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Drug Interactions between ceritinib and procainamide

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

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Interactions between your drugs

Major

procainamide ceritinib

Applies to: procainamide and ceritinib

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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Drug and food interactions

Major

ceritinib food

Applies to: ceritinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of ceritinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because ceritinib is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death. Other, more common side effects such as diarrhea, nausea, vomiting, abdominal pain, hyperglycemia, and bradycardia may also increase.

ADJUST DOSING INTERVAL: Food increases the oral bioavailability of ceritinib. The mechanism of interaction is unknown. Compared to the fast state, administration of a single 500 mg dose of ceritinib with a high-fat meal (approximately 1000 calories; 58 grams of fat) increased ceritinib peak plasma concentration (Cmax) and systemic exposure (AUC) by 41% and 73%, respectively, and administration with a low-fat meal (approximately 330 calories; 9 grams of fat) increased ceritinib Cmax and AUC by 43% and 58%, respectively. A dose of 600 mg or higher taken with a meal is expected to produce systemic exposure exceeding that from a 750 mg dose taken in the fasted state, which may lead to increased adverse effects.

MANAGEMENT: Patients treated with ceritinib should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Ceritinib should be administered on an empty stomach (i.e., avoid administration within 2 hours of a meal).

References

  1. "Product Information. Zykadia (ceritinib)." Novartis Pharmaceuticals (2014):

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Minor

procainamide food

Applies to: procainamide

Ethanol may increase the acetylation of procainamide. Subtherapeutic plasma levels of procainamide may result in some patients. Because the acetylated metabolite of procainamide also possesses antiarrhythmic properties, the clinical effects are unclear.

References

  1. Olsen H, Morland J "Ethanol-induced increase in procainamide acetylation in man." Br J Clin Pharmacol 13 (1982): 203-8

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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

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

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