CYTOVENE
General description

Cytovene is the name for the drug ganciclovir, or ganciclovir sodium, put out by Roche Laboratories. Ganciclovir is a synthetic guanine derivative and an active antiviral agent for cytomegalovirus (CMV) infections. It is available in two forms: Cytovene-IV is found as a sterile lyophilized powder for use with intravenous administration. Each vial contains 500 mg of ganciclovir, which can be reconstituted with 10 mL of sterile water for injection (see usage). Cytovene is the capsular form available in 250 mg and 500 mg dosages.

Mechanism

Ganciclovir acts to inhibit CMV replication. It is phosphorylated to ganciclovir triphosphate in the body by cellular kinases whereupon the drug enters the infected cells where it persists for days. Ganciclovir triphosphate then inhibits DNA synthesis by competitively inhibiting DNA polymerases and incorporating itself into the viral DNA, terminating viral DNA elongation.

Indications

Cytovene-IV is indicated for treating immunocompromised patients infected with CMV. This includes patients already infected with HIV. It is also indicated as a preventive agent for transplant recipients at risk for CMV infection.

Cytovene capsules are indicated for prevention of CMV infection in organ transplant recipients and for patients with advanced HIV infection at risk for CMV infection. Capsules are also indicated as alternative treatment to Cytovene-IV intravenous administration for maintaining treatment for CMV retinitis and for cases where the benefit of avoiding intravenous administration outweighs the risk of more rapid progression of disease course.

Usage/Dosage

preparation
Reconstitute Cytovene-IV by adding 10 mL of sterile water to the ganciclovir vial. Shake the vial to dissolve the drug and inspect the solution for particles or discoloration (vial should be discarded if particulate matter or discoloration is observed). Reconstituted solution should be stable at room temperature for 12 hours. For IV infusion, concentrations greater than 10 mg/mL are not recommended.

CMV retinitis
induction treatment: recommended initial dosage for normal renal function patients is 5mg/kg intravenously at a constant rate over 1 your every 12 hours for 14 to 21 days.
maintenance treatment: following induction treatment, Cytovene-IV can be given intravenously at 5 mg/kg in a constant rate IV infusion over 1 hour daily, 7 days per week or 6 mg/kg once daily, 5 days a week. Or Cytovene capsules can be used at 1000 mg tid with food. Alternatively, a dosage of 500 mg 6 times daily every 3 hours with food during waking hours can be used. if CMV retinitis progresses, reinduction treatment is recommended.

Preventing CMV disease in patients with advanced HIV disease and normal renal function
recommended prophylactic treatment is Cytovene capsules at 1000 mg tid with food.

Preventing CMV in Transplant recipients with normal renal function
Cytovene-IV can be used initially at at 5 mg/kg every 12 hours for 7 to 14 days followed by 5 mg/kg once daily7 days per week or 6 mg/kg once daily, 5 days per week. Cytovene capsules can be used at 1000 mg tid with food. Duration of treatment for either form is dependent on the degree and duration of immunosuppression

With Renal impairment
Dosing for patients receiving hemodialysis treatment should not exceed 1.25 mg/kg 3 times per week. Treatment should be administered shortly following hemodialysis. Dosage should be adjusted as according to the following tables:

Creatine Clearance* (mL/min>	Cytovene-IV induction Dose	Dosing Interval (hrs)	Cytovene-IV maintenance Dose (mg/kg)	Dosing Interval (hrs)
>70	5.0	12	5.0	24
50-69	2.5	12	2.5	24
25-49	2.5	24	1.25	24
10-24	1.25	24	0.625	24
<10	1.25	3 times per week, following hemodialysis	0.625	3 times per week, following hemodialysis

Creatine Clearance* (mL/min)	Cytovene Capsule Dosages
>70	1000 mg tid or 500 mg q3h, 6x/day
50-69	1500 mg qd or 500 mg tid
25-49	1000 mg qd or 500 mg bid
10-24	500 mg qd
<10	500 mg 3 times per week, following hemodialysis

*Creatine Clearance can be calculated in the following manner:

For males = ((140-age[yrs])(body wt.[kg]))/((72)(serum creatine[mg/mL]))
For females = 0.85 x male value

Precautions

Overdose can lead to toxicity. The major elimination pathway for ganciclovir is renal, so adequate hydration should be performed following IV administration. Cytovene-IV should not be administered by rapid or bolus intravenous injection or by intramuscular or subcutaneous injection. Cytovene has potential negative interactions with didanosine, zidovudine, probenecid, imipenem-cilastatin, and potentially drugs that inhibit replication of rapidly dividing cell populations. Ganciclovir is a potential long term carcinogen, teratogen, and source of reproductive impairment.

Contraindications

Cytovene should be used with caution in patients with a history of cytopenic drug reactions. Although it has not been tested in humans yet, it has been found that Cytovene caused reversible infertility in animals at lower doses and irreversible infertility in animals at higher doses. Since it is a teratogen, men and women should practice effective contraception during and 90 days following treatment with Cytovene or Cytovene-IV.

Potential Adverse Effects

Abdominal pain, nausea, flatulence, pneumonia, paresthesia, and rash are the most frequently observed effects in clinical trials, but occur with equal or greater frequency than placebo controlled subjects.