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Drug Interactions between flecainide and fluoxetine

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

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Interactions between your drugs

Moderate

flecainide FLUoxetine

Applies to: flecainide and fluoxetine

MONITOR: Coadministration with certain selective serotonin reuptake inhibitors (SSRIs) may increase the plasma concentrations of antiarrhythmic agents that are metabolized by CYP450 2D6 such as encainide, flecainide, mexiletine, and propafenone. The mechanism is decreased drug clearance due to inhibition of the isoenzyme by some SSRIs. The interaction has been studied specifically with fluoxetine and propafenone. In nine healthy 2D6-extensive metabolizers, fluoxetine pretreatment (20 mg once a day for 10 days) significantly increased the elimination half-life, peak plasma concentration (Cmax), and area under the concentration-time curve (AUC) of both the S- and R-enantiomers of propafenone (400 mg single dose). Oral clearance decreased by about 34% for both enantiomers. In vitro inhibition data suggest that fluoxetine and paroxetine have the most significant effects on 2D6 metabolism of propafenone, while fluvoxamine and sertraline have only modest effects.

MANAGEMENT: Caution is advised if certain SSRIs, particularly fluoxetine or paroxetine, must be used concomitantly with antiarrhythmic agents that are metabolized by CYP450 2D6. Lower initial dosages of the antiarrhythmic agent may be appropriate. Patients who are already stabilized on their antiarrhythmic regimen should be monitored for altered effects on myocardial conduction following addition or discontinuation of SSRI therapy (up to 2 weeks for most SSRIs and 5 weeks for fluoxetine due to its long half-life), and the antiarrhythmic dosage adjusted if necessary. Alternatively, an antidepressant that does not interfere with 2D6 metabolism may be considered, such as citalopram, escitalopram, or venlafaxine.

References (7)
  1. (2001) "Product Information. Zoloft (sertraline)." Roerig Division
  2. (2001) "Product Information. Prozac (fluoxetine)." Dista Products Company
  3. (2001) "Product Information. Paxil (paroxetine)." GlaxoSmithKline
  4. Alfaro CL, Lam YWF, Simpson J, Ereshefsky L (1999) "CYP2D6 status of extensive metabolizers after multiple-dose fluoxetine, fluvoxamine, paroxetine, or sertraline." J Clin Psychopharmacol, 19, p. 155-63
  5. Cai WM, Chen B, Zhou Y, Zhang YD (1999) "Fluoxetine impairs the CYP2D6-mediated metabolism of propafenone enantiomers in healthy Chinese volunteers." Clin Pharmacol Ther, 66, p. 516-21
  6. Hemeryck A, DeVriendt C, Belpaire FM (2000) "Effect of selective serotonin reuptake inhibitors on the oxidative metabolism of propafenone: In vitro studies using human liver microsomes." J Clin Psychopharmacol, 20, p. 428-34
  7. Kusumoto M, Ueno K, Oda A, Takeda K, Mashimo K, Takaya K, Fujimura Y, Nishihori T, Tanaka K (2001) "Effect of fluvoxamine on the pharmacokinetics of mexiletine in healthy Japanese men." Clin Pharmacol Ther, 69, p. 104-7

Drug and food interactions

Moderate

FLUoxetine food

Applies to: fluoxetine

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
Moderate

flecainide food

Applies to: flecainide

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.

References (4)
  1. (2024) "Product Information. Cytisine (cytisinicline)." Consilient Health Ltd
  2. jeong sh, Newcombe D, sheridan j, Tingle M (2015) "Pharmacokinetics of cytisine, an a4 b2 nicotinic receptor partial agonist, in healthy smokers following a single dose." Drug Test Anal, 7, p. 475-82
  3. Vaughan DP, Beckett AH, Robbie DS (1976) "The influence of smoking on the intersubject variation in pentazocine elimination." Br J Clin Pharmacol, 3, p. 279-83
  4. Zevin S, Benowitz NL (1999) "Drug interactions with tobacco smoking: an update" Clin Pharmacokinet, 36, p. 425-38

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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