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Drug Interactions between st. john's wort and Viekira XR

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

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Interactions between your drugs

Major

ritonavir St. John's wort

Applies to: Viekira XR (dasabuvir / ombitasvir / paritaprevir / ritonavir) 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. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. Cerner Multum, Inc. "Australian Product Information."
  4. Cerner Multum, Inc. (2015) "Canadian Product Information."
View all 4 references

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Major

St. John's wort ombitasvir

Applies to: st. john's wort and Viekira XR (dasabuvir / ombitasvir / paritaprevir / ritonavir)

CONTRAINDICATED: Coadministration with potent inducers of CYP450 isoenzymes may significantly decrease the plasma concentrations of ombitasvir, paritaprevir, ritonavir, and dasabuvir. In 12 study subjects, administration of single-dose ombitasvir, paritaprevir, ritonavir, and dasabuvir with the potent CYP450 inducer carbamazepine (200 mg once daily followed by 200 mg twice daily) decreased ombitasvir peak plasma concentration (Cmax) by 31% and systemic exposure (AUC) by 31%; paritaprevir Cmax by 66% and AUC by 70%; ritonavir Cmax by 83% and AUC by 87%; and dasabuvir Cmax by 55% and AUC by 70%. Loss of therapeutic effects and development of resistance may occur.

MANAGEMENT: Concomitant use of ombitasvir/paritaprevir/ritonavir plus dasabuvir with potent CYP450 inducers such as carbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort is considered contraindicated.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. van Erp NP, Guchelaar HJ, Ploeger BA, Romijn JA, Hartigh J, Gelderblom H (2011) "Mitotane has a strong and a durable inducing effect on CYP3A4 activity." Eur J Endocrinol, 164, p. 621-6
  3. (2012) "Product Information. Xtandi (enzalutamide)." Astellas Pharma US, Inc
  4. (2022) "Product Information. Viekira Pak (dasabuvir/ombitasvir/paritaprev/ritonav)." AbbVie US LLC
View all 4 references

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Major

St. John's wort dasabuvir

Applies to: st. john's wort and Viekira XR (dasabuvir / ombitasvir / paritaprevir / ritonavir)

CONTRAINDICATED: Coadministration with potent inducers of CYP450 isoenzymes may significantly decrease the plasma concentrations of ombitasvir, paritaprevir, ritonavir, and dasabuvir. In 12 study subjects, administration of single-dose ombitasvir, paritaprevir, ritonavir, and dasabuvir with the potent CYP450 inducer carbamazepine (200 mg once daily followed by 200 mg twice daily) decreased ombitasvir peak plasma concentration (Cmax) by 31% and systemic exposure (AUC) by 31%; paritaprevir Cmax by 66% and AUC by 70%; ritonavir Cmax by 83% and AUC by 87%; and dasabuvir Cmax by 55% and AUC by 70%. Loss of therapeutic effects and development of resistance may occur.

MANAGEMENT: Concomitant use of ombitasvir/paritaprevir/ritonavir plus dasabuvir with potent CYP450 inducers such as carbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort is considered contraindicated.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. van Erp NP, Guchelaar HJ, Ploeger BA, Romijn JA, Hartigh J, Gelderblom H (2011) "Mitotane has a strong and a durable inducing effect on CYP3A4 activity." Eur J Endocrinol, 164, p. 621-6
  3. (2012) "Product Information. Xtandi (enzalutamide)." Astellas Pharma US, Inc
  4. (2022) "Product Information. Viekira Pak (dasabuvir/ombitasvir/paritaprev/ritonav)." AbbVie US LLC
View all 4 references

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Drug and food interactions

Moderate

ritonavir food

Applies to: Viekira XR (dasabuvir / ombitasvir / paritaprevir / ritonavir)

ADJUST DOSING INTERVAL: Administration with food may modestly affect the bioavailability of ritonavir from the various available formulations. When the oral solution was given under nonfasting conditions, peak ritonavir concentrations decreased 23% and the extent of absorption decreased 7% relative to fasting conditions. Dilution of the oral solution (within one hour of dosing) with 240 mL of chocolate milk or a nutritional supplement (Advera or Ensure) did not significantly affect the extent and rate of ritonavir absorption. When a single 100 mg dose of the tablet was administered with a high-fat meal (907 kcal; 52% fat, 15% protein, 33% carbohydrates), approximately 20% decreases in mean peak concentration (Cmax) and systemic exposure (AUC) were observed relative to administration after fasting. Similar decreases in Cmax and AUC were reported when the tablet was administered with a moderate-fat meal. In contrast, the extent of absorption of ritonavir from the soft gelatin capsule formulation was 13% higher when administered with a meal (615 KCal; 14.5% fat, 9% protein, and 76% carbohydrate) relative to fasting.

MANAGEMENT: Ritonavir should be taken with meals to enhance gastrointestinal tolerability.

References

  1. (2001) "Product Information. Norvir (ritonavir)." Abbott Pharmaceutical

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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 (2002) "Hypertensive crisis associated with St. John's Wort." Am J Med, 112, p. 507-8

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Moderate

paritaprevir food

Applies to: Viekira XR (dasabuvir / ombitasvir / paritaprevir / ritonavir)

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of ombitasvir, paritaprevir, ritonavir, and dasabuvir. Relative to fasting conditions, administration of ombitasvir, paritaprevir, ritonavir, and dasabuvir with a moderate-fat meal (approximately 600 Kcal; 20% to 30% calories from fat) increased the mean systemic exposure (AUC) by 82%, 211%, 49%, and 30%, respectively. Relative to fasting conditions, administration of ombitasvir, paritaprevir, ritonavir, and dasabuvir with a high-fat meal (approximately 900 Kcal; with 60% calories from fat) increased the mean AUC by 76%, 180%, 44%, and 22%, respectively.

MANAGEMENT: Ombitasvir/paritaprevir/ritonavir plus dasabuvir should always be administered with a meal. The fat or calorie content does not matter.

References

  1. (2022) "Product Information. Viekira Pak (dasabuvir/ombitasvir/paritaprev/ritonav)." AbbVie US LLC

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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.