Compatibility of aminophylline and verapamil in intravenous admixtures

The chemical and visual compatibility of aminophylline and verapamil hydrochloride in intravenous admixtures was evaluated. Verapamil hydrochloride injection was added to a solution of aminophylline 1.0 mg/mL in 5% dextrose injection (D5W) to yield final verapamil hydrochloride concentrations of 0.1 and 0.4 mg/mL. Each solution type was prepared in triplicate. An aliquot from each of these solutions was assayed in duplicate for theophylline and verapamil by high-performance liquid chromatography at 0, 4, 8, 12, and 24 hours after mixing. All aliquots were filtered with a 0.22-micron filter immediately before assay. At each time interval, samples were assessed for pH and inspected visually and microscopically for evidence of incompatibility. Theophylline concentrations showed less than 10% change over 24 hours in the two-drug admixtures. Less than 1% of the original verapamil concentrations remained immediately after mixing with aminophylline injection in D5W. Turbidity was readily apparent in the admixture containing verapamil hydrochloride 0.4 mg/mL; however, microscopic evaluation revealed precipitate in both solutions. Solution pH was determined to be a primary cause of precipitation. The mean pH values for the verapamil hydrochloride 0.1 and 0.4 mg/mL control solutions were 4.09 and 4.36, respectively. The mean pH of the aminophylline 1.0 mg/mL control solution was 8.35. The mean pH of the aminophylline-verapamil admixtures at verapamil hydrochloride concentrations of 0.1 and 0.4 mg/mL was 8.14 and 8.06, respectively. Verapamil hydrochloride injection in final concentrations of 0.1 and 0.4 mg/mL is incompatible with aminophylline 1.0 mg/mL in D5W.