Globiga

Package leaflet: Information for the user

Globiga

100 mg/ml infusion solution
Normal human immunoglobulin (IVIg)
Please read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Globiga is and what it is used for
2. What you need to know before using Globiga
3. How to use Globiga
4. Possible side effects
5. How to store Globiga
6. Contents of the pack and other information

1. What Globiga is and what it is used for

What Globiga is
Globiga is a solution of normal human immunoglobulins (IgG), that is, a solution of human antibodies for intravenous administration (i.e. infusion into a vein). Immunoglobulins are normal components of human blood and support the body's immune defense. Globiga contains only IgG derived from blood donated by healthy individuals. With appropriate doses of Globiga, abnormally low IgG levels can be restored to within the normal range.
Globiga contains a broad spectrum of antibodies against various infectious agents.

What Globiga is used for
Globiga is used as replacement therapy in children and adolescents (0–18 years) and adults in different patient groups:

• Patients with congenital antibody deficiency (primary immunodeficiency syndromes), for example: congenital agammaglobulinemia and hypogammaglobulinemia, common variable immunodeficiency, severe combined immunodeficiencies
• Patients with acquired antibody deficiency (secondary immunodeficiency) caused by specific diseases and/or treatments, who experience severe or recurrent infections

Globiga may be used for the treatment of susceptible adults, children, and adolescents (0–18 years) who have been exposed to measles or are at risk of exposure to measles, and in whom active vaccination against measles is not indicated or not recommended.

Globiga may also be used in the treatment of the following autoimmune disorders (immunomodulation):

• In patients with immune thrombocytopenia (ITP), a condition in which platelets are reduced due to destruction, who are at high risk of bleeding or who require correction of platelet count prior to surgical procedures
• In patients with Kawasaki disease, a condition causing inflammation of various organs
• In patients with Guillain-Barré syndrome, a condition causing inflammation of certain parts of the nervous system
• In patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), a disease causing chronic inflammation of the peripheral nervous system leading to muscle weakness and/or numbness, primarily in the legs and arms
• In patients with multifocal motor neuropathy (MMN), a disease characterized by slowly progressive limb weakness without loss of sensation

2. What you need to know before using Globiga

DO NOT use Globiga:

• if you are allergic to normal human immunoglobulins or to any of the other ingredients of Globiga (listed in section 6).
• if you have immunoglobulin A deficiency (IgA deficiency) and have developed antibodies against IgA-type immunoglobulins.

Warnings and precautions
Talk to your doctor or pharmacist before using Globiga.
It is strongly recommended to record, at each administration of Globiga, the name and batch number of the product to ensure traceability of the batch used.
Adverse reactions may occur more frequently:

• if the infusion rate is high
• when receiving Globiga for the first time or, rarely, after a long interval since the previous infusion
• if you have an untreated infection or underlying chronic inflammation

In case of an adverse reaction, your doctor will reduce the rate of administration or stop the infusion.
Management of the adverse event will depend on its nature and severity.
Circumstances and conditions that increase the risk of undesirable effects

• Very rarely, thromboembolic events such as myocardial infarction, stroke, deep vein thrombosis (e.g. in the calf), or pulmonary vessel occlusion may occur after administration of Globiga. These events are more common in patients with risk factors such as obesity, advanced age, high blood pressure, diabetes, previous thromboembolic events, prolonged immobilization, or use of certain hormones (e.g. oral contraceptives). Adequate hydration and the slowest possible infusion rate of Globiga are essential.
• If you have previously had kidney problems, or if you have certain risk factors such as diabetes, overweight, or are over 65 years of age, Globiga must be administered as slowly as possible, as cases of acute renal failure have been reported in patients with these risk factors. Inform your doctor about these conditions, even if they occurred in the past.
• Patients with blood group A, B, or AB and patients with certain inflammatory conditions have an increased risk of red blood cell destruction (hemolysis) caused by the administered immunoglobulins.

When may it be necessary to slow down or stop the infusion?

• Severe headache and neck stiffness may occur several hours to 2 days after treatment with Globiga.

• Allergic reactions are rare but may cause anaphylactic shock, even in patients who previously tolerated treatment. A sudden drop in blood pressure or shock may be consequences of an anaphylactic reaction.

• In very rare cases, transfusion-related acute lung injury (TRALI) may occur after administration of immunoglobulins, including Globiga. This may lead to fluid accumulation in the lung air spaces not due to cardiac causes. You may recognize TRALI by:

  severe breathing difficulty, normal heart function, and increased body temperature (fever).
  Symptoms typically appear within 1–6 hours after administration of the treatment.
  Inform your doctor or healthcare provider immediately if you experience any of the symptoms listed above during or after Globiga infusion. The doctor will decide whether to reduce the infusion rate, stop the infusion completely, or take further measures.

