Rhophylac

Name: Rhophylac

Description

Rhophylac is a sterile Rh0(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 Rh0(D) in a 2 mL solution, sufficient to suppress the immune response to at least 15 mL of Rh-positive RBCs.2 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 Rh0(D)-negative donors who have been immunized with Rh0(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-½, 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 credit plasma is also tested by NAT for hepatitis A virus (HAV) and B19 virus (B19V).

Rhophylac is produced by an ion-exchange chromatography isolation procedure4, using pooled plasma obtained by plasmapheresis of immunized Rh0(D)-negative US donors. The manufacturing process includes a solvent/detergent treatment step (using tri-n-butyl phosphate and Triton™ X-100) that is effective in inactivating enveloped viruses such as HIV, HCV, and HBV.5,6 Rhophylac is filtered using a Planova® 15 nanometer (nm) virus filter that has been validated to be effective in removing both enveloped and nonenveloped viruses. Table 3 presents viral clearance and inactivation data from validation studies, expressed as the mean log10 reduction factor (LRF).

Table 3: Virus Inactivation and Removal in Rhophylac

  HIV PRV BVDV MVM
Virus property
Genome RNA DNA RNA DNA
Envelope Yes Yes Yes No
Size (nm) 80-100 120-200 40-70 18-24
Manufacturing step Mean LRF
Solvent/detergent treatment ≥ 6.0 ≥ 5.6 ≥ 5.4 Not tested
Chromatographic process steps 4.5 ≥ 3.9 1.6 ≥ 2.6
Virus filtration ≥ 6.3 ≥ 5.6 ≥ 5.5 3.4
Overall reduction ≥ 16.8 ≥ 15.1 ≥ 12.5 ≥ 6.0
HIV, a model for HIV-1 and HIV-2; PRV, pseudorabies virus, a model for large, enveloped DNA viruses (e.g., herpes virus); BVDV, bovine viral diarrhea virus, a model for HCV and West Nile virus; MVM, minute virus of mice, a model for B19V and other small, non-enveloped DNA viruses.

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.

REFERENCES

2. Gaines AR. Disseminated intravascular coagulation associated with acute hemoglobinemia or hemoglobinuria following Rh0(D) immune globulin intravenous administration for immune thrombocytopenic purpura. Blood. 2005;106:1532- 1537.

4. Stucki M, Moudry R, Kempf C, Omar A, Schlegel A, Lerch PG. Characterisation of a chromatographically produced anti-D immunoglobulin product. J Chromatogr B. 1997;700:241-248.

5. Horowitz B, Chin S, Prince AM, Brotman B, Pascual D, Williams B. Preparation and characterization of S/D-FFP, a virus sterilized “fresh frozen plasma”. J Thromb Haemost. 1991;65:1163.

6. Horowitz B, Bonomo R, Prince AM, Chin S, Brotman B, Shulman RW. Solvent/ detergent-treated plasma: a virus-inactivated substitute for fresh frozen plasma. Blood. 1992;79:826-831.

What happens if i miss a dose?

Call your doctor for instructions if you miss an appointment for your RHo (D) immune globulin injection.

Uses of Rhophylac

Rhophylac is a prescription medication used to prevent Rh immunization, also known as Rh incompatibility. Rhophylac can also be used to treat immune thrombocytopenia purpura (ITP), a bleeding disorder, in adults.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Rhophylac Interactions

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you require immunizations. Rhophylac may impair the efficacy of live vaccines such as measles, mumps, and varicella.

This is not a complete list of Rhophylac drug interactions. Ask your doctor or pharmacist for more information.

Rhophylac Usage

Receive Rhophylac exactly as prescribed.

This medication is available in an injectable form to be given directly into a muscle (IM) or a vein (IV) by a healthcare professional.

Forms of Medication


What do I need to tell my doctor BEFORE I take Rhophylac?

For all patients taking this medicine:

  • If you have an allergy to Rho(D) immune globulin or any other part of Rhophylac.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have any of these health problems: Anemia, other blood or bleeding problems, or you have had your spleen removed.
  • If you have IgA deficiency.
  • If you have recently had a live vaccine

Children:

  • If your child is a newborn. Some brands of this medicine are not for use in newborns.

This is not a list of all drugs or health problems that interact with Rhophylac.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Warnings and Precautions

Both Indications

5.1.1 Hypersensitivity

Severe hypersensitivity 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, 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 greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. Rhophylac is contraindicated in patients with antibodies against IgA and a history of hypersensitivity reactions (see Contraindications [4]).

5.1.2 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.

5.1.3 Transmissible Infectious Agents

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.

