50 mg / ml solution for infusion .
Human normal immunoglobulin (IVIg)
1. What Flebogamma DIF is and what it is used for
What Flebogamma DIF is
Phlebogamma DIF contains human normal immunoglobulin, a highly purified protein derived from human plasma (part of the blood from blood donors). It belongs to a group of medicines called immunoglobulin for intravenous use. These are used to treat conditions where the body’s defenses against infection do not work properly.
What Flebogamma DIF is used for
Treatment of adults, children, and adolescents (2-18 years) who do not have enough antibodies (Flebogamma DIF is used as substitution therapy ). There are TV groups:
- Patients with primary immunodeficiency syndrome (PID) with congenital deficiency of antibodies (group 1).
- Patients with secondary immunodeficiency (SID) with severe or recurrent infection, ineffective antimicrobial treatment, and either inability to respond to a specific antigen, so-called PSAF ( proven specific antibody failure ) * or IgG levels in serum <4 g / l (group 2).
* PDF = inability to obtain at least one doubled IgG antibody titer against pneumococcal polysaccharide and polypeptide antigen vaccines.
Treatment of adults, children, and adolescents (2–18 years) with certain autoimmune diseases (immune modulation). There are five groups:
- Primary immune thrombocytopenia (ITP) is a condition in which the number of platelets in the blood has decreased sharply. Platelets play an important role in blood clotting and patients who do not have enough platelets are at high risk for unwanted bleeding and bruising. The drug is also used in patients at high risk of bleeding or who will be operated on shortly.
- Guillain-Barré syndrome in which the immune system damages the nerves and prevents them from functioning properly.
- Kawasaki disease (in this case together with treatment with aspirin ), a disease in children where the blood vessels ( arterial s) in the body are enlarged.
- Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), a rare and progressive disease that causes weakness in the arms and legs, numbness, pain, and fatigue.
- Multifocal motor neuropathy (MMN), a rare disease that causes slowly progressing asymmetric weakness in the arms and legs without loss of sensation.
2. What you need to know before using Flebogamma DIF
Do not use Flebogamma DIF
- if you are allergic to human normal immunoglobulin or any of the other ingredients of this medicine (listed in section 6)
- if you do not have enough immunoglobulins of the type IgA in your blood or have developed IgA antibody is
- If you suffer from fructose intolerance, a very rare inherited disease, the enzyme that breaks down fructose is not produced. Infants and young children (0-2 years) should not use this medicine as they may not yet be diagnosed with hereditary fructose intolerance ( hereditary fructose intolerance, HFI), which can be fatal. (see special warnings about excipients at the end of this section).
Warnings and cautions
Talk to your doctor, pharmacist, or nurse before using Flebogamma DIF.
Some side effects may occur more often:
- at high infusion rate.
- if this is the first time you are receiving Flebogamma DIF, or when switching from a product with human normal immunoglobulin (IVIg), or if it is a long time since your last infusion (eg several weeks), you will be closely monitored for up to one hour after infusion to detect signs of possible side effects.
Allergic reactions are rare. This can happen especially if you do not have enough IgA- type immunoglobulin in your blood or have developed antibodies to IgA.
Patients with previous risk factors
Tell your doctor if you have any other condition and/or disease, as control is required in patients with pre-existing risk factors for thrombotic events (blood clots form in your blood). Be especially careful to tell your doctor if you have:
- diabetes
- high blood pressure
- previously affected by vascular disease or thrombosis
- overweight
- decreased blood volume
- a disease that increases blood viscosity (blood sluggishness unit)
- age over 65 years
Patients with kidney problems
If you have kidney disease and this is the first time you are getting Flebogamma DIF, you may have kidney problems.
Your doctor will consider your risk factors and take measures such as reducing the infusion or stopping treatment.
Effects on blood tests
After receiving Flebogamma DIF, the results of certain blood tests (serological tests) may be affected for some time. If you are taking a blood sample after receiving Flebogamma DIF, inform the person taking the sample or your doctor that you are taking this medicine.
Special safety warning
When drugs are made from human blood or plasma, several measures are taken to prevent the transmission of infection to patients. This includes:
- careful selection of blood and plasma donors to ensure that those who can carry your infection have been excluded
- testing of all donations and collections of plasma for signs of open viruses/infections
- introduction of blood or plasma processing measures that can inactivate or remove viruses.
Despite these measures, the risk of transmission of infectious agents cannot be completely ruled out when medicinal products derived from human blood or plasma are administered. This also applies to new, hitherto unknown viruses or other types of infection.
