Varizig

Serious side effects have been reported with Varizig including the following:

Thrombotic Events. Varizig can increase your risk for developing blood clots, especially if you have a history of atherosclerosis (a disease where plaque builds up in your arteries), heart problems, or a disorder in which your body ability to control blood clotting is impaired. 

Hypersensitivity. Severe allergic reactions can occur with Varizig. Tell your healthcare provider about any signs or symptoms of hypersensitivity, which include the following:

• chest pain
• swelling of the face, eyes, lips, tongue, arms, or legs
• difficulty breathing or swallowing
• rash

Transmissible Infectious Agents. Since Varizig is made from human plasma, it may contain infectious agents that could cause disease. Certain measures are taken to reduce this risk, but the possbility still exists that Varizig can transmit disease.

You should not receive Varizig if you:

• are allergic to Varizig or to any of its ingredients
• have had an allergic reaction to another human immune globulin preparation
• have an IgA-deficiency

The dose of Varizig your doctor recommends will be based on your weight. The minimum dose for infants who weight less than 2 kilograms is 62.5 International Units (IU). The maximum dose, which should be given to all patients who weigh more than 40 kilograms, is 625 International Units (IU).

Depending on your dose and size, you may receive the dose in 2 or more injection sites.

Other drugs may interact with varicella zoster immune globulin, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Contraindications

• History of anaphylactic or severe systemic (hypersensitivity) reactions to any human immune globulin preparation.1

• IgA deficiency with antibodies against IgA and history of hypersensitivity reaction.1 (See IgA Deficiency under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Severe hypersensitivity reactions may occur.1

Administer in a setting with appropriate equipment, medication, and personnel trained in management of hypersensitivity, anaphylaxis, and shock.1

If hypersensitivity reaction occurs, discontinue immediately and initiate appropriate therapy as indicated.1

Individuals with IgA deficiency and antibodies to IgA are at greater risk of severe hypersensitivity and anaphylactic reactions.1

Varizig contains trace amounts (<40 mcg/mL) of IgA.1 As little as 15 mcg of IgA per mL of blood product may elicit an anaphylactic reaction in individuals with IgA deficiency.5

Thrombotic Events

Thrombotic events may occur during or following treatment with immune globulin preparations.1

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

Coagulation Disorders

Because VZIG is administered IM (see Administration under Dosage and Administration), do not use in individuals with severe thrombocytopenia or any coagulation disorder that contraindicates IM injection unless expected benefits outweigh potential risks.1

Risk of Transmissible Infectious Agents in Plasma-derived Preparations

Because VZIG is prepared from pooled human plasma, it is a potential vehicle for transmission of infectious agents, including the causative agents of viral hepatitis and HIV infection, and theoretically may carry a risk of transmitting the causative agent of Creutzfeldt-Jakob disease (CJD) or variant CJD (vCJD).1 20

Improved donor screening, viral-inactivation procedures (e.g., solvent/detergent treatment), and/or filtration procedures have reduced, but not completely eliminated, risk of pathogen transmission with plasma-derived preparations.1

Manufacturing process for VZIG includes a solvent/detergent inactivation process and a filtering procedure to remove both enveloped and non-enveloped viruses.1

Because no purification method has been shown to be totally effective in removing risk of viral infectivity from plasma-derived preparations and because new blood-borne viruses or other disease agents may emerge that may not be inactivated by the manufacturing process or chemical (solvent/detergent) treatment procedures currently used, administer VZIG only when a benefit is expected.1

Report any infection believed to have been transmitted by VZIG to manufacturer at 800-768-2304.1

Individuals with Altered Immunocompetence

May be administered to individuals immunosuppressed as the result of disease or immunosuppressive therapy.27 143 144

Immunocompromised individuals without evidence of varicella immunity are at high risk of severe or disseminated varicella and generally should receive VZIG for postexposure prophylaxis.27 100

Recommended for postexposure prophylaxis in individuals without evidence of varicella immunity who are immunosuppressed because they are receiving corticosteroid therapy in a dosage ≥2 mg/kg daily or ≥20 mg daily (prednisone or equivalent).27

