Irinotecan hydrochloride is available as a concentrate for injection in 2-, 5-, 15-, and 25-mL single-use vials containing 40, 100, 300, and 500 mg of drug, respectively, on the basis of the trihydrate.3202; 3203 Each mL of solution contains irinotecan hydrochloride trihydrate 20 mg, sorbitol 45 mg, lactic acid 0.9 mg, and hydrochloric acid or sodium hydroxide to adjust the pH in water for injection.3202; 3203 The product must be diluted prior to use.3202; 3203
Irinotecan hydrochloride concentrate for injection should be visually inspected for particulate matter and discoloration in the vial and again once the solution has been drawn from the vial into the syringe.3202; 3203 Irinotecan hydrochloride concentrate for injection should be diluted to a final concentration of 0.12 to 2.8 mg/mL with dextrose 5% (preferred) or sodium chloride 0.9% prior to administration.3202; 3203
CAUTION: Care should be taken to ensure that the correct drug product, dose, and administration procedures are used and that no confusion with other products occurs.
pH
Irinotecan hydrochloride concentrate for injection has a pH from 3 to 4.3202; 3203; 3204
Trade Name(s)
Camptosar
Irinotecan hydrochloride is administered by intravenous infusion over 90 minutes after dilution to a final concentration in the range of 0.12 to 2.8 mg/mL in dextrose 5% (preferred) or sodium chloride 0.9%.3203; 3203
As with other toxic drugs, caution should be exercised in the handling and preparation of irinotecan hydrochloride solutions for infusion.3202; 3203 Manufacturers recommend the use of gloves.3202; 3203 If skin contact with the drug occurs, the affected area(s) should be washed immediately and thoroughly with soap and water; for mucosal membrane contact, the affected(s) area should be flushed thoroughly with water.3202; 3203 Extravasation should be avoided.3202; 3203
CAUTION: Care should be taken to ensure that the correct drug product, dose, and administration procedures are used and that no confusion with other products occurs.
Irinotecan hydrochloride injection is a clear pale yellow solution.3202; 3203 Intact vials should be stored upright at controlled room temperature and in the original carton to protect from light until use.3202; 3203
Manufacturers recommend that diluted solutions of irinotecan hydrochloride for infusion should be used immediately or within 4 hours after dilution if stored at room temperature (in dextrose 5% or sodium chloride 0.9%) or 24 hours if stored at 2 to 8°C (in dextrose 5% only).3202; 3203 Refrigeration of admixtures of the drug prepared with sodium chloride 0.9% should be avoided because of the potential for a low and sporadic incidence of visible particulate formation.3202; 3203
Irinotecan hydrochloride (Aventis Pharma) 0.35 mg/mL in sodium chloride 0.9% did not result in the loss of viability of Staphylococcus aureus, Enterococcus faecium, Pseudomonas aeruginosa, and Candida albicans within 120 hours at room temperature of 22°C. Diluted solutions should be stored under refrigeration whenever possible, and the potential for microbiological growth should be considered when assigning expiration periods.2740
pH Effects
Irinotecan hydrochloride stability is pH dependent. In solution at acidic pH the drug is stable, but neutral and alkaline solutions are problematic. Maximum stability is demonstrated at pH 6 or lower. Increasing solution pH to more than pH 6.5 has resulted in 10% loss in as little as 3 hours. At pH 7.4, decomposition is rapid. Mixing irinotecan hydrochloride with neutral or alkaline drugs and solutions should be avoided.1881; 2274; 2375
Light Effects
Irinotecan hydrochloride is subject to photodegradation, including the formation of a precipitate. The structural changes exhibited by the decomposition products would indicate that they are unlikely to be active antineoplastic compounds.1997; 1998; 2137 Exposure to ultraviolet light for 3 days produced a darkening in the solution color and the formation of a yellow precipitate composed of several decomposition products.1997 Photodegradation of irinotecan hydrochloride occurs under any pH condition but is accelerated in neutral and alkaline solutions compared with acidic solutions. At pH 10, photodegradation is very rapid; at pH 3 it is much slower. At pH 7, irinotecan 0.34 mg/mL lost 32% in 6 hours exposed to a daylight lamp and 19% exposed to a white fluorescent light. In infusion solutions having neutral pH, irinotecan hydrochloride exposed to lighting (such as that of a medical facility) may have rapid decomposition. Protection from light exposure has been recommended to maintain product quality during administration.1998 Other researchers have found that unacceptable losses occur within 7 days when exposed to fluorescent light but that light protection during administration is not needed.2419
Freezing Solutions
Precipitation may result from freezing irinotecan hydrochloride concentrate for injection and diluted solutions for infusion; freezing should be avoided.3202; 3203
For a list of references cited in the text of this monograph, search the monograph titled References.