Isosorbide dinitrate is available as a 0.1% concentrate for injection in 10-mL ampuls and 50- and 100-mL vials and bottles; each mL contains isosorbide dinitrate 1 mg with sodium chloride in water for injection.3573; 3574 Hydrochloric acid and sodium hydroxide may be present to adjust the pH.3573 The concentrate for injection must be diluted prior to intravenous administration.3573; 3574 Manufacturers state that 50 mL (50 mg) of isosorbide dinitrate 0.1% concentrate for injection may be diluted in 450 mL of a compatible infusion solution for a final isosorbide dinitrate concentration of 0.1 mg/mL.3573; 3574 If reduced fluid intake is necessary, 100 mL (100 mg) of isosorbide dinitrate 0.1% concentrate for injection may be diluted to a total volume of 500 mL using a compatible infusion solution for a final isosorbide dinitrate concentration of 0.2 mg/mL; if fluid intake is strictly limited, a 50% dilution of the concentrate for injection (i.e., to a final isosorbide dinitrate concentration of 0.5 mg/mL) is recommended.3573; 3574
The drug also is available as a 0.05% solution in 50-mL vials and bottles and 10-mL prefilled syringes; each mL contains isosorbide dinitrate 0.5 mg with sodium chloride in water for injection.3571; 3572 Hydrochloric acid and sodium hydroxide also may be present to adjust the pH.3571
Sodium Content
Each mL of isosorbide dinitrate 0.05 or 0.1% solution contains 3.543571; 3572; 3573 or 3.6 mg3574 of sodium.
Trade Name(s)
Isoket, Risordan
Isosorbide dinitrate is administered by intravenous infusion.3571; 3572; 3573; 3574 Only the 0.05% solution may be administered undiluted by slow infusion using a syringe pump; alternatively, the 0.05% solution may be diluted in a compatible infusion solution for administration.3571; 3572 The 0.1% concentrate for injection must be diluted in a compatible infusion solution prior to intravenous administration.3573; 3574
Isosorbide dinitrate also may be administered as an intracoronary bolus injection during percutaneous transluminal coronary angioplasty.3571; 3572; 3573; 3574 Manufacturers recommend a 50% dilution of the 0.1% concentrate for injection (i.e., to a final isosorbide dinitrate concentration of 0.5 mg/mL) if administered by the intracoronary route.3573; 3574
Once opened, containers should be used immediately, and any remainder should be discarded.3571; 3572; 3573; 3574 Specific product labeling should be consulted for additional storage details.
One manufacturer (Merus Labs) states that isosorbide dinitrate diluted in a compatible infusion solution (e.g., sodium chloride [concentration unspecified], dextrose 5 to 30%, Ringer’s injection) is physically and chemically stable for 24 hours at 2 to 8°C.3571; 3573 Another manufacturer (Torbay) states that isosorbide dinitrate diluted in sodium chloride (concentration unspecified) or dextrose (concentration unspecified) has been shown to be physically and chemically stable for 72 hours at 25°C when stored protected from light in polypropylene or glass containers.3572; 3574
Syringes
Isosorbide dinitrate (Rhone-Poulenc) 1 mg/mL was repackaged in polypropylene syringes (Plastipak, Becton Dickinson) and stored for 8 hours at room temperature and 4°C. No loss of drug was found.1799
Isosorbide dinitrate (Takeda) 30 mg/50 mL in sodium chloride 0.9% in a 50-mL polypropylene syringe (BD) was physically stable for 48 hours at room temperature.3545
Isosorbide dinitrate (Takeda) 0.6 mg/mL in sodium chloride 0.9% in a 50-mL polypropylene syringe (BD) was physically stable with a mean loss of 5.4% in 28 days at 2 to 8°C protected from light.3570
Sorption
Isosorbide dinitrate undergoes rapid and extensive sorption to polyvinyl chloride (PVC) and polyamide containers and PVC administration tubing. Studies have reported isosorbide dinitrate losses ranging from about 15 to 50%, depending on concentration, flow rate, contact time, length of tubing, and temperature. The majority of loss occurs at the beginning of contact with the plastic and then declines as saturation occurs. Isosorbide dinitrate also undergoes sorption of about 16 to 26% to cellulose propionate and butadiene styrene burette chambers but only 2% to methacrylate butadiene styrene burette chambers. However, little or no sorption occurs to glass, polyethylene, polybutadiene, nylon, and polypropylene containers and administration equipment. Consequently, glass, polyethylene, polypropylene, polybutadiene, and polytetrafluoroethylene containers and equipment are recommended while PVC, polyurethane, and polyamide are not.769; 782; 795; 1027; 1392; 1464; 1465; 1466; 1467; 1619; 2143; 2289; 3571; 3572; 3573; 3574
Filtration
Losses due to sorption of isosorbide dinitrate 250 mg/L in sodium chloride 0.9% delivered at 20 mL/hr through cellulose acetate filters (Sterifix, Ivex HP) were 15 to 26%. Losses to polyamide filters (Pall) were 9 to 13% under the same conditions.1465
The loss of isosorbide dinitrate due to sorption to filters extends to filters used in hemodialysis. Isosorbide dinitrate 0.1 mg/mL in sodium chloride 0.9% during simulated hemodialysis using 5 different filter media underwent substantial drug losses from the solution and binding to some of the filters. Losses of approximately 86% with polysulfone (Fresenius), 72% with cellulose acetate (Baxter), 43% with polyacrylonitrile (Hospal), and 12% cuprophan (Gambro) were found. However, with hemophan filters (Gambro), no loss of drug due to sorption occurred.2138
For a list of references cited in the text of this monograph, search the monograph titled References.