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Drug Interactions between Tarka and Timolide 10-25

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

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Major

verapamil timolol

Applies to: Tarka (trandolapril / verapamil) and Timolide 10-25 (hydrochlorothiazide / timolol)

MONITOR CLOSELY: Additive reductions in heart rate, cardiac conduction, and cardiac contractility may occur when calcium channel blockers, especially verapamil and diltiazem, are used concomitantly with beta blockers. 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. Ventricular asystole, sinus arrest, and heart block have also been reported. The risk is increased with high dosages, IV administration, left ventricular dysfunction, or AV conduction abnormalities. Beta blocker ophthalmic solutions may also interact, as they are systemically absorbed and can produce clinically significant systemic effects even at low or undetectable plasma levels. Bradycardia (36 bpm) with wandering atrial pacemaker occurred in a patient taking oral verapamil and timolol ophthalmic drops. 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, verapamil and diltiazem may decrease the clearance of some beta blockers and use of diltiazem with beta blockers has been associated with an increased risk of depression.

MANAGEMENT: Close clinical monitoring of patient hemodynamic response and tolerance is recommended if these agents are used together, and the dosage of one or both agents adjusted as necessary. Patients should be advised to promptly report any symptoms including fatigue, headache, fainting, swelling of the extremities, weight gain, shortness of breath, chest pain, increased or decreased heartbeat, or irregular heartbeat.

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. Misra M, Thakur R, Bhandari K "Sinus arrest caused by atenolol-verapamil combination." Clin Cardiol 10 (1987): 365-7
  3. Keech AC, Harper RW, Harrison PM, Pitt A, McLean AJ "Extent and pharmacokinetic mechanisms of oral atenolol-verapamil interaction in man." Eur J Clin Pharmacol 35 (1988): 363-6
  4. Sagie A, Strasberg B, Kusnieck J, Sclarovsky S "Symptomatic bradycardia induced by the combination of oral diltiazem and beta blockers." Clin Cardiol 14 (1991): 314-6
  5. Murdoch DL, Thomson GD, Thompson GG, et al. "Evaluation of potential pharmacodynamic and pharmacokinetic interactions between verapamil and propranolol in normal subjects." Br J Clin Pharmacol 31 (1991): 323-32
  6. Lee TH, Salomon DR, Rayment CM, Antman EM "Hypotension and sinus arrest with exercise-induced hyperkalemia and combined verapamil/propranolol therapy." Am J Med 80 (1986): 1203-4
  7. McCourty JC, Silas JH, Tucker GT, Lennard MS "The effect of combined therapy on the pharmacokinetics and pharmacodynamics of verapamil and propranolol in patients with angina pectoris." Br J Clin Pharmacol 25 (1988): 349-57
  8. McTavish D, Sorkin EM "Verapamil: an updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension." Drugs 38 (1989): 19-76
  9. Zatuchni J "Bradycardia and hypotension after propranolol HCI and verapamil." Heart Lung 14 (1985): 94-5
  10. Keech AC, Harper RW, Harrison PM, et al. "Extent and pharmacokinetic mechanisms of oral atenolol-verapamil interaction in man." Eur J Clin Pharmacol 35 (1988): 363-6
  11. Pieper JA, Miller JH "Serum protein binding interactions between propranolol and calcium channel blockers." Drug Intell Clin Pharm 18 (1984): 492
  12. Reddy PS, Uretsky BF, Steinfeld M "The hemodynamic effects of intravenous verapamil in patients on chronic propranolol therapy." Am Heart J 107 (1984): 97-101
  13. Winniford MD, Fulton KL, Hillis LD "Symptomatic sinus bradycardia during concomitant propranolol-verapamil administration." Am Heart J 110 (1985): 498
  14. Lee TH, Salomon DR, Rayment CM, Antman EM "Hypotension and sinus arrest with exercise-induced hyperkalemia and combined verapamil-propranolol therapy." Am J Med 80 (1986): 1203-4
  15. Bailey DG, Carruthers SG "Interaction between oral verapamil and beta-blockers during submaximal exercise: relevance of ancillary properties." Clin Pharmacol Ther 49 (1991): 370-6
  16. Carruthers SG, Freeman DJ, Bailey DG "Synergistic adverse hemodynamic interaction between oral verapamil and propranolol." Clin Pharmacol Ther 46 (1989): 469-77
  17. Eisenberg JN, Oakley GD "Probable adverse interaction between oral metoprolol and verapamil." Postgrad Med J 60 (1984): 705-6
  18. 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
  19. McLean AJ, Knight R, Harrison PM, Harper RW "Clearance-based oral drug interaction between verapamil and metoprolol and comparison with atenolol." Am J Cardiol 55 (1985): 1628-9
  20. Wayne VS, Harper RW, Laufer E, et al. "Adverse interaction between beta-adrenergic blocking drugs and verapamil: report of three cases." Aust N Z J Med 12 (1982): 285-9
  21. Sinclair NI, Benzie JL "Timolol eye drops and verapamil: a dangerous combination." Med J Aust 1 (1983): 548
  22. Pringle SD, MacEwen CJ "Severe bradycardia due to interaction of timolol eye drops and verapamil." Br Med J 294 (1987): 155-6
  23. 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
  24. Hunt BA, Bottorff MB, Herring VL, Self Th, Lalonde RL "Effects of calcium channel blockers on the pharmacokinetics of propranolol stereoisomers." Clin Pharmacol Ther 47 (1990): 584-91
  25. 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
  26. 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
  27. 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
  28. 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
  29. Packer M "Combined beta-adrenergic and calcium-entry blockage in angina pectoris." N Engl J Med 320 (1989): 709-18
  30. 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
  31. Levine MA, Ogilvie RI, Leenen FH "Pharmacokinetic and pharmacodynamic interactions between nisoldipine and propranolol." Clin Pharmacol Ther 43 (1988): 39-48
  32. Anastassiades CJ "Nifedipine and beta-blocker drugs." Br Med J 281 (1980): 1251-2
  33. Bleske BE, Welage LS, Touchette MA, Edwards DJ, Rodman DP, Shea MJ "Evaluation of dosage-release formulations on inhibition of drug clearance - effect of sustained-release and immediate-release verapamil on propranolol pharmacokinetic parameters." Ther Drug Monit 16 (1994): 216-20
  34. "Product Information. Covera-HS (verapamil)." Searle PROD (2001):
  35. "Product Information. Toprol-XL (metoprolol)." Astra-Zeneca Pharmaceuticals PROD (2001):
  36. Minish T, Herd A "Symptomatic bradycardia secondary to interaction between topical timolol maleate, verapamil, and flecainide: a case report." J Emerg Med 22 (2002): 247-9
View all 36 references

