Rho(D) immune globulin

Action and Spectrum

Actions and Spectrum: 

Rho(D) immune globulin, also known as Rh immune globulin or anti-D immunoglobulin, is a medication used to prevent complications related to Rh incompatibility during pregnancy. Rh incompatibility can occur when a pregnant woman with an Rh-negative blood type carries a fetus with an Rh-positive blood type. 

Rho(D) immune globulin prevents the mother’s immune system from producing antibodies against the Rh factor, a protein found on the surface of red blood cells. When an Rh-negative woman is exposed to Rh-positive blood (typically during childbirth or through a miscarriage, abortion, or trauma), her immune system might produce antibodies against the Rh factor. These antibodies might cross the placenta and attack the red blood cells (R.B.C) of an Rh-positive fetus, leading to a condition known as hemolytic disease of the newborn (HDN). 

Rho(D) immune globulin contains antibodies targeted explicitly against the Rh factor. When administered to an Rh-negative woman, the immune globulin binds to any Rh-positive red blood cells that may have entered her bloodstream, preventing her immune system from recognizing and producing antibodies against them. By blocking this immune response, Rho(D) immune globulin helps to prevent the sensitization of the mother and subsequent complications for the fetus in future pregnancies. 

The spectrum of Rho(D) immune globulin primarily focuses on preventing Rh sensitization and the resulting hemolytic disease of the newborn. It is typically given to Rh-negative women in the following situations: 

• During pregnancy: Rho(D) immune globulin is commonly administered to Rh-negative women around 28 weeks of gestation to prevent sensitization in case fetal and maternal blood is mixed during pregnancy. It is also administered within 72 hours after delivery if the newborn is Rh-positive. 
• Following potentially sensitizing events: Rho(D) immune globulin may be given after events that could lead to the mixing of fetal and also maternal blood, such as miscarriage, ectopic pregnancy, abortion, amniocentesis, chorionic villus sampling, or trauma during pregnancy. This helps to prevent sensitization in case the fetus is Rh-positive. 
• After blood transfusion: Rho(D) immune globulin may be given to prevent sensitization if an Rh-negative person receives an Rh-positive blood transfusion. 

It’s important to note that Rho(D) immune globulin does not treat an existing sensitization or HDN. Its primary purpose is to prevent sensitization in Rh-negative women and subsequent complications in future pregnancies. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Allergic reaction 

Tenderness 

Urticaria 

Infrequent elevation in the total bilirubin 

Angioedema 

Black Box Warning

Black Box Warning: 

A black box warning is associated with one specific formulation called WinRho SDF (Rho(D) immune globulin intravenous). The black box warning for WinRho SDF is related to the risk of intravascular hemolysis (IVH), where red blood cells are destroyed in the bloodstream. The black box warning highlights the potential for IVH using WinRho SDF and emphasizes the need for close monitoring and careful dosing. 

Here is an example of the black box warning for WinRho SDF regarding IVH: 

“WARNING: INTRAVASCULAR HEMOLYSIS (IVH) AND ACUTE RENAL DYSFUNCTION 

• Intravascular hemolysis leading to clinically compromising anemia, multi-system organ failure, and disseminated intravascular coagulation (DIC) has been reported in patients treated with WinRho SDF. 
• Acute renal dysfunction/failure, acute respiratory distress syndrome (ARDS), circulatory overload, and pulmonary edema have been reported in patients treated with WinRho SDF. 

Consequently, WinRho SDF should be administered only by intravenous injection. 

Careful patient monitoring and judicious use of diuretics are recommended to avoid the occurrence of circulatory overload, particularly in elderly patients or in those with preexisting cardiac or renal impairment. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

The contraindications of Rho(D) immune globulin (Rh immune globulin or anti-D immunoglobulin) can vary based on the specific product and formulation. However, there are a few general contraindications that may apply. It’s essential to consult the specific product’s prescribing information or seek medical advice for accurate and up-to-date information. Here are some common contraindications associated with Rho(D) immune globulin: 

• Known severe allergic reaction: Rho(D) immune globulin should not be generally administered to people with a prior history of severe allergic reactions (anaphylaxis) or hypersensitivity to human immunoglobulin products or any formulation component. 
• Immunoglobulin A (IgA) deficiency: Individuals with selective IgA deficiency or a history of IgA deficiency and known antibodies against IgA should not receive Rho(D) immune globulin, as it contains small amounts of IgA. 
• Active hemolysis: Rho(D) immune globulin is not recommended for individuals with ongoing hemolysis (destruction of red blood cells), as it may not be effective in preventing sensitization in such cases. 
• Prior sensitization: If a woman has been previously sensitized to the Rh factor, Rho(D) immune globulin is ineffective in preventing the development of the hemolytic disease of the newborn (HDN) in subsequent pregnancies. 

