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Drug Interactions between amiodarone and Bethaprim Pediatric

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

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Interactions between your drugs

Minor

amiodarone sulfamethoxazole

Applies to: amiodarone and Bethaprim Pediatric (sulfamethoxazole / trimethoprim)

Limited data suggest that sulfamethoxazole-trimethoprim (SMX-TMP) may rarely prolong the QT interval of the electrocardiogram. Theoretically, a pharmacodynamic interaction may occur with other agents that can prolong the QT interval, resulting in increased risk of ventricular arrhythmias including ventricular tachycardia and torsade de pointes. There have been isolated reports of QT prolongation and ventricular arrhythmias occurring in patients treated with SMX-TMP intravenously. However, a causal relationship has not been established, and the risk of clinically significant QT prolongation is unlikely at recommended dosages of SMX-TMP. 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). Patients at increased risk for QT prolongation should be advised to seek medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, palpitations, or syncope.

References

  1. Wiener I, Rubin D, Martinez E, et al. "QT prolongation and paroxysmal ventricular tachycardia occurring during fever following trimethoprim-sulfamethoxazole administration." Mt Sinai J Med 48 (1981): 53-5
  2. Crouch MA, Limon L, Cassano AT "Clinical relevance and management of drug-related QT interval prolongation." Pharmacotherapy 23 (2003): 881-908
  3. Lopez JA, Harold JG, Rosenthal MC, Oseran DS, Schapira JN, Peter T "QT prolongation and torsades de pointes after administration of trimethoprin-sulfamethoxazole." Am J Cardiol 59 (1987): 376-7
  4. Darpo B "Spectrum of drugs prolonging QT interval and the incidence of torsades de pointes." Eur Heart J Suppl 3(Suppl K) (2001): K70-80
View all 4 references

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Drug and food interactions

Major

amiodarone food

Applies to: amiodarone

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of orally administered amiodarone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In 11 nonsmoking, healthy volunteers, grapefruit juice (300 mL with drug administration, then 3 hours and 9 hours later) increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amiodarone (17 mg/kg single dose) by 84% and 50%, respectively, compared to water. Formation of the pharmacologically active metabolite, N-desethylamiodarone (N-DEA), was completely inhibited. Clinically, this interaction can lead to altered efficacy of amiodarone, since antiarrhythmic properties of amiodarone and N-DEA appear to differ. In the study, mean increases in PR and QTc intervals of 17.9% and 11.3%, respectively, were observed 6 hours postdose with water, while increases of 10.2% and 3.3%, respectively, were observed after administration with grapefruit juice.

ADJUST DOSING INTERVAL: Food increases the rate and extent of absorption of amiodarone. The mechanism appears to involve the effect of food-induced physiologic changes on drug release from its formulation. In 30 healthy volunteers, administration of a single 600 mg dose of amiodarone following a high-fat meal resulted in a Cmax and AUC that were 3.8 and 2.4 times the respective values under fasting conditions. The time to reach peak plasma concentration (Tmax) was decreased by 37%, indicating an increased rate of absorption. Mean Cmax and AUC for the active metabolite, N-DEA, also increased by 32% and 55%, respectively, but there was no change in the Tmax.

MANAGEMENT: Patients treated with oral amiodarone should avoid consumption of grapefruits and grapefruit juice. In addition, oral amiodarone should be administered consistently with regard to meals.

References

  1. "Product Information. Cordarone (amiodarone)." Wyeth-Ayerst Laboratories PROD (2002):
  2. Libersa CC, Brique SA, Motte KB, et al. "Dramatic inhibition of amiodarone metabolism induced by grapefruit juice." Br J Clin Pharmacol 49 (2000): 373-8
  3. Meng X, Mojaverian P, Doedee M, Lin E, Weinryb I, Chiang ST, Kowey PR "Bioavailability of Amiodarone tablets administered with and without food in healthy subjects." Am J Cardiol 87 (2001): 432-5

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Moderate

sulfamethoxazole food

Applies to: Bethaprim Pediatric (sulfamethoxazole / trimethoprim)

MONITOR: Two cases have been reported in which patients on sulfamethoxazole-trimethoprim therapy, after consuming beer, reported flushing, heart palpitations, dyspnea, headache, and nausea (disulfiram - alcohol type reactions). First-generation sulfonylureas have been reported to cause facial flushing when administered with alcohol by inhibiting acetaldehyde dehydrogenase and subsequently causing acetaldehyde accumulation. Since sulfamethoxazole is chemically related to first-generation sulfonylureas, a disulfiram-like reaction with products containing sulfamethoxazole is theoretically possible. However, pharmacokinetic/pharmacodynamic data are lacking and in addition, the two reported cases cannot be clearly attributed to the concomitant use of sulfamethoxazole-trimethoprim and alcohol.

MANAGEMENT: Patients should be alerted to the potential for this interaction and although the risk for this interaction is minimal, caution is recommended while taking sulfamethoxazole-trimethoprim concomitantly with alcohol.

References

  1. Heelon MW, White M "Disulfiram-cotrimoxazole reaction." Pharmacotherapy 18 (1998): 869-70
  2. Mergenhagen KA, Wattengel BA, Skelly MK, Clark CM, Russo TA "Fact versus fiction: a review of the evidence behind alcohol and antibiotic interactions." Antimicrob Agents Chemother 64 (2020): e02167-19

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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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