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Drug Interactions between flecainide and givosiran

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

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Interactions between your drugs

Moderate

flecainide givosiran

Applies to: flecainide and givosiran

MONITOR: Coadministration with givosiran may increase the plasma concentrations and the risk of adverse effects of drugs that are substrates of CYP450 1A2 and/or CYP450 2D6. The proposed mechanism is decreased clearance due to givosiran-mediated inhibition of CYP450 1A2 and 2D6 isoenzymes. Concomitant administration of a single subcutaneous dose of givosiran (2.5 mg/kg) increased the systemic exposure (AUC) and peak plasma concentration (Cmax) of caffeine (sensitive CYP450 1A2 substrate) by 3.1-fold and 1.3-fold, respectively, and dextromethorphan (sensitive CYP450 2D6 substrate) by 2.4-fold and 2.0-fold, respectively.

MANAGEMENT: Caution and monitoring are recommended when givosiran is given with drugs that are substrates of CYP450 1A2 and/or 2D6. Concomitant use should generally be avoided with CYP450 1A2 or 2D6 substrates that have a narrow therapeutic range where minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, the dosage of the CYP450 1A2 or 2D6 substrate should be reduced according to approved product labeling or clinical response and tolerance. Dosage adjustments as well as clinical and laboratory monitoring should be considered whenever givosiran is added to or withdrawn from therapy with these drugs.

References (1)
  1. (2019) "Product Information. Givlaari (givosiran)." Alnylam Pharmaceuticals

Drug and food interactions

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

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

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