Octagam

Package leaflet: Information for the user

Octagam

50 mg/ml infusion solution
Normal human immunoglobulin (IVIg)
Please read this leaflet carefully before 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 give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Octagam is and what it is used for

What Octagam is:
Octagam is a solution of normal human immunoglobulin (IgG) (i.e. a solution of human antibodies) for intravenous administration (i.e. infusion into a vein). Immunoglobulins are natural components of the human body and contribute to the body's immune defenses. Octagam contains all IgG activities found in the normal population. Adequate doses of this medicine can correct abnormally low IgG levels, restoring them to the normal range.
Octagam has a broad spectrum of antibodies active against various infectious agents.

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

• Patients with congenital antibody deficiency (primary immunodeficiency syndromes such as 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

Octagam 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 measles exposure, and in whom active measles vaccination is not indicated or not recommended.
Octagam may also be used in the treatment of the following autoimmune diseases (immunomodulation):

• In patients with immune thrombocytopenia (ITP), a condition in which platelets are destroyed and their number is therefore reduced, and who are at high risk of bleeding or require correction of platelet count prior to surgery.
• In patients with Kawasaki disease, a condition leading to 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 peripheral parts of the nervous system, resulting in muscle weakness and/or numbness, primarily in the legs and arms.
• In patients with multifocal motor neuropathy (MMN), a disease characterized by slowly progressive, asymmetric limb weakness without loss of sensation.

2. What you should know before using Octagam

Do not use Octagam

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

Warnings and precautions
Talk to your doctor or pharmacist before using Octagam. It is strongly recommended to record, for each administration of Octagam, the product name and batch number to ensure traceability of the batch used.

Adverse reactions may occur more frequently:

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

If an adverse reaction occurs, the rate of administration should be reduced or the infusion stopped. The treatment required for the adverse event will depend on the nature and severity of the side effect.

Circumstances and conditions that increase the risk of experiencing side effects

• Very rarely, thromboembolic events such as heart attack, stroke, or blockage of a deep vein (e.g., in the calf) or of a blood vessel in the lungs may occur after administration of Octagam. These types of events, although very rare, occur more commonly in patients with risk factors such as obesity, advanced age, high blood pressure, diabetes, previous similar events, prolonged immobilization, or use of certain hormones (e.g., oral contraceptives). Ensure adequate hydration; in addition, Octagam should be administered as slowly as possible.

• If you have previously had kidney problems or have certain risk factors such as diabetes, overweight, or are over 65 years of age, Octagam should be administered as slowly as possible, as cases of acute renal failure, although very rare, have been reported in patients with these risk factors. Inform your doctor if any of the above-mentioned conditions have occurred in the past.

• Patients with blood group A, B, or AB, as well as patients affected by certain inflammatory diseases, are at increased risk of red blood cell destruction (hemolysis) caused by the administered immunoglobulins.

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

• Severe headaches and neck stiffness may rarely occur from several hours up to 2 days after treatment with Octagam.

• Allergic reactions are rare but may lead to anaphylactic shock, even in patients who previously tolerated treatment well. 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 receiving immunoglobulins including Octagam. This leads to fluid accumulation unrelated to cardiac causes in the air spaces of the lungs. TRALI is recognized by the sudden onset of severe breathing difficulties, normal heart function, and increased body temperature (fever). Symptoms typically appear within 1–6 hours after administration of the treatment.

Immediately notify your doctor or healthcare provider if you notice such reactions during or after infusion of Octagam. They will decide whether to reduce the infusion rate, stop the infusion completely, or take further measures.

• Sometimes immunoglobulin solutions such as Octagam may cause a decrease in the number of white blood cells. This condition usually resolves spontaneously within 1–2 weeks.

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

• careful selection of blood and plasma donors to exclude individuals at risk of carrying infectious diseases;
• testing of each donation and plasma pools for signs of viruses/infections;
• inclusion of processing steps that can inactivate or remove viruses.

Despite these measures, when administering medicines prepared from human blood or plasma, it is not possible to completely exclude the risk of transmitting an infection. This also applies to viruses of unknown nature or emerging viruses, or other types of infections. The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus.

The measures may have limited effectiveness against 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 the antibodies against these infections contained in the medicine are protective.

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

Other medicines and Octagam
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 vaccination within the last three months.

The infusion line may be flushed before and after administration of Octagam with 0.9% saline solution or 5% dextrose solution.

Concomitant use of loop diuretics should be avoided.