Not indicated for individuals who previously received age-appropriate varicella vaccination and subsequently became immunocompromised as the result of disease or immunosuppressive therapy later in life.27

Consider bone marrow transplant recipients susceptible to varicella regardless of previous history of varicella or varicella vaccination in themselves or in their donors.27 However, those who develop varicella or herpes zoster after transplantation should be considered immune to varicella.27

Varicella developed in some immunocompromised individuals who received VZIG postexposure prophylaxis.1 Varicella pneumonitis not reported in these patients; some had received concomitant acyclovir.1

Limitations of Effectiveness

May prevent or modify varicella if given within 10 days of exposure.46 Limited data suggest incidence of varicella is comparable when VZIG is given within 4 days or >4 days (up to 10 days) after VZV exposure; attenuation of varicella might be achieved when given up to 10 days after exposure.46

Immune globulins not effective once disease is established.100

Use of VZIG for postexposure prophylaxis in pregnant women exposed to VZV may prevent or reduce severity of varicella in the woman, but such prophylaxis in the mother does not prevent fetal infection.27 100

VZIG may not prevent varicella and may prolong the incubation period from 10–21 days to ≥28 days.27 100 Closely observe patient for signs and symptoms of varicella for 28 days after exposure; immediately initiate antiviral therapy if signs or symptoms of varicella occur.27

VZIG provides only short-term passive immunity against VZV (see Duration of Immunity under Cautions).27 100 Unless varicella vaccine is contraindicated, administer active immunization with the vaccine ≥5 months after VZIG.27 100 (See Specific Drugs and Laboratory Tests under Interactions.) Varicella vaccine not needed if patient developed varicella despite administration of VZIG.27 100

Duration of Immunity

Duration of protection against VZV following administration of VZIG unknown.27 Single VZIG dose provides passive immunity to VZV that should last about 3 weeks.27

In susceptible individuals at high risk who cannot receive varicella vaccine, consider a second VZIG dose if another exposure to VZV occurs ≥3 weeks after first VZIG dose.27

Improper Storage and Handling

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

Do not administer VZIG 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 VZIG is usable.36

Serologic Testing

After VZIG dose, passively acquired anti-VZV antibodies are present in serum and may interfere with some serologic tests, including tests used to determine immunity to VZV.5 (See Specific Drugs and Laboratory Tests under Interactions.)

Because some patients who receive VZIG for postexposure prophylaxis may have asymptomatic varicella infection, some experts recommend follow-up serologic testing ≥2 months after VZIG to determine immune status in case a subsequent exposure occurs.100 Other experts suggest that serologic tests are unreliable in immunocompromised individuals and asymptomatic infection in such individuals may not confer lasting protection; these experts recommend use of VZIG in immunocompromised individuals after subsequent VZV exposure, regardless of serologic test results.100

When serologic testing is performed to determine immune status after natural varicella, positive antibody results are reliable but negative antibody results may not be reliable.100

Specific Populations

Category C.1

Use during pregnancy only when clearly needed.1 (See Uses.)

ACIP states there are no known risks for the fetus from use of immune globulin preparations for passive immunization in pregnant women.36

Not known whether VZIG is distributed into milk; use with caution.1

Safety and efficacy established for postexposure prophylaxis of varicella in pediatric patients, including preterm neonates and infants, term neonates and infants, children, and adolescents.1

Clinical studies did not include sufficient numbers of individuals ≥65 years of age to determine whether geriatric individuals respond differently than younger adults.1

Use with caution in individuals ≥65 years of age who are at increased risk of thrombotic events.1 (See Thrombotic Events under Cautions.)

Administer only by IM injection; do not exceed recommended dosage.1

Common Adverse Effects

Pain at injection site, headache, chills, rash, nausea.1

Live Vaccines

Antibodies present in immune globulin preparations, including VZIG, may interfere with immune responses to some live virus vaccines, including measles, mumps, and rubella virus vaccine live (MMR) and varicella virus vaccine live (VAR);1 27 36 no evidence that immune globulin preparations interfere with immune responses to influenza virus vaccine live intranasal, yellow fever virus vaccine live, or typhoid vaccine live oral.36 (See Specific Drugs and Laboratory Tests under Interactions.)

