Hi. I was wondering about the differences in the therapeutic use of ganciclovir vs. valganciclovir. The latter is a pro-drug which is rapidly and nearly completely converted to ganciclovir. Since toxicity is similar, why would we ever use ganciclovir with this oral option available?
As you know, ganciclovir was the first anti-CMV drug approved, and hence there is more experience and more clinical studies available with this drug. You are right in the fact that they are very similar; most of the differences in how these two are used is simply due to lack of data that supports the use of valganciclovir as opposed to any negative comparative data. Here is a summary of the different indications.
For CMV retinitis, it takes slightly longer for valganciclovir to achieve therapeutic levels in the vitrious humor. It is therefore recommended that initial treatment be started with IV ganciclovir in cases of sight-threatening or severe retinitis, or otherwise intravitreal co-administration is recommended.
CMV disease is most common in the GI tract. For these patients (usually end-stage AIDS), we start with IV ganciclovir because we don’t trust the absorption of valganciclovir in GI disease. However, we can transition to valganciclovir quickly, so here the only barrier to oral is the patient being able to take drugs PO. If the disease is mild to start off, or if we trust the oral absorption, we can simply start with valganciclovir.
For pulmonary CMV in HIV patients only ganciclovir has been studied. I think that valganciclovir could reasonably be used, but there is no data to support that. In my opinion, the studies fall short for ganciclovir, but it’s currently still the preferred agent.
For prevention, usually in transplant patients, the story is different. Valganciclovir is very well studied and it is actually the preferred agent. For prevention for renal transplant patients, it is guideline recommended first line therapy due to convenience and cost, and the robust data that shows efficacy. I don’t see ganciclovir used for prophylaxis at all, aside from perhaps a very short duration immediately post-transplant when the patient is not eating properly.
For lung transplant, the guidelines still recommend ganciclovir initially, with PO switch shortly after the patient is stable (few days). However, some start valganciclovir right away in those patients too.
Finally, for HCT patients, we usually use pre-emptive treatment as opposed to prophylactic because of the myelosupression of these two antivirals. These patients usually have significant GVHD, and oral absorption may not be great during that state. Therefore, for the most part, these patients get ganciclovir. The data for valganciclovir is less robust. However, I have seen valganciclovir too, but there are no clear-cut guidelines on its use.
I hope this is helpful. Sorry if this is a grey area.
Answered by Jolanta Piszczek.