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Respiratory Syncytial
Virus Immune Globulin
Intravenous (HUMAN), [RSV-IGIV]
LIMITED AVAILABILITY
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DESCRIPTION:
| • |
RespiGam™, Respiratory Syncytial Virus Immune Globulin Intravenous (Human) (RSV-IGIV) is a sterile liquid immunoglobulin G containing neutralizing antibody to Respiratory Syncytial Virus (RSV). Each lot of RespiGam™ meets the minimum potency specifications when compared to the validated Reference Standard. The globulin is stabilized with 5% sucrose and 1% Albumin (Human). RespiGam™ contains no preservative. The immunoglobulin is purified from pooled adult human plasma selected for high titers of neutralizing antibody against RSV using a proprietary patented screening assay(1). Source material for fractionation may be obtained from another U.S.-licensed manufacturer. Pooled plasma is fractionated by ethanol precipitation of the proteins according to Cohn Method 6 and Oncley Method 9, with additional steps to yield a product suitable for intravenous administration. A widely utilized solvent-detergent viral inactivation process is used to decrease the possibility of transmission of bloodborne pathogens (2). Certain manufacturing operations may be performed by other firms. Each milliliter contains 50 ± 10 mg immunoglobulin, primarily IgG, and trace amounts of IgA and IgM; 50 mg sucrose; and 10 mg Albumin (Human). The sodium content is 20-30 mEq per liter, i.e., 1.0-1.5 mEq per 50 ml. The solution should appear colorless and translucent.
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CLINICAL PHARMACOLOGY
| • |
RespiGam™ contains IgG antibodies representative of the large number of normal healthy persons who contributed to the plasma pools from which the product was derived. The immune globulin contains a high concentration of neutralizing and protective antibodies directed against RSV (3). In vitro tests demonstrated that RespiGam™ neutralized each of 62 different RSV clinical isolates of both subgroup A (n=39) and subgroup B (n=23). In the PREVENT study monthly doses of 750mg/kg of RespiGam™ attained trough geometric mean serum RSV neutralization antibody titers of 1:297 ± 38 (SE) one month after the first infusion, 1:477 ± 85 one month after the second infusion, 1:490 ± 61 one month after the third infusion and 1:429 ± 23 one month after the fourth infusion. The mean half-life of serum RSV neutralizing antibodies after RespiGam™ infusion is 22-28 days (4).
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INDICATIONS AND USAGE:
| • |
RespiGam™ is indicated for the prevention of serious lower respiratory tract infection caused by RSV in children under 24 months of age with bronchopulmonary dysplasia (BPD) or a history of premature birth (less than or equal to 35 weeks gestation). RespiGam™ has been demonstrated to be safe and effective in reducing the incidence and duration of RSV hospitalization and the severity of RSV illness in these high risk infants.
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CLINICAL STUDIES
| • |
In randomized, controlled studies of RSV disease prophylaxis, monthly doses of 750 mg/kg of RespiGam™ were effective in reducing the incidence of RSV hospitalization in high-risk children. Children with BPD may be at high risk for serious RSV disease up to 60 months of age(5). Children born prematurely may be at high risk for serious RSV disease during the first year of life(6). Summarized below are the results of the pivotal trial and three additional studies supportive of the safety and efficacy of RespiGam™.
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PREVENT TRIAL:
| • |
The pivotal trial known as the PREVENT trial was a 54 center, randomized, placebo-controlled, double-blind study of the safety and effectiveness of RespiGam™ in the prophylaxis of RSV disease in infants and children with BPD less than or equal to 24 months of age or premature birth (less than or equal to 35 weeks gestation) less than or equal to 6 months of age at study entry. The age of premature infants at the end of the study ranged from 4.8 to 11.4 months. In this trial, 510 patients were randomized to receive monthly infusions in November through April of either 750 mg/kg (15 ml/kg) RespiGam™ or 15 ml/kg 1% Albumin (Human) serum as a control. The efficacy analyses of this study were conducted on an "intent-to-treat" basis that included all randomized patients. The prospectively defined endpoints for the study are shown in Table 1. RespiGam™ reduced the incidence of RSV hospitalization by 41%, (p=0.047) total days of RSV hospitalization by 53%, (p=0.045) total RSV hospital days with increased supplemental oxygen requirement by 60%, (p=0.007) and total RSV hospital days with a moderate or severe lower respiratory tract infection by 54% (p=0.049). A trend in reduction in total intensive care unit (ICU) days (44%) was observed although it was not statistically significant (p=0.407).