Inactivated Vaccines and Toxoids

Immune globulin preparations not expected to have clinically important effects on immune responses to inactivated vaccines or toxoids; therefore, 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 VZIG.36 Neonates who received VZIG at birth can receive age-appropriate inactivated vaccines according to the usually recommended childhood immunization schedule.100

Specific Drugs and Laboratory Tests

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

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

• If you have an allergy to varicella zoster immune globulin or any other part of VariZIG (varicella-zoster immune globulin (human)).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have IgA deficiency.
• If you have any of these health problems: Bleeding problems or low platelet count.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take VariZIG with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache.
• Pain where the shot was given.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Varizig® [Varicella Zoster Immune Globulin (Human)] is indicated for post-exposure prophylaxis of varicella in high risk individuals. High risk groups include:

• immunocompromised children and adults,
• newborns of mothers with varicella shortly before or after delivery,
• premature infants,
• neonates and infants less than one year of age,
• adults without evidence of immunity,
• pregnant women.

Varizig administration is intended to reduce the severity of varicella. Administer Varizig as soon as possible following varicella zoster virus (VZV) exposure, ideally within 96 hours for greatest effectiveness.

• There is no convincing evidence that Varizig reduces the incidence of chickenpox infection after exposure to VZV.
• There is no convincing evidence that established infections with VZV can be modified by Varizig administration.
• There is no indication for the prophylactic use of Varizig in immunodeficient children or adults when there is a past history of varicella, unless the patient is undergoing bone marrow transplantation.

Pregnancy

Pregnancy category C. Animal reproduction studies have not been conducted with Varizig. It also is not known whether Varizig can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Varizig should be given to a pregnant woman only if clearly needed.

The safety and effectiveness of Varizig have been evaluated for post-exposure prophylaxis in clinical trials in 166 pregnant women [see 6 ADVERSE REACTIONS and 14 CLINICAL STUDIES].

Nursing Mothers

It is not known whether Varizig is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Varizig is administered to a nursing mother.

Pediatric Use

The dosing recommendations in the treatment of pediatric patients are by body weight [see 2 DOSAGE AND ADMINISTRATION].

The safety and effectiveness of Varizig have been evaluated for post-exposure prophylaxis in the Varizig expanded access clinical trial in 374 pediatric patients, including immunocompromised pediatric patients:

• 94 preterm newborns and infants,
• 53 term newborns,
• 45 infants and toddlers,
• 176 children and,
• 43 adolescents.

In the EAP, follow up data were available for 110 Varizig treatments in infants (including newborns, pre-term infants, and infants <1 year old). Three severe infections were reported, all three with pox count >100, one of which also had pneumonia and another one also developed probable varicella encephalitis.

Geriatric Use

Clinical studies of Varizig administered intramuscularly for post-exposure prophylaxis did not include sufficient numbers of geriatric subjects (aged 65 and over) to determine whether they respond differently from younger subjects.

Use caution when administering Varizig to patients age 65 and over who are judged to be at increased risk of thrombotic events [see 5 WARNINGS AND PRECAUTIONS]. Do not exceed recommended doses and administer Varizig intramuscularly only.

Immunocompromised Patients

In the EAP, both adult (n=37) and pediatric immunocompromised subjects (n=235) were treated. Twelve immunocompromised subjects developed clinical varicella and none developed varicella pneumonitis; however at least five are reported to have received concomitant acyclovir and due to incomplete reporting, it is not known if others also received acyclovir.

How Supplied

NDC 70504-0126-2: Varizig [Varicella Zoster Immune Globulin (Human)] is supplied as a sterile liquid approximately 125 IU of anti-VZV in a 3 mL type 1 glass tubing vial fitted with a 13 mm rubber stopper and a 13 mm flip-off seal, and a package insert.

Storage and Handling

Store Varizig at 2 to 8°C (36 to 46°F). Do not freeze. Do not use after expiration date.