Introduction

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

Uses for Cytomegalovirus Immune Globulin IV

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). Generally used in conjunction with an antiviral (e.g., acyclovir, ganciclovir); has been used alone.

CMV prophylaxis in liver, lung, pancreas, or heart transplant recipients. Usually used in conjunction with an antiviral (e.g., ganciclovir, acyclovir).

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).

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 transplant^{† [off-label]} or to prevent or attenuate secondary CMV disease (reactivation of CMV) in individuals who are CMV-seropositive prior to transplant^{† [off-label]}.

Most effective regimen for CMV prophylaxis in allogeneic BMT patients at risk for CMV infection and disease not established; conflicting results regarding possible benefits of CMV-IGIV prophylaxis in this patient population.

Treatment of CMV Pneumonitis in Transplant Recipients

Has been used in conjunction with ganciclovir for treatment of CMV pneumonitis in allogeneic BMT recipients^{† [off-label]} or CMV pneumonitis in solid organ transplant recipients^{† [off-label]} (e.g., liver transplant patients). 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.

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

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^{† [off-label]}.

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

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. 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.

Cytomegalovirus Immune Globulin IV Dosage and Administration

General

• Prior to administration, ensure patient is adequately hydrated.

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

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

Administration

IV Administration

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

Do not shake vial; avoid foam formation.

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

Administer via a separate IV infusion line. 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.

Do not dilute prior to IV infusion.

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

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

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

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.

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.

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

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

Dosage

Pediatric Patients

Prevention of CMV Disease in Solid Organ Transplant Recipients

Kidney Transplant Recipients

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

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.

Liver, Lung, Pancreas, or Heart Transplant Recipients

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

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.

Adults

Prevention of CMV Disease in Solid Organ Transplant Recipients

Kidney Transplant Recipients

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

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.

Liver, Lung, Pancreas, or Heart Transplant Recipients

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

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.

Prescribing Limits

Pediatric Patients

Prevention of CMV Disease in Solid Organ Transplant Recipients

IV

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

Adults

Prevention of CMV Disease in Solid Organ Transplant Recipients

IV

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

Special Populations

Renal Impairment

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

Contraindications

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

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

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

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

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.

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

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

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.

CMV-IGIV contains trace amounts of IgA.

Renal Effects

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

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. CMV-IGIV contains 5% sucrose as a stabilizer.

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.

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.

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

Administration Precautions

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

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

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

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).

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.

Report any infection believed to have been transmitted by CMV-IGIV to the manufacturer at 866-915-6958.

Aseptic Meningitis Syndrome

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

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.

Perform complete neurologic examination in patients exhibiting such symptoms to rule out other causes of meningitis. 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.

Syndrome generally resolved within several (3–5) days without sequelae following IGIV discontinuance.

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.

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

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

Transfusion-related Acute Lung Injury

Transfusion-related acute lung injury (TRALI; noncardiogenic pulmonary edema) reported in patients receiving IGIV. 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.

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

Manage using oxygen therapy with adequate ventilatory support.

Thrombotic Effects

Thrombotic events reported in patients receiving IGIV.

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.

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

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).

Improper Storage and Handling

Improper storage or handling of immune globulins may affect efficacy.

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

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

Specific Populations

Pregnancy

Category C.

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.

Lactation

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

Pediatric Use

Has been used in pediatric renal transplant recipients as young as 1 year of age, in liver transplant patients^† as young as 4 years of age, and in allogeneic BMT patients^† as young as 1–8 years of age without unusual adverse effects.

Geriatric Use

Use with caution in patients >65 years of age. (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).

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

Common Adverse Effects

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

General

• Prior to administration, ensure patient is adequately hydrated.

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

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

Administration

IV Administration

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

Do not shake vial; avoid foam formation.

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

Administer via a separate IV infusion line. 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.

Do not dilute prior to IV infusion.

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

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

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

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.

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.

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

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

Dosage

Pediatric Patients

Prevention of CMV Disease in Solid Organ Transplant Recipients

Kidney Transplant Recipients

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

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.

Liver, Lung, Pancreas, or Heart Transplant Recipients

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

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.

Adults

Prevention of CMV Disease in Solid Organ Transplant Recipients

Kidney Transplant Recipients

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

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.

Liver, Lung, Pancreas, or Heart Transplant Recipients

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

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.

Prescribing Limits

Pediatric Patients

Prevention of CMV Disease in Solid Organ Transplant Recipients

IV

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

Adults

Prevention of CMV Disease in Solid Organ Transplant Recipients

IV

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

Special Populations

Renal Impairment

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

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); 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. (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.

Specific Drugs