Cimetidine hydrochloride compatibility. III: Room temperature stability in drug admixtures

The stability of cimetidine hydrochloride mixed in intravenous solutions individually with 37 additives was investigated. Recommended doses of cimetidine hydrochloride injection and the other additives were diluted aseptically in varying concentrations in compatible intravenous solutions. The admixtures were stored at room temperature for 24 hours. Initial and 24-hour samples were evaluated visually on the basis of color, clarity, and pH. Cimetidine content was determined with a high-pressure liquid chromatographic procedure. The following drugs formed a precipitate with some dilutions of cimetidine hydrochloride injection in i.v. solutions: amphotericin B, cefamandole nafate, cefazolin sodium, and cephalothin sodium. The combination of cimetidine hydrochloride (300 mg) and cephalothin sodium (100 mg) resulted in a cimetidine concentration that was 77% of theory. Cimetidine hydrochloride injection was visually and chemically stable in the other admixtures examined. The results of this investigation suggest that incompatibility may be expected when cimetidine hydrochloride is combined with some antibiotics, and cimetidine incompatibilities may be concentration dependent.