Download 1. name of the medicinal product

SUMMARY OF PRODUCT CHARACTERISTICS
1.
NAME OF THE MEDICINAL PRODUCT
Alphalipid
200 mg/ml emulsion for infusion
2.
QUALITATIVE AND QUANTITATIVE COMPOSITION
1000 ml of the emulsion contain:
Soya-bean oil, refined
200 g
Energy content:
2000 kcal/l (8.4 MJ/l)
Excipient with known effect:
Sodium 0.03 mg/ml (see section 4.4)
For the full list of excipients, see section 6.1.
3.
PHARMACEUTICAL FORM
Alphalipid is a milky white emulsion for infusion.
Osmolality:
pH:
about 350 mOsm/kg water
6.0-8.5
4.
CLINICAL PARTICULARS
4.1
Therapeutic indications
Medical conditions that require parenteral nutrition for supply of energy and essential fatty acids.
4.2
Posology and method of administration
Posology
Adults
The patient’s ability to eliminate the infused fat should determine the dosage (see Treatment
monitoring below).
The quantity of fat administered intravenously should normally not exceed 3 g/kg bodyweight/day.
The highest permitted infusion rate is 1.6 ml/min, equivalent to an infusion time of at least 5 hours for
500 ml.
Paediatric population
The child’s ability to eliminate fat should determine the dosage (see Treatment monitoring below).
The recommended daily dose is 0.5-4 g fat/kg bodyweight. The infusion rate should not exceed 0.17 g
fat/kg bodyweight/hour (4 g fat/kg per 24 hours). In premature and very low birth weight infants
Alphalipid should preferably be administered continuously over 24 hours. The initial dosage should be
0.5-1 g fat/kg bodyweight/day. The dose should then be increased gradually by 0.5-1 g fat/kg
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bodyweight/day up to 2 g fat/kg bodyweight/day. The dosage may be increased to 4 g/kg/day only
under close monitoring of serum triglyceride concentrations, liver function and oxygen saturation.
Method of administration
Alphalipid should be administered as an intravenous infusion.
Treatment monitoring
Adults: where intravenous fat emulsion is indicated for more than a week, the patient’s ability to
eliminate fat should be checked. A sample of blood should be taken before the start of the infusion and
centrifuged. If the plasma is milky or opalescent, the planned infusion should be postponed. Be aware
that hypertriglyceridaemia may pass undetected with this method. In patients in whom impaired fat
tolerance may be expected, measurement of the serum triglyceride concentration is therefore
recommended. The elimination of fat should be checked daily in the medical conditions mentioned in
section 4.4.
Paediatric population: in infants treated with Alphalipid the ability to eliminate fat should be tested
regularly. In infants receiving long-term parenteral nutrition, particularly premature infants, platelet
count, liver function and serum triglycerides should be monitored daily. Specific measurement of the
serum triglyceride concentration is recommended for this group.
4.3
Contraindications
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




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Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Hypersensitivity to egg protein.
Hypersensitivity to soya-bean protein or peanut protein. Alphalipid contains soya-bean oil.
Cross-allergy occurs between peanuts and soya-beans.
Acute shock.
Conditions involving severe hyperlipidaemia.
Severe hepatic failure.
Haemophagocytic syndrome.
4.4
Special warnings and precautions for use
Caution should be observed in conditions with impaired fat metabolism, such as renal impairment,
uncontrolled diabetes, pancreatitis, hepatic impairment, hypothyroidism (if hypertriglyceridaemia is
present) and sepsis. If Alphalipid is given in these conditions, the serum triglyceride concentration
should be monitored closely.
Paediatric population
Alphalipid should be given with caution to neonates and premature infants with hyperbilirubinaemia
and in cases of suspected pulmonary hypertension.
Interference with serological testing
Alphalipid may interfere with certain laboratory tests (bilirubin, lactate dehydrogenase, oxygen
saturation, Hb, etc.) if blood is sampled before the administered fat has been cleared from the blood. In
most patients fat is cleared from the blood 5-6 hours after the end of the infusion.
