HEMOGLOBIN GLUTAMER-200 (BOVINE)
OXYGLOBIN®Chemistry - Oxyglobin® is a sterile, clear, dark purple solution containing 13 g/dL purified, polymerized hemoglobin of bovine origin in a modified lactated Ringer's solution. It has an osmolality of 300 mOsm/kg and a pH of 7.8. Less than 5% of the hemoglobin are as unstabilizedtetramers, and approximately 50% have a molecular weight between 65 and 130 kD, with no morethan 10% having a molecular weight >500 kD. The product contains less than the detectable level of3.5 mcg/ml free-glutaraldehyde and 0.05 EU/mL endotoxin.
The manufacturer states that Oxyglobin® is compatible with any other IV fluid, but should not bemixed with other solutions or medications in the bag. Other intravenous solutions and medicationsmay be administered via a separate site and line, however,
Oxyglobin® also has colloidal properties similar to dextran 70 and hetastarch.
As with endogenous hemoglobin, Oxyglobin® is metabolized and eliminated by the reticuloendothelial system. Small amounts of unstabilized hemoglobin (<5%) may be excreted through the kidneys, causing discoloration (red) of the urine.
The safety and efficacy of Oxyglobin® has not been evaluated in dogs with DIC, thrombocytopeniawith active bleeding, hemoglobinemia and hemoglobinuria, or autoagglutination.
Administration of any foreign protein has the potential to cause immunologic reactions; while low levels of IgG antibodies have been detected after multiple dosages, no anaphylactic reactions have been reported thus far. If an immediate hypersensitivity reaction occurs, infusion should be immediately discontinued and appropriate treatment administered. If a delayed type of hypersensitivity reaction occurs, immunosuppressant therapy is recommended.
Safe use in breeding dogs and pregnant or lactating bitches has not been determined.
Adverse reactions occurring in 4% of the dogs treated with Oxyglobin® included: coughing, disseminated intravascular coagulopathy, melena, nasal discharge/crusts (red), peritoneal effusion, respiratory arrest, and weight loss (5-7% body weight). Adverse reactions occurring in less than 2%of the dogs treated with Oxyglobin® included: abdominal discomfort on palpation, acidosis, cardiacarrest, cardiovascular volume overload (by echocardiography), collapse, cystitis, dark stool, discolored soft stool (red-brown) and tongue (purple), focal hyperemic areas on gums, forelimbcellulitis/lameness, hematemesis or hemoptysis (unable to differentiate), hypernatremia, hypotension, hypoxemia, lack of neurologic responses, left forebrain signs, nystagmus, pancreatitis, pendulous abdomen, polyuria, pulmonary thromboembolism, ptosis, reddened pinnae withpapules/head shaking, reduction in heart rate, thrombocytopenia (worsening), and venousthrombosis.
Small amounts of unstabilized hemoglobin (<5%) may be excreted through the kidneys, resultingin transient discoloration (red) of the urine following the infusion. This discoloration of the urineshould not be interpreted as due to intravascular hemolysis and has no effect on renal function.
Increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) not associatedwith histopathologic changes in the liver, increase in serum total protein, and hemoglobinuria mayalso be seen.
Overdosage - The clinical signs associated with Oxyglobin® administered at 1, 2, and 3 times therecommended dose twice, 3 days apart include yellow-orange discoloration of skin, ear canals, pinnae, mucous membranes (gums), and sclera, red-dark-green-black discoloration of feces, brown-black discoloration of urine, red spotting of skin and/or lips (less common finding), decreasedappetite and thirst, vomiting, diarrhea, and decreased skin elasticity. The frequency and/or intensityof these signs increased with repeated dose and with increasing dose. Healthy dogs administered3X overdoses twice, all survived.
Overdosage or an excessively rapid administration rate (i.e., > 10 ml/kg/hr) may result in circulatory overload.
Drug Interactions/Drug Lab Interactions - Other than concerns with compatibility (noted above), no specific drug interactions have been noted.
The presence of Oxyglobin® in serum may cause artifactual increases or decreases in the results of serum chemistry tests, depending on the type of analyzer and reagents used. Refer to the actual package insert for specific information.
There is reportedly no interference with hematology tests, but due to the dilutional effects of
Oxyglobin®, PCV and RBC count are not accurate measures of the degree of anemia for 24 hours following administration. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) determined using methods that are mechanical, magnetic and light scattering are accurate, but optical methods are not reliable while Oxyglobin® is present.
Urine dipstick measurements (i.e., pH, glucose, ketones, protein) are inaccurate while gross discoloration of the urine is present.
Storage, Stability, Compatibility
The product remains stable at room temperature or refrigerated (2°-30°C) for 2 years. Do not freeze. It must remain in its overwrap during storage; onceremoved, it should be used within 24 hours. The foil overwrap serves as an oxygen barrier, protecting the hemoglobin from conversion to methemoglobin.The manufacturer states that Oxyglobin® is compatible with any other IV fluid, but should not bemixed with other solutions or medications in the bag. Other intravenous solutions and medicationsmay be administered via a separate site and line, however,
Pharmacology - HEMOGLOBIN GLUTAMER-200 (BOVINE)
The bovine hemoglobin in the product is polymerized into larger molecules toincrease safety, efficacy and intravascular persistence, and is shipped in a deoxygenated state andbecomes oxygenated once circulated through the lungs. Oxyglobin® releases oxygen to tissue in amechanism similarly to endogenous hemoglobin. Oxyglobin® thereby increases plasma and totalhemoglobin concentrations and increases systemic oxygen content.Oxyglobin® also has colloidal properties similar to dextran 70 and hetastarch.
