Drug Interactions between enalapril / felodipine and iron dextran

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

enalapril/felodipine
iron dextran

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Major

enalapril iron dextran

Applies to: enalapril / felodipine and iron dextran

MONITOR CLOSELY: Limited data suggest that ACE inhibitors may increase the risk of systemic adverse effects associated with the use of iron dextran. The exact mechanism of interaction is unclear. Certain systemic reactions stemming from parenteral iron therapy are thought to be mediated by inflammatory substances such as bradykinin in response to iron-catalyzed generation of toxic free radicals. Since ACE inhibitors decrease the breakdown of kinins, it is conceivable that they may potentiate these reactions. Anaphylactic-type reactions, including fatalities, have followed the parenteral administration of iron dextran. Such reactions occur most often within the first several minutes of administration and are generally characterized by sudden onset of respiratory difficulty and/or cardiovascular collapse. The extent of risk for anaphylactic-type reactions following exposure to any specific iron dextran product is unknown, but may vary among the products due to differences in chemical characteristics. Other systemic adverse effects reported with iron dextran include hypotension, flushing, dizziness, headache, chest pain, cardiac arrest, arthralgia, myalgia, back pain, fever, chills, pruritus, rash, nausea, vomiting, diarrhea, and abdominal pain. The noncardiovascular reactions are frequently delayed by 24 to 48 hours after administration and subside within 3 to 4 days.

MANAGEMENT: Patients should be closely monitored during and after parenteral administration of iron dextran, regardless of whether they are being treated with an ACE inhibitor. This is particularly important in patients with a history of drug allergy or multiple drug allergies or an immune/inflammatory condition such as systemic lupus erythematosus or rheumatoid arthritis. Resuscitation techniques and personnel trained in the detection and treatment of anaphylactic-type reactions should be readily available. Prior to the first therapeutic dose, a test dose corresponding to 25 mg iron should be injected gradually. Although anaphylactic reactions are usually evident within a few minutes, observe patients for at least one hour before administering the remainder of the therapeutic dose. Administration must be stopped immediately if signs of an anaphylactoid reaction are observed. Patients should also be closely monitored during each subsequent administration of iron dextran. Fatal reactions have occurred following the test dose and also in situations where the test dose was tolerated. Iron dextran should only be used in patients in whom clinical and laboratory investigations have established an iron-deficient state not amenable to oral iron therapy. According to some studies, non-dextran parenteral iron formulations may be associated with a lower risk of adverse effects, especially death and life-threatening reactions such as anaphylaxis, cardiac arrest, and respiratory depression.

References (9)

"Product Information. Infed (iron dextran)." Schein Pharmaceuticals Inc
Rolla G, Bucca C, Brussino L (1994) "Systemic reactions to intravenous iron therapy in patients receiving angiotensin converting enzyme inhibitor ." J Allergy Clin Immunol, 93, p. 1074-5
Faich G, Strobos J (1999) "Sodium ferric gluconate complex in sucrose: Safer intravenous iron therapy than iron dextrans." Am J Kidney Dis, 33, p. 464-70
Michael B, Coyne DW, Fishbane S, et al. (2002) "Sodium ferric gluconate complex in hemodialysis patients: Adverse reactions compared to placebo and iron dextran." Kidney Int, 61, p. 1830-1839
Chertow GM, Mason PD, Vaage-Nilsen O, Ahlmen J (2006) "Update on adverse drug events associated with parenteral iron." Nephrol Dial Transplant, 21, p. 378-82
Bailie GR, Clark JA, Lane CE, Lane PL (2005) "Hypersensitivity reactions and deaths associated with intravenous iron preparations." Nephrol Dial Transplant, 20, p. 1443-9
Chertow GM, Mason PD, Vaage-Nilsen O, Ahlmen J (2004) "On the relative safety of parenteral iron formulations." Nephrol Dial Transplant, 19, p. 1571-5
Michael B, Coyne DW, Folkert VW, Dahl NV, Warnock DG (2004) "Sodium ferric gluconate complex in haemodialysis patients: a prospective evaluation of long-term safety." Nephrol Dial Transplant, 19, p. 1576-80
Fishbane S, Kowalski EA (2000) "The comparative safety of intravenous iron dextran, iron saccharate, and sodium ferric gluconate." Semin Dial, 13, p. 381-4

Minor

enalapril felodipine

Applies to: enalapril / felodipine and 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 (4)

Kaplan NM (1991) "Amlodipine in the treatment of hypertension." Postgrad Med J, 67 Suppl 5, s15-9
DeQuattro V (1991) "Comparison of benazepril and other antihypertensive agents alone and in combination with the diuretic hydrochlorothiazide." Clin Cardiol, 14, iv28-32;
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
Di Somma S, et al. (1992) "Antihypertensive effects of verapamil, captopril and their combination at rest and during dynamic exercise." Arzneimittelforschung, 42, p. 103