CMV Retinitis Medication

Updated: Oct 20, 2016
  • Author: Michael Altaweel, MD, FRCSC; Chief Editor: Hampton Roy, Sr, MD  more...
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Medication

Medication Summary

A number of different antiviral medications are available for the treatment of CMV retinitis. [90, 91, 92, 93, 94] Routes of delivery and adverse effect profiles vary significantly, [95] so treatment programs are tailored to individual patients and their response to treatment. Current therapies use an induction dose to halt active disease followed by a lower maintenance dose that must be continued indefinitely unless immune recovery occurs. [96, 97] In recent years, several developments have drastically improved the quality of life for patients with CMV retinitis. [98]

HAART therapy has allowed immune recovery that may allow discontinuation of anti-CMV medication. [99, 100] This often obviates the need for multiple implant procedures or the long-term dose related adverse effects of anti-CMV medications.

Valganciclovir, a prodrug of ganciclovir that possesses excellent oral bioavailability and antiviral activity, has been shown to be effective in both the induction phase [101] and the maintenance phase of CMV retinitis treatment. [102] It is available in convenient once daily or twice daily dosing. Valganciclovir has largely replaced other treatments [103, 104, 105, 106] since it avoids the need for frequent intravenous infusions and long-term intravenous access ports. [107, 108, 109, 110]

Neupogen (granulocyte colony stimulating factor) can be used in conjunction with ganciclovir or valganciclovir in patients experiencing neutropenia. This has helped to lessen one of the most common treatment terminating adverse effects of a very convenient and useful medication.

Foscarnet [111] and cidofovir [112, 113, 114, 115, 116] are effective alternatives in the treatment of CMV retinitis. [117, 118, 119, 116] However, because of their adverse effect profiles [120, 121, 122, 123] and the lack of an orally bioavailable form, they have become second-line treatments. Combination treatment has been used for resistant disease. [124, 125, 126, 127] Intravitreal implants or intravitreal injections are used less frequently but are still needed in patients who have reactivation of retinitis despite systemic treatment or in those who cannot tolerate systemic treatment.

At this time, primary treatment generally consists of induction with either valganciclovir (900 mg PO bid for 2-3 wk) or ganciclovir (5 mg/kg IV bid for 2-3 wk) followed by maintenance with valganciclovir (900 mg PO qd) until the CD4 count is above 100 cells/μL.

Finally, immune recovery uveitis has added a new postscript to the treatment of CMV retinitis. [22] Treatment is based on managing the uveitis, primarily with topical, subtenons, or intravitreal steroids, and close follow-up is needed to guard against vision-threatening complications.

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Antivirals

Class Summary

Direct action is to inhibit the DNA polymerase of CMV, preventing viral replication.

Ganciclovir (Cytovene, Vitrasert)

Analog of guanosine, 10-100 times more potent than acyclovir versus CMV in vitro. Selectively inhibits DNA polymerase of CMV cells. Renal excretion.

Virostatic - Discontinuation of use leads to 100% relapse rate within 4 weeks.

Effective - 88% complete response, 9% partial.

Long-term IV access is necessary. Oral administration is possible, but the bioavailability of oral ganciclovir is limited to less than 10%. Although use of this medication for prophylaxis reduces the incidence of CMV end-organ disease by up to 50%, its use usually is not recommended because most patients would be using it unnecessarily and the incidence of side effects is high. A valine ester prodrug of ganciclovir, valganciclovir, has good bioavailability and can be used in place of intravenous ganciclovir for maintenance dosing and for the prevention of recurrences.

Oral ganciclovir - Two trials for maintenance treatment. A faster rate of progression was found in the first trial. With higher dosing (1 g tid), there was an equal rate of progression. A dose dependent increase in neutropenia exists.

Foscarnet (Foscavir)

Analog of pyrophosphate. Inhibits DNA polymerase of CMV and reverse transcriptase of HIV. Virostatic; renal excretion. As effective as ganciclovir. Median time to relapse on Rx is 53 d. Foscarnet/ganciclovir CMV retinitis trial: 234 newly diagnosed patients randomized. Same efficacy for controlling retinitis and preserving vision. Survival with foscarnet 12.6 mo versus 8.5 for ganciclovir group; mortality risk 1.79x. Controlling for antiretroviral use, still better survival with foscarnet. Foscarnet has anti-HIV activity but has more dose-limiting toxicity.

Cidofovir (Vistide)

Nucleotide analog that selectively inhibits viral DNA production in CMV and other herpes viruses.

Valganciclovir (Valcyte)

L-valyl ester prodrug of ganciclovir used to treat CMV retinitis in patients with AIDS. Ganciclovir is synthetic analogue of 2'-deoxyguanosine, which inhibits replication of human CMV in vitro and in vivo. Inhibits viral activity by inhibiting viral DNA synthesis. Has the advantage of qd or bid PO administration. Achieves levels comparable to those obtained with IV ganciclovir.

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Antisense medications

Class Summary

Inhibit viral replication by interfering with the regulation of viral gene expression.

Fomivirsen sodium (Vitravene)

A phosphorothioate oligonucleotide. The nucleotide sequence is complimentary to the CMV viral mRNA, which encodes proteins responsible for regulation of viral gene expression. Inhibition of viral protein synthesis is achieved when fomivirsen binds the target mRNA. Second-line management.

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Colony stimulating factors

Class Summary

Stimulation of stem cells to produce differentiation, proliferation, and increased functional activity of neutrophils, monocytes, eosinophils, and macrophages.

Filgrastim (Neupogen)

Up to 40% of ganciclovir users experience dose-limiting neutropenia, which may require discontinuation. GCSF has limited this effect markedly in some studies.

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