Suppression of Rh Isoimmunization

5.2.1 Postpartum Use Following an Rh-incompatible Pregnancy

Administer Rhophylac to the mother only. Do not administer to the newborn infant (see Pediatric Use [8.4]).

ITP

5.3.1 Intravascular Hemolysis

Intravascular hemolysis has occurred in a clinical study with Rhophylac. All cases resolved completely. However, as reported in the literature, some Rh0(D)-positive patients treated with Rh0(D) Immune Globulin Intravenous (Human) for ITP developed clinically compromising anemia, acute renal insufficiency, and, very rarely, disseminated intravascular coagulation (DIC) and death.1 Note: This warning does not apply to Rh0(D)-negative patients treated for the suppression of Rh isoimmunization.

Closely 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, Rh0(D)-negative packed RBCs should be used to avoid exacerbating ongoing hemolysis.

5.3.2 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.

What is Rhophylac?

Rhophylac contains RHo (D) immune globulin. RHo (D) immune globulin is a sterilized solution made from human blood. Rh is a substance that most people have in their blood (Rh positive) but some people don't (Rh negative). A person who is Rh negative can be exposed to Rh positive blood through a mismatched blood transfusion or during pregnancy when the baby has the opposite blood type. When this exposure happens, the Rh negative blood will respond by making antibodies that will try to destroy the Rh positive blood cells. This can cause medical problems such as anemia (low red blood cells), kidney failure, or shock.

Rhophylac is used to prevent an immune response to Rh positive blood in people with an Rh negative blood type. Rhophylac may also be used in the treatment of immune thrombocytopenic purpura (ITP).

Rhophylac may also be used for purposes not listed in this medication guide.

What happens if I miss a dose?

Call your doctor for instructions if you miss an appointment for your Rhophylac injection.

What other drugs will affect Rhophylac?

Other drugs may interact with Rhophylac, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

For Healthcare Professionals

Applies to rho (d) immune globulin: injectable powder for injection, injectable solution, intramuscular powder for injection, intramuscular solution

Other

Very common (10% or more): Chills (34.7%), pyrexia/increased body temperature (32.6%)
Uncommon (0.1% to 1%): Malaise
Very rare (less than 0.01%): Death
Frequency not reported: Shivering, weakness
Postmarketing reports: Chest pain, fatigue, edema[Ref]

Hematologic

Hemolytic reaction includes hypotension, nausea, chills, headache, and a decrease in haptoglobin and hemoglobin.[Ref]

Very rare (less than 0.01%): Disseminated intravascular coagulation
Frequency not reported: Intravascular hemolysis, hemolysis resulting in death, clinically compromising anemia, extravascular hemolysis, hemolytic reaction
Postmarketing reports: Hemoglobinemia, disseminated intravascular coagulation[Ref]

Local

Uncommon (0.1% to 1%): Injection site swelling, injection site pain
Rare (less than 0.1%): Injection site erythema, injection site induration, injection site warmth, injection site pruritus, injection site rash[Ref]

Nervous system

Very common (10% or more): Headache (14.3%)
Uncommon (0.1% to 1%): Dizziness, vertigo[Ref]

Gastrointestinal

Uncommon (0.1% to 1%): Nausea, vomiting
Rare (less than 0.1%): Diarrhea[Ref]

Cardiovascular

Rare (less than 0.1%): Tachycardia, hypotension
Frequency not reported: Increase in blood pressure
Postmarketing reports: Cardiac arrest, cardiac failure, myocardial infarction[Ref]

Dermatologic

Uncommon (0.1% to 1%): Skin reaction, erythema, pruritus, pallor, rash
Postmarketing reports: Hyperhidrosis[Ref]

Musculoskeletal

Rare (less than 0.1%): Arthralgia, back pain
Postmarketing reports: Myalgia, muscle spasm, pain in extremities[Ref]

Hepatic

Very common (10% or more): Increase in blood bilirubin (21.4%)
Postmarketing reports: Jaundice[Ref]

Hypersensitivity

Rare (less than 0.1%): Hypersensitivity, anaphylactic shock, anaphylactic reaction[Ref]

General

The most common adverse events were chills, pyrexia, increased bilirubin, and headache.[Ref]

Respiratory

Rare (less than 0.1%): Dyspnea
Postmarketing reports: Acute respiratory distress syndrome, transfusion related acute lung injury[Ref]

Renal

Frequency not reported: Acute renal insufficiency
Postmarketing reports: Renal failure, renal impairment[Ref]

Immunologic

Uncommon (0.1% to 1%): Transient positive anti-C antibody test
Frequency not reported: Sensitization to repeated injections of human globulin[Ref]

Genitourinary

Postmarketing reports: Hemoglobinuria, anuria, chromaturia, hematuria[Ref]

Some side effects of Rhophylac may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

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