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Drug Interactions between Inderide LA and Lexxel

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

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Interactions between your drugs

Moderate

propranolol felodipine

Applies to: Inderide LA (hydrochlorothiazide / propranolol) and Lexxel (enalapril / felodipine)

MONITOR: Additive reductions in heart rate, cardiac conduction, and cardiac contractility may occur when calcium channel blockers are used concomitantly with beta blockers, particularly in patients with ventricular or conduction abnormalities. While this combination may be useful and effective in some situations, potentially serious cardiovascular adverse effects such as congestive heart failure, severe hypotension, and/or exacerbation of angina may occur. The proposed mechanisms include additive slowing in AV conduction, reduced cardiac contractility secondary to beta-blockade, and decreased peripheral vascular resistance secondary to calcium channel blockade. In addition, some calcium channel blockers may inhibit the CYP450 metabolism of hepatically metabolized beta blockers, resulting in increased serum concentrations.

MANAGEMENT: Close clinical monitoring of patient hemodynamic response and tolerance is recommended if a calcium channel blocker is prescribed with a beta blocker, and the dosage of one or both agents adjusted as necessary. The same precaution should be observed when beta blocker ophthalmic solutions are used, since they are systemically absorbed and can produce clinically significant systemic effects even at low or undetectable plasma levels.

References

  1. Henry M, Kay MM, Viccellio P "Cardiogenic shock associated with calcium-channel and beta blockers: reversal with intravenous calcium chloride." Am J Emerg Med 3 (1985): 334-6
  2. Rosenkranz B, Ledermann H, Frolich JC "Interaction between nifedipine and atenolol: pharmacokinetics and pharmacodynamics in normotensive volunteers." J Cardiovasc Pharmacol 8 (1986): 943-9
  3. Tateishi T, Nakashima H, Shitou T, et al. "Effect of diltiazem on the pharmacokinetics of propranolol, metoprolol and atenolol." Eur J Clin Pharmacol 36 (1989): 67-70
  4. Oesterle SN, Alderman EL, Beier-Scott L, Bain DS, Rothman MT, Schroder JS "Diltiazem and propranolol in combination: hemodynamic effects following acute intravenous administration." Am Heart J 111 (1986): 489-97
  5. Yust I, Hoffman M, Aronson RJ "Life-threatening bradycardic reactions due to beta blocker-diltiazem interactions." Isr J Med Sci 28 (1992): 292-4
  6. Hartwell BL, Mark JB "Combinations of beta blockers and calcium channel blockers: a cause of malignant perioperative conduction disturbances?" Anesth Analg 65 (1986): 905-7
  7. Hossack KF "Conduction abnormalities due to diltiazem." N Engl J Med 307 (1982): 953-4
  8. Strauss WE, Egan T, McIntyre KM, Parisi AF "Combination therapy with diltiazem and propranolol: precipitation of congestive heart failure." Clin Cardiol 8 (1985): 363-6
  9. Ohman KP, Weiner L, von Schenck H, Karlberg BE "Antihypertensive and metabolic effects of nifedipine and labetalol alone and in combination in primary hypertension." Eur J Clin Pharmacol 29 (1985): 149-54
