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Drug Interactions between A-G Profen and diltiazem / enalapril

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

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Interactions between your drugs

Moderate

enalapril ibuprofen

Applies to: diltiazem / enalapril and A-G Profen (ibuprofen)

MONITOR: Nonsteroidal anti-inflammatory drugs (NSAIDs) may attenuate the antihypertensive effects of ACE inhibitors. The proposed mechanism is NSAID-induced inhibition of renal prostaglandin synthesis, which results in unopposed pressor activity producing hypertension. In addition, NSAIDs can cause fluid retention, which also affects blood pressure. Some NSAIDs may also alter the pharmacokinetics of certain ACE inhibitors. For example, oxaprozin has been shown to reduce the systemic exposure (AUC) of enalapril and its active metabolite, enalaprilat.

MONITOR: Concomitant use of NSAIDs and ACE inhibitors may cause deterioration in renal function, particularly in patients who are elderly or volume-depleted (including those on diuretic therapy) or have compromised renal function. Acute renal failure may occur, although effects are usually reversible. Chronic use of NSAIDs alone may be associated with renal toxicities, including elevations in serum creatinine and BUN, tubular necrosis, glomerulitis, renal papillary necrosis, acute interstitial nephritis, nephrotic syndrome, and renal failure. Additionally, in patients with prerenal conditions whose renal perfusion may be dependent on the function of prostaglandins, NSAIDs may precipitate overt renal decompensation via a dose-related inhibition of prostaglandin synthesis. ACE inhibitors can further worsen renal function by blocking the effect of angiotensin II-mediated efferent arteriolar vasoconstriction, thereby decreasing glomerular filtration.

MANAGEMENT: Patients receiving ACE inhibitors who require prolonged (greater than 1 week) concomitant therapy with an NSAID should have blood pressure monitored more closely following initiation, discontinuation, or change of dosage of the NSAID. Renal function should also be evaluated periodically during prolonged coadministration. The interaction is not expected to occur with low doses (e.g., low-dose aspirin) or intermittent short-term administration of NSAIDs.

References

  1. Moore TJ, Crantz FR, Hollenberg NK "Contribution of prostaglandins to the antihypertensive action of captopril in essential hypertension." Hypertension 3 (1981): 168-73
  2. Radack KL, Deck CC, Bloomfield SS "Ibuprofen interferes with the efficacy of antihypertensive drugs: a randomized, double-blind, placebo-controlled trial of ibuprofen compared with acetaminophen." Ann Intern Med 107 (1987): 628-35
  3. Silberbauer K, Stanek B, Templ H "Acute hypotensive effect of captopril in man modified by prostaglandin synthesis inhibition." Br J Clin Pharmacol 14 (1982): s87-93
  4. Ahmad S "Indomethacin-enalapril interaction: an alert." South Med J 84 (1991): 411-2
  5. Allon M, Pasque CB, Rodriguez M "Interaction of captopril and ibuprofen on glomerular and tubular function in humans." Am J Physiol 259 (1990): f233-8
  6. Seto S, Aoi W, Iwami K, et al. "Effect of propranolol and indomethacin on the depressor action of captopril in patients with essential hypertension." Clin Exp Hypertens 9 (1987): 623-7
  7. "Product Information. Toradol (ketorolac)." Roche Laboratories PROD (2002):
  8. Abdel-Haq B, Magagna A, Favilla S, Salvetti A "Hemodynamic and humoral interactions between perindopril and indomethacin in essential hypertensive subjects." J Cardiovasc Pharmacol 18 (1991): s33-6
  9. Morgan T, Anderson A "Interaction of indomethacin with felodipine and enalapril." J Hypertens 11 (1993): S338-9
  10. "Product Information. Daypro (oxaprozin)." Searle PROD (2001):
  11. Townend JN, Doran J, Lote CJ, Davies MK "Peripheral haemodynamic effects of inhibition of prostaglandin synthesis in congestive heart failure and interactions with captopril." Br Heart J 73 (1995): 434-41
  12. Polonia J, Boaventura I, Gama G, Camoes I, Bernardo F, Andrade P, Nunes JP, Brandao F, Cerqueiragomes M "Influence of non-steroidal anti-inflammatory drugs on renal function and 24h ambulatory blood pressure-reducing effects of enalapril and nifedipine gastrointestinal therapeutic system in hypertensive patients." J Hypertens 13 (1995): 925-31
  13. "Product Information. Celebrex (celecoxib)." Searle PROD (2001):
View all 13 references

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Moderate

ibuprofen dilTIAZem

Applies to: A-G Profen (ibuprofen) and diltiazem / enalapril

MONITOR: Limited data indicate that some cyclooxygenase inhibitors may attenuate the antihypertensive effects of some calcium channel blockers. The mechanism appears to be related to an alteration of vascular tone, which is dependent on prostacyclins and other vasodilatory prostanoids. When a nonsteroidal anti-inflammatory drug (NSAID) is added to the regimen of a patient who is already taking a calcium channel blocker, increased blood pressure may result. Also, the clinician should be aware that the risk of hypotension is increased when NSAIDs are withdrawn from the regimen.

