Clonazepam is available as a concentrate for injection in 1-mL ampuls containing 1 mg of the drug in a solvent composed of ethanol, benzyl alcohol, propylene glycol, and glacial acetic acid.3406; 3407 Each ampul of the drug is packaged with an ampul containing 1 mL of sterile water for injection diluent.3406; 3407
For intravenous injection, the contents of the clonazepam ampul must be mixed thoroughly with the contents of the diluent ampul of sterile water for injection; to avoid local irritation of the veins, the mixture should be prepared immediately prior to administration.3406; 3407
For intravenous infusion, the contents of each clonazepam ampul (1 mg) should be diluted to at least 85 mL (e.g., 3 mg of clonazepam in 250 mL) with sodium chloride 0.9%, dextrose 2.5% in sodium chloride 0.45%, dextrose 5%, or dextrose 10% to avoid precipitation.3406; 3407
pH
Clonazepam (Roche) 0.125, 0.222, and 0.5 mg/mL in sodium chloride 0.9% for continuous subcutaneous infusion had pH values of 3.6, 3.5, and 3.6, respectively.2161
Trade Name(s)
Rivotril
Clonazepam is administered after dilution by slow intravenous injection or intravenous infusion.3406; 3407 When administered by intravenous injection, the diluted drug must be administered very slowly into a sufficiently large vein at a rate not exceeding 0.25 to 0.5 mg/min.3406; 3407 If the injection is administered rapidly or the vein into which the diluted drug is administered is not sufficiently large, there is a risk of thrombophlebitis and subsequent thrombosis.3406; 3407
Clonazepam has been administered intramuscularly after being mixed thoroughly with the contents of the diluent ampul of sterile water for injection, but this route should be used only in exceptional cases or if intravenous administration is not possible.3407 Efficacy of clonazepam administered by the intramuscular route has not been demonstrated.3406
Clonazepam concentrate for injection is a colorless to slightly green-yellow solution.3406; 3407 Intact ampuls should be stored below 253406 or 30°C3407 in the outer carton to protect from light.3406; 3407 If intended for administration by slow intravenous injection, the manufacturer recommends that the drug be used immediately after mixing with the supplied sterile water for injection diluent.3406; 3407 After clonazepam is diluted in a compatible infusion solution as instructed, the infusion is stated to be stable for 24 hours at room temperature;3406; 3407 however, if prepared in a polyvinyl chloride (PVC) container, the infusion should be infused immediately and usually within 4 hours, and the infusion time should not exceed 8 hours.3407
Clonazepam should not be mixed with sodium bicarbonate because of the potential for precipitation.3406; 3407
Syringes
Clonazepam (Roche) 5 and 10 mg, diluted to 48 mL with sodium chloride 0.9% and stored in polyethylene syringes, was physically compatible and exhibited no clonazepam loss in 10 hours at room temperature.1708
Reconstituted clonazepam (Roche) 0.5 mg/mL packaged in polypropylene syringes was evaluated. Less than 2% clonazepam loss occurred in 48 hours stored at room temperature exposed to normal room light.2172
Sorption
Clonazepam can adsorb to plastic infusion bags and infusion sets, especially those made of PVC.3406; 3407 Clonazepam has demonstrated sorption losses of up to 50% when in contact with PVC, especially when prepared bags are stored for more than 24 hours and/or when bags are stored in warm ambient conditions or when long tubing sets or slow rates of infusion are used.3406; 3407 It is recommended that PVC-containing bags and infusion sets be avoided if possible and that alternative materials be used.3406; 3407 If PVC bags are used, the admixture should be infused immediately and usually within 4 hours, and the infusion time should not exceed 8 hours.3407 Caution should be exercised when switching between PVC and non-PVC-containing bags and infusion sets.3406; 3407
Hooymans et al. compared losses of clonazepam to PVC and polyethylene-lined infusion tubing. Clonazepam (Roche) 5 and 10 mg, diluted in sodium chloride 0.9% to a final volume of 48 mL in polyethylene syringes, was delivered at room temperature through tubing at flow rates of 2 or 4 mL/hr (5 mg in 48 mL) and 2 mL/hr (10 mg in 48 mL). No losses were observed in the plastic syringes or to the polyethylene-lined tubing over 10 hours. Losses to the PVC tubing were dependent on the flow rate and concentration, being greater at 2 mL/hr and at 5 mg/48 mL, respectively. Potency decreased to approximately 40 and 55% of the original strength after 0.6 hour for the 5-mg/48 mL concentration at 2 and 4 mL/hr, respectively. After 0.6 hour, the 10-mg/48 mL concentration retained 55% of original potency when delivered at 2 mL/hr. Effluent concentrations gradually increased after the first hour, reaching approximately 80 to 90% of original concentrations after 10 hours.1708
Clonazepam (Roche) (concentration unspecified) in dextrose 5% in PVC containers was delivered over 4 hours through PVC administration sets. Losses due to sorption ranged from about 13 to 18% determined by UV spectroscopy.2045
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