Fomivirsen

Fomivirsen is an injectable prescription drug that is used to treat a viral infection of the eye called cytomegalovirus (CMV) retinitis. This retinitis almost exclusively manifests itself in persons with HIV/AIDS Due to their weakened immune systems. Fomivirsen is not a cure for this eye infection, but it does keep the symptoms from becoming worse.

Fomivirsen is the first "antisense" drug to hit the market and is marketed by Isis Pharmaceuticals under the name Vitravene. The Food and Drug Administration approved its use on August 26, 1998.

Uses

Fomivirsen is used for the treatment of CMV retinitis. It is prescribed for patients who are unable to use, or unresponsive to, other treatments for CMV retinitis.

How Fomivirsen is Taken

Fomivirsen is given by injection into the affected eye following application of a local anesthetic. It is available at a concentration of 6.6 mg/ml, but typically only 0.05 ml (330 µg (micrograms)) is injected.

Treatment with fomivirsen involves two phases: an initial induction phase and a follow-up maintenance phase. The induction phase is one injection every other week for a total of two doses. Subsequent maintenance doses are given once every four weeks thereafter.

How Fomivirsen Works

Fomivirsen is an antisense drug made up of a string of 21 nucleotides (molecules called bases that make up DNA and RNA). Antisense drugs prevent mRNA (messenger RNA) from making proteins. Fomivirsen binds to a specific region of the mRNA of CMV. Binding to this region of mRNA inhibits the synthesis of the protein IE2, which is essential for production of infectious CMV.

Antisense drugs are fundamentally different than many other drugs because they target RNA rather than products of RNA translation, such as enzymes and receptors. See diagram below for an illustration of how antisense drugs work.

Antisense DNA oligonucleotide; Source: Wikimedia Commons

How the Body Affects Fomivirsen

Source:National Cancer Institute

The fluid in the eye is called vitreous humor (see diagram of the eye). Fomivirsen is injected into the vitreous humor and is found in the retina several hours after injection. It accumulates in the eye over three to five days. Fomivirsen is cleared out of the eye seven to ten days after the injection. Very little fomivirsen leaks out of the eye and into the body’s circulation.

Fomivirsen is primarily eliminated from the eye by metabolism, which is a process that alters the structure of a drug. Fomivirsen is metabolized by enzymes that cleave it into smaller strands of nucleotides.

Side Effects

The most common side effect of fomivirsen is eye inflammation (uveitis). Uveitis has been reported to occur in approximately 25% of patients.

Below are some side effects reported in approximately 5% to 20% of patients:

• Eye-related: blurred vision, cataract, decreased visual acuity (sharpness), effects to color vision, eye pain, "floaters", increased intraocular pressure, hypersensitivity to light (photophobia), and various retinal problems

• abdominal pain
• feelings of weakness
• diarrhea
• fever
• headache
• infection (e.g., pneumonia and systemic CMV
• nausea
• rash
• sinusitis
• vomiting

Risks and Precautions

The influence of fomivirsen on the fetus is not known. Fomivirsen is only used during pregnancy if the benefits outweigh the risks. Many drugs enter breast milk, but whether fomivirsen does this is not known. Again, the risks to a nursing infant need to be considered.

Drug Interactions

Fomivirsen is not recommended for use in patients who have been recently treated with either intravenous (IV) or intravitreal (into the eye) cidofovir (Vistide) because of the increased risk of eye inflammation.

Alternatives

Three other drugs can be used to treat CMV retinitis:

• Ganciclovir (Cytovene)or the combination of ganciclovir and valganciclovir (Valcyte)
• Foscarnet (Foscavir) or the combination of foscarnet and ganciclovir
• Cidofovir

Clinical Trials

One study assessed the effectiveness of fomivirsen in newly diagnosed CMV retinitis in patients with AIDS who had never received treatment for CMV retinitis before. Fomivirsen was shown to be effective: time to first progression of disease after immediate treatment was 71 days in more than half the patients. Disease progression occurred in only 44% of patients after immediate treatment.^[1]

Another study compared the effectiveness of fomivirsen for the treatment of CMV retinitis that had reactivated or was persistently active despite other therapies in patients with AIDS. Vitravene was shown to be effective: CMV activity decreased in 80% of patients and became inactive in 55% of patients during therapy.^[2]

References

1. ↑ Vitravene Study Group. A randomized controlled clinical trial of intravitreous fomivirsen for treatment of newly diagnosed peripheral cytomegalovirus retinitis in patients with AIDS. Am J Ophthalmol. 2002 Apr;133(4):467-74. PMID 11931780
2. ↑ Vitravene Study Group. Randomized dose-comparison studies of intravitreous fomivirsen for treatment of cytomegalovirus retinitis that has reactivated or is persistently active despite other therapies in patients with AIDS. Am J Ophthalmol. 2002 Apr;133(4):475-83. PMID 11931781

External Links

Isis Pharmaceuticals: Vitravene

FDA: Vitravene Consumer Information

Rx List: Vitravene (Fomivirsen)

Stanford University: Fomivirsen

Drugs.com: Vitravene (Parenteral-Local)