Two additional endpoints were evaluated. The incidence of any hospitalization due to respiratory illness was compared between placebo control and children receiving RespiGam™. The incidence in placebo controls was 69/260 (26.5% ) versus 41/250 (16.4%) in the RespiGam™ recipients.This represents a 38% reduction (p=0.005) in the incidence of respiratory hospitalization for RespiGam™ recipients. The total days of hospitalization for respiratory illness per 100 randomized children were compared between placebo controls and RespiGam™ recipients. There were 317 days per 100 control children and 170 days per 100 RespiGam™ children.This represents a 46% reduction (p=0.005) in the total days of hospitalization for respiratory illness per 100 randomized children for RespiGam™ recipients.
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| Clinical Endpoint |
Control N=260 |
Respigam™ (RSV-IGIV) (750 mg/kg) N = 250 |
% Reduction |
| Incidence of RSV Hospitalization |
35 (13.5%) |
20 (8.0%) |
41% |
| RSV Hospital Days/100 Children |
129 |
60 |
53% |
| RSV Hospital Days with Increased Supplemental O2/100 Children |
85 |
34 |
60% |
| RSV Hospital Days with Moderate to Severe LRI*/100 Children |
106 |
49 |
54% |
| RSV ICU Days/100 Children |
50 |
28 |
44% |
Days of RSV Mechanical
Ventilation/100 Children |
20 |
18 |
10% |
| * Lower Respiratory Tract Infection/Illness |
PREVENT was not designed nor powered to detect treatment differences among subsets of participants. Reductions in RSV hospitalization ranging from 17% to 58% were observed in RespiGam™ treated subgroups defined by gender, categorical age (< or > 6 months at entry) and diagnosis. The largest reductions were seen in children > 6 months of age, all of whom had BPD. The smallest observed reduction was seen among children age < 6 months. This subgroup also had a low incidence of RSV hospitalization which limited the ability to quantify the magnitude of the treatment effect. Consequently, the effectiveness of RespiGam™ in the subgroup of premature infants without BPD could not be definitively established in this study. Analyses using weight as a categorical variable revealed that children with entry weight below the median (4.3 kg) had a 49% observed reduction in the incidence of RSV hospitalization.
RespiGam™ has not been investigated for it's effect in the prevention of RSV related apnea or RSV related apnea-hypothermia-sepsis syndrome.
NIAID TRIAL
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The NIAID study was a supportive, multi-center, randomized, non-placebo controlled, single-blind study of the safety and effectiveness of RespiGam™ in the prophylaxis of RSV disease in 274 infants and children at high risk of RSV disease due to chronic pulmonary disease (principally BPD), congenital heart disease (CHD), or premature birth (less than or equal to 35 weeks gestation)(7,8,9). Compared to control children (n=90), children randomized to receive 750 mg/kg RespiGam™, Respiratory Syncytial Virus Immune Globulin Intravenous (Human) (RSV-IGIV) (n=92) showed a 57% (p=0.029) reduction in the incidence of RSV hospitalization, a 59% (p=0.030) reduction in total days of RSV hospitalization per 100 children, a 97% (p=0.049) reduction in RSV ICU days per 100 children and 100% reduction in mechanical ventilation per 100 children.
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CARDIAC TRIAL
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The CARDIAC trial was a supportive multi-center, randomized non-placebo controlled, single-blind study conducted to further assess the safety and efficacy of RespiGam™ in 429 children with congenital heart disease (CHD) of less than 48 months of age at enrollment. The mean age of children at entry was 9 months and ranged from 0 to 47 months. Although trends toward RespiGam™ efficacy were observed, the data were not statistically significant. The efficacy and safety of RespiGam™ has not been established in children with CHD (SEE WARNING SECTION).
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OPEN LABEL TRIAL
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A third supportive clinical trial was conducted to determine the safety and pharmacokinetics of monthly 750 mg/kg doses of RespiGam™ in 68 children with BPD or prematurity. This multi-center study was open-label in design. During the study, seven children (10.3%) were hospitalized for RSV. RSV hospital days were 54 per 100 children (mean = 5.3 days, n=7) and RSV ICU days were 15 per 100 children (mean = 10 days, n=1).