The measures taken are considered to be effective for enveloped viruses such as human immunodeficiency virus ( HIV ), hepatitis B virus, or hepatitis C virus,s, and the non-enveloped hepatitis A virus or parvovirus B19.
Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infection possibly because antibodies to these infections, which are present in the product, are protective.
It is strongly recommended that the product name and batch number (indicated on the label and carton after Lot) be registered each time Flebogamma DIF is administered to maintain a register of used batches.
Children and young people
Vital signs (body temperature, blood pressure, heart rate, and respiratory rate) should be followed during infusion one of Flebogamma DIF.
Other medicines and Flebogamma DIF
- Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.
- Vaccine effects: Flebogamma DIF may reduce the effect of certain types of vaccines (live attenuated viral vaccines). In cases such as rubella, mumps, and chickenpox, a period of up to 3 months should run from the time you receive the medicine until you receive the vaccine. In the case of measles, this period is up to one year.
- You should avoid using concomitant medicines that increase the excretion of water from the body (loop diuretics) during treatment with Flebogamma DIF.
Pregnancy and breastfeeding
If you are pregnant or breast-feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Driving and using machines
Patients may experience reactions (such as dizziness and nausea) during treatment that may affect their ability to drive and use machines.
Flebogamma DIF contains sorbitol
This medicine contains 50 mg sorbitol per ml. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
In people older than 2 years who do not tolerate fructose, a spontaneous reaction to fructose-containing food develops which can cause the following symptoms: vomiting, disorders of the gastrointestinal tract, apathy, poor height growth, and weight loss. Therefore, patients should be carefully examined for symptoms of hereditary fructose intolerance before receiving Flebogamma DIF.
Flebogamma DIF contains sodium
This medicine contains less than 1 mmol (23 mg) sodium per vial of 10 ml, 50 ml, 100 ml, and 200 ml, ie essentially ‘sodium-free’. This product contains less than 29.41 mg sodium (the main ingredient in saline/table salt) per vial with 400 ml. This corresponds to 1.5% of the highest recommended daily intake of sodium for adults. Depending on the dose prescribed by your doctor, you may receive more than 1 vial.
3. How to use Flebogamma DIF
Flebogamma DIF is given as an injection into a vein ( intravenous administration ). It can be given by yourself if you have received full training from hospital staff. You need to prepare the infusion exactly as you were shown to prevent bacteria from entering. You must never give it to yourself when you are alone; a responsible adult must always be present.
The dose you receive varies depending on your illness and body weight and is calculated by your doctor (see section Instructions for healthcare professionals, given at the end of this leaflet).
At the beginning of infusion one, you will receive Flebogamma DIF at a slow rate (0.01-0.02 ml/kg/min). Depending on how you feel, your doctor may then slowly increase the infusion rate (up to 0.1 ml/kg/min).
Use for children over 2 years of age
Dose one in children is not considered different than in adults because dosage one is given according to the child’s disease and body weight.
If you take more Flebogamma DIF then you should
If you ingest more Flebogamma DIF than you should, your body may accumulate too much fluid. This can happen especially if you are a risk patient, e.g. an elderly patient or a patient who has heart or kidney problems. Tell your doctor immediately.
If you forget to take Flebogamma DIF
Tell your doctor or pharmacist immediately and follow his / her instructions.
You must not be given a double dose to make up for a forgotten dose.
If you have any further questions on the use of this product, ask your doctor, pharmacist, or nurse.
4. Possible side effects
Like all medicines, this medicine can cause side effects, although not everybody gets them.
In rare and isolated cases, the following side effects have been reported for immunoglobulin drugs. Seek medical attention without delay if any of the following side effects occur during or after the infusion:
- A sudden drop in blood pressure and, in some cases, anaphylactic shock (signs of this may include rash, low blood pressure, palpitations, wheezing, coughing, sneezing, and difficulty breathing) even if you have not shown any hypersensitivity when previously given the medicine.
- Cases of transient meningitis (signs of this may be headache, photosensitivity or light intolerance, neck stiffness).
- Cases of a transient decrease in red blood cell count ( reversible hemolytic anemia/hemolysis).
- Cases of transient skin reactions ( side effects on the skin).
- Increased serum creatinine content (a test that measures your kidney function) and/or acute renal impairment (signs of this are low back pain, fatigue, decreased amount of urine).
- Blood clots such as heart attack (pressure over the chest with the feeling that the heart is beating too fast), stroke (muscle weakness in the face, arms, or legs, difficulty speaking or understanding other people’s speech), blood clots in the lungs (shortness of breath, chest pain, and fatigue), deep vein thrombosis (pain and swelling in one extremity ).
