Cytomegalovirus (CMV) Medication

Updated: Jul 07, 2021
  • Author: Ricardo Cedeno-Mendoza, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Medication

Medication Summary

The goals of pharmacotherapy are to prevent outbreaks of the disease and its complications and to reduce morbidity. Several agents are currently available for the treatment of cytomegalovirus (CMV) infection and disease.

In addition, multiple agents are being looked at for the treatment of CMV disease. These include (1) CMX001 (hexadecyloxypropyl-cidofovir, an ester of cidofovir), which is under development for ganciclovir-resistant CMV disease [84] ; (2) leflunomide, a pyrimidine synthesis inhibitor [85] (Leflunomide has been successfully used in solid organ transplant recipients for both CMV treatment and prophylaxis. Unfortunately, leflunomide failure has been reported in hematopoietic stem cell transplant recipients. [79] ); and (3) artesunate, an antimalarial with some in vitro activity against CMV. [86, 87]

Letermovir, a member of the novel class of 3,4-dihydroquinazolinyl acetic acids, is indicated for CMV prophylaxis in adult CMV-seropositive recipients of an allogeneic HSCT. [61]

Letermovir has also been studied for lung transplantation and was administered to a transplant recipient with multidrug-resistant disseminated CMV infection (viremia, pneumonitis, colitis, retinitis) in combination with reduced immunosuppression. [88] The patient experienced rapid clinical, virologic, and radiographic resolution of disease.

Maribavir, a benzimidazole antiviral agent, has been used as salvage therapy in a small number of patients with multidrug-resistant CMV, [73] but was unsuccessful when used as CMV prophylaxis in allogeneic stem cell transplant patients [74] or in liver transplant recipients.

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Antivirals

Class Summary

There are multiple antivirals with different mechanisms of action, these include DNA polymerase inhibitors like Ganciclovir (nucleoside analog), Cidofovir (nucleotide analog) as well as Pyrophosphate analogues such as Forcarnet. Ganciclovir is considered the treatment of choice for CMV infections

Ganciclovir (Cytovene)

Ganciclovir is a synthetic guanine derivative nucleoside analog active against CMV. It inhibits replication of herpes viruses both in vitro and in vivo. In patients with HIV infection, resistance manifests as progressive disease.

Foscarnet (Foscavir)

Foscarnet inhibits viral replication of herpesviruses (CMV, HSV-1, HSV-2) at pyrophosphate-binding site on virus-specific DNA polymerases. It is used for ganciclovir-resistant CMV retinitis and herpes simplex disease.

Cidofovir (Vistide)

Cidofovir is approved for the treatment of CMV retinitis in AIDS. It is a nucleotide analog, whose active metabolite inhibits herpes virus polymerases at concentrations that are 8- to 600-fold lower than those needed to inhibit human cellular DNA polymerases alpha, beta, and gamma. Incorporation of cidofovir into the growing viral DNA chain results in reductions in the rate of viral DNA synthesis.

Valganciclovir (Valcyte)

Valganciclovir is an L-valyl ester prodrug of ganciclovir. It is used for CMV disease prophylaxis in various solid organ transplant recipients. It inhibits the replication of human CMV in vitro and in vivo. Valganciclovir achieves serum levels comparable to those obtained with IV ganciclovir.

Letermovir (Prevymis)

Letermovir is part of a new class of non-nucleoside CMV inhibitors, the 3,4 dihydro-quinazoline-4-yl-acetic acid derivatives, and has activity in the late stages of viral replication rather than against the viral DNA polymerase like other anti-CMV therapies. It is used as prophylaxis of CMV infections. Advantages of Letermovir use include oral route and fewer side effects (no myelosupression, no nephrotoxicity).

Specifically, Letermovir inhibits the viral terminase complex at pUL56 and pUL89, which leads to compromised viral replication by preventing genomes of proper unit length and the accumulation of immature viral DNA. The approved dose of letermovir is 480 mg once daily and it is recommended as prophylaxis in CMV seropositive adult recipients of an allo-HCT between day 0 and 28 and continue until day 100 post-transplant. There are ongoing studies on Letermovir in regards to effectivity and side effects

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Immune Globulin

Class Summary

Consists of administration of immunoglobulin pooled from serum of immunized subjects.

Cytomegalovirus immune globulin (CMV IG)

CMV immune globulin (CMV-IG) is a preparation of immunoglobulin derived from pooled healthy blood donors with high CMV titers; administration provides a passive source of antibodies against cytomegalovirus. It is used for CMV pneumonia treatment. It may also be used for CMV prophylaxis in heart, lung, kidney, liver and pancreas transplant recipients, in addition to ganciclovir.

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Antimetabolite

Class Summary

These agents inhibit cell growth and proliferation.

Leflunomide (Arava)

Leflunomide has been used off-label in the treatment of cytomegalovirus (CMV) disease in transplant recipients, as well as in the prevention of acute and chronic rejection in recipients of solid organ transplants. It inhibits pyrimidine synthesis (via dihydroorotate dehydrogenase inhibition), leading to immunomodulatory and antiproliferative activity.

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