Drug Interactions between Capozide 50/25 and Dexferrum

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.

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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.

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