This medicinal product contains 0,65 mmol sodium (15 mg) per 500 ml, i.e. essentially ‘sodium- free’.
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4.5
Interaction with other medicinal products and other forms of interaction
Certain medicinal products such as insulin can affect the body’s lipase system. This type of
interaction, however, is considered to be of limited clinical significance.
Heparin in clinical doses causes a transient increase in lipolysis in plasma, resulting in a transient
decrease in triglyceride clearance due to depletion of lipoprotein lipase.
Soya-bean oil has a natural content of vitamin K1. This is considered important only in patients treated
with coumarin derivatives, which interact with vitamin K1.
4.6
Fertility, pregnancy and lactation
Pregnancy
Data on a limited number of exposed pregnancies indicate no adverse effects of Alphalipid on
pregnancy or on the health of the fetus/newborn child. To date, no other relevant epidemiological data
are available. Caution should be exercised when prescribing to pregnant women.
Breastfeeding
There is insufficient information on the excretion of soya-bean oil in human milk.
Fertility
There is insufficient information on the effect on fertility.
4.7
Effects on ability to drive and use machines
Alphalipid has no or negligible influence on the ability to drive and use machines.
4.8
Undesirable effects
The following frequencies are taken as a basis when evaluating undesirable effects:
Very common:
Common:
Uncommon:
Rare:
Very rare:
Not known:
1/10
1/100 to <1/10
1/1000 to <1/100
1/10,000 to <1/1,000
<1/10,000
cannot be estimated from the available data
Following undesirable effects were reported for the reference soya-bean emulsion for infusion:
System organ class
Blood and lymphatic system disorders
Frequency
Rare
Event
Haemolysis, reticulocytosis,
thrombocytopenia (in association with
long-term treatment in infants)
Vascular disorders
Rare
Hypertension, hypotension
Respiratory, thoracic and mediastinal
disorders
Rare
Tachypnoea
Hepatobiliary disorders
Rare
Hepatic impairment
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System organ class
Skin and subcutaneous tissue disorders
Frequency
Uncommon
Event
Flushing
Rare
Skin rash, urticaria
Reproductive system and breast disorders
Rare
Priapism
General disorders and administration site
conditions
Uncommon
Fever, chills, nausea
Rare
Anaphylactic reaction, headache,
abdominal pain, tiredness
The rare side effects can occur during or following infusion (early effects) or after extended treatment.
Early effects that occur at the recommended dose include allergic reactions, abdominal pain,
haemolysis, headache, hypertension, hypotension, priapism, reticulocytosis, tachypnoea and tiredness.
Effects reported in long-term treatment include thrombocytopenia in infants.
Fat overload syndrome
An impaired ability of the patient to eliminate Alphalipid can lead to fat overload syndrome, which
may be caused by overdose. This syndrome may appear during severe hypertriglyceridaemia, even at
the recommended infusion rate, and in association with a sudden change in the patient’s clinical
condition, such as renal function impairment or infection.
Fat overload syndrome is characterised by hyperlipidaemia, fever, fat infiltration, hepatomegaly,
splenomegaly, anaemia, leukopenia, thrombocytopenia, coagulation disorder and coma. The
symptoms are usually reversible if the treatment is discontinued.
Transient changes in liver function have been noted in association with intravenous nutrition, but the
cause is unknown.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare
professionals are asked to report any suspected adverse reaction via the national reporting system
listed in Appendix V*.
4.9
Overdose
See section 4.8 under “Fat overload syndrome”.
A marked overdose of fat emulsions containing triglycerides can result in metabolic acidosis,
particularly if carbohydrates are not given concomitantly.
5.
PHARMACOLOGICAL PROPERTIES
5.1
Pharmacodynamic properties
Pharmacotherapeutic group: Solutions for parenteral nutrition, fat emulsions, ATC code: B05BA02.
