This warning does not apply to Rh(D)-negative patients treated for the suppression of Rh isoimmunization. Intravascular hemolysis leading to death has been reported in Rh(D)-positive patients treated for immune thrombocytopenic purpura (ITP) with Rh(D) Immune Globulin Intravenous (Human) products. Intravascular hemolysis can lead to clinically compromising anemia and multi-system organ failure including acute resp...
RHOPHYLAC is a Rh(D) Immune Globulin Intravenous (Human) (anti-D) product that is indicated for the suppression of Rh isoimmunization in non-sensitized Rh(D)-negative patients and for the treatment of immune thrombocytopenic purpura (ITP) in Rh(D)-positive patients. Pregnancy and Obstetric Conditions RHOPHYLAC is indicated for suppression of rhesus (Rh) isoimmunization in non-sensitized Rh(D)-negative women with a...
Observe patients for at least 20 minutes following administration of RHOPHYLAC. RHOPHYLAC is a clear or slightly opalescent, colorless to pale yellow solution. Inspect RHOPHYLAC visually for particulate matter and discoloration prior to administration. Do not use if the solution is cloudy or contains particulates. Prior to intravenous use, ensure that the needle-free intravenous administration system is compatible...
RHOPHYLAC 1500 IU (300 mcg) is supplied in packages of one or ten (10) single-dose, prefilled, ready-to-use, glass syringe(s), each containing 2 mL liquid for injection. Each syringe is accompanied by a SafetyGlide™ needle for intravenous or intramuscular use. Each product presentation includes a package insert and the following components: Table 7. How Supplied Presentation Carton NDC Number Components 1500 IU (3...
www.fda.gov/medwatchRHOPHYLAC®
Rh0(D) Immune Globulin Intravenous (Human)
This warning does not apply to Rh(D)-negative patients treated for the suppression of Rh isoimmunization.
RHOPHYLAC is a Rh(D) Immune Globulin Intravenous (Human) (anti-D) product that is indicated for the suppression of Rh isoimmunization in non-sensitized Rh(D)-negative patients and for the treatment of immune thrombocytopenic purpura (ITP) in Rh(D)-positive patients.
Pregnancy and Obstetric Conditions
RHOPHYLAC is indicated for suppression of rhesus (Rh) isoimmunization in non-sensitized Rh(D)-negative women with an Rh-incompatible pregnancy, including:
An Rh-incompatible pregnancy is assumed if the fetus/baby is either Rh(D)-positive or Rh(D)-unknown or if the father is either Rh(D)-positive or Rh(D)-unknown.
Incompatible Transfusions
RHOPHYLAC is indicated for the suppression of Rh isoimmunization in Rh(D)-negative individuals transfused with Rh(D)-positive red blood cells (RBCs) or blood components containing Rh(D)-positive RBCs.
Treatment can be given without a preceding exchange transfusion when the transfused blood represents less than 20% of the total circulating RBCs. If the volume exceeds 20%, an exchange transfusion should be considered prior to administering RHOPHYLAC.
RHOPHYLAC is indicated in Rh(D)-positive, non-splenectomized adult patients with chronic ITP to raise platelet counts.
Observe patients for at least 20 minutes following administration of RHOPHYLAC.
DO NOT confuse micrograms (mcg) with International Units (IU) when calculating the dose of RHOPHYLAC. Miscalculations could result in a significant overdose or underdose of the product. Note that 1 mcg = 5 IU of RHOPHYLAC.
Suppression of Rh Isoimmunization
RHOPHYLAC should be administered by intravenous or intramuscular injection. If large doses (greater than 5 mL) are required and intramuscular injection is chosen, it is advisable to administer RHOPHYLAC in divided doses at different sites.
Ensure the site of administration will allow the injection to reach the muscle if RHOPHYLAC is administered intramuscularly. Consider intravenous administration if reaching the muscle is of concern [see Adverse Reactions (6.2)]. Do not administer RHOPHYLAC subcutaneously into the fatty tissue.
