Cytogam

Generic Name: Cytomegalovirus Immune Globulin IV
Class: Serums
ATC Class: J06BB09
VA Class: IM500

Introduction

Specific immune globulin (hyperimmune globulin).36 Cytomegalovirus immune globulin IV (CMV-IGIV) contains IgG prepared from plasma of adults selected for high titers of CMV antibody.1

Uses for Cytogam

Prevention of CMV Disease in Solid Organ Transplant Recipients

CMV prophylaxis in kidney transplant recipients at risk for primary CMV infection and disease (i.e., CMV-seronegative recipients of a kidney from a CMV-seropositive donor).1 4 5 7 8 10 15 Generally used in conjunction with an antiviral (e.g., acyclovir, ganciclovir); has been used alone.10 13 15 70 75 76

CMV prophylaxis in liver,1 16 20 54 60 61 lung,1 19 53 81 pancreas,1 or heart1 37 40 55 transplant recipients.1 11 13 16 17 19 20 40 76 Usually used in conjunction with an antiviral (e.g., ganciclovir, acyclovir).1 19 53 54 55 61 75 76 81

Slideshow: 18 Herbal Supplements with Risky Drug Interactions

Herbal and Dietary Supplements Deserve Your Attention

Optimum regimens for CMV prophylaxis based on type of organ being transplanted and degree of risk for CMV infection or disease not identified, especially for those at greatest risk (e.g., CMV-seronegative recipients of organs from CMV-seropositive donors, patients receiving muromonab-CD3 [OKT3 monoclonal antibodies] or other immunosuppressive therapy).13 40 58 60 86

Prevention of CMV Disease in Bone Marrow Transplant (BMT) Recipients

Has been used in individuals undergoing allogeneic BMT in an attempt to prevent primary CMV infection in those who are CMV-seronegative prior to transplant17 18 41 45 49 57 62 63 or to prevent or attenuate secondary CMV disease (reactivation of CMV) in individuals who are CMV-seropositive prior to transplant.18

Most effective regimen for CMV prophylaxis in allogeneic BMT patients at risk for CMV infection and disease not established;57 conflicting results regarding possible benefits of CMV-IGIV prophylaxis in this patient population.17 18 56 57 62 63 75 76

Treatment of CMV Pneumonitis in Transplant Recipients

Has been used in conjunction with ganciclovir for treatment of CMV pneumonitis in allogeneic BMT recipients18 22 23 24 or CMV pneumonitis in solid organ transplant recipients (e.g., liver transplant patients).16 25 Additional study needed to determine whether combined ganciclovir and CMV-IGIV therapy has any effect on long-term survival rate in allogeneic BMT patients who develop CMV pneumonitis.18 23 56

Do not use alone for treatment of CMV pneumonia in BMT recipients.18 44

Congenital or Neonatal CMV Infection

Has been used in limited number of pregnant women with primary CMV infection in an attempt to treat or prevent congenital CMV infection.38 79 83

Not currently recommended for prevention of maternal-fetal transmission of CMV;38 82 additional study needed to evaluate possible benefits and risks of antenatal CMV-IGIV.79 80 82

CMV Infection in HIV-Infected Individuals

Potential role, if any, for prevention or treatment of CMV infection or disease in HIV-infected individuals not evaluated to date.75 76 Recommendations from CDC, National Institutes of Health (NIH), and HIV Medicine Association of the Infectious Diseases Society of America (IDSA) regarding CMV prophylaxis and treatment in such individuals include information on antivirals, but do not address CMV-IGIV.68

Cytogam Dosage and Administration

General

  • Prior to administration, ensure patient is adequately hydrated.1

  • Assess vital signs prior to starting, midway through, and after completion of infusion.1 Also assess vital signs before, during, and after any change in rate of administration.1

  • Assess renal function (BUN, Scr, urine output) prior to and at appropriate intervals after administration.1 If renal function decreases, consider discontinuing CMV-IGIV.1 (See Renal Effects under Cautions.)

Administration

IV Administration

Administer only by IV infusion.1 Do not administer IM or sub-Q.1

Do not shake vial; avoid foam formation.1

Use inline filter (pore size 15 mcm preferred; pore size 0.2 mcm acceptable) and controlled-infusion device (i.e., IVAC pump or equivalent) to control flow rate.1

Administer via a separate IV infusion line.1 If necessary, may be piggy-backed into a preexisting line containing 0.9% sodium chloride injection or 2.5, 5, 10, or 20% dextrose injection (with or without sodium chloride), provided dilution of CMV-IGIV with such fluid does not exceed 1:2.1

Do not dilute prior to IV infusion.1

Do not admix with other drugs;1 information on physical and/or chemical compatibility with other IV infusion fluids or other drugs not available.1

Initiate IV infusion within 6 hours and complete infusion within 12 hours of entering vial.1

Does not contain a preservative;1 administer only if solution is colorless and not turbid.1

Rate of Administration

Give initial IV infusion at 15 mg/kg per hour for first 30 minutes; if well tolerated, increase rate to 30 mg/kg per hour for next 30 minutes and, if well tolerated, increase to 60 mg/kg per hour for remainder of infusion.1

