on every occasion [0.001):<0.001) 1 (> <0.001) 0 (0.000) 2 (0.001) One subject withdrew from the study after 10 treatments with Gammagard Liquid subcutaneous infusion (2.5 months) due to increased fatigue and malaise. The overall rate of local AEs (excluding infections) during the subcutaneous treatment periods was 2.8% per infusion. In subcutaneous naïve patients, the incidence of local AEs (N = 1757 infusions) was 3.3% (2.6% mild and 0.7% moderate with no severe AEs). In the subjects who were subcutaneous experienced (N = 537 infusions), the incidence of local AEs was 1.1% (1.1% mild, and no moderate or severe AEs). In the clinical study after all subcutaneous doses were adjusted, all subjects but one reached their maximum rate allowed in the protocol, 20 mL/site/hour if weight was below 40 kg and 30/mL/hour for weight 40 kg and greater, for one or more of the infusions. 70% (31 of 44) of these subjects opted for the highest rate for all infusions. No subject restricted the rate due to an ADR. In the clinical study, median duration of each weekly infusion was 1.2 hours (range: 0.8 2.3 hours) after all subcutaneous doses were adjusted. The rate set on the pump was that rate per site multiplied by the number of sites, with no maximum. During all subcutaneous treatment periods, 99.8% of infusions were completed without a reduction, interruption, or discontinuation for tolerability reasons. The proportion of subjects who experienced local AEs (excluding infections) was highest immediately following the switch from intravenous to subcutaneous treatment in all age groups. Over subsequent subcutaneous infusions, there was a decrease of local AEs. The rate of all local AEs per infusion immediately after switching from intravenous to subcutaneous treatment was 4.9% (29/595), decreasing to 1.5% (8/538) by the end of the study and to 1.1% (10/893) in the Study Extension. Eight (17%) subjects experienced a local adverse reaction during the first infusion, but that decreased to 1 (2.1%) for the subsequent infusions, ranging from 0 to 4 (8.7%) during the first year of subcutaneous treatment. No subject reported a local adverse reaction from week 53 to end of study at week 68. Postmarketing Experience Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure. Intravenous ADRs Hematologic Hemolysis, Leukopenia, positive direct Coombs test Infusion Reactions Hypersensitivity, anaphylactic shock, anaphylactic reaction Neurological Transient ischemic attack, tremor, burning sensation, cerebral vascular accident Cardiovascular Deep vein thrombosis, hypotension, phlebitis, hypertension, myocardial infarction, chest pain Respiratory Pulmonary embolism, pulmonary edema, dyspnea, oxygen saturation decreased, Transfusion-Related Acute Lung Injury (TRALI) Gastrointestinal Abdominal pain Integumentary Hyperhidrosis, allergic dermatitis Psychiatric Anxiety, insomnia General/Body as a Whole Edema Renal Acute renal dysfunction/failure In addition to the events listed above which were observed for Gammagard Liquid, the following events have been identified for IGIV products in general: Renal Osmotic nephropathy Respiratory Cyanosis, hypoxemia, bronchospasm, apnea, Acute Respiratory Distress Syndrome (ARDS) Integumentary Bullous dermatitis, epidermolysis, erythema multiforme, Stevens-Johnson Syndrome Cardiovascular Cardiac arrest, vascular collapse Neurological Coma, seizures, loss of consciousness, aseptic meningitis syndrome Hematologic Gastrointestinal Pancytopenia Hepatic dysfunction Drug Interactions Passive transfer of antibodies may transiently impair the immune responses to live attenuated virus vaccines such as mumps, rubella and varicella for up to 6 months and for a year or more to measles (rubeola). Inform the immunizing physician of recent therapy with Gammagard Liquid so that appropriate precautions can be taken ( see PATIENT COUNSELING INFORMATION [ 17 ] ). USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category C. Animal reproduction studies have not been conducted with Gammagard Liquid. It is also not known whether Gammagard Liquid can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Immune globulins cross the placenta from maternal circulation increasingly after 30 weeks of gestation. Gammagard Liquid should be given to a pregnant woman only if clearly indicated. Nursing Mothers It is not known whether Gammagard Liquid is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Gammagard Liquid is administered to a nursing woman. Pediatric Use The safety and effectiveness of Gammagard Liquid have been established