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ANATERA 100 MG/ML SOLUTION FOR INJECTION

Active substance: FLUORESCEIN SODIUM

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Anatera 100 mg/ml solution for injection

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml solution contains 100 mg fluorescein (as 113.2 mg fluorescein sodium)
One 5 ml vial contains 500 mg fluorescein (as 566 mg fluorescein sodium)
Contains sodium (from fluorescein sodium and sodium hydroxide) at amounts
up to 1.45% (approximately 3.15 mmol) per dose. For a full list of excipients,
see section 6.1.

3

PHARMACEUTICAL FORM
Solution for injection
Clear, red-orange solution

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
This medicinal product is for diagnostic use only.
For fluorescein angiography of the ocular fundus.

4.2

Posology and method of administration

Posology
Use in adults, including the elderly:
Inject 5 ml of Anatera 100 mg/ml solution for injection rapidly into the antecubital
vein after taking precautions to avoid extravasation. In cases when highly sensitive
imaging systems e.g., scanning laser ophthalmoscope are used, the dose of this
product should be reduced to 2 ml of Anatera 100 mg/ml solution for injection.

Use in paediatric patients:
Anatera 100 mg/ml solution for injection has not been studied in children and doseadaptation data are not available. Therefore, Anatera 100 mg/ml solution for injection
should not be used in patients below 18 years as efficacy and safety in this group have
not been established.
Use in patients with renal insufficiency (glomerular filtration rate below 20 ml/min):
Limited experience in renally impaired subjects (glomerular filtration rate below 20
ml/min) suggests that, in general, no dose adjustment is required although a longer
excretion rate in patients with renal impairment is possible (see section 5.2).
Dialysed patients: Reduce dose to 2.5 ml (half a vial)

Method of administration and fluorescence angiography
Anatera 100 mg/ml solution for injection should be used exclusively by qualified
physicians with technical expertise in performing and interpreting fluorescence
angiography.
This product should only be administered intravenously.
Flush intravenous cannulas with sterile sodium chloride solution (0.9%) before and
after medicinal products are injected to avoid physical incompatibility reactions. The
injection should be administered rapidly (1 ml per second is normally recommended)
into the antecubital vein, after taking precautions to avoid extravasation using a 23
gauge butterfly needle for injection. Luminescence usually appears in the retina and
choroidal vessels in 7 to 14 seconds.
For further instructions on the correct administration/use of this product, see sections
6.2 and 6.6.

4.3

Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section
6.1.
Anatera 100 mg/ml solution for injection should not be injected intrathecally or intraarterially.

4.4

Special warnings and precautions for use
Fluorescein sodium can induce serious intolerance reactions.
The benefit to risk of the angiography procedure should be considered in
elderly patients with pre-existing conditions such as cardiovascular disease,
diabetes mellitus, and multiple concomitant drug therapies.

Detailed questioning of each patient must be carried out before the
angiography to search for any history of cardiopulmonary disease or allergy or
concomitant medications (such as beta-blocking agents, including eye-drops
solutions). If the examination appears to be really necessary for a patient
treated with beta-blocking agents (including eye-drops solutions), this
examination should be performed under the supervision of a physician
experienced in intensive care (resuscitation). Beta-blocking agents could
reduce the vascular compensation reactions to anaphylactic shock and reduce
the effectiveness of adrenaline in the case of cardiovascular collapse. Before
any fluorescein sodium injection, the physician should seek information about
concomitant treatment with a beta-blocking agent.
In the event of serious intolerance reactions during a first angiography, the
benefit of an additional fluorescein angiography should be balanced with the
risk of severe hypersensitivity reactions (with fatal outcome in some cases).
These reactions of intolerance are always unpredictable but they are more
frequent in patients who have previously experienced an adverse reaction after
fluorescein injection (symptoms other than nausea and vomiting) or in patients
with history of allergy such as food or drug induced urticaria, asthma, eczema,
allergic rhinitis. Intradermal skin tests are not reliable in predicting these
intolerance reactions and so their use can be dangerous. A specialized allergy
consultation should be undertaken to make this diagnosis.
Premedication can be undertaken. However, the risk of occurrence of severe
adverse drug reactions still remains. Premedication includes mainly oral
antihistaminic H1 drugs, followed by corticosteroids, before injection of
fluorescein. Given the low incidence of these adverse reactions, such premedication is not recommended for all patients.
The risk of hypersensitivity reactions with fluorescein sodium requires:
Close monitoring of the patient by the ophthalmologist performing the
examination, throughout the examination and for at least 30 minutes after;
Maintaining the infusion line for at least 5 minutes, to treat a possible severe
adverse reaction without delay;
To have at one’s disposal appropriate material for emergency resuscitation
which is based at first on the installation of a 2nd intravenous line, allowing
the restoration of the plasma volume (aqueous solution polyionic or colloidal
substitute of plasma) and the intravenous injection of adrenaline at the
recommended dosage (see section 4.5).
Note:
Extravasation should be avoided due to the high pH of fluorescein solution
which can result in severe local tissue damage (severe pain in the arm for
several hours, sloughing of the skin; superficial phlebitis). When extravasation
occurs, the injection should be immediately discontinued.
If an X-ray procedure is conducted within 36 hours of injection (maximum
duration of fluorescein elimination from the body), the resultant high visibility
of the excretory organs in the X-ray image may lead to misinterpretation.