RespiGam™ has not been demonstrated to be effective for the treatment of RSV infection.
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CONTRAINDICATIONS
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RespiGam™ should not be used in patients with a history of a severe prior reaction associated with the administration of RespiGam™ or other human immunoglobulin preparations. Patients with selective IgA deficiency have the potential for developing antibodies to IgA and could have anaphylactic or allergic reactions to subsequent administration of blood products that contain IgA, including RespiGam™.
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WARNINGS:
| • |
Infants with underlying pulmonary disease may be sensitive to extra fluid volume. Infusion of RespiGam™, particularly in children with BPD, may precipitate symptoms of fluid overload. Overall, 8.4% of participants (1% premature and 13% BPD) received new or extra diuretics during the period 24 hours before through 48 hours after at least one of their infusions in the PREVENT trial. The reason for this use was not recorded (e.g. prophylaxis, treatment, or part of routine care during a clinical visit). RespiGam™ -related fluid overload was reported in 3 patients (1.2%) and RespiGam™ - related respiratory distress was reported in 4 patients (1.6%); all had underlying BPD. With the exception of one child with respiratory distress (part of an acute allergic reaction) for whom RespiGam™ was discontinued, these children were managed with diuretics and/or modification of the infusion rate and went on to receive subsequent infusions. Complications related to fluid volume were recorded as a reason for incomplete or prolonged infusion in 2.0% of children receiving RespiGam™ (2.5% BPD and 1.1% premature) and in 1.5% of children receiving placebo in the PREVENT trial. Children with clinically apparent fluid overload should not be infused with RespiGam™.
RespiGam™ should be administered cautiously (see DOSAGE AND ADMINISTRATION). During administration, a patient's vital signs should be monitored frequently, and a patient should be observed for increases in heart rate, respiratory rate, retractions, and rales. A loop diuretic such as furosemide or bumetanide should be available for management of fluid overload.
Severe reactions, such as anaphylaxis or angioneurotic edema, have been reported in association with intravenous immunoglobulins even in patients not known to be sensitive to human immunoglobulins or blood products. Serious allergic reaction was noted in 2 patients in the PREVENT trial. These reactions were manifest as an acute episode of cyanosis, mottling and fever in one patient and respiratory distress in the other. The rate of allergic reaction appears to be low and consistent with rates observed for other Immune Globulin Intravenous (Human)[IGIV] products. If hypotension, anaphylaxis, or severe allergic reaction occurs, discontinue infusion and administer epinephrine (1:1000), as required.
The safety and efficacy of RespiGam™ in children with CHD has not been established. Although equivalent proportions of children in the RespiGam™ and control groups in the CARDIAC trial had adverse events, a larger number of RespiGam™ recipients had severe or life-threatening adverse events. These events were most frequently observed in infants with CHD with right to left shunts who underwent cardiac surgery.
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PRECAUTIONS
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Except for hypersensitivity reactions, adverse reactions to IGIVs may be related to the rate of administration. Careful adherence to the infusion rate outlined under DOSAGE AND ADMINISTRATION is therefore important. Loop diuretics should be available for the management of patients who are at risk for fluid overload. Although systemic allergic reactions are rare (see ADVERSE REACTIONS), epinephrine and diphenhydramine should be available for treatment of acute allergic symptoms.
Rare occurrences of aseptic meningitis syndrome (AMS) have been reported in association with Immune Globulin Intravenous (Human) (IGIV) treatment (10,11,12,13). AMS usually begins within several hours to two days following IGIV treatment and is characterized by symptoms and signs including severe headache, drowsiness, fever, photophobia, painful eye movements, muscle rigidity, and nausea and vomiting. Cerebrospinal fluid studies generally demonstrate pleocytosis, predominantly granulocytic, and elevated protein levels. Patients exhibiting such symptoms and signs should be thoroughly evaluated to rule out other causes of meningitis. AMS may occur more frequently in association with high dose (2 g/kg) IGIV treatment. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae.