in the age groups 2 to 16. Use of Gammagard Liquid in these age groups is supported by evidence from adequate and well-controlled studies of Gammagard Liquid including pediatric subjects. Gammagard Liquid administered intravenously was evaluated in 15 pediatric subjects with PI (7 were 2 to> <12 years old and 8 were 12 to> <16) in a multicenter clinical study. Gammagard Liquid administered subcutaneously was evaluated in 18 pediatric subjects with PI (14 were 2 to> <12 years old and 4 were 12 to> <16) in another multicenter clinical study (see CLINICAL STUDIES [ 14 ]). There were no differences in the safety and efficacy profiles as compared with adult subjects. No pediatric-specific dose requirements were necessary to achieve the desired serum IgG levels. Safety and efficacy of Gammagard Liquid in pediatric patients below the age of 2 have not been established. Geriatric Use Limited information is available for the geriatric use of Gammagard Liquid. Gammagard Liquid administered intravenously and subcutaneously was evaluated in two studies with a total of 8 subjects over the age of 65 years. No overall differences in safety or efficacy were observed for this group. Caution should be exercised in administering Gammagard Liquid to patients who are at an increased risk for developing renal failure or thrombotic events. Do not exceed the recommended dose, and infuse Gammagard Liquid at the minimum intravenous infusion rate practicable (See BOXED WARNING, WARNINGS AND PRECAUTIONS [ 5.2 , 5.4 ] and DOSAGE AND ADMINISTRATION [ 2.3 ] ). Overdosage With intravenous administration, overdose of Gammagard Liquid may lead to fluid overload and hyperviscosity. Patients at risk of complications of fluid overload and hyperviscosity include elderly patients and those with cardiac or renal impairment. Gammagard Liquid Description Gammagard Liquid is a ready-for-use sterile, liquid preparation of highly purified and concentrated immunoglobulin G (IgG) antibodies. The distribution of the IgG subclasses is similar to that of normal plasma. The Fc and Fab functions are maintained in Gammagard Liquid. Pre-kallikrein activator activity is not detectable. Gammagard Liquid contains 100 mg/mL protein. At least 98% of the protein is immune globulin, the average immunoglobulin A (IgA) concentration is 37 μg/mL, and immunoglobulin M is present in trace amounts. Gammagard Liquid contains a broad spectrum of IgG antibodies against bacterial and viral agents. Glycine (0.25M) serves as a stabilizing and buffering agent, and there are no added sugars, sodium or preservatives. The pH is 4.6 to 5.1. The osmolality is 240 to 300 mOsmol/kg, which is similar to physiological osmolality (285 to 295 mOsmol/kg). Gammagard Liquid is manufactured from large pools of human plasma. IgG preparations are purified from plasma pools using a modified Cohn-Oncley cold ethanol fractionation process, as well as cation and anion exchange chromatography. Screening against potentially infectious agents begins with the donor selection process and continues throughout plasma collection and plasma preparation. Each individual plasma donation used in the manufacture of Gammagard Liquid is collected only at FDA approved blood establishments and is tested by FDA licensed serological tests for Hepatitis B Surface Antigen (HBsAg), and for antibodies to Human Immunodeficiency Virus (HIV-1/HIV-2) and Hepatitis C Virus (HCV) in accordance with U.S. regulatory requirements. As an additional safety measure, mini-pools of the plasma are tested for the presence of HIV-1 and HCV by FDA licensed Nucleic Acid Testing (NAT) and found to be negative. To further improve the margin of safety, three dedicated, independent and effective virus inactivation/removal steps have been integrated into the manufacturing and formulation processes, namely solvent/detergent (S/D) treatment 7 , 35 nm nanofiltration, and a low pH incubation at elevated temperature 30°C to 32°C. The S/D process includes treatment with an organic mixture of tri-n-butyl phosphate, octoxynol 9 and polysorbate 80 at 18°C to 25°C for a minimum of 60 minutes. S/D treatment inactivates the lipid-enveloped viruses investigated to below detection limits within minutes. In vitro virus spiking studies have been used to validate the capability of the manufacturing process to inactivate and remove viruses. To establish the minimum applicable virus clearance capacity of the manufacturing process, these virus clearance studies were performed under extreme conditions (e.g., at minimum S/D concentrations, incubation time