Rhesonativ^® (Solution) Instructions for Use

Marketing Authorization Holder

Octapharma AB (Sweden)

ATC Code

J06BB01 (Human anti-Rho(D) immunoglobulin)

Active Substance

Human anti-D immunoglobulin (Ph.Eur.)

Dosage Forms

	Rhesonativ®	Solution for intramuscular administration 625 IU/1 ml: amp. 1 pc.
		Solution for intramuscular administration 1250 IU/2 ml: amp. 1 or 10 pcs.

Dosage Form, Packaging, and Composition

Solution for intramuscular administration transparent or slightly opalescent, from colorless to pale yellow or light brown.

Excipients: glycine, sodium acetate, sodium chloride, water for injections.

1 ml – ampoules of colorless glass (1) – plastic blister packs (1) – cardboard packs.

Solution for intramuscular administration transparent or slightly opalescent, from pale yellow to light brown.

Excipients: glycine, sodium acetate, sodium chloride, water for injections.

2 ml – ampoules of colorless glass (1) – plastic blister packs (1) – cardboard packs.
2 ml – ampoules of colorless glass (5) – plastic blister packs (2) – cardboard packs.

Clinical-Pharmacological Group

Drug for the prevention of Rh-conflict. Specific immunoglobulin

Pharmacotherapeutic Group

Immunoglobulin

Pharmacological Action

An immunologically active protein fraction isolated from human plasma or serum of donors tested for the absence of antibodies to HIV (HIV-1, HIV-2), hepatitis C virus and hepatitis B surface antigen.

It prevents isoimmunization of the Rho(D)-negative mother exposed to Rh₀(D)-positive fetal blood during the birth of an Rh₀(D)-positive child, during abortion (both spontaneous and artificial), in case of amniocentesis or abdominal trauma during pregnancy.

It reduces the frequency of Rh-isoimmunization of the mother when the drug is administered within 48-72 hours after the birth of a full-term Rh₀(D)-positive child by an Rh₀(D)-negative mother.

Pharmacokinetics

C_max of antibodies in the blood is reached after 24 hours. The half-life of human anti-Rhesus Rh₀(D) immunoglobulin is 23-26 days. T_1/2 of antibodies 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., who have not developed Rh antibodies) provided the first pregnancy and birth of an Rh-positive child whose blood is compatible with the mother’s blood according to the ABO blood group system; during artificial termination of pregnancy in Rh-negative women, also not sensitized to the Rh₀(D) antigen, in case of the husband’s Rh-positive blood type.

ICD codes

Dosage Regimen

Do not administer intravenously.

Intramuscularly, 1 dose, once: to the postpartum woman – within the first 48-72 hours after delivery, during artificial termination of pregnancy – immediately after the end of the operation. One dose is 300 mcg with a titer of 1:2000 or 600 mcg with a titer of 1:1000.

The need for a specific dose in the case of a full-term pregnancy may vary depending on the volume of fetal blood that has entered the maternal bloodstream. One dose (300 mcg) contains a sufficient amount of antibodies to prevent sensitization to the Rh factor if the volume of red blood cells that have entered the bloodstream does not exceed 15 ml.

In cases where a larger volume of fetal red blood cells is suspected to have entered the maternal bloodstream (more than 30 ml of whole blood or more than 15 ml of red blood cells), a count of fetal red blood cells should be performed using an approved laboratory method (for example, the modified acid elution-staining method by Kleihauer and Betke) to determine the required dose of immunoglobulin. The calculated volume of fetal red blood cells that entered the maternal bloodstream is divided by 15 ml to obtain the number of drug doses 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 (600 mcg) of the drug should be administered).

To carry out prophylaxis in the prenatal period, 1 dose of the drug (300 mcg) should be administered approximately at the 28th week of pregnancy. Then, it is imperative to administer another 1 dose (300 mcg), preferably within 48-72 hours after delivery, if the newborn is Rh-positive.

If the pregnancy continues after a threatened abortion at any stage of pregnancy, another 1 dose (300 mcg) of the drug should be administered. If more than 15 ml of fetal red blood cells are suspected to have entered the maternal bloodstream, the dose should be adjusted as described above.

After spontaneous abortion, induced abortion, or termination of an ectopic pregnancy at a gestational age of more than 13 weeks, it is recommended to administer 1 dose (300 mcg) of the drug (or more if more than 15 ml of fetal red blood cells are suspected to have entered the maternal bloodstream).

If the pregnancy is terminated at less than 13 weeks of gestation, a single use of a mini-dose (approximately 50 mcg) is possible.

After amniocentesis, either at 15-18 weeks of pregnancy or during the third trimester of pregnancy, or after abdominal trauma during the second or third trimester, it is recommended to administer 1 dose (300 mcg) of the drug (or more if more than 15 ml of fetal red blood cells are suspected to have entered the maternal bloodstream). If abdominal trauma, amniocentesis, or other adverse circumstance requires administration of the drug at 13-18 weeks of gestation, another 1 dose (300 mcg) should be administered at 26-28 weeks. To maintain protection throughout pregnancy, the concentration of passively acquired anti-Rh₀(D) antibodies must not fall below the level necessary to prevent an immune response to Rh-positive fetal red blood cells.

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, the postpartum dose can be omitted (except in cases where more than 15 ml of fetal red blood cells have entered the maternal bloodstream).

Adverse Reactions

Possible hyperemia and hyperthermia up to 37.5°C (99.5°F) (within the first 24 hours after administration), dyspepsia; rarely (in case of hypersensitivity, including IgA deficiency) – allergic reactions (up to anaphylactic shock).

Contraindications

Hypersensitivity; Rh-negative postpartum women sensitized to the Rh₀(D) antigen, in whose serum Rh antibodies are detected; newborns.

Use in Pregnancy and Lactation

Used according to indications during pregnancy.

Pediatric Use

Contraindicated in newborns.

Geriatric Use

Not applicable.

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.

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

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

If the father is 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 anti-shock therapy means. In case of anaphylactoid reactions, antihistamines, corticosteroids and alpha-adrenergic agonists are used.

The drug is not administered to Rh-positive postpartum women.

Drug Interactions

Can be used in combination with other drugs (including antibiotics).

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.