Endobulin Uses

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• Endobulin indications
• Uses of Endobulin in details
• Endobulin description
• Endobulin dosage
• Endobulin interactions
• Endobulin side effects
• Endobulin contraindications

What is Endobulin?

Endobulin injection is used to prevent or treat diseases that occur when your body has a weak immune system. Endobulin contains antibodies that make your immune system stronger. It is used for patients who have primary humoral immunodeficiency (PI), idiopathic thrombocytopenic purpura (ITP), chronic immune thrombocytopenic purpura, or chronic inflammatory demyelinating polyneuropathy (CIDP). It is also used to improve muscle strength and disability in patients with multifocal motor neuropathy (MMN). Endobulin injection belongs to a group of medicines known as immunizing agents.

Endobulin is to be given only by or under the supervision of your doctor.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, Endobulin is used in certain patients with the following medical conditions:

• Chronic parvovirus B19 infection (treatment).
• Dermatomyositis (treatment).
• Guillain-Barré syndrome (treatment).
• Hyperimmunoglobulinemia E syndrome (treatment).
• Infections in low birth weight preterm high-risk neonates (prevention and treatment).
• Lambert-Eaton myasthenic syndrome (treatment).
• Relapsing-remitting multiple sclerosis (treatment).

Endobulin indications

Hepatitis A

The prophylactic value of Endobulin is greatest when given before or soon after exposure to hepatitis A. Endobulin is not indicated in persons with clinical manifestations of hepatitis A or in those exposed more than 2 weeks previously.

Measles (Rubeola)

Endobulin should be given to prevent or modify measles in a susceptible person exposed fewer than 6 days previously.(7) A susceptible person is one who has not been vaccinated and has not had measles previously. Endobulin may be especially indicated for susceptible household contacts of measles patients, particularly contacts under 1 year of age, for whom the risk of complications is highest.(7) Endobulin and measles vaccine should not be given at the same time.(7) If a child is older than 12 months and has received Endobulin, he should be given measles vaccine about 3 months later when the measles antibody titer will have disappeared.

If a susceptible child exposed to measles is immunocompromised, Endobulin should be given immediately.(8)

Children who are immunocompromised should not receive measles vaccine or any other live viral vaccine.

Varicella

Passive immunization against varicella in immunosuppressed patients is best accomplished by use of Varicella-Zoster Endobulin (Human) [VZIG]. If VZIG is unavailable, Endobulin, promptly given, may also modify varicella.(5)

Rubella

The routine use of Endobulin for prophylaxis of rubella in early pregnancy is of dubious value and cannot be justified.(6) Some studies suggest that the use of Endobulin in exposed, susceptible women can lessen the likelihood of infection and fetal damage; therefore, Endobulin may benefit those women who will not consider a therapeutic abortion.(4)

Immunoglobulin Deficiency

In patients with immunoglobulin deficiencies, Endobulin may prevent serious infection. However, Endobulin may not prevent chronic infections of the external secretory tissues such as the respiratory and gastrointestinal tract.

Prophylactic therapy, especially against infections due to encapsulated bacteria, is effective in Bruton-type, sex-linked, congenital agammaglobulinemia, agammaglobulinemia associated with thymoma, and acquired agammaglobulinemia.

How should I use Endobulin?

Use Endobulin as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet may be available with Endobulin. Talk to your pharmacist if you have questions about this information.
• Endobulin is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using Endobulin at home, a health care provider will teach you how to use it. Be sure you understand how to use Endobulin. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
• If you will be using Endobulin as an injection or infusion under the skin, be sure NOT to inject it into a muscle or vein. Be sure you know how and where to inject Endobulin. Do not use a site that is very bony.
• Be sure to rotate infusion sites as directed by your health care provider.
• Do not use Endobulin if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• Do not use Endobulin if it has ever been frozen.
• Do not shake Endobulin.
• Do not mix Endobulin with any other medicine.
• Do NOT use Endobulin as an injection under the skin for ITP or CIDP. If you have ITP or CIDP, it should only be given as an injection in your vein at your doctor's office, hospital, or clinic. Discuss any questions or concerns with your doctor.
• Throw away any medicine that is left in the vial after you use a dose of Endobulin.
• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of Endobulin, contact your doctor right away.

