Administration of Amoxicillin-Clavulanic Acid injection: Things to know

Amoxicillin plus Clavulanic acid injection is commonly used to treat severe infection at health care facilities. The dosage strengths on the market are 600mg and 1.2g. The usual dosage for the injections is 25mg of Amoxicillin and 5mg of Clavulanic acid per kg body weight per dose. The available dosage strengths pose challenges particularly after reconstitution and the temptation on the part of health care workers to store remaining for re-use. I have used information from the product (Amoxicillin plus Clavulanic acid injection).

INDICATIONS

Amoxicillin Sodium and Potassium Clavulanate for Injection (Co-Amoxiclav for injection) is indicated for the treatment of infections in adult and pediatric patients: Severe infections of the ear, nose and throat, Acute exacerbations of chronic bronchitis, community acquired pneumonia, Cystitis, Pyelonephritis, Skin and soft tissue infections, Bone and joint infections, Intra-abdominal infections, Female genital infections.

It is used as prophylaxis against infections associated with major surgical procedures.

DOSAGE AND ADMINISTRATION

Dosing Considerations

The daily dose of Amoxicillin Sodium and Potassium Clavulanate for Injection is determined based on the indication, severity and site of the infection, susceptibility of the pathogen(s) to Amoxicillin Sodium and Potassium Clavulanate for Injection and renal function. In pediatric patients, it is also determined by age and body weight.

Doses are expressed throughout in terms of amoxicillin/clavulanic acid content, i.e. Amoxicillin 25mg/Clavulanic acid 5mg per kg per dose 8 hourly.

Amoxicillin Sodium and Potassium Clavulanate for injection (Co-Amoxiclav for injection) 500 mg/100 mg powder for solution consists of vials of sterile white to off-white powder providing amoxicillin sodium equivalent to 500 mg amoxicillin and potassium clavulanate equivalent to 100 mg clavulanic acid.

Amoxicillin Sodium and Potassium Clavulanate for Injection 1000 mg/200 mg: Amoxicillin Sodium and Potassium Clavulanate for injection (Co-Amoxiclav for injection) 1000 mg/200 mg powder for solution consists of vials of sterile white to off-white powder providing amoxicillin sodium equivalent to 1 g amoxicillin and potassium clavulanate equivalent to 200 mg clavulanic acid.

The maximum daily dose is dependent on the Clavulanic acid which should be a total of 600mg per day (24hrs).

For Adults and Pediatrics ≥ 40 kg and Pediatrics < 40 kg Aged ≥ 3 months, the dose is 25 mg/5 mg/kg every 8 hours.

For Infants Aged < 3 months or weighing < 4 kg or for very young children (including preterm newborns) in the first week of life the interval of administration should not exceed twice daily (i.e. 25mg/5mg/kg every 12 hours) administration due to immaturity of the renal pathway of elimination.

Reconstitution

Reconstituted Amoxicillin Sodium and Potassium Clavulanate for Injection solutions are stable when stored at room temperature with the diluent sterile water for injection (WFI). The reconstituted solution should be diluted within 15 minutes or administered immediately.

Reconstitution of powder and stability of reconstituted solutions: For the 600mg injectable (500 mg/100 mg) we use 10 mL water for injection administer intravenously within 15 minutes after reconstitution. For the 1.2g injectable (1000 mg/200 mg) we use 20 mL water for injection. °

Table 1: Reconstitution Of Powder And Stability Of Reconstituted Solutions

Preparation of Infusion

Chemical and physical in-use stability has been demonstrated for 60 minutes at 25°C, or 4 hours at 5°C.

From a microbiological point of view, the reconstituted and diluted solution (1 reconstituted vial in a minimum volume of 50 mL of infusion fluid) should be used immediately.

Table 2: Stability Of Infusion

Do Not Multi-Dose With The Same Reconstituted Solution

Amoxicillin Sodium and Potassium Clavulanate for Injection. Amoxicillin Sodium and Potassium Clavulanate for Injection vials are not suitable for multi-dose use. Product is for single use in one patient only. Discard any residue. After dissolution in water for injection, a transient pink colour may occur; the solution will become clear again rapidly afterwards. The solution is to be inspected visually for particulate matter prior to administration. The solution should only be used if the solution is clear and free from particles. Any unused medicinal product or waste material should be disposed of in accordance with local guidelines.

Table 3: Colour and pH Changes of Reconstituted Co-Amoxiclav Injectable Solutions Under

                Different Storage Conditions

Administration

Amoxicillin Sodium and Potassium Clavulanate for Injection is for administration by intravenous route after reconstitution. Amoxicillin Sodium and Potassium Clavulanate for Injection is not suitable for intramuscular administration.

5:1 ratio (500/100 mg and 1000/200 mg). Amoxicillin Sodium and Potassium Clavulanate for Injection may be administered either by slow intravenous injection over a period of three to four minutes directly into a vein or via a drip tube or by infusion over 30 to 40 minutes.

Commentary

The combination of amoxicillin and clavulanic acid (Co-Amoxiclav) is widely used as an antibiotic of choice for wide range of infections. Amoxicillin is penicillin, and clavulanic acid is a β-lactamase inhibitor. These drugs together with cephalosporins form the broad class of antibiotics known as the β-lactam antibiotics.

The main problem with the use of penicillins and the rest of β-lactam antibiotics in general is the instability of the β- lactam ring in aqueous solutions. Due to this instability, the injections of β-lactam antibiotics are formulated as powders to be reconstituted immediately prior to use. The British Pharmacopoeia (2015) stated that all penicillins injections should be used immediately after reconstitution.

The manufacturers of co-amoxiclav in particular stated the reconstituted solution should be used within 20 minutes of reconstitution. However, in pediatric patients, only a small part of the reconstituted solution is used in single dose based on patients’ relatively low body weight. The remaining reconstituted solution should be discarded due to instability. Some find this not cost effective and may want to store for re-use as second dose (after eight hours).

Studies have showed that Amoxicillin in co-amoxiclav degrades to less than 90 per cent within one hour when stored at both 4-8°C and at 30°C with clavulanic acid showing more degradation. After eight hours less than 70 per cent of the initial content of amoxicillin and less than 35 per cent of clavulanic acid will be administered to the patient when administering a second dose from a vial stored in the refrigerator after reconstitution.

The situation is worse when the reconstituted solution is stored at room temperature- less than 45 per cent of the initial content of amoxicillin and less than 15 per cent of clavulanic acid will be administered.

Therefore, it is necessary for co-amoxiclav injection to be used immediately (or within 60mins) after reconstitution and should not be stored for further use (Maiwada et al. Post Reconstitution Stability of Co-Amoxiclav Injection for Multiple Usages in Developing Countries. Journal of Global Pharma Technology | 2020| Vol. 12| Issue 02 (Suppl.) |252-258. Osman Nur et al. Stability of Co-Amoxiclav Reconstituted Injectable Solution. European Journal Pharmaceutical and Medical Research. May 2015).

DR. EDWARD O. AMPORFUL

CHIEF PHARMACIST

COCOA CLINIC