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Drug Interactions between alprazolam 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

ALPRAZolam St. John's wort

Applies to: alprazolam and st. john's wort

MONITOR: Long-term (10 days or more) administration of St. John's wort may significantly decrease the oral bioavailability and/or plasma concentrations of benzodiazepines that are exclusively metabolized by CYP450 3A4 such as alprazolam, midazolam, and triazolam. The proposed mechanism is induction of CYP450 3A4-mediated intestinal (first-pass) and hepatic metabolism by constituents of St. John's wort. In 12 healthy volunteers, pretreatment with St. John's wort (300 mg, containing 0.9 mg hypericin, orally 3 times a day for 2 weeks) decreased the mean peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and bioavailability of oral midazolam (5 mg single dose) by 43%, 52% and 45%, respectively, compared to administration of midazolam alone. The oral clearance of midazolam approximately doubled with St. John's wort, while the elimination half-life was not significantly altered. In contrast, St. John's wort decreased the AUC of intravenous midazolam (0.05 mg/kg single dose) by only 21% and increased its clearance by 27% compared to control, and the difference was not statistically significant. Another study found that systemic clearance of IV midazolam increased by 44% while oral clearance increased by 168% after pretreatment with St. John's wort for 12 days. The interaction has also been reported with alprazolam. In 12 heathy volunteers, mean AUC and elimination half-life of alprazolam (2 mg single dose) reduced by approximately one-half and oral clearance more than doubled following treatment with St. John's wort for 2 weeks. However, effects of the interaction may be highly variable due to differences in composition of commercial St. John's wort products and deviation from labeled claims of many herbal products. A clinical study found no consistent effects on alprazolam with the use of recommended dosages of St. John's wort in seven healthy subjects.

MANAGEMENT: In general, patients should be advised to consult their healthcare provider before using any herbal or alternative medicines. If St. John's wort is prescribed with alprazolam, midazolam or triazolam, the possibility of a diminished therapeutic response to the benzodiazepine should be considered. Patients should be monitored more closely following the addition, withdrawal or change of dosage of St. John's wort, and the benzodiazepine dosage adjusted as necessary.

References

  1. Markowitz JS, DeVane CL, Boulton DW, Carson SW, Nahas Z, Risch SC (2000) "Effect of St. John's wort (Hypericum perforatum) on cytochrome P-450 2D6 and 3A4 activity in healthy volunteers." Life Sci, 66, pl133-9
  2. Roby CA, Anderson GD, Kantor E, Dryer DA, Burstein AH (2000) "St John's Wort: Effect on CYP3A4 activity." Clin Pharmacol Ther, 67, p. 451-7
  3. (2001) St. John's wort plus prescriptions equals trouble. Available from: URL:http://dailynews.yahoo.com/h/nm/20010312/hl/herb_1.html
  4. Durr D, Stieger B, KullakUblick GA, Rentsch KM, Steinert HC, Meier PJ, Fattinger K (2000) "St John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4." Clin Pharmacol Ther, 68, p. 598-604
  5. Wang Z, Gorski JC, Hamman MA, Huang SM, Lesko LJ, Hall SD (2001) "The effects of St John's wort (Hypericum perforatum) on human cytochrome P450 activity." Clin Pharmacol Ther, 70, p. 317-26
  6. Dresser GK, Schwarz UI, Wilkinson GR, Kim RB (2003) "Coordinate induction of both cytochrome P4503A and MDR1 by St John's wort in healthy subjects." Clin Pharmacol Ther, 73, p. 41-50
  7. Markowitz JS, Donovan JL, DeVane CL, et al. (2003) "Effect of St John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme." JAMA, 290, p. 1500-4
  8. Izzo AA (2004) "Drug interactions with St. John's Wort (Hypericum perforatum): a review of the clinical evidence." Int J Clin Pharmacol Ther, 42, p. 139-48
  9. Mannel M (2004) "Drug Interactions with St John's Wort : Mechanisms and Clinical Implications." Drug Saf, 27, p. 773-97
  10. Zhou S, Chan E, Pan SQ, Huang M, Lee EJ (2004) "Pharmacokinetic interactions of drugs with St John's wort." J Psychopharmacol, 18, p. 262-76
View all 10 references

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Drug and food interactions

Moderate

ALPRAZolam food

Applies to: alprazolam

GENERALLY AVOID: The pharmacologic activity of oral midazolam, triazolam, and alprazolam may be increased if taken after drinking grapefruit juice. The proposed mechanism is CYP450 3A4 enzyme inhibition. In addition, acute alcohol ingestion may potentiate CNS depression and other CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MANAGEMENT: The manufacturer recommends that grapefruit juice should not be taken with oral midazolam. Patients taking triazolam or alprazolam should be monitored for excessive sedation. Alternatively, the patient could consume orange juice which does not interact with these drugs. Patients should be advised to avoid alcohol during benzodiazepine therapy.

References

  1. (2002) "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn
  2. (2002) "Product Information. Valium (diazepam)." Roche Laboratories
  3. (2001) "Product Information. Halcion (triazolam)." Pharmacia and Upjohn
  4. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  5. Kupferschmidt HHT, Ha HR, Ziegler WH, Meier PJ, Krahenbuhl S (1995) "Interaction between grapefruit juice and midazolam in humans." Clin Pharmacol Ther, 58, p. 20-8
  6. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  7. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
View all 7 references

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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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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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