Background Information Or Related Documents:
The HPRA wishes to address two potential causes of confusion for prescribers, pharmacists, nurses and other healthcare professionals regarding the strength of products containing active substances in their salt form and the importance of reading the statement of active substance(s) on the labelling (pack), section 2 of the Summary of Product Characteristics (SmPC) or section 6 of the package leaflet and considering the clinical relevance of any difference in strength.
Example 1: Free Drug vs Salt Form
Two different products, Alpha (A) and Beta (B), contain the same active substance, ‘drug’, in its salt form, ‘drug bromide’. However, the active substances are presented differently on the labelling as shown below:
10 mg in A refers to the amount of ‘drug’, whereas 10 mg in B refers to the amount of ‘drug bromide’, so the strength of both products are not equivalent. For this example, if only 80% of the mass of ‘drug bromide’ is ‘drug’, then the strength of B is 20% less than that of A as illustrated below:
Example: the ratio of this active component to its salt component is 4:1
Example 2: Multiple Salt Forms
In this case, the strength of Beta (B) is being compared against Gamma (C) - a product with the same drug which is present as a different salt form, ‘drug hydrochloride’. The name on the labelling is presented as below:
B and C are not equivalent, as 10 mg in B refers to the amount of ‘drug bromide’, whereas 10 mg in C refers to the amount of ‘drug hydrochloride’. These salts have a different molecular mass, and hence the proportion of the active component in both of them is different. In this example, the difference in mass is shown below:
Example: The ratio of this active component to its salt components is 4:1 and 9:1 in B and C respectively.
Healthcare professionals are reminded to refer to the statement of active substance(s) on the labelling (pack), section 2 of the SmPC or section 6 of the package leaflet for the equivalent quantity of free drug when interpreting the quantity of an active substance expressed in the salt form and to consider the clinical relevance of any difference in strength. This is particularly important when switching between products or interpreting dosage guidance for products commonly present in their salt form.
The SmPCs for all nationally authorised medicines can be accessed through the HPRA website. The SmPCs for medicines authorised through the centralised procedure can be accessed through the EMA website.