This medicinal product contains up to 3.15 mmol (72.45 mg) sodium per dose.
This should be taken into consideration by patients on a controlled sodium
diet.

4.5

Interaction with other medicinal products and other forms of interaction

Fluorescein is a relatively inert dye and specific drug interaction studies have not
been reported. There are few case reports on potential interactions with organic anion
transporters and interference with certain laboratory tests. Compounds that inhibit or
compete with the active transport of organic anions (e.g., probenicid) may affect the
systemic profile of fluorescein.
The concomitant use of Anatera 100 mg/ml solution for injection with beta-blocking
agents (including eye-drops solutions) may rarely provoke severe anaphylactic
reactions.
Beta-blocking agents could reduce the vascular compensation reactions to
anaphylactic shock
and also reduce the effectiveness of adrenaline in the presence of cardiovascular
collapse that may require intensive pharmacologic therapy and even resuscitative
measures (see section 4.4).
Concomitant intravenous injection of other solutions or the mixing of Anatera 100
mg/ml solution for injection with other solutions should be avoided as the possibility
of interactions cannot be excluded.
It is possible that fluorescein may influence certain blood and urine values for 3 to 4
days after application.

4.6

Fertility, pregnancy and lactation

Pregnancy
There are no or limited data available concerning the use of Anatera 100 mg/ml
solution for injection in pregnancy. Animal studies do not indicate teratogenic effects
(see section 5.3). As a precautionary measure, it is preferable to avoid the use of
Anatera 100 mg/ml solution for Injection during pregnancy.
Breast-feeding
Fluorescein sodium is excreted in human milk following systemic administration for
up to 7 days. A risk to the suckling child cannot be excluded. Following fluorescein
angiography, breast-feeding should therefore be discontinued for 7days and the milk
should be pumped off and discarded during this period.
Fertility

Studies have not been performed to evaluate the effect of intravenous administration
of fluorescein on fertility.

4.7

Effects on ability to drive and use machines
If mydriasis is necessary for the examination with fluorescence angiography visual
acuity is influenced and thus affects the ability to react in traffic or use machinery.
The patient must be made aware that after application and until visual acuity returns
to normal, driving a vehicle or operating dangerous machinery is prohibited.

Undesirable effects
Summary of safety profile
The most frequently reported treatment related undesirable effects were nausea,
vomiting, syncope and pruritus. Less frequent but more severe adverse reactions have
been reported shortly after fluorescein injection such as: angioedema, respiratory
disorders (bronchospasm, laryngeal oedema and respiratory failure), anaphylactic
shock, hypotension, loss of consciousness, convulsion, respiratory arrest, and cardiac
arrest.
Tabulated list of adverse reactions
The following adverse reactions were assessed to be treatment-related and are
classified according to the following convention: very common ( 1/10), common
( 1/100 to <1/10), uncommon ( 1/1000 to <1/100), rare ( 1/10,000 to <1/1,000),
very rare (<1/10,000), or not known (cannot be estimated from the available data).
Within each frequency-grouping, adverse reactions are presented in order of
decreasing seriousness.





Nervous system disorders

Cardiac disorders

Vascular disorders



System Organ Classification
Immune system disorders



4.8

MedDRA Term (v.14.0)
Uncommon: hypersensitivity
Rare: anaphylactic reaction
Very Rare: anaphylactic shock
Common: syncope
Uncommon: dysphasia, paraesthesia,
dizziness, headache
Very Rare: convulsion
Not Known: cerebrovascular accident ,
vertebrobasilar insufficiency, loss of
consciousness, tremor, hypoaesthesia,
dysgeusia,
Rare: cardiac arrest
Very Rare: angina pectoris, bradycardia,
tachycardia
Not Known: myocardial infarction,
Uncommon: thrombophlebitis
Rare: hypotension, shock

Respiratory, thoracic and
mediastinal disorders

Gastrointestinal disorders

Skin and subcutaneous tissue
disorders

General disorders and
administration site conditions

Very Rare: hypertension, vasospasm,
vasodilatation, pallor, hot flush
Uncommon: cough, throat tightness
Rare: bronchospasm
Very Rare: respiratory arrest, pulmonary
oedema, asthma, laryngeal oedema, dyspnoea,
sneezing, nasal oedema
Not Known: throat irritation
Very Common: nausea
Common: abdominal discomfort, vomiting
Uncommon: abdominal pain
Not Known: retching
Common: pruritus
Uncommon: urticaria
Not known: rash, cold sweat, eczema,
erythema, hyperhidrosis, skin discolouration
Common: extravasation
Uncommon:, pain, feeling hot
Not known: chest pain, oedema, malaise,
asthenia

Description of selected adverse reactions.
A yellowish discolouration of the skin could appear but usually disappears within 6 to
12 hours. Urine, which may also exhibit a bright yellow colouration, returns to its
normal colour after 24 to 36 hours.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of benefit/risk balance of the medicinal
product. Health care professionals are asked to report any suspected adverse reactions
via the national reporting system:
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard

4.9

Overdose
No toxic effects are expected given the minimal risk of overdose with Anatera 100
mg/ml solution for injection.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: DIAGNOSTIC AGENTS, Colouring agents
ATC code: S01JA01

Fluorescein sodium is a fluorochrome used in medicine as a diagnostic stain.
Fluorescein is used to make the blood vessels of the ocular fundus visible
(