Refer to Table 1 (for dosing instructions in micrograms) and Table 2 (for dosing instructions in International Units) by indication.
| MICROGRAMS (mcg) | ||
|---|---|---|
| Indication | Timing of Administration | Dose*
(Administer by intravenous (IV) or intramuscular (IM) injection) |
| Rh-incompatible pregnancy | ||
| Routine antepartum prophylaxis | Week 28-30 of pregnancy | 300 mcg |
| Postpartum prophylaxis (required only if the newborn is Rh(D)-positive, or of unknown status) | Within 72 hours of birth | 300 mcg† |
| Obstetric complications (e.g., miscarriage, abortion, threatened abortion, ectopic pregnancy or hydatidiform mole, transplacental hemorrhage resulting from antepartum hemorrhage) | Within 72 hours of complication | 300 mcg† |
| Invasive procedures during pregnancy (e.g., amniocentesis, chorionic biopsy) or obstetric manipulative procedures (e.g., external version, abdominal trauma) | Within 72 hours of procedure | 300 mcg† |
| Excessive fetomaternal hemorrhage (>15 mL fetal RBCs) | Within 72 hours of complication | 300 mcg plus:
|
| Incompatible transfusions | Within 72 hours of exposure | 20 mcg per 2 mL transfused Rh(D)-positive whole blood or per 1 mL Rh(D)-positive RBCs |
* A 300 mcg dose of RHOPHYLAC will suppress the immunizing potential of ≤15 mL of fetal Rh(D)-positive RBCs.1
† The dose of RHOPHYLAC must be increased if the patient is exposed to >15 mL of fetal Rh(D)-positive RBCs; in this case, follow the dosing guidelines for excessive fetomaternal hemorrhage.
| INTERNATIONAL UNITS (IU) | ||
|---|---|---|
| Indication | Timing of Administration | Dose*
(Administer by intravenous (IV) or intramuscular (IM) injection) |
| Rh-incompatible pregnancy | ||
| Routine antepartum prophylaxis | Week 28-30 of pregnancy | 1500 IU |
| Postpartum prophylaxis (required only if the newborn is Rh(D)-positive, or of unknown status) | Within 72 hours of birth | 1500 IU† |
| Obstetric complications (e.g., miscarriage, abortion, threatened abortion, ectopic pregnancy or hydatidiform mole, transplacental hemorrhage resulting from antepartum hemorrhage) | Within 72 hours of complication | 1500 IU† |
| Invasive procedures during pregnancy (e.g., amniocentesis, chorionic biopsy) or obstetric manipulative procedures (e.g., external version, abdominal trauma) | Within 72 hours of procedure | 1500 IU† |
| Excessive fetomaternal hemorrhage (>15 mL fetal RBCs) | Within 72 hours of complication | 1500 IU plus:
|
| Incompatible transfusions | Within 72 hours of exposure | 100 IU per 2 mL transfused Rh(D)- positive whole blood or per 1 mL RBCs |
Treatment of ITP
For treatment of ITP, ADMINISTER RHOPHYLAC BY THE INTRAVENOUS ROUTE ONLY [see Dosage and Administration (2.1)]. Do not administer intramuscularly.
Calculate the dose of RHOPHYLAC for ITP on the basis of the patient's weight in kilograms (kg). Inappropriate use of pounds (lbs) will result in an overdose.
| Dose (mcg) | Rate of administration | |
|---|---|---|
| mcg = microgram | ||
| 50 mcg per kg body weight | 2 mL per 15 to 60 seconds | |
The following formula can be used to calculate the number of syringes of RHOPHYLAC to administer:
Dose (50 mcg) x body weight (kg) = Total mcg / 300 mcg per syringe = Number of syringes
1500 IU (300 mcg) per 2 mL single-dose, prefilled, ready-to-use, glass syringe for IV or IM use
RHOPHYLAC is contraindicated in:
Severe hypersensitivity reactions may occur even in patients who have tolerated previous administrations. If symptoms of allergic or early signs of hypersensitivity reactions (including generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis) occur, discontinue RHOPHYLAC administration immediately and institute appropriate treatment. Medications such as epinephrine should be available for immediate treatment of acute hypersensitivity reactions.
RHOPHYLAC contains trace amounts of IgA (less than 5 mcg/mL) [see Description (11)]. Patients with known antibodies to IgA have a risk of developing potentially severe hypersensitivity and anaphylactic reactions. RHOPHYLAC is contraindicated in patients with antibodies against IgA and a history of hypersensitivity reactions to RHOPHYLAC or any of its components [see Contraindications (4)].
The administration of Rh (D) immune globulin may affect the results of blood typing, the antibody screening test, and the direct antiglobulin (Coombs') test. Antepartum administration of Rh(D) immune globulin to the mother can also affect these tests in the newborn infant.
