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Drug Interactions between fosamprenavir and Quinidex Extentabs

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

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Interactions between your drugs

Major

quiNIDine fosamprenavir

Applies to: Quinidex Extentabs (quinidine) and fosamprenavir

MONITOR CLOSELY: Coadministration with amprenavir or its prodrug, fosamprenavir, may significantly increase the plasma concentrations of antiarrhythmic agents that are primarily metabolized by CYP450 3A4 such as amiodarone, bepridil, systemic lidocaine, and quinidine. The proposed mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by amprenavir. The interaction has not been specifically studied, but could conceivably lead to serious and/or life-threatening reactions including cardiac arrhythmias and other toxicities if levels are substantially increased. The use of amiodarone, bepridil, and quinidine has been associated with dose-related prolongation of the QT interval, thus elevated plasma levels may potentiate the risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes as well as cardiac arrest and sudden death.

MANAGEMENT: Caution is advised if amprenavir or fosamprenavir must be used with antiarrhythmic agents that are substrates of CYP450 3A4. Pharmacologic response and plasma antiarrhythmic drug levels should be monitored more closely whenever amprenavir or fosamprenavir is added to or withdrawn from therapy, and the antiarrhythmic dosage adjusted as necessary. Concomitant use with amiodarone, bepridil, lidocaine, or quinidine is specifically contraindicated according to Canadian and European labeling.

References

  1. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  2. (2003) "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
View all 4 references

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Drug and food interactions

Moderate

quiNIDine food

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

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Moderate

fosamprenavir food

Applies to: fosamprenavir

ADJUST DOSING INTERVAL: Food may reduce the systemic bioavailability of amprenavir from fosamprenavir oral suspension. The mechanism of interaction has not been described. According to the product labeling, administration of fosamprenavir oral suspension (1400 mg single dose) with a high-fat meal (967 kcal, 67 g fat, 33 g protein, 58 g carbohydrate) reduced amprenavir peak plasma concentration (Cmax) by 46% and systemic exposure (AUC) by 28% compared to administration in a fasted state. The time to reach peak plasma level (Tmax) was delayed by 0.72 hours. In contrast, the same high-fat meal did not affect the pharmacokinetics of amprenavir from fosamprenavir tablets.

MANAGEMENT: Fosamprenavir suspension should be administered on an empty stomach in adults, but with food in pediatric patients to aid palatability and compliance. If emesis occurs within 30 minutes after dosing the suspension, the dose should be repeated. Fosamprenavir tablets may be taken with or without food.

References

  1. (2003) "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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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

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