Give subsequent IV infusions at 15 mg/kg per hour for first 15 minutes; if well tolerated, increase rate to 30 mg/kg per hour for next 15 minutes and, if well tolerated, increase to 60 mg/kg per hour for remainder of infusion.1

Do not exceed infusion rate of 60 mg/kg per hour (75 mL/hour) for initial or subsequent doses.1

If relatively minor adverse effects (e.g., flushing, back pain, nausea) occur, reduce infusion rate or temporarily interrupt infusion until manifestations subside;1 infusion may then be resumed at previously tolerated rate.76 If more severe reactions (e.g., anaphylaxis, drop in BP) occur, immediately discontinue infusion and administer appropriate therapy (e.g., epinephrine, diphenhydramine).1

Dosage

Pediatric Patients

Prevention of CMV Disease in Solid Organ Transplant Recipients
Kidney Transplant Recipients
IV

Initial 150-mg/kg dose within 72 hours after transplantation.1 87

Additional 100-mg/kg doses once every 2 weeks at 2, 4, 6, and 8 weeks after transplantation, then 50-mg/kg doses once at 12 and 16 weeks after transplantation.1 87

Liver, Lung, Pancreas, or Heart Transplant Recipients
IV

Initial 150-mg/kg dose within 72 hours after transplantation.1 87

Additional 150-mg/kg doses once every 2 weeks at 2, 4, 6, and 8 weeks after transplantation, then 100-mg/kg doses once at 12 and 16 weeks after transplantation.1 87

Adults

Prevention of CMV Disease in Solid Organ Transplant Recipients
Kidney Transplant Recipients
IV

Initial 150-mg/kg dose within 72 hours after transplantation.1

Additional 100-mg/kg doses once every 2 weeks at 2, 4, 6, and 8 weeks after transplantation, then 50-mg/kg doses once at 12 and 16 weeks after transplantation.1

Liver, Lung, Pancreas, or Heart Transplant Recipients
IV

Initial 150-mg/kg dose within 72 hours after transplantation.1

Additional 150-mg/kg doses once every 2 weeks at 2, 4, 6, and 8 weeks after transplantation, then 100-mg/kg doses once at 12 and 16 weeks after transplantation.1

Prescribing Limits

Pediatric Patients

Prevention of CMV Disease in Solid Organ Transplant Recipients
IV

Maximum dose 150 mg/kg;1 87 maximum infusion rate 60 mg/kg per hour (75 mL/hour).1 87

Adults

Prevention of CMV Disease in Solid Organ Transplant Recipients
IV

Maximum dose 150 mg/kg;1 maximum infusion rate 60 mg/kg per hour (75 mL/hour).1

Special Populations

Renal Impairment

Do not exceed recommended dosage;1 use minimum practicable concentration and IV infusion rate.1 (See Renal Impairment under Cautions.)

Cautions for Cytogam

Contraindications

  • History of prior severe reaction to CMV-IGIV or any other human immune globulin preparation.1

  • Selective IgA deficiency.1 (See IgA Deficiency under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Precipitous fall in BP and clinical manifestations of anaphylaxis reported with IGIV.30

Hypotension and serious reactions such as angioedema or anaphylaxis not reported to date in clinical studies of CMV-IGIV, but possibility exists that these reactions could occur.1

Epinephrine and other appropriate agents should be readily available to treat acute allergic manifestations or anaphylactoid reactions if they occur.1

If anaphylaxis or change in BP occurs, immediately discontinue infusion and initiate appropriate therapy (e.g., epinephrine) as indicated.1

IgA Deficiency

Individuals with IgA deficiency may have antibodies to IgA (or develop such antibodies following administration of CMV-IGIV); anaphylaxis could occur following administration of CMV-IGIV or other blood product containing IgA.1

CMV-IGIV contains trace amounts of IgA.1

Renal Effects

Renal dysfunction, acute renal failure, acute tubular necrosis, proximal tubular nephropathy, osmotic nephrosis, and death reported in patients receiving IGIV.1 Increases in BUN and Scr have occurred as soon as 1–2 days following IGIV treatment and has progressed to oliguria or anuria (requiring dialysis).1

Available data indicate that IGIV preparations stabilized with sucrose and administered at daily dosages ≥350 mg/kg are associated with greater risk of developing IGIV-associated renal dysfunction.1 77 CMV-IGIV contains 5% sucrose as a stabilizer.1

Patients predisposed to acute renal failure include those who are >65 years of age; have preexisting renal insufficiency, diabetes mellitus, volume depletion, sepsis, or paraproteinemia; or are receiving nephrotoxic drugs.1

Ensure that patients (especially those at increased risk of acute renal failure) are adequately hydrated and infuse CMV-IGIV at the minimum concentration and rate that is practicable.1

Assess renal function, including measurement of BUN, Scr, and urine output, before and at appropriate intervals after administration.1 If renal function decreases, consider discontinuing CMV-IGIV.1

Administration Precautions

Some adverse effects (e.g., flushing,1 5 7 8 chills,1 7 muscle cramps,1 5 7 back pain,1 5 7 8 fever,1 nausea,1 5 vomiting,1 arthralgia,1 8 wheezing/shortness of breath/chest tightness)1 5 7 8 may be related to IV infusion rate.1 7

Do not exceed recommended infusion rate; follow recommended infusion schedule.1 (See Rate of Administration under Dosage and Administration.)