MANAGEMENT: Monitoring for altered blood pressure control is recommended.

References

  1. Ring ME, Corrigan JJ, Fenster PE "Effects of oral diltiazem on platelet function: alone and in combination with "low dose" aspirin." Thromb Res 44 (1986): 391-400
  2. Altman R, Scazziota A, Dujovne C "Diltiazem potentiates the inhibitory effect of aspirin on platelet aggregation." Clin Pharmacol Ther 44 (1988): 320-5
  3. Cremer KF, Pieper JA, Joyal M, Mehta J "Effects of diltiazem, dipyridamole, and their combination on hemostasis." Clin Pharmacol Ther 36 (1984): 641-4
  4. Minuz P, Pancera P, Ribul M, et al. "Amlodipine and haemodynamic effects of cyclo-oxygenase inhibition." Br J Clin Pharmacol 39 (1995): 45-50
  5. Houston MC, Weir M, Gray J, et al. "The effects of nonsteroidal anti-inflammatory drugs on blood pressures of patients with hypertension controlled by verapamil." Arch Intern Med 155 (1995): 1049-54
  6. Deleeuw PW "Nonsteroidal anti-inflammatory drugs and hypertension: the risks in perspective." Drugs 51 (1996): 179-87
  7. "Product Information. DurAct (bromfenac)." Wyeth-Ayerst Laboratories PROD
  8. "Product Information. Arthrotec (diclofenac-misoprostol)." Searle PROD (2001):
  9. Zanchetti A, Hansson L, Leonetti G, et al. "Low-dose aspirin does not interfere with the blood pressure-lowering effects of antihypertensive therapy." J Hypertens 20 (2002): 1015-1022
View all 9 references

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Minor

enalapril dilTIAZem

Applies to: diltiazem / enalapril and diltiazem / enalapril

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: diltiazem / enalapril

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

dilTIAZem food

Applies to: diltiazem / enalapril

MONITOR: Like many CNS-active agents, alcohol can exhibit hypotensive effects. Coadministration with antihypertensive agents including diltiazem may result in additive effects on blood pressure and orthostasis.

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered diltiazem in some patients. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In a study of ten healthy male volunteers, administration of a single 120 mg oral dose of immediate-release diltiazem in combination with 250 mL of grapefruit juice increased the diltiazem peak plasma concentration (Cmax) and systemic exposure (AUC) by an average of 22% and 20%, respectively, compared to administration with water. The time to reach Cmax (Tmax) and the terminal half-life were not affected, and no statistically significant differences in blood pressure and heart rate were observed during administration with grapefruit juice relative to water. In a different study, repeated administration of 200 mL of grapefruit juice at 0, 2, 4, 8 and 12 hours had no significant effect on the Cmax or AUC of a single 120 mg oral dose of diltiazem, but increased its half-life from 4.1 to 5.1 hours. The ratios for the N-demethyl and deacetyl metabolites to diltiazem were also not affected by grapefruit juice. However, because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients should be advised that alcohol may potentiate the hypotensive effects of diltiazem, especially during the initiation of therapy and following a dosage increase. Caution should be exercised when rising from a sitting or recumbent position, and patients should notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients who regularly consume grapefruit or grapefruit juice should be monitored for increased adverse effects of diltiazem such as such as headache, irregular heartbeat, edema, unexplained weight gain, and chest pain. Grapefruit and grapefruit juice should be avoided if an interaction is suspected.

References

  1. Bailey DG, Arnold JMO, Spence JD "Grapefruit juice and drugs - how significant is the interaction." Clin Pharmacokinet 26 (1994): 91-8
  2. Sigusch H, Henschel L, Kraul H, Merkel U, Hoffmann A "Lack of effect of grapefruit juice on diltiazem bioavailability in normal subjects." Pharmazie 49 (1994): 675-9
  3. Bailey DG, Malcolm J, Arnold O, Spence JD "Grapefruit juice-drug interactions." Br J Clin Pharmacol 46 (1998): 101-10
  4. Christensen H, Asberg A, Holmboe AB, Berg KJ "Coadministration of grapefruit juice increases systemic exposure of diltiazem in healthy volunteers." Eur J Clin Pharmacol 58 (2002): 515-520
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
View all 5 references

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Moderate

enalapril food

Applies to: diltiazem / enalapril

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

ibuprofen food

Applies to: A-G Profen (ibuprofen)

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

References

  1. "Product Information. Motrin (ibuprofen)." Pharmacia and Upjohn PROD (2002):

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Moderate

dilTIAZem food

Applies to: diltiazem / enalapril

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

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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