and temperature for the S/D treatment). Virus clearance studies for Gammagard Liquid performed in accordance with good laboratory practices are summarized in Table 10 . Table 10. Three Dedicated Independent Virus Inactivation/Removal Steps Mean Log 10 Reduction Factors * (RFs) For Each Virus and Manufacturing Step * For the calculation of these RF data from virus clearance study reports, applicable manufacturing conditions were used. Log 10 RFs on the order of 4 or more are considered effective for virus clearance in accordance with the Committee for Medicinal Products for Human Use (CHMP, formerly CPMP) guidelines. † No RF obtained due to immediate neutralization of HAV by the anti-HAV antibodies present in the product. Virus type Enveloped RNA Enveloped DNA Non-enveloped RNA Non-enveloped DNA Family Retroviridae Flaviviridae Herpesviridae Picornaviridae Parvoviridae Virus HIV-1 BVDV WNV PRV HAV EMCV MMV SD treatment >4.5 >6.2 n.a. >4.8 n.d. n.d. n.d 35 nm nanofiltration >4.5 >5.1 > 6.2 >5.6 5.7 1.4 2.0 Low pH treatment >5.8 >5.5 > 6.0 >6.5 n.d. † > 6.3 3.1 Overall log reduction factor (ORF) >14.8 >16.8 >12.2 >16.9 5.7 b >7.7 5.1 Abbreviations: HIV-1, Human Immunodeficiency Virus Type 1; BVDV, Bovine Viral Diarrhea Virus (model for Hepatitis C Virus and other lipid enveloped RNA viruses); WNV, West Nile Virus; PRV, Pseudorabies Virus (model for lipid enveloped DNA viruses, including Hepatitis B Virus); EMCV, Encephalomyocarditis Virus (model for non-lipid enveloped RNA viruses, including Hepatitis A virus [HAV]); MMV, Mice Minute Virus (model for non-lipid enveloped DNA viruses, including B19 virus [B19V]); n.d. (not done), n.a. (not applicable). Gammagard Liquid - Clinical Pharmacology Mechanism of Action Gammagard Liquid supplies a broad spectrum of opsonizing and neutralizing IgG antibodies against a wide variety of bacterial and viral agents. Gammagard Liquid also contains a spectrum of antibodies capable of interacting with and altering the activity of cells of the immune system as well as antibodies capable of reacting with cells such as erythrocytes. The role of these antibodies and the mechanisms of action of IgG in Gammagard Liquid have not been fully elucidated. Pharmacokinetics Intravenous Administration Following intravenous infusion, IGIV products show a biphasic decay curve. The initial (α) phase is characterized by an immediate post-infusion peak in serum IgG and is followed by rapid decay due to equilibration between the plasma and extravascular fluid compartments. The second (β) phase is characterized by a slower and constant rate of decay. The commonly cited normal half-life of 18 to 25 days is based on studies in which tiny quantities of radiolabeled IgG are injected into healthy individuals. When radiolabeled IgG was injected into patients with hypogammaglobulinemia or agammaglobulinemia, highly variable half-lives ranging from 12 to 40 days were observed. In other radiolabeled studies, high serum concentrations of IgG, and hypermetabolism associated with fever and infection, have been seen to coincide with a shortened half-life of IgG. In contrast, however, pharmacokinetic studies in immunodeficient patients are based on the decline of IgG concentrations following infusions of large quantities of immune globulin. In such trials, investigators have reported uniformly prolonged half-lives of 26 to 35 days. Pharmacokinetic parameters for Gammagard Liquid were determined from total IgG levels following the fourth infusion in 61 subjects with primary humoral immunodeficiency treated intravenously with the product every 3 or 4 weeks according to the regimen used prior to entering the study. Of these, 57 had sufficient pharmacokinetic data to be included in the dataset. The median weight-adjusted dose per subject was 455 mg/kg/4 weeks with a range of 262 to 710. Pharmacokinetic parameters are presented in Table 11 . Table 11. Summary of Intravenous Pharmacokinetic Parameters in 57 Subjects Parameter Median 95% Confidence Interval Dose of IgG (mg/kg/4 weeks) 455 Range: 262-710 Elimination Half-Life ( T ½ days) 35 (31, 42) AUC 0-21d (mg days/dL) 29139 (27494, 30490) C max (Peak, mg/dL) 2050 (1980, 2200) C min (Trough, mg/dL) 1030 (939, 1110) Incremental recovery (mg/dL)/(mg/kg) 2.3 (2.2, 2.6) Abbreviations: AUC = area under the curve; C max = maximum concentration; C min = minimum concentration. Median IgG trough levels were maintained between 960 to 1120 mg/dL. These dosing regimens maintained serum trough IgG levels generally considered adequate to prevent bacterial infections. The