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Drug Interactions between B-Nexa and hydrochlorothiazide / timolol

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

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Interactions between your drugs

Moderate

timolol hydroCHLOROthiazide

Applies to: hydrochlorothiazide / timolol and hydrochlorothiazide / timolol

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

timolol calcium phosphate, tribasic

Applies to: hydrochlorothiazide / timolol and B-Nexa (calcium / folic acid / ginger / pyridoxine)

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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Moderate

hydroCHLOROthiazide calcium phosphate, tribasic

Applies to: hydrochlorothiazide / timolol and B-Nexa (calcium / folic acid / ginger / pyridoxine)

MONITOR: Coadministration of thiazide diuretics with high dosages of calcium and/or vitamin D has been associated with reports of hypercalcemia in some patients. Thiazide diuretics inhibit the renal excretion of calcium and may also enhance responsiveness of bone and renal tubule to parathyroid hormone, thus concurrent use of large amounts of calcium or vitamin D can lead to excessively high plasma levels of calcium. Patients who are particularly susceptible include those with hyperparathyroidism, those being treated for osteoporosis, and those receiving high dosages of vitamin D for hypoparathyroidism. Metabolic alkalosis and the milk-alkali syndrome have been reported during prolonged therapy with thiazide diuretics and calcium.

MANAGEMENT: Patients receiving thiazide diuretic therapy should be cautioned against self-treatment with calcium and vitamin D supplements without first talking to their healthcare provider. Serum calcium should be monitored if thiazide diuretics are coadministered with high dosages of calcium and/or vitamin D. Patients should be advised to seek medical attention if they experience signs and symptoms of hypercalcemia such as dizziness, weakness, lethargy, headache, myalgia, anorexia, nausea, vomiting, and seizures.

References

  1. Alon U, Costanzo LS, Chan JC (1984) "Additive hypocalciuric effects of amiloride and hydrochlorothiazide in patients treated with calcitriol." Miner Electrolyte Metab, 10, p. 379-86
  2. Parfitt AM (1972) "Thiazide-induced hypercalcemia in vitamin D-treated hypoparathyroidism." Ann Intern Med, 77, p. 557-63
  3. Popovtzer MM, Subryan VL, Alfrey AC, Reeve EB, Schrier RW (1975) "The acute effect of chlorothiazide on serum-ionized calcium. Evidence for a parathyroid hormone-dependent mechanism." J Clin Invest, 55, p. 1295-302
  4. Parfitt AM (1972) "The interactions of thiazide diuretics with parathyroid hormone and vitamin D. Studies in patients with hypoparathyroidism." J Clin Invest, 51, p. 1879-88
  5. Middler S, Pak CY, Murad F, Bartter FC (1973) "Thiazide diuretics and calcium metabolism." Metabolism, 22, p. 139-46
  6. Parfitt AM (1969) "Chlorothiazide-induced hypercalcemia in juvenile osteoporosis and hyperparathyroidism." N Engl J Med, 281, p. 55-9
  7. Gora ML, Seth SK, Bay WH, Visconti JA (1989) "Milk-alkali syndrome associated with use of chlorothiazide and calcium carbonate." Clin Pharm, 8, p. 227-9
  8. Hakim R, Tolis G, Goltzman D, Meltzer S, Friedman R (1979) "Severe hypercalcemia associated with hydrochlorothiazide and calcium carbonate therapy." Can Med Assoc J, 121, p. 591-4
  9. Duarte CG, Winnacker JL, Becker KL, Pace A (1971) "Thiazide-induced hypercalcemia." N Engl J Med, 284, p. 828-30
  10. Franciosa JA, Pierpont G (1981) "Cardiovascular clinical pharmacology of impedance reducing agents." J Chronic Dis, 34, p. 341-52
  11. Santos F, Smith MJ, Chan JC (1986) "Hypercalciuria associated with long-term administration of calcitriol (1,25-dihydroxyvitamin D3). Action of hydrochlorothiazide." Am J Dis Child, 140, p. 139-42
  12. Riis B, Christiansen C (1985) "Actions of thiazide on vitamin D metabolism: a controlled therapeutic trial in normal women early in the postmenopause." Metabolism, 34, p. 421-4
  13. Ljunghall S, Backman U, Danielson BG, Fellstrom B, Johansson G, Wikstrom B (1981) "Calcium and magnesium metabolism during long-term treatment with thiazides." Scand J Urol Nephrol, 15, p. 257-62
  14. Drinka PJ, Nolten WE (1984) "Hazards of treating osteoporosis and hypertension concurrently with calcium, vitamin D, and distal diuretics." J Am Geriatr Soc, 32, p. 405-7
  15. Braunwald E, Hauser SL, Kasper DL, Fauci AS, Isselbacher KJ, Longo DL, Martin JB, eds., Wilson JD (1998) "Harrison's Principles of Internal Medicine." New York, NY: McGraw-Hill Health Professionals Division
View all 15 references

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Drug and food interactions

Moderate

folic acid food

Applies to: B-Nexa (calcium / folic acid / ginger / pyridoxine)

MONITOR: Ethanol may increase folic acid elimination and folic acid absorption is decreased in chronic alcoholics. Excessive alcohol consumption may lead to folate deficiency.

MANAGEMENT: Monitoring of patient response to folic acid supplementation if they also consume alcohol regularly may be recommended.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. Agencia Española de Medicamentos y Productos Sanitarios Healthcare (2008) Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html
  4. Cerner Multum, Inc (2015) "ANVISA Bulário Eletrônico."
  5. (2017) "Product Information. Folic Acid (folic acid)." Method Pharmaceuticals, LLC
View all 5 references

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Moderate

calcium phosphate, tribasic food

Applies to: B-Nexa (calcium / folic acid / ginger / pyridoxine)

ADJUST DOSING INTERVAL: Administration with food may increase the absorption of calcium. However, foods high in oxalic acid (spinach or rhubarb), or phytic acid (bran and whole grains) may decrease calcium absorption.

MANAGEMENT: Calcium may be administered with food to increase absorption. Consider withholding calcium administration for at least 2 hours before or after consuming foods high in oxalic acid or phytic acid.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  3. Cerner Multum, Inc. "Australian Product Information."
  4. Agencia Española de Medicamentos y Productos Sanitarios Healthcare (2008) Centro de información online de medicamentos de la AEMPS - CIMA. https://cima.aemps.es/cima/publico/home.html
  5. Mangels AR (2014) "Bone nutrients for vegetarians." Am J Clin Nutr, 100, epub
  6. Davies NT (1979) "Anti-nutrient factors affecting mineral utilization." Proc Nutr Soc, 38, p. 121-8
View all 6 references

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Moderate

timolol food

Applies to: hydrochlorothiazide / 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: hydrochlorothiazide / 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

timolol food

Applies to: hydrochlorothiazide / 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.

Further information

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

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