Varicella-zoster immune globulin is an intramuscularly administered preparation of purified human immune globulin G (IgG) containing antibodies to varicella-zoster virus (anti-VZV). It is indicated for passive immunity in high-risk individuals after exposure to varicella (i.e., post-exposure prophylaxis). High-risk individuals for which the immune globulin is indicated include immunocompromised children and adults, newborns of mothers with varicella shortly before or after delivery, premature infants, neonates and infants younger than 1 year of age, adults without evidence of immunity, and pregnant women. Varicella-zoster immune globulin is intended to reduce the severity of varicella infections; however, there is no convincing evidence that post-exposure prophylaxis reduces the incidence of infection or alters disease progression after the appearance of varicella rash (i.e., established infection). To provide the greatest effectiveness, the immune globulin should be administered as soon as possible after exposure to the virus, ideally within 96 hours (can be given up to 10 days after exposure). Varicella-zoster immune globulin may be obtained through a drug expanded access program by contacting FFF Enterprises at 1-800-843-7477 or ASD Healthcare at 1-800-746-6273.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use if the solution is cloudy or contains particulates.
Intramuscular Administration
Preparation:
-Calculate the number of vials needed for the dose.
-Bring vial(s) to room temperature prior to use.
-Each vial is for single use only and contains a minimum potency of 125 International Units in 1.2 mL.
Intramuscular injection:
-Divide the calculated dose and administer in 2 or more injection sites, depending on patient size. DO NOT exceed 3 mL per injection site.
-Inject into the deltoid muscle or the anterolateral aspects of the upper thigh. Do not use the gluteal region as a routine injection site. If the gluteal region is used, only use the upper, outer quadrant because of the risk of sciatic nerve injury.
An injection site reaction (i.e., injection site pain) was reported by 3% of varicella-zoster immune globulin recipients during clinical trials. Other adverse reactions reported by at least 1% of patients included rash (1%; erythematous rash, vesicular rash, pruritus, and urticaria), headache (2%), fatigue (1%), chills (1%), and nausea (1%). A single incidence of serum sickness (approximately 1 in 600 patients) was observed in an immunocompromised adolescent patient.
Severe hypersensitivity reactions such as anaphylactic shock may occur after varicella-zoster immune globulin receipt. Administer the product in a setting with appropriate equipment, medication, and personnel trained in the management of hypersensitivity, anaphylaxis, and shock. If a hypersensitivity reaction occurs, immediately and permanently discontinue varicella-zoster immune globulin administration and provide appropriate treatment.
Thrombotic and hemorrhagic adverse events may occur during or after treatment with immune globulin products such as varicella-zoster immune globulin. Among 621 individuals to receive the varicella-zoster immune globulin in the Expanded Access Protocol (EAP), 8 adverse events related to the coagulation system were reported. Specifically, the adverse events included deep vein thrombosis (n=1), disseminated intravascular coagulation (DIC) (n=1), intracranial bleeding (n=2), coagulopathy (n=2), intraventricular hemorrhage (n=1), and pulmonary hemorrhage (n=1). However, the study was not designed to differentiate between adverse events attributed to the underlying medical condition and adverse reactions to varicella-zoster immune globulin.
Varicella-zoster immune globulin is made from human plasma and, thus, may carry a risk of transmitting infectious agents. No cases of transmission of viral diseases, variant Creutzfeldt-Jakob disease agent, or the Creutzfeldt-Jakob disease have been associated with the use of varicella-zoster immune globulin. Report any infection thought by a physician to have been transmitted by the product to the manufacturer at 1-833-644-4216.
Varicella-zoster immune globulin is contraindicated for use by patients known to have anaphylactic or severe systemic reactions to human immune globulin preparations. Varicella-zoster immune globulin is also contraindicated for use by IgA-deficient patients with antibodies against IgA and a history of hypersensitivity, as they may have an anaphylactoid reaction. Patients with IgA deficiency often develop antibodies against IgA and are more likely to have anaphylactic or immune-mediated adverse reactions to pooled immunoglobulin products. Varicella-zoster immune globulin contains less than 40 mcg/mL of IgA.
As with other products derived from or purified with human blood components, the possibility of transmission of infectious agents such as the variant Creutzfeldt-Jakob disease agent and, theoretically, the Creutzfeldt-Jakob disease agent exists in patients receiving varicella-zoster immune globulin. Screening plasma donors for prior exposure to certain viruses, testing for the presence of viruses, and inactivating or reducing viruses has reduced the risk of infection transmission from varicella-zoster immune globulin. The manufacturing processes are designed to reduce the risk of transmitting viral infection; however, none of the processes are completely effective. There is also the possibility that unknown infectious agents may be present in this product. Discuss the risks and benefits of this product with the patient before administration.
Only administer varicella-zoster immune globulin to patients who have severe thrombocytopenia or any coagulopathy like hemophilia that would contraindicate intramuscular injections if the expected benefits outweigh the potential risks.
