"The U.S. Food and Drug Administration today approved Tretten, Coagulation Factor XIII A-Subunit (Recombinant), the first recombinant product for use in the routine prevention of bleeding in adults and children who have a rare clotting disorder, k"...
The most serious adverse reactions in patients receiving Rh0(D) Immune Globulin Intravenous (Human) have been observed in the treatment of ITP and include intravascular hemolysis, clinically compromising anemia, acute renal insufficiency, and, very rarely, DIC and death [see BOXED WARNING, WARNINGS AND PRECAUTIONS].1
The most common adverse reactions observed in the use of Rhophylac for suppression of Rh isoimmunization ( ≥ 0.5% of subjects) are nausea, dizziness, headache, injection-site pain, and malaise.
The most common adverse reactions observed in the treatment of ITP ( > 14% of subjects) are chills, pyrexia/increased body temperature, and headache. Hemolysis (manifested by an increase in bilirubin, a decrease in hemoglobin, or a decrease in haptoglobin) was also observed.
Clinical Studies Experience
Because clinical studies are conducted under different protocols and 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.
Suppression Of Rh Isoimmunization
In two clinical studies, 447 Rh0(D)-negative pregnant women received either an intravenous or intramuscular injection of Rhophylac 1500 IU (300 mcg) at Week 28 of gestation. A second 1500 IU (300 mcg) dose was administered to 267 (9 in Study 1 and 258 in Study 2) of these women within 72 hours of the birth of an Rh0(D)-positive baby. In addition, 30 women in Study 2 received at least one extra antepartum 1500 IU (300 mcg) dose due to obstetric complications [see Clinical Studies].
The most common adverse reactions in study subjects were nausea (0.7%), dizziness(0.5%), headache (0.5%), injection-site pain (0.5%), and malaise (0.5%). A laboratory finding of a transient positive anti-C antibody test was observed in 0.9% of subjects.
In a clinical study, 98 Rh0(D)-positive adult subjects with chronic ITP received anintravenous dose of Rhophylac 250 IU (50 mcg) per kg body weight [see Clinical Studies]. Premedication to alleviate infusion-related side effects was not used except in a single subject who received acetaminophen and diphenhydramine.
Eighty-four (85.7%) subjects experienced 392 treatment-emergent adverse events(TEAEs). Sixty-nine (70.4%) subjects had 186 drug-related TEAEs (defined as TEAEs with a probable, possible, definite, or unknown relationship to the study drug). Within 24 hours of dosing, 73 (74.5%) subjects experienced 183 TEAEs, and 66 (67%) subjects experienced 156 drug-related TEAEs.
Hemolysis (manifested as an increase in bilirubin, a decrease in hemoglobin, or a decrease in haptoglobin) was observed. An increase in blood bilirubin was seen in 21% of subjects. The median decrease in hemoglobin was greatest (0.8 g/dL) at Day 6 and Day 8 following administration of Rhophylac.
Table 2 shows the most common TEAEs observed in the clinical study.
Table 2: Most Common Treatment-Emergent Adverse Events
(TEAEs) in Subjects with ITP
|TEAE||Number of Subjects (%) With a TEAE
|Number of Subjects (%) With a Drug-Related TEAE*
|Chills||34 (34.7%)||34 (34.7%)|
|Pyrexia/ Increased body temperature||32 (32.6%)||30 (30.6%)|
|Increased blood bilirubin||21 (21.4%)||21 (21.4%)|
|Headache||14 (14.3%)||11 (11.2%)|
|* Defined as TEAEs with a possible, probable, definite, or unknown relationship to the study drug.|
Serious adverse events (SAEs) were reported in 10 (10.2%) subjects. SAEs considered to be drug-related were intravascular hemolytic reaction (hypotension, nausea, chills and headache, and a decrease in haptoglobin and hemoglobin) in two subjects; headache, dizziness, nausea, pallor, shivering, and weakness requiring hospitalization in one subject; and an increase in blood pressure and severe headache in one subject. All four subjects recovered completely.
Because postmarketing adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to product exposure. The following adverse reactions have been identified during post-approval use of Rhophylac:
Suppression Of Rh Isoimmunization
Hypersensitivity reactions, including rare cases of anaphylactic shock or anaphylactoid reactions, headache, dizziness, vertigo, hypotension, tachycardia, dyspnea, nausea, vomiting, rash, erythema, pruritus, chills, pyrexia, malaise, diarrhea and back pain have been reported. Transient injection-site irritation and pain have been observed following intramuscular administration.
Transient hemoglobinuria has been reported in a patient being treated with Rhophylac for ITP.
Read the Rhophylac (immune globulin intravenous (human) solution) Side Effects Center for a complete guide to possible side effects
Live Virus Vaccines
1. Pollack W, Ascari WQ, Kochesky RJ, O'Connor RR, Ho TY, Tripodi D. Studies on Rh prophylaxis. 1. relationship between doses of anti-Rh and size of antigenic stimulus. Transfusion. 1971;11:333-339.
Read the Rhophylac Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 3/18/2016
Additional Rhophylac Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.