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Drug Interactions between bendroflumethiazide / nadolol and Cardura XL

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

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Interactions between your drugs

Moderate

nadolol bendroflumethiazide

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

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Moderate

nadolol doxazosin

Applies to: bendroflumethiazide / nadolol and Cardura XL (doxazosin)

MONITOR: Additive hypotensive effects may occur when beta-blockers are used in combination with alpha-blockers. In the presence of beta-blockade, the risk and/or severity of first-dose effects associated with alpha-blockers such as postural hypotension and syncope may be increased. Beta-blockers may also blunt the reflex tachycardia that occurs in response to postural hypotension. In a study of eight normotensive male subjects, the lowest mean standing systolic blood pressure after 1 mg of oral prazosin was 88 mmHg, which was associated with a tachycardia of 117 bpm and an increase in mean plasma norepinephrine concentration. Concurrent administration of propranolol 80 mg or primidolol (a cardioselective beta-blocker) 100 mg increased the severity and duration of the postural hypotensive response, with lowest mean standing systolic blood pressure declining to 79 and 75 mmHg, respectively. Beta-blockade had no effect on the orthostatic release of norepinephrine, but attenuation of the postural tachycardia was observed. A similar exaggeration of first-dose response has been reported with prazosin administered in the presence of alprenolol. In another study, terazosin or placebo was given to nearly 100 patients with essential hypertension who had an inadequate response to atenolol 50 mg daily for eight weeks. After 10 weeks of coadministration, patients treated with terazosin (given at increasing daily dosages of 1, 2, 5, and up to 10 mg at two-week intervals) had significant mean decreases from baseline in supine blood pressure (systolic/diastolic = -8.8/-8.5 mmHg) and standing BP (-10.9/-9.5 mmHg), whereas the decreases in placebo-treated patients (supine, -2.3/-2.6 mmHg; standing, -1.4/-1.3 mmHg) were not significant. Terazosin produced similar effects in another study examining terazosin use against a background of hypotensive medications including beta-blockers. Theoretically, the interaction may also occur with beta-blocker ophthalmic preparations, since they may be systemically absorbed and can produce clinically significant systemic effects even at low or undetectable plasma levels.

MANAGEMENT: Caution is advised during coadministration of these agents, particularly when initiating an alpha-blocker in the presence of a beta-blocker, including ophthalmic formulations. Small initial dosages of the alpha-blocker should be considered and gradually titrated to desired effect, while the systemic beta-blocker dosage may also need to be reduced. Hemodynamic responses should be monitored, especially during the first few weeks of therapy. Taking the alpha-blocker at bedtime may minimize the occurrence of orthostatic effects. 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. Patients should also avoid driving or operating hazardous machinery until they know how the medications affect them.

References

  1. Stokes GS, Mennie BA, Gellatly R, Hill A "On the combination of alpha- and beta-adrenoceptor blockade in hypertension." Clin Pharmacol Ther 34 (1983): 576-82
  2. Elliott HL, McLean K, Sumner DJ, Meredith PA, Reid JL "Immediate cardiovascular responses to oral prazosin: effects of concurrent beta-blockers." Clin Pharmacol Ther 29 (1981): 303-9
  3. Seideman P, Grahnen A, Haglund K, Lindstrom B, Von Bahr C "Prazosin first dose phenomenon during combined treatment with a B-adrenoceptor blocker in hypertensive patients." Br J Clin Pharmacol 13 (1982): 865-70
  4. Pool JL "Combination antihypertensive therapy with terazosin and other antihypertensive agents: results of clinical trials." Am Heart J 122 (1991): 926-31
  5. Chrysant SG "Experience with terazosin administered in combination with other antihypertensive agents." Am J Med 80 (1986): 55-61
  6. Holtzman JL, Kaihlanen PM, Rider JA, Lewin AJ, Spindler JS, Oberlin JA "Concomitant administration of terazosin and atenolol for the treatment of essential hypertension." Arch Intern Med 148 (1988): 539-43
  7. Rubin P, Jackson G, Blaschke T "Studies on the clinical pharmacology of prazosin II: the influence of indomethacin and of propranolol on the action and disposition of prazosin." Br J Clin Pharmacol 10 (1980): 33-9
  8. "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc (2002):
View all 8 references

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Moderate

bendroflumethiazide doxazosin

Applies to: bendroflumethiazide / nadolol and Cardura XL (doxazosin)

MONITOR: The hypotensive effects of thiazide diuretics and alpha-adrenergic blockers may be additive. Postural hypotension may occur.

MANAGEMENT: Hemodynamic responses should be monitored during coadministration, especially during the first few weeks of therapy. Patients should be advised to take the alpha-blocker at bedtime and to notify their physician if they experience dizziness or syncope while awake.

References

  1. Achari R, Laddu A "Terazosin: a new alpha adrenoceptor blocking drug." J Clin Pharmacol 32 (1992): 520-3
  2. Kuokkanen K, Mattila MJ "Demonstration of an additive antihypertensive effect of prazosin and polythiazide in out-patient." Curr Ther Res Clin Exp 17 (1975): 431-6
  3. Pool JL "Combination antihypertensive therapy with terazosin and other antihypertensive agents: results of clinical trials." Am Heart J 122 (1991): 926-31
  4. Cohen J "Long-term efficacy and safety of terazosin alone and in combination with other antihypertensive agents." Am Heart J 122 (1991): 919-25
  5. "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc (2002):
View all 5 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. "Green tea ingestion greatly reduces plasma concentrations of nadolol in healthy subjects." Clin Pharmacol Ther 95 (2014): 432-8
  2. Roth M, Timmermann BN, Hagenbuch B "Interactions of green tea catechins with organic anion-transporting polypeptides." Drug Metab Dispos 39 (2011): 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 "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

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 "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

doxazosin food

Applies to: Cardura XL (doxazosin)

GENERALLY AVOID: The concurrent use of ethanol and alpha-1 adrenergic blockers may cause increased hypotensive effects. Patients with aldehyde dehydrogenase deficiencies (primarily Asians) may be at a higher risk of this interaction. The mechanism has not been determined. Data exist for prazosin and other alpha adrenergic blockers are expected to interact also. In addition, any patients taking alpha adrenergic blockers may experience excessive orthostatic hypotension with ethanol ingestion, due to ethanol's unopposed vasodilatory effects in the presence of alpha adrenergic blockade.

MANAGEMENT: Patients who develop a flushing reaction after ethanol ingestion (indicates a possible aldehyde dehydrogenase deficiency) should be advised to avoid ethanol or limit their intake. All patients should be warned about the possibility of orthostatic hypotension with concurrent ethanol use.

References

  1. Kawano Y, Abe H, Kojima S, Takishita S, Omae T "Interaction of alcohol and an a1-blocker on ambulatory blood pressure in patients with essential hypertension." Am J Hypertens 13 (2000): 307-12
  2. "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc (2002):

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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 "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.

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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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