RHOPHYLAC Solution for injection Ref.[6195] Active ingredients: Anti-D (rh) immunoglobulin

Posology

The dose of anti-D immunoglobulin should be determined according to the level of exposure to Rh(D) positive red blood cells (RBCs) and based on the knowledge that 0.5 ml of packed Rh(D) positive RBCs or 1 ml of Rh(D) positive blood is neutralised by approximately 10 micrograms (50 IU) of anti-D immunoglobulin.

The following doses are recommended based on the clinical studies performed with Rhophylac. For specific study details see section 5.1.

Consideration should also be given to dose and dose schedules for human anti-D immunoglobulin for intramuscular and intravenous use recommended in other official guidance.

Prevention of Rh(D) isoimmunisation in Rh(D) negative women

• Antepartum prophylaxis: The recommended dose is a single dose of 300 micrograms (1500 IU) administered by intravenous or intramuscular injection.
  • Planned antepartum prophylaxis: A single dose of 300 micrograms at 28-30 weeks of pregnancy. If the need for antepartum prophylaxis is identified in the period beyond 30 weeks of pregnancy, Rhophylac should not be withheld but administered as soon as possible.
  • Antepartum prophylaxis following complications of pregnancy: A single dose of 300 micrograms should be administered as soon as possible and within 72 hours. If more than 72 hours have elapsed, the product should not be withheld but administered as soon as possible. If necessary, the dose may be repeated at 6-12 week intervals throughout the pregnancy.
• Postpartum prophylaxis: The recommended dose is a single dose of 300 micrograms (1500 IU), administered by intravenous or intramuscular injection. When administered intravenously, a minimum dose of 200 micrograms may be sufficient provided large foeto-maternal haemorrhage can be excluded.

For postpartum use, the product should be administered to the mother as soon as possible within 72 hours of delivery of a Rh(D) positive (D, D^weak, D^partial) infant. If more than 72 hours have elapsed, the product should not be withheld but administered as soon as possible.

The postpartum dose must still be given even when antepartum prophylaxis has been administered and even if residual activity from antepartum prophylaxis can be demonstrated in maternal serum.

If a large foeto-maternal haemorrhage (haemorrhage volume >4 ml of Rh(D) positive foetal blood) is suspected, e.g. in the event of foetal/neonatal anaemia or intrauterine foetal death, its extent should be determined by a suitable method, e.g. Kleihauer-Betke acid elution test to detect foetal haemoglobin (HbF) or flow cytometry which specifically identifies Rh(D) positive RBCs.

Additional doses of anti-D immunoglobulin should be administered accordingly (10 micrograms (50 IU) per 0.5 ml Rh(D) positive foetal RBCs or per 1ml Rh(D) positive foetal blood).

Incompatible transfusions of RBCs in Rh(D) negative patients

The recommended dose is 20 micrograms (100 IU) anti-D immunoglobulin per 2 ml of transfused Rh(D) positive blood or per 1 ml of Rh(D) positive RBC concentrate. The appropriate dose should be determined in consultation with a specialist in blood transfusion. Follow-up tests for Rh(D) positive RBCs should be done every 48 hours and further anti-D administered until all Rh(D) positive RBCs have cleared from the circulation.

A maximum dose of 3000 micrograms (15,000 IU) is sufficient even if more than 300 ml of Rh(D) positive blood or 150 ml of Rh(D) positive erythrocyte concentrate was transfused. Due to possible risk of haemolysis, however, it is suggested to not exceed the dose of 3000 micrograms (15000 IU).

Intravenous use is recommended as it will achieve adequate plasma levels immediately.

If given by intramuscular injection the large volume should be administered over a period of several days.

The dose recommendations for prevention of Rh(D) isoimmunisation are summarised in the following table:

^† The Rhophylac dose may need to be increased if the patient is exposed to >15 ml of Rh(D) positive foetal RBCs. In this case, follow the dosing guidelines for large foeto-maternal haemorrhage.

Paediatric population

As the posology in case of incompatible transfusion depends on the volume of Rh(D) positive blood or RBC concentrate transfused, the recommended dose in children and adolescents (0-18 years) is not considered to be different to that of adults. However, the appropriate dose should be determined in consultation with a specialist in blood transfusion.

Use in the elderly

As the posology in case incompatible transfusion depends on the volume of Rh(D) positive blood or Rh(D) positive RBC concentrate transfused, the recommended dose in elderly patients (≥ 65 years of age) is not considered to be different to that of adults. The appropriate dose should be determined in consultation with a specialist in blood transfusion.

Method of administration

As with all blood products, patients should be observed for at least 20 minutes following administration of Rhophylac.

For intravenous or intramuscular use, to be administered by slow injection.

If a large volume (>2 ml for children or >5 ml for adults) is required and intramuscular injection is chosen, it is recommended to administer this in divided doses at different sites.

If intramuscular administration is contraindicated (bleeding disorders), Rhophylac should be administered intravenously.

Obesity

In patients with a body mass index (BMI) ≥30 intravenous administration should be considered (see section 4.4).

No data are available on overdosage. Consequences of an overdose are not known.

3 years.

Store in a refrigerator (+2°C to +8°C). Do not freeze.

The product must not be used after the expiry date (EXP) printed on the outer carton.

Keep the syringe originally blistered in the outer carton in order to protect from light.

2 ml solution in a pre-filled syringe (type I glass) with 1 injection needle in a pack size of 1 or in a multi-pack consisting of 5 single packs.

Not all pack sizes may be marketed.

Rhophylac should be brought to room temperature (25°C) before use.

Rhophylac should be inspected visually for particulate matter and discolouration prior to administration.

Do not use solutions which are cloudy or have deposits.

Rhophylac is for single use only (one syringe – one patient).

Any unused product or waste material should be disposed of in accordance with local requirements.