  10. Bauer LA, Murray K, Horn JR, et al. "Influence of nifedipine therapy on indocyanine green and oral propranolol pharmacokinetics." Eur J Clin Pharmacol 37 (1989): 257-60
  11. Ronn O, Bengtsson B, Edgar B, Raner S "Acute haemodynamic effects of felodipine and verapamil in man, singly and with metoprolol." Drugs 29 (1985): 16-25
  12. Sinclair NI, Benzie JL "Timolol eye drops and verapamil: a dangerous combination." Med J Aust 1 (1983): 548
  13. Pringle SD, MacEwen CJ "Severe bradycardia due to interaction of timolol eye drops and verapamil." Br Med J 294 (1987): 155-6
  14. Rocha P, Guerret M, David D, Marchand X, Kahn JC "Kinetics and hemodynamic effects of intravenous nicardipine modified by previous propranolol oral treatment." Cardiovasc Drugs Ther 4 (1990): 1525-32
  15. Smith SR, Wilkins MR, Jack DB, Kendall MJ, Laugher S "Pharmacokinetic interactions between felodipine and metoprolol." Eur J Clin Pharmacol 31 (1987): 575-8
  16. Pouleur H, Etienne J, Van Mechelen H, et al. "Effects of nicardipine or nifedipine added to propranolol in patients with coronary artery disease." Postgrad Med J 60 (1984): 23-8
  17. Schoors DF, Vercruysse I, Musch G, Massart DL, Dupont AG "Influence of nicardipine on the pharmacokinetics and pharmacodynamics of propranolol in healthy volunteers." Br J Clin Pharmacol 29 (1990): 497-501
  18. Nievel JG, Havard CW, Douglas-Jones AP "Comparison of concomitant nicardipine hydrochloride and propranolol with propranolol alone in patients with essential hypertension." Eur J Clin Pharmacol 33 (1987): 21-5
  19. Maclean D, Mitchell ET, Coulson RR, Fitzsimons TJ, McDevitt DG "Atenolol-nifedipine combinations compared to atenolol alone in hypertension: efficacy and tolerability." Br J Clin Pharmacol 25 (1988): 425-31
  20. Leon MB, Rosing DR, Bonow RO, Epstein SE "Combination therapy with calcium-channel blockers and beta blockers for chronic stable angina pectoris." Am J Cardiol 55 (1985): b69-80
  21. Packer M "Combined beta-adrenergic and calcium-entry blockage in angina pectoris." N Engl J Med 320 (1989): 709-18
  22. Strauss WE, Parisi AF "Combines use of calcium-channel and beta-adrenergic blockers for the treatment of chronic stable angina." Ann Intern Med 109 (1988): 570-81
  23. Levine MA, Ogilvie RI, Leenen FH "Pharmacokinetic and pharmacodynamic interactions between nisoldipine and propranolol." Clin Pharmacol Ther 43 (1988): 39-48
  24. Anastassiades CJ "Nifedipine and beta-blocker drugs." Br Med J 281 (1980): 1251-2
  25. Tateishi T, Ohashi K, Fujimura A, Ebihara A "The influence of diltiazem versus cimetidine on propranolol metabolism." J Clin Pharmacol 32 (1992): 1099-104
  26. Vinceneux P, Canal M, Domart Y, Roux A, Cascio B, Orofiamma B, Larribaud J, Flouvat B, Carbon C "Pharmacokinetic and pharmacodynamic interactions between nifedipine and propranolol or betaxolol." Int J Clin Pharmacol Ther Toxicol 24 (1986): 153-8
  27. Takahashi H, Ohashi N, Motokawa K, Sato S, Naito H "Poisoning caused by the combined ingestion of nifedipine and metoprolol." J Toxicol Clin Toxicol 31 (1993): 631-7
View all 27 references