Alphalipid is a fat emulsion for intravenous use containing soya-bean oil emulsified with egg
phospholipids. Particle size and biological properties are similar to those of natural chylomicrons.
Unlike chylomicrons, Alphalipid does not contain cholesterol esters or apolipoproteins, while its
phospholipid content is significantly higher.
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5.2
Pharmacokinetic properties
The fat particles in Alphalipid are in principle distributed and eliminated in the same way as natural
chylomicrons.
5.3
Preclinical safety data
Refined soya-bean oil emulsion for infusion has been used clinically for many years. Its safety is
based on clinical experience.
6.
PHARMACEUTICAL PARTICULARS
6.1
List of excipients
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purified egg yolk phospholipids
glycerol
sodium oleate
sodium hydroxide
water for injections
6.2
Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in
section 6.6.
6.3
Shelf life
Shelf life in the unopened bottle:
2 years
Shelf life in the opened container:
Because of the risk of microbial contamination the product should be used immediately. Any unused
infusion should be discarded.
Shelf life after compounding:
Chemical and physical in-use stability has been demonstrated for 4 weeks at 25°C under light
protection.
From a microbiological point of view, the product should be used immediately. If not used
immediately, in-use storage times and conditions prior to use are the responsibility of the user
and would normally not be longer than 24 hours at 2 to 8°C, unless compounding has taken
place in controlled and validated aseptic conditions.
Do not freeze the compounded emulsion.
6.4
Special precautions for storage
Do not freeze.
For storage conditions after compounding, see section 6.3.
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6.5
Nature and contents of container
Type II glass bottle with 100 ml, 250 ml or 500 ml infusion, closed with a chlorobutyl rubber stopper
sealed with an aluminium capsule.
Pack sizes:
Glass bottle:
20 x 100 ml
20 x 250 ml
10 x 500 ml
Not all pack sizes may be marketed.
6.6
Special precautions for disposal and other handling
Do not use the product if the package is damaged.
Do not use if you notice phase separation of the emulsion.
Compounding
Alphalipid may be compounded with medicinal products containing amino acids, glucose and
electrolyte solutions under aseptic conditions to produce Intradialytic Parenteral Nutrition (IDPN) and
Total Parenteral Nutrition (TPN) admixtures.
Medicinal products with the volume of 5 ml and more should be mixed with Alphalipid at once, using
an automatic filling system. Volumes below 5 ml may be added separately to the pre-mixture. These
processes should be executed under aseptic conditions (see section 6.3).
The table below shows the highest concentration of components for which the chemical and physical
stability has been demonstrated (see section 6.3):
Components
Composition for
Intradialytic Parenteral
Nutrition per 100 ml
Composition for
Total Parenteral Nutrition
per 100 ml
Soya-bean oil [g]
(source: Alphalipid)
4.7
4.0
Amino acids [g]
Glucose [g]
5.4
15.9
4.3
13.4
Overall omega 3-fatty
acids [g]
max. 0.58
max. 0.49
Omega 3-fatty acids from
fish oil [g]
(source: Omegaven)
max. 0.06
max. 0.05
Omega 3-fatty acids
from soya-bean oil [g]
(source: Alphalipid)
max. 0.52
max. 0.44
Electrolytes
Sodium [mmol]
0
5.460
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Calcium [mmol]
Magnesium [mmol]
Zinc [µmol]
Potassium [mmol]
Chloride [mmol]
Phosphate [mmol]
Acetate [mmol]
Citrate [mmol]
Malate [mmol]
Saccharate [mmol]
Gluconate [mmol]
0.606
0.550
1.006
3.371
6.965
1.195
0.000
0.129
0.302
0.049
0.701
Water for injections can be used to adjust the target concentrations of the corresponding components.
7.
MARKETING AUTHORISATION HOLDER
ALPHA PHARMACEUTICALS GmbH
Hauptstraße 61 A
D-16348 Wandlitz
Germany
8.
MARKETING AUTHORISATION NUMBER
9.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
10.
DATE OF REVISION OF THE TEXT
2015-10-09
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