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Drug Interactions between Digitek 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

digoxin St. John's wort

Applies to: Digitek (digoxin) and st. john's wort

MONITOR: Coadministration with St. John's wort may decrease the plasma concentrations of digoxin. The proposed mechanism is induction of the P-glycoprotein-mediated intestinal efflux and renal tubular secretion of digoxin by constituents of St. John's wort. In 18 healthy volunteers, administration of a single 0.25 mg dose of digoxin on the last day of St. John's wort treatment (300 mg three times a day for 14 days, standardized to contain 3% hyperforin) resulted in a 36% decrease in digoxin peak plasma concentration (Cmax) and 23% decrease in systemic exposure (AUC) compared to administration of digoxin alone. Likewise, 10 days of treatment with an herbal extract of St. John's wort (900 mg/day) in 13 healthy volunteers reduced the steady-state Cmax, AUC and trough concentration (Cmin) of digoxin (0.25 mg/day for 15 days) by 26%, 25% and 33%, respectively, compared to placebo. No statistically significant change was observed in digoxin pharmacokinetics after the first dose of St. John's wort extract starting on day 6 of digoxin administration; however, the effect became increasingly pronounced until the tenth day of comedication, which suggests a time-dependent interaction.

MANAGEMENT: Patients should consult a healthcare provider before taking any herbal or alternative medicine. If concomitant use of St. John's wort is required, digoxin levels should be checked more frequently and the dosage adjusted accordingly, particularly following initiation, discontinuation or change of dosage of St. John's wort in patients who are stabilized on their digoxin regimen. Patients should be advised to notify their physician if they experience a worsening of their heart symptoms. Due to differences in phytochemical content and potency of commercial herbal products in general, the pharmacokinetic effects of St. John's wort may vary depending on the specific preparation.

References (12)
  1. Johne A, Brockmoller J, Bauer S, Maurer A, Langheinrich M, Roots I (1999) "Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum)." Clin Pharmacol Ther, 66, p. 338-45
  2. Fugh-Berman A (2000) "Herb-drug interactions." Lancet, 355, p. 134-8
  3. De Smet PA, Touw DJ (2000) "Safety of St John's wort (Hypericum perforatum)." Lancet, 355, p. 575-6
  4. Yue QY, Berquist C, Gerden B (2000) "Safety of St John's wort (Hypericum perforatum)." Lancet, 355, p. 576-7
  5. Westphal K, Weinbrenner A, Giessmann T, Stuhr M, Franke G, Zschiesche M, Oertel R, Terhaag B, Kroemer HK, Siegmund W (2000) "Oral bioavailability of digoxin is enhanced by talinolol: Evidence for involvement of intestinal P-glycoprotein." Clin Pharmacol Ther, 68, p. 6-12
  6. Cheng TO (2000) "St John's wort interaction with digoxin." Arch Intern Med, 160, p. 2548
  7. 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
  8. Izzo AA, Ernst E (2001) "Interactions between herbal medicines and prescribed drugs: a systematic review." Drugs, 61, p. 2163-75
  9. Kurata Y, Ieiri I, Kimura M, et al. (2002) "Role of human MDR1 gene polymorphism in bioavailability and interaction of digoxin, a substrate of P-glycoprotein." Clin Pharmacol Ther, 72, p. 209-19
  10. Lin JH (2003) "Drug-drug interaction mediated by inhibition and induction of P-glycoprotein." Adv Drug Deliv Rev, 55, p. 53-81
  11. Drescher S, Glaeser H, Murdter T, Hitzl M, Eichelbaum M, Fromm MF (2003) "P-glycoprotein-mediated intestinal and biliary digoxin transport in humans." Clin Pharmacol Ther, 73, p. 223-31
  12. Gurley BJ, Swain A, Williams DK, Barone G, Battu SK (2008) "Gauging the clinical significance of P-glycoprotein-mediated herb-drug interactions: comparative effects of St. John's wort, Echinacea, clarithromycin, and rifampin on digoxin pharmacokinetics." Mol Nutr Food Res, 52, p. 772-9

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

digoxin food

Applies to: Digitek (digoxin)

Administration of digoxin with a high-fiber meal has been shown to decrease its bioavailability by almost 20%. Fiber can sequester up to 45% of the drug when given orally. Patients should be advised to maintain a regular diet without significant fluctuation in fiber intake while digoxin is being titrated.

Grapefruit juice may modestly increase the plasma concentrations of digoxin. The mechanism is increased absorption of digoxin due to mild inhibition of intestinal P-glycoprotein by certain compounds present in grapefruits. In 12 healthy volunteers, administration of grapefruit juice with and 30 minutes before, as well as 3.5, 7.5, and 11.5 hours after a single digoxin dose (0.5 mg) increased the mean area under the plasma concentration-time curve (AUC) of digoxin by just 9% compared to administration with water. Moreover, P-glycoprotein genetic polymorphism does not appear to influence the magnitude of the effects of grapefruit juice on digoxin. Thus, the interaction is unlikely to be of clinical significance.

References (2)
  1. Darcy PF (1995) "Nutrient-drug interactions." Adverse Drug React Toxicol Rev, 14, p. 233-54
  2. Becquemont L, Verstuyft C, Kerb R, et al. (2001) "Effect of grapefruit juice on digoxin pharmacokinetics in humans." Clin Pharmacol Ther, 70, p. 311-6

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.