Octagam may impair the efficacy of vaccines containing live attenuated viruses, such as measles, mumps, rubella, and varicella.

Therefore, a 3-month interval should be observed between administration of this product and live attenuated virus vaccines. For measles, this period of reduced vaccine efficacy may last up to 1 year.

Effects on blood tests
If blood tests are performed after administration of Octagam, inform the person drawing the blood or your doctor that you have been administered a solution of normal human immunoglobulins, as this treatment may affect test results.

Blood glucose testing
Some types of blood glucose monitoring systems (so-called glucometers) may misinterpret the maltose present in Octagam as glucose. This may lead to falsely elevated blood glucose readings and, consequently, inappropriate administration of insulin, resulting in hypoglycemia (i.e., low blood sugar levels) that may be life-threatening.

In addition, actual cases of hypoglycemia may be overlooked if the hypoglycemic state is masked by falsely elevated glucose readings.

Therefore, when administering Octagam or other products containing maltose, blood glucose levels must be measured using test systems based on a glucose-specific method. Systems based on the glucose dehydrogenase-pyrrroloquinoline quinone (GDH-PQQ) method or on the colorimetric glucose oxidoreductase method must not be used.

Carefully read the product information of the glucose test system, including that of the test strips, to determine whether the system is suitable for use with parenteral products containing maltose. If in doubt, consult your physician to determine whether the glucose test system you are using is appropriate for use with parenteral products containing maltose.

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

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 for advice before taking any medicine.

The safety of this medicine during pregnancy in humans has not been evaluated in controlled clinical studies, and therefore it should be administered only with extreme caution in pregnant and breastfeeding women. It has been shown that immunoglobulin products 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. No negative effects on newborns/infants are expected.

Clinical experience with immunoglobulins suggests that no harmful effects on fertility are expected.

Driving and using machines
Octagam does not affect or has a negligible effect on the ability to drive or use machines. However, patients who experience adverse reactions during treatment should wait until these have resolved before driving or operating machinery.

Octagam contains sodium
100 ml of this medicinal product contains 35 mg of sodium (the main component of table salt), equivalent to 1.75% of the maximum daily recommended dietary intake of sodium for an adult.
This should be taken into consideration by patients on a controlled sodium diet.

3. How to use Octagam

It is your doctor's responsibility to decide whether and at what dose Octagam should be administered to you. Octagam is administered by healthcare personnel as an intravenous infusion (infusion into a vein). The dose and dosing regimen depend on the indication, and may need to be individualized for each patient.

• If you have any questions about the use of this medicine, consult your doctor or pharmacist.

Use in children and adolescents
The (intravenous) administration of Octagam in children and adolescents (age 0–18 years) is not different from that in adults.
If you receive more Octagam than you should
Overdose is very unlikely, as Octagam is generally administered under medical supervision. Nevertheless, if you do receive more Octagam than you should, your blood may become too thick (hyperviscous), which may increase the risk of developing blood clots. This may occur especially in at-risk patients, for example the elderly or patients with heart or kidney disease. Make sure to maintain adequate hydration. Inform your doctor if you have any known medical conditions.
If you forget to use Octagam
Contact your doctor to discuss how to proceed.

4. Possible side effects

Like all medicines, Octagam can cause side effects, although not everyone experiences them.
If you experience any of the side effects listed below ( all very rare and may affect up to 1 in 10,000 infusions), contact your doctor as soon as possible.
In some cases, your doctor may consider it necessary to stop the treatment, reduce the dose, or discontinue therapy:

• Swelling of the face, tongue, and trachea, which may cause significant breathing difficulties;
• Sudden allergic reaction with shortness of breath, 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, causing chest pain;
• Thrombus causing pain and swelling in the limbs;
• Anaemia, causing breathlessness or paleness;
• Pulmonary thromboembolism, causing chest pain and shortness of breath;
• Severe kidney damage, which may lead to failure to excrete urine;
• A lung disease called transfusion-related acute lung injury (TRALI), causing breathing difficulties, bluish skin discoloration, fever, and a drop in blood pressure;
• Severe headache in combination with any of the following symptoms: neck stiffness, drowsiness, fever, light sensitivity, nausea, vomiting (these may be signs of meningitis). If you experience any of the symptoms listed above, contact your doctor immediately.

