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Drug Interactions between emtricitabine / nelfinavir / tenofovir and st. john's wort

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

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Interactions between your drugs

Major

nelfinavir St. John's wort

Applies to: emtricitabine / nelfinavir / tenofovir and st. john's wort

CONTRAINDICATED: Coadministration with St. John's wort may significantly reduce the plasma concentrations of HIV protease inhibitors and result in a potential loss of virologic response. The mechanism is induction of CYP450 3A4 metabolism by constituents of St. John's wort. In 8 healthy volunteers, St. John's wort (300 mg, standardized to 0.3% hypericin, 3 times a day for 14 days) decreased the 8-hour area under the plasma concentration-time curve (AUC) and extrapolated 8-hour trough of indinavir (800 mg every 8 hours for 4 doses) by a mean of 57% and 81%, respectively, compared to administration of indinavir alone. All participants showed a reduction in the indinavir 8-hour postdose concentration ranging from 49% to 99%.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiretroviral drug levels, concomitant use of HIV protease inhibitors with St. John's wort is considered contraindicated. The enzyme induction may last for up to 2 weeks after the last dose of St. John's wort. Patients should be advised to consult with their caregivers before using any herbal or alternative medicines.

References

  1. "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical PROD (2001):
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. Cerner Multum, Inc. "Canadian Product Information." O 0 (2015):
View all 4 references

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Major

St. John's wort tenofovir

Applies to: st. john's wort and emtricitabine / nelfinavir / tenofovir

GENERALLY AVOID: Coadministration with inducers of P-glycoprotein (P-gp) may decrease the oral bioavailability and plasma concentrations of tenofovir alafenamide (TAF), which is a substrate of the efflux transporter. In 26 healthy study subjects, administration of TAF (25 mg once daily) with the P-gp inducer carbamazepine (300 mg twice daily) decreased TAF plasma concentration (Cmax) and systemic exposure (AUC) by an average of 57% and 55%, respectively, compared to TAF administered alone. It is not known if, and to what extent, tenofovir disoproxil fumarate (TDF), another prodrug of tenofovir, may interact with P-gp inducers. The interaction has not been studied with TDF, and no information is found in the labeling of various products containing TDF, although it has been reported to be a P-gp substrate also.

MANAGEMENT: Given the risk of reduced viral susceptibility and resistance development associated with subtherapeutic antiviral drug levels, concomitant use of tenofovir alafenamide fumarate with P-gp inducers is not recommended. Whether this also applies to tenofovir disoproxil fumarate has not been established.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. "Product Information. Descovy (emtricitabine-tenofovir)." Gilead Sciences (2016):
  4. "Product Information. Vemlidy (tenofovir)." Gilead Sciences (2017):
View all 4 references

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Drug and food interactions

Moderate

St. John's wort food

Applies to: st. john's wort

GENERALLY AVOID: An isolated case report suggests that foods containing large amounts of tyramine may precipitate a hypertensive crisis in patients treated with St. John's wort. The mechanism of interaction is unknown, as St. John's wort is not thought to possess monoamine oxidase (MAO) inhibiting activity at concentrations achieved in vivo. The case patient was a 41-year-old man who had been taking St. John's wort for seven days prior to presentation at the emergency room with confusion and disorientation. The patient recalled last eating aged cheese and having a glass of red wine approximately 10 hours prior to admission. No other cause of delirium or hypertension could be identified. In addition, alcohol may potentiate some of the pharmacologic effects of St. John's wort. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Until further information is available, patients treated with St. John's wort should consider avoiding consumption of protein foods in which aging or breakdown of protein is used to increase flavor. These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, yogurt, papaya products, meat tenderizers, fava beans, protein extracts, and dietary supplements. Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well. Patients should also be advised to avoid or limit consumption of alcohol.

References

  1. Patel S, Robinson R, Burk M "Hypertensive crisis associated with St. John's Wort." Am J Med 112 (2002): 507-8

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Minor

tenofovir food

Applies to: emtricitabine / nelfinavir / tenofovir

Food enhances the oral absorption and bioavailability of tenofovir, the active entity of tenofovir disoproxil fumarate. According to the product labeling, administration of the drug following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of tenofovir by approximately 14% and 40%, respectively, compared to administration in the fasting state. However, administration with a light meal did not significantly affect the pharmacokinetics of tenofovir compared to administration in the fasting state. Food delays the time to reach tenofovir Cmax by approximately 1 hour. Tenofovir disoproxil fumarate may be administered without regard to meals.

References

  1. "Product Information. Viread (tenofovir)." Gilead Sciences (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

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