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Drug Interactions between bendroflumethiazide / nadolol and Lanoxicaps

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

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Interactions between your drugs

Moderate

nadolol digoxin

Applies to: bendroflumethiazide / nadolol and Lanoxicaps (digoxin)

MONITOR: Concomitant use of digitalis glycosides and beta-blockers may increase the risk of bradycardia. These agents slow atrioventricular conduction and decrease heart rate, hence they may have additive cardiac effects during coadministration. Some beta-blockers such as carvedilol, esmolol, and talinolol have also been reported to increase the systemic bioavailability of digoxin. The mechanism may involve enhanced absorption as well as reduced renal excretion of digoxin due to inhibition of intestinal and renal P-glycoprotein efflux transporter.

MANAGEMENT: Caution is advised during coadministration of digitalis glycosides and beta-blockers. Serum digitalis levels, heart rate, and blood pressure should be monitored closely, particularly during the first few weeks of concomitant therapy. Patients should be advised to notify their physician if they experience anorexia, nausea, visual changes, irregular heartbeat, slow pulse, dizziness, or syncope. Beta-blockers should not be used in patients with overt or decompensated congestive heart failure, as sympathetic stimulation may be a vital component in maintaining hemodynamic function in these patients and its inhibition by beta blockade may worsen the heart failure.

References

  1. LeWinter MM, Crawford MH, O'Rourke RA, Karliner JS "The effects of oral propranolol, digoxin and combination therapy on the resting and exercise electrocardiogram." Am Heart J 93 (1977): 202-9
  2. Watt DA "Sensitivity to propranolol after digoxin intoxication." Br Med J 2 (1968): 413-4
  3. De Mey C, Brendel E, Enterling D "Carvedilol increases the systemic bioavailability of oral digoxin." Br J Clin Pharmacol 29 (1990): 486-90
  4. Lowenthal DT, Porter RS, Saris SD, Bies CM, Slegowski MB, Staudacher A "Clinical pharmacology, pharmacodynamics and interactions with esmolol." Am J Cardiol 56 (1985): f14-8
  5. "Product Information. Inderal (propranolol)." Wyeth-Ayerst Laboratories PROD (2001):
  6. Lowenthal DT, Porter RS, Achari R, Turlapaty P, Laddu AR, Matier WL "Esmolol-digoxin drug interaction" J Clin Pharmacol 27 (1987): 561-6
  7. "Product Information. Zebeta (bisoprolol)." Lederle Laboratories PROD (2001):
  8. Wermeling DP, Field CJ, Smith DA, Chandler MH, Clifton GD, Boyle DA "Effects of long-term oral carvedilol on the steady-state pharmacokinetics of oral digoxin in patients with mild to moderate hypertension." Pharmacotherapy 14 (1994): 600-6
  9. "Product Information. Coreg (carvedilol)." SmithKline Beecham PROD (2001):
  10. Eichhorn EJ, Lukas MA, Wu B, Shusterman N "Effect of concomitant digoxin and carvedilol therapy of mortality and morbidity in patients with chronic heart failure." Am J Cardiol 86 (2000): 1032-5
  11. Ratnapalan S, Griffiths K, Costei AM, Benson L, Koren G "Digoxin-carvedilol interactions in children." J Pediatr 142 (2003): 572-574
  12. Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K "Interaction of digoxin with antihypertensive drugs via MDR 1." Life Sci 70 (2002): 1491-1500
View all 12 references

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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

digoxin bendroflumethiazide

Applies to: Lanoxicaps (digoxin) and bendroflumethiazide / nadolol

MONITOR: Although diuretics and digitalis glycosides are frequently and appropriately used together, diuretic-induced hypokalemia and hypomagnesemia may predispose patients on digitalis to arrhythmias.

MANAGEMENT: Digoxin, potassium and magnesium levels should be followed closely. Hypokalemia and hypomagnesemia should be treated appropriately. Digitalis dose adjustments may be required. Patients should be advised to notify their physicians if they experience signs of possible digoxin toxicity or electrolyte disturbances, such as weakness, lethargy, muscle pains or cramps, nausea, anorexia, visual disturbances, or irregular heartbeats.

References

  1. Tilstone WJ, Semple PF, Lawson DH, Boyle JA "Effects of furosemide on glomerular filtration rate and clearance of practolol, digoxin, cephaloridine, and gentamicin." Clin Pharmacol Ther 22 (1977): 389-94
  2. Semple P, Tilstone WJ, Lawson DH "Furosemide and urinary digoxin clearance." N Engl J Med 293 (1975): 612-3
  3. Brown DD, Dormois JC, Abraham GN, et al. "Effect of furosemide on the renal excretion of digoxin." Clin Pharmacol Ther 20 (1976): 395-400
  4. McAllister RG, Howell SM, Gomer MS, Selby JB "Effect of intravenous furosemide on the renal excretion of digoxin." J Clin Pharmacol 16 (1976): 110-7
  5. Malcolm AD, Leung FY, Fuchs JC, Duarte JE "Digoxin kinetics during furosemide administration." Clin Pharmacol Ther 21 (1977): 567-74
  6. Waldorff S, Hansen PB, Kjaergard H, Buch J, Egeblad H, Steiness E "Amiloride-induced changes in digoxin dynamics and kinetics: abolition of digoxin-induced inotropism with amiloride." Clin Pharmacol Ther 30 (1981): 172-6
  7. Macolic V, Vrhovac B "Pharmacokinetics and interactions of digoxin, theophylline and furosemide in diseases with edema." Int J Clin Pharmacol Ther Toxicol 31 (1993): 6-11
  8. Whang R, Oei TO, Watanabe A "Frequency of hypomagnesemia in hospitalized patients receiving digitalis." Arch Intern Med 145 (1985): 655-6
  9. Cohen L, Kitzes R "Magnesium Sulfate and digitalis-toxic arrhythmias." JAMA 249 (1983): 2808-10
  10. Leary WP, Reyes AJ "Drug interactions with diuretics." S Afr Med J 65 (1984): 455-61
View all 10 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

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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Minor

digoxin food

Applies to: Lanoxicaps (digoxin)

Administration of digoxin with a high-fiber meal has been shown to decrease its bioavailability by almost 20%. Fiber can sequester up to 45% of the drug when given orally. Patients should be advised to maintain a regular diet without significant fluctuation in fiber intake while digoxin is being titrated.

Grapefruit juice may modestly increase the plasma concentrations of digoxin. The mechanism is increased absorption of digoxin due to mild inhibition of intestinal P-glycoprotein by certain compounds present in grapefruits. In 12 healthy volunteers, administration of grapefruit juice with and 30 minutes before, as well as 3.5, 7.5, and 11.5 hours after a single digoxin dose (0.5 mg) increased the mean area under the plasma concentration-time curve (AUC) of digoxin by just 9% compared to administration with water. Moreover, P-glycoprotein genetic polymorphism does not appear to influence the magnitude of the effects of grapefruit juice on digoxin. Thus, the interaction is unlikely to be of clinical significance.

References

  1. Darcy PF "Nutrient-drug interactions." Adverse Drug React Toxicol Rev 14 (1995): 233-54
  2. Becquemont L, Verstuyft C, Kerb R, et al. "Effect of grapefruit juice on digoxin pharmacokinetics in humans." Clin Pharmacol Ther 70 (2001): 311-6

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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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