1. Name of the medicinal product
Berinert® 500 IU
Powder and solvent for solution for injection / infusion
2. Qualitative and quantitative composition
Active substance: C1-esterase inhibitor, human
Berinert contains 500 IU C1-esterase inhibitor per injection vial.
The potency of C1-esterase inhibitor is expressed in International Units (IU), which are related to the current WHO Standard for C1-esterase inhibitor products.
The product contains 50 IU/ml C1-esterase inhibitor after reconstitution with 10 ml water for injections.
The total protein content of the reconstituted solution is 6.5 mg/ml.
Excipients with known effect:
Sodium up to 486 mg (approximately 21 mmol) per 100 ml solution.
For the full list of excipients, see section 6.1.
3. Pharmaceutical form
Powder (white lyophilisate) and solvent for solution for injection / infusion.
4. Clinical particulars
4.1 Therapeutic indications
Hereditary angioedema type I and II (HAE)
Treatment and pre-procedure prevention of acute episodes.
4.2 Posology and method of administration
Treatment should be initiated under the supervision of a physician experienced in the treatment of C1-esterase inhibitor deficiency.
Posology
Adults
Treatment of acute angioedema attacks:
20 IU per kilogram body weight (20 IU/kg b.w.)
Pre-procedure prevention of angioedema attacks:
1000 IU less than 6 hours prior to a medical, dental, or surgical procedure.
Children
Treatment of acute angioedema attacks:
20 IU per kilogram body weight (20 IU/kg b.w.).
Pre-procedure prevention of angioedema attacks:
15 to 30 IU per kilogram body weight (15-30 IU/kg b.w.) less than 6 hours prior to a medical, dental, or surgical procedure. Dose should be selected taking into account clinical circumstances (e.g. type of procedure and disease severity).
Method of administration
Berinert is to be reconstituted according to section 6.6. The reconstituted solution is to be administered by slow i.v. injection or infusion (4 ml/minute).
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
In patients with known tendency towards allergies, antihistamines and corticosteroids should be administered prophylactically.
If allergic or anaphylactic-type reactions occur, the administration of Berinert has to be stopped immediately (e.g. discontinue injection/infusion) and an appropriate treatment has to be initiated. Therapeutic measures depend on the kind and severity of the undesirable effect. The current medical standards for shock treatment are to be observed.
Patients with laryngeal oedema require particularly careful monitoring with emergency treatment in stand-by.
Unlicenced use or treatment of Capillary Leak Syndrome (CLS) with Berinert (see also section "4.8 Undesirable effects") is not advised.
Berinert contains up to 486 mg sodium (approximately 21 mmol) per 100 ml solution. To be taken into consideration by patients on a controlled sodium diet.
Home treatment and self-administration
There are limited data on the use of this medicinal product in home treatment or self-administration. Potential risks associated with home treatment are related to the administration itself as well as the handling of adverse drug reactions, particularly hypersensitivity. The decision on the use of home treatment for an individual patient should be made by the treating physician, who should ensure that appropriate training is provided and the use reviewed at intervals.
Virus safety
Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.
The measures taken are considered effective for enveloped viruses such as HIV, HBV, HCV and for the non-enveloped viruses HAV and parvovirus B19.
Appropriate vaccination (hepatitis A and B) should be generally considered for patients in regular/repeated receipt of human plasma-derived products.
It is strongly recommended that every time Berinert is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed.
4.6 Fertility, pregnancy and lactation
Pregnancy
There are limited amount of data that indicate no increased risk from the use of Berinert in pregnant women. Berinert is a physiological component of human plasma. Therefore, no studies on reproduction and developmental toxicity have been performed in animals and no adverse effects on fertility, pre- and postnatal development are expected in humans.
Therefore, Berinert should be given to a pregnant woman only if clearly needed.
Breastfeeding
It is unknown whether Berinert is excreted in human milk, but due to its high molecular weight, the transfer of Berinert into breast milk seems unlikely. However, breastfeeding is questionable in women suffering from hereditary angioedema. A decision must be made whether to discontinue breastfeeding or to discontinue the Berinert therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.
Fertility
Berinert is a physiological component of human plasma. Therefore, no studies on reproduction and developmental toxicity have been performed in animals and no adverse effects on fertility, pre- and postnatal development are expected in humans.
4.7 Effects on ability to drive and use machines
Berinert has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
The following adverse reactions are based on post marketing experience as well as scientific literature. The following standard categories of frequency are used:
Very common:
 ≥
1/10

Common:
 ≥
1/100 and < 1/10
Uncommon:
 ≥
1/1,000 and < 1/100
Rare:
 ≥
1/10,000 and < 1/1,000
Very rare:
 <
1/10,000 (including reported single cases)
Undesired reactions with Berinert are rare.