Varicella-zoster immune globulin is indicated for post-exposure prophylaxis in high-risk patients such as pregnant women. The manufacturer recommends use during pregnancy only when clearly needed; FDA pregnancy category C drug. According to the recommendations of the Advisory Committee on Immunization Practices, strongly consider varicella zoster immune globulin for pregnant women without evidence of immunity who have been exposed because pregnant women might be at higher risk for severe varicella and complications. Administration of varicella-zoster immune globulin to these women has not been found to prevent viremia, fetal infection, congenital varicella syndrome, or neonatal varicella. Thus, the primary indication for varicella-zoster immune globulin in pregnant women is to prevent complications of varicella in the mother rather than to protect the fetus.
No data are available from the manufacturer regarding the use of varicella-zoster immune globulin during breast-feeding; excretion into breast milk is unknown. Case reports of 2 nursing mothers receiving intravenous immune globulin therapy suggest transfer of IgG and IgM into the colostrum and breast milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
The immune globulins present in varicella-zoster immune globulin may impair the efficacy of live virus vaccination such as varicella vaccine, measles, mumps, and rubella (MMR) vaccine, and the measles, mumps, rubella, and varicella vaccine. Antibodies in immune globulin products may interfere with patient responses to live vaccines because the continued presence of high concentrations of passively acquired antibody may interfere with an active antibody response. According to the manufacturer, delay live virus vaccinations until approximately 3 months after varicella-zoster immune globulin administration. However, guidelines recommend waiting at least 5 months after receipt of the varicella-zoster immune globulin before administering either the measle or varicella vaccines. Conversely, if either measles or varicella vaccines are given, 2 weeks are recommended to elapse before varicella-zoster immune globulin administration. The yellow fever vaccine, rotavirus vaccine, oral Ty21a typhoid vaccine, live attenuated influenza vaccine, and the zoster vaccine may be administered at any time in relation to receipt of an antibody-containing product. Inform the immunizing physician about recent therapy with immune globulin products prior to vaccination.
Thrombotic events may occur during or after treatment with immune globulin products. Cautious use of varicella-zoster immune globulin is warranted in patients with a history of cardiac disease or thromboembolic disease. Patients at risk for thrombotic events are geriatric patients, those with a history of atherosclerosis (coronary artery disease), multiple cardiovascular risk factors, impaired cardiac output (heart failure), coagulation disorders, prolonged periods of immobilization, obesity, diabetes mellitus, acquired or inherited thrombophilic disorder, a history of vascular disease, a history of a previous thrombotic or thromboembolic event, and/or known or suspected hyperviscosity. Assessment of baseline blood viscosity may be warranted for patients at risk for hyperviscosity such as those with cryoglobulins, fasting chylomicronemia, hypertriglyceridemia, or monoclonal gammopathies.
General Information on Prophylaxis against Varicella using Varicella-Zoster Immune Globulin:
Both healthy and immunocompromised patients who have verified positive histories of varicella (except for bone-marrow transplant recipients) may be considered immune. Consider persons who receive bone marrow transplants non-immune regardless of the previous history of varicella disease or varicella vaccination in themselves or in their donors. However, consider bone marrow transplant recipients in whom varicella or herpes zoster develops after transplantation immune. According to the Centers for Disease Control (CDC), the patient groups listed below are at risk for severe disease and complications and should receive varicella-zoster immune globulin if exposed to varicella or herpes zoster. The FDA-approved product labeling also includes infants less than 1 year of age as a high-risk group. Of note, patients receiving monthly infusions of high-dose intravenous immune globulin (IVIG greater than or equal to 400 mg/kg) are likely to be protected and probably do not require varicella-zoster immune globulin if the last dose of IVIG was administered 3 weeks or less before exposure.
-pregnant women without evidence of immunity.
-immunocompromised patients without evidence of immunity; immunocompromised persons include those with primary and acquired immune-deficiency disorders, neoplastic diseases, or are receiving immunosuppressives such as the equivalent of greater than or equal to 2 mg/kg or 20 mg/day of prednisone. Varicella-zoster immune globulin is NOT indicated for persons who received 2 doses of varicella vaccine and became immunocompromised as a result of disease or treatment later in life.
-premature neonates born at less than 28 weeks gestation or who weigh less than or equal to 1,000 grams at birth exposed any time during the period of hospitalization for prematurity regardless of maternal immunity.
-premature neonates born at 28 weeks or later gestation exposed any time during the period of hospitalization for prematurity and whose mothers do not have evidence of immunity.
-neonates whose mothers have signs and symptoms of varicella from 5 days before to 2 days after delivery.
For post-exposure varicella (chickenpox) infection prophylaxis:
NOTE: Varicella-zoster immune globulin has an orphan drug status for the passive immunization of exposed, susceptible individuals who are at risk of complications from varicella.
Intramuscular dosage:
Adults: 625 International Units/dose (5 vials) IM for adults weighing more than 40 kg. Administer as soon as possible (preferably within 96 hours), but up to 10 days after exposure. Consider a second dose if additional varicella exposures occur more than 3 weeks after initial administration.
