KamRho (Solution) Instructions for Use

Marketing Authorization Holder

Kamada Ltd. (Israel)

Contact Information

Kamada Ltd. (Israel)

ATC Code

J06BB01 (Human anti-Rho(D) immunoglobulin)

Active Substance

Human anti-D immunoglobulin (Ph.Eur. European Pharmacopoeia)

Dosage Form

KamRho

Solution for intramuscular administration 150 mcg/1 ml (750 IU/1 ml): 0.85 ml or 2 ml bottle 1 pc. with filter needle

Dosage Form, Packaging, and Composition

Solution for intramuscular administration transparent or opalescent, colorless or light yellow in color; may contain a small amount of suspended protein particles.

Excipients: glycine, water for injections.

2 ml – glass vials (1) in a kit with a filter needle – cardboard packs.

Clinical-Pharmacological Group

Immunological preparation. Immunoglobulin

Pharmacotherapeutic Group

Immunoglobulin

Pharmacological Action

Human anti-Rhesus Rh₀(D) immunoglobulin. It is an immunologically active protein fraction isolated from human plasma or serum of donors tested for the absence of antibodies to the human immunodeficiency virus (HIV), hepatitis C virus (anti-HCV) and hepatitis B surface antigen (HBsAg). The active component of the drug is immunoglobulin G, containing incomplete anti-Rh₀(D) antibodies.

It is used to prevent isoimmunization of a Rh-negative mother exposed to Rh-positive fetal blood at the birth of a Rh-positive child, during abortion (both spontaneous and artificial), in the case of amniocentesis, or in the event of an abdominal organ injury during pregnancy. It reduces the frequency of Rh isoimmunization of the mother when the drug is administered within 72 hours after the birth of a full-term Rh-positive child by a Rh-negative mother.

Pharmacokinetics

C_max of antibodies in the blood is reached 24 hours after intramuscular administration of human anti-Rhesus Rh0 (D) immunoglobulin. T_1/2 of human anti-Rhesus Rh₀(D) immunoglobulin from the body is 4-5 weeks.

Indications

Prevention of Rh conflict in Rh-negative women not sensitized to the Rh₀(D) antigen (i.e., in the absence of Rh antibodies) provided

• First pregnancy and birth of a Rh-positive child;
• During artificial or spontaneous abortion;
• During termination of ectopic pregnancy;
• In case of threatened abortion;
• During amniocentesis and other procedures associated with the risk of fetal blood entering the mother’s bloodstream;
• Rh-positive blood type of the husband;
• In case of abdominal trauma.

Treatment of Rh-negative patients in case of transfusion of Rh-positive blood or erythrocyte-containing drugs.

ICD codes

Dosage Regimen

The drug is administered intramuscularly. It must not be administered intravenously.

Before administration, the vials with the drug should be kept for 2 hours at room temperature (from 18°C (64.4°F) to 22°C (71.6°F)). To avoid foam formation, the drug is drawn into the syringe with a needle with a wide lumen. The drug in an opened vial must not be stored.

The drug is administered only intramuscularly, as a single dose: to a postpartum woman – within the first 48-72 hours after delivery; in case of artificial termination of pregnancy – immediately after the end of the operation.

One dose is 300 mcg at a titer of 1:2000 or 600 mcg at a titer of 1:1000.

Human anti-Rhesus Rh₀(D) immunoglobulin is administered as one dose of 300 mcg (1500 IU), sometimes two doses of 600 mcg (3000 IU) intramuscularly as a single dose: to a postpartum woman – within 72 hours after delivery; during termination of pregnancy – immediately after the end of the operation.

The following criteria must be met

1. The mother must be Rh-negative and must not already be sensitized to the Rh₀(D) factor.
2. Her child must be Rh-positive.

If the drug is administered before delivery, it is essential that the mother receives another dose of the drug after the birth of a Rh-positive child within 72 hours after delivery. If the father is determined to be Rh-negative, there is no need to administer the drug.