RHOPHYLAC can contain antibodies to other Rh antigens (e.g., anti-C antibodies), which might be detected by sensitive serological tests following administration.
Because RHOPHYLAC is made from human blood, it may carry a risk of transmitting infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. The risk of infectious agent transmission has been reduced by screening plasma donors for prior exposure to certain viruses, testing for the presence of certain current virus infections, and including virus inactivation/removal steps in the manufacturing process for RHOPHYLAC.
Report any infections thought to be possibly transmitted by RHOPHYLAC to CSL Behring Pharmacovigilance at 1-866-915-6958.
Serious intravascular hemolysis has occurred in a clinical study with RHOPHYLAC. All cases resolved completely. However, as reported in the literature, some Rh(D)-positive patients treated with Rh(D) Immune Globulin Intravenous (Human) for ITP developed clinically compromising anemia, acute renal insufficiency, and, very rarely, disseminated intravascular coagulation (DIC) and death.2 Note: This warning does not apply to Rh(D)-negative patients treated for the suppression of Rh isoimmunization.
Monitor patients in a healthcare setting for at least 8 hours after administration of RHOPHYLAC. Perform a dipstick urinalysis at baseline, 2 hours and 4 hours after administration, and prior to the end of the monitoring period.
Alert patients to, and monitor them for, the signs and symptoms of intravascular hemolysis, including back pain, shaking chills, fever, and discolored urine or hematuria. Absence of these signs and/or symptoms of intravascular hemolysis within 8 hours do not indicate intravascular hemolysis cannot occur subsequently.
If signs and/or symptoms of intravascular hemolysis are present or suspected after RHOPHYLAC administration, perform post-treatment laboratory tests, including plasma hemoglobin, haptoglobin, LDH, and plasma bilirubin (direct and indirect). DIC may be difficult to detect in the ITP population; the diagnosis is dependent mainly on laboratory testing.
If patients who develop hemolysis with clinically compromising anemia after receiving RHOPHYLAC are to be transfused, Rh(D)-negative packed RBCs should be used to avoid exacerbating ongoing hemolysis.
The safety of RHOPHYLAC in the treatment of ITP has not been established in patients with pre-existing anemia. RHOPHYLAC may increase the severity of anemia.
The most serious adverse reactions in patients receiving Rh(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, and Warnings and Precautions (5.4)].2
The most common adverse reactions observed with 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.
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 Rh(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 Rh(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 (14.1)].
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.
ITP
In a clinical study, 98 Rh(D)-positive adult subjects with chronic ITP received an intravenous dose of RHOPHYLAC 250 IU (50 mcg) per kg body weight [see Clinical Studies (14.2)]. Premedication to alleviate infusion-related side effects was not used except in a single subject who received acetaminophen and diphenhydramine.
Sixty-nine (70.4%) subjects had 186 adverse events. Within 24 hours of dosing, 73 (74.5%) subjects experienced 183 Treatment Emergent Adverse Events, and 66 (67%) subjects experienced 156 adverse reactions.
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 4 shows the most common adverse reactions observed in the clinical study.
| TEAR | Number of Subjects (%) With a TEAR n=98 |
|---|---|
| Chills | 34 (34.7%) |
| Pyrexia/ Increased body temperature | 30 (30.6%) |
| Increased blood bilirubin | 21 (21.4%) |
| Headache | 11 (11.2%) |
Serious adverse reactions (SARs) were reported in 4 (4.1%) subjects. SARs 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.
There have been reports of lack of effect in patients with a body mass index ≥30 when administration via the intramuscular route was attempted [see Dosing and Administration (2.2)].
ITP
Transient hemoglobinuria has been reported in a patient being treated with RHOPHYLAC for ITP.
Passive transfer of antibodies may transiently impair the immune response to live attenuated virus vaccines such as measles, mumps, rubella, and varicella [see Patient Counseling Information (17)]. Do not immunize with live vaccines within 3 months after the final dose of RHOPHYLAC. If RHOPHYLAC is administered within 14 days after administration of a live vaccine, the immune response to the vaccination may be inhibited.3
Risk Summary
Animal reproduction studies have not been conducted with Rhophylac.
