The fixed combination of amoxicillin sodium-clavulanate potassium is available as a powder for injection in single-use vials or bottles containing 600 mg (amoxicillin 500 mg as the sodium salt plus clavulanate potassium equivalent to clavulanic acid 100 mg), 1.2 g (amoxicillin 1 g as the sodium salt plus clavulanate potassium equivalent to clavulanic acid 200 mg), and 2.2 g (amoxicillin 2 g as the sodium salt plus clavulanate potassium equivalent to clavulanic acid 200 mg).3558; 3559; 3560 The 600-mg and 1.2-g vials should be reconstituted with 10 and 20 mL, respectively, of sterile water for injection, resulting in an amoxicillin to clavulanic acid ratio of 5:1.3358; 3359; 3360 The 2.2-g vials should be reconstituted with 20 mL of sterile water for injection, resulting in an amoxicillin to clavulanic acid ratio of 10:1.3558
For administration by intravenous infusion, the reconstituted solution containing 500 mg of amoxicillin plus 100 mg of clavulanic acid should be diluted in 50 mL of, or to 50 mL with, a compatible diluent and the reconstituted solution containing 1 or 2 g of amoxicillin plus 200 mg of clavulanic acid should be diluted in 100 mL of, or to 100 mL with, a compatible diluent.3558; 3559; 3560 (See Solution Compatibility.)
Sodium and Potassium Content
Sodium and potassium content of amoxicillin sodium-clavulanate potassium vials is variable.3558; 3559; 3560 Several manufacturers state that 600-mg vials contain 1.4 mmol of sodium and 0.5 mmol of potassium.3558; 3560 Manufacturers state that 1.2-g vials contain either 2.73558; 3560 or 3.1 mmol of sodium3359 and 1 mmol of potassium. One manufacturer states that 2.2-g vials contain 5.5 mmol of sodium and 1 mmol of potassium.3558 Specific product labeling should be consulted for additional formulation details.
Trade Name(s)
Augmentin, Clavulin, Flanamox
Amoxicillin sodium-clavulanate potassium is administered intravenously, either by slow injection over 3 to 4 minutes directly into a vein or via intravenous tubing or by intermittent infusion over 30 to 40 minutes following dilution.3558; 3559; 3560 Some patients (e.g., pediatric patients younger than 3 months of age) should receive the drug only by intravenous infusion.3558 Reconstituted solutions prepared from 2.2-g vials and resulting in an amoxicillin to clavulanic acid ratio of 10:1 should be administered only by intravenous infusion following dilution.3558 Amoxicillin sodium-clavulanate potassium is not suitable for intramuscular administration.3558; 3559; 3560
Intact vials of the fixed combination of amoxicillin sodium-clavulanate potassium should be stored at 15 to 30°C3558 or at a temperature not exceeding 25°C.3559; 3560 After reconstitution with sterile water for injection, a transient pink color may appear,3558; 3559; 3560 with solutions quickly becoming clear again thereafter.3558 Reconstituted solutions are normally colorless or a yellow color.3559; 3560 The injection should be administered by slow intravenous injection, if appropriate, or further diluted for intravenous infusion within 153558 or 20 minutes3559; 3560 after reconstitution.
Amoxicillin-clavulanic acid is less stable in dextrose, dextran, or bicarbonate-containing infusion solutions and should not be mixed with such solutions.3559; 3560 Manufacturers state that amoxicillin-clavulanic acid also should not be added to proteinaceous fluids (e.g., protein hydrolysates) or intravenous lipid emulsions.3559; 3560
The stability of amoxicillin-clavulanic acid is governed by the more rapid degradation of clavulanic acid compared with amoxicillin.1474
Stability of amoxicillin-clavulanic acid also is concentration dependent;3559; 3560 amoxicillin-clavulanic acid is less stable in high concentrations. Therefore, it is suggested that reconstituted solutions be used immediately or diluted without delay.1474; 3558; 3559; 3560 If a more concentrated solution of amoxicillin-clavulanic acid is required, one manufacturer states that the stability period should be adjusted accordingly.3559; 3560
Freezing Solutions
The fixed combination of amoxicillin sodium-clavulanate potassium 1.2 g (amoxicillin 1 g as the sodium salt plus clavulanate potassium equivalent to clavulanic acid 200 mg) reconstituted with 20 mL and diluted in 100 mL of sterile water for injection was frozen at -20°C for 4 hours, followed by microwave thawing. Solutions retained only 65% of the initial clavulanic acid content.1474
Sorption
Amoxicillin-clavulanic acid did not undergo sorption to polyvinyl chloride (PVC) containers or administration tubing.1474
Y-Site Injection Compatibility (1:1 Mixture)
Additional Compatibility Information
Infusion Solutions
One manufacturer (Sandoz Canada) states that satisfactory concentrations of the drug are retained for 1 hour at 25°C when prepared as directed in sterile water for injection, compound sodium lactate (Hartmann’s solution), and sodium chloride with potassium chloride (concentrations unspecified).3558
One manufacturer (GlaxoSmithKline New Zealand) states that satisfactory concentrations of the drug are retained for 3 hours at 25°C when prepared as directed in compound sodium lactate (Hartmann’s solution) and sodium chloride with potassium chloride (concentrations unspecified) and for 4 hours at 25°C and 8 hours at 5°C when prepared as directed in sterile water for injection.3559
One manufacturer (GlaxoSmithKline UK) states that satisfactory concentrations of the drug are retained for 2 hours at 25°C when prepared as directed in compound sodium lactate (Hartmann’s solution) and for 3 hours at 25°C and 8 hours at 5°C when prepared as directed in sterile water for injection,3560
For a list of references cited in the text of this monograph, search the monograph titled References.