotherapy, hypotension attributable to additive peripheral
a-blockade is sometimes reported.
Duraquin potentiates the actions of depolarizing (succinylcholine, decamethonium) and nondepolarizing
(d-tubocurarine, pancuronium) neuromuscular blocking agents. These phenomena are not well understood, but they
are observed in animal models as well as in humans. In addition, in vitro addition of quinidine to the serum
of pregnant women reduces the activity of pseudocholinesterase, an enzyme that is essential to the metabolism of
Non-interactions of quinidine with other drugs: Duraquin has no clinically significant effect on the
pharmacokinetics of diltiazem, flecainide, mephenytoin, metoprolol, propafenone, propranolol, quinine,
timolol, or tocainide.
Conversely, the pharmacokinetics of quinidine are not significantly affected by caffeine,
ciprofloxacin, digoxin, diltiazem, felodipine, omeprazole, or quinine. Duraquins pharmacokinetics are
also unaffected by cigarette smoking.