Vaccinia Immune Globulin (Intravenous)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, solution [preservative free; solvent-detergent treated]:

CNJ-016: ≥50,000 units/15 mL (15 mL) [contains maltose 10% and polysorbate 80 0.03%]

Pharmacology

Mechanism of Action

Antibodies obtained from pooled human plasma of individuals immunized with the smallpox vaccine provide passive immunity

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: 6.6 L

Time to Peak

Plasma: 1.8 to 2.6 hours

Half-Life Elimination

30 days (range: 13 to 67 days)

Use: Labeled Indications

Vaccinia conditions: Treatment and/or modification of the following conditions:

- Aberrant infections induced by vaccinia virus that include its accidental implantation in eyes (except in cases of isolated keratitis), mouth, or other areas where vaccinia infection would constitute a special hazard.

- Eczema vaccinatum

- Progressive vaccinia

- Severe generalized vaccinia

- Vaccinia infections in individuals who have skin conditions such as burns, impetigo, varicella-zoster, or poison ivy; or in individuals who have eczematous skin lesions because of either the activity or extensiveness of such lesions

The Advisory Committee on Immunization Practices (ACIP) recommends the following (CDC 2009; CDC [Rotz 2001]; CDC [Wharton 2003]):

Use is recommended for:

- Inadvertent inoculation (considering severity, toxicity of affected person, and pain)

- Eczema vaccinatum

- Generalized vaccinia (severe form or if underlying illness is present)

- Progressive vaccinia

Use may be considered for:

- Severe ocular complications except isolated keratitis

Use is not recommended for:

- Inadvertent inoculation that is not severe

- Mild or limited generalized vaccinia

- Nonspecific rashes, erythema multiforme, or Stevens-Johnson syndrome

- Postvaccinial encephalitis or encephalomyelitis

Contraindications

Isolated vaccinia keratitis; history of anaphylaxis or prior severe systemic reaction associated with the parenteral administration of VIGIV or other human immune globulin preparations; IgA-deficient patients with antibodies against IgA and a history of IgA hypersensitivity

Dosage and Administration

Dosing: Adult

Vaccinia conditions: IV: 6,000 units/kg as soon as symptoms appear; may repeat dose based on severity of symptoms and response to treatment (specific data are lacking); 9,000 units/kg may be considered if patient does not respond to initial dose. Single doses up to 24,000 unit/kg were tolerated in healthy volunteers. Note: Maximum dose for patients with risk factors for thrombosis: 12,000 units/kg/day.

Dosing: Pediatric

Vaccinia treatment/modification: Adolescents ≥16 years: Refer to adult dosing.

Reconstitution

Do not shake; avoid foaming. Do not administer if solution is turbid. Remove the entire contents of the vial to obtain the labeled dosage; if partial vials are required for the dosage calculation, the entire contents of the vial should be withdrawn to ensure accurate calculation of the dosage requirement. Do not dilute more than 1:2 (v/v). Infusion should begin within 4 hours after entering vial.

Administration

IV: For IV infusion only. If dedicated line is not available, flush with NS prior to administration of VIGIV. Do not exceed recommended rates of infusion.

Patients ≥50 kg: Infuse at ≤2 mL/minute; Patients <50 kg: Infuse at ≤0.04 mL/kg/minute. Maximum rate of infusion: 4 mL/minute. Decrease rate of infusion in patients who develop minor adverse reactions (eg, flushing) and in patients with risk factors for thrombosis/thromboembolism and/or renal insufficiency.

Storage

Store at 2°C to 8°C (36°F to 46°F); may also be frozen (≤15°C [≤5°F]). If frozen, use within 60 days of thawing at 2°C to 8°C (36°F to 46°F).

Drug Interactions

Vaccines (Live): Immune Globulins may diminish the therapeutic effect of Vaccines (Live). Management: Consult full interaction monograph for dose interval recommendations. This interaction does not apply to oral Ty21a typhoid vaccine or others listed as exceptions. Exceptions: Adenovirus (Types 4, 7) Vaccine; Cholera Vaccine; Influenza Virus Vaccine (Live/Attenuated); Poliovirus Vaccine (Live/Bivalent/Oral); Poliovirus Vaccine (Live/Trivalent/Oral); Rotavirus Vaccine; Yellow Fever Vaccine; Zoster Vaccine (Live/Attenuated). Consider therapy modification

Test Interactions

[US Boxed Warning]: Maltose in vaccinia immune globulin can interact with glucose monitoring systems and test strips. CNJ-016® contains maltose. Falsely-elevated blood glucose levels may occur when glucose monitoring devices and test strips utilizing the glucose dehydrogenase pyrroloquinolinequinone (GDH-PQQ) based methods are used. Glucose monitoring devices and test strips which utilize the glucose-specific method are recommended.

