Ronapreve Injection

This is indicated for:

• Treatment of COVID-19 in adults and adolescents aged 12 years and older weighing at least 40 kg who do not require supplemental oxygen and who are at increased risk of progressing to severe COVID-19.
• Prevention of COVID-19 in adults and adolescents aged 12 years and older weighing at least 40 kg.

Casirivimab (IgG1κ) and imdevimab (IgG1λ) are two recombinant human monoclonal antibodies which are unmodified in the Fc regions. Casirivimab and imdevimab bind to non-overlapping epitopes of the spike protein receptor-binding domain (RBD) of SARS-CoV-2. This prevents RBD binding to the human ACE2 receptor, so preventing virus entry into cells.

The dosage in adult patients and in adolescent patients 12 years of age and older weighing at least 40 kg is 600 mg of casirivimab and 600 mg of imdevimab administered as a single intravenous infusion or by subcutaneous injection.

Post-exposure prophylaxis: The dosage in adult patients and in adolescent patients 12 years of age and older weighing at least 40 kg is 600 mg of casirivimab and 600 mg of imdevimab administered as a single intravenous infusion or by subcutaneous injection. Casirivimab with imdevimab should be given as soon as possible after contact with a case of COVID-19.

Pre-exposure prophylaxis: The initial dose in adult patients and in adolescent patients 12 years of age and older weighing at least 40 kg is 600 mg of casirivimab and 600 mg of imdevimab administered as a single intravenous infusion or by subcutaneous injection. Subsequent doses of 300 mg of casirivimab and 300 mg of imdevimab administered as a single intravenous infusion or by subcutaneous injection may be given every 4 weeks until prophylaxis is no longer required. There are no data on repeat dosing beyond 24 weeks (6 doses).

Hypersensitivity to the active substances or to any of the excipients.

Pregnancy: There are no or limited amount of data from the use of casirivimab and imdevimab in pregnant women. Animal studies have not been performed with respect to reproductive toxicity. Human immunoglobulin G1 (IgG1) antibodies are known to cross the placenta. It is unknown whether the potential transfer of casirivimab and imdevimab provides any treatment benefit or risk to the developing foetus. However, as casirivimab and imdevimab directly target the spike protein of SARS-CoV-2 and in view of lack of cross reactivity with reproductive or foetal tissues in the tissue cross reactivity studies, negative effects on developing foetus are not expected. This drug should be used during pregnancy only if the potential benefit justifies the potential risk for the mother and the foetus considering all associated health factors. If a woman becomes pregnant while taking this medicine, the individual should be informed that any potential risk to the foetus is unknown.

Breast-feeding: It is unknown whether casirivimab and imdevimab are excreted in human milk, but maternal IgG is known to be transferred to milk during the first days after birth. As casirivimab and imdevimab directly target the spike protein of SARS-CoV-2 and in view of low systemic absorption after oral ingestion of antibodies, administration of this drug whilst breast-feeding can be considered when clinically indicated.

Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Subcutaneous administration for treatment of COVID-19: The clinical efficacy of this drug when administered by the subcutaneous route for treatment of COVID-19 has not been evaluated in clinical trials. The pharmacokinetics of casirivimab and imdevimab in the first 48 hours after subcutaneous administration of 600 mg of each monoclonal antibody indicate lower serum exposures compared to intravenous administration of the same dose. It is unknown whether differences in initial systemic exposure result in differences in clinical efficacy. It is recommended that the subcutaneous route of administration is used only if intravenous administration is not feasible and would lead to a delay in treatment.

Hypersensitivity reactions including anaphylaxis: Hypersensitivity reactions, including anaphylaxis, have been reported with administration of casirivimab and imdevimab. If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive care.

Infusion-related reactions: Infusion-related reactions (IRRs) have been observed with intravenous administration of casirivimab and imdevimab. IRRs observed in clinical studies were mostly moderate in severity and were typically observed during or within 24 hours of infusion. The frequently reported signs and symptoms for these reactions included nausea, chills, dizziness (or syncope), rash, urticaria and flushing. However, infusion-related reactions may present as severe or life threatening events and may include other signs and symptoms. If an IRR occurs, the infusion may be interrupted, slowed or stopped.

Doses up to 4 000 mg each of casirivimab and imdevimab (approximately 7-times the recommended dose) have been administered in clinical trials. The safety profile for 8 000 mg intravenous was not substantially different to that for the recommended dose. There is no known specific antidote for casirivimab and imdevimab overdose. Treatment of overdose should consist of general supportive measures including monitoring of vital signs and observation of the clinical status of the patient.

• Elderly: No dosage adjustment is required.
• Renal impairment: No dosage adjustment is required.
• Hepatic impairment: No dosage adjustment is required (see section 5.2).
• Pediatric population: The safety and efficacy of casirivimab and imdevimab in children <12 years of age has not yet been established. No data are available.

Store in a refrigerator (2°C-8°C). Do not freeze. Do not shake. Keep the vials in the original carton in order to protect from light.