How Do Immune Globulins Work?

Immune globulins (also called gamma globulin or immunoglobulin) are made from human blood plasma. The plasma processed from donated human blood contains antibodies (substances made by the body’s immune system in response to bacteria, viruses, fungus, or cancer cells) that protect the body against diseases. These immune globulins are collected from the pooled blood of donors and purified to prevent the passage of diseases to the person who receives them. This therapy is useful in people with weakened immune systems to fight in the following cases: thrombocytopenia (low blood platelet count), postexposure prophylaxis in certain serious viral infections (cytomegalovirus, hepatitis, measles, tetanus, and rubella), hemolytic disease, neurological diseases, organ transplantations, etc.

Over the course of life, the body produces thousands of different antibodies as and when exposed to different infectious organisms that the body considers to be "foreign."

The five major types of antibodies are:

• IgA: found in the nose, breathing passages, digestive tract, ears, eyes, and vagina. Approximately 10% to 15% of the antibodies present in the body are IgA antibodies.
• IgG: found in all the body fluids and is the most commonly found antibody (75% to 80% of all the antibodies in the body). These are the only type of antibodies that can cross the placenta in a pregnant woman to help protect their baby.
• IgM: found in the blood and lymph fluid and is the first type of antibody made in response to an infection, approximately 5% to 10% of all antibodies in the body.
• IgE: found in the lungs, skin, and mucous membranes. IgE antibody levels are often high in people with allergies and involved in allergic reactions to milk, some medicines, and poisons.
• IgD: found in small amounts in the tissues that line the abdomen or chest. 
• Immunoglobulins are prescription-only medicines and are administered via intravenous route (through a vein) in an infusion that usually takes one to four hours and intramuscular route (injected into a muscle).

Immunoglobulins work in the following ways:

• They are made from healthy human blood that has a high level of certain defensive substances (antibodies) that help fight off infections during the transplant process, as the body's defense system (immune system) is weakened to prevent the body from attacking (rejecting) the new organ as the immune system treats the new organ as an invader.
• They reduce the body’s natural defense system which helps in preventing the body from rejecting the kidney transplant so that it can work normally.
• Immunoglobulin provides short-term protection against or reduces the severity of certain diseases.
• They decrease the immune system’s ability to attack body tissues in some cases of autoimmune diseases (a condition in which the immune system mistakenly attacks the healthy cells in the body).
• In addition, they help in conditions wherein there is an inherited inability to produce antibodies or those who are having treatment for certain types of cancer.

Immune globulins are used in conditions such as:

• Primary immunodeficiency syndrome (rare, genetic disorders that impair the immune system)
• Immune thrombocytopenic purpura (a blood disorder characterized by a decrease in the blood platelet count that can lead to easy or excessive bruising and bleeding)
• Aplastic anemia (a condition that damages stem cells in the bone marrow)
• Chronic inflammatory demyelinating polyneuropathy (a neurological disorder characterized by progressive weakness and impaired sensory function in the legs and arms)
• B-cell chronic lymphocytic leukemia (a cancer of lymphocytes [a type of white blood cell involved in the body’s immune system])
• Multifocal motor neuropathy (a disease that affects the body’s motor nerves [nerves that control muscles])
• Dermatomyositis (a rare disease that causes muscle inflammation and skin rash)
• Guillain-Barre syndrome (a rare neurological disorder in which the body's immune system mistakenly attacks part of its peripheral nervous system)
• Lambert-Eaton myasthenic syndrome (a condition in which the immune system attacks the neuromuscular junctions—the areas where the nerves and muscles connect)
• Stiffman syndrome (a rare acquired neurological disorder characterized by progressive muscle stiffness [rigidity] and repeated episodes of painful muscle spasms)
• Neonatal hemochromatosis (a disorder affecting fetuses and newborns. It is characterized by liver disease associated with the accumulation of excess iron in the liver and other areas of the body)
• Administration to mother to prevent hemolytic disease in newborn
• Abortion/miscarriage
• Rh sensitization (when an Rh-negative woman becomes pregnant with an Rh-positive fetus [which can occur when the father’s blood is Rh-positive]; the pregnant woman’s immune system makes antibodies that can destroy the fetus’s blood in a future pregnancy)
• Myelodysplastic syndrome (conditions that can occur when the blood-forming cells in the bone marrow become abnormal)
• Graft versus host disease (a life-threatening complication that can occur after certain stem cell or bone marrow transplants)
• Acute renal graft rejection (when the immune system identifies a grafted organ as foreign and attacks it)
• Kawasaki disease (an illness that causes inflammation [swelling and redness] in blood vessels throughout the body, most commonly affects infants and young children)
• Myositis (chronic, progressive inflammation of the muscles)
• Multiple sclerosis (a potentially disabling disease of the brain and spinal cord) 
• Myasthenia gravis (a rare neuromuscular disorder that causes weakness in the skeletal muscles)
• Lupus (a chronic autoimmune condition that can cause inflammation throughout the body)
• Prophylaxis in organ transplantation:
  • Kidney
  • Heart
  • Lungs
  • Liver
  • Pancreas
  • Bone marrow
• As postexposure prophylaxis for viral infections such as:
  • Cytomegalovirus (CMV)
  • CMV pneumonia (a type of viral pneumonitis and occurs because of infection with CMV)
  • Hepatitis A 
  • Hepatitis B 
  • Rubella
  • Varicella
  • Tetanus
  • Rabies
  • Vaccinia

