Solution for infusion. Octaplas is supplied as a frozen solution, which appears slightly yellow.

Octaplas is presented as a solution for infusion containing 45 - 70 mg/mL human plasma proteins.

Indications for Octaplas are identical to those for fresh-frozen plasma (FFP):

• Complex deficiencies of coagulation factors such as coagulopathy due to severe hepatic failure or massive transfusion.

• Substitution therapy in coagulation factor deficiencies, in emergency situations, when a specific coagulation factor concentrate, e.g. factor V or factor XI, is not available or when a precise laboratory diagnosis is not possible.

• Reversal of the effect on fibrinolysis and rapid reversal of effects of oral anticoagulants (coumarin or indanedione type), when vitamin K is insufficient due to impaired liver function or in emergency situations.

• Thrombotic thrombocytopenic purpura (TTP), usually in conjunction with plasma exchange.

• In intensive plasma exchange procedures, Octaplas should only be used to correct the coagulation abnormality when abnormal haemorrhage occurs

Dosage:

The dosage depends upon the clinical situation and underlying disorder, but 12-15 ml Octaplas/kg body weight is a generally accepted starting dose (this should increase the patient's plasma coagulation factor levels by approximately 25%). It is important to monitor the response, both clinically and with measurement of prothrombin time (PT), partial thromboplastin time (PTT) and/or specific coagulation factor assays.

Dosage for coagulation factor deficiencies:

An adequate haemostatic effect in minor and moderate haemorrhages or surgery in coagulation factor deficient patients is normally achieved after the infusion of 5-20 ml Octaplas/kg body weight (this should increase the patient's plasma coagulation factor levels by approximately 10-33 %).

In the event of major haemorrhage or surgery the expert advice of a haematologist should be sought.

Dosage for TTP and haemorrhages in intensive plasma exchange:

In TTP patients the whole plasma volume exchanged should be replaced with Octaplas.

For the treatment of haemorrhages in intensive plasma exchange procedures the expert advice of a haematologist should be sought.

Method of administration:

Administration of Octaplas must be based on ABO-blood group compatibility. In emergency cases, Octaplas blood group AB can be regarded as universal plasma since it can be given to all patients.

Octaplas must be administered by intravenous infusion after thawing as described in section 6.6, using an infusion set with a filter. An aseptic technique must be used throughout the infusion.

Due to the risk of citrate toxicity, the infusion rate should not exceed 0.020-0.025 mmol citrate/kg body weight/min equal to 1 ml Octaplas/kg body weight/min. Toxic effects of citrate can be minimised by giving calcium gluconate i.v. into another vein.

The experience in children is limited.

- Contra-indications for Octaplas are identical to those for FFP

- IgA deficiency with documented antibodies against IgA

- Severe deficiencies of protein S

Hypersensitivity to the active substance, to any of the excipients or to residues from the manufacturing process.

Octaplas should be used with caution under the following conditions:

• IgA deficiency.

• Plasma protein allergy.

• Previous reactions to FFP.

• Manifest or latent cardiac decompensation.

• Pulmonary oedema.

Octaplas should be used with caution in patients with risks for thrombotic complications because of potential increased risk of venous thromboembolism due to reduced protein S activity of Octaplas compared with single donor FFP.

Octaplas should not be used as volume expander in patients where no coagulation factor deficiency has been documented.

Octaplas should not be used in cases of bleeding caused by von Willebrand's Disease or other coagulation factor deficiencies where a specific factor concentrate is available for use.

Octaplas should not be used to correct hyperfibrinolysis caused by a deficiency of the plasmin inhibitor, named alpha2-antiplasmin as dilution with solvent/detergent (S/D) treated plasma (which contains low levels of alpha2-antiplasmin) will further reduce alpha2-antiplasmin levels. Special attention must be paid to signs of excessive bleeding tendency in patients likely to require massive transfusions e.g. in liver transplantation or other conditions with complex disturbances of haemostasis.

Standard measures to prevent infections resulting from the use of medical products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pool for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown and emerging viruses and other pathogens.

The measures taken are considered effective for enveloped viruses such as HIV, HBV and HCV.

The measures taken may be of limited value against non-enveloped virus such as HAV, HEV and Parvovirus B19. However, the risk of transmission of infective agents is reduced by testing of each plasma pool for genomic material. Only plasma pools that are negative in all applicable serological tests as well as in NAT for HIV, HBV, HCV and HAV, and that contain a maximum of 10.0 IU/μl Parvovirus B19 are accepted.

Parvovirus B19 infection may be serious for pregnant woman (fetal infection) and for individuals with immunodeficiency or increased erythropoiesis (e.g. haemolytic anaemia). HEV may also seriously affect seronegative pregnant women. Therefore Octaplas should only be administered to these patients if strongly indicated.

A maximum of 1520 single donations are used for the manufacture of Octaplas.

Octaplas is produced from plasma pools containing a specified minimum antibody level which has been shown to have neutralising effect against HAV, HEV and Parvovirus B19. A possible risk of infection by non-enveloped viruses should be weighed against the benefit of the inactivation of lipid-enveloped viruses such as HIV, HBV and HCV by the S/D treatment.

Appropriate vaccination (e.g. against HAV and HBV) for patients in regular receipt of medicinal products derived from human blood or plasma should be considered.

Administration of Octaplas must be based on ABO-blood group compatibility. In emergency cases, Octaplas blood group AB can be regarded as universal plasma since it can be given to all patients.

It is strongly recommended that every time that Octaplas is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.

Patients should be observed for at least 20 minutes after the administration.

In case of anaphylactic reaction or shock, the infusion must be stopped immediately. Treatment should follow the guidelines for shock therapy.

Data on the use of Octaplas in premature babies are very limited, therefore, the product should only be administered to these individuals if the likely benefits clearly outweigh potential risks.

During clinical trials, Octaplas has been administered in association with various concomitant medications, and no interactions have been identified.

Incompatibilities are identical to those of FFP:

• Octaplas must not be mixed with other drugs as inactivation and precipitation may occur. The product can be mixed with red blood cells and platelets.

• To avoid the possibility of clot formation, solutions containing calcium must not be administered by the same intravenous line as Octaplas.

• Interactions with other drugs are unknown.

Acute mild allergic reaction due to hypersensitivity to infused proteins and characterised by urticaria, fever, chills, nausea, vomiting, and abdominal or back pain may commonly be observed.

Acute and sometimes severe allergic (anaphylactic or anaphylactoid) type of reactions characterised by flushing, hypotension, chest pain, bronchospasms, dyspnoea, and cardio-respiratory collapse may rarely be observed.

High infusion rates may rarely cause cardiovascular effects as a result of citrate toxicity (fall in ionised calcium), especially in patients with liver function disorders. In the course of plasma exchange procedures, symptoms attributable to citrate toxicity such as fatigue, paraesthesia, tremor, and hypocalcemia may be observed rarely.

Very rarely incompatibility between antibodies in Octaplas and antigens of recipient red blood cells can result in immediate or delayed type of haemolytic transfusion reactions, especially in cases of transfusion errors. Therefore, administration of Octaplas must be based on ABO-blood group compatibility.

Octapharma Limited