Effect of coadministration of verapamil and quinidine on serum digoxin concentration

Abstract

Both quinidine and verapamil are known to increase the serum digoxin concentration (SDC), and other calcium channel blockers may have a similar effect. Since an increasing number of patients is likely to be treated concurrently with digoxin, quinidine and a calcium channel blocker, a study was done to show whether coadministered quinidine and verapamil would cooperate to elevate the SDC. Nine healthy volunteers on basic digoxin treatment (Leanoxin 0.125 mg t.i.d.) were treated with placebo, verapamil 80 mg t.i.d. and the combination (verapamil 80 mg plus quinidine base 160 mg t.i.d.), for 2 weeks in a randomized sequence. Drug concentration and various cardiovascular parameters were measured each week and/or at the end of each treatment period. Steady state concentrations were always obtained within 1 week and drug levels at the end of the first and second weeks of treatment were almost identical. The plasma verapamil concentration (PVC) was 25.8 +/- 9.9 ng/ml during coadministration of verapamil and digoxin, and 15.7 +/- 6.9 ng/ml during combined verapamil-quinidine coadministration, when the serum quinidine concentration (SQC) was 1.26 +/- 0.50 micrograms/ml. Compared to placebo SDC rose by 53% from 0.62 +/- 0.16 to 0.95 +/- 0.29 ng/ml (p less than 0.001) during verapamil treatment and further to 1.58 +/- 0.38 ng/ml (155% rise; p less than 0.001) during combined verapamil-quinidine coadministration. Thus each drug maintained its own effect on SDC in the presence of the other, and their actions became combined in increasing the SDC.(ABSTRACT TRUNCATED AT 250 WORDS)

Application of Receiver Operating Characteristic Analysis to Refine the Prediction of Potential Digoxin Drug Interactions

“…Several perpetrator drugs such as carvedilol, diltiazem, and felodopine resulted in both positive and negative digoxin drug interactions, i.e., changes in digoxin plasma exposure were less than or greater than the clinical threshold value of 1.25. (Doering, 1983) a Amiodarone: doses are from the same study; 800 mg was dosed for 1 week (maintenance dose) and concentration represents the 1 week dosing and the 400 mg was the next 5 weeks.…”

The Effect of Telmisartan on the Steady‐State Pharmacokinetics of Digoxin in Healthy Male Volunteers

“…Increased serum concentrations of digoxin-like immunoreactivity of a similar magnitude have been reported to occur when digoxin is coadministered with other classes of antihypertensive agents. These include calcium channel blockers, 14,[17][18][19][20][21][22][23][24][25][26][27][28] angiotensin-converting enzyme inhibitors such as captopril, 15 and betablockers such as carvedilol. 16 The antiarrhythmic agents quinidine, amiodarone, and propafenone also interact pharmacokinetically with digoxin, producing increased glycoside effects.…”

“…Because telmisartan and digoxin have different pharmacologic modes of action, coadministration of the two drugs could occasionally be considered for patients with congestive heart failure. Digoxin has a narrow therapeutic index and has been shown to interact with a wide range of drugs, 13 including antihypertensive agents [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] and antiarrhythmic drugs. 14,17,29 The present study was designed to investigate whether multiple-dose administration of telmisartan has any effect on the steady-state pharmacokinetics of digoxin in healthy male volunteers.…”

Poisoning Due to Calcium Antagonists

“…With the narrow therapeutic window of digoxin, this interaction could lead to toxic effects. The action of both verapamil and quinidine in raising digoxin concentrations appears to be additive when these agents are used together (Doering 1983). For example, combined therapy can cause undesirable bradyarrhythmia in people with underlying cardiac conduction disease, but could facilitate control of ventricular response rate in atrial fibrillation.…”