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Drug Interactions between fosamprenavir and modafinil

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

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Interactions between your drugs

Moderate

modafinil fosamprenavir

Applies to: modafinil and fosamprenavir

MONITOR: Coadministration with modafinil (the racemate) or armodafinil (the R-enantiomer) may decrease the plasma concentrations of protease inhibitors (PIs). The mechanism involves induction of intestinal CYP450 3A4-mediated first-pass metabolism by modafinil and armodafinil, with possible secondary induction of hepatic 3A4 metabolism. Significant intestinal metabolism appears to occur with indinavir and saquinavir but has not been studied with other PIs. Conversely, PIs may increase the plasma concentrations of modafinil via inhibition of hepatic CYP450 3A4 metabolism. The clinical significance is unknown. However, the possibility of prolonged and/or increased pharmacologic effects of modafinil should be considered.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with decreased or subtherapeutic antiretroviral drug levels, caution is advised if modafinil or armodafinil must be used in patients treated with PIs, particularly if they are using only one PI in their antiretroviral regimen. Clinical monitoring for altered effects of both modafinil and the PI may be appropriate following addition or withdrawal of one or the other drug.

References (7)
  1. Barry M, Gibbons S, Back D, Mulcahy F (1997) "Protease inhibitors in patients with HIV disease. Clinically important pharmacokinetic considerations." Clin Pharmacokinet, 32, p. 194-209
  2. (2001) "Product Information. Provigil (modafinil)." Cephalon, Inc
  3. Sommadossi JP (1999) "HIV protease inhibitors: pharmacologic and metabolic distinctions." AIDS, 13, s29-40
  4. Durant J, Clevenbergh P, Garraffo R, Halfon P, Icard S, DelGiudice P, Montagne N, Schapiro JM, Dellamonica P (2000) "Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: pharmacological data from the Viradapt Study." Aids, 14, p. 1333-9
  5. Robertson P, Decory HH, Madan A, Parkinson A (2000) "In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil." Drug Metab Dispos, 28, p. 664-71
  6. Doherty MM, Charman WN (2002) "The mucosa of the small intestine: how clinically relevant as an organ of drug metabolism?" Clin Pharmacokinet, 41, p. 235-53
  7. (2007) "Product Information. Nuvigil (armodafinil)." Cephalon Inc

Drug and food interactions

Moderate

fosamprenavir food

Applies to: fosamprenavir

ADJUST DOSING INTERVAL: Food may reduce the systemic bioavailability of amprenavir from fosamprenavir oral suspension. The mechanism of interaction has not been described. According to the product labeling, administration of fosamprenavir oral suspension (1400 mg single dose) with a high-fat meal (967 kcal, 67 g fat, 33 g protein, 58 g carbohydrate) reduced amprenavir peak plasma concentration (Cmax) by 46% and systemic exposure (AUC) by 28% compared to administration in a fasted state. The time to reach peak plasma level (Tmax) was delayed by 0.72 hours. In contrast, the same high-fat meal did not affect the pharmacokinetics of amprenavir from fosamprenavir tablets.

MANAGEMENT: Fosamprenavir suspension should be administered on an empty stomach in adults, but with food in pediatric patients to aid palatability and compliance. If emesis occurs within 30 minutes after dosing the suspension, the dose should be repeated. Fosamprenavir tablets may be taken with or without food.

References (1)
  1. (2003) "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline
Minor

modafinil food

Applies to: modafinil

Administration with food may delay the absorption of modafinil (the racemate) and armodafinil (the R-enantiomer) without significantly affecting their overall bioavailability. According to the product labeling, modafinil's absorption may be delayed by approximately one hour if taken with food. Similarly, the time to reach peak plasma concentration (Tmax) of armodafinil may be delayed by approximately 2 to 4 hours in the fed state.

References (2)
  1. (2001) "Product Information. Provigil (modafinil)." Cephalon, Inc
  2. (2007) "Product Information. Nuvigil (armodafinil)." Cephalon Inc

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.

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