annex-eur
annex-eur
annex-eur
EMA/CHMP/302620/2017 Rev. 2*
Adopted by EMA Committee for Medicinal Products for Human Use (CHMP) 20 July 2017
This document replaces the Annex previously included in the Guideline CPMP/463/00 Rev. 1.
It is an integral part of the European Commission guideline on ‘Excipients in the labelling and package
leaflet of medicinal products for human use’ (SANTE-2017-11668).
© European Medicines Agency, 2022. Reproduction is authorised provided the source is acknowledged.
Excipients and information for the package leaflet
Name Updated on Route of Threshold Information for the Package Comments
Administration Leaflet
Aprotinin Topical Zero May cause hypersensitivity or The topical route in this case refers to
severe allergic reactions. sites that may have access to the
circulation (e.g. wounds, body cavities
etc.).
Arachis oil (peanut oil) All Zero <Medicinal product> contains Purified arachis oil may contain peanut
arachis oil (peanut oil). If you are protein. The PhEur monograph does
allergic to peanut or soya, do not not contain a test for residual protein.
use this medicinal product.
SmPC: contraindication.
Aspartame (E 951) 09/10/2017 Oral Zero This medicine contains x mg Aspartame is hydrolysed in the
aspartame in each <dosage gastrointestinal tract when orally
unit><unit volume> <which is ingested. One of the major hydrolysis
equivalent to products is phenylalanine.
x mg/<weight><volume>>.
Information to consider for the SmPC:
Aspartame is a source of Neither non-clinical nor clinical data
phenylalanine. It may be harmful are available to assess aspartame use
if you have phenylketonuria in infants below 12 weeks of age.
(PKU), a rare genetic disorder in
which phenylalanine builds up
because the body cannot remove
it properly.
e.g.:
Tartrazine (E 102)
Sunset yellow FCF (E
110)
Azorubine, carmoisine (E
122)
Amaranth (E 123)
Ponceau 4R, cochineal
Red A (E 124)
Brilliant black BN, black
PN (E 151)
Balsam of Peru Topical Zero May cause skin reactions.
Benzalkonium chloride 09/10/2017 Nasal Zero Benzalkonium chloride may cause Long-term use may cause oedema of
irritation or swelling inside the the nasal mucosa.
nose, especially if used for a long
time.
Benzalkonium chloride 09/10/2017 Inhalation Zero Benzalkonium chloride may cause
wheezing and breathing
difficulties (bronchospasm),
especially if you have asthma.
Benzalkonium chloride 09/10/2017 Cutaneous Zero Benzalkonium chloride may Use during pregnancy and lactation is
irritate the skin. not expected to be associated with
harmful effects to the mother as
You should not apply this cutaneous absorption of benzalkonium
medicine to the breasts if you are chloride is minimal.
breast-feeding because the baby
may take it in with your milk. Not for application to mucosa.
Benzalkonium chloride 09/10/2017 Oromucosal, Zero Benzalkonium chloride may cause
rectal and local irritation.
vaginal
Benzoic acid (E 210) 09/10/2017 Oral, parenteral Zero <Benzoic acid/Benzoate salt> Increase in bilirubinaemia following its
and benzoates may increase jaundice (yellowing displacement from albumin may
of the skin and eyes) in newborn increase neonatal jaundice which may
e.g.: babies (up to 4 weeks old). develop into kernicterus (non-
Sodium benzoate (E 211) conjugated bilirubin deposits in the
Potassium benzoate (E brain tissue).
212)
Benzoic acid (E 210) 09/10/2017 Topical Zero <Benzoic acid/Benzoate salt> May cause non-immunologic
and benzoates may cause local irritation. immediate contact reactions by a
possible cholinergic mechanism.
e.g.:
Sodium benzoate (E 211)
Potassium benzoate (E
212)
Benzoic acid (E 210) 09/10/2017 Topical Zero <Benzoic acid/Benzoate salt> Absorption through the immature skin
and benzoates may increase jaundice (yellowing of neonates is significant.
of the skin and eyes) in newborn
e.g.: babies (up to 4 weeks old).
Sodium benzoate (E 211)
Potassium benzoate (E
212)
Benzyl alcohol 09/10/2017 Oral, parenteral Zero Benzyl alcohol has been linked Intravenous administration of benzyl
with the risk of severe side effects alcohol has been associated with
including breathing problems serious adverse events and death in
(called “gasping syndrome”) in neonates (“gasping syndrome”). The
young children. minimum amount of benzyl alcohol at
which toxicity may occur is not known.
Do not give to your newborn baby
(up to 4 weeks old), unless Warning in section 4.4 in the SmPC
recommended by your doctor. should be given if used in neonates.
Benzyl alcohol 09/10/2017 Oral, parenteral Zero Do not use for more than a week Increased risk due to accumulation in
in young children (less than 3 young children.
years old), unless advised by your
doctor or pharmacist.
Benzyl alcohol 09/10/2017 Oral, parenteral Zero Ask your doctor or pharmacist for
advice if you are pregnant or
breast-feeding. This is because
large amounts of benzyl alcohol
can build-up in your body and
may cause side effects (called
“metabolic acidosis”).