Suppression of Rh Isoimmunization
RHOPHYLAC is used in pregnant women for the suppression of Rh isoimmunization. When administered to pregnant women in a clinical trial to evaluate RHOPHYLAC for suppression of Rh isoimmunization [see Clinical Studies (14.1) ] following dosing regimens similar to Table 1 or 2 [see Dosage and Administration (2.2) ], RHOPHYLAC was not shown to harm the fetus or newborn.11 In general, anti-D immunoglobulins have been shown to not harm the fetus or affect future pregnancies or reproduction capacity when given to pregnant Rh(D)-negative women for suppression of Rh isoimmunization.4
ITP
RHOPHYLAC has not been evaluated in pregnant women with ITP.
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.
Risk Summary
There is no information regarding the presence of RHOPHYLAC in human milk, the effect on the breastfed infant, and the effects on milk production. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for RHOPHYLAC and any potential adverse effects on the breastfed child from RHOPHYLAC or from the underlying maternal condition.
Suppression of Rh Isoimmunization
RHOPHYLAC is used in nursing mothers for the suppression of Rh isoimmunization.
ITP
RHOPHYLAC has not been evaluated in nursing mothers with ITP.
Suppression of Rh Isoimmunization in Incompatible Transfusions
The safety and effectiveness of RHOPHYLAC have not been established in pediatric subjects being treated for an incompatible transfusion. The physician should weigh the potential risks against the benefits of RHOPHYLAC, particularly in girls whose later pregnancies may be affected if Rh isoimmunization occurs.
Chronic ITP
The safety and effectiveness of RHOPHYLAC have not been established in pediatric subjects with chronic ITP. Dosing in the treatment of children with chronic ITP is expected to be similar to adults.
Suppression of Rh Isoimmunization in Incompatible Transfusions
RHOPHYLAC has not been evaluated for treating incompatible transfusions in subjects 65 years of age and older.
ITP
Of the 98 subjects evaluated in the clinical study of RHOPHYLAC for treatment of ITP [see Clinical Studies (14.2)], 19% were 65 years of age and older. No overall differences in effectiveness or safety were observed between these subjects and younger subjects.
During clinical trials, there were no reports of known overdoses in patients being treated for suppression of Rh isoimmunization or ITP. In postmarketing reporting, there have been a limited number of overdose reports including medication error reports related to dosage calculations in which higher doses than that recommended for RHOPHYLAC were administered potentially due to confusion between mcg and international units (IU). In these reports there were no adverse reactions identified due to overdose. Patients with incompatible transfusion or ITP who receive an overdose of Rh(D) immune globulin should be monitored because of the potential risk for hemolysis.
RHOPHYLAC is a sterile Rh(D) Immune Globulin Intravenous (Human) (anti-D) solution in a ready-to-use prefilled glass syringe for intravenous or intramuscular injection. One syringe contains at least 1500 IU (300 mcg) of IgG antibodies to Rh(D) in a 2 mL solution, sufficient to suppress the immune response to at least 15 mL of Rh(D)-positive RBCs.1 The product potency is expressed in IUs by comparison to the World Health Organization (WHO) standard, which is also the US and the European Pharmacopoeia standard.
Plasma is obtained from healthy Rh(D)-negative donors who have been immunized with Rh(D)-positive RBCs. The donors are screened carefully to reduce the risk of receiving donations containing blood-borne pathogens. Each plasma donation used in the manufacture of RHOPHYLAC is tested for the presence of HBV surface antigen (HBsAg), HIV-1/2, and HCV antibodies. In addition, plasma used in the manufacture of RHOPHYLAC is tested by FDA-licensed Nucleic Acid Testing (NAT) for HBV, HCV, and HIV-1 and found to be negative. The source plasma is also tested by NAT for hepatitis A virus (HAV) and B19 virus (B19V).
RHOPHYLAC is produced by an ion-exchange chromatography isolation procedure5, using pooled plasma obtained by plasmapheresis of immunized Rh(D)-negative US donors.
The manufacturing process of RHOPHYLAC includes two dedicated virus reduction steps (i.e., solvent/detergent treatment and virus filtration with a Planova® 15 nanometer (nm) virus filter) as well as one ion exchange chromatography step contributing to virus reduction.6,7 All three virus reduction steps have been independently validated in a series of in vitro experiments for their capacity to inactivate or remove enveloped and/or non-enveloped viruses. Virus models were chosen to cover a broad selection of viruses, including the major blood-transmissible viruses like human immunodeficiency virus, hepatitis B and hepatitis C virus, as well as small, non-enveloped viruses like hepatitis A virus and human parvovirus B19. Viral clearance data from validation studies of the dedicated virus reduction steps for both enveloped and nonenveloped viruses will be provided upon request by calling 1-800-504-5434. Overall virus reduction expressed as mean log10 reduction factor of model enveloped and non-enveloped viruses has been shown to be ≥11 log10 and ≥9 log10 respectively.
