VARIZIG Solution for injection Ref.[27439] Active ingredients: Human varicela zoster immunoglobulin

5.1 Thrombotic Events

Thrombotic events may occur during or following treatment with immune globulin products (1,2,3). 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.

5.2 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.

5.3 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 reactions [see 4 CONTRAINDICATIONS].

5.4 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 [see11 DESCRIPTION]. 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 Cangene Corporation at 1-800-768-2304. Discuss the risks and benefits of this product with the patient before administering it to the patient [see 17 PATIENT COUNSELING INFORMATION].

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 ≥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%.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Six hundred and one (n=601) high risk individuals received VARIZIG intramuscularly in two clinical trials which included pregnant women, infants and immunocompromised pediatric and adult patients. The highest incidence of adverse reactions occurred in pregnant women (n=166), including injection site pain (7%), rash (including terms pruritus, rash, rash erythematous, and rash vesicular) (4%), headache (3%), and fatigue (2%). All other adverse reactions occurred in 1% or less of clinical trial subjects within each high risk group. A single incidence of serum sickness (approximately one in 600 patients treated with VARIZIG) was observed in an immunocompromised adolescent patient.

There were eight reported adverse events associated with the coagulation system including, deep vein thrombosis (n=1), disseminated intravascular coagulation (n=1), intracranial hemorrhage (n=2), coagulopathy (n=2), intraventricular hemorrhage (n=1), and pulmonary hemorrhage (n=1) in 621 subjects in the open-label, Expanded Access Protocol (EAP); the study was not designed to differentiate between adverse events attributed to the underlying medical condition and adverse reactions to VARIZIG.

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 [see 17 PATIENT COUNSELING INFORMATION].

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].

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.

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.

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.

8.6 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.