elimination half-life of Gammagard Liquid of 35 days was similar to the half-lives reported for other IGIV products. Subcutaneous Administration Pharmacokinetic (PK) parameters of subcutaneously administered Gammagard Liquid were evaluated in subjects with primary immunodeficiency (PI) who were 12 years and older during a clinical study ( see CLINICAL STUDIES [ 14 ]) . Subjects were treated intravenously for 12 weeks with Gammagard Liquid and then switched to weekly subcutaneous Gammagard Liquid infusions. Initially, all subjects were treated for a minimum of 12 weeks at a subcutaneous dose that was 130% of the intravenous dose. A comparison of the area under the curve (AUC) for intravenous and subcutaneous infusions done on the first 15 adult subjects determined that the subcutaneous dose required to provide an exposure from subcutaneous administration that was not inferior to the exposure from intravenous administration was 137% of the intravenous dose. Subsequently, all subjects were treated with this dose for 6 weeks after which the dose was individualized for all subjects using the trough IgG levels, as described below. After a minimum of 8 weeks at this subcutaneous dose, the PK evaluation was conducted on 32 subjects 12 years of age or older. The mean adjusted dose at the end of the study was 137.3% (125.7-150.8) of the intravenous dose for subjects 12 years and older, and 141.0% (100.5 to 160.0) for subjects under the age of 12. Thus, there was not a significant dosing difference required for children. At this dose adjustment, the geometric mean ratio of the AUC for subcutaneous vs. intravenous Gammagard Liquid administration was 95.2% (90% confidence limit 92.3 to 98.2). The peak IgG level occurred 2.9 (1.2 to 3.2) days after subcutaneous administration. The pharmacokinetic parameters of Gammagard Liquid administered intravenously compared to subcutaneously in the clinical trial are shown in Table 12 . The mean peak IgG levels were lower (1393 289 mg/dL) during subcutaneous treatment with Gammagard Liquid compared to when it was administered intravenously (2240 536 mg/dL), consistent with the lower weekly dose compared to the dose administered every 3 or 4 weeks intravenously. In contrast, the mean trough levels were higher with Gammagard Liquid given subcutaneously (1202 282 mg/dL), compared to those when given intravenously (1050 260 mg/dL), a result of both higher monthly dose and more frequent dosing. The median IgG trough level during intravenous treatment in this clinical trial, 1010 mg/dL (95% CI: 940-1240), was similar to the median value of 1030 mg/dL (95% CI: 939 to 1110) during the intravenous clinical trial shown above in Table 11 . By contrast, the median trough IgG level during subcutaneous treatment for the study was higher, at 1260 mg/dL (95% CI: 1060 to 1400). Table 12. Pharmacokinetic Parameters of Subcutaneously Administered Gammagard Liquid Compared to Gammagard Liquid Administered Intravenously * Weekly equivalent dose † Standardized to a 7 day interval Subcutaneous Administration Intravenous Administration Number of Subjects 32 32 Dose * (mg/kg) Mean SD 182.6 48.4 133.2 36.9 Range (min to max) 94.2 to 293.8 62.7 to 195.4 IgG Peak Levels (mg/dL) Mean SD 1393 289 2240 536 Range (min to max) 734 to 1900 1130 to 3610 IgG Trough Levels (mg/dL) Mean SD 1202 282 1050 260 Range (min to max) 621 to 1700 532 to 1460 AUC † (days*mg/dL) Mean SD 9176 1928 9958 2274 Range (min to max) 4695 to 12468 5097 to 13831 Clearance [mL/kg/day] Mean SD 2.023 0.528 1.355 0.316 Range (min to max) 1.225 to 3.747 0.880 to 2.340 Clinical Studies Clinical Study of Intravenous Administration Intravenous use of Gammagard Liquid in patients with PI is supported by the Phase 3 clinical study of subjects who were treated with 300 to 600 mg/kg every 21 to 28 days for 12 months. The 61 subjects in this study were between 6 to 72 years of age, 54% female and 46% male, and 93% Caucasian, 5% African-American, and 2% Asian. Three subjects were excluded from the per-protocol analysis due to non-study product related reasons. The annualized rate of specified acute serious bacterial infections, i.e., the mean number of specified acute serious bacterial infections per subject per year was studied (see Table 13 ). Table 13. Summary of Validated Acute Serious Bacterial Infections for the Per-Protocol Analysis * Serious acute bacterial infections were defined by FDA and met specific diagnostic requirements. † The rate of validated infections was compared with a rate of 1 per subject per year, in accordance with recommendations