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Drug Interaction Report

7 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Moderate

nadolol betamethasone

Applies to: bendroflumethiazide / nadolol, betamethasone

MONITOR: Corticosteroids may antagonize the effects of antihypertensive medications by inducing sodium and fluid retention. These effects may be more common with the natural corticosteroids (cortisone, hydrocortisone) because they have greater mineralocorticoid activity. Conversely, some calcium channel blockers such as diltiazem and verapamil may increase corticosteroid plasma levels and effects by inhibiting their clearance via CYP450 3A4 metabolism.

MANAGEMENT: Patients on prolonged (i.e., longer than about a week) or high-dose corticosteroid therapy should have blood pressure, electrolyte levels, and body weight monitored regularly, and be observed for the development of edema and congestive heart failure. The dosages of antihypertensive medications may require adjustment.

References

  1. "Multum Information Services, Inc. Expert Review Panel"
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."

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Moderate

nadolol bendroflumethiazide

Applies to: bendroflumethiazide / nadolol, bendroflumethiazide / nadolol

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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Moderate

betamethasone bendroflumethiazide

Applies to: betamethasone, bendroflumethiazide / nadolol

MONITOR: The concomitant use of corticosteroids and agents that deplete potassium (e.g., potassium-wasting diuretics, amphotericin B, cation exchange resins) may result in increased risk of hypokalemia. Corticosteroids can produce hypokalemia and other electrolyte disturbances via mineralocorticoid effects, the degree of which varies with the agent (from most to least potent: fludrocortisone - cortisone/hydrocortisone - prednisolone/prednisone - other glucocorticoids) and route of administration (i.e. systemic vs. local). However, large systemic doses of any corticosteroid can demonstrate these effects, particularly if given for longer than brief periods. When used pharmacologically, adrenocorticotropic agents such as corticotropin have similar mineralocorticoid activities as cortisone and hydrocortisone.

MANAGEMENT: Patients receiving potassium-depleting agents with corticosteroids should be monitored closely for development of hypokalemia, particularly if fludrocortisone or large doses of another corticosteroid or adrenocorticotropic agent is given. Potassium supplementation may be necessary. Patients should be advised to notify their physician if they experience signs of electrolyte disturbances such as weakness, lethargy, and muscle pains or cramps.

References

  1. Thomas TP (1984) "The complications of systemic corticosteroid therapy in the elderly." Gerontology, 30, p. 60-5
  2. Seale JP, Compton MR (1986) "Side-effects of corticosteroid agents." Med J Aust, 144, p. 139-42
  3. Morris GC, Egan JG, Jones MK (1992) "Hypokalaemic paralysis induced by bolus prednisolone in Graves' disease." Aust N Z J Med, 22, p. 312
  4. Powell JR (1969) "Steroid and hypokalemic myopathy after corticosteroids for ulcerative colitis. Systemic and tropical application." Am J Gastroenterol, 52, p. 425-32
  5. Chrousos GA, Kattah JC, Beck RW, Cleary PA (1993) "Side effects of glucocorticoid treatment. Experience of the Optic Neuritis Treatment Trial." JAMA, 269, p. 2110-2
  6. Thorn GW (1966) "Clinical considerations in the use of corticosteroids." N Engl J Med, 274, p. 775-81
  7. (2001) "Product Information. Hydeltrasol (prednisolone)." Merck & Co., Inc
  8. Ramsahoye BH, Davies SV, el-Gaylani N, Sandeman D, Scanlon MF (1995) "The mineralocorticoid effects of high dose hydrocortisone." BMJ, 310, p. 656-7
View all 8 references

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Drug and food interactions

Moderate

nadolol food

Applies to: bendroflumethiazide / nadolol

GENERALLY AVOID: Coadministration with green tea may significantly decrease the plasma concentrations of nadolol. The mechanism of interaction has not been established, but may involve inhibition of OATP1A2-mediated uptake of nadolol in the intestine by catechins in green tea. In a study with ten healthy volunteers, administration of a single 30 mg oral dose of nadolol following repeated consumption of green tea (700 mL/day for 14 days) resulted in decreases of 85% in nadolol peak plasma concentration (Cmax) and systemic exposure (AUC) compared to administration with water. The renal clearance of nadolol was not altered. Green tea also markedly reduced the effects of nadolol on systolic blood pressure.

MANAGEMENT: Based on available data, patients should be advised to limit their consumption of green tea and green tea extracts during treatment with nadolol.

References

  1. Misaka S, Yatabe J, Muller F, et al. (2014) "Green tea ingestion greatly reduces plasma concentrations of nadolol in healthy subjects." Clin Pharmacol Ther, 95, p. 432-8
  2. Roth M, Timmermann BN, Hagenbuch B (2011) "Interactions of green tea catechins with organic anion-transporting polypeptides." Drug Metab Dispos, 39, p. 920-6

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Moderate

nadolol food

Applies to: bendroflumethiazide / nadolol

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

bendroflumethiazide food

Applies to: bendroflumethiazide / nadolol

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

nadolol food

Applies to: bendroflumethiazide / nadolol

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 duplication 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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Further information

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