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Drug Interactions between roflumilast 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

Moderate

St. John's wort roflumilast

Applies to: st. john's wort and roflumilast

GENERALLY AVOID: Coadministration with potent CYP450 inducers may significantly reduce the systemic exposure to roflumilast and its pharmacologically active N-oxide metabolite, the former of which is metabolized by CYP450 1A2 and 3A4, and the latter of which is metabolized by CYP450 2C19 and 3A4. In 15 healthy volunteers, administration of a single 500 mcg oral dose of roflumilast in combination with the potent CYP450 3A4 inducer rifampin (600 mg once daily for 11 days) resulted in a 68% reduction of roflumilast peak plasma concentration (Cmax) and 80% reduction of systemic exposure (AUC) compared to administration of roflumilast alone. In addition, rifampin increased the Cmax of roflumilast N-oxide by 30% and decreased its AUC and half-life by 56% and 2.5-fold (from 24 to 9.9 hours), respectively. Total phosphodiesterase 4 inhibitory activity (i.e., combined effect of both roflumilast and roflumilast N-oxide) decreased by 58% in association with these changes.

MANAGEMENT: Due to the potential for reduced therapeutic effectiveness of roflumilast, concomitant use with potent CYP450 enzyme inducers such as carbamazepine, phenobarbital, phenytoin, rifampin, and St. John's wort is not recommended.

References (2)
  1. Nassr N, Huennemeyer A, Herzog R, et al. (2009) "Effects of rifampicin on the pharmacokinetics of roflumilast and roflumilast N-oxide in healthy subjects." Br J Clin Pharmacol, 68, p. 580-7
  2. (2011) "Product Information. Daliresp (roflumilast)." Astra-Zeneca Pharmaceuticals

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

roflumilast food

Applies to: roflumilast

Food intake does not affect the total exposure to roflumilast and its pharmacologically active N-oxide metabolite, but delays the time to maximum concentration (Tmax) of roflumilast by one hour and reduces its peak plasma concentration (Cmax) by approximately 40%. The Tmax and Cmax of
roflumilast N-oxide are unaffected. Roflumilast may be taken with or without food.

References (3)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. (2011) "Product Information. Daxas (roflumilast)." Nycomed Inc
  3. (2011) "Product Information. Daliresp (roflumilast)." Astra-Zeneca Pharmaceuticals

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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