What is the meaning of "co-formulated"?

Question

I was reading the The right drug for the right patient section of the University of Sydney website, which provides these clinical guidelines (flow chart), and says (bold my own):

There are no studies directly comparing these treatment options and their relative effectiveness is unclear. Inhaled corticosteroids (budesonide or ciclesonide) can be considered for adjunctive use with other treatment options; however, the added benefit of adjunctive use is unclear. There is currently no evidence available on the effectiveness of concurrent use of monoclonal antibodies or antivirals for COVID-19, except where co-formulated.

I do not understand the meaning of co-formulated (nor coformulated), and cannot infer its meaning from the context.

What is the meaning of 'co-formulated'?

Answer 1

From Chauhan, V. M., Zhang, H., Dalby, P. A., & Aylott, J. W. (2020). Advancements in the co-formulation of biologic therapeutics. Journal of Controlled Release, 327, 397-405.:

Co-formulation can be considered as the purist view of a combination therapy and can be described as consisting of more than one drug substance in a single formulation, with the intention of delivering multiple therapeutic agents at the same time for maximum therapeutic benefit

Co-formulated in the context of a therapeutic drug/treatment means that two or more components are part of the same combined treatment, for example existing in the same pill or solution for injection. In this form, they are not separable.

It's not clear to me that this is specifically what the chart you linked means, though, rather they are saying that some treatment options have not been compared independent of the others, but were always given together within trials. That might be better described as "co-administered".

From the context of the flow chart, it is not immediately clear to me which specific combinations they are referring to.

Answer 2

There is currently no evidence available on the effectiveness of concurrent use of monoclonal antibodies or antivirals for Covid-19, except when co-formulated.

As they have used or, I think they are trying to say that no evidence is available for taking two different antivirals together(except the co-administered Nimratrelvir/Ritonavir) or two different monoclonal antibodies together except when they are co-formulated i.e. Evusheld.

A similar type of wording is used by them in the sourced page below, from where I think they have created the flowchart.

The concurrent use of two or more monoclonal antibodies should be avoided except where co-formulated.

Source: https://covid19evidence.net.au/#living-guidelines (See Evusheld section)

Answer 3

In this context, they're saying that the only combination therapies that have been been tested for efficacy are those that those contained in products that have been explicitly produced and released as a single product.

I believe in context they're making the point that while Paxlovid and Evusheld are combination therapy products, they have explicitly been tested for efficacy. One shouldn't see that Paxlovid is a dual-therapy antiviral and conclude that administering some other combination of antiviral medications would be more effective than a single antiviral alone.