Uses, Indications
Oxyglobin® is indicated for the treatment of dogs with anemia, regardless ofthe cause of anemia (hemolysis, blood loss, or ineffective erythropoiesis). From a prognosticstandpoint, the drug should be more valuable in dog's with regenerative anemias (versus nonregenerative anemias).Pharmacokinetics - HEMOGLOBIN GLUTAMER-200 (BOVINE)
In dogs receiving 15 ml/kg, peak plasma hemoglobin concentrations increased approximately 2.5 g/dL; at 30 ml/kg, approximately 4 mg/dl. Duration of effect continues for at least 24 hours. The plasma half-life in dogs at present labeled dosages is approximately 30-40 hours and Oxyglobin® can be detected in the plasma for 5-7 days after a single dose.As with endogenous hemoglobin, Oxyglobin® is metabolized and eliminated by the reticuloendothelial system. Small amounts of unstabilized hemoglobin (<5%) may be excreted through the kidneys, causing discoloration (red) of the urine.
Contraindications, Precautions, Reproductive Safety
As safe use of Oxyglobin® has not beentested for the following conditions and plasma expanders are generally contraindicated in them, theproduct is labeled as contraindicated in dogs with advanced cardiac disease (i.e., congestive heartfailure) or otherwise severely impaired cardiac function or renal impairment with oliguria or anuria.The safety and efficacy of Oxyglobin® has not been evaluated in dogs with DIC, thrombocytopeniawith active bleeding, hemoglobinemia and hemoglobinuria, or autoagglutination.
Administration of any foreign protein has the potential to cause immunologic reactions; while low levels of IgG antibodies have been detected after multiple dosages, no anaphylactic reactions have been reported thus far. If an immediate hypersensitivity reaction occurs, infusion should be immediately discontinued and appropriate treatment administered. If a delayed type of hypersensitivity reaction occurs, immunosuppressant therapy is recommended.
Safe use in breeding dogs and pregnant or lactating bitches has not been determined.
Adverse Effects, Warnings
The package insert lists the following frequency of adverse reactionsthat occurred in greater than 4% of dogs treated with Oxyglobin® (Note: first figure is % of dogstreated; in parentheses: % treated having hemolytic anemia): Discolored mucous membranes 69%(47%); discolored sclera (yellow, red, brown) 56% (48%); discolored urine (orange, red, brown)52% (41%); discolored skin (yellow) 12% (83%); increased central venous pressure (CVP) 33%(47%); ventricular arrhythmias (AV block, tachycardia, ventricular premature contractions) 15%(78%); ecchymoses/petechiae 8% (50%); bradycardia 6% (67%); vomiting 35% (72%); diarrhea15% (50%); anorexia 8% (25%); tachypnea 15% (50%); dyspnea 14% (71%); pulmonary edema12% (67%); harsh lung sounds/crackles 8% (50%); pleural effusion 6% (67%); fever 17%(40%); death/euthanasia 15% (63%); peripheral edema 8% (25%); hemoglobinuria 6% (67%);dehydration 6% (33%).Adverse reactions occurring in 4% of the dogs treated with Oxyglobin® included: coughing, disseminated intravascular coagulopathy, melena, nasal discharge/crusts (red), peritoneal effusion, respiratory arrest, and weight loss (5-7% body weight). Adverse reactions occurring in less than 2%of the dogs treated with Oxyglobin® included: abdominal discomfort on palpation, acidosis, cardiacarrest, cardiovascular volume overload (by echocardiography), collapse, cystitis, dark stool, discolored soft stool (red-brown) and tongue (purple), focal hyperemic areas on gums, forelimbcellulitis/lameness, hematemesis or hemoptysis (unable to differentiate), hypernatremia, hypotension, hypoxemia, lack of neurologic responses, left forebrain signs, nystagmus, pancreatitis, pendulous abdomen, polyuria, pulmonary thromboembolism, ptosis, reddened pinnae withpapules/head shaking, reduction in heart rate, thrombocytopenia (worsening), and venousthrombosis.
Small amounts of unstabilized hemoglobin (<5%) may be excreted through the kidneys, resultingin transient discoloration (red) of the urine following the infusion. This discoloration of the urineshould not be interpreted as due to intravascular hemolysis and has no effect on renal function.
Increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) not associatedwith histopathologic changes in the liver, increase in serum total protein, and hemoglobinuria mayalso be seen.
Overdosage - The clinical signs associated with Oxyglobin® administered at 1, 2, and 3 times therecommended dose twice, 3 days apart include yellow-orange discoloration of skin, ear canals, pinnae, mucous membranes (gums), and sclera, red-dark-green-black discoloration of feces, brown-black discoloration of urine, red spotting of skin and/or lips (less common finding), decreasedappetite and thirst, vomiting, diarrhea, and decreased skin elasticity. The frequency and/or intensityof these signs increased with repeated dose and with increasing dose. Healthy dogs administered3X overdoses twice, all survived.
Overdosage or an excessively rapid administration rate (i.e., > 10 ml/kg/hr) may result in circulatory overload.
Drug Interactions/Drug Lab Interactions - Other than concerns with compatibility (noted above), no specific drug interactions have been noted.
The presence of Oxyglobin® in serum may cause artifactual increases or decreases in the results of serum chemistry tests, depending on the type of analyzer and reagents used. Refer to the actual package insert for specific information.
There is reportedly no interference with hematology tests, but due to the dilutional effects of
Oxyglobin®, PCV and RBC count are not accurate measures of the degree of anemia for 24 hours following administration. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) determined using methods that are mechanical, magnetic and light scattering are accurate, but optical methods are not reliable while Oxyglobin® is present.
Urine dipstick measurements (i.e., pH, glucose, ketones, protein) are inaccurate while gross discoloration of the urine is present.