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Drug Interactions between Cardioquin and Cordarone IV

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

amiodarone quiNIDine

Applies to: Cordarone IV (amiodarone) and Cardioquin (quinidine)

GENERALLY AVOID: Coadministration of amiodarone and quinidine may increase the risk of new arrhythmias due to additive depressant effects on cardiac conduction. There have been reports of torsade de pointes arrhythmia in association with significantly prolonged QT interval in patients receiving concomitant therapy. Serious exacerbation of preexisting arrhythmia may also be more likely during coadministration relative to either agent alone. Despite the potential toxicities, amiodarone and quinidine have been used together successfully in the treatment of certain arrhythmias.

ADJUST DOSE: Amiodarone may increase the plasma concentrations of quinidine. The mechanism of interaction has not been established, but may involve inhibition of quinidine clearance via CYP450 3A4 metabolism and/or P-glycoprotein efflux. In 11 patients stabilized on quinidine (1.2 to 4.2 gm/day), the addition of amiodarone (600 mg every 12 hours for 5 to 7 days, followed by 600 mg daily) increased mean serum quinidine concentrations by approximately 33%. Signs of toxicity including diarrhea, nausea, vomiting, and hypotension were reported in some patients, necessitating dosage reductions by an average of 37%. Due to the long and variable half-life of amiodarone, potential for interaction may exist even after its discontinuation.

MANAGEMENT: The concurrent use of amiodarone with other antiarrhythmic agents, including quinidine, should be reserved for patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent or to amiodarone alone. A dosage reduction for quinidine is recommended during coadministration. In general, if adding or transferring to oral amiodarone, the dosages of previously administered agents should be reduced by 30% to 50% several days after initiation of amiodarone, when onset of arrhythmia suppression is expected to occur. The continued need for other antiarrhythmic agents should be evaluated after the effects of amiodarone have been established, and discontinuation should ordinarily be attempted. If the combination is continued, patients should be monitored closely for adverse effects including conduction disturbances and exacerbation of tachyarrhythmias. Conversely, in amiodarone-treated patients who require additional antiarrhythmic agents, the initial dosage of such agents should be approximately one-half the usual recommended dosage. Patients should be advised to seek medical attention if they experience potential signs of quinidine toxicity such as nausea, vomiting, diarrhea, tinnitus, hearing loss, vertigo, visual disturbances, dizziness, headache and confusion, or symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitations, irregular heartbeat, shortness of breath and syncope.

References

  1. Lesko LJ "Pharmacokinetic drug interactions with amiodarone." Clin Pharmacokinet 17 (1989): 130-40
  2. Gill J, Heel RC, Fitton A "Amiodarone: an overview of its pharmacological properties, and review of its therapeutic use in cardiac arrhythmias." Drugs 43 (1992): 69-110
  3. Saal AK, Werner JA, Greene HL, Sears GK, Graham EL "Effect of amiodarone on serum quinidine and procainamide levels." Am J Cardiol 53 (1984): 1264-7
  4. Tartini R, Kappenberger L, Steinbrunn W, Meyer UA "Dangerous interaction between amiodarone and quinidine." Lancet 1 (1982): 1327-9
  5. "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories PROD (2002):
  6. Kerin NZ, Ansari-Leesar M, Faitel K, Narala C, Frumin H, Cohen A "The effectiveness and safety of the simultaneous administration of quinidine and amiodarone in the conversion of chronic atrial fibrillation." Am Heart J 125 (1993): 1017-21
  7. Hoffman A, Follathe F, Burckhardt D "Safe treatment of resistant ventricular arrhythmias with a combination of amiodarone and quinidine or mexiletine." Lancet i (1983): 704
View all 7 references

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Drug and food interactions

Major

amiodarone food

Applies to: Cordarone IV (amiodarone)

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of orally administered amiodarone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In 11 nonsmoking, healthy volunteers, grapefruit juice (300 mL with drug administration, then 3 hours and 9 hours later) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amiodarone (17 mg/kg single dose) by 84% and 50%, respectively, compared to water. Formation of the pharmacologically active metabolite, N-desethylamiodarone (N-DEA), was completely inhibited. Clinically, this interaction can lead to altered efficacy of amiodarone, since antiarrhythmic properties of amiodarone and N-DEA appear to differ. In the study, mean increases in PR and QTc intervals of 17.9% and 11.3%, respectively, were observed 6 hours postdose with water, while increases of 10.2% and 3.3%, respectively, were observed after administration with grapefruit juice.

ADJUST DOSING INTERVAL: Food increases the rate and extent of absorption of amiodarone. The mechanism appears to involve the effect of food-induced physiologic changes on drug release from its formulation. In 30 healthy volunteers, administration of a single 600 mg dose of amiodarone following a high-fat meal resulted in a Cmax and AUC that were 3.8 and 2.4 times the respective values under fasting conditions. The time to reach peak plasma concentration (Tmax) was decreased by 37%, indicating an increased rate of absorption. Mean Cmax and AUC for the active metabolite, N-DEA, also increased by 32% and 55%, respectively, but there was no change in the Tmax.

MANAGEMENT: Patients treated with oral amiodarone should avoid consumption of grapefruits and grapefruit juice. In addition, oral amiodarone should be administered consistently with regard to meals.

References

  1. "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories PROD (2002):
  2. Libersa CC, Brique SA, Motte KB, et al. "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol 49 (2000): 373-8
  3. Meng X, Mojaverian P, Doedee M, Lin E, Weinryb I, Chiang ST, Kowey PR "Bioavailability of Amiodarone tablets administered with and without food in healthy subjects." Am J Cardiol 87 (2001): 432-5

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Moderate

quiNIDine food

Applies to: Cardioquin (quinidine)

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.

References

  1. Ace LN, Jaffe JM, Kunka RL "Effect of food and an antacid on quinidine bioavailability." Biopharm Drug Dispos 4 (1983): 183-90
  2. Min DI, Ku YM, Geraets DR, Lee HC "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol 36 (1996): 469-76
  3. Ha HR, Chen J, Leuenberger PM, Freiburghaus AU, Follah F "In vitro inhibition of midazolam and quinidine metabolism by flavonoids." Eur J Clin Pharmacol 48 (1995): 367-71
  4. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
View all 4 references

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Antiarrhythmics

Therapeutic duplication

The recommended maximum number of medicines in the 'antiarrhythmics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antiarrhythmics' category:

  • Cardioquin (quinidine)
  • Cordarone IV (amiodarone)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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