It is key to note that the contraindications may vary among different formulations and products of Rho(D) immune globulin. 

Caution 

Specific cautions associated with Rho(D) immune globulin: 

• Allergic reactions: Although severe allergic reactions are infrequent, Rho(D) immune globulin is derived from human plasma and can potentially cause allergic reactions. Healthcare providers should closely monitor individuals for any signs of allergic reactions during and after administration. 
• Transmissible infectious agents: As with any blood-derived product, Rho(D) immune globulin risks containing infectious agents, including viruses and prions. Donors are screened, and strict manufacturing processes are followed to minimize this risk. However, it is key to consider the potential risk and benefit when using Rho(D) immune globulin. 
• Interference with blood typing: Rho(D) immune globulin can interfere with blood typing, leading to inaccurate results. This interference can last for several weeks following administration. It’s crucial to inform healthcare providers about the recent administration of Rho(D) immune globulin when blood typing or crossmatching is required. 
• Administration of live vaccines: Rho(D) immune globulin might interfere with the immune response to live vaccines, such as measles, mumps, rubella, varicella, and rotavirus vaccines. It is recommended to wait nearly three months after administering Rho(D) immune globulin before administering live vaccines. 
• Monitoring of Rh status: Rho(D) immune globulin administration does not change the Rh status of an individual. Rh-negative individuals should continue to be identified as such for appropriate medical management. 

These are general cautions associated with Rho(D) immune globulin and specific instructions and precautions may vary among different products.

Pregnancy / Lactation

Pregnancy consideration:  

AU TGA pregnancy category: C
US FDA pregnancy category: C 

Lactation:   

Excreted into human milk: Yes 

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    
• Category N: There is no data available for the drug under this category 

Pharmacology

Pharmacology: 

Rho(D) immune globulin (Rh immune globulin or anti-D immunoglobulin) is a sterile solution containing antibodies targeted explicitly against the Rh factor, a protein found on the surface of R.B.C (red blood cells). The pharmacology of Rho(D) immune globulin involves its mechanism of action, distribution, metabolism, and elimination from the body. 

Rho(D) immune globulin works by binding to any Rh-positive R.B.C (red blood cells) that may have entered the bloodstream of an Rh-negative individual. Binding to these Rh-positive red blood cells prevents the individual’s immune system from recognizing them as foreign and producing antibodies against them. This mechanism helps to prevent sensitization, which could lead to complications in subsequent pregnancies. 

Pharmacodynamics: 

Mechanism of action: The action of Rho(D) immune globulin (Rh immune globulin or anti-D immunoglobulin) involves its specific binding to the Rh factor on the surface of red blood cells. Here’s a detailed explanation of its mechanism of action: 

• Prevention of Antibody Formation: Rho(D) immune globulin is administered to Rh-negative individuals to prevent the formation of antibodies against the Rh factor. If an Rh-negative individual is exposed to Rh-positive blood (such as during pregnancy or after certain events like miscarriage or transfusion), there is a risk of sensitization. Sensitization occurs when the Rh-negative individual’s immune system recognizes the Rh-positive blood as foreign and produces antibodies against the Rh factor. 
• Binding to Rh-Positive Red Blood Cells: Rho(D) immune globulin contains antibodies targeted explicitly against the Rh factor. When administered, these antibodies bind to Rh-positive red blood cells that have entered the bloodstream of an Rh-negative individual. By binding to the Rh-positive red blood cells, Rho(D) immune globulin prevents the individual’s immune system from recognizing them as foreign. 
• Prevention of Immune Response: The binding of Rho(D) immune globulin to Rh-positive red blood cells prevents the individual’s immune system from initiating an immune response. Usually, when Rh-negative individuals encounter Rh-positive blood, their immune system might produce antibodies against the Rh factor, leading to sensitization. By binding to the Rh-positive cells, Rho(D) immune globulin masks the Rh factor and prevents the immune system from recognizing it as foreign. This prevents the production of antibodies against the Rh factor, thus preventing sensitization. 
• Clearance of Rh-Positive Red Blood Cells: Additionally, Rho(D) immune globulin aids in the clearance of any Rh-positive red blood cells that have already entered the circulation of an Rh-negative individual. The bound immune globulin can help remove Rh-positive cells from the bloodstream through mechanisms like phagocytosis by immune system cells. 