Children and Adolescent weighing 40.1 kg and more: 625 International Units/dose (5 vials) IM. Administer as soon as possible (preferably within 96 hours), but up to 10 days after exposure. Consider a second dose if additional varicella exposures occur more than 3 weeks after initial administration.
Children and Adolescents weighing 30.1 to 40 kg: 500 International Units/dose (4 vials) IM. Administer as soon as possible (preferably within 96 hours), but up to 10 days after exposure. Consider a second dose if additional varicella exposures occur more than 3 weeks after initial administration.
Children and Adolescents weighing 20.1 to 30 kg: 375 International Units/dose (3 vials) IM. Administer as soon as possible (preferably within 96 hours), but up to 10 days after exposure. Consider a second dose if additional varicella exposures occur more than 3 weeks after initial administration.
Infants and Children weighing 10.1 to 20 kg: 250 International Units/dose (2 vials) IM. Administer as soon as possible (preferably within 96 hours), but up to 10 days after exposure. Consider a second dose if additional varicella exposures occur more than 3 weeks after initial administration.
Neonates, Infants, and Children weighing 2.1 to 10 kg: 125 International Units/dose (1 vial) IM. Administer as soon as possible (preferably within 96 hours), but up to 10 days after exposure. Consider a second dose if additional varicella exposures occur more than 3 weeks after initial administration.
Neonates and Infants weighing 2 kg and less: 62.5 International Units/dose (one-half vial) IM. Administer as soon as possible (preferably within 96 hours), but up to 10 days after exposure. Consider a second dose if additional varicella exposures occur more than 3 weeks after initial administration.
Maximum Dosage Limits:
-Adults
625 International units/dose IM.
-Geriatric
625 International units/dose IM.
-Adolescents
40.1 kg and more: 625 International units/dose IM.
30.1 to 40 kg: 500 International units/dose IM.
20.1 to 30 kg: 375 International units/dose IM.
-Children
40.1 kg and more: 625 International units/dose IM.
30.1 to 40 kg: 500 International units/dose IM.
20.1 to 30 kg: 375 International units/dose IM.
10.1 to 20 kg: 250 International units/dose IM.
2.1 to 10 kg: 125 International units/dose IM.
-Infants
10.1 to 20 kg: 250 International units/dose IM.
2.1 to 10 kg: 125 International units/dose IM.
-Neonates
2.1 to 10 kg: 125 International units/dose IM.
2 kg and less: 62.5 International units/dose IM.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Efficacy of live attenuated virus vaccines such as measles/mumps/rubella Vaccines, MMR; rotavirus vaccine; and varicella virus vaccine live may be impaired by varicella-zoster immune globulin administration; revaccination may be necessary. As the passive transfer of antibodies may impair the efficacy of live attenuated virus vaccines, defer vaccination with live virus vaccines until approximately 3 months after varicella-zoster immune globulin administration. Inform the immunizing physician of recent therapy with varicella-zoster immune globulin, so that appropriate measures can be taken.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Efficacy of live attenuated virus vaccines such as measles/mumps/rubella Vaccines, MMR; rotavirus vaccine; and varicella virus vaccine live may be impaired by varicella-zoster immune globulin administration; revaccination may be necessary. As the passive transfer of antibodies may impair the efficacy of live attenuated virus vaccines, defer vaccination with live virus vaccines until approximately 3 months after varicella-zoster immune globulin administration. Inform the immunizing physician of recent therapy with varicella-zoster immune globulin, so that appropriate measures can be taken.
Rotavirus Vaccine: (Major) Defer vaccination with live virus vaccines until approximately 3 months after Varicella Zoster immune globulin administration. Inform the immunizing physician of recent therapy with varicella-zoster immune globulin, so that appropriate measures can be taken. The efficacy of live attenuated virus vaccines such as Rotavirus Vaccine may be impaired by Varicella Zoster immune globulin administration; revaccination may be necessary. The passive transfer of antibodies from the immune globulin may impair the efficacy of live attenuated virus vaccines.
Varicella-zoster immune globulin is a preparation of purified human immune globulin G (IgG) containing antibodies to varicella-zoster virus (anti-VZV) and, thus, provides passive immunization for non-immune individuals exposed to the varicella-zoster virus. The product may reduce the severity of varicella infections. No convincing evidence exists that the product reduces the incidence of chickenpox infection after exposure to the virus or that established varicella infections can be modified with the product. Of note, varicella-zoster immune globulin might extend the incubation period of the virus from 10 to 21 days to 28 days or more.
Varicella-zoster immune globulin is administered via intramuscular (IM) injection. Antibody protection against the varicella zoster virus generally lasts for 3 weeks after product administration in both children and adults. The exact fate of human immunoglobulin products is not well defined, but the mean serum half-life is 26.2 +/- 4.6 days after receipt of 12.5 International units/kg IM.
-Route-Specific Pharmacokinetics
Intramuscular Route
The mean peak of varicella antibodies occurred 4.5 +/- 2.8 days after receipt of 12.5 International units/kg IM. Administer varicella-zoster immune globulin as soon as possible after varicella zoster virus exposure.