• Occasionally, immunoglobulin solutions such as Globiga may trigger a decrease in white blood cell count. This condition usually resolves spontaneously within 1–2 weeks.

Effects on blood tests
Globiga contains a wide variety of different antibodies, some of which may affect blood test results. If you need to have a blood test after receiving Globiga, inform the laboratory staff or your doctor that you have received normal human immunoglobulin solution.

Viral safety
When medicines are produced from human blood or plasma, certain measures are taken to prevent the transmission of infections to patients. These measures include:

• careful selection of blood and plasma donors to exclude donors at risk of carrying infections
• testing each donation and plasma pool for viruses or infections
• specific manufacturing procedures used by producers to inactivate or remove viruses.

Despite these measures, it is not possible to completely exclude the risk of transmitting infections when administering medicines derived from human blood or plasma. This applies also to unknown or emerging viruses or other types of infections.
These measures are considered effective against enveloped viruses such as HIV (human immunodeficiency virus), hepatitis B virus, and hepatitis C virus, as well as non-enveloped viruses such as hepatitis A virus and parvovirus B19.
Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, probably because antibodies against these infections are present in the product and provide protective effects.

Children and adolescents
There are no specific or additional warnings or precautions for children and adolescents.

Other medicines and Globiga
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those without a prescription, or if you have received a vaccine within the last three months.
Concomitant use of drugs that increase water elimination from the body (loop diuretics) should be avoided during treatment with Globiga. Your doctor will decide whether you should use or continue treatment with loop diuretics.
Globiga may alter the effect of vaccines containing live attenuated viruses such as:

• measles
• rubella
• mumps
• varicella.

An interval of 3 months should elapse between administration of this product and a live attenuated virus vaccine. For measles, interference may persist up to 1 year.

Globiga with food, drinks and alcohol
No effects have been observed. Adequate hydration should be ensured before infusion with Globiga.

Pregnancy, breastfeeding and fertility
If you are pregnant, think you may be pregnant, are planning a pregnancy, or are breastfeeding, ask your doctor or pharmacist whether you can take Globiga or continue treatment with Globiga.
The safety of this medicine during pregnancy in humans has not been evaluated in controlled clinical trials; therefore, it should be administered only with extreme caution to pregnant or breastfeeding women. Immunoglobulin-based products have been shown to cross the placenta, increasingly during the third trimester of pregnancy. Clinical experience with immunoglobulins suggests that harmful effects on the course of pregnancy or on the fetus and newborn are unlikely.
Immunoglobulins are excreted in breast milk. Negative effects on newborns/infants are not expected.

Driving and using machines
Globiga does not affect or affects negligibly the ability to drive vehicles or use machines.
However, patients experiencing adverse reactions during treatment should wait until symptoms resolve before driving or operating machinery.

Globiga contains sodium
This medicine contains 69 mg of sodium (the main component of table salt) per 100 ml vial. This corresponds to 3.45% of the maximum daily recommended dietary intake for an adult.
This should be taken into account for patients on a low-sodium diet.

3. How to use Globiga

Your doctor will decide whether you need Globiga and at what dose. Globiga is administered by
intravenous infusion (infusion into a vein) by clinical staff. The dose and dosing regimen
depend on the indication, and may need to be adjusted for individual patients.
If you have any doubts about the use of this medicine, consult your doctor or pharmacist.
Use in children and adolescents
The administration (by intravenous route) of Globiga in children and adolescents (0–18 years) is not
different from that in adults.
If you receive more Globiga than you should
It is very unlikely that an overdose will occur, as Globiga is generally administered under medical supervision. However, if you do receive more Globiga than you should, your blood may become too thick (hyperviscous), which may increase the risk of developing blood clots. This is especially possible in patients at risk, for example, elderly patients or patients with heart or kidney disease. Make sure you maintain adequate hydration. Inform your doctor if you have any known medical conditions.
If you forget to use Globiga
Consult your doctor to discuss how to proceed.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor as soon as possible if you experience any of the following side effects (all of these are
very rare and may affect up to 1 in 10,000 infusions). In some cases, your doctor may need to
stop treatment and reduce the dose or discontinue treatment:

• Swelling of the face, tongue and trachea, which may cause severe breathing difficulties
• Sudden allergic reaction with shortness of breath, skin rash, wheezing and drop in blood pressure
• Stroke which may cause weakness and/or loss of sensation on one side of the body
• Heart attack which may cause chest pain
• Blood clot which may cause pain and swelling in the limbs
• Blood clot in the lung causing chest pain and difficulty breathing
• Anaemia causing shortness of breath or pale appearance
• Severe kidney disease which may cause inability to urinate
• A lung condition called transfusion-related acute lung injury (TRALI) which causes breathing difficulties, bluish skin colour, fever, and a drop in blood pressure