The following side effects have also been reported:

Common side effects (may affect up to 1 in 10 infusions):

• Hypersensitivity (allergic reaction)
• Headache

Uncommon side effects (may affect up to 1 in 100 infusions):

• Low white blood cell count
• Changes in heart rhythm
• Changes in blood pressure
• Vomiting
• Back pain
• Chest pain
• Chills
• Nausea
• Fever
• Feeling of fatigue
• Skin reactions at the injection site
• Abnormal liver function blood tests

Other side effects not observed in clinical studies but reported are:

• Fluid overload
• Low sodium levels in the blood
• Feeling agitated, anxious, confused, or nervous
• Migraine
• Speech disorders
• Loss of consciousness
• Dizziness
• Skin itching sensation
• Reduced sense of touch or sensitivity
• Light sensitivity
• Involuntary muscle contractions
• Weakened vision
• Angina pectoris
• Palpitations
• Temporary bluish discoloration of the lips or other areas of the skin
• Circulatory collapse or shock
• Vein inflammation
• Pale skin
• Cough
• Breathing disorders
• Pulmonary edema (fluid accumulation in the lungs)
• Bronchospasm (difficulty breathing or wheezing)
• Respiratory failure
• Low blood oxygen levels
• Diarrhea, abdominal pain
• Hives, skin itching
• Skin redness
• Skin rash
• Skin peeling
• Skin inflammation
• Hair loss
• Joint or muscle pain
• Muscle weakness or stiffness
• Severe painful muscle cramps
• Neck pain, leg or arm pain
• Kidney pain
• Skin swelling (edema)
• Facial flushing, increased sweating
• Chest discomfort
• Flu-like symptoms
• Feeling cold or hot, or general malaise and weakness
• Drowsiness
• Burning sensation
• Incorrect blood glucose measurement readings

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the national reporting system at the website:
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 Octagam

Keep this medicine out of the sight and reach of children.
Do not use Octagam after the expiry date stated on the label and carton.
Store below 25 °C. Do not freeze.
Keep the vial in the outer packaging to protect it from light.
After first opening, the medicine should be used immediately.
Do not use Octagam if you notice that the solution is cloudy, contains deposits, or has become markedly discoloured.
Do not dispose of medicines 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 Octagam contains

• The active substance is human normal immunoglobulin (human antibodies), at a concentration of 50 mg/ml (of which at least 95% is immunoglobulin G).
• The other components are maltose and water for injections. The components used in the Octagam packaging are latex-free.

Description of the appearance of Octagam and contents of the pack
Octagam is an infusion solution available in vials (1 g/20 ml) and bottles (2.5 g/50 ml,
5 g/100 ml, 10 g/200 ml, 25 g/500 ml).
Pack sizes:
1 g in 20 ml
2.5 g in 50 ml
5 g in 100 ml
10 g in 200 ml
2 x 10 g in 2 x 200 ml
3 x 10 g in 3 x 200 ml
25 g in 500 ml
Not all pack sizes may be marketed.
The solution is clear or slightly opalescent, colourless or pale yellow.

Marketing Authorisation Holder
OCTAPHARMA Italy S.p.A.
Via Cisanello 145,
56124 Pisa
Italy

Manufacturer
Octapharma Pharmazeutika Produktionsges.m.b.H.
Oberlaaer Strasse 235, A-1100 Vienna, Austria
Octapharma S.A.S.
70-72 rue de Marèchal Foch, BP 33, F-67381 Lingolsheim, France
Octapharma AB
SE-112 75 Stockholm, Sweden

This medicinal product is authorised in the European Economic Area and in the United Kingdom (Northern Ireland) under the following names:
Belgium, Croatia, Cyprus, Czech Republic, Denmark, Estonia, Octagam 50 mg/ml
Finland, France, Hungary, Iceland, Latvia, Lithuania,
Luxembourg, Malta, Netherlands, Norway, Portugal,
Romania, Slovenia, Sweden, United Kingdom (Northern Ireland):
Italy: Octagam
Austria, Bulgaria, Germany, Poland, Slovakia: Octagam 5%
Spain: Octagamocta 50 mg/ml

This leaflet was last approved on

The following information is intended for healthcare professionals only:

• The product should be brought to room or body temperature before use.
• The solution should be clear or slightly opalescent, colourless or pale yellow.
• Do not use solutions that are cloudy or contain deposits.
• Any unused product or waste material must be disposed of in accordance with applicable regulations.
• This medicinal product must not be mixed with other medicinal products.
• The infusion line must be flushed before and after administration of Octagam with 0.9% sodium chloride solution or 5% glucose solution.