Adult and pediatric dosage

Subcutaneous injectable solution

• 10% (100 mg/mL) (Gamunex-C, Gammagard Liquid)
• 10% (100 mg/mL) duovial set with recombinant human hyaluronidase 160 units/mL (HyQvia)
• 16.5% (165 mg/mL) (Cutaquig)
• 20% (200 mg/mL) (Hizentra, Cuvitru, Xembify)

Primary Humoral Immunodeficiency

Adult dosage

Hizentra

• May be administered as a subcutaneous infusion at regular intervals as daily up to biweekly (i.e., every 2 weeks)
• Before initiating, obtain serum IgG trough level to guide subsequent dose adjustments.
• Weekly dosing
  • Start 1 week after the last IGIV infusion.
  • Initial weekly dose: 1.37 x previous IVIG dose (in grams) divided by the number of weeks between IVIG doses.
• Biweekly dosing (ie, every 2 weeks)
  • Start treatment 1 or 2 weeks after the last IGIV infusion or 1 week after that last weekly Hizentra infusion.
  • Administer twice the calculated weekly dose.
• Frequent dosing (2-7 times/week)
  • Divide the calculated weekly dose by the desired number of dosage times per week.

Gamunex-C

• Administered as a weekly subcutaneous infusion.
• Initial SC dose: 1.37 x current IVIG dose in mg/kg divided by the number of weeks between intravenous doses.
• Not to exceed 20 mL/hour/infusion site

Gammagard Liquid

• Administered as a weekly subcutaneous infusion.
• Initial subcutaneous dose: Initial subcutaneous dose: 1.37 x current IVIG dose in mg/kg divided by the number of weeks between intravenous doses.
• Above 40 kg: Not to exceed 30 mL/infusion site at the rate of 20 mL/hour/site; for maintenance dose, may increase to 30 mL/hour site.
• Below 40 kg: Not to exceed 20 mL/infusion site at the rate of 15 mL/hour site; for maintenance dose, may increase to 20 mL/hour site.