RespiGam™ is made from human plasma and, like other plasma products, carries the possibility for transmission of bloodborne pathogenic agents. The risk of transmission of recognized blood-borne viruses is considered to be low because of screening of plasma donors, an added viral inactivation step and removal properties in the Cohn-Oncley cold ethanol precipitation procedure used for purification of immune globulin products (14,15,16). Until 1993, cold ethanol manufactured immune globulins licensed in the United States had not been documented to transmit any viral agent. However, during a brief period in late 1993 to early 1994, intravenous immune globulin made by one U.S. manufacturer was associated with transmission of Hepatitis C virus (17). To further guard against possible transmission of blood-borne viruses, RespiGam™ is treated with a solvent-detergent viral inactivation procedure (2) known to inactivate a wide spectrum of lipid enveloped viruses, including HIV-1, HIV-2, Hepatitis B Virus and Hepatitis C Virus (18). However, because new blood-borne agents may yet emerge, some of which may not be inactivated or eliminated by the manufacturing process or by solvent-detergent treatment, RespiGam™, like any other blood product, should be given only if a benefit is expected.
RespiGam™ does not contain a preservative. The single-use vial should be entered only once for administration purposes and the infusion should begin within 6 hours. The infusion schedule should be adhered to closely (see DOSAGE AND ADMINISTRATION). Do not use if the solution is turbid.
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DRUG INTERACTIONS:
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Antibodies present in immune globulin preparations may interfere with the immune response to live virus vaccines, such as mumps, rubella, and particularly measles. If such vaccines are given during or within 10 months after RespiGam™ infusion, reimmunization is recommended, if appropriate (19). Studies have suggested that responses to non-live childhood vaccines (e.g. DPT) are not substantially influenced by IGIVs administration (20). Limited information available from infants who received RespiGam™ concurrently with one or more doses of their primary immunization series indicates that antibody responses to diphtheria, tetanus pertussis and H. Influenza b may be lower in RespiGam™ recipients than in controls. It is not known whether antibody responses to trivalent oral polio vaccine might be affected by concurrent RespiGam™. Physicians may wish to consider giving a booster dose of these vaccines three or four months after the last dose of RespiGam™ in order to ensure immunity to DPT (diphtheria, pertussis, tetanus), DaPT (Diphtheria, acellular pertussis, tetanus), Hib (hemophilus influenza b) and OPV (oral poliovirus). The effect of human immunoglobulin on immunization with eIPV (enhanced, inactivated poliovirus vaccine) has not been evaluated.
Admixtures of RespiGam™ with other drugs have not been studied; however, it is recommended that RespiGam™ be administered separately from other drugs or medications that the patient may be receiving (see DOSAGE and ADMINISTRATION).
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PREGNANCY CATEGORY C:
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Animal reproduction studies have not been conducted with RespiGam™, Respiratory Syncytial Virus Immune Globulin Intravenous (Human) (RSV-IGIV). It is also not known whether RespiGam™ can cause fetal harm when administered to a pregnant woman or could affect reproduction capacity. RespiGam™ should be given to a pregnant woman only if clearly indicated.
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ADVERSE REACTIONS:
| • |
RespiGam™ is generally well tolerated. In the PREVENT trial of RespiGam™ in children with BPD or prematurity, there was no difference in the proportion of children in the RespiGam™ and placebo groups who reported adverse events.
Table 2 illustrates adverse events which the investigator judged potentially related to study drug (RespiGam™ or Placebo) and which were reported at an incidence of 1% or greater in the RespiGam™ group in the PREVENT trial. The number of children reporting one or more of these adverse events were evenly distributed between the two treatment groups (35 of 260 in placebo, and 43 of 250 in RespiGam™ patients, p=0.269). In addition, the distribution of severity of adverse events was not significantly different between the two groups (p=0.216). Respiratory distress occurred in 2% (6 of 250) of children receiving RespiGam™. Patients in the RespiGam™ group reported a slightly higher incidence of fever compared to the placebo group.