Benzyl alcohol 09/10/2017 Oral, parenteral Zero Ask your doctor or pharmacist for High volumes should be used with
advice if you have a liver or caution and only if necessary,
kidney disease. This is because especially in subjects with liver or
large amounts of benzyl alcohol kidney impairment because of the risk
can build-up in your body and of accumulation and toxicity (metabolic
may cause side effects (called acidosis).
“metabolic acidosis”).
Benzyl alcohol 09/10/2017 Topical Zero Benzyl alcohol may cause mild
local irritation.
Bergamot oil Topical Zero May increase sensitivity to UV Does not apply when bergapten is
(containing light (natural and artificial shown to be absent from the oil.
bergapten) sunlight).
Cyclodextrins 09/10/2017 Parenteral 200 If you have a kidney disease, talk In children less than 2 years, the lower
mg/kg/day to your doctor before you receive glomerular function may protect
e.g.: and use for this medicine. against renal toxicity, but can lead to
Alfadex > 2 weeks higher blood levels of cyclodextrins.
Betadex (E 459)
γ-cyclodextrin In patients with moderate to severe
Sulfobutyl-ether-β- renal dysfunction accumulation of
cyclodextrin (SBE-β-CD) cyclodextrins may occur.
Hydroxypropyl betadex
Randomly methylated β-
cyclodextrin (RM-β-CD)
Ethanol 22/11/2019 Oral 75 mg/kg This medicine contains x mg of See comments above.
Parenteral per dose alcohol (ethanol) in each <dosage
Inhalation unit><unit volume> <which is
equivalent to x
mg/<weight><volume>> (y%
w/<w><v>). The amount in
<dose><volume> of this
medicine is equivalent to A ml
beer or B ml wine.
Fructose 09/10/2017 Oral Zero [If the medicine is in contact with Oral products used frequently or over a
teeth (e.g. oral liquids, lozenges long period of time, e.g. for two weeks
or chewable tablets) and is or longer.
intended for long term use:]
Fructose may damage teeth.
Glucose Oral liquids, Zero May be harmful to the teeth. Information to be included only when
lozenges and the medicinal product may be intended
chewable tablets for chronic use, e.g. for two weeks or
more.
Glycerol (E 422) Oral 10 g per May cause headache, stomach
dose upset and diarrhea.
Glycerol (E 422) Rectal 1g May have a mild laxative effect.
Lactose Oral Zero If you have been told by your SmPC proposal: Patients with rare
doctor that you have an hereditary problems of galactose
intolerance to some sugars, intolerance, total lactase deficiency or
contact your doctor before taking glucose-galactose malabsorption
this medicinal product. should not take this medicine.
Lactose Oral 5g Contains x g lactose (x/2 g
glucose and x/2 g galactose) per
dose. This should be taken into
account in patients with diabetes
mellitus.
Latex All Zero The container of this medicinal Not a typical excipient, but a warning
Natural Rubber (latex) product contains latex rubber. is considered necessary.
May cause severe allergic
reactions.
Macrogolglycerol Parenteral Zero May cause severe allergic
ricinoleate (castor oil reactions.
polyoxyl)
Macrogolglycerol
hydroxystearate (castor
oil polyoxyl
hydrogenated)
Maltitol (E 965) Oral Zero If you have been told by your SmPC proposal: Patients with rare
Isomalt (E 953) doctor that you have an hereditary problems of fructose
(isomaltitol) intolerance to some sugars, intolerance should not take this
Maltitol liquid contact your doctor before taking medicine.
(hydrogenated glucose this medicinal product.
syrup)
Organic mercury Ocular Zero May cause allergic reactions. See EMEA Public Statement, 8 July
compounds 1999, Ref. EMEA/20962/99
e.g.:
Thiomersal
Phenylmercuric
nitrate/acetate/borate
Organic mercury Parenteral Zero This medicinal product contains See EMEA Public Statement, 8 July
compounds (thiomersal) as a preservative and 1999, Ref. EMEA/20962/99
it is possible that <you/your
e.g.: child> may experience an allergic
Thiomersal reaction. Tell your doctor if
Phenylmercuric <you/your child> have/has any
nitrate/acetate/borate known allergies.
Organic mercury Parenteral Zero Tell your doctor if you/your child Additional statement to be mentioned
compounds have/has experienced any health for vaccines.
problems after previous
e.g.: administration of a vaccine.
Thiomersal
Phenylmercuric
nitrate/acetate/borate
Sorbic acid (E 200) and Topical Zero May cause local skin reactions,
salts (e.g. contact dermatitis).
Sorbitol (E 420) 09/10/2017 Oral, parenteral Zero This medicine contains x mg The additive effect of concomitantly
sorbitol in each <dosage administered products containing
unit><unit volume> <which is sorbitol (or fructose) and dietary
equivalent to intake of sorbitol (or fructose) should
x mg/<weight><volume>>. be taken into account.
Sucrose Oral liquids, Zero May be harmful to the teeth. Information to be included only when
lozenges and the medicinal product may be intended
chewable tablets for chronic use, e.g. for two weeks or
more.
Sulphites including Oral Zero May rarely cause severe
metabisulphites Parenteral hypersensitivity reactions and
Inhalation bronchospasm.
e.g.:
Sulphur dioxide (E 220)
Sodium sulphite (E 221)
Sodium bisulphite (E 222)
Sodium metabisulphite (E
223)
Potassium metabisulphite
(E 224)
Potassium bisulphite (E
228)