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Drug Interactions between dofetilide and Sustiva

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

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Interactions between your drugs

Major

efavirenz dofetilide

Applies to: Sustiva (efavirenz) and dofetilide

GENERALLY AVOID: Efavirenz can cause significant QT interval prolongation in patients with the CYP450 2B6 *6/*6 genotype due to reduced metabolic clearance of the drug stemming from decreased levels of functional CYP450 2B6 isoenzyme. 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 a QT study conducted in 58 healthy subjects enriched for CYP450 2B6 polymorphisms, mean efavirenz peak plasma concentration (Cmax) in subjects with the CYP450 2B6 *6/*6 genotype was 2.25-fold that observed in subjects with the CYP450 2B6 *1/*1 genotype following administration of efavirenz 600 mg daily for 14 days. A positive relationship between efavirenz concentration and QTc prolongation was observed, with mean QTc prolongation and its upper bound 90% confidence interval at 8.7 ms and 11.3 ms in subjects with the CYP450 2B6 *6/*6 genotype. 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: Alternatives to efavirenz should be considered in patients receiving other drugs that can prolong the QT interval. Patients treated with any medication that can cause QT prolongation 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. Sustiva (efavirenz)." DuPont Pharmaceuticals PROD (2001):

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Drug and food interactions

Moderate

efavirenz food

Applies to: Sustiva (efavirenz)

ADJUST DOSING INTERVAL: Administration with food increases the plasma concentrations of efavirenz and may increase the frequency of adverse reactions. According to the product labeling, administration of efavirenz capsules (600 mg single dose) with a high-fat/high-caloric meal (894 kcal, 54 g fat, 54% calories from fat) or a reduced-fat/normal-caloric meal (440 kcal, 2 g fat, 4% calories from fat) was associated with mean increases of 39% and 51% in efavirenz peak plasma concentration (Cmax) and 22% and 17% in systemic exposure (AUC), respectively, compared to administration under fasted conditions. For efavirenz tablets, administration of a single 600 mg dose with a high-fat/high-caloric meal (approximately 1000 kcal, 500-600 kcal from fat) resulted in a 79% increase in mean Cmax and a 28% increase in mean AUC of efavirenz relative to administration under fasted conditions.

MANAGEMENT: Efavirenz should be taken on an empty stomach, preferably at bedtime. Dosing at bedtime may improve the tolerability of nervous system symptoms such as dizziness, insomnia, impaired concentration, somnolence, abnormal dreams and hallucinations, although they often resolve on their own after the first 2 to 4 weeks of therapy . Patients should be advised of the potential for additive central nervous system effects when efavirenz is used concomitantly with alcohol or psychoactive drugs, and to avoid driving or operating hazardous machinery until they know how the medication affects them.

References

  1. "Product Information. Sustiva (efavirenz)." DuPont Pharmaceuticals PROD (2001):

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Minor

dofetilide food

Applies to: dofetilide

In vitro data suggest that grapefruit juice may inhibit the CYP450 3A4 first-pass metabolism of dofetilide. Decreased first-pass metabolism may increase dofetilide concentrations and increase the risk of QT interval prolongation and arrhythmias. The clinical significance is unknown, since dofetilide has a high oral bioavailability and a low affinity for CYP450 3A4. The manufacturer recommends caution.

References

  1. "Product Information. Tikosyn (dofetilide)." Pfizer U.S. Pharmaceuticals PROD (2001):

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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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