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Moderate

enalapril hydroCHLOROthiazide

Applies to: Lexxel (enalapril / felodipine) and Inderide LA (hydrochlorothiazide / propranolol)

MONITOR: Although they are frequently combined in clinical practice, diuretics and angiotensin converting enzyme (ACE) inhibitors may have additive effects. Coadministration makes hypotension and hypovolemia more likely than does either drug alone. Some ACE inhibitors may attenuate the increase in the urinary excretion of sodium caused by some loop diuretics. Some patients on diuretics, especially those on dialysis or a dietary salt restriction, may experience acute hypotension with lightheadedness and dizziness after receiving the first dose of the ACE inhibitor. In addition, ACE inhibitors may cause renal insufficiency or acute renal failure in patients with sodium depletion or renal artery stenosis.

MANAGEMENT: Monitoring of blood pressure, diuresis, electrolytes, and renal function is recommended during coadministration. The possibility of first-dose hypotensive effects may be minimized by initiating therapy with small doses of the ACE inhibitor, or either discontinuing the diuretic temporarily or increasing the salt intake approximately one week prior to initiating an ACE inhibitor. Alternatively, the patient may remain under medical supervision for at least two hours after the first dose of the ACE inhibitor, or until blood pressure has stabilized.

References

  1. Reader C, Peyregne EA, Suarez LD "Amrinone therapy in congestive cardiomyopathy." Am Heart J 105 (1983): 1045
  2. Fujimura A, Shimokawa Y, Ebihara A "Influence of captopril on urinary excretion of furosemide in hypertensive subjects." J Clin Pharmacol 30 (1990): 538-42
  3. Funck-Brentano C, Chatellier G, Alexandre JM "Reversible renal failure after combined treatment with enalapril and furosemide in a patient with congestive heart failure." Br Heart J 55 (1986): 596-8
  4. Weisser K, Schloos J, Jakob S, et al. "The influence of hydrochlorothiazide on the pharmacokinetics of enalapril in elderly patients." Eur J Clin Pharmacol 43 (1992): 173-7
  5. Motwani JG, Fenwick MK, Morton JJ, Struthers AD "Furosemide-induced natriuresis is augmented by ultra-low-dose captopril but not by standard doses of captopril in chronic heart failure." Circulation 86 (1992): 439-45
  6. Burnakis TG, Mioduch HJ "Combined therapy with captopril and potassium supplementation: a potential for hyperkalemia." Arch Intern Med 144 (1984): 2371-2
  7. Murphy BF, Whitworth JA, Kincaid-Smith P "Renal insufficiency with combinations of angiotensin converting enzyme inhibitors and diuretics." Br Med J 288 (1984): 844-5
  8. Thind GS "Renal insufficiency during angiotensin-converting enzyme inhibitor therapy in hypertensive patients with no renal artery stenosis." J Clin Hypertens 1 (1985): 337-43
  9. Radley AS, Fitzpatrick RW "An evaluation of the potential interaction between enalapril and amiloride." J Clin Pharm Ther 12 (1987): 319-23
  10. Champ JD "Case report: azotemia secondary to enalapril and diuretic use and the diagnosis of renovascular hypertension." Am J Med Sci 305 (1993): 25-7
  11. Hume AL, Murphy JL, Lauerman SE "Angiotensin-converting enzyme inhibitor-induced cough." Pharmacotherapy 9 (1989): 88-90
  12. Lee HB, Blaufox MD "Renal functional response to captopril during diuretic therapy." J Nucl Med 33 (1992): 739-43
  13. DeQuattro V "Comparison of benazepril and other antihypertensive agents alone and in combination with the diuretic hydrochlorothiazide." Clin Cardiol 14 (1991): iv28-32;
  14. "Product Information. Vasotec (enalapril)." Merck & Co., Inc PROD (2002):
  15. McLay JS, McMurray JJ, Bridges AB, Fraser CG, Struthers AD "Acute effects of captopril on the renal actions of furosemide in patients with chronic heart failure." Am Heart J 126 (1993): 879-86
  16. Sudoh T, Fujimura A, Shiga T, et al. "Influence of lisinopril on urinary electrolytes excretion after furosemide in healthy subjects." J Clin Pharmacol 33 (1993): 640-3
  17. Lederle RM "Captopril and hydrochlorothiazide in the fixed combination multicenter trial." J Cardiovasc Pharmacol 7 (1985): S63-9
  18. "Product Information. Aceon (perindopril)." Solvay Pharmaceuticals Inc PROD (2001):
  19. Good JM, Brady AJ, Noormohamed FH, Oakley CM, Cleland JG "Effect of intense angiotensin II suppression on the diuretic response to furosemide during chronic ACE inhibition." Circulation 90 (1994): 220-4
  20. "Product Information. Capoten (captopril)." Bristol-Myers Squibb PROD (2001):
  21. "Product Information. Lexxel (enalapril-felodipine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  22. "Product Information. Zestril (lisinopril)." Astra-Zeneca Pharmaceuticals PROD
  23. Cerner Multum, Inc. "Australian Product Information." O 0
View all 23 references

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Moderate

propranolol hydroCHLOROthiazide

Applies to: Inderide LA (hydrochlorothiazide / propranolol) and Inderide LA (hydrochlorothiazide / propranolol)

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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Minor

enalapril felodipine

Applies to: Lexxel (enalapril / felodipine) and Lexxel (enalapril / felodipine)

Calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors may have additive hypotensive effects. While these drugs are often safely used together, careful monitoring of the systemic blood pressure is recommended during coadministration, especially during the first one to three weeks of therapy.