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Moderate

timolol hydroCHLOROthiazide

Applies to: Timolide 10-25 (hydrochlorothiazide / timolol) and Timolide 10-25 (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 "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

hydroCHLOROthiazide trandolapril

Applies to: Timolide 10-25 (hydrochlorothiazide / timolol) and Tarka (trandolapril / verapamil)

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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Minor

verapamil trandolapril

Applies to: Tarka (trandolapril / verapamil) and Tarka (trandolapril / verapamil)

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

verapamil food

Applies to: Tarka (trandolapril / verapamil)

GENERALLY AVOID: Consumption of large quantities of grapefruit juice may be associated with significantly increased plasma concentrations of oral verapamil. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. One study reported no significant effect of a single administration of grapefruit juice on the pharmacokinetics of verapamil in ten hypertensive patients receiving chronic therapy. In another study conducted in nine healthy male volunteers, administration of 120 mg oral verapamil twice daily for 3 days following pretreatment with 200 mL grapefruit juice twice daily for 5 days resulted in a 57% increase in S-verapamil peak plasma concentration (Cmax), a 36% increase in S-verapamil systemic exposure (AUC), a 40% increase in R-verapamil Cmax, and a 28% increase in R-verapamil AUC compared to administration following orange juice. Elimination half-life and renal clearance of both S- and R-verapamil were not affected by grapefruit juice, and there were no significant effects on blood pressure, heart rate, or PR interval. A third study reported a 1.63-fold increase in Cmax and a 1.45-fold increase in AUC of (R,S)-verapamil in 24 young, healthy volunteers given verapamil sustained-release 120 mg twice daily for 7 days with 250 mL grapefruit juice four times daily on days 5 through 7. Two subjects developed PR interval prolongation of more than 350 ms during grapefruit juice coadministration. A high degree of interindividual variability has been observed in these studies. The interaction was also suspected in a case report of a 42-year-old woman who developed complete heart block, hypotension, hypoxic respiratory failure, severe anion gap metabolic acidosis, and hyperglycemia following accidental ingestion of three verapamil sustained-release 120 mg tablets over a span of six hours. The patient's past medical history was remarkable only for migraine headaches, for which she was receiving several medications including verapamil. Prior to admission, the patient had a 2-week history of poorly controlled migraine, and the six hours preceding hospitalization she suffered from worsening headache and palpitations progressing to altered sensorium. An extensive workup revealed elevated verapamil and norverapamil levels more than 4.5 times above the upper therapeutic limits. These levels also far exceeded those reported in the medical literature for patients taking verapamil 120 mg every 6 hours, or 480 mg in a 24-hour period. The patient recovered after receiving ventilator and vasopressor support. Upon questioning, it was discovered that the patient had been drinking large amounts of grapefruit juice (3 to 4 liters total) the week preceding her admission due to nausea. No other sources or contributing factors could be found for the verapamil toxicity.

