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Drug Interactions between hydralazine and licorice

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

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Moderate

hydrALAZINE licorice

Applies to: hydralazine and licorice

GENERALLY AVOID: Licorice use has been associated with hypertension and may antagonize the effects of antihypertensive agents. Glycyrrhizic acid, a component of licorice, is hydrolyzed in the intestine to a metabolite (glycyrrhetinic acid) that causes mineralocorticoid and renin-suppressing effects. In one study, licorice was found to increase blood pressure in a dose-dependent manner. Healthy volunteers who consumed licorice 50 to 200 g/day (corresponding to 75 to 540 mg/day of glycyrrhetinic acid) for two to four weeks had a 3.1 to 14.4 mmHg increase in their systolic blood pressure. Even the lowest dosage demonstrated a significant effect. In another study, plasma potassium levels decreased by 0.3 to 1.5 mEq/L in 12 out of 14 healthy volunteers who ingested licorice 100 or 200 g/day (equivalent to 700 to 1400 mg/day of glycyrrhizic acid) for one to four weeks, including four who had to be withdrawn from the study because of hypokalemia. Two more subjects were withdrawn due to edema of the face, hands, and ankles. Other side effects reported include mild, transient generalized edema; headache; sodium retention; and weight gain (1 to 4 kg, mean 1.5 kg). Signs of renin-angiotensin-aldosterone suppression were observed in all subjects, especially plasma renin activity and urinary aldosterone concentrations, which fell to subnormal or undetectable levels in the majority of subjects. There have been various published case reports of refractory hypertension, severe hypokalemia (life-threatening hypokalemic paralysis, myopathy, arrhythmia, or cardiac arrest), and hypertensive encephalopathy in association with licorice intoxication. Hypertension and hypokalemia have also been reported with moderate doses of licorice in the form of licorice-flavored chewing gum or candy, chewing tobacco, or licorice-based foods and beverages consumed on a chronic basis. Prolonged use of licorice has led to a hypermineralocorticoid (pseudohyperaldosteronism) syndrome characterized by hypertension, hypernatremia, hypokalemia, metabolic alkalosis, renin-angiotensin-aldosterone suppression, and edema. In studies and case reports, licorice toxicity has generally been completely reversible within one to several weeks of licorice discontinuation. However, renin-angiotensin-aldosterone axis may be suppressed for up to several months.

MANAGEMENT: Patients receiving antihypertensive therapy should avoid or limit the consumption of licorice-containing products. Even relatively moderate doses of licorice may be problematic in susceptible patients when ingested regularly for prolonged periods.

References

  1. Ishikawa S, Kato M, Tokuda T, Momoi H, Sekijima Y, Higuchi M, Yanagisawa N (1999) "Licorice-induced hypokalemic myopathy and hypokalemic renal tubular damage in anorexia nervosa." Int J Eating Disorder, 26, p. 111-4
  2. Cumming AM, Boddy K, Brown JJ, et al. (1980) "Severe hypokalaemia with paralysis induced by small doses of liquorice." Postgrad Med J, 56, p. 526-9
  3. Cumming A (1976) "Severe reduction of serum potassium induced by licorice." Nurs Times, 72, p. 367-70
  4. Lin SH, Yang SS, Chau T, Halperin ML (2003) "An unusual cause of hypokalemic paralysis: chronic licorice ingestion." Am J Med Sci, 325, p. 153-6
  5. de Klerk GJ, Nieuwenhuis MG, Beutler JJ (1997) "Lesson of the week: hypokalaemia and hypertension associated with use of liquorice flavoured chewing gum." BMJ, 314, p. 731
  6. Edwards CR (1991) "Lessons from licorice." N Engl J Med, 325, p. 1242-3
  7. Stewart PM, Wallace AM, Valentino R, Burt D, Shackleton CH, Edwards CR (1987) "Mineralocorticoid activity of liquorice: 11-beta-hydroxysteroid dehydrogenase deficiency comes of age." Lancet, 2, p. 821-4
  8. Nielsen I, Pedersen RS (1984) "Life-threatening hypokalaemia caused by liquorice ingestion." Lancet, 1, p. 1305
  9. Rosseel M, Schoors D (1993) "Chewing gum and hypokalaemia." Lancet, 341, p. 175
  10. Clyburn EB, DiPette DJ (1995) "Hypertension induced by drugs and other substances." Semin Nephrol, 15, p. 72-86
  11. Farese RV, Biglieri EG, Shackleton CH, Irony I, Gomez-Fontes R (1991) "Licorice-induced hypermineralocorticoidism." N Engl J Med, 325, p. 1223-7
  12. Elinav E, Chajek-Shaul T (2003) "Licorice consumption causing severe hypokalemic paralysis." Mayo Clin Proc, 78, p. 767-8
  13. Richard CL, Jurgens TM (2005) "Effects of natural health products on blood pressure." Ann Pharmacother, 39, p. 712-20
  14. Sigurjonsdottir HA, Franzson L, Manhem K, Ragnarsson J, Sigurdsson G, Wallerstedt S (2001) "Liquorice-induced rise in blood pressure: a linear dose-response relationship." J Hum Hypertens, 15, p. 549-52
  15. Dellow EL, Unwin RJ, Honour JW (1999) "Pontefract cakes can be bad for you: refractory hypertension and liquorice excess." Nephrol Dial Transplant, 14, p. 218-20
  16. Epstein MT, Espiner EA, Donald RA, Hughes H (1977) "Effect of eating liquorice on the renin-angiotensin aldosterone axis in normal subjects." Br Med J, 1, p. 488-90
  17. Epstein MT, Espiner EA, Donald RA, Hughes H (1977) "Liquorice toxicity and the renin-angiotensin-aldosterone axis in man." Br Med J, 1, p. 209-10
  18. Cumming AM (1977) "Metabolic effects of licorice." Br Med J, 1, p. 906
  19. Bannister B, Ginsburg R, Shneerson J (1977) "Cardiac arrest due to liquorice-induced hypokalaemia." Br Med J, 2, p. 738-9
  20. Holmes AM, Young J, Marrott PK, Prentice E (1970) "Pseudohyperaldosteronism induced by habitual ingestion of liquorice." Postgrad Med J, 46, p. 625-9
View all 20 references

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Drug and food interactions

Moderate

hydrALAZINE food

Applies to: hydralazine

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation. Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution and close monitoring for development of hypotension is advised during coadministration of these agents. Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

References

  1. Sternbach H (1991) "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol, 11, p. 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA (1984) "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med, 101, p. 498-9
  3. Feder R (1991) "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry, 52, p. 139
  4. Ellison JM, Milofsky JE, Ely E (1990) "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry, 51, p. 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. (2001) "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit, 23, p. 435-40
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Pacher P, Kecskemeti V (2004) "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des, 10, p. 2463-75
  8. Andrews C, Pinner G (1998) "Postural hypotension induced by paroxetine." BMJ, 316, p. 595
View all 8 references

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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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