References

  1. Kaplan NM "Amlodipine in the treatment of hypertension." Postgrad Med J 67 Suppl 5 (1991): s15-9
  2. DeQuattro V "Comparison of benazepril and other antihypertensive agents alone and in combination with the diuretic hydrochlorothiazide." Clin Cardiol 14 (1991): iv28-32;
  3. Sun JX, Cipriano A, Chan K, John VA "Pharmacokinetic interaction study between benazepril and amlodipine in healthy subjects." Eur J Clin Pharmacol 47 (1994): 285-9
  4. Di Somma S, et al. "Antihypertensive effects of verapamil, captopril and their combination at rest and during dynamic exercise." Arzneimittelforschung 42 (1992): 103
View all 4 references

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Drug and food interactions

Moderate

enalapril food

Applies to: Lexxel (enalapril / felodipine)

GENERALLY AVOID: Moderate-to-high dietary intake of potassium can cause hyperkalemia in some patients who are using angiotensin converting enzyme (ACE) inhibitors. In some cases, affected patients were using a potassium-rich salt substitute. ACE inhibitors can promote hyperkalemia through inhibition of the renin-aldosterone-angiotensin (RAA) system.

MANAGEMENT: It is recommended that patients who are taking ACE inhibitors be advised to avoid moderately high or high potassium dietary intake. Particular attention should be paid to the potassium content of salt substitutes.

References

  1. "Product Information. Vasotec (enalapril)." Merck & Co., Inc PROD (2002):
  2. Good CB, McDermott L "Diet and serum potassium in patients on ACE inhibitors." JAMA 274 (1995): 538
  3. Ray K, Dorman S, Watson R "Severe hyperkalaemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life threatening interaction." J Hum Hypertens 13 (1999): 717-20

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Moderate

propranolol food

Applies to: Inderide LA (hydrochlorothiazide / propranolol)

ADJUST DOSING INTERVAL: The bioavailability of propranolol may be enhanced by food.

MANAGEMENT: Patients may be instructed to take propranolol at the same time each day, preferably with or immediately following meals.

References

  1. Olanoff LS, Walle T, Cowart TD, et al. "Food effects on propranolol systemic and oral clearance: support for a blood flow hypothesis." Clin Pharmacol Ther 40 (1986): 408-14
  2. Byrne AJ, McNeil JJ, Harrison PM, Louis W, Tonkin AM, McLean AJ "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 (1984): s45-50

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Moderate

felodipine food

Applies to: Lexxel (enalapril / felodipine)

GENERALLY AVOID: The consumption of grapefruit juice may be associated with significantly increased plasma concentrations of some calcium channel blockers (CCBs) when they are administered orally. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. The interaction has been reported with the dihydropyridine CCBs (in roughly decreasing order of magnitude) felodipine, nisoldipine, nifedipine, and nimodipine, often with a high degree of interindividual variability. Grapefruit juice caused more than twofold increases in felodipine, nifedipine, and nisoldipine AUCs.

MANAGEMENT: The manufacturers of nifedipine and nisoldipine recommend avoiding grapefruit juice. Patients treated orally with other calcium channel blockers should be advised to avoid consumption of large amounts of grapefruits and grapefruit juice to prevent any undue fluctuations in serum drug levels. Increased effects on blood pressure may persist for up to 4 days after the consumption of grapefruit juice. Monitoring for calcium channel blocker adverse effects (e.g., headache, hypotension, syncope, tachycardia, edema) is recommended.

References

  1. Edgar B, Bailey D, Bergstrand R, Johnsson G, Regardh CG "Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics of felodipine--and its potential clinical relevance." Eur J Clin Pharmacol 42 (1992): 313-7
  2. "Product Information. Plendil (felodipine)." Merck & Co., Inc PROD (2002):
  3. "Product Information. Procardia (nifedipine)." Pfizer U.S. Pharmaceuticals PROD (2002):
  4. Bailey DG, Arnold JM, Munoz C, Spence JD "Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin." Clin Pharmacol Ther 53 (1993): 637-42
  5. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  6. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD "Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics." Clin Pharmacol Ther 54 (1993): 589-94
  7. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG "Drug-food interactions in clinical practice." J Fam Pract 40 (1995): 376-84
  8. "Grapefruit juice interactions with drugs." Med Lett Drugs Ther 37 (1995): 73-4
  9. "Product Information. Sular (nisoldipine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  10. Josefsson M, Zackrisson AL, Ahlner J "Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers." Eur J Clin Pharmacol 51 (1996): 189-93
  11. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  12. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans." Clin Pharmacol Ther 64 (1998): 248-56
  13. Fuhr U, Maier-Bruggemann A, Blume H, et al. "Grapefruit juice increases oral nimodipine bioavailability." Int J Clin Pharmacol Ther 36 (1998): 126-32
  14. Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41
  15. Takanaga H, Ohnishi A, Maatsuo H, et al. "Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model." Br J Clin Pharmacol 49 (2000): 49-58
  16. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
  17. Ho PC, Ghose K, Saville D, Wanwimolruk S "Effect of grapefruit juice on pharmacokinetics and pharmacodynamics of verapamil enantiomers in healthy volunteers." Eur J Clin Pharmacol 56 (2000): 693-8
  18. Fuhr U, Muller-Peltzer H, Kern R, et al. "Effects of grapefruit juice and smoking on verapamil concentrations in steady state." Eur J Clin Pharmacol 58 (2002): 45-53
  19. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
View all 19 references