RHOPHYLAC contains a maximum of 30 mg/mL of human plasma proteins, 10 mg/mL of which is human albumin added as a stabilizer. Prior to the addition of the stabilizer, RHOPHYLAC has a purity greater than 95% IgG. RHOPHYLAC contains less than 5 mcg/mL of IgA, which is the limit of detection. Additional excipients are approximately 20 mg/mL of glycine and up to 0.25 M of sodium chloride. RHOPHYLAC contains no preservative. Human albumin is manufactured from pooled plasma of US donors by cold ethanol fractionation, followed by pasteurization.
Suppression of Rh Isoimmunization
The mechanism by which Rh(D) immune globulin suppresses immunization to Rh(D)-positive RBCs is not completely known.
In a clinical study of Rh(D)-negative healthy male volunteers, both the intravenous and intramuscular administration of a 1500 IU (300 mcg) dose of RHOPHYLAC 24 hours after injection of 15 mL of Rh(D)-positive RBCs resulted in an effective clearance of Rh(D)-positive RBCs. On average, 99% of injected RBCs were cleared within 12 hours following intravenous administration and within 144 hours following intramuscular administration.
ITP
RHOPHYLAC has been shown to increase platelet counts and to reduce bleeding in non-splenectomized Rh(D)-positive subjects with chronic ITP. The mechanism of action is thought to involve the formation of Rh(D) immune globulin RBC complexes, which are preferentially removed by the reticuloendothelial system, particularly the spleen. This results in Fc receptor blockade, thus sparing antibody-coated platelets.8
Suppression of Rh Isoimmunization
In a clinical study comparing the pharmacokinetics of intravenous versus intramuscular administration, 15 Rh(D)-negative pregnant women received a single 1500 IU (300 mcg) dose of RHOPHYLAC at Week 28 of gestation.9
Following intravenous administration, peak serum levels of Rh(D) immune globulin ranged from 62 to 84 ng/mL after 1 day (i.e., the time the first blood sample was taken following the antepartum dose). Mean systemic clearance was 0.20 ± 0.03 mL/min, and half-life was 16 ± 4 days.
Following intramuscular administration, peak serum levels ranged from 7 to 46 ng/mL and were achieved between 2 and 7 days. Mean apparent clearance was 0.29 ± 0.12 mL/min, and half-life was 18 ± 5 days. The absolute bioavailability of RHOPHYLAC was 69%.
Regardless of the route of administration, Rh(D) immune globulin titers were detected in all women up to at least 9 weeks following administration of RHOPHYLAC.
ITP
Pharmacokinetic studies with RHOPHYLAC were not performed in Rh(D)-positive subjects with ITP. Rh(D) immune globulin binds rapidly to Rh(D)-positive erythrocytes.10
In two clinical studies, 447 Rh(D)-negative pregnant women received a 1500 IU (300 mcg) dose of RHOPHYLAC during Week 28 of gestation. The women who gave birth to an Rh(D)-positive baby received a second 1500 IU (300 mcg) dose within 72 hours of birth.
In an open-label, single-arm, multicenter study, 98 Rh(D)-positive adult subjects with chronic ITP and a platelet count of 30 × 109/L or less were treated with RHOPHYLAC. Subjects received a single intravenous dose of 250 IU (50 mcg) per kg body weight.
The primary efficacy endpoint was the response rate defined as achieving a platelet count of ≥30 × 109/L as well as an increase of >20 × 109/L within 15 days after treatment with RHOPHYLAC. Secondary efficacy endpoints included the response rate defined as an increase in platelet counts to ≥50 × 109/L within 15 days after treatment and, in subjects who had bleeding at baseline, the regression of hemorrhage defined as any decrease from baseline in the severity of overall bleeding status.
