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The most serious adverse reaction observed in clinical study subjects receiving Privigen™ (immune globulin intravenous) for PI was hypersensitivity in one subject. The most serious adverse reactions observed in subjects receiving Privigen™ (immune globulin intravenous) for chronic ITP were aseptic meningitis syndrome in one subject and hemolysis in two subjects. Six other subjects in the ITP study experienced hemolysis as documented from clinical laboratory data. (WARNINGS and PRECAUTIONS).
The most common adverse reactions observed in subjects with PI were headache, pain, nausea, fatigue, and chills. The most common adverse reactions observed in subjects with chronic ITP were headache, pyrexia/hyperthermia, and anemia.
In general, reported adverse reactions to Privigen™ (immune globulin intravenous) in subjects with either PI or chronic ITP were similar in kind and frequency to those observed with other IGIV products.
Clinical Studies Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in practice.
Treatment of Primary Immunodeficiency
In a prospective, open-label, single-arm, multicenter clinical study, 80 subjects with PI received median doses of Privigen™ (immune globulin intravenous) ranging from 200 to 888 mg/kg every 3 weeks (median dose 428.3 mg/kg) or 4 weeks (median dose 440.6 mg/kg) for up to 12 months (see CLINICAL STUDIES).
Routine premedication was not allowed. However, subjects who experienced two consecutive infusion-related adverse events (AEs) that were likely to be prevented by premedication were permitted to receive antipyretics, antihistamines, NSAIDs, or antiemetic agents. During the study, 8 (10%) subjects received premedication prior to 51 (4.9%) of the 1038 infusions administered.
Temporally associated AEs are those occurring during or within 72 hours after the end of an infusion, irrespective of causality. In this study, the upper bound of the 1-sided 97.5% confidence interval for the proportion of Privigen™ (immune globulin intravenous) infusions with temporally associated AEs was 23.8% (actual proportion: 20.8%). This is below the target of 40% for this safety endpoint.11 The total number of temporally associated AEs was 397 (a rate of 0.38 AEs per infusion).
Table 1 lists the temporally associated AEs that occurred in more than 5% of subjects within 72 hours after the end of a Privigen™ (immune globulin intravenous) infusion, irrespective of causality.
Table 1: Temporally Associated Adverse Events* (TAAEs) in
> 5% of Subjects With PI
Within 72 Hours After the End of a Privigen™ (immune globulin intravenous) Infusion, Irrespective of Causality
|TAAE||No. Subjects Reporting
TAAE (% of Subjects
|No. TAAEs Reported (as
% Rate of Infusions
|No. Infusions With
TAAE (% of Infusions
|Headache||35 (43.8)||90 (8.7)||82 (7.9)|
|Pain||20 (25.0)||51 (4.9)||44 (4.2)|
|Fatigue||13 (16.3)||29 (2.8)||27 (2.6)|
|Nausea||10 (12.5)||22 (2.1)||19 (1.8)|
|Chills||9 (11.3)||15 (1.4)||15 (1.4)|
|Vomiting||7 (8.8)||13 (1.3)||13 (1.3)|
|Pyrexia||6 (7.5)||11 (1.1)||10 (1.0)|
|Cough||5 (6.3)||5 (0.5)||5 (0.5)|
|Diarrhea||5 (6.3)||5 (0.5)||5 (0.5)|
|Stomach discomfort||5 (6.3)||5 (0.5)||5 (0.5)|
Of the 397 temporally associated AEs reported for the 80 subjects with PI, the investigators judged 192 to be related to the infusion of Privigen™ (immune globulin intravenous) (including 5 serious, severe AEs described below). Of the 187 non-serious AEs related to the infusion of Privigen™ (immune globulin intravenous) , 91 were mild, 81 were moderate, 14 were severe, and 1 was of unknown severity. The most common temporally associated AEs judged by the investigators to be “at least possibly” related to the infusion were headache (29% of subjects), pain (14% of subjects), nausea (11% of subjects), fatigue (11% of subjects), and chills (11% of subjects).
Sixteen subjects (20%) experienced 41 serious AEs. Five of these were related severe AEs (hypersensitivity, chills, fatigue, dizziness, and increased body temperature) that occurred in one subject and resulted in the subject's withdrawal from the study. Two other subjects withdrew from the study due to AEs related to Privigen™ (immune globulin intravenous) (chills and headache in one subject; vomiting in the other).
Seventy-seven of the 80 subjects enrolled in this study had a negative direct antiglobulin test (DAT) at baseline. Of these 77 subjects, 36 (46.8%) developed a positive DAT at some time during the study. However, no subjects showed evidence of hemolytic anemia.
Treatmentof Chronic Immune Thrombocytopenic Purpura
In a prospective, open-label, single-arm, multicenter clinical study, 57 subjects with chronic ITP received a 2 g/kg dose of Privigen™ (immune globulin intravenous) administered daily as two 1 g/kg intravenous infusions for 2 consecutive days (see CLINICAL STUDIES).
Concomitant medications affecting platelets or other treatments for chronic ITP were not allowed. Thirty-two (56.1%) subjects received premedication with acetaminophen and/or an antihistamine.
Table 2 lists the temporally associated AEs that occurred in more than 5% of subjects with chronic ITP within 72 hours after the end of a treatment cycle (two consecutive infusions) with Privigen™ (immune globulin intravenous) , irrespective of causality.