Pharmacokinetics: 

Absorption 

Rho(D) immune globulin is typically administered via intramuscular injection. The immune globulin is expected to be readily absorbed into the bloodstream following injection. The absorption rate might vary depending on the injection site, technique, and individual patient characteristics. 

Distribution 

Once in the bloodstream, Rho(D) immune globulin is distributed throughout the body. It binds to Rh-positive red blood cells that are present in the circulation. Rho(D) immune globulin distribution is expected to be similar to other immunoglobulin products. 

Metabolism 

The metabolism of Rho(D) immune globulin is not extensively characterized. It is an immunoglobulin product composed of human antibodies and is expected to undergo degradation and catabolism within the body. Metabolism may involve processes such as proteolysis and recycling of the constituent amino acids. 

Elimination and Excretion 

The specific excretion pathway of Rho(D) immune globulin has yet to be well-defined. Like other proteins, it is likely to be eliminated from the body through various routes, including renal and hepatic clearance. The exact mechanisms and rates of excretion need to be well-documented. 

Adminstartion

Administration: 

Intramuscular/Intravenous administration 

The administration of Rho(D) immune globulin (Rh immune globulin or anti-D immunoglobulin) should be done under the supervision of a healthcare professional. The specific administration instructions may vary depending on the product and formulation, so it’s essential to consult the prescribing information and follow the guidance provided. Here are some general guidelines for the administration of Rho(D) immune globulin: 

• Timing of administration: Rho(D) immune globulin is typically administered at specific time points during pregnancy and after potential sensitizing events. The timing may vary depending on the healthcare provider’s recommendations and the specific circumstances. Expected administration time points include around 28 weeks of gestation and within three days after delivery if the newborn is Rh-positive. After potential sensitizing events, such as miscarriage, abortion, or trauma, Rho(D) immune globulin may be administered within a specific timeframe as advised by the healthcare provider. 
• Route of administration: Rho(D) immune globulin is usually administered by intramuscular injection. The selected injection site is the deltoid muscle (upper arm) or the gluteus maximus muscle (buttocks). The healthcare provider will determine the appropriate injection site based on factors such as the volume of the medication and patient preference. 
• Dosage: Rho(D) immune globulin dosage is determined based on the specific product and the individual’s circumstances. The dosage may depend on factors such as the patient’s Rh-negative status, the volume of fetal-maternal hemorrhage, or the potential sensitizing event. The healthcare provider will calculate and administer the appropriate dosage for each individual. 
• Monitoring and observation: After the administration of Rho(D) immune globulin, the healthcare provider may monitor the individual for a period to ensure no adverse reactions. This may involve observing for signs of allergic reactions or other potential side effects. It’s essential to promptly report any unusual symptoms or concerns to the healthcare provider. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: Rho(D) immune globulin 

Why do we use Rho(D) immune globulin? 

Rho(D) immune globulin (Rh immune globulin or anti-D immunoglobulin) is primarily used to prevent complications related to Rh incompatibility during pregnancy. Rh incompatibility can occur when a pregnant woman with an Rh-negative blood type carries a fetus with an Rh-positive blood type. The primary uses of Rho(D) immune globulin include: 

• Prevention of sensitization during pregnancy: Rho(D) immune globulin is commonly administered to Rh-negative women during pregnancy to prevent sensitization. It is typically given around 28 weeks of gestation. The purpose is to prevent the mother’s immune system from producing antibodies against the Rh factor, which could potentially lead to complications in subsequent pregnancies. 
• Prevention of sensitization after potential sensitizing events: Rho(D) immune globulin may be administered after certain events that can result in mixing fetal and maternal blood. These events include miscarriage, abortion, ectopic pregnancy, amniocentesis, chorionic villus sampling, trauma during pregnancy, or any other circumstance with a risk of fetal-maternal hemorrhage. The administration of Rho(D) immune globulin in such situations helps to prevent sensitization in case the fetus is Rh-positive. 
• Prevention of sensitization after delivery: Rho(D) immune globulin is also given within 72 hours after delivery if the newborn is Rh-positive. This is done to prevent sensitization in case fetal and maternal blood is mixed during the birth process. 

The primary goal of using Rho(D) immune globulin is to prevent sensitization of the Rh-negative mother to the Rh factor and subsequent complications in future pregnancies. By administering Rho(D) immune globulin, the formation of Rh antibodies is inhibited, reducing the risk of hemolytic disease of the newborn in subsequent pregnancies.