Ask your health care provider any questions you may have about how to use Endobulin.

Uses of Endobulin in details

This medication is used to provide protection (antibodies) against certain virus infections (hepatitis A, measles, chickenpox, rubella) in people who have not been vaccinated or have not had the infection before. It is also used to strengthen the body's natural defense system (immune system) to lower the risk of infection in persons with a certain immune system problem (immunoglobulin deficiency). This medication is made from healthy human blood that has high levels of certain defensive substances (antibodies), which help fight infections. Routine vaccination is usually the best way to protect against infection. Talk with your doctor about a recommended vaccination schedule.

How to use Endobulin intramuscular

This medication is injected into a muscle as directed by your doctor. The dosage and schedule of injections depends on your medical condition, weight, and response to treatment. Large doses (more than 10 milliliters) should be divided into 2 or more injections and given at separate injection sites.

This medication is given as soon as possible after you have had contact with (been exposed to) someone with hepatitis A, measles, chicken pox, or rubella. If you wait too long after being exposed, the medication may not be effective. Not everyone who is exposed to these infections should receive immunoglobulin. Discuss the risks and benefits with your doctor.

If you are traveling to an area where hepatitis A is common, this medication may be given along with the hepatitis A vaccine (in a separate injection). This medication will help protect you until your body can make antibodies from the vaccine. If you cannot use the hepatitis A vaccine, you may need to receive more doses of Endobulin if you are staying in the area for a long time (more than 3 months). Do not receive live virus vaccines (e.g., measles) at the same time as Endobulin. Ask your doctor or pharmacist for more details and a recommended vaccination schedule.

If you are giving this medication to yourself at home, learn all preparation and usage instructions from your health care professional. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Learn how to store and discard medical supplies safely.

If you are using this medication for an immune system problem, it is usually given every 3 to 4 weeks or as directed by your doctor. Use this medication regularly in order to get the most benefit from it. Keep all your medical/lab appointments.

Endobulin description

One (1) ml of solution contains 100 mg human plasma protein with an IgG content of at least 98% (10% solution). Endobulin is isotonic, with an osmolality of 320 mOsmol/kg. Endobulin has a low sodium content of ≤1 mmol/L.

Endobulin also contains L-proline and water for injection a excipients. Distribution of the IgG subclasses (average values): IgG1 67.8%, IgG2 28.7%, IgG3 2.3%, IgG4 1.2%.

The maximum IgA content is 0.025 mg/mL.

Endobulin dosage

For intravenous use only

Endobulin (Endobulin intravenous (human) 10%) consists of 9%–11% protein in 0.16–0.24 M glycine. The buffering capacity of Endobulin (Endobulin intravenous (human) 10%) is 35.0 mEq/L (0.35 mEq/g protein). A dose of 1 g/kg body weight therefore represents an acid load of 0.35 mEq/kg body weight. The total buffering capacity of whole blood in a normal individual is 45–50 mEq/L of blood, or 3.6 mEq/kg body weight. Thus, the acid load delivered with a dose of 1 g/kg of Endobulin (Endobulin intravenous (human) 10%) would be neutralized by the buffering capacity of whole blood alone, even if the dose was infused instantaneously.

Preparation and Handling

• Endobulin (Endobulin intravenous (human) 10%) should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if turbid.
• Do not freeze. Solutions that have been frozen should not be used.
• The Endobulin (Endobulin intravenous (human) 10%) vial is for single use only. Endobulin (Endobulin intravenous (human) 10%) contains no preservative. Any vial that has been entered should be used promptly. Partially used vials should be discarded.
• Endobulin (Endobulin intravenous (human) 10%) should be infused using a separate line by itself, without mixing with other intravenous fluids or medications the subject might be receiving.
• Endobulin (Endobulin intravenous (human) 10%) is not compatible with saline. If dilution is required, Endobulin (Endobulin intravenous (human) 10%) may be diluted with 5% dextrose in water (D5/W). No other drug interactions or compatibilities have been evaluated.
• Content of vials may be pooled under aseptic conditions into sterile infusion bags and infused within 8 hours after pooling.
• Do not mix with Endobulin intravenous (IGIV) products from other manufacturers.
• Do not use after expiration date.