Table 5 presents the primary response rates for the intent-to-treat (ITT) and per-protocol (PP) populations.
| Primary Response Rate at Day 15 | ||||
|---|---|---|---|---|
| Analysis Population | No. Subjects | No. Responders | % Responders | 95% Confidence Interval (CI) |
| ITT | 98 | 65 | 66.3% | 56.5%, 74.9% |
| PP | 92 | 62 | 67.4% | 57.3%, 76.1% |
The primary efficacy response rate (ITT population) demonstrated a clinically relevant response to treatment, i.e., the lower bound of the 95% confidence interval (CI) was greater than the predefined response rate of 50%. The median time to platelet response was 3 days, and the median duration of platelet response was 22 days.
Table 6 presents the response rates by baseline platelet count for subjects in the ITT population.
| Response Rates at Day 15 | |||
|---|---|---|---|
| Baseline Platelet count (× 109/L) | Total No. Subjects | No. (%) Subjects Achieving a Platelet Count of ≥30 × 109/L and an Increase of >20 × 109/L | No. (%) Subjects With an Increase in Platelet Counts to ≥50 × 109/L |
| ≤10 | 38 | 15 (39.5) | 10 (26.3) |
| >10 to 20 | 28 | 22 (78.6) | 17 (60.7) |
| >20 to 30 | 27 | 24 (88.9) | 22 (81.5) |
| >30* | 5 | 4 (80.0) | 5 (100.0) |
| Overall (all subjects) | 98 | 65 (66.3) | 54 (55.1) |
* Reflects subjects with a platelet count of ≤30 × 109/L at screening but >30 × 109/L immediately before treatment.
During the study, an overall regression of hemorrhage was seen in 44 (88%, 95% CI: 76% to 94%) of the 50 subjects with bleeding at baseline. The percentage of subjects showing a regression of hemorrhage increased from 20% at Day 2 to 64% at Day 15. There was no evidence of an association between the overall hemorrhage regression rate and baseline platelet count.
Approximately half of the 98 subjects in the ITT population had evidence of bleeding at baseline. Post-baseline, the percentage of subjects without bleeding increased to a maximum of 70.4% at Day 8.
Each product presentation includes a package insert and the following components:
| Presentation | Carton NDC Number | Components |
|---|---|---|
| 1500 IU (300 mcg) | 44206-300-01 |
|
| 1500 IU (300 mcg) Multipack | 44206-300-10 |
|
Storage and Handling
Please inform patients of the following:
Manufactured by:
CSL Behring AG
Bern, Switzerland
US License No. 1766
Distributed by:
CSL Behring LLC
Kankakee, IL 60901 USA
Planova® is a registered trademark of Asahi Kasei Medical Co., Ltd.
SafetyGlide™ is a trademark of Becton, Dickinson and Company
NDC 44206-300-01
300 mcg
Rh₀(D) Immune Globulin Intravenous (Human)
Rhophylac®
1500 IU
For Intravenous or Intramuscular Injection. Rx only
CSL Behring
NDC 44206-300-10
300 mcg
Rh₀(D) Immune Globulin
Intravenous (Human)
Rhophylac®
1500 IU
For Intravenous or Intramuscular Injection.
Rx only
CSL Behring
| RxCUI | RxNorm string | TTY | SPL version |
|---|---|---|---|
| 1117759 | rho(D) immune globulin, human 1500 UNT in 2 ML Prefilled Syringe | PSN | 15 |
