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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.
If Cuvitru is accidentally administered into a blood vessel, patients could develop shock.
The recommended infusion rate and administration instructions given in Dosage & Administration must be closely followed. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period. If the product remains in a siliconized syringe for more than two hours, visible particles may form.
Certain adverse reactions may occur more frequently in patients who receive human normal immunoglobulin for the first time or, in rare cases, when the human normal immunoglobulin product is switched or when there has been a long interval since the previous infusion.
Potential complications can often be avoided by: initially injecting the product slowly (see Dosage & Administration); ensuring that patients are carefully monitored for any symptoms throughout the infusion period. In particular, patients naïve to human normal immunoglobulin, patients switched from an alternative immunoglobulin product or when there has been a long interval since the previous infusion should be monitored during the first infusion and for the first hour after the first infusion, in order to detect potential adverse signs.
All other patients should be observed for at least 20 minutes after administration.
In case of adverse reaction, either the rate of administration must be reduced or the infusion stopped. Suspicion of severe hypersensitivity or anaphylactic-type reactions requires immediate discontinuation of the injection. The treatment required depends on the nature and severity of the adverse reaction.
In case of shock, standard medical treatment for shock should be implemented.
Hypersensitivity: True allergic reactions are rare. They can particularly occur in patients with anti-IgA antibodies who should be treated with particular caution. Patients with anti-IgA antibodies, in whom treatment with subcutaneous IgG products remains the only option, should be treated with Cuvitru only under close medical supervision.
Cuvitru contains trace amounts of IgA (not more than 280 micrograms/ml).
Rarely, human normal immunoglobulin can induce a fall in blood pressure with anaphylactic reaction, even in patients who had tolerated previous treatment with human normal immunoglobulin.
Thromboembolism: Arterial and venous thromboembolic events including myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism have been associated with the use of immunoglobulins. Caution should be exercised in patients with preexisting risk factors for thrombotic events (such as advanced age, hypertension, diabetes mellitus and a history of vascular disease or thrombotic episodes, patients with acquired or inherited thrombophilic disorders, patients with prolonged periods of immobilization, severely hypovolemic patients, patients with diseases which increase blood viscosity). Patients should be informed about first symptoms of thromboembolic events including shortness of breath, pain and swelling of a limb, focal neurological deficits and chest pain and should be advised to contact their physician immediately upon onset of symptoms.
Ensure adequate hydration in patients before administration. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk for hyperviscosity.
Care should be taken when Cuvitru is given to individuals determined to be at increased risk of thrombosis.
Patients at increased risk of thrombosis include those with acquired or hereditary hypercoagulable states, prolonged immobilization, in-dwelling vascular catheters, advanced age, estrogen use, a history of venous or arterial thrombosis, cardiovascular risk factor (including history of atherosclerosis and/or impaired cardiac output), and hyperviscosity (including cryoglobulins, fasting chylomicronemia and/or high triglyceride levels, and monoclonal gammopathies).
Patients at risk for thrombosis should receive Cuvitru at the slowest infusion rate practicable, and these individuals should be monitored for thrombotic complications.
Consideration should also be given to measurement of baseline blood viscosity in individuals at risk of hyperviscosity.
Renal complications: Severe renal adverse reactions have been reported in patients receiving immune globulin treatment, particularly those products containing sucrose (Cuvitru does not contain sucrose). These include acute renal failure, acute tubular necrosis, proximal tubular nephropathy and osmotic nephrosis. Factors that increase the risk of renal complications include, but are not limited to preexisting renal insufficiency, diabetes mellitus, hypovolemia, concomitant nephrotoxic medicinal products, age over 65, sepsis, hyperviscosity and paraproteinemia.
Aseptic Meningitis Syndrome (AMS): Aseptic meningitis syndrome (AMS) has been reported to occur in association with immune globulin treatments, including Cuvitru (see Table 3 in Adverse Reactions). AMS may occur more frequently in female patients.
Discontinuation of Ig treatment may result in remission of AMS within several days without sequelae. The symptoms usually begins within several hours to 2 days following Ig treatment. Cerebrospinal fluid studies are frequently positive with pleocytosis up to several thousand cells per mm3, predominantly from the granulocytic series, and elevated protein levels up to several hundred mg/dl.
Patients should be informed about first symptoms which encompass severe headache, neck stiffness, drowsiness, fever, photophobia, nausea, and vomiting.
Haemolysis: Cuvitru contains blood group antibodies that may act as haemolysins and induce in vivo coating of red blood cells (RBC) with immunoglobulin. This may cause a positive direct antiglobulin reaction (DAT, direct Coombs test) and, rarely, haemolysis. Delayed haemolytic anaemia can develop subsequent to Ig therapy due to enhanced RBC sequestration. Acute haemolytic anaemia, consistent with intravascular haemolysis, has been reported.
Heightened awareness of the potential for hemolysis is recommended in individuals receiving Cuvitru, particularly those who are determined to be at increased risk.
Patients at increased risk for hemolysis following treatment with Cuvitru include those with non-O blood group types, those who have underlying associated inflammatory conditions, and those receiving high cumulative doses of Cuvitru over the course of several days.
Patients receiving Cuvitru should be monitored for hemolysis, particularly those at increased risk.
Clinical symptoms and signs of hemolysis include fever, chills and dark urine. If these occur, appropriate laboratory testing should be obtained.
Interference with serological testing: After injection of immunoglobulin, the transitory rise of the various passively transferred antibodies in the patient's blood may result in misleading positive results in serological testing, for example, Hepatitis A, Hepatitis B, measles, and varicella. Passive transmission of antibodies to erythrocyte antigens, e.g. A, B, D, may interfere with some serological tests for red cell antibodies, for example the direct antiglobulin test (DAT, direct Coombs test).
Administration of Cuvitru can lead to false positive readings in assays that depend on detection of beta-D-glucans for diagnosis of fungal infections; this may persist during the weeks following infusion of the product.
Transmissible agents: Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools 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 infectious agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.
The measures taken are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), and for the non-enveloped viruses hepatitis A and parvovirus B19.
There is reassuring clinical experience regarding the lack of hepatitis A or Parvovirus B19 transmission with immunoglobulins and it is also assumed that the antibody content makes an important contribution to the viral safety.
It is strongly recommended that every time that Cuvitru 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.
Sodium Content: Cuvitru is essentially sodium-free.
Effects on ability to drive and use machines: The ability to drive and operate machines may be impaired by some adverse reactions associated with Cuvitru. Patients who experience adverse reactions during treatment should wait for these to resolve before driving or operating machines.
Use in Children: The listed warnings and precautions apply both to adults and children.