by the FDA Blood Products Advisory Committee Number of Events Validated Infections * Bacteremia / Sepsis 0 Bacterial Meningitis 0 Osteomyelitis / Septic Arthritis 0 Bacterial Pneumonia 0 Visceral Abscess 0 Total 0 Hospitalizations Secondary to Infection 0 Mean Number of Validated Infections per Subject per Year 0 p-value † p> < 0.0001 95% Confidence Interval † (0.000, 0.064) The annualized rate of other specified validated bacterial infections (see Table 14 ), and the number of hospitalizations secondary to all validated infectious complications were also studied (see Table 13 and Table 14 ). Table 14. Summary of Validated Other Bacterial Infections * Other bacterial infections that met specific diagnostic requirements Number of Events Validated Infections * Urinary Tract Infection 1 Gastroenteritis 1 Lower Respiratory Tract Infection: Tracheobronchitis, Bronchiolitis (Without Evidence of Pneumonia) 0 Lower Respiratory Tract Infection: Other Infections (e.g., Lung Abscess, Empyema) 0 Otitis Media 2 Total 4 Hospitalizations Secondary to Infection 0 Mean Number of Validated Infections per Subject per Year 0.07 95% Confidence Interval (0.018, 0.168) In this study, there were no validated acute serious bacterial infections in any of the treated subjects. The annualized rate of acute serious bacterial infections was significantly less than (p < 0.0001) the rate of one infection per year, in accordance with recommendations by the FDA Blood Products Advisory Committee . Four of the 61 subjects reported a total of 4 other specified validated bacterial infections. None were serious or severe, none resulted in hospitalization, and all resolved completely. The rate of all clinically-defined but non-validated infections was 3.4 infections per patient per year. These consisted primarily of recurrent episodes of commonly observed infections in this patient population - sinusitis, bronchitis, nasopharyngitis, urinary tract infections, and upper respiratory infections. During the pivotal clinical study, viral safety was assessed by serological screening for HBsAg and antibodies to HCV, HIV-1, and HIV-2 prior to, during, and at the end of the study and by Polymerase Chain Reaction (PCR) tests for HBV, HCV, and HIV-1 genomic sequences prior to and at the end of the study. None of the 61 treated subjects were positive prior to study entry and none converted from negative to positive during the 12-month period of study. Clinical Study of Subcutaneous (SC) Administration A prospective, open-label, non-controlled, multi-center study was conducted in the US to determine the efficacy, tolerability and PK of Gammagard Liquid subcutaneous infusion in 49 adult and pediatric subjects with PID. All subjects were treated for 12 weeks with Gammagard Liquid intravenous infusion every 3 or 4 weeks. Subjects who were on intravenous treatment prior to entering the study were switched to Gammagard Liquid at the same dose and frequency. Subjects who were receiving subcutaneous immune globulin were switched to Gammagard Liquid at the intravenous dose they had been given prior to switching to subcutaneous treatment. A PK analysis was performed at the end of the intravenous period in all subjects aged 12 years and older. One week after the last intravenous infusion, each subject began subcutaneous treatment with Gammagard Liquid at 130% of the weekly equivalent of the intravenous dose for a minimum of 12 weeks. PK data from the first 15 adult subjects were used to determine the dose required to ensure that the IgG exposure with subcutaneous treatment was not inferior to that with intravenous treatment. The median dose determined from these subjects was 137% of the intravenous dose, and subsequently all subjects were treated for a minimum of 6 weeks at this dose. After 6 subcutaneous infusions, a trough IgG level was obtained and used to individually adapt the subcutaneous dose of Gammagard Liquid to compensate for individual variation from the mean value of 137% ( See Pharmacokinetics [ 12.3 ] and DOSAGE AND ADMINISTRATION [ 2.1 ] ). All subjects received a minimum of 12 infusions at this individually adapted dose. Following the formal protocol, all subjects continued to receive subcutaneous treatment with Gammagard Liquid until the last subject completed the study. There were 47 subjects treated with 2,294 subcutaneous infusions of Gammagard Liquid: 4 subjects treated for up to 29 weeks, 17 subjects for 30 to 52 weeks, and 26 subjects for 53 weeks or longer. The median duration of subcutaneous treatment was 379 days (range: 57 to 477 