Is it okay to take reconstituted Curam that has been left outside the fridge for 10 hours?

My friend asked me this question the other day.

First of all, a little bit of background on the drug. Curam or Augmentin (both brand names for the antibiotic combination amoxicillin/clavulanate) is commonly handed to the patient in two ways:

1)       In a bottle of powder. The patient brings home the bottle, adds water up to the mark indicated on the bottle to make a suspension – this is known as reconstitution.

2)       In a bottle of reconstituted suspension. The pharmacist or clinic assistant first reconstitutes the drug before giving it to the patient.

In both instances, the reconstituted drug should be refrigerated (stored at 2°C to 8°C) as soon as practicable to maintain the efficacy (usefulness) of the drug (manufacturer’s recommendation) for the entire dosing regimen (5 to 7 days). The powder on the other hand can be stored under room conditions for as long as the expiry date allows.

Thus, it is fairly common to receive calls from a family – who had left the reconstituted suspension out on the kitchen counter overnight – asking if the drug can still be used or do they need to go to the clinic to get a new prescription/bottle. There is also the possibility that you’d be bringing along a reconstituted suspension for your sick child (who had no choice but to travel with you) and may take some time before you have access to a refrigerator. So, how long can it stay outside the fridge?

Several studies have been performed to compare the stability of the reconstituted suspension when stored out at room temperature. The findings of these studies were:

1)       For the brand Augmentin, when stored at room temperature (25°C), Amoxycillin maintained its efficacy (defined as at least 90% of its initial concentration) throughout the 7 days dosing regimen, while clavulate drops to 90% of its value by day 2.

2)       Different brands have different stability profiles (see figures 1 and 2).

3)       In general, amoxicillin maintained its efficacy even if it has been stored out at room temperature and at 40°C for as long as 24 hours. Clavulanate is less stable and there could be a 30% drop in potency within the first 24 hours when stored at 40°C.

Figure 1. Concentration of Amoxicillin of various brands when stored at room temperature 25 °C

Figure 2. Concentration of Clavulanate of various brands when stored at room temperature 25 °C

Would I give my child Curam/Augmentin after it has been left outside the fridge for 24 hours? It is probably okay to give because:

1)       The efficacy of Amoxicillin is still maintained for all brands

2)       Clavulanate’s effectiveness may have dropped 30% but clavulanate’s inclusion is to counter infections that resistant to amoxicillin and I view this as secondary

3)       I’d consider getting a new bottle / prescription the next practicable time depending on the severity of the illness.

Oh and one last thing, do reconstitute the amoxicillin/clavulanate combination drug with boiled-and-cooled tap water or distilled water to improve its stability. The drug is most stable when dissolved with soft water (no mineral water) at neutral pH (no alkaline water).

REFERENCES

1. J Clin Pharm Ther. 1994;19(5):313-5.
2. Journal of Chemical and Pharmaceutical Research, 2013, 5(5):293-296
3. International Journal of Pharmaceutical Science and Practice, 2014,03(01): 1-12
4. Journal of Applied Pharmaceutical Science , 2012, 02(01): 28-31
5. Acta Vet Hung. 2009;57(4):485-93