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Drug Interactions between Akynzeo and Quin-G

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

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Interactions between your drugs

Major

quiNIDine palonosetron

Applies to: Quin-G (quinidine) and Akynzeo (netupitant / palonosetron)

GENERALLY AVOID: Class IA (e.g., disopyramide, quinidine, procainamide) and class III (e.g., amiodarone, dofetilide, sotalol) antiarrhythmic agents can cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Coadministration of class IA or class III antiarrhythmic agents with other drugs that can prolong the QT interval should preferably be avoided unless benefits are anticipated to outweigh the risks. Caution and clinical monitoring are recommended if concomitant use is required. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories PROD (2002):
  2. "Product Information. Vascor (bepridil)." McNeil Pharmaceutical PROD (2002):
  3. "Product Information. Procan SR (procainamide)." Parke-Davis PROD (2001):
  4. "Product Information. Quiniglute (quinidine)." Berlex, Richmond, CA.
  5. "Product Information. Betapace (sotalol)." Berlex Laboratories PROD (2001):
  6. "Product Information. Norpace (disopyramide)." Searle PROD (2001):
  7. Trujillo TC, Nolan PE "Antiarrhythmic agents - Drug interactions of clinical significance." Drug Safety 23 (2000): 509-32
  8. Yamreudeewong W, DeBisschop M, Martin L, Lower D "Potentially Significant Drug Interactions of Class III Antiarrhythmic Drugs." Drug Saf 26 (2003): 421-38
  9. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  10. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  11. Cerner Multum, Inc. "Australian Product Information." O 0
  12. EMA. European Medicines Agency. European Union "EMA - List of medicines under additional monitoring. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852" (2013):
  13. Maxa JL, Hebeler RF, Adeeko MA "Torsades de pointes following concurrent amiodarone and levofloxacin therapy." Proc (Bayl Univ Med Cent) 19 (2006): 345-6
View all 13 references

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Moderate

quiNIDine netupitant

Applies to: Quin-G (quinidine) and Akynzeo (netupitant / palonosetron)

MONITOR: Coadministration with netupitant or its prodrug, fosnetupitant, may increase the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by netupitant and its desmethyl metabolite. When a single 7.5 mg oral dose of midazolam, a CYP450 3A4 probe substrate, was administered with netupitant 300 mg, mean midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 36% and 126%, respectively. When a 500 mg dose of erythromycin, another CYP450 3A4 substrate, was coadministered with netupitant 300 mg, the mean Cmax and AUC of erythromycin were increased by 92% and 56%, respectively, although the systemic exposure of erythromycin was highly variable.

MANAGEMENT: Caution is advised when netupitant or fosnetupitant is used concomitantly with drugs that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever netupitant or fosnetupitant is added to or withdrawn from therapy. The inhibitory effect on CYP450 3A4 can last for 6 days after administration of a single dose of netupitant or fosnetupitant.

References

  1. Cerner Multum, Inc. "Australian Product Information." O 0
  2. "Product Information. Akynzeo (netupitant-palonosetron)." Eisai Inc (2014):
  3. "Product Information. Akynzeo for Injection (fosnetupitant-palonosetron)." Helsinn Therapeutics Inc (2018):

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Drug and food interactions

Moderate

quiNIDine food

Applies to: Quin-G (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

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.

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

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