Anti-Cytomegalovirus Agents

Agents: ganciclovir, valganciclovir, foscarnet,  cidofovir

The common virus known as cytomegalovirus (CMV)  causes infections that are usually asymptomatic in immunocompetent patients but can be devastating in immunocompromised patients. Approximately 60% of Americans become seropositive for CMV by adulthood, and infection is lifelong. If a patient be-comes immunocompromised, the infection can reactivate and the patient will need pharmacotherapy.  Anti-cytomegalovirus agents work by preventing viral replication. They also all have appreciable toxicity that must be respected and monitored.

Spectrum

Good: CMV, HSV-1, HSV-2, VZV, EBV

Poor: HIV

Adverse Effects

Ganciclovir and valganciclovir are the same active drug and have the same adverse reactions. They both have dose-dependent myelosuppression that is relatively common, particularly when used in higher doses or in renally impaired patients with-out dose adjustment. Foscarnet is nephrotoxic and neurotoxic, and it is reserved for patients who have failed other therapy. Nausea, vomiting, and diar-rhea can occur from any of these agents. Foscarnet can also cause penile ulcers. Cidofovir is an uncommonly used agent that also exhibits nephrotoxicity.

Important Facts

• Oral ganciclovir has been replaced by valganciclovir, which has much better bioavailability.

• Ganciclovir must be carefully dosed by patient weight and renal function. Monitor patients closely for changes in renal function when they are on therapy.

• The package insert for valganciclovir specifies dose adjustment for renal dysfunction but not weight. It comes in two strengths: 900 mg and 450 mg. The dose of 900 mg BID is considered to be equivalent to 5 mg/kg q12h of IV ganciclovir, but it may be much more than that for an underweight patient because it is approximately 60% bioavailable. Consider this example for a 50-kg patient:

• Ganciclovir dose  = 50 kg  * 5 mg/kg  = 250 mg ganciclovir

• Valganciclovir dose = 900 mg * 0.60 bioavailability = 540 mg of active ganciclovir This patient would receive more than double the amount of active ganciclovir if 900 mg BID of valganciclovir are used. It may be worth considering dose reduction in underweight patients, particularly if they are at high risk of toxicity.

• Foscarnet has significant nephrotoxicity. This can be somewhat attenuated through hydration with normal saline. Cidofovir is also nephrotoxic.

• Even if a patient’s isolate of CMV is resistant to both ganciclovir and foscarnet, it may still be susceptible to the combination.

What They’re Good For

Ganciclovir and valganciclovir are first-line drugs for the treatment and prevention of CMV infections. Valganciclovir is often given to prevent CMV infection after transplant. Foscarnet is a second-line agent for CMV that can also be used for severe or resistant HSV infections. Cidofovir is a second-line agent for CMV.

Don’t Forget!

Although valganciclovir is oral, it is highly bio-available and has adverse effects similar to those of ganciclovir. Valganciclovir use requires monitoring for toxicity that is just as rigorous as that for ganciclovir.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.