If minor adverse effects occur, decrease infusion rate or temporarily interrupt infusion.1

Risk of Transmissible Infectious Agents in Plasma-derived Preparations

Because CMV-IGIV is prepared from pooled human plasma and contains albumin human, it is a potential vehicle for transmission of human viruses and theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD).1 31

Although donors are screened for certain viruses (e.g., HIV, HBV, HCV) and CMV-IGIV undergoes certain procedures (cold ethanol fractionation, solvent/detergent viral inactivation) that reduce viral infectious potential, some unrecognized blood-borne infectious agents may not be inactivated and a risk for transmission of infectious agents still remains.1 3 32 33 34 35 75

Report any infection believed to have been transmitted by CMV-IGIV to the manufacturer at 866-915-6958.1

Aseptic Meningitis Syndrome

Aseptic meningitis syndrome reported rarely in patients receiving IGIV;1 26 27 occurs more frequently in patients receiving high total doses of IGIV (e.g., 2 g/kg).1 26 27

Symptoms include severe headache, nuchal rigidity, drowsiness, lethargy, fever, photophobia, painful eye movements, nausea, and vomiting; usually evident within several hours to 2 days after IGIV.1 26 27 28 29

Perform complete neurologic examination in patients exhibiting such symptoms to rule out other causes of meningitis.1 CSF analysis frequently reveals pleocytosis (up to several thousand cells per mm3), predominantly from the granulocytic series, and protein concentrations up to several hundred mg/dL.1 26 27 28 29

Syndrome generally resolved within several (3–5) days without sequelae following IGIV discontinuance.1 26 27 28 29

Hemolysis

Immune globulin preparations may contain blood group antibodies that can act as hemolysins and induce in vivo coating of RBCs with immunoglobulin, causing a positive direct antiglobulin reaction and, rarely, hemolysis.1

Hemolytic anemia also can develop following immune globulin therapy due to enhanced RBC sequestration.1

Monitor for clinical signs and symptoms of hemolysis during and after CMV-IGIV treatment and, if necessary, perform appropriate confirmatory laboratory testing.1

Transfusion-related Acute Lung Injury

Transfusion-related acute lung injury (TRALI; noncardiogenic pulmonary edema) reported in patients receiving IGIV.1 Typically occurs within 1–6 hours after IGIV infusion and is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever.1

Monitor for adverse pulmonary reactions.1 If TRALI is suspected, perform appropriate tests to determine whether antineutrophil antibodies are present in the product or patient serum.1

Manage using oxygen therapy with adequate ventilatory support.1

Thrombotic Effects

Thrombotic events reported in patients receiving IGIV.1

Patients at risk of thrombotic events include those with history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, and/or known or suspected hyperviscosity.1

Weigh potential risks and benefits of CMV-IGIV against those of alternative therapies.1

Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity (e.g., those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols [triglycerides], monoclonal gammopathies).1

Improper Storage and Handling

Improper storage or handling of immune globulins may affect efficacy.36

Do not administer CMV-IGIV that has been mishandled or has not been stored at the recommended temperature.36 (See Storage under Stability.)

Inspect all immune globulins upon delivery and monitor during storage to ensure that the appropriate temperature is maintained.36 If there are concerns about mishandling, contact the manufacturer or state or local health departments for guidance on whether CMV-IGIV is usable.36

Specific Populations

Pregnancy

Category C.1

US Public Health Service Advisory Committee on Immunization Practices (ACIP) states there are no known risks for the fetus from use of immune globulin preparations for passive immunization in pregnant women.36

Lactation

Information on distribution into milk not available; not known if transmission of CMV-IGIV to nursing infant presents any unusual risk.75 76

Pediatric Use

Has been used in pediatric renal transplant recipients5 7 8 as young as 1 year of age,75 in liver transplant patients as young as 4 years of age,54 and in allogeneic BMT patients as young as 1–8 years of age17 22 23 44 without unusual adverse effects.16 44 75

Geriatric Use

Use with caution in patients >65 years of age.1 (See Renal Impairment under Cautions.)

Renal Impairment

Use with caution in patients with preexisting renal impairment and in patients judged to be at increased risk of developing renal impairment (e.g., those >65 years of age; with diabetes mellitus, volume depletion, paraproteinemia, or sepsis; or receiving nephrotoxic drugs).1

Do not exceed recommended dosage, concentration, and IV infusion rate in patients with or at increased risk for renal impairment.1

Common Adverse Effects

Flushing,1 5 7 8 chills,1 7 muscle cramps,1 5 7 back pain,1 5 7 8 fever,1 nausea,1 5 vomiting,1 arthralgia,1 8 wheezing/shortness of breath/chest tightness.1 5 7 8

Interactions for Cytogam

Live Vaccines

Antibodies present in immune globulin preparations may interfere with immune responses to some live virus vaccines, including measles, mumps, and rubella virus vaccine live (MMR), varicella virus vaccine live, and fixed combination of MMR and varicella vaccine (MMRV);1 36 no evidence that immune globulin preparations interfere with immune responses to rotavirus vaccine live oral, influenza virus vaccine live intranasal, yellow fever virus vaccine live, typhoid vaccine live oral, or zoster vaccine live.36 (See Specific Drugs under Interactions.)