Treatment of Primary Humoral Immunodeficiency

As there are significant differences in the half-life of IgG among patients with primary immunodeficiencies, the frequency and amount of immunoglobulin therapy may vary from patient to patient. The proper amount can be determined by monitoring clinical response.

The dose of Endobulin (Endobulin intravenous (human) 10%) for replacement therapy in primary immune deficiency diseases is 300 to 600 mg/kg body weight (3-6 mL/kg) administered every 3 to 4 weeks. The dosage may be adjusted over time to achieve the desired trough levels and clinical responses.

Treatment of Idiopathic Thrombocytopenic Purpura

Endobulin (Endobulin intravenous (human) 10%) may be administered at a total dose of 2 g/kg, divided in two doses of 1 g/kg (10 mL/kg) given on two consecutive days or into five doses of 0.4 g/kg (4 mL/kg) given on five consecutive days. If after administration of the first of two daily 1 g/kg (10 mL/kg) doses, an adequate increase in the platelet count is observed at 24 hours, the second dose of 1g/kg (10 mL/kg) body weight may be withheld.

Forty-eight ITP subjects were treated with 2 g/kg Endobulin (Endobulin intravenous (human) 10%), divided in two 1 g/kg doses (10 mL/kg) given on two successive days. With this dose regimen 35/39 subjects (90%) responded with a platelet count from less than or equal to 20 x10/L within 7 days after treatment. The high dose regimen (1 g/kg

Endobulin interactions

See also:
What other drugs will affect Endobulin?

Endobulin (Endobulin intravenous (human) 10%) may be diluted with 5% dextrose in water (D5/W). Admixtures of Endobulin (Endobulin intravenous (human) 10%) with other drugs and intravenous solutions have not been evaluated. It is recommended that Endobulin (Endobulin intravenous (human) 10%) be administered separately from other drugs or medications which the patient may be receiving. The product should not be mixed with IGIVs from other manufacturers.

The infusion line may be flushed before and after administration of Endobulin (Endobulin intravenous (human) 10%) with 5% dextrose in water. Various passively transferred antibodies in immunoglobulin preparations can confound the results of serological testing.

Antibodies in Endobulin (Endobulin intravenous (human) 10%) may interfere with the response to live viral vaccines such as measles, mumps and rubella. Physicians should be informed of recent therapy with IGIVs, so that administration of live viral vaccines, if indicated, can be appropriately delayed 3 or more months from the time of IGIV administration.

REFERENCES

1. Kelleher J, F.G., Cyrus P, Schwartz L,, A Randomized, Double-Blind, Multicenter, Parallel Group Trial Comparing the Safety and Efficacy of IGIV-Chromatography, 10% (Experimental) with IGIV-Solvent Detergent Treated, 10% (Control) in Patients with Primary Immune Deficiency (PID), 2000. Report on file.

3. Bayever E, M.F., Sundaresan P, Collins S, Randomized, Double-Blind, Multicenter, Repeat Dosing, Cross-Over Trial Comparing the Safety, Pharmacokinetics, and Clinical Outcomes of IGIV-Chromatography, 10% (Experimental) with IGIV-Solvent Detergent Treated, 10% (Control) in Patients with Primary Humoral Immune Deficiency (BAY-41-1000-100152). MMRR-1512/1, 1999.

4. Lathia C, E.B., Sundaresan PR, Schwartz L, A Randomized, Open-Label, Multicenter, Repeat Dosing, Cross-Over Trial Comparing the Safety, Pharmacokinetics, and Clinical Outcomes of IGIV-Chromatography, 5% with IGIV-Chromatography 10% in Patients with Primary Humoral Immune Deficiency (BAY-41-1000-100174). 2000.

