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Drug Interactions between Lexxel and Oralair

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

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Interactions between your drugs

Major

enalapril mixed grass pollens allergen extract

Applies to: Lexxel (enalapril / felodipine) and Oralair (mixed grass pollens allergen extract)

GENERALLY AVOID: Concomitant use of angiotensin converting enzyme (ACE) inhibitors may pose a greater risk of more serious systemic reactions, including anaphylaxis, to allergen immunotherapy. The proposed mechanism is inhibition by ACE inhibitors of the degradation of bradykinin, an inflammatory vasoactive peptide that causes vasodilation of blood vessels and increased vascular permeability of the postcapillary venules. Elevated bradykinin levels have been associated with ACE inhibitor-related angioedema of the face, extremities, lips, tongue, glottis, and/or larynx. Two patients who were undergoing desensitizing treatment with hymenoptera venom during ACE inhibitor therapy sustained life-threatening anaphylactoid reactions, which were avoided when ACE inhibitors were temporarily withheld but reappeared upon inadvertent rechallenge.

MANAGEMENT: Immunotherapy with allergenic extracts may not be appropriate in patients receiving ACE inhibitors due to the potential for more serious systemic reactions. Close monitoring is advised if coadministration is required.

References

  1. (2002) "Product Information. Vasotec (enalapril)." Merck & Co., Inc
  2. (2014) "Product Information. Oralair (mixed grass pollens allergen extract)." Greer Laboratories Inc

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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 (1991) "Amlodipine in the treatment of hypertension." Postgrad Med J, 67 Suppl 5, s15-9
  2. DeQuattro V (1991) "Comparison of benazepril and other antihypertensive agents alone and in combination with the diuretic hydrochlorothiazide." Clin Cardiol, 14, iv28-32;
  3. Sun JX, Cipriano A, Chan K, John VA (1994) "Pharmacokinetic interaction study between benazepril and amlodipine in healthy subjects." Eur J Clin Pharmacol, 47, p. 285-9
  4. Di Somma S, et al. (1992) "Antihypertensive effects of verapamil, captopril and their combination at rest and during dynamic exercise." Arzneimittelforschung, 42, p. 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. (2002) "Product Information. Vasotec (enalapril)." Merck & Co., Inc
  2. Good CB, McDermott L (1995) "Diet and serum potassium in patients on ACE inhibitors." JAMA, 274, p. 538
  3. Ray K, Dorman S, Watson R (1999) "Severe hyperkalaemia due to the concomitant use of salt substitutes and ACE inhibitors in hypertension: a potentially life threatening interaction." J Hum Hypertens, 13, p. 717-20

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

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Moderate

mixed grass pollens allergen extract food

Applies to: Oralair (mixed grass pollens allergen extract)

ADJUST DOSING INTERVAL: Since sublingual preparations of allergenic extracts are meant to be absorbed directly from tissues under the tongue into the blood stream, consuming food or beverage during or immediately after administration may reduce the systemic bioavailability of the medication.

MONITOR: Coadministration of allergenic extracts for allergy immunotherapy with alcohol may potentiate the risk of allergic reactions, including anaphylaxis. According to some studies, alcohol is an augmenting factor influencing immunological mechanisms that can induce more severe allergic reactions and is involved in up to 15% of cases of anaphylactic reactions. Proposed mechanisms include an increase in allergen absorption from altered permeability of the intestinal epithelial barrier, enhancing mast cell and basophil activation, and an increase in serum IgE concentrations. A causal relationship with all allergenic extracts has not been established.

MANAGEMENT: Food or beverage should not be taken with, or for at least 5 minutes after, the administration of sublingual allergenic extracts. Patients should also avoid swallowing for about 1 minute following placement of the allergen extract under the tongue. Caution is advised if allergenic extracts for immunotherapy are used concomitantly with alcohol. Some manufacturers of peanut allergen extract recommend alcohol not be consumed for 2 hours before, or 2 hours after taking peanut allergen extract and if alcohol use cannot be avoided, that withholding or decreasing peanut allergen dosage should be considered. Individual prescribing information should be consulted for further guidance and clinical monitoring may be considered.

References

  1. (2014) "Product Information. Grastek (timothy grass pollen allergen extract)." Merck & Co., Inc
  2. (2014) "Product Information. Ragwitek (ragweed pollen allergen extract)." Merck & Co., Inc
  3. (2014) "Product Information. Oralair (mixed grass pollens allergen extract)." Greer Laboratories Inc
  4. Cerner Multum, Inc. (2015) "Canadian Product Information."
  5. (2023) "Product Information. Palforzia (peanut allergen extract)." Aimmune Therapeutics
  6. (2022) "Product Information. Palforzia Level 1 (peanut allergen extract)." Aimmune Therapeutics UK Ltd
  7. Munoz-Cano R, Pascal M, Araujo G, et al. (2023) Mechanisms, Cofactors, and Augmenting Factors Involved in Anaphylaxis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623009/pdf/fimmu-08-01193.pdf
  8. (2023) "Product Information. Odactra (house dust mite allergen extract)." ALK-Abello Inc
View all 8 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 (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

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 (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

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

Further information

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