Inactivated Vaccines and Toxoids

Immune globulin preparations are not expected to have a clinically important effect on immune responses to inactivated vaccines or toxoids; inactivated vaccines, recombinant vaccines, polysaccharide vaccines, and toxoids may be administered simultaneously with (using different syringes and different injection sites) or at any interval before or after CMV-IGIV.36

Specific Drugs

Drug

Interaction

Comments

Influenza vaccine

Intranasal live influenza vaccine: No evidence that immune globulin preparations interfere with immune response to the vaccine36

Parenteral inactivated influenza vaccine: No evidence that immune globulin preparations interfere with immune response to the vaccine36

Intranasal live influenza vaccine: May be given simultaneously with or at any interval before or after immune globulin preparations36

Parenteral inactivated influenza vaccine: May be given simultaneously (at a different site) or at any interval before or after immune globulin preparations36

Measles, mumps, rubella, and varicella virus vaccines

Antibodies in immune globulin preparations can interfere with immune response to measles and rubella antigens contained in MMR or MMRV;36 effect on immune response to mumps or varicella antigens unknown, but an effect is possible36

Duration of interference depends on amount of antigen-specific antibody in the immune globulin preparation36

MMR, MMRV, or varicella vaccine should not be administered simultaneously with CMV-IGIV; defer for at least 6 months after CMV-IGIV36

Revaccination with MMR, MMRV, or varicella vaccine may be necessary if vaccine was given <6 months after CMV-IGIV 36

Revaccination with MMR, MMRV, or varicella vaccine is necessary at least 6 months after CMV-IGIV if the immune globulin preparation was administered <14 days after vaccine dose, unless serologic testing is feasible and indicates an adequate vaccine response36

Typhoid vaccine

Oral live typhoid vaccine: No evidence that immune globulin preparations interfere with immune response to the vaccine36

Oral live typhoid vaccine: May be given simultaneously with or at any interval before or after immune globulin preparations36

Yellow fever vaccine

No evidence that immune globulin preparations interfere with immune response to the vaccine36

Yellow fever vaccine may be given simultaneously (at a different site) or at any interval before or after immune globulin preparations36

Zoster vaccine

No evidence that immune globulin preparations interfere with immune response to the vaccine36

Zoster vaccine may be given simultaneously (at a different site) or at any interval before or after immune globulin preparations36

Cytogam Pharmacokinetics

Absorption

Bioavailability

Pharmacokinetics not fully elucidated.1

Elimination

Half-life

Renal transplant patients receiving 50-mg/kg doses once daily for first 3 days posttransplant followed by once every 21 days for 4 months: 5–13 days during first 2 months posttransplant and 13–45 days during third to fifth month posttransplant.4 CMV antibody detectable for up to 2 months following last dose.4

Stability

Storage

Parenteral

Injection, for IV Infusion

2–8°C.1 Discard if inadvertently frozen.75

Actions

  • CMV-IGIV is prepared from pooled plasma of healthy adults selected for high titers of CMV antibodies.1 5 6

  • Contains CMV antibody titer1 >1:7000 by enzyme-linked immunosorbent assay (ELISA);75 this CMV antibody titer is at least 4–8 times higher than that contained in IGIV or immune globulin IM (IGIM).6 10 11 13

  • Each mL contains 40–60 mg of immunoglobulin, primarily IgG with trace amounts of IgA and IgM;1 also contains 5% sucrose and 1% albumin as stabilizing agents.1

  • CMV-specific antibodies contained in CMV-IGIV can neutralize CMV.55 65 66 However, CMV is largely a cell-associated virus and antibody-neutralization of the virus alone may not be sufficient to prevent or ameliorate active CMV disease in individuals already infected.42 55 63 65 75

  • There is evidence that cell-mediated immunity is important in determining severity and outcome of CMV disease in immunocompromised individuals; in addition to antibody-neutralization, CMV-IGIV may exert some immunomodulating effects (e.g., potentiation of antibody-dependent cell-mediated cytotoxic reactions) that contribute to prevention or amelioration of CMV disease in such patients.42 55 63 65 66

  • Actual serum titer of CMV antibody associated with immunity against primary CMV infection in CMV-seronegative individuals or suppression or amelioration of reactivated infections in CMV-seropositive individuals unknown.4 43

Advice to Patients

  • Advise patient of the risks and benefits of CMV-IGIV.1

  • Importance of immediately reporting symptoms of decreased urine output, sudden weight gain, and/or shortness of breath (which may suggest renal damage) to a clinician.1

  • Advise patient that CMV-IGIV is prepared from pooled human plasma.1 Although improved donor screening and viral-inactivating and purification procedures used in manufacture of plasma-derived preparations have reduced the risk of pathogen transmission, CMV-IGIV is a potential vehicle for transmission of infectious agents.1 Importance of reporting any infections to clinician and to manufacturer at 866-915-6958.1

  • Advise patient that CMV-IGIV may interfere with the immune response to certain live virus vaccines (e.g., MMR, varicella vaccines); importance of informing clinicians administering vaccines about recent use of CMV-IGIV.1 (See Interactions.)

