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Drug Interactions between amprenavir and lacosamide

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

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Interactions between your drugs

Moderate

amprenavir lacosamide

Applies to: amprenavir and lacosamide

MONITOR: Coadministration of strong inhibitors of CYP450 3A4 and/or CYP450 2C9 in patients with renal or hepatic impairment may significantly increase lacosamide plasma concentrations and increase the risk of lacosamide toxicity. The presumed mechanism is additive reduction in lacosamide clearance. Pharmacokinetic studies have shown lacosamide systemic exposure (AUC) may increase by 25% to 60% in patients with renal and/or hepatic impairment. Additional increases in lacosamide plasma concentrations are possible due to inhibition of the CYP450 3A4 and 2C9-mediated formation of O-desmethyl metabolite (inactive). Approximately 30% of a lacosamide dose is excreted as O-desmethyl metabolite in the urine. This interaction has not been established in vivo but is possible based on in vitro data.

MANAGEMENT: For patients with renal and/or hepatic impairment concomitantly receiving a strong CYP450 3A4 and/or CYP450 2C9 inhibitor, lacosamide dose reductions in addition to those recommended for renal and/or hepatic impairment may be necessary. Manufacturer labeling should be consulted for dose recommendations in renal and/or hepatic impairment. Patients should be advised to notify their physician if they experience dizziness, lightheadedness, fainting, or irregular heartbeat. Lacosamide dose adjustments may be necessary whenever a strong CYP450 3A4 and/or 2C9 inhibitor is added to or withdrawn from therapy in patients with renal and/or hepatic impairment.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2008) "Product Information. Vimpat (lacosamide)." UCB Pharma Inc

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Drug and food interactions

Moderate

amprenavir food

Applies to: amprenavir

GENERALLY AVOID: Administration with a high-fat meal may decrease the oral bioavailability of amprenavir. The mechanism is unknown. In healthy volunteers, consumption of a standardized high-fat meal decreased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amprenavir (1200 mg single oral dose) by 36% and 21%, respectively, compared to administration in the fasted state. The time to reach Cmax (Tmax) was increased 44% following a high-fat meal.

Grapefruit juice does not appear to significantly affect the pharmacokinetics of amprenavir. In 12 healthy volunteers, administration with grapefruit juice (200 mL) decreased the mean peak plasma concentration (Cmax) of amprenavir (1200 mg single oral dose) by 22% compared to water. The median time to reach Cmax (Tmax) was prolonged from 0.75 to 1.13 hours. These pharmacokinetic changes are not thought to be clinically significant, since antiretroviral response is more closely associated with systemic exposure (AUC) and trough plasma concentration (Cmin), which were not affected in the study.

MANAGEMENT: Amprenavir may be taken with or without food, but should not be taken with a high-fat meal.

References

  1. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  2. Demarles D, Gillotin C, Bonaventure-Paci S, Vincent I, Fosse S, Taburet AM (2002) "Single-dose pharmacokinetics of amprenavir coadministered with grapefruit juice." Antimicrob Agents Chemother, 46, p. 1589-1590

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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.

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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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