Table 2: Temporally Associated Adverse Events (TAAEs) in
> 5% Subjects With Chronic
ITP Within 72 hours After the End of a Treatment Cycle* With Privigen™ (immune globulin intravenous) ,
Irrespective of Causality
|TAAE||No. Subjects Reporting
TAAE (% of Subjects
|No. TAAEs Reported
(as % Rate of
|No. Infusions With
TAAE (% of Infusions
|Headache||37 (64.9)||48 (42.1)||41 (36.0)|
|Pyrexia/hyperthermia||21 (36.8)||23 (20.2)||22 (19.3)|
|Nausea||6 (10.5)||8 (7.0)||6 (5.3)|
|Epistaxis||6 (10.5)||8 (7.0)||6 (5.3)|
|Vomiting||6 (10.5)||7. (6.1)||6 (5.3)|
|Blood unconjugated bilirubin increased||6 (10.5)||6 (5.3)||6 (5.3)|
|Blood conjugated bilirubin increased||5 (8.8)||5 (4.4)||5 (4.4)|
|Blood total bilirubin increased||4 (7.0)||4 (3.5)||4 (3.5)|
|Hematocrit decreased||3 (5.3)||3 (2.6)||3 (2.6)|
|* Two consecutive daily infusions.|
Of the 183 temporally associated AEs reported for the 57 subjects with chronic ITP, the investigators judged 150 to be related to the infusion of Privigen™ (immune globulin intravenous) (including the one serious AE described below). Of the 149 non-serious AEs related to the infusion of Privigen™ (immune globulin intravenous) , 103 were mild, 37 were moderate, and 9 were severe. The most common temporally associated AEs judged by the investigators to be “at least possibly” related to the infusion were headache (65% of subjects) and pyrexia/hyperthermia (35% of subjects).
Three subjects experienced three serious AEs, one of which (aseptic meningitis) was related to the infusion of Privigen™ (immune globulin intravenous) .
One subject withdrew from the study due to gingival bleeding, which was not related to Privigen™ (immune globulin intravenous) .
Eight subjects, all of whom had a positive DAT, experienced transient drug-related hemolytic reactions, which were associated with elevated bilirubin, elevated lactate dehydrogenase, and a decrease in hemoglobin level within two days after the infusion of Privigen™ (immune globulin intravenous) . Two of the eight subjects were clinically anemic but did not require clinical intervention.
Four other subjects with active bleeding were reported to have developed anemia without evidence of hemolysis.
In this study, there was a decrease in hemoglobin after the first Privigen™ (immune globulin intravenous) infusion (median decrease of 1.2 g/dL by Day 8) followed by a return to near baseline by Day 29.
Fifty-six of the 57 subjects in this study had a negative DAT at baseline. Of these 56 subjects, 12 (21.4%) developed a positive DAT during the 29-day study period.
The following mild to moderate reactions may occur with the administration of IGIV products: headache, diarrhea, tachycardia, fever, fatigue, dizziness, malaise, chills, flushing, skin reactions, wheezing or chest tightness, nausea, vomiting, rigors, back pain, chest pain, myalgia, arthralgia, and changes in blood pressure. Immediate hypersensitivity and anaphylactic reactions are also a possibility.
The following adverse reactions have been identified and reported during the postapproval use of IGIV products.12
- Respiratory: Apnea, Acute Respiratory Distress Syndrome (ARDS), TRALI, cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm
- Cardiovascular:Cardiac arrest, thromboembolism, vascular collapse, hypotension
- Neurological:Coma, loss of consciousness, seizures, tremor
- Integumentary: Stevens-Johnson syndrome, epidermolysis, erythema multiforme, bullous dermatitis
- Hematologic: Pancytopenia, leukopenia, hemolysis, positive direct antiglobulin (Coombs') test
- General/Body as a Whole:Pyrexia, rigors
- Musculoskeletal:Back pain
- Gastrointestinal:Hepatic dysfunction, abdominal pain
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. Evaluation and interpretation of these postmarketing reactions is confounded by underlying diagnosis, concomitant medications, preexisting conditions, and inherent limitations of passive surveillance.
Read the Privigen (immune globulin intravenous) Side Effects Center for a complete guide to possible side effects
Live Virus Vaccines
Immunoglobulin administration may transiently impair the efficacy of live attenuated virus vaccines such as measles, mumps, and rubella because the continued presence of high levels of passively acquired antibody may interfere with an active antibody response.13 The immunizing physician should be informed of recent therapy with Privigen™ (immune globulin intravenous) so that appropriate measures may be taken (see Patient Counseling Information).
11. Center for Biologics Evaluation and Research. Guidance for Industry:
Safety, Efficacy, and Pharmacokinetic Studies to Support Marketing of Immune
Globulin Intravenous (Human) as Replacement Therapy for Primary Humoral Immunodeficiency
[Draft Guidance]. Rockville, Md: U.S. Department of Health and Human Services,
Food and Drug Administration; November 2005.
12. Pierce LR, Jain N. Risks associated with the use of intravenous immunoglobulin. Trans Med Rev 2003;17:241-251.
Last reviewed on RxList: 8/27/2007
Additional Privigen Information
Report Problems to the Food and Drug Administration
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