CYTOGAM Solution for infusion Ref.[10798] Active ingredients: Cytomegalovirus immunoglobulin

Clinical studies have shown a 50% reduction in primary CMV disease in renal transplant patients given CMV-IGIV ³ and a 56% reduction in serious CMV disease⁴ in liver transplant patients given CMV-IGIV. CMV-IGIV prophylaxis was associated with increased survival in liver transplant recipients.⁵

In two separate clinical trials, CYTOGAM was shown to provide effective prophylaxis in renal transplant recipients at risk for primary CMV disease. In the first randomized trial,³ the incidence of virologically confirmed CMV-associated syndromes was reduced from 60% in controls (n=35) to 21% in recipients of CMV immune globulin (n=24) (P<0.01); marked leukopenia was reduced from 37% in controls to 4% in globulin recipients (P<0.01); and fungal or parasitic superinfections were not seen in globulin recipients but occurred in 20% of controls (P=0.05). Serious CMV disease was reduced from 46% to 13%. There was a concomitant but not statistically significant reduction in the incidence of CMV pneumonia (17% of controls as compared with 4% of globulin recipients). There was no effect on rates of viral isolation or seroconversion although the rate of viremia was less in CYTOGAM recipients. In a subsequent non-randomized trial in renal transplant recipients (n=36),⁶ the incidence of virologically confirmed CMV-associated syndrome was reduced to 36% in the globulin recipients in comparison to a 60% incidence in control patients (n=35) in the randomized trial. The rates of serious CMV disease, and concomitant fungal and parasitic superinfection were similar to patients receiving CMV-IGIV in the first trial.

In a randomized, double-blind, placebo-controlled trial in liver transplant recipients,⁴ the incidence of serious CMV-associated disease was reduced from 26% in the 72 control patients to 12% in the 69 CMV-IGIV recipients (p=0.02); serious CMV-associated disease included CMV disease in 2 or more organs, CMV pneumonia, or CMV-associated invasive fungal infection, the incidence of which was 18% in controls and 7% in CMV-IGIV recipients (p=0.04). In follow-up⁵ of the liver transplant patients studied in this randomized controlled trial and a subsequent open-label trial,⁷ the one year survival of the 72 control patients was 72% versus 86% in the 90 recipients of CMV-IGIV (p=0.03). In the randomized control trial, the reduction in serious CMV-associated disease in CMV seronegative recipients of livers from a CMV seropositive donor (7/19 in the CMV-IGIV group vs. 9/19 in control) was less than in transplants with other donor and recipient serologic status (1/50 in the CMV-IGIV group vs. 10/53 in the control group). This finding was similar to that of Merigan et al.⁸ in a study of ganciclovir prophylaxis after heart transplantation. In this study, patients received ganciclovir IV at 5 mg/kg twice a day for the initial 14 days post-transplant, then at 6 mg/kg each day for 5 days per week through day 28.

Recent studies of combined prophylaxis with CMV-IGIV and ganciclovir have shown reductions in the incidence of serious CMV associated disease in CMV seronegative recipients of CMV seropositive organs below that expected from one drug alone.^9-12

Ham et al.⁹ used CMV-IGIV with a dosage schedule of 150 mg/kg CMV-IGIV within 72 hours of transplant; 100 mg/kg at two, four, six and eight weeks following liver transplant and then 50 mg/kg at 12 and 16 weeks post-transplant in combination with ganciclovir (10 mg/kg/day for 14 days). The incidence of CMV disease was reduced from an expected 60-80% rate to 7% in 15 seronegative recipients of a seropositive organ.

Snydman¹⁰ using the CMV-IGIV dosage schedule listed under DOSAGE AND ADMINISTRATION section in combination with ganciclovir (10 mg/kg/day for 14 days) reduced the incidence of serious CMV disease in D+R- liver transplant recipients receiving placebo or one drug from 16/47 (34%) to 3/41 (7%) in patients receiving both drugs for prophylaxis.

Martin¹¹ using CMV-IGIV 100 mg/kg every two weeks for six weeks followed by 50 mg/kg every two weeks with a final dose at week 16, in combination with ganciclovir 10 mg/kg/day for 14 days after transplantation, observed severe CMV disease in 1/74 (1%) of CMV seronegative recipients of a kidney from a CMV seropositive donor, in 0/14 (0%) of CMV seronegative recipients of a kidney-pancreas transplant from a CMV seropositive donor and in 1/12 (8%) of CMV seronegative recipients of a liver from a CMV seropositive donor. The incidence of serious CMV disease with combined CMV-IGIV and ganciclovir prophylaxis was lower than previous experience with single drug prophylaxis.

Valantine and Luikart¹² compared prophylaxis with CMV-IGIV (biweekly for three months) in combination with ganciclovir prophylaxis (IV at 5 mg/kg twice a day for the initial 14 days post-transplant, then at 6 mg/kg through day 28) in 16 CMV seronegative recipients of hearts from CMV seropositive donors with 16 matched controls receiving ganciclovir alone. The actuarial incidence of CMV disease was reduced from 55% in the ganciclovir group to 46% in the combined group (p≤0.06) and survival was increased from 61% to 94% (p≤0.001). In heart-lung or lung transplant patients in whom either the donor or recipient was CMV seropositive, the actuarial incidence of CMV disease in patients receiving ganciclovir alone (n=25) was 85% as compared to 36% of the 33 patients receiving both CMV-IGIV and ganciclovir (p≤0.05). Survival was 60% in the ganciclovir group and 80% in patients receiving CMV-IGIV and ganciclovir (p≤0.01).