HyQvia

• Initiating
  • For patients previously on another IgG treatment, administer the first dose approximately 1 week after the last infusion of their previous treatment.
  • Increase the dose and frequency from a 1-week dose to a 3- or 4-week dose (see titration schedule)
  • Initiating treatment at a full monthly dose was not evaluated in clinical trials.
• Titration schedule
• Titrate to dosage interval of every 3-4 weeks.
• Week 1: 1st infusion (weekly dose) at 25% of the targeted dose
• Week 2: 2nd infusion (every 2-week dose) at 50% of the targeted dose
• Week 3: No infusion
• Week 4: 3rd infusion (every 3-week dose) at 75% of the targeted dose
• Week 5: No infusion
• Week 6: No infusion
• Week 7: 4th infusion (every 4week dose) at 100% of the targeted dose (if required)

Switching from IVIG

• Administer HyQvia at the same dose and frequency as the previous intravenous treatment, after the initial dose titration.
• Patients naïve to IgG treatment or switching from Immune Globulin to human subcutaneous.
  • 300-600 mg/kg subcutaneous at 3 to 4-week intervals, after initial titration

Cuvitru or Cutaquig

• Can be administered at regular intervals from daily up to every 2 weeks.
• Initiating
  • Individualize the dose based on the patient’s pharmacokinetic and clinical response.
  • Monitor serum IgG trough levels regularly to guide subsequent dose adjustments and dosing intervals as needed.
• Switching from IVIG or adults switching from HyQvia
  • Begin 1 week after the patient’s last IGIV or HyQvia infusion.
  • Establish the initial weekly dose by converting the monthly IGIV or HyQvia dose into an equivalent weekly dose and increasing it using a dose adjustment factor.
  • To calculate the initial weekly dose, divide the previous IGIV or HyQvia dose in grams by the number of weeks between Intravenous doses; then multiply this dose by the dose adjustment factor of 1.3.
  • Doses divided over the course of a week, once weekly, or biweekly, achieve similar exposure when administered regularly at steady-state.
• Switching from another Immune Globulin human subcutaneous (IGSC)
  • Weekly dose (in grams) is recommended to be the same as the weekly dose of prior IGSC treatment (in grams)
  • Doses divided over the course of a week, once weekly, or biweekly, achieve similar exposure when administered regularly at steady-state.

Xembify

• Before initiating, obtain serum IgG trough level to guide subsequent dose adjustments.
• Doses divided over the course of a week, or every week achieve similar exposure when administered regularly at steady-state
• For frequent dosing (2-7 times/week), divide the calculated weekly dose by the desired number of dosage times per week.
• Monitor IgG trough level every 2-3 months to determine subsequent dose adjustments and dosing intervals as needed.
• Consider the patient’s clinical response in dose adjustment; if an adequate clinical response or a serum IgG trough level equivalent to that of a previous treatment is not maintained, adjust the dose; accordingly, refer to the prescribing information for further information.
• Switching from IVIG
  • Start 1 week after the last IGIV infusion.
  • Initial weekly dose: 1.37 x previous IVIG dose (in grams) divided by the number of weeks between IVIG doses
• Switching from another IGSC
  • Administer the same weekly dose of Xembify (in grams) as the weekly dose of prior IGSC treatment (in grams)
• Pediatric dosage
  • Below 2 years: Safety and efficacy not established.
  • Individualize dose based on patient’s clinical response and serum IgG trough levels; obtain baseline serum IgG trough level to guide subsequent dosage adjustments.
  • Before initiating, ensure that patients have received IGIV treatment at regular intervals for at least 3 months.

Hizentra

• May be administered as a weekly or biweekly (i.e., every 2 weeks) subcutaneous infusion.
• Initial subcutaneous weekly dose: 1.53 x current IVIG dose in mg/kg divided by the number of weeks between Intravenous doses.
• Initial subcutaneous biweekly dose: For biweekly dosing, start treatment 1 or 2 weeks after the last IGIV infusion or 1 week after that last weekly Hizentra infusion.
• subcutaneous infusion volume: Not to exceed 15 mL/infusion site; for maintenance dose, may increase to 20 mL/site after 4th infusion, and then 25 mL/site as tolerated.
• subcutaneous infusion rate: Not to exceed 15 mL/hour/site for 1st dose; may increase to 25 mL/hour/site for subsequent infusions.