11. Cyrus P, F.G., Kelleher J, Schwartz L,, A Randomized, Double-Blind, Multicenter, Parallel Group Trial Comparing the Safety, and Efficacy of IGIV-Chromatography, 10% (Experimental) with IGIV-Solvent Detergent Treated, 10% (Control) in Patients with Idiopathic (Immune) Thrombocytopenic Purpura (ITP), 2000. Report on file.

36. Kelleher J, S.L., IGIV-C 10% Rapid Infusion Trial in Idiopathic (Immune) Thrombocytopenic Purpura (ITP), 2001. Report on file.

37. Pierce LR, Jain N. Risks associated with the use of intravenous immunoglobulin. Trans Med Rev 2003; 17,241-251.

Endobulin side effects

See also:
What are the possible side effects of Endobulin?

Adverse Drug Reaction Overview

The most serious adverse reaction observed in clinical study subjects receiving Endobulin (Endobulin intravenous (human) 10%) for PI was an exacerbation of autoimmune pure red cell aplasia in one subject.

The most serious adverse reaction observed in clinical study subjects receiving Endobulin (Endobulin intravenous (human) 10%) for ITP was myocarditis in one subject that occurred 50 days post study drug infusion and was not considered drug related.

The most serious adverse reaction observed in clinical study subjects receiving Endobulin (Endobulin intravenous (human) 10%) for CIDP was pulmonary embolism (PE) in one subject with a history of PE.

The most common drug related adverse reactions observed at a rate >5% in subjects with PI were headache, cough, injection site reaction, nausea, pharyngitis and urticaria.

The most common drug related adverse reactions observed at a rate >5% in subjects with ITP were headache, vomiting, fever, nausea, back pain and rash.

The most common drug related adverse reactions observed at a rate >5% in subjects with CIDP were headache, fever, chills and hypertension

Clinical Trials Adverse Drug Reactions

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed cannot be directly compared to rates in other clinical trials and may not reflect the rates observed in practice.

Adverse events similar to those previously reported with the administration of intravenous and intramuscular immunoglobulin products may occur. Cases of reversible aseptic meningitis, migraine, isolated cases of reversible hemolytic anemia and reversible increases in liver function tests have been observed with Endobulin (Endobulin intravenous (human) 10%). Immediate anaphylactic reactions can possibly occur (<0.01%). Epinephrine should be available for treatment of any acute anaphylactoid reaction.

Treatment of Primary Humoral Immunodeficiency

The following table shows the number of subjects treated with Endobulin (Endobulin intravenous (human) 10%) in clinical trials to study PI, and the reason for discontinuation due to adverse events:

Table 1: Reasons for Discontinuation Due to Adverse Events: All PI Studies

In study 100175, 9 subjects in each treatment group were pretreated with non-steroidal medication prior to infusion. Generally, diphenhydramine and acetaminophen were used.

Any adverse events in trial 100175, irrespective of the causality assessment, are given in the following table.

Table 2: Subjects with At Least One Adverse Event Irrespective of Causality (Study 100175)

The subset of drug related adverse events in trial 100175 reported by at least 5% of subjects during the 9-month treatment are given in the following table.

Table 3: Subjects with At Least One Drug Related Adverse Event (Study 100175)

Adverse events, which were reported by at least 5% of subjects, were also analyzed by frequency and in relation to infusions administered. The analysis is displayed in the following table.

Table 4: Adverse Event Frequency (Study 100175)

The mean number of adverse events per infusion that occurred during or on the same day as an infusion was 0.21 in both the Endobulin (Endobulin intravenous (human) 10%) and Endobulin treatment groups.

In all three trials in primary humoral immundeficiencies, the maximum infusion rate was 0.08 mL/kg/min (8 mg/kg/min). The infusion rate was reduced for 11 of 222 exposed subjects (7 Endobulin (Endobulin intravenous (human) 10%), 4 Endobulin) at 17 occasions. In most instances, mild to moderate hives/urticaria, itching, pain or reaction at infusion site, anxiety or headache was the main reason. There was one case of severe chills. There were no anaphylactic or anaphylactoid reactions to Endobulin (Endobulin intravenous (human) 10%) or Endobulin.