Positive direct Coombs' test due to transitory increase of antibodies.

Adverse Reactions

Frequency not defined. Actual frequency varies by dose and rate of infusion.

Cardiovascular: Peripheral edema

Central nervous system: Dizziness, fatigue, feeling hot, headache, pain, paresthesia, rigors, sensation of cold

Dermatologic: Diaphoresis, erythema, pallor

Gastrointestinal: Decreased appetite, nausea, vomiting

Local: Injection site reaction

Neuromuscular & skeletal: Back pain, muscle spasm, tremor, weakness

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Abdominal pain, acute intravascular hemolysis, acute renal failure, altered blood pressure, anaphylaxis, apnea, acute respiratory distress, arthralgia, aseptic meningitis, bronchospasm, bullous rash, chills, circulatory shock, coma, cyanosis, diarrhea, dyspnea, epidermolysis, erythema multiforme, flushing, hemolysis, hepatic insufficiency, hypersensitivity reaction, hypoxemia, hypotension, leukopenia, loss of consciousness, malaise, myalgia, pancytopenia, positive direct Coombs test, proximal tubular nephropathy, pulmonary edema, renal disease (osmotic nephropathy), renal insufficiency, seizure, Stevens-Johnson syndrome, syncope, tachycardia, thrombocytopenia, thromboembolism, transfusion-related acute lung injury (TRALI), urticaria, wheezing

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis/hypersensitivity reactions: Hypersensitivity and anaphylactic reactions can occur; discontinue therapy and institute immediate treatment (including epinephrine 1 mg/mL). Contains trace amounts of IgA; use caution in IgA-deficient patients; contraindicated in IgA-deficient patients with antibodies against IgA and a history of IgA hypersensitivity.
• Aseptic meningitis: Aseptic meningitis syndrome (AMS) has been reported with intravenous immune globulin administration and usually begins within several hours to 2 days following treatment; may occur more frequently with high total doses (2 g/kg). Discontinuation of treatment has resulted in remission of AMS within several days without sequelae.
• Hemolysis: Intravenous immune globulin has been associated with antiglobulin hemolysis; monitor for signs of hemolytic anemia. Risk factors for hemolysis include high doses given either as a single administration or divided over several days, underlying associated inflammatory conditions (eg, elevated C-reactive protein or erythrocyte sedimentation rate), and non-O blood group. If signs/symptoms of hemolysis are present, perform appropriate laboratory testing for confirmation.
• Infusion reactions: Adverse reactions may be related to rate of infusion; closely monitor patient during and immediately following infusion. Closely follow the recommended infusion rates.
• Pulmonary edema: Monitor for transfusion-related acute lung injury (TRALI); noncardiogenic pulmonary edema has been reported with intravenous immune globulin use. TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, and fever in the presence of normal left ventricular function. Usually occurs within 1 to 6 hours after infusion. If TRALI is suspected, perform appropriate tests for the presence of antineutrophil antibodies in both the product and patient’s serum.
• Renal effects: Renal dysfunction, acute renal failure, osmotic nephropathy, proximal tubular nephropathy, and fatalities may occur; usually occurs in patients receiving total doses containing ≥400 mg/kg of sucrose (VIGIV does not contain sucrose).
• Thrombotic events: Thrombotic events have been reported with administration of intravenous immune globulin; use with caution in patients with a history of cardiovascular risk factors or arterial or venous thrombosis, advanced age, estrogen use, indwelling central venous catheters, impaired cardiac output, hypercoagulable disorders, prolonged periods of immobilization, and/or known or suspected hyperviscosity. Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia/markedly high triglycerides, or monoclonal gammopathies. For patients at risk for of thrombosis, administer at the minimum dose (do not exceed maximum dose), minimum concentration available, and minimum infusion rate practicable, ensure adequate hydration before administration.

