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Drug Interactions between hydralazine and metoprolol

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

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Interactions between your drugs

Minor

hydrALAZINE metoprolol

Applies to: hydralazine and metoprolol

Hydralazine may increase serum levels of some oral beta blockers. The proposed mechanism is reduced hepatic blood flow resulting in decreased biotransformation of beta blockers that undergo extensive first-pass metabolism. The interaction is less likely to occur with sustained-release preparations. Renally excreted beta-blockers such as atenolol, carteolol, nadolol, or sotalol are not expected to interact. This combination generally tends to have beneficial effects and is used commonly in the treatment of hypertension. The patient's clinical response should be monitored. A dosage adjustment for the beta blocker may be required when given concomitantly with hydralazine.

References

  1. Schneck DW, Vary JE "Mechanism by which hydralazine increases propranolol bioavailability." Clin Pharmacol Ther 35 (1984): 447-53
  2. Stagni G, Davis PJ, Ludden TM "Human pharmacokinetics of betaxolol enantiomers." J Pharm Sci 80 (1991): 321-4
  3. Janku I, Perlik F, Tkaczykova M, Brodanova M "Disposition kinetics and concentration-effect relationship of metipranolol in patients with cirrhosis and healthy subjects." Eur J Clin Pharmacol 42 (1992): 337-40
  4. Lindeberg S, Holm B, Lundborg P, Regardh CG, Sandstrom B "The effect of hydralazine on steady-state plasma concentrations of metoprolol in pregnant hypertensive women." Eur J Clin Pharmacol 35 (1988): 131-5
  5. Piquette-Miller M, Foster RT, Kappagoda CT, Jamali F "Effect of aging on the pharmacokinetics of acebutolol enantiomers." J Clin Pharmacol 32 (1992): 148-56
  6. McLean AJ, Skews H, Bobik A, Dudley FJ "Interaction between oral propranolol and hydralazine." Clin Pharmacol Ther 27 (1980): 726-32
  7. Byrne AJ, McNeil JJ, Harrison PM, Louis W, Tonkin AM, McLean AJ "Stable oral availability of sustained release propranolol when co-administered with hydralazine or food: evidence implicating substrate delivery rate as a determinant of presystemic drug interactions." Br J Clin Pharmacol 17 Suppl (1984): s45-50
  8. Smith RL "Polymorphic metabolism of the beta-adrenoreceptor blocking drugs and its clinical relevance." Eur J Clin Pharmacol 28 (1985): 77-84
  9. McGourty JC, Silas JH, Fleming JJ, McBurney A, Ward JW "Pharmacokinetics and beta-blocking effects of timolol in poor and extensive metabolizers of debrisoquin." Clin Pharmacol Ther 38 (1985): 409-13
  10. Le Coz F, Sauleman P, Poirier JM, Cuche JL, Midavaine M, Rames A, Lecocq B, Jaillon P "Oral pharmacokinetics of bisoprolol in resting and exercising healthy volunteers." J Cardiovasc Pharmacol 18 (1991): 28-34
  11. Amemiya M, Tabei K, Furuya H, Sakairi Y, Asano Y "Pharmacokinetics of carteolol in patients with impaired renal function." Eur J Clin Pharmacol 43 (1992): 417-21
  12. "Product Information. Tenormin (atenolol)." ICN Pharmaceuticals Inc PROD (2002):
  13. "Product Information. Normodyne (labetalol)." Schering Corporation PROD (2002):
  14. "Product Information. Corgard (nadolol)." Bristol-Myers Squibb PROD (2002):
  15. "Product Information. Inderal (propranolol)." Wyeth-Ayerst Laboratories PROD (2001):
  16. McLean AJ, Wilhelm D, Heinzow BG "Stable oral availability of atenolol coadministered with hydralazine. Comparison with propranolol, metoprolol and other B-Adrenoceptor antagonists." Drugs 25 (1983): 131-5
  17. "Product Information. Blocadren (timolol)." Merck & Co., Inc PROD (2001):
  18. "Product Information. Brevibloc (esmolol)." DuPont Pharmaceuticals PROD (2001):
  19. "Product Information. Cartrol (carteolol)." Abbott Pharmaceutical PROD (2001):
  20. "Product Information. Betapace (sotalol)." Berlex Laboratories PROD (2001):
  21. "Product Information. Levatol (penbutolol)." Reed and Carnrick PROD (2001):
  22. Morgan T "Clinical pharmacokinetics and pharmacodynamics of carvedilol." Clin Pharmacokinet 26 (1994): 335-46
  23. McTavish D, Campoli-Richards D, Sorkin EM "Carvedilol. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy." Drugs 45 (1993): 232-58
  24. Seffart G ed. "Drug Dosage in Renal Insufficiency." Dordrecht, South Holland, : Kluwer Academic Publishers (1991):
  25. Limbird LE eds., Gilman AG, Hardman JG "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: McGraw-Hill (1995):
View all 25 references

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Drug and food interactions

Moderate

metoprolol food

Applies to: metoprolol

ADJUST DOSING INTERVAL: The bioavailability of metoprolol may be enhanced by food.

MANAGEMENT: Patients may be instructed to take metoprolol at the same time each day, preferably with or immediately following meals.

References

  1. "Product Information. Lopressor (metoprolol)." Novartis Pharmaceuticals PROD (2001):
  2. Darcy PF "Nutrient-drug interactions." Adverse Drug React Toxicol Rev 14 (1995): 233-54

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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 "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1
  2. Shook TL, Kirshenbaum JM, Hundley RF, Shorey JM, Lamas GA "Ethanol intoxication complicating intravenous nitroglycerin therapy." Ann Intern Med 101 (1984): 498-9
  3. Feder R "Bradycardia and syncope induced by fluoxetine." J Clin Psychiatry 52 (1991): 139
  4. Ellison JM, Milofsky JE, Ely E "Fluoxetine-induced bradycardia and syncope in two patients." J Clin Psychiatry 51 (1990): 385-6
  5. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40
  6. Cerner Multum, Inc. "Australian Product Information." O 0
  7. Pacher P, Kecskemeti V "Cardiovascular side effects of new antidepressants and antipsychotics: new drugs, old concerns?" Curr Pharm Des 10 (2004): 2463-75
  8. Andrews C, Pinner G "Postural hypotension induced by paroxetine." BMJ 316 (1998): 595
View all 8 references

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Moderate

metoprolol food

Applies to: metoprolol

ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers. The exact mechanism of interaction is unknown. In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively. The elimination half-life increased by 44%. Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone. However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments. The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

MANAGEMENT: It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours. Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.

References

  1. Kirch W, Schafer-Korting M, Axthelm T, Kohler H, Mutschler E "Interaction of atenolol with furosemide and calcium and aluminum salts." Clin Pharmacol Ther 30 (1981): 429-35

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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.

See also

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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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