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| Number in Study |
Placebo |
Respigam |
|
n=260 |
n=250 |
| Number of children with any drug related adverse event |
n |
% |
n |
% |
| 35 |
13 |
43 |
15 |
| Number of children with drug related [1] |
|
|
|
|
| fever/pyrexia |
6 |
2% |
15 |
6% |
| respitory distress |
1 |
<1% |
6 |
2% |
| vomiting/emesis |
3 |
1% |
5 |
2% |
| wheezing |
4 |
2% |
4 |
2% |
| diarrhea |
1 |
<1% |
3 |
1% |
| rales |
0 |
0% |
3 |
1% |
| fluid overload |
0 |
0% |
3 |
1% |
| tachycardia/increased pulse rate |
0 |
0% |
3 |
1% |
| rash |
5 |
2% |
3 |
1% |
| hypertension |
0 |
0% |
2 |
1% |
| hypoxia/hypoxemia |
2 |
1% |
2 |
1% |
| tachypnea |
1 |
<1% |
2 |
1% |
| gastroenteritis |
1 |
<1% |
2 |
1% |
| injection site inflammation |
2 |
1% |
2 |
1% |
| overdose effect |
1 |
<1% |
2 |
1% |
* = events possibly, probably, or definitely related to study drug.
[1] a child may be represented in more than one category. |
The incidence of serious adverse events potentially related to study drug was equivalent for both treatment groups with 2% of children in the placebo group and 2% of children in the RespiGam™ group reporting such events (p=0.538). The rate of serious adverse events is similar to the rate reported for other IGIVs.
Infrequent adverse reactions were reported (rate of less than one percent) in the PREVENT trial as potentially related to the use of RespiGam™ including: edema, pallor, hypotension, heart murmur, gagging, cyanosis, sleepiness, cough, rhinorrhea, eczema, skin cold and clammy, and conjunctival hemorrhage. Adverse events occurring only in the placebo group are not listed.
Reactions similar to those reported with other IGIVs may occur with RespiGam™. These include: dizziness, flushing, blood pressure changes, anxiety, palpitations, chest tightness, dyspnea, abdominal cramps, pruritus, myalgia or arthralgia (see WARNINGS). Such reactions are often related to the rate of infusion. Immediate allergic, anaphylactic, or hypersensitivity reactions may be observed (see CONTRAINDICATIONS). Rarely, aseptic meningitis syndrome (AMS) has been reported in association with IGIV treatment, particularly at high dosage (2g/kg)(10-13) (see PRECAUTIONS). In the PREVENT trial, 3 children developed aseptic meningitis of unknown etiology; one had a presumptive diagnosis of enteroviral infection, another child had an unconfirmed diagnosis of Herpes simplex meningitis which improved in association with acyclovir treatment and a third child developed fever, vomiting and malaise associated with 21 cells/mm3 in cerebrospinal fluid. Also, one child was initially reported to have hepatitis but was subsequently diagnosed with hemosiderosis judged unrelated to RespiGam™.
OTHER SAFETY EXPERIENCE:
| • |
Antibodies present in immune globulin preparations may interfere with the immune response to live virus vaccines, such as mumps, rubella, and particularly measles. If such vaccines are given during or within 10 months after RespiGam™ infusion, reimmunization is recommended, if appropriate (19). Studies have suggested that responses to non-live childhood vaccines (e.g. DPT) are not substantially influenced by IGIVs administration (20). Limited information available from infants who received RespiGam™ concurrently with one or more doses of their primary immunization series indicates that antibody responses to diphtheria, tetanus pertussis and H. Influenza b may be lower in RespiGam™ recipients than in controls. It is not known whether antibody responses to trivalent oral polio vaccine might be affected by concurrent RespiGam™. Physicians may wish to consider giving a booster dose of these vaccines three or four months after the last dose of RespiGam™ in order to ensure immunity to DPT (diphtheria, pertussis, tetanus), DaPT (Diphtheria, acellular pertussis, tetanus), Hib (hemophilus influenza b) and OPV (oral poliovirus). The effect of human immunoglobulin on immunization with eIPV (enhanced, inactivated poliovirus vaccine) has not been evaluated.
Admixtures of RespiGam™ with other drugs have not been studied; however, it is recommended that RespiGam™ be administered separately from other drugs or medications that the patient may be receiving (see DOSAGE and ADMINISTRATION).
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OVERDOSAGE:
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Although few data are available, clinical experience with other immune globulin preparations suggests that the major manifestations would be those related to fluid volume overload.