Disease-related concerns:

• Hypovolemia: Patients should not be volume depleted prior to therapy.
• Postvaccinial encephalitis: Not effective for use in postvaccinial encephalitis.
• Renal impairment: Use with caution in patients with preexisting renal insufficiency and in patients at risk of developing renal insufficiency (eg, diabetes mellitus, patients >65 years, volume depletion, paraproteinemia, sepsis, patients receiving known nephrotoxic drugs); administer at the minimum rate of infusion (do not exceed the recommended infusion rate). Ensure patients are not volume depleted prior to VIGIV infusion. Monitor renal function and urine output closely. If renal function deteriorates, consider discontinuing therapy.
• Vaccinia keratitis: Exercise caution when using VIGIV in the treatment of patients with complications due to vaccinia vaccination that include concomitant vaccinia keratitis, because a single study in rabbits demonstrated increased corneal scarring upon intramuscular vaccinia immune globulin administration in vaccinia keratitis.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in the elderly; may be at increased risk for renal dysfunction/failure and thromboembolic events.

Dosage form specific issues:

• Human plasma: Product of human plasma; may potentially contain infectious agents which could transmit disease. Screening of donors, as well as testing and/or inactivation or removal of certain viruses, reduces the risk. Infections thought to be transmitted by this product should be reported to the manufacturer.
• Maltose: Product may contain maltose. [US Boxed Warning]: Maltose in IGIV products may give falsely high blood glucose levels in certain types of glucose tests systems. Falsely-elevated blood glucose readings may result in unnecessary insulin use and life-threatening hypoglycemia; cases of true hypoglycemia may go untreated if the hypoglycemic state is masked by falsely elevated glucose readings. Glucose specific monitoring systems and test strips are recommended.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.

Other warnings/precautions:

• Appropriate use: Vaccinia immune globulin is currently not recommended for use in persons with contraindications to smallpox vaccine; inadvertent exposure to smallpox vaccine in high-risk populations should be reported to the CDC so that standardized treatment may be provided. VIGIV is not considered to be effective in the treatment of postvaccinial encephalitis.

Monitoring Parameters

Renal function (including BUN, serum creatinine) and urine output (before initial infusion and at clinically appropriate intervals). Baseline assessment of blood viscosity in patients at risk for hyperviscosity. During infusion, monitor patient for signs of infusion-related reactions, including (but not limited to) flushing, fever, chills, respiratory distress, blood pressure or heart rate changes; transfusion-related lung injury (typically 1 to 6 hours after infusion) and signs/symptoms of hemolysis (prior to infusion and ~36 to 96 hours postinfusion).

Pregnancy

Pregnancy Risk Factor

C

Pregnancy Considerations

Animal reproduction studies have not been conducted. Immune globulins cross the placenta in increased amounts after 30 weeks gestation. There are no adequate and well-controlled studies in pregnant women. Vaccinia immune globulin is currently not recommended for use in persons with contraindications to smallpox vaccine; inadvertent exposure to smallpox vaccine in high risk populations (eg pregnant women) should be reported to the CDC so that standardized treatment may be provided.

Patient Education

What is this drug used for?

• It is used to treat certain infections caused by the vaccinia virus.

Frequently reported side effects of this drug

• Sensation of cold or warmth
• Headache
• Vomiting
• Lack of appetite
• Muscle spasm
• Back pain
• Tremors
• Sweating a lot
• Nausea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Kidney problems like not able to pass urine, blood in urine, change in amount of urine passed, or weight gain
• Severe cerebrovascular disease like change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or change in eyesight
• Severe pulmonary disorder like lung or breathing problems like trouble breathing, shortness of breath, or a cough that is new or worse
• Aseptic meningitis like headache, fever, chills, severe nausea or vomiting, stiff neck, rash, bright lights that bother eyes, fatigue, or illogical thinking
• Blood clots like numbness or weakness on one side of the body; pain, redness, tenderness, warmth, or swelling in the arms or legs; change in color of an arm or leg; chest pain; shortness of breath; fast heartbeat; or coughing up blood
• Severe loss of strength and energy
• Dark urine
• Yellow skin or eyes
• Severe dizziness
• Passing out
• Injection site pain
• Chills
• Joint pain
• Burning or numbness feeling
• Pale skin
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.