days). Efficacy was determined throughout the entire subcutaneous phase. There were 31 adults 16 years or older, 4 adolescents between 12 and < 16 years of age, and 14 children between 2 years and <12. The volume of Gammagard Liquid infused was 30 mL per site for patients weighing 40 kg and greater, and 20 mL per site for those weighing less than 40 kg. The total weekly dose was divided by those values to determine the number of sites. Mean weekly subcutaneous doses ranged from 181.9 mg/kg to 190.7 mg/kg (at 130% to 137% of the intravenous dose). In the study, the number of infusion sites per infusion was dependent on the dose of IgG and ranged from 2 to 10. In 75% of infusions, the number of infusion sites was 5 or fewer. There were 3 serious validated bacterial infections, all bacterial pneumonia. None of these subjects required hospitalization to treat their infection. The annual rate of acute serious bacterial infections while on Gammagard Liquid subcutaneous treatment was 0.067, with an upper 99% confidence limit of 0.133, which is lower than the minimal goal of achieving a rate of> <1 bacterial infection per patient-year. The summary of infections and associated events for subjects during subcutaneous treatment with Gammagard Liquid is summarized in Table 15 . The annual rate of any infection in this study during subcutaneous treatment, including viral and fungal infections, was 4.1 infections per subject per year. This is consistent with the rate of infections observed in other clinical studies of intravenous and subcutaneous immune globulin 8,9 . Table 15. Summary of Infections and Associated Events * Included systemic and topical antibacterial, anti-fungal, anti-viral, and anti-protozoal antimicrobials. Number of subjects (efficacy phase) Total number of subject years Annual rate of any infections 47 44 4.1 (95% CI 3.2 to 5.1) infections/subject year Antibiotic use * (prophylaxis or treatment) Number of subjects (%) Annual rate 40 (85.1%) 50.2 (95% CI 33.4 to 71.9) days/subject year Days out of work/school/day care or unable to perform normal activities Number of subjects (%) Annual rate 25 (53.2%) 4.0 (95% CI 2.5 to 6.1) days/subject year Hospitalizations due to infections Number of subjects (%) Annual rate 0 (0.0%) 0.0 (95% CI 0.0 to 0.1) days/subject year REFERENCES Orange JS, Hossny EM, Weiler CR, Ballow M, Berger M, Bonilla FA, Buckley R, Chinen J, El-Gamal Y, Mazer BD, Nelson Jr. RP, Patel DD, Secord E, Sorenson RU, Wasserman RL, Cunningham-Rundles C, Use of Intravenous Immunoglobulin in Human Disease: A Review of Evidence by Members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma, and Immunology. J Allergy Clin Immunol 2006; 117:S525-53. Bonilla FA, Bernstein IL, Khan DA, Ballas ZK, Chinen J, Frank MM, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol. 2005; 94(suppl 1):S1-63. Pierce LR, Jain N. Risks associated with the use of intravenous immunoglobulin. Transfusion Med Rev. 2003;17:241-251. Katz U, Sheonfeld Y. Review: intravenous immunoglobulin therapy and thromboembolic complications. Lupus 2005;14:802-8 Daw Z, Padmore R, Neurath D, Cober N, Tokessy M, Desjardins D, et al. Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin: a case series analysis. Transfusion. 2008; 48:1598-601 Church JA, Leibl H, Stein MR, et al. Efficacy, safety and tolerability of a new 10% liquid intravenous immune globulin (IGIV 10%) in patients with primary immunodeficiency. J Clin Immunol 2006; 26(4):388-395. Kreil TR, Berting A, Kistner O, Kindermann J. West Nile virus and the safety of plasma derivatives: verification of high safety margins, and the validity of predictions based on model virus data. Transfusion 2003;43:1023-1028. Ochs HD, Gupta S, Kiessling P et al. Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases. J.Clin.Immunol. 2006;26:265-273. Gardulf A, Nicolay U, Asensio, et al. Rapid subcutaneous IgG replacement therapy is effective and safe in children and adults with primary immunodeficiencies A prospective, Multi-National Study. J Clin Immunol. 