Pharmaceutical Name

Trade (marketing or proprietary) name: Rhophylac®

Generic (nonproprietary or active ingredient) name: Rh0 (D) Immune Globulin Intravenous (Human). Also known as “Anti-D” in the United Kingdom.

Indication and Usage

Reason the product has been approved for sale on the market.

This sterile Rh0 (D) Immune Globulin Intravenous (Human) solution is approved to be used in two main scenarios: Suppression of rhesus (Rh) isoimmunization and Immune thrombocytopenic purpura (ITP).

Manufacturer Insert

Ingredients

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.

Contraindications

Per the FDA, contraindications are conditions in a recipient that increases the risk for a serious adverse reaction. Product should not be administered when a patient has a listed contraindication.

Individuals known to have had an anaphylactic or severe systemic reaction to the administration of human immune globulin products should not receive Rh0 (D) immune globulin.

Warnings and Precautions

Per the FDA, warnings are clinically significant adverse reactions or risks. According to the CDC, a precaution is a condition in a recipient that might increase the risk for a serious adverse reaction, might cause diagnostic confusion, or might compromise the effectiveness of the product. In general, a product should be deferred when a precaution is present.

Both Indications

Allergic Reactions: Allergic reactions may occur. If symptoms of allergic or early signs of
hypersensitivity reactions (including generalized urticaria, tightness of the chest, wheezing, hypotension, and anaphylaxis) occur, immediately discontinue administration. The treatment required depends on the nature and severity of the side effect. If necessary, the current medical standards for shock treatment should be observed.

Selective IgA Deficiency: Individuals with selective IgA deficiency can develop antibodies to IgA and anaphylactic reactions (including anaphylaxis and shock) after administration of blood components containing IgA. Although the concentration of IgA was found to be below the detection limit of 5 mcg/mL, Rhophylac® may contain trace amounts of IgA. Those with known antibodies to IgA may have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. Therefore, the physician must weigh the expected benefits of treatment with Rhophylac® against the potential risks.

Interference With Laboratory Tests: The administration of Rh0 (D) immune globulin may affect the results of blood typing, the antibody screening test, and the direct antiglobulin (Coombs’) test. Antepartum administration of Rh0 (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.

Transmissible Infectious Agents: Rhophylac® is made from human plasma. Products made from human plasma may contain infectious agents, e.g., viruses and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent, that can cause disease. The risk that such products will transmit an infectious agent has been reduced by screening plasma donors for prior exposure to certain viruses, by testing for the presence of certain current virus infections, and by inactivating and/or removing certain viruses during manufacturing through solvent/detergent treatment and virus filtration. The solvent/detergent treatment step is effective in inactivating enveloped viruses such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV). The virus filtration step is effective in removing both enveloped and non-enveloped viruses.

Despite these measures, such products can still potentially transmit disease. There is also the possibility that unknown infectious agents may be present in such products. All infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to CSL Behring at 1-866-915-6958. The physician should discuss the risks and benefits of this product with the patient.

Suppression of Rh Isoimmunization: Postpartum Use Following an Rh-incompatible Pregnancy Rhophylac® should not be given to the newborn infant.

ITP

Intravascular Hemolysis: Intravascular hemolysis has occurred in a clinical study with Rhophylac®. All cases resolved completely. However, as reported in the literature, some patients treated with Rh0 (D) immune globulin (anti-D) developed clinically compromising anemia, acute renal insufficiency, and, very rarely, disseminated intravascular coagulation (DIC) and death.

Following administration of Rhophylac®, patients should be monitored for signs and/or symptoms of intravascular hemolysis and its complications including clinically compromising anemia, acute renal insufficiency, and DIC. Patients experiencing intravascular hemolysis may present with back pain, shaking chills, fever, and, most consistently, hemoglobinuria. ITP patients presenting with signs and/or symptoms of intravascular hemolysis and its complications after Rh0 (D) immune globulin administration should have confirmatory laboratory tests. 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, Rh0 (D)-negative packed RBCs should be used to avoid exacerbating ongoing hemolysis.

Pre-existing Anemia: The safety of Rhophylac® in the treatment of ITP has not been established in patients with pre-existing anemia. The physician must weigh the benefits of Rhophylac® against the potential risk of increasing the severity of the anemia.

Manufacturer-Listed Adverse Reactions

Per the CDC, adverse reactions are an undesirable medical condition that has been demonstrated to be caused by a vaccine. Evidence for the causal relation is usually obtained through randomized clinical trials, controlled epidemiologic studies, isolation of the vaccine strain from the pathogenic site, or recurrence of the condition with repeated vaccination (i.e., rechallenge); synonyms include side effect and adverse effect.

RhoGAM can cause

in Suppression of Rh isoimmunization: Nausea/Vomiting, Dizziness/Headache, Injection-site pain, Malaise (discomfort), Vertigo/Chills, Hypotension (low blood pressure), Tachycardia (fast heartbeat), Dyspnea (shortness of breath), Rash, erythema, pruritus (hives), Backpain, Pyrexia/increased body temperature, Diarrhea.

in ITP: Chills, Pyrexia/increased body temperature, Headache, Mild extravascular hemolysis (increased bilirubin, decreased hemoglobin), Anemia, Acute renal insufficiency, Disseminated intravascular coagulation (DIC) and is difficult to detect, diagnosis is dependent mainly on laboratory testing, Death, Patients experiencing intravascular hemolysis may present with back pain, shaking chills, fever, and, most consistently, hemoglobinuria, as well as discolored urine, decreased urine output, sudden weight gain, edema, and/or shortness of breath.

Drug Interactions

Live Virus Vaccines: Immunoglobulin administration may transiently impair the efficacy of live attenuated virus vaccines such as measles, mumps, rubella, and varicella. The immunizing physician should be informed of recent therapy with Rhophylac® so that appropriate measures can be taken.

Specific Populations

Pregnancy

Pregnancy Category C. Animal reproduction studies have not been conducted with
Rhophylac®. The available evidence suggests that Rhophylac® does not harm the fetus or affect future pregnancies or reproduction capacity when given to pregnant Rh0 (D)- negative women for suppression of Rh isoimmunization.

Fertility

The insert does not have a Section 13.1.

Pediatric

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.

Mechanism of Action

This is the specific biochemical interaction through which a drug or vaccine substance produces its pharmacological effect. This section also includes the minimum protective level designated for a certain disease.

The mechanism by which Rh0 (D) immune globulin suppresses immunization to Rh0 (D) positive RBCs is not completely known. In a clinical study of Rh0 (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 Rh0 (D)-positive RBCs resulted in an effective clearance of Rh0 (D)-positive RBCs. On average, 99% of injected RBCs were cleared within 12 hours following intravenous administration and within 144 hours following intramuscular administration.

Analytical Deep Dive

Rhophylac®

Learn more about Suppression of Rh isoimmunization:

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