In trial 100175, serum samples were drawn to monitor the viral safety at baseline and one week after the first infusion (for parvovirus B19), eight weeks after first and fifth infusion, and 16 weeks after the first and fifth infusion of IGIV (for hepatitis C) and at any time of premature discontinuation of the study. Viral markers of hepatitis C, hepatitis B, HIV-1, and parvovirus B19 were monitored by nucleic acid testing (NAT, Polymerase Chain Reaction (PCR), and serological testing. There were no treatment emergent findings of viral transmission for either Endobulin (Endobulin intravenous (human) 10%), or Endobulin. [1, 3, 4]

Treatment of Idiopathic Thrombocytopenic Purpura

The following table shows the number of subjects treated with Endobulin (Endobulin intravenous (human) 10%) in clinical trials to study ITP, and the reason for discontinuation due to adverse events:

Table 5: Reasons for Discontinuation Due to Adverse Events: All ITP Studies

One subject, a 10-year-old boy, died suddenly from myocarditis 50 days after his second infusion of Endobulin (Endobulin intravenous (human) 10%). The death was judged to be unrelated to Endobulin (Endobulin intravenous (human) 10%).

No pre-medication with corticosteroids was permitted by the protocol. Twelve (12) ITP subjects treated in each treatment group were pretreated with medication prior to infusion. Generally, diphenhydramine and/or acetaminophen were used. More than 90% of the observed drug related adverse events were of mild to moderate severity and of transient nature.

The infusion rate was reduced for 4 of the 97 exposed subjects (1 Endobulin (Endobulin intravenous (human) 10%), 3 Endobulin) on 4 occasions. Mild to moderate headache, nausea, and fever were the reported reasons. There were no anaphylactic or anaphylactoid reactions to Endobulin (Endobulin intravenous (human) 10%) or Endobulin.

Any adverse events in trial 100176, irrespective of the causality assessment, reported by at least 5% of subjects during the 3-month trial are given in the following table.

Table 6: Subjects with At Least One Adverse Event Irrespective of Causality (Study 100176)

The subset of drug related adverse events in trial 100176 reported by at least 5% of subjects during the 3-month trial are given in the following table.

Table 7: Subjects with At Least One Drug Related Adverse Event (Study 100176)

Serum samples were drawn to monitor the viral safety of the ITP subjects at baseline, nine days after the first infusion (for parvovirus B19), and 3 months after the first infusion of IGIV and at any time of premature discontinuation of the study. Viral markers of hepatitis C, hepatitis B, HIV-1, and parvovirus B19 were monitored by nucleic acid testing (NAT, PCR), and serological testing. There were no treatment related emergent findings of viral transmission for either Endobulin (Endobulin intravenous (human) 10%), or Endobulin.

Treatment of Chronic Inflammatory Demyelinating Polyneuropathy

In study 100538, 113 subjects were exposed to Endobulin and 95 were exposed to Placebo. As a result of the study design, the drug exposure with Endobulin (Endobulin intravenous (human) 10%) was almost twice that of Placebo, with 1096 Endobulin (Endobulin intravenous (human) 10%) infusions versus 575 Placebo infusions. Therefore, adverse reactions are reported per infusion (represented as frequency) to correct for differences in drug exposure between the 2 groups. The majority of loading-doses were administered over 2 days. The majority of maintenance-doses were administered over 1 day. Infusions were administered in the mean over 2.7 hours.

The following table shows the numbers of subjects per treatment group in the CIDP clinical trial, and the reason for discontinuation due to adverse events:

Table 8: Reasons for Discontinuation Due to Adverse Events: CIDP

Adverse events reported by at least 5% of subjects in any treatment group irrespective of causality are shown in the following table.