Cuvitru or Cutaquig

• Can be administered at regular intervals from daily up to every 2 weeks.
• Initiating
  • Individualize the dose based on the patient’s pharmacokinetic and clinical response.
  • Monitor serum IgG trough levels regularly to guide subsequent dose adjustments and dosing intervals as needed.
• Switching from IVIG or adults switching from HyQvia
  • Begin 1 week after the patient’s last IGIV or HyQvia infusion.
  • Establish the initial weekly dose by converting the monthly IGIV or HyQvia dose into an equivalent weekly dose and increasing it using a dose adjustment factor.
  • To calculate the initial weekly dose, divide the previous IGIV or HyQvia dose in grams by the number of weeks between intravenous doses; then multiply this dose by the dose adjustment factor of 1.3.
  • Doses divided over the course of a week, once weekly, or biweekly, achieve similar exposure when administered regularly at steady-state.
• Switching from another Immune Globulin human subcutaneous
  • Weekly dose (in grams) is recommended to be the same as the weekly dose of prior IGSC treatment (in grams)
  • Doses divided over the course of a week, once weekly, or biweekly, achieve similar exposure when administered regularly at steady-state.

Gamunex-C

• Administered as a weekly subcutaneous infusion.
• Initial weekly subcutaneous dose: 1.37 x current IVIG dose in mg/kg divided by the number of weeks between intravenous doses.

Gammagard Liquid

• Administered as a weekly subcutaneous infusion.
• Initial SC dose: Initial SC dose: 1.37 x current IVIG dose in mg/kg divided by the number of weeks between intravenous doses.
• Above 40 kg: Not to exceed 30 mL/infusion site at a rate of 20 mL/hour/site; for maintenance dose, may increase to 30 mL/hour site.
• Below 40 kg: Not to exceed 20 mL/infusion site at a rate of 15 mL/hour site; for maintenance dose, may increase to 20 mL/hour site.

Xembify

• Before initiating, obtain serum IgG trough level to guide subsequent dose adjustments.
• Doses divided over the course of a week or every Week achieve similar exposure when administered regularly at steady-state
• For frequent dosing (2-7 times/week), divide the calculated weekly dose by the desired number of dosage times per week
• Monitor IgG trough level every 2-3 months to determine subsequent dose adjustments and dosing intervals as needed
• Consider the patient’s clinical response in dose adjustment; if an adequate clinical response or a serum IgG trough level equivalent to that of a previous treatment is not maintained, adjust the dose; accordingly, refer to the prescribing information for further information
• Switching from IVIG
  • Start 1 week after the last IGIV infusion.
  • Initial weekly dose: 1.37 x previous IVIG dose (in grams) divided by the number of weeks between IVIG doses.
• Switching from another IGSC
  • Administer the same weekly dose of Xembify (in grams) as the weekly dose of prior IGSC treatment (in grams)

Chronic Inflammatory Demyelinating Polyneuropathy

Adult dosage

Hizentra only

• Initiate weekly dosing 1 week after the patient’s last IGIV dose.
• Initial dose
  • 0.2 g/kg (1 mL/kg) SC per week, administered in 1 or 2 sessions over 1 or 2 consecutive days.
• If CIDP symptoms worsen
  • If CIDP symptoms worsen at 0.2 g/kg/week, consider increasing the dose to 0.4 g/kg/week Subcutaneous administered in 2 sessions per week over 1-2 consecutive days.
  • If CIDP symptoms worsen at 0.4 g/kg/week, consider reinitiating therapy with an IGIV product approved for the treatment of CIDP, while discontinuing Hizentra
  • Monitor the patient’s clinical response and adjust the duration of therapy based on the patient’s needs.