| 1117765 | Rhophylac 1500 UNT in 2 ML Prefilled Syringe | PSN | 15 |
| 1117765 | 2 ML Rho(D) immune globulin, human 750 UNT/ML Prefilled Syringe [Rhophylac] | SBD | 15 |
| 1117759 | 2 ML Rho(D) immune globulin, human 750 UNT/ML Prefilled Syringe | SCD | 15 |
| 1117765 | 2 ML Rhophylac 750 UNT/ML Prefilled Syringe | SY | 15 |
| 1117759 | rho(D) immune globulin, human 1500 UNT per 2 ML Prefilled Syringe | SY | 15 |
| 1117765 | Rhophylac 1500 UNT per 2 ML Prefilled Syringe | SY | 15 |
| Class | Version | Type | Effective |
|---|---|---|---|
| HUMAN RHO(D) IMMUNE GLOBULIN Pharmacologic Class Indexing | 2 | Indexing - Pharmacologic Class | 20180813 |
| Product concept | Relation | Version | Effective |
|---|---|---|---|
| 0ca1d589-929b-4b33-bc5b-1d84abdafa6a | Product name | 1 | 20150324 |
| fc363c46-397b-4476-ac0f-70e43e8e4592 | Product name | 1 | 20150324 |
| Package NDC | Product | Description | Form | Quantity | Strength | SPL version |
|---|---|---|---|---|---|---|
| 44206-300-01 | Rhophylac | 1 in 1 CARTON | SOLUTION | 1 | 15 | |
| 44206-300-10 | Rhophylac | 10 in 1 CARTON | SOLUTION | 10 | 15 | |
| 44206-300-90 | Rhophylac | 2 mL in 1 SYRINGE, GLASS | SOLUTION | 2 | 15 |
| Package NDC | Billing unit | Product NDC | DailyMed indexing SPL | SPL version | Effective |
|---|---|---|---|---|---|
| 44206-300-01 | ML - Milliliter | 44206-300 | 684a85fa-cf37-470b-96c2-7f3b452f0ea7 | 1 | 2012-07-24 |
| 44206-300-10 | ML - Milliliter | 44206-300 | a304dd5e-ea2f-4b7a-883a-26c15e281984 | 1 | 2012-07-24 |
| 44206-300-90 | ML - Milliliter | 44206-300 | 0f9064af-27d7-4475-9e78-1fc7bc443edb | 1 | 2017-03-06 |
| Ingredient | Type | UNII | SPL version | Uploaded |
|---|---|---|---|---|
| HUMAN RHO(D) IMMUNE GLOBULIN | ACTIVE INGREDIENT | 48W7181FLP | 7 | |
| HUMAN RHO(D) IMMUNE GLOBULIN | ACTIVE MOIETY | 48W7181FLP | 7 | |
| Albumin Human | INACTIVE INGREDIENT | ZIF514RVZR | 7 | |
| Glycine | INACTIVE INGREDIENT | TE7660XO1C | 7 | |
| Human Immunoglobulin A | INACTIVE INGREDIENT | 741C1PWQ88 | 7 | |
| Sodium Chloride | INACTIVE INGREDIENT | 451W47IQ8X | 7 |
Every source-derived product name is available through these pages.
| Product NDC | Package NDC |
|---|---|
| 44206-300 | 44206-300-90, 44206-300-01, 44206-300-10 |
| BLA | Proprietary name | Proper name | License type | Status | Latest source |
|---|---|---|---|---|---|
| 125070 | Rhophylac | Rho(D) Immune Globulin Intravenous (Human) | 351(a) | Rx | 2026-09-01 |
Every source-derived ingredient row is available through these pages.
| Name | UNII | Kind |
|---|---|---|
| HUMAN RHO(D) IMMUNE GLOBULIN | 48W7181FLP | ACTIB |
| Albumin Human | ZIF514RVZR | IACT |
| Human Immunoglobulin A | 741C1PWQ88 | IACT |
| Glycine | TE7660XO1C | IACT |
| Sodium Chloride | 451W47IQ8X | IACT |
Inactive Ingredient Database values describe FDA-listed use contexts. The match method and ambiguity count are shown because ingredient names, routes, and dosage forms are not always unique. Browse recovered IID releases and source provenance.