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of informing patient of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Cytomegalovirus Immune Globulin IV (Human)

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion

50 ±10 mg (of immunoglobulin) per mL

Cytogam

CSL Behring

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions September 1, 2012. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. CSL Behring. CytoGam (cytomegalovirus immune globulin intravenous [human][CMV-IGIV]) liquid formulation solvent detergent treated prescribing information. Kankakee, IL; 2010 Nov.

3. Horowitz B, Wiebe ME, Lippin A et al. Inactivation of viruses in labile blood derivatives: I. Disruption of lipid-enveloped viruses by tri(n-butyl)phosphate detergent combinations. Transfusion. 1985; 25:516-22. [PubMed 3934801]

4. Snydman DR, McIver J, Leszczynski J et al. A pilot trial of a novel cytomegalovirus immune globulin in renal transplant recipients. Transplantation. 1984; 38:553-7. [PubMed 6093299]

5. Snydman DR, Werner BG, Heinze-Lacey B et al. Use of cytomegalovirus immune globulin to prevent cytomegalovirus disease in renal-transplant recipients. N Engl J Med. 1987; 317:1049-54. [IDIS 234462] [PubMed 2821397]

6. Snydman DR. Prevention of cytomegalovirus-associated diseases with immunoglobulin. Transplant Proc. 1991; 23(Suppl 3):131-5. [PubMed 1648817]

7. Snydman DR, Werner BG, Tilney NL et al. Final analysis of primary cytomegalovirus disease prevention in renal transplant recipients with a cytomegalovirus-immune globulin: comparison of the randomized and open-label trials. Transplant Proc. 1991; 23:1357-60. [PubMed 1846464]

8. Werner BG, Snydman DR, Freeman R et al et al. Cytomegalovirus immune globulin for the prevention of primary CMV disease in renal transplant patients: analysis of usage under treatment IND status. Transplant Proc. 1993; 25:1441-3. [PubMed 8382875]

9. Ho M. Cytomegalovirus. In: Mandell GL, Bennett JE, Dolin R eds. Mandell, Douglas and Bennett’s principles and practice of infectious diseases. 4th ed. New York: Churchill Livingstone; 1995:1351-64.

10. Dickinson BI, Gora-Harper ML, McCraney SA et al. Studies evaluating high-dose acyclovir, intravenous immune globulin, and cytomegalovirus hyperimmunoglobulin for prophylaxis against cytomegalovirus in kidney transplant recipients. Ann Pharmacother. 1996; 30:1452-64. [IDIS 376986] [PubMed 8968459]

11. Snydman DR. Cytomegalovirus immunoglobulins in the prevention and treatment of cytomegalovirus disease. Clin Infect Dis. 1990; 12(Suppl 7):S839-48.

12. Snydman DR. Cytomegalovirus prophylaxis strategies in high-risk transplantation. Transplant Proc. 1994; 26(Suppl 1):20-2. [IDIS 337694] [PubMed 7940971]

13. Patel R, Snydman DR, Rubin RH et al. Cytomegalovirus prophylaxis in solid organ transplant recipients. Transplantation. 1996; 61:1279-89. [IDIS 366072] [PubMed 8629285]

14. Food and Drug Administration. FDA Application: Search Orphan Drug Designations and Approvals. Rockville, MD. From FDA website. Accessed 2012 Mar 12.

15. Bulinski P, Toledo-Pereyra LH, Dalal S et al. Cytomegalovirus infection in kidney transplantation: prophylaxis and management. Transplant Proc. 1996; 28:3310-1. [IDIS 377194] [PubMed 8962286]

16. Snydman DR, Werner BG, Dougherty NN et al et al. Cytomegalovirus immune globulin prophylaxis in liver transplantation: a randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1993; 119:984-91. [IDIS 322034] [PubMed 8214995]

17. Bowden RA, Sayers M, Flournoy N et al. Cytomegalovirus immune globulin and seronegative blood products to prevent primary cytomegalovirus infection after marrow transplantation. N Engl J Med. 1986; 314:1006-10. [IDIS 713752] [PubMed 3007984]

18. Tsinontides AC, Bechtel TP. Cytomegalovirus prophylaxis and treatment following bone marrow transplantation. Ann Pharmacother. 1996; 30:1277-90. [IDIS 375321] [PubMed 8913411]

19. Zamora MR, Fullerton DA, Campbell DN et al. Use of cytomegalovirus (CMV) hyperimmune globulin for prevention of CMV disease in CMV-seropositive lung transplant recipients. Transplant Proc. 1994; 26(Suppl 1):49-51. [IDIS 337697] [PubMed 7940974]

20. Snydman DR, Werner BG, Dougherty NN et al et al. A further analysis of the use of cytomegalovirus immune globulin in orthotopic liver transplant patients at risk for primary infection. Transplant Proc. 1994; 26(Suppl 1):23-7.

