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Drug Interactions between Apresazide and timolol

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

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Interactions between your drugs

Moderate

hydrALAZINE hydroCHLOROthiazide

Applies to: Apresazide (hydralazine / hydrochlorothiazide) and Apresazide (hydralazine / hydrochlorothiazide)

MONITOR: Concomitant treatment with other antihypertensive agents or vasodilators, including alpha-adrenoreceptor antagonists, angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), beta-adrenergic blockers, calcium channel blockers, diuretics and nitrates, may potentiate the hypotensive effects of hydralazine and dihydralazine.

MANAGEMENT: Blood pressure and heart rate should be closely monitored when hydralazine or dihydralazine is used with other agents that can induce hypotension.

References

  1. (2022) "Product Information. Apresoline (hydralazine)." Sterimax Inc
  2. (2022) "Product Information. Hydralazine (hydralazine)." Advanz Pharma

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Moderate

timolol hydroCHLOROthiazide

Applies to: timolol and Apresazide (hydralazine / hydrochlorothiazide)

MONITOR: Although they are often combined in clinical practice, diuretics and beta-blockers may increase the risk of hyperglycemia and hypertriglyceridemia in some patients, especially in patients with diabetes or latent diabetes. In addition, the risk of QT interval prolongation and arrhythmias (e.g. torsades de pointes) due to sotalol may be increased by potassium-depleting diuretics.

MANAGEMENT: Monitoring of serum potassium levels, blood pressure, and blood glucose is recommended during coadministration. Patients should be advised to seek medical assistance if they experience dizziness, weakness, fainting, fast or irregular heartbeats, or loss of blood glucose control.

References

  1. Dornhorst A, Powell SH, Pensky J (1985) "Aggravation by propranolol of hyperglycaemic effect of hydrochlorothiazide in type II diabetics without alteration of insulin secretion." Lancet, 1, p. 123-6
  2. Roux A, Le Liboux A, Delhotal B, Gaillot J, Flouvat B (1983) "Pharmacokinetics in man of acebutolol and hydrochlorothiazide as single agents and in combination." Eur J Clin Pharmacol, 24, p. 801-6
  3. Dean S, Kendall MJ, Potter S, Thompson MH, Jackson DA (1985) "Nadolol in combination with indapamide and xipamide in resistant hypertensives." Eur J Clin Pharmacol, 28, p. 29-33
  4. (2002) "Product Information. Lozol (indapamide)." Rhone Poulenc Rorer
  5. Marcy TR, Ripley TL (2006) "Aldosterone antagonists in the treatment of heart failure." Am J Health Syst Pharm, 63, p. 49-58
View all 5 references

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Minor

hydrALAZINE timolol

Applies to: Apresazide (hydralazine / hydrochlorothiazide) and timolol

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

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Drug and food interactions

Moderate

hydrALAZINE food

Applies to: Apresazide (hydralazine / hydrochlorothiazide)

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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Moderate

timolol food

Applies to: timolol

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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Moderate

hydroCHLOROthiazide food

Applies to: Apresazide (hydralazine / hydrochlorothiazide)

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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Moderate

timolol food

Applies to: timolol

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 (1981) "Interaction of atenolol with furosemide and calcium and aluminum salts." Clin Pharmacol Ther, 30, p. 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.

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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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Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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