Octagam 5%

Primary Humoral Immunodeficiency Diseases (PI)

Octagam is an immune globulin intravenous (human) 5% liquid indicated for treatment of primary humoral immunodeficiency (PI), such as congenital agammaglobulinemia, common variable immunodeficiency, X-linked agammaglobulinemia, Wiskott-Aldrich syndrome and severe combined immunodeficiencies.

Dose

As there are significant differences in the half-life of IgG among patients with primary humoral immunodeficiencies, the frequency and amount of immunoglobulin therapy may vary from patient to patient. The proper amount can be determined by monitoring clinical response.

The dose of Octagam 5% liquid for replacement therapy in primary humoral immunodeficiency diseases is 300 to 600 mg/kg body weight (6-12 mL/kg) administered every 3 to 4 weeks. Adjust the dosage over time to achieve the desired trough levels and clinical responses. If a patient on regular treatment missed a dose, administer the missed dose as soon as possible, and then continue treatment as before.

Measles Exposure

If a patient with primary humoral immunodeficiency has been exposed to measles, it may be prudent to administer an extra dose of IGIV as soon as possible and within 6 days of exposure. A dose of 400 mg/kg should provide a serum level > 240 mIU/mL of measles antibodies for at least two weeks.

If a patient with primary humoral immunodeficiency is at risk of future measles exposure and receives a dose of less than 530 mg/kg every 3-4 weeks, the dose should be increased to at least 530 mg/kg. This should provide a serum level of 240 mIU/mL of measles antibodies for at least 22 days after infusion.

Preparation

• Inspect each vial of Octagam 5% liquid visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if the solution is turbid and/or a discoloration is observed.
• Do not freeze. Do not use solutions that have been frozen.
• Octagam 5% liquid contains no preservative. The Octagam 5% liquid bottle is for single use only. Promptly use any bottle that has been entered.
• Prior to use, allow the solution to reach ambient room temperature.
• Do not use after expiration date.
• The content of Octagam 5% liquid bottles may be pooled under aseptic conditions into sterile infusion bags and infused within 8 hours after pooling.
• Do not dilute Octagam 5% liquid. Do not mix Octagam 5% liquid with other medicinal products.
• Do not mix with immune globulin intravenous (IGIV) products from other manufacturers.

Administration

Octagam 5% liquid is for intravenous use only.

• The infusion line may be flushed before and after administration of Octagam 5% liquid with either normal saline or 5% dextrose in water.
• Administer Octagam 5% liquid at room temperature.
• Do not administer Octagam 5% liquid simultaneously with other intravenous preparations in the same infusion set.
• Octagam 5% liquid is not supplied with an infusion set. If using an in-line filter, choose a filter with a pore size of 0.2 – 200 microns.
• Do not use a needle of larger than 16 gauge to prevent the possibility of coring. Insert needle only once within the stopper area delineated (by the raised ring for penetration). Penetrate the stopper within the ring and perpendicularly to the plane of the stopper.
• Monitor the patient carefully throughout the infusion. Certain adverse drug reactions may be related to the rate of infusion. Slowing or stopping the infusion usually allows the symptoms to [subside or] disappear promptly. Once the symptoms subside, the infusion may then be resumed at a lower rate.
• Ensure that patients with pre-existing renal insufficiency are not volume depleted. For patients at risk of renal dysfunction or thromboembolic events, administer Octagam 5% at the minimum infusion rate practicable, not to exceed 3.3mg/kg/min (0.07 mL/kg/min). Discontinue Octagam 5% if renal function deteriorates.

Rate of Administration

Initially infuse Octagam 5% liquid at infusion rates stated below, at least until the physician has had adequate experience with a given patient.

Infusion rates (see also Table 1): 0.5 mg/kg/min (30 mg/kg/hr) for the first 30 minutes; if tolerated, advance to 1 mg/kg/min (60 mg/kg/hr) for the second 30 minutes; and if still tolerated, advance to 2 mg/kg/min (120 mg/kg/hr) for the third 30 minutes. If tolerated the infusion rate can be increased to and maintained at a maximum rate of 3.33 mg/kg/min (200 mg/kg/hr)

For patients judged to be at risk for developing renal dysfunction, administer Octagam 5% liquid at the minimum infusion rate practicable, not to exceed 0.07 mL/kg (3.3 mg/kg)/min (200 mg/kg/hr).

Table 1: Infusion Rates

• Certain severe adverse drug reactions may be related to the rate of infusion. Slowing or stopping the infusion usually allows the symptoms to disappear promptly.
• Ensure that patients with pre-existing renal insufficiency are not volume depleted; discontinue Octagam 5% liquid if renal function deteriorates.
• For patients at risk of renal dysfunction or thromboembolic events, administer Octagam 5% liquid at the minimum infusion rate practicable.

Pregnancy

Risk Summary

No human data are available to indicate the presence or absence of drug-associated risk. Animal reproduction studies have not been conducted with Octagam 5% liquid. It is not known whether Octagam 5% liquid can cause fetal harm when administered to a pregnant woman. Immune globulins cross the placenta from maternal circulation increasingly after 30 weeks of gestation. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Lactation

Risk Summary

No human data are available to assess the presence or absence of Octagam 5% in human milk, the effects of Octagam 5% on the breastfed child, and the effects of Octagam 5% on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Octagam 5% liquid and any potential adverse effects on the breastfed infant from Octagam 5% liquid or from the underlying maternal condition. Immunoglobulins are excreted into the milk and may contribute to the transfer of protective antibodies to the neonate.

Pediatric Use

Octagam 5% liquid was evaluated in 11 pediatric subjects (age range 6 – 16 years). There were no obvious differences observed between adults and pediatric subjects with respect to pharmacokinetics, efficacy and safety. No pediatric specific dose requirements were necessary to achieve the desired serum IgG levels.

Geriatric Use

Patients > 65 years of age may be at increased risk for developing certain adverse reactions such as thromboembolic events and acute renal failure (See Boxed Warning, Warnings and Precautions [ 5]).

Clinical studies of Octagam 5% liquid did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.