21. Rowe JM, Ciobanu N, Ascensao J et al et al. Recommended guidelines for the management of autologous and allogeneic bone marrow transplantation: a report from the Eastern Cooperative Oncology Group (ECOG). Ann Intern Med. 1994; 120:143-58. [IDIS 323859] [PubMed 8256974]

22. Ljungman P, Engelhard D, Link H et al. Treatment of interstitial pneumonitis due to cytomegalovirus with ganciclovir and intravenous immune globulin: experience of European Bone Marrow Transplant Group. Clin Infect Dis. 1992; 14:831-5. [IDIS 293956] [PubMed 1315585]

23. Reed EC, Bowden RA, Dandliker PS et al. Treatment of cytomegalovirus pneumonia with ganciclovir and intravenous cytomegalovirus immunoglobulin in patients with bone marrow transplants. Ann Intern Med. 1988; 109:783-8. [IDIS 248033] [PubMed 2847610]

24. Reed EC, Bowden RA, Dandliker PS et al. Treatment of cytomegalovirus (CMV) pneumonia in bone marrow transplant (BMT) patients (pts) with ganciclovir (GCV) and CMV immunoglobulin (CMV-IG). Blood. 1987; 70(Suppl 1):313.

25. D’Alessandro AM, Pirsch JD, Stratta RJ et al. Successful treatment of severe cytomegalovirus infections with ganciclovir and CMV hyperimmune globulin in liver transplant recipients. Transplant Proc. 1989; 21:3560-1. [PubMed 2545018]

26. Sekul EA, Cupler EJ, Dalakas MC. Aseptic meningitis associated with high-dose intravenous immunoglobulin therapy: frequency and risk factors. Ann Intern Med. 1994; 121:259-62. [IDIS 333948] [PubMed 8037406]

27. Scribner CL, Kapit RM, Phillips ET et al. Aseptic meningitis and intravenous immunoglobulin therapy. Ann Intern Med. 1994; 121:305-6. [IDIS 333955] [PubMed 8037414]

28. Kato E, Shindo S, Eto Y et al. Administration of immune globulin associated with aseptic meningitis. JAMA. 1988; 259:3269-71. [IDIS 242242] [PubMed 2453686]

29. Casteels-Van Daele M, Wijndaele L, Hunninck K et al. Intravenous immune globulin and acute aseptic meningitis. N Engl J Med. 1990; 323:614-5.

30. Talecris. Gamimune N, 10% (immune globulin intravenous [human]) 10% solvent/detergent treated prescribing information. Research Triangle Park,NC; 2005 Jan.

31. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research (CBER). Guidance for industry. Revised preventive measures to reduce the possible risk of transmission of Creutzfeldt-Jakob disease (CJD) and variant Creutzfeldt-Jakob disease (vCJD) by blood and blood products. January 2002. From FDA website.

32. Wells MA, Wittek AE, Epstein JS et al. Inactivation and partition of human T-cell lymphotrophic virus, type III, during ethanol fractionation of plasma. Transfusion. 1986; 26:210-3. [PubMed 3006303]

33. Centers for Disease Control and Prevention. Outbreak of hepatitis C associated with intravenous immunoglobulin administration—United States, October 1993–June 1994. MMWR Morb Mortal Wkly Rep. 1994; 43:505-9. [IDIS 333044] [PubMed 8022396]

34. Horowitz B, Wiebe ME, Lippin A et al. Inactivation of viruses in labile blood derivatives. I. Disruption of lipid-enveloped viruses by tri(n-butyl)phosphate detergent combinations. Transfusion. 1985; 25:516-22. [PubMed 3934801]

35. Edwards CA, Piet MPJ, Chin S et al. Tri(n-butyl) phosphate/detergent treatment of licensed therapeutic and experimental blood derivatives. Vox Sang. 1987; 52:53-9. [PubMed 3111089]

36. National Center for Immunization and Respiratory Diseases. General recommendations on immunization --- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2011; 60:1-64.

37. Metselaar HJ, Velzing J, Rothbarth PH et al. A pharmacokinetic study of anti-cytomegalovirus hyperimmunoglobulins in cytomegalovirus seronegative cardiac transplant recipients. Transplant Proc. 1987; 19:4063-5. [PubMed 2823431]

38. American Academy of Pediatrics. Red Book: 2009 Report of the Committee on Infectious Diseases. 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009.

39. Snydman DR, Werner BG, Meissner HC et al. Use of cytomegalovirus immunoglobulin in multiply transfused premature neonates. Pediatr Infect Dis J. 1995; 14:34-40. [IDIS 341231] [PubMed 7715987]

40. Aguado JM, Gomez-Sanchez MA, Lumbreras C et al. Prospective randomized trial of efficacy of ganciclovir versus that of anti-cytomegalovirus (CMV) immunoglobulin to prevent CMV-seropositive heart transplant recipients treated with OKT3. Antimicrob Agents Chemother. 1995;39:1643-5.

41. Ruutu T, Ljungman P, Brinch L et al and the Nordic BMT Group. No prevention of cytomegalovirus infection by anti-cytomegalovirus hyperimmune globulin in seronegative bone marrow transplant recipients. Bone Marrow Transplant. 1997; 19:233-6. [IDIS 384560] [PubMed 9028551]

42. Grundy JE. Virologic and pathogenetic aspects of cytomegalovirus infection. Clin Infect Dis. 1990; 12(Suppl 7):S711-9.

