VARIZIG® [Varicella Zoster Immune Globulin (Human)]

VARIZIG® [Varicella Zoster Immune Globulin (Human)]

VARIZIG [Varicella Zoster Immune Globulin (Human)]

VARIZIG [Varicella Zoster Immune Globulin (Human)] is a solvent/detergent-treated sterile liquid preparation of purified human immune globulin G (IgG) containing antibodies to varicella zoster virus (anti-VZV). VZV is the causative agent of chickenpox. VARIZIG is prepared from plasma donated by healthy, screened donors with high titers of antibodies to VZV, which is purified by an anion-exchange column chromatography manufacturing method. This donor selection process includes donors with high anti-VZV titers due to recent natural infection by VZV, or due to recurrent zoster infection (shingles).

VARIZIG is intended for single use and should be administered intramuscularly

The product potency is expressed in international units by comparison to the World Health Organization (WHO) international reference preparation for anti-VZV immune globulin. Each vial contains 125 international units of anti-VZV. VARIZIG is formulated with 10% maltose and 0.03% polysorbate 80. VARIZIG has a pH of 5.0 – 6.5 and contains no preservative.

The presence of anti-Protein S antibodies has been reported to arise transiently in patients after VZV infection. Low levels of anti-Protein S antibodies have been reported in VARIZIG.

The manufacturing process contains two steps implemented specifically for virus clearance. The solvent/detergent step (using tri-n-butyl phosphate and Triton® X-100) is effective in the inactivation of enveloped viruses, such as HBV, HCV and HIV-1. Virus filtration, using a Planova® 20N virus filter, is effective for the removal of viruses based on their size, including some non-enveloped viruses. These two viral clearance steps are designed to increase product safety by reducing the risk of transmission of enveloped and non-enveloped viruses. In addition to these two specific steps, the process step of anion-exchange chromatography was identified as contributing to the overall viral clearance capacity for small non-enveloped viruses.

INDICATIONS AND USAGE

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

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  • 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.

Mechanism of Action

VARIZIG provides passive immunization for non-immune individuals exposed to VZV, reducing the severity of varicella infections.

DOSAGE AND ADMINISTRATION

Preparation and Handling

Each vial of VARIZIG contains a minimum potency of 125 international units in 1.2 mL.

  • Bring VARIZIG to room temperature prior to use.
  • Inspect VARIZIG for particulate matter and discoloration prior to administration. Do not use if the solution is cloudy or contains particulates.
  • VARIZIG is for single use only. Discard any unused portion.

Dosing of VARIZIG is based on body weight.

The minimum dose is 62.5 international units for small infants under two kilograms body weight; the maximum dose of 625 international units should be administered for all patients greater than 40 kilograms in weight.

Consider a second full dose of VARIZIG for high-risk patients who have additional exposures to varicella greater than three weeks after initial VARIZIG administration.

Administration

For intramuscular use only.

Divide the intramuscular dose and administer in two or more injection sites, depending on patient size. Do not exceed 3 milliliters per injection site.

Inject into the deltoid muscle or the anterolateral aspects of the upper thigh. Due to the risk of sciatic nerve injury, do not use the gluteal region as a routine injection site. If the gluteal region is used, only use the upper, outer quadrant.

To prevent the transmission of infectious agents from one person to another, use a new disposable sterile syringe and needle for each individual patient.

CONTRAINDICATIONS

  • Individuals known to have anaphylactic or severe systemic (hypersensitivity) reactions to human immune globulin preparations should not receive VARIZIG.
  • IgA-deficient patients with antibodies against IgA and a history of hypersensitivity may have an anaphylactoid reaction.
  • VARIZIG contains less than 40 micrograms per milliliter of IgA.

WARNINGS AND PRECAUTIONS

Thrombotic Events: Thrombotic events may occur during or following treatment with immune globulin products. Patients at risk include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, coagulation disorders, prolonged periods of immobilization, and/or known/suspected hyperviscosity. Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies.

Coagulation Disorders: Administer VARIZIG intramuscularly only. In patients who have severe thrombocytopenia or any coagulation disorder that would contraindicate intramuscular injections, only administer VARIZIG if the expected benefits outweigh the potential risks.

Hypersensitivity: Severe hypersensitivity reactions may occur following VARIZIG administration. Administer VARIZIG in a setting with appropriate equipment, medication and personnel trained in the management of hypersensitivity, anaphylaxis and shock. In the case of hypersensitivity, discontinue administration of VARIZIG immediately and provide appropriate treatment.

VARIZIG contains trace amounts of IgA (less than 40 micrograms per milliliter). Patients with known antibodies to IgA have a greater risk of severe hypersensitivity and anaphylactic reactions. VARIZIG is contraindicated in IgA deficient patients with antibodies against IgA and history of hypersensitivity

Transmissible Infectious Agents: Because VARIZIG is made from human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The plasma donors are screened for the presence of certain infectious agents and the manufacturing process for VARIZIG includes measures to inactivate and remove certain viruses

Despite these measures, products derived from human plasma can still potentially transmit diseases. No cases of transmission of viral diseases, vCJD or CJD have been associated with the use of VARIZIG.

Report all infections thought by a physician to have been transmitted by VARIZIG to Saol Therapeutics at 1-833-644-4216. Discuss the risks and benefits of this product with the patient before administering it to the patient

ADVERSE REACTIONS

The most serious adverse drug reactions observed in clinical trials for all subjects and patients (n=601) include pyrexia, nausea, and vomiting.

The most common adverse drug reactions (reported by greater than or equal to 1% of subjects) observed in clinical trials for all subjects and patients (n=601) are the following:

  • injection site pain (3%),
  • headache (2%),
  • rash (including terms pruritus, rash, rash erythematous, rash vesicular and urticaria) (1%),
  • fatigue (1%),
  • chills (1%),
  • nausea (1%).

All other adverse drug reactions occurred in less than 1%.

To report SUSPECTED ADVERSE REACTIONS, contact Saol Therapeutics at 1-833-644-4216 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

DRUG INTERACTIONS

The passive transfer of antibodies with immune globulin administration may impair the efficacy of live attenuated virus vaccines such as measles, rubella, mumps and varicella. Defer vaccination with live virus vaccines until approximately three months after VARIZIG administration. Inform the immunizing physician of recent therapy with VARIZIG so that appropriate measures can be taken

Efficacy of live attenuated virus vaccines may be impaired by immune globulin administration; revaccination may be necessary

USE IN SPECIFIC POPULATIONS

Pregnancy: 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.

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The safety and effectiveness of VARIZIG have been evaluated for post-exposure prophylaxis in clinical trials in 166 pregnant women

Lactation: 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

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. 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.

OVERDOSAGE

Manifestations of an overdose of VARIZIG administered intramuscularly are expected to be pain and tenderness at the injection site.

How Supplied

NDC 70257-126-51: VARIZIG [Varicella Zoster Immune Globulin (Human)] is supplied as a sterile liquid approximately 125 international units of anti-VZV in a glass tubing vial 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.

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