MANAGEMENT: Patients treated with oral verapamil should avoid the consumption of large amounts of grapefruit or grapefruit juice to prevent any undue fluctuations in serum drug levels. Patients should be advised to seek medical attention if they experience edema or swelling of the lower extremities; sudden, unexplained weight gain; difficulty breathing; chest pain or tightness; or hypotension as indicated by dizziness, fainting, or orthostasis.

References

  1. McAllister RG, Jr "Clinical pharmacology of slow channel blocking agents." Prog Cardiovasc Dis 25 (1982): 83-102
  2. "Product Information. Covera-HS (verapamil)." Searle PROD (2001):
  3. Zaidenstein R, Dishi V, Gips M, Soback S, Cohen N, Weissgarten J, Blatt A, Golik A "The effect of grapefruit juice on the pharmacokinetics of orally administered verapamil." Eur J Clin Pharmacol 54 (1998): 337-40
  4. 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
  5. 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
  6. Bailey DG, Dresser GK "Natural products and adverse drug interactions." Can Med Assoc J 170 (2004): 1531-2
  7. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions. 1998." Br J Clin Pharmacol 58 (2004): S831-40; discussion S841-3
  8. Arayne MS, Sultana N, Bibi Z "Review: grape fruit juice - drug interactions." Pak J Pharm Sci 18 (2005): 45-57
  9. Pillai U, Muzaffar J, Sandeep S, Yancey A "Grapefruit juice and verapamil: a toxic cocktail." South Med J 102 (2009): 308-9
View all 9 references

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Moderate

trandolapril food

Applies to: Tarka (trandolapril / verapamil)

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

verapamil food

Applies to: Tarka (trandolapril / verapamil)

GENERALLY AVOID: Verapamil may increase the blood concentrations and intoxicating effects of ethanol. The exact mechanism of interaction is unknown but may involve verapamil inhibition of ethanol metabolism. In 10 healthy, young volunteers, verapamil (80 mg orally every 8 hours for 6 days) increased the mean peak blood concentration (Cmax) and the 12-hour area under the concentration-time curve (AUC) of ethanol (0.8 g/kg single oral dose) by 17% and 30%, respectively, compared to placebo. Verapamil AUCs were positively correlated to increased ethanol blood AUC values. Subjectively (i.e. each subject's perception of intoxication as measured on a visual analog scale), verapamil also significantly increased the area under the ethanol effect versus time curve but did not change the peak effect or time to peak effect.

MANAGEMENT: Patients treated with verapamil should be counseled to avoid alcohol consumption.

References

  1. Bauer LA, Schumock G, Horn J, Opheim K "Verapamil inhibits ethanol elimination and prolongs the perception of intoxication." Clin Pharmacol Ther 52 (1992): 6-10
  2. "Product Information. Isoptin (verapamil)." Knoll Pharmaceutical Company PROD (2001):

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Moderate

timolol food

Applies to: Timolide 10-25 (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 "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: Timolide 10-25 (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 "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

verapamil food

Applies to: Tarka (trandolapril / verapamil)

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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Moderate

timolol food

Applies to: Timolide 10-25 (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 "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.

Further information

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

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