Compatibility of premixed theophylline and verapamil intravenous admixtures

The stability of verapamil hydrochloride injection when mixed with a commercial product of premixed theophylline in 5% dextrose injection was studied. Solutions containing theophylline in concentrations of 4.0 and 0.4 mg/mL were used. Verapamil hydrochloride was added to each theophylline solution to produce final verapamil concentrations of 0.4 mg/mL and 0.1 mg/mL. Each admixture was prepared in triplicate, and samples were kept at room temperature in glass. Immediately after mixing and at 4, 8, 12, and 24 hours, samples were visually inspected, tested for pH, filtered, and assayed in duplicate by high-performance liquid chromatography for theophylline and verapamil concentrations. Control solutions containing only one of the two drugs were also tested. No visual changes were observed. The addition of the verapamil hydrochloride injection to the theophylline in 5% dextrose injection resulted in decreased mean pH values of 4.29 and 4.37 for all solutions compared with 4.80 and 4.90 for the verapamil control samples at concentrations of 0.4 and 0.1 mg/mL. These values did not vary significantly throughout the study period. Theophylline and verapamil concentrations did not change significantly compared with baseline or control solutions during the study period. Verapamil hydrochloride injection in final concentrations of 0.1 to 0.4 mg/mL can be added to a commercial preparation of premixed theophylline in 5% dextrose injection in concentrations of 0.4 to 4.0 mg/mL and administered intravenously within 24 hours of mixing without loss of potency of either drug.