43. Rubin RH. Impact of cytomegalovirus infection on organ transplant recipients. Clin Infect Dis. 1990; 12(Suppl 7):754-66.

44. Reed EC, Bowden RA, Dandliker PS et al. Efficacy of cytomegalovirus immunoglobulin in marrow transplant recipients with cytomegalovirus pneumonia. J Infect Dis. 1987; 156:641-5. [IDIS 234925] [PubMed 3040870]

45. Bowden RA, Fisher LD, Rogers K et al. Cytomegalovirus (CMV)-specific intravenous immunoglobulin for the prevention of primary CMV infection and disease after marrow transplant. J Infect Dis. 1991; 164:483-7. [IDIS 288689] [PubMed 1651360]

46. Filipovich AH, Peltier MH, Bechtel MK et al. Circulating cytomegalovirus (V) neutralizing activity in bone marrow transplant recipients: comparison of passive immunity in a randomized study of four intravenous IgG products administered to CMV-seronegative patients. Blood. 1992; 80:2656-60. [IDIS 305808] [PubMed 1330079]

47. Zaia JA. Prevention and treatment of cytomegalovirus pneumonia in transplant recipients. Clin Infect Dis. 1993; 17(Suppl 2):S392-9. [IDIS 323663] [PubMed 8274605]

48. Emanuel D, Cunningham I, Jules-Elysee K et al. Cytomegalovirus pneumonia after bone marrow transplantation successfully treated with the combination of ganciclovir and high-dose intravenous immune globulin. Ann Intern Med. 1988; 109:777-82. [IDIS 248032] [PubMed 2847609]

49. Condie RM, O’Reilly RJ. Prevention of cytomegalovirus infection by prophylaxis with an intravenous, hyperimmune, native, unmodified cytomegalovirus globulin. Am J Med. 1984; 76(Suppl 3A):134-41. [IDIS 183531] [PubMed 6324587]

50. Glowacki LS, Small FM. Use of immune globulin to prevent symptomatic cytomegalovirus disease in transplant recipients—a meta-analysis. Clin Transplant. 1994; 8:10-8. [IDIS 326206] [PubMed 8136560]

51. Snydman DR. Use of immune globulin to prevent symptomatic cytomegalovirus disease in transplant recipients—a meta-analysis. Clin Transplant. 1995; 9:490-1. [IDIS 359916] [PubMed 8645893]

52. Dunn DL, Gillingham KJ, Kramer MA et al. A prospective randomized study of acyclovir versus ganciclovir plus human immune globulin prophylaxis of cytomegalovirus infection after solid organ transplantation. Transplantation. 1994; 57:876-84. [IDIS 327671] [PubMed 8154035]

53. Kathawalla SA, Stillwell PC, Gordon S et al. Cytomegalovirus infection in seromismatched lung transplant recipients with and without prophylaxis with CMV immunoglobulin. Transplant Proc. 1996; 28(Suppl 2):16. [IDIS 377219] [PubMed 9037272]

54. Ham J, Shelen SL, Godkin RR et al. Cytomegalovirus prophylaxis with ganciclovir, acyclovir, and CMV hyperimmune globulin in liver transplant patients receiving OKT3 induction. Transplant Proc. 1995; 27(Suppl 1):31-3. [IDIS 355365] [PubMed 7482814]

55. Valantine HA. Prevention and treatment of cytomegalovirus disease in thoracic organ transplant patients: evidence for a beneficial effect of hyperimmune globulin. Transplant Proc. 1995; 27(Suppl 1):49-57. [IDIS 355370] [PubMed 7482821]

56. Reusser P. The challenge of cytomegalovirus infection after bone arrow transplantation: epidemiology, prophylaxis, and therapy. Bone Marrow Transplant. 1996; 18:107-9. [IDIS 380276] [PubMed 8932809]

57. Badas A, Stoukides CA. Guidelines for prophylaxis of cytomegalovirus disease in bone marrow transplant patients. Ann Pharmacother. 1996; 30:1483-6. [IDIS 376989] [PubMed 8968462]

58. Paya CV. Defining an optimal regimen for cytomegalovirus prophylaxis in organ transplant recipients. Transplant Proc. 1996; 28(Suppl 2):9-11. [IDIS 377216] [PubMed 9037269]

59. Wittes JT, Kelly A, Plante KM. Meta-analysis of CMVIG studies for the prevention an treatment of CMV infection in transplant patients. Transplant Proc. 1996; 28(Suppl 2):17-24. [IDIS 377220] [PubMed 9037273]

60. Trulock EP. Lung transplantation. Am J Respir Crit Care Med. 1997; 155:789-818. [IDIS 383403] [PubMed 9117010]

61. Wood DE, Raghu G. Lung transplantation. Part II. Postoperative management and results. West J Med. 1997; 166:45-55. [IDIS 383175] [PubMed 9074338]

62. Guglielmo BJ, Wong-Beringer A, Linker CA. Immune globulin therapy in allogeneic bone marrow transplant: a critical review. Bone Marrow Transplant. 1994; 13:499-510. [IDIS 329710] [PubMed 8054903]

63. Bass EB, Powe NR, Goodman SN et al. Efficacy of immune globulin in preventing complications of bone marrow transplantation: a meta-analysis. Bone Marrow Transplant. 1993; 12:273-82. [PubMed 8241987]

64. So S, Mayo C, McCullough C et al. Cytomegalovirus prophylaxis in pediatric renal transplant recipients. Transplant Proceed. 993; 25:1414-5.