HyQvia

• 80 U/g immune globulin (IgG) corresponds to 0.5 mL rHuPH20 solution per 10 mL immune globulin infusion 10% (human) solution
• General instructions
• Before initiating, calculate the weekly equivalent dose to plan for the ramp-up schedule
• Adjust dose and dosing frequency based on individual clinical response
• Dose ramp-up schedule recommended by gradually increasing SC infusion volume until full dose is reached to ensure tolerability
• Depending on the treating physician's discretion, if the first 2 infusions were well tolerated, subsequent infusions may be administered by gradually increasing doses and decreasing dose intervals, considering the volume and total infusion time
• Doses less than or equal to 0.4 g/kg may be administered without ramp-up provided acceptable patient tolerance
• Switching from IGIV
  • Administer HyQvia at the same dose and frequency as previous IVIG treatment, after initial dose titration
  • Administer calculated one-week dose (1st infusion) at 2 weeks after last IGIV infusion
  • 1 week after the first dose, administer another weekly equivalent dose (2nd infusion)
• Titration schedule
  • Gradually increase dose and frequency from every 1-week dose to every 3-or 4-week
  • Week 1: 1st SC infusion (weekly dose) at 25% of the targeted dose
  • Week 2: 2nd infusion (every 2 weeks dose) at 50% of the targeted dose
  • Week 3: No infusion
  • Week 4: 3rd infusion (every 3 weeks dose) at 75% of the targeted dose
  • Week 5: No infusion
  • Week 6: No infusion
  • Week 7: 4th infusion (every 4 weeks dose) at 100% of the targeted dose (if required)
• Patients naïve to IgG treatment or switching from immune globulin human SC
  • 300-600 mg/kg SC at 3-4 week intervals, after initial titration

Dosage Considerations – Should be Given as Follows: 

• See "Dosages”

Common side effects include:

• Abdominal pain 
• Asthenia (physical weakness or a lack of energy)
• Chills 
• Diarrhea 
• Dyspnea (shortness of breath)
• Fever 
• Headache 
• Malaise (a feeling of weakness, overall discomfort, and illness)
• Nausea
• Vomiting
• Flushing
• Muscle cramps
• Back/joint pain 
• Drowsiness (feeling abnormally sleepy during the day)
• Pain/tenderness at the injection site

Other rare side effects include:

• Hyperkalemia (high potassium levels)
• Leukopenia (reduced number of white blood cells)
• Peripheral edema (swelling of lower legs or hands)
• Tachycardia (a fast heart rate—more than 100 beats per minute)
• Thrombocytopenia (low blood platelet count)
• Dizziness (feeling faint, weak, or unsteady)
• Increased sweating
• Urinary tract infection
• Hypertension (high blood pressure)
• Rapid and shallow breathing
• Chest pain/heaviness
• Swelling of the ankles, feet, and hands
• Signs of kidney problems
• Change in the amount of urine
• Pink/bloody/frothy urine

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of immune globulins include:

• Antithymocyte globulin rabbit
• Asceniv
• ATG rabbit
• BabyBIG
• Bivigam
• Botulism immune globulin iv
• Carimune
• Carimune NF
• Cmv ig
• Cutaquig
• Cuvitru
• CytoGam
• Cytomegalovirus immune globulin (CMV IG)
• Flebogamma
• Flebogamma 10% DIF
• Flebogamma 5% DIF
• GamaSTAN
• GamaSTAN S/D
• Gammagard
• Gammagard liquid SC
• Gammagard S/D
• Gammaked
• Gammaplex
• Gamulin Rh
• Gamunex-C
• Gamunex-C SC
• H big
• Hep B gammagee
• HepaGam B
• Hepatitis B immune globulin (HBIG)
• Hizentra
• Hyper tet
• HyperHep
• HyperHEP B S/D
• HyperRAB S/D
• HyperRHO
• HyperTET S/D
• HypRho D
• HyQvia
• IM Immune globulins
• Immune globulin IM (IGIM)
• Immune globulin IV (IGIV)
• Immune globulin SC
• Immune globulin SC-klhw
• Imogam rabies HT
• ISG
• IV Immune globulin
• IVIG
• KedRab
• MicRhoGAM
• Octagam
• Panzyga
• Privigen
• Rabies immune globulin, human (RIG)
• Rhesonativ
• Rho(D) immune globulin
• RhoGAM
• Rhophylac
• RIG
• Tetanus immune globulin (TIG)
• Thymoglobulin
• TIG
• Vaccinia immune globulin intravenous
• Varicella zoster immune globulin, human
• VariZIG
• VIGIV
• WinRho SDF
• Xembify