Pregnancy and other conditions related to pregnancy and childbirth

1. For prophylaxis in the postpartum period, one dose of 300 mcg (1500 IU) of KamRho should be administered preferably within 72 hours after delivery. The need for a specific dose in the case of a full-term pregnancy varies depending on the volume of fetal blood that has entered the maternal bloodstream. One dose of 300 mcg (1500 IU) contains a sufficient amount of antibodies to prevent sensitization to the Rh factor if the volume of fetal erythrocytes that entered the maternal bloodstream does not exceed 15 ml. In cases where a larger volume of fetal erythrocytes is suspected to have entered the maternal bloodstream (more than 30 ml of whole blood or more than 15 ml of erythrocytes), a count of fetal erythrocytes should be performed using an approved laboratory method (for example, the modified acid elution-staining method according to Kleihauer and Betke) to determine the required dose of immunoglobulin. The calculated volume of fetal erythrocytes that entered the maternal bloodstream is divided by 15 ml to obtain the number of doses of KamRho that need to be administered. If the calculated dose results in a fraction, the number of doses should be rounded up to the next whole number (for example, if the result is 1.4, 2 doses of the drug should be administered – 600 mcg (3000 IU)).
2. For prophylaxis in the prenatal period, approximately at the 28th week of pregnancy, one dose of the drug 300 mcg (1500 IU) is administered. This must be followed by another dose of 300 mcg (1500 IU), preferably within 48-72 hours after delivery, if the newborn is Rh-positive.
3. In case of continuation of pregnancy after a threatened abortion at any stage of pregnancy, it is recommended to administer one dose of the drug 300 mcg (1500 IU). If more than 15 ml of fetal erythrocytes are suspected to have entered the maternal bloodstream, the dose should be adjusted as described in point 1.
4. After spontaneous abortion, artificial abortion, or termination of ectopic pregnancy at a gestational age of more than 13 weeks, it is recommended to administer one dose of the drug 300 mcg (1500 IU). If more than 15 ml of fetal erythrocytes are suspected to have entered the maternal bloodstream, the dose should be adjusted as described in point 1. If the pregnancy is terminated at less than 13 weeks, a single use of a mini-dose of KamRho (approximately 50 mcg (250 IU)) is possible.
5. After amniocentesis, either at 15-18 weeks of pregnancy or during the III trimester of pregnancy, or in case of abdominal organ injury during the II and/or III trimester, it is recommended to administer one dose of the drug 300 mcg (1500 IU). If more than 15 ml of erythrocytes are suspected to have entered the maternal bloodstream, the dose should be adjusted as described in point 1. If abdominal organ injury, amniocentesis, or other adverse circumstance requires administration of the drug at 13-18 weeks of pregnancy, another dose of the drug 300 mcg (1500 IU) should be administered at 26-28 weeks. To maintain protection throughout pregnancy, the level of passively acquired anti-Rh₀(D) antibodies must not fall below the level required to prevent an immune response to Rh-positive fetal erythrocytes. The T_1/2 of human anti-Rhesus Rh₀(D) immunoglobulin is 28-35 days. In any case, the dose of the drug should be administered within 48-72 hours after delivery – if the child is Rh-positive. If delivery occurs within 3 weeks after the last dose is received, the postpartum dose may be omitted (except in cases where more than 15 ml of fetal erythrocytes have entered the maternal bloodstream).

Adverse Reactions

From the body as a whole hyperthermia up to 37.5°C (99.5°F) (within the first 24 hours after administration).

From the digestive system: dyspepsia.

Allergic reactions: rarely (in case of hypersensitivity, including IgA deficiency) – allergic reactions up to anaphylactic shock.

Local reactions: discomfort, swelling and hyperemia at the injection site.

Contraindications

• Rh-negative postpartum women sensitized to the Rh₀(D) antigen, in whose serum Rh antibodies are detected;
• Newborns;
• Rh-positive patients;
• Hypersensitivity to the components of the drug.

Use in Pregnancy and Lactation

Used during pregnancy and after delivery in accordance with the indications.

Special Precautions

In children born to women who received human anti-Rhesus Rh₀(D) immunoglobulin before delivery, weakly positive results of direct antiglobulin tests may be obtained at birth.

Passively acquired anti-Rh₀(D) antibodies may be detected in the mother’s serum if antibody screening tests are performed after prenatal or postpartum administration of human anti-Rh₀(D) immunoglobulin.

If the father is determined to be Rh₀(D)-negative, there is no need to administer the drug.

After administration of the drug, patients should be observed for 30 minutes. Medical offices should have means for anti-shock therapy.

Drugs in vials and syringes with damaged integrity or labeling, with changed physical properties (change in color, turbidity of the solution, presence of non-dispersible flakes), with an expired shelf life, or stored incorrectly are not suitable for use.

Overdose

No cases of overdose in Rh-negative women have been described.

Drug Interactions

Immunoglobulin therapy can be combined with other drugs, including antibiotics.

Immunization of women with live vaccines should be carried out no earlier than 3 months after the administration of anti-Rhesus immunoglobulin.

Storage Conditions

The drug should be stored out of the reach of children, protected from light, at a temperature of 2°C (35.6°F) to 8°C (46.4°F); do not freeze.

Shelf Life

Shelf life – 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.