65. Meyers JD. Prevention of cytomegalovirus infection after marrow transplantation. Rev Infect Dis. 1989; 11(Suppl 7):S1691-705. [IDIS 307687] [PubMed 2557664]

66. Winston DJ, Ho WG, Champlin RE. Cytomegalovirus infections after allogeneic bone marrow transplantation. Clin Infect Dis. 1990; 12(Suppl 7):S776-87.

67. Hirsch MS. Cytomegalovirus and human herpesvirus types 6, 7, and 8. In: Fauci AS, Braunwald E, Isselbacher KJ et al, eds. Harrison’s principles of internal medicine. l4th ed. New York: McGraw-Hill Company; 1998:1092-5.

68. Kaplan JE, Benson C, Holmes KH et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009; 58(RR-4):1-207; quiz CE1-4.

69. Griffiths PD. Prophylaxis against CMV infection in transplant patients. J Antimicrob Chemother. 1997; 39:299-301. [IDIS 384980] [PubMed 9096177]

70. Conti DJ, Shen G, Singh T et al. Ganciclovir prophylaxis of cytomegalovirus disease. Transplant Proc. 1997; 29:804-6. [IDIS 381942] [PubMed 9123534]

71. Prentice HG, Kho P. Clinical strategies for the management of cytomegalovirus infection and disease in allogeneic bone marrow transplant. Bone Marrow Transplant. 1997; 19:135-42. [IDIS 384620] [PubMed 9116610]

72. Winston DJ. Prevention of cytomegalovirus disease in transplant recipients. Lancet. 1995; 346:1380-1. [IDIS 357086] [PubMed 7475816]

73. Winston DJ, Wirin D, Shaked A et al. Randomised comparison of ganciclovir and high-dose acyclovir for long-term cytomegalovirus prophylaxis in liver-transplant recipients. Lancet. 1995; 346:69-74. [IDIS 351694] [PubMed 7603215]

74. Verdonck LF, Dekker AW, Rozenberg-Arska M et al. A risk-adapted approach with a short course of ganciclovir to prevent cytomegalovirus (CMV) pneumonia in CMV-seropositive recipients of allogeneic bone marrow transplants. Clin Infect Dis. 1997; 24:901-7. [IDIS 386049] [PubMed 9142790]

75. MedImmune, Inc., Gaithersburg, MD: Personal communication.

76. Reviewers’ comments (personal observations).

77. Epstein JS, Zoon KC. Dear healthcare provider letter regarding important drug warning of Immune Globulin IV. Rockville, MD: US Food and Drug Administration; 1999 Sep 24.

78. Centers for Disease Control and Prevention. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients: recommendations of CDC, the Infectious Diseases Society of America, and the American Society of Blood and Marrow Transplantation. MMWR Morb Mortal Wkly Rep. 2000; 49(No. RR-10):1-125. [IDIS 439515] [PubMed 10993565]

79. Nigro G, Adler SP, La Torre R et al. Passive immunization during pregnancy for congenital cytomegalovirus infection. N Engl J Med. 2005; 353:1350-62 [PubMed 16192480]

80. Duff P. Immunotherapy for congenital cytomegalovirus infection. N Engl J Med. 2005; 353:1402-4. [PubMed 16192488]

81. Ruttmann E, Geltner C, Bucher B et al. Combined CMV prophylaxis improves outcome and reduces the risk for bronchiolitis obliterans syndrome (BOS) after lung transplantation. Transplantation. 2006; 81:1415-20. [PubMed 16732179]

82. McCarthy FP, Giles ML, Rowlands S et al. Antenatal interventions for preventing the transmission of cytomegalovirus (CMV) from the mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant. Cochrane Database Syst Rev. 2011; :CD008371.

83. Nigro G, Adler SP, Parruti G et al. Immunoglobulin therapy of fetal cytomegalovirus infection occurring in the first half of pregnancy--a case-control study of the outcome in children. J Infect Dis. 2012; 205:215-27. [PubMed 22140265]

84. Hodson EM, Jones CA, Strippoli GF et al. Immunoglobulins, vaccines or interferon for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2007; :CD005129.

85. Bonaros N, Mayer B, Schachner T et al. CMV-hyperimmune globulin for preventing cytomegalovirus infection and disease in solid organ transplant recipients: a meta-analysis. Clin Transplant. 2008 Jan-Feb; 22:89-97.

86. Stratta RJ, Pietrangeli C, Baillie GM. Defining the risks for cytomegalovirus infection and disease after solid organ transplantation. Pharmacotherapy. 2010; 30:144-57. [PubMed 20099989]

87. CSLBehring, Kankakee, IL: Personal communication.

Hide
(web4)