| DailyMed ingredient | IID ingredient | UNII | Dosage form / route | Potency | Maximum daily exposure | Match |
|---|---|---|---|---|---|---|
| Glycine | GLYCINE | TE7660XO1C | INJECTION / INTRAVENOUS | 200 mg | ||
| Sodium Chloride | SODIUM CHLORIDE | 451W47IQ8X | SOLUTION / INTRAMUSCULAR | 90 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION, POWDER, FOR SOLUTION / INTRAVENOUS | 3.76 mg | ||
| Glycine | GLYCINE | TE7660XO1C | SOLUTION / ORAL | 50 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION, SOLUTION / INTRAVENOUS | 0.42 %w/v | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION, POWDER, FOR SOLUTION / INTRAMUSCULAR | 40 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION, POWDER, FOR SOLUTION / INTRAVENOUS | 3.76 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION / INTRAVENOUS | 200 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 200 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION, SOLUTION / INTRAVENOUS | 0.42 %w/v | ||
| Albumin Human | ALBUMIN HUMAN | ZIF514RVZR | INJECTION, POWDER, FOR SUSPENSION / INTRAVENOUS | 4212 mg | ||
| Glycine | GLYCINE | TE7660XO1C | SOLUTION / ORAL | 50 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION, SOLUTION / INTRAVENOUS | 0.42 %w/v | ||
| Sodium Chloride | SODIUM CHLORIDE | 451W47IQ8X | SOLUTION / INTRAMUSCULAR | 90 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 200 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION / INTRAVENOUS | 200 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTABLE, LIPOSOMAL / INTRAVENOUS | 0.38 %w/v | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 200 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION / INTRAMUSCULAR | 68 mg | ||
| Glycine | GLYCINE | TE7660XO1C | SOLUTION / ORAL | 50 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTABLE, LIPOSOMAL / INTRAVENOUS | 0.38 %w/v | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION / INTRAMUSCULAR | 68 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION / INTRAVENOUS | 200 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION, POWDER, FOR SOLUTION / INTRAVENOUS | 3.76 mg | ||
| Sodium Chloride | SODIUM CHLORIDE | 451W47IQ8X | SOLUTION / INTRAVENOUS | 90 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTABLE, LIPOSOMAL / INTRAVENOUS | 0.38 %w/v | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION / INTRAMUSCULAR | 68 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION, POWDER, FOR SOLUTION / INTRAMUSCULAR | 40 mg | ||
| Glycine | GLYCINE | TE7660XO1C | SOLUTION / ORAL | 50 mg | ||
| Sodium Chloride | SODIUM CHLORIDE | 451W47IQ8X | SOLUTION / INTRAVENOUS | 90 mg | ||
| Glycine | GLYCINE | TE7660XO1C | SOLUTION / ORAL | 50 mg | ||
| Glycine | GLYCINE | TE7660XO1C | SOLUTION / ORAL | 50 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION, POWDER, FOR SOLUTION / INTRAMUSCULAR | 40 mg | ||
| Sodium Chloride | SODIUM CHLORIDE | 451W47IQ8X | SOLUTION / INTRAMUSCULAR | 90 mg | ||
| Albumin Human | ALBUMIN HUMAN | ZIF514RVZR | INJECTION, POWDER, FOR SUSPENSION / INTRAVENOUS | 4212 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION, POWDER, FOR SOLUTION / INTRAVENOUS | 3.76 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION / INTRAMUSCULAR | 68 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION, POWDER, FOR SOLUTION / INTRAMUSCULAR | 40 mg | ||
| Glycine | GLYCINE | TE7660XO1C | SOLUTION / ORAL | 50 mg | ||
| Sodium Chloride | SODIUM CHLORIDE | 451W47IQ8X | SOLUTION / INTRAVENOUS | 90 mg | ||
| Albumin Human | ALBUMIN HUMAN | ZIF514RVZR | INJECTION, POWDER, FOR SUSPENSION / INTRAVENOUS | 4212 mg | ||
| Sodium Chloride | SODIUM CHLORIDE | 451W47IQ8X | SOLUTION / INTRAVENOUS | 90 mg | ||
| Glycine | GLYCINE | TE7660XO1C | SOLUTION / ORAL | 50 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION, SOLUTION / INTRAVENOUS | 0.42 %w/v | ||
| Sodium Chloride | SODIUM CHLORIDE | 451W47IQ8X | SOLUTION / INTRAMUSCULAR | 90 mg | ||
| Albumin Human | ALBUMIN HUMAN | ZIF514RVZR | INJECTION, POWDER, FOR SUSPENSION / INTRAVENOUS | 4212 mg | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTABLE, LIPOSOMAL / INTRAVENOUS | 0.38 %w/v | ||
| Glycine | GLYCINE | TE7660XO1C | INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION / INTRAVENOUS | 200 mg |
OpenFDA label data provides additional search and identifier links. DailyMed’s Structured Product Label is the canonical label on FDA.report. Matching records are deduplicated before they are shown below.
| Brand | Generic | Manufacturer | SPL set ID | Effective date | Available safety fields | Join |
|---|---|---|---|---|---|---|
| 1b2389ac-8403-4888-9221-0045996130b9 | c1b5d801-336f-4541-a7d9-a8d4a110a4cc | 2010-09-29 | Boxed warning, Warnings, Adverse reactions | c1b5d801-336f-4541-a7d9-a8d4a110a4cc |
Adverse event summaries are temporarily unavailable. Other product information remains available.