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Moderate

enalapril food

Applies to: Lexxel (enalapril / felodipine)

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

felodipine food

Applies to: Lexxel (enalapril / felodipine)

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

hydroCHLOROthiazide food

Applies to: Inderide LA (hydrochlorothiazide / propranolol)

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

propranolol food

Applies to: Inderide LA (hydrochlorothiazide / propranolol)

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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Moderate

felodipine food

Applies to: Lexxel (enalapril / felodipine)

MONITOR: Calcium-containing products may decrease the effectiveness of calcium channel blockers by saturating calcium channels with calcium. Calcium chloride has been used to manage acute severe verapamil toxicity.

MANAGEMENT: Management consists of monitoring the effectiveness of calcium channel blocker therapy during coadministration with calcium products.

References

  1. Henry M, Kay MM, Viccellio P "Cardiogenic shock associated with calcium-channel and beta blockers: reversal with intravenous calcium chloride." Am J Emerg Med 3 (1985): 334-6
  2. Moller IW "Cardiac arrest following intravenous verapamil combined with halothane anaesthesia." Br J Anaesth 59 (1987): 522-6
  3. Oszko MA, Klutman NE "Use of calcium salts during cardiopulmonary resuscitation for reversing verapamil-associated hypotension." Clin Pharm 6 (1987): 448-9
  4. Schoen MD, Parker RB, Hoon TJ, et al. "Evaluation of the pharmacokinetics and electrocardiographic effects of intravenous verapamil with intravenous calcium chloride pretreatment in normal subjects." Am J Cardiol 67 (1991): 300-4
  5. O'Quinn SV, Wohns DH, Clarke S, Koch G, Patterson JH, Adams KF "Influence of calcium on the hemodynamic and anti-ischemic effects of nifedipine observed during treadmill exercise testing." Pharmacotherapy 10 (1990): 247
  6. Woie L, Storstein L "Successful treatment of suicidal verapamil poisoning with calcium gluconate." Eur Heart J 2 (1981): 239-42
  7. Morris DL, Goldschlager N "Calcium infusion for reversal of adverse effects of intravenous verapamil." JAMA 249 (1983): 3212-3
  8. Guadagnino V, Greengart A, Hollander G, Solar M, Shani J, Lichstein E "Treatment of severe left ventricular dysfunction with calcium chloride in patients receiving verapamil." J Clin Pharmacol 27 (1987): 407-9
  9. Luscher TF, Noll G, Sturmer T, Huser B, Wenk M "Calcium gluconate in severe verapamil intoxication." N Engl J Med 330 (1994): 718-20
  10. Bar-Or D, Gasiel Y "Calcium and calciferol antagonise effect of verapamil in atrial fibrillation." Br Med J (Clin Res Ed) 282 (1981): 1585-6
  11. Lipman J, Jardine I, Roos C, Dreosti L "Intravenous calcium chloride as an antidote to verapamil-induced hypotension." Intensive Care Med 8 (1982): 55-7
  12. McMillan R "Management of acute severe verapamil intoxication." J Emerg Med 6 (1988): 193-6
  13. Perkins CM "Serious verapamil poisoning: treatment with intravenous calcium gluconate." Br Med J 2 (1978): 1127
  14. Moroni F, Mannaioni PF, Dolara A, Ciaccheri M "Calcium gluconate and hypertonic sodium chloride in a case of massive verapamil poisoning." Clin Toxicol 17 (1980): 395-400
View all 14 references

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Therapeutic duplication warnings

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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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