- Cases of transfusion-related acute lung injury (TRALI) causing hypoxia (lack of oxygen), dyspnoea (difficulty breathing), tachypnea (rapid breathing), cyanosis (lack of oxygen in the blood), fever, and hypotension (low blood pressure ).
Other side effects:
V antigen (may affect up to 1 in 10 people):
- headache
- fever (elevated body temperature)
- tachycardia (rapid heartbeat)
- low blood pressure
Uncommon (may affect up to 1 in 100 people):
- bronchitis ( tracheal catarrh )
- nasopharyngitis / (cold symptoms)
- dizziness (motion sickness)
- high blood pressure
- high blood pressure
- hissing breathing
- Mud-mixed cough
- abdominal pain (also includes upper abdomen)
- diarrhea
- vomiting
- nausea
- urticaria ( hives )
- pruritus ( itching )
- rash
- back pain
- myalgia (muscle pain)
- arthralgia (joint pain)
- frostbite
- pain
- injection site reaction
- positive Coombs test
- lowered blood pressure
Rare (may affect up to 1 in 1,000 infusions ):
- hypersensitivity
- abnormally behaving
- migraine
- fluctuating blood pressure
- herds (to blush)
- cough
- asthma
- dyspnoea (difficulty breathing)
- epistaxis (nosebleeds)
- discomfort from the nose
- pain in the throat
- contact dermatitis
- hyperhidrosis (heavy sweating)
- rash
- muscle twitching
- neck pain
- pain in arms and legs
- urinary retention (difficulty urinating)
- asthenia (weakness)
- chest pain
- infusion site reactions ( redness, drug leakage, inflammation, and pain)
- injection site reactions (such as edema, pain, itching, and swelling)
- fluid accumulation in the arms and legs (peripheral edema )
- elevated alanine aminotransferase (liver transaminase)
- movement of e.g. needle or infusion line
Additional side effects are in children and adolescents
The proportion of headache, fever, increased heart rate, and low blood pressure in children was found to be higher than in adults.
Reporting of side effects ar
If you get any side effects, talk to your doctor, pharmacist, or nurse. This also applies to side effects that are not mentioned in this information. By reporting side effects, you can help increase drug safety information.
5. How to store Flebogamma DIF
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton after “EXP”.
Do not store above 30 ° C. Do not freeze.
The solution should be clear to slightly translucent. Do not use this medicine if you find that the solution is cloudy or contains precipitates.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.
6. Contents of the packaging and other information
Content declaration
The active substance is human normal immunoglobulin (IVIg). One ml contains 50 mg of human normal immunoglobulin of which at least 97% is IgG.
Each vial with 10 ml: 0.5 g of normal human
Each vial with 50 ml: 2.5 g of normal human
Each vial with 100 ml: 5 g of normal human
Each vial with 200 ml: 10 g of normal human
Each vial with 400 ml: 20 g of normal human
Distribution of IgG subclasses is approximately 66.6% IgG 1 , 28.5% IgG 2 , 2.7% IgG 3 and 2.2% IgG 4 . The product contains trace amounts of IgA (less than 0.05 mg / ml).
The other ingredients are sorbitol and water for injections (see section 2 for more information on the ingredients).
What the medicine looks like and the contents of the pack
Flebogamma DIF is an infusion solution. The solution is clear or slightly translucent and colorless or slightly yellow.
Flebogamma DIF is supplied in vials of 0.5 g / 10 ml, 2.5 g / 50 ml, 5 g / 100 ml, 10 g / 200 ml and 20 g / 400 ml.
Pack size: 1 vial.
Not all volumes may be marketed.
Marketing Authorization Holder and Manufacturer
Instituto Grifols, SA
Can Guasc, 2 – Parets del Vallès
08150 Barcelona – Spain
Contact the representative of the marketing authorization holder to find out more about this medicine:
| AT / BE / BG / CY / EE / EL / ES / HR / HU / IE / LV /LT / LU / MT / NL / RO / SI / SKInstituto Grifols, SATel: +34 93 571 01 00 | CZGrifols SROTel: +4202 2223 1415 |
| THEGrifols Deutschland GmbHTel: +49 69 660 593 100 | DK / FI / IS / NO / SEGrifols Nordic ABTel: +46 8 441 89 50 |
| FRLaboratory Novex PharmaTel: +33 (0) 1 41 27 59 56 | ITGrifols Italia SpATel: +39 050 8755 113 |
| PLGrifols Polska Sp. z ooTel: +48 22 378 85 60 | PTGrifols Portugal, Lda.Tel: +351 219 255 200 |
| UKGrifols UK Ltd.Tel: +44 845 2413090 |