Table 9: Subjects with At Least One Adverse Event Irrespective of Causality (Study 100538)

Laboratory Abnormalities

During the course of the clinical program, ALT and AST elevations were identified in some subjects.

• For ALT, in the primary humoral immunodeficiency (PI) study (100175) treatment emergent elevations above the upper limit of normal were transient and observed among 14/80 (18%) of subjects in the Endobulin (Endobulin intravenous (human) 10%) group versus 5/88 (6%) of subjects in the Endobulin group (p = 0.026).
• In the ITP study which employed a higher dose per infusion, but a maximum of only two infusions, the reverse finding was observed among 3/44 (7%) of subjects in the Endobulin (Endobulin intravenous (human) 10%) group versus 8/43 (19%) of subjects in the Endobulin group (p = 0.118).
• In the CIDP study (100538), 15/113 (13%) of subjects in the Endobulin (Endobulin intravenous (human) 10%) group and 7/95 (7%) in the Placebo group (p=0.168) had a treatment emergent transient elevation of ALT.

Elevations of ALT and AST were generally mild (<3 times upper limit of normal), transient, and were not associated with obvious symptoms of liver dysfunction.

Endobulin (Endobulin intravenous (human) 10%) class. may contain low levels of anti-Blood Group A and B antibodies primarily of the IgG4

Direct antiglobulin tests (DAT or direct Coombs tests), which are carried out in some centers as a safety check prior to red blood cell transfusions, may become positive temporarily. Hemolytic events not associated with positive DAT findings were observed in clinical trials.[1, 3, 4, 11, 36]

Postmarketing Experience

Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate the frequency of these reactions or establish a causal relationship to product exposure.

Endobulin (Endobulin intravenous (human) 10%) Postmarketing Experience

The following adverse reactions have been identified and reported during the post marketing use of Endobulin (Endobulin intravenous (human) 10%) :

• Hematologic:Hemolytic anemia
• Infections and Infestations: Aseptic meningitis

General

The following adverse reactions have been identified and reported during the post marketing use of IGIV products :

• Respiratory: Apnea, Acute Respiratory Distress Syndrome (ARDS), TRALI, cyanosis, hypoxemia, pulmonary edema, dyspnea, bronchospasm
• Cardiovascular:Cardiac arrest, thromboembolism, vascular collapse, hypotension
• Neurological: Coma, loss of consciousness, seizures/convulsions, tremor
• Integumentary: Stevens-Johnson syndrome, epidermolysis, erythema multiforme, bullous dermatitis
• Hematologic: Pancytopenia, leukopenia, hemolysis, positive direct antiglobulin (Coombs test)
• General/Body as a Whole: Pyrexia, rigors
• Musculoskeletal: Back pain
• Gastrointestinal:Hepatic dysfunction, abdominal pain

Endobulin contraindications

See also:
What is the most important information I should know about Endobulin?

Endobulin can harm your kidneys, and this effect is increased when you also use certain other medicines harmful to the kidneys. Before using Endobulin, tell your doctor about all other medications you use. Many other drugs (including some over-the-counter medicines) can be harmful to the kidneys.

Before using Endobulin intravenous, tell your doctor if you have kidney disease, diabetes (especially if you use insulin), a history of stroke or blood clot, heart disease, high blood pressure, a condition called paraproteinemia, or if you are over 65 years old.

To be sure this medicine is helping your condition and is not causing harmful effects, your blood will need to be tested often. Your kidney function may also need to be tested. Visit your doctor regularly.

This medication can cause unusual results with certain blood glucose tests. Tell any doctor who treats you that you are using Endobulin.

Endobulin is made from human plasma (part of the blood) which may contain viruses and other infectious agents. Donated plasma is tested and treated to reduce the risk of it containing infectious agents, but there is still a small possibility it could transmit disease. Talk with your doctor about the risks and benefits of using this medication.

Active ingredient matches for Endobulin:

Immune Globulin in South Africa.

A normal immunoglobulin in United Kingdom, Israel.

Human Immunoglobulin

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Information checked by Dr. Sachin Kumar, MD Pharmacology