If you experience any of the symptoms listed above, seek medical advice immediately.
The following side effects have also been reported:
Common side effects (may occur in up to 1 in 10 infusions):
Headache, fever
Uncommon side effects (may occur in up to 1 in 100 infusions):

• Vomiting, abdominal pain, nausea
• Skin peeling, skin inflammation, itchy rash, rash, itching
• Weakness
• Drowsiness, dizziness
• Flu-like illness, chills
• Rapid heartbeat
• Increased blood pressure
• Cough
• Decrease in white blood cells, decrease in red blood cells
• Changes in blood tests related to liver function

Rare side effects (may occur in up to 1 in 1,000 infusions):

• Discomfort in chest or abdomen, diarrhoea
• Skin redness, itching at the infusion site
• Muscle stiffness or pain, muscle pain, joint pain, pain
• Aseptic meningitis (see also section “Warnings and precautions”), reduced tactile sensation
• Peripheral swelling, fatigue, feeling cold
• Chest pain
• Decreased blood pressure
• Breathing difficulties, rapid breathing
• Destruction of red blood cells, reduced haemoglobin in the blood
• Itchy eyes
• Ear pain

Frequency not known (cannot be estimated from the available data):

• Severe and sudden allergic reaction, allergic reactions, facial swelling, sudden swelling under the skin
• Stroke, loss of consciousness, confusion, migraine, sensations such as numbness, tingling, pins and needles, nervousness, agitation
• Excessive contraction of the airway muscles causing breathing difficulties, lack of oxygen in body tissues, lung swelling, wheezing
• Muscle spasms, neck pain, limb pain
• Flushing, hot flushes, excessive sweating, swelling, injection site reaction, burning sensation, feeling unwell, sensation of warmth, chills, lack of energy
• Chest, jaw and back pain due to physical exertion and problems with blood flow to the heart, low heart rate, pounding heartbeat, pallor, bluish skin and lips
• Abnormal sensitivity of the eyes to light
• Abnormal lung function test result.

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or pharmacist.
You can also report side effects directly via the national reporting system at: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse .
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Globiga

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label and the carton. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C–8°C). Keep the container in the outer packaging to protect it from light. Do not freeze.
The product may be removed from the refrigerator for up to 12 months (without exceeding the expiry date) and stored at temperatures between +8°C and +25°C. During this period, the product must not be returned to the refrigerator.
Discard the product if it is not used within this period or after the expiry date, whichever comes first. Record the date on which the product was removed from the refrigerator on the outer carton.
Do not use this medicine if you notice that the solution is cloudy, contains visible particles, or has an intense colour.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Globiga contains

• The active substance is human normal immunoglobulin (human antibodies). Globiga contains 100 mg/ml of human protein, of which at least 95% are immunoglobulins G (IgG).
• The other components are glycine and water for injections.

Description of the appearance of Globiga and contents of the pack
Globiga is an infusion solution available in vials (1 g/10 ml, 2.5 g/25 ml) or bottles (5 g/50 ml, 6 g/60 ml, 10 g/100 ml, 20 g/200 ml, 30 g/300 ml).
Pack sizes:
1 vial (1 g/10 ml or 2.5 g/25 ml)
1 bottle (5 g/50 ml, 6 g/60 ml, 10 g/100 ml, 20 g/200 ml or 30 g/300 ml)
3 bottles (3 x 10 g/100 ml or 3 x 20 g/200 ml)
Transparent or slightly opalescent solution, colourless to pale yellow.
Not all pack sizes may be marketed.

Marketing Authorization Holder
OCTAPHARMA ITALY S.p.A.
Via Cisanello, 145
56100 Pisa
Italy

Manufacturers
Octapharma
72 rue du Maréchal Foch, 67380 Lingolsheim, France
Octapharma Pharmazeutika Produktionsges.m.b.H.
Oberlaaer Strasse 235, 1100 Vienna, Austria

This medicinal product is authorized in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Austria, Belgium, Bulgaria, Croatia, Denmark, Estonia, Finland, France, Germany, Ireland, Iceland, Latvia, Lithuania, Luxembourg, Malta, Norway, Netherlands, Portugal, United Kingdom (Northern Ireland), Czech Republic, Slovakia, Romania, Slovenia, Spain, Sweden, Hungary:
Italy: Globiga

The following information is intended exclusively for healthcare professionals:

• The product must be brought to room temperature or body temperature before use.
• The solution should be clear or slightly opalescent, colorless to slightly yellow.
• Do not use if the solution is cloudy or contains visible particles.
• Unused medicine and waste material resulting from this medicine must be disposed of in accordance with local regulations.
• This medicine must not be mixed with other medicinal products.
• To administer any residual product remaining in the infusion tubing at the end of the infusion, the tubing may be flushed with 0.9% sodium chloride solution (9 mg/ml) or 5% dextrose solution (50 mg/ml).