2006; 26:177-85. How Supplied/Storage and Handling Gammagard Liquid is supplied in single use bottles containing the labeled amount of functionally active IgG. The packaging of this product is not made with natural rubber latex. The following presentations of Gammagard Liquid are available: NDC Number Volume Grams Protein 0944-2700-02 10 mL 1.0 0944-2700-03 25 mL 2.5 0944-2700-04 50 mL 5.0 0944-2700-05 100 mL 10.0 0944-2700-06 200 mL 20.0 0944-2700-07 300 mL 30.0 Do not freeze. Refrigeration : 36 months storage at temperature 2 to 8 C (36 - 46 F). Room Temperature : 12 months storage at room temperature 25 C, (77 F) within the first 24 months of the date of manufacture. See below for detailed storage information. The total storage time of Gammagard Liquid depends on the point of time the vial is transferred to room temperature. Examples for total storage times are illustrated in Figure 1 . The new expiration date must be recorded on the package when the product is transferred to room temperature. Figure 1 Storage Guidelines Months from Date of Manufacture Product cannot be stored at room temperature after 24 months from date of manufacture. Example 1: If the product is taken out of the refrigerator after 3 months from date of manufacture, it can be stored for 12 months at room temperature. Total storage time is 15 months. Example 2: If the product is taken out of the refrigerator after 21 months from the date of manufacture, it can be stored for 3 months at room temperature. Total storage time is 24 months. Patient Counseling Information See FDA approved patient labeling (Information for Patients) and instructions for use Inform patients to immediately report the following signs and symptoms to their healthcare provider: Decreased urine output, sudden weight gain, fluid retention/edema, and/or shortness of breath ( see WARNINGS AND PRECAUTIONS [ 5.2 ] ) Acute chest pain, shortness of breath, leg pain, and swelling of the legs/feet, numbness in the face or extremities, weakness or paralysis, severe headache, confusion, visual disturbances ( see WARNINGS AND PRECAUTIONS [ 5.4 ] ). Severe headache, neck stiffness, drowsiness, fever, sensitivity to light, painful eye movements, nausea, and vomiting (see WARNINGS AND PRECAUTIONS [ 5.5 ]). Increased heart rate, fatigue, yellowing of the skin or eyes, and dark-colored urine (see WARNINGS AND PRECAUTIONS [ 5.6 ]). Trouble breathing, chest pain, blue lips or extremities, or fever that can occur 1 to 6 hours after an infusion of Gammagard Liquid ( see WARNINGS AND PRECAUTIONS [ 5.7 ] ). Prior to starting Gammagard Liquid ask about a history of IgA deficiency, allergic reactions to immune globulin or other blood products. Patients with a history of allergic reactions should not be treated subcutaneously at home until several treatments have been administered and tolerated under medical supervision. Inform patients that Gammagard Liquid is made from human plasma and may contain infectious agents that can cause disease (e.g., viruses and, theoretically, the vCJD agent). The risk of Gammagard Liquid transmitting an infectious agent has been reduced by screening plasma donors for prior exposure, testing donated plasma, and inactivating or removing certain viruses during manufacturing. Patients should report any symptoms that concern them which might be caused by virus infections (see WARNINGS AND PRECAUTIONS [ 5.8 ] ). Inform patients that Gammagard Liquid can interfere with their immune response to live viral vaccines such as measles, mumps, rubella and varicella, and instruct patients to notify their healthcare professional of this potential interaction when they are receiving vaccinations (see DRUG INTERACTIONS [ 7 ] ). Subcutaneous (SC) Administration Only Self-administration If self-administration is deemed to be appropriate by the physician, clear instructions and training on subcutaneous infusion should be given to the patient/caregiver, and the demonstration of their ability to independently administer subcutaneous infusions should be documented. Ensure the patient understands the importance of consistent weekly subcutaneous infusion to maintain appropriate steady IgG levels. Instruct the patient to keep a treatment diary/log book. This diary/log book should include information about each infusion such as, the time, date, dose, lot number(s) and any reactions. Inform the patient that mild to moderate local infusion-site reactions (e.g., swelling and redness) are a common side effect of subcutaneous treatment, but to contact their healthcare professional if a local reaction increases in severity or persists for more than a few days. Patient package insert Information For Patients Gammagard Liquid Immune Globulin Infusion (Human) 10% For Intravenous and Subcutaneous Administration Information for Patients The following summarizes important information about Gammagard Liquid. Please read it carefully before using this medicine. This information does not take the place of talking with your healthcare provider, and it sufficient
guidelines Gammagard Liquid training session
EmoticonEmoticon