Drug interactions between Hexabrix and Inderide

propranolol ↔ ioxaglate

Applies to:Inderide (hydrochlorothiazide/propranolol) and Hexabrix (ioxaglate)

MONITOR: Limited data suggest that patients receiving beta-blockers may have an increased risk of severe hypotensive and/or hypersensitivity reactions to parenteral iodinated contrast media. In addition, allergic/anaphylactoid reactions in these patients may be more difficult to treat. The mechanism is unknown. Theoretically, 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.

MANAGEMENT: Patients who have received beta-blockers should be closely monitored for adverse reactions to iodinated contrast media. If anaphylaxis occurs, clinicians should be aware that beta-blockers may attenuate the response to epinephrine. Thus, larger doses of epinephrine may be necessary to overcome the bronchospasm, although such large doses can also cause excessive alpha-adrenergic stimulation resulting in hypertension, reflex bradycardia, heart block, and possible potentiation of bronchospasm. Alternative treatments recommended include vigorous supportive care (e.g., fluids) and the use of parenteral beta-agonists for bronchospasm and norepinephrine for hypotension.

hydrochlorothiazide ↔ ioxaglate

Applies to:Inderide (hydrochlorothiazide/propranolol) and Hexabrix (ioxaglate)

MONITOR: Forced diuresis during administration of radiocontrast agents may increase the risk of renal impairment in patients who are at high risk for contrast-induced nephropathy. Patients considered at high risk include those with diabetes (especially diabetic nephropathy), preexisting renal insufficiency (serum creatinine >1.5 mg/dL or GFR <60 mL/min/1.73 m2), volume depletion, advanced age (>70 years), congestive heart failure, and/or concurrent use of nephrotoxic drugs (e.g., NSAIDs). Diuretics have been studied for use in the prevention of contrast-induced nephropathy because investigators theorized that they may reduce medullary ischemia by decreasing oxygen demands. In published studies, however, maintenance intravenous fluids plus forced diuresis with furosemide, mannitol, or a combination of both given at the time of radiocontrast exposure generally produced similar or even higher rates of nephropathy compared with intravenous fluids alone. Meta-analyses of published data suggest that furosemide-based interventions significantly increase the risk of contrast-induced nephropathy compared with hydration alone, and one study found that hospitalization for all patients who developed contrast-induced nephropathy was increased by 4 days in those who received concomitant diuretic therapy. Contrast-induced nephropathy is most commonly defined as an increase in serum creatinine >=0.5 mg/dL or 25% from baseline within 48 to 72 hours of intravascular contrast administration in the absence of alternative etiologies, although nephropathy may occur up to a week after contrast exposure. While the condition is usually transient and asymptomatic, it can be associated with increased risk of renal failure, dialysis, prolonged hospitalization, significant long-term morbidity, and mortality.

MANAGEMENT: Whenever possible, alternative imaging techniques should be considered in patients who are at high risk for contrast-induced nephropathy. Otherwise, some experts recommend discontinuing diuretics 1 to 2 days before administration of contrast media, depending on the clinical feasibility of doing so. The smallest effective dose of a nonionic, hypo- or iso-osmolar contrast medium (e.g., iohexol, iodixanol, iopamidol) should be used, since the risk of nephropathy is increased with increasing contrast dose and/or osmolarity. Repeat procedures with contrast media, if necessary, should not occur until at least 72 hours after the previous contrast exposure and renal function has fully recovered. Although it is not necessary to measure the serum creatinine levels of every patient before contrast administration, measurements should generally be made in patients receiving contrast agent by intraarterial administration (which is associated with increased risk of nephropathy relative to intravenous administration) and patients with a history of kidney disease, proteinuria, kidney surgery, diabetes, hypertension, gout, or other risk factors for nephropathy. Creatinine measurements should be continued for 24 to 48 hours after administration of contrast medium. It is important that patients be adequately hydrated with either saline or sodium bicarbonate.