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DOSAGE AND ADMINISTRATION
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The maximum recommended total dosage per monthly infusion is 750 mg/kg, administered according to the following schedule:
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| Time After Start of Infusion |
Rate of Infusion
(ml/kg of Body Mass Per Hour) |
| 0-15 minutes |
1.5ml/kg/hr |
| 15-30 minutes |
3.0ml/kg/hr |
| 30 minutes to end of infusion |
6.0ml/kg/hr |
Administer RespiGam™ intravenously at 1.5 ml/kg/hr for 15 minutes. If the clinical condition does not contraindicate a higher rate, increase the rate to 3.0 ml/kg/hr for 15 minutes and finally increase to a maximum rate of 6.0 ml/kg/hr. DO NOT EXCEED THIS RATE OF ADMINISTRATION. Monitor the patient closely during and after each rate change. In especially ill children with BPD, slower rates of infusion may be indicated.
A physician may want to consider factors such as other clinical illness, how well the child has grown and the risk of exposure from siblings or daycare when determining whether to use RespiGam™, Respiratory Syncytial Virus Immune Globulin Intravenous (Human) (RSV-IGIV). The first dose should be administered prior to commencement of the RSV season and subsequent doses should be administered monthly throughout the RSV season in order to maintain protection. In the Northern Hemisphere the RSV season typically commences in November and runs through April. Children should be infused from early November through April, unless RSV activity begins earlier or persists later in a community. It is recommended that RespiGam™ be administered separately from other drugs or medications that the patient may be receiving. It is recommended that children infected with RSV continue to receive monthly doses of RespiGam™ for the duration of the RSV season.
PREPERATION FOR ADMINISTRATION:
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Remove the tab portion of the vial cap and clean the rubber stopper with 70% alcohol or equivalent. RespiGam™ , like all parenteral drug products, should be inspected for particulate matter and discoloration prior to administration. Infuse the solution only if it is colorless and not turbid. DO NOT SHAKE VIAL; AVOID FOAMING.
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INFUSION:
| • |
Infusion should begin within 6 hours and should be completed within 12 hours after the single-use vial is entered. The patient's vital signs and cardiopulmonary status should be assessed prior to infusion, before each rate increase, and thereafter at 30-minute intervals until 30 minutes following completion of the infusion. RespiGam™ should be administered through an intravenous line using a constant infusion pump (i.e. IVAC pump or equivalent). Predilution of RespiGam™ before infusion is not recommended. If possible, RespiGam™ should be administered through a separate intravenous line, although it may be "piggy-backed" into a pre-existing line if that line contains one of the following dextrose solutions (with or without sodium chloride): 2.5%, 5%, 10%, or 20% dextrose in water. If a pre-existing line must be used, the RespiGam™ should not be diluted more than 1:2 with any other of the above-named solutions. Admixtures of RespiGam™ with any other solutions have not been evaluated. While filters are not necessary, an in-line filter with a pore size larger than 15 micrometers may be used for the infusion of RespiGam™ .
To prevent the transmission of hepatitis viruses or infectious agents from one person to another, sterile disposable syringes and needles should be used. Do not reuse syringes and needles.
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HOW SUPPLIED:
| • |
RespiGam™, Respiratory Syncytial Virus Immune Globulin Intravenous (Human) is supplied in two single-use vials containing:
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| NCD no. |
Total Quantity of Immunoglobin |
Volume |
Concentration |
| 60574-2102-1 |
1000 mg ± 200 mg |
20 ml |
50 mg ± 10 mg/ml |
| 60574-2101-1 |
2500 mg ± 500 mg |
50 ml |
50 mg ± 10 mg/ml |
STORAGE:
| • |
RespiGam™ should be stored between 2° C and 8° C (35.6° F and 46.4° F). Do not freeze.
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| 1 |
Siber GR, Leszczynski J, Pena-Cruz V, et al. Protective Activity of a Human Respiratory Syncytial Virus Immune Globulin Prepared from Donors Screened by Microneutralization Assay. J. Infect. Dis; 165:456-463, 1992. |
| 2 |
Horowitz B, Wiebe ME, Lippin A, et al. Inactivation of Viruses in Labile Blood Derivatives. Transfusion; 25:516-522, 1985. |
| 3 |
Siber GR, Leombruno D, Leszczynski J, et al. Comparison of Antibody Concentrations and Protective Activity of Respiratory Syncytial Virus (RSV) Immune Globulin and Conventional Immune Globulin. J. Infect Dis; 169:1368-1373, 1994. |
| 4 |
Groothuis JR, Simoes EAF, Lehr MV, et al. Safety and Bioequivalency of Three Formulations of Respiratory Syncytial Virus-enriched Immunoglobulin. Antimicrob. Agents Chemother; 39:668-671, 1995. |
| 5 |
Groothuis JR, Gutierrez M, Lauer B, Respiratory Syncytial Virus Infection in Children with Bronchopulminary Dysplasia. Pediatrics; 82: 199-203, 1988. |
| 6 |
Green, Brayer, Schenkman and Wald, Ped. Inf. Dis. J;. 8:601-605, 1989. |
| 7 |
Groothuis JR, Simoes EAF, Hemming VG, et al. Prophylactic Administration of Respiratory Syncytial Virus (RSV) Immune Globulin in High Risk Infants and Young Children. N. Engl. J. Med; 329:1524-30, 1993. |
| 8 |
Ellenberg SS, Epstein JS, Fratantoni JC, et al. A Trial of RSV Immune Globulin in Infants and Young Children; The FDA's View. N. Engl. J Med; 331:203-204, 1994. |
| 9 |
Groothuis JR, Hemming VR, Siber GR, et al. Reply to ibid. N. Engl.J. Med. 331:204- 205, 1994. |
| 10 |
Sekul E, Culper E, Dalaks M. Aseptic Meningitis Associated with High-dose Intravenous Immunoglobulin Therapy: Frequency and Risk Factors. Ann. Int. Med; 123:259-262, 1994. |
| 11 |
Kato E, Shindo S, Eto Y, et al. Administration of Immune Globulin Associated with Aseptic Meningitis. JAMA; 3269-3270, 1988. |
| 12 |
Casteels Van Daele M, Wijndaele L, Hunnick K, et al. Intravenous Immunoglobulin and Acute Aseptic Meningitis. N Eng J Med; 323:614-615, 1990. |
| 13 |
Scribner C, Kapit R, Phillips E, et al. Aseptic Meningitis and Intravenous Immunoglobulin Therapy. Ann. Int. Med; 121:305-306, 1994. |
| 14 |
Bossell J, Safety of Therapeutic Immune Globulin Preparations with Respect to Transmission of Human T-lymphotropic Virus Type III/Lymphadenopathy-Associated Virus Infection. MMWR; 35:231-233, 1986. |
| 15 |
Wells MA, Wittek AE, Epstein JS, et al. Inactivation and Partition of Human T-cell Lymphotrophic Virus, Type III, During Ethanol Fractionation of Plasma. Transfusion; 26:210-213, 1986. |
| 16 |
McIver J, Grady G. Immunoglobulin Preparations. In: Churchill WH and Kurtz S R, (ed): Transfusion Medicine. Boston: Blackwell; 1988. |
| 17 |
Schneider L, Geha R. Outbreak of Hepatitis C Associated with Intravenous Immunoglobulin Administration - United States October 1993 - June 1994. MMWR; 43:505-509, 1994. |
| 18 |
Edwards CA, Piet MPJ, Chin S, et al. Tri(n Butyl) Phosphate Detergent Treatment of Licensed Therapeutic and Experimental Blood Derivatives. Vox Sang; 52:53-59, 1987. |
| 19 |
Siber G R, Werner BG, Halsey NA, et al. Interference of Immune Globulin with Measles and Rubella Immunization. J. Pediatrics; 122:204-211, 1993. |
| 20 |
General Recommendations on Immunization. Recommendations of the Advisory Committee on Immunization Practices. MMWR; 43:1-38, 1994. |
For additional information concerning RespiGam™ (Respiratory Syncytial Virus Immune Globulin Intravenous [Human]) (RSV-IGIV), contact:
Professional Services
MedImmune, Inc.
35 West Watkins Mill Road,
Gaithersburg, MD 20878, USA
1-800-949-3789
Manufactured by:
MASSACHUSETTS PUBLIC HEALTH BIOLOGIC LABORATORIES
Boston, Massachusetts 02130, USA
U.S. Govt. License No. 64
Selling Agent:
MedImmune Inc.
35 West Watkins Mill Road
Gaithersburg, MD 20878 USA
Product information as of March, 1996
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