Ganciclovir (Cymevene)

Ganciclovir (Cymevene) is an anti-cytomegalovirus drug that works by inhibiting DNA polymerase. It can prevent cytomegalovirus from reproducing and infecting new cells, but it cannot eliminate it from the body. Ganciclovir may also be active against a range of other viruses. However, it is not effective at preventing cytomegalovirus in HIV-positive patients.¹

Ganciclovir is manufactured by Roche. In the United States its trade name is Cytovene.

Ganciclovir is available in several formulations: oral, intravenous and intravitreal (into the eye).

Intravenous ganciclovir is an approved drug for treating cytomegalovirus retinitis and preventing or delaying recurrences. Intravenous ganciclovir may be used in combination with foscarnet (Foscavir). Before the development of oral forms of ganciclovir, the drug was administered intravenously through an implanted central venous catheter to achieve the high levels needed. Each infusion normally takes one hour. Treatment for cytomegalovirus retinitis is usually continued at a dose of 10 to 15mg/kg per day for three weeks. The usual dose for maintenance therapy is 5mg/kg per day. As maintenance therapy, this was highly inconvenient and provided the motivation for the subsequent development of oral forms of ganciclovir.

The oral capsule formulation of ganciclovir is approved for the maintenance therapy of cytomegalovirus retinitis. Oral ganciclovir is less effective than intravenous ganciclovir at preventing relapses, but it does remove the need to have a catheter implanted, and thus reduces the risk of catheter-borne infections. Oral ganciclovir maintenance therapy is taken at a dose of 1000mg three times daily with food. Alternatively, a dose of 500mg can be taken six times daily. Oral ganciclovir capsules should be handled with care. They must not be opened or crushed, and any powder from inside the capsules should be washed off the skin immediately.

Ganciclovir delivered directly into the eye is also effective against cytomegalovirus. It is administered either by injection or by implanting devices in the eye that slowly release ganciclovir. Ganciclovir implants were marketed under the trade name Vitrasert. However, the marketing authorisation in Europe was voluntarily withdrawn in 2002 due to a lack of demand. Furthermore, the implant only provides local protection against cytomegalovirus, so oral ganciclovir must be taken by people with implants to prevent disease in other locations in the body.²

The development of strains of cytomegalovirus that are resistant to ganciclovir has been reported. These do not seem to develop any faster with oral ganciclovir than with the intravenous formulation.

Antiretroviral therapy has transformed the treatment of certain opportunistic infections such as cytomegalovirus. Oral ganciclovir treatment may only be necessary in people experiencing viral rebound and immunological deterioration following a period of successful response to antiretroviral therapy.

Ganciclovir suppresses the activity of the bone marrow. Its main side effects are therefore blood disorders such as neutropenia (low levels of neutrophils, a type of white blood cell), anaemia and thrombocytopenia (low levels of platelets). People taking ganciclovir require close monitoring to ensure blood disorders are promptly detected. Other side-effects include rash, low blood pressure, nausea, diarrhoea, vomiting, headache, dizziness and confusion. More than 10% of intravenous ganciclovir recipients have to stop treatment because of side-effects. Side-effects are significantly less common with the oral version of ganciclovir.

Since AZT (zidovudine, Retrovir) also affects the bone marrow it is usually recommended that people should not take AZT at the same time as ganciclovir.³ The alternative is to try to reduce the risk of anaemia by using blood cell stimulating treatments such as granulocyte colony stimulating factor (G-CSF). Test-tube studies have suggested that when ganciclovir and AZT are taken together their anti-viral effects are reduced.⁴ When ddI (didanosine, Videx / VidexEC) is taken within two hours before or simultaneously with oral ganciclovir, the concentration of ddI in the blood is increased.⁵ This can lead to an increased risk of serious ddI toxicities such as pancreatitis. Ganciclovir does not interact with any currently-available protease inhibitors or non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Ganciclovir has been reported to reduce levels of serum testosterone. This may exacerbate AIDS-related wasting. Ganciclovir can also damage the reproductive system. When used by men, it may decrease the number of sperms in the semen. This may be complete and irreversible. In women, ganciclovir may suppress fertility and treatment during pregnancy is likely to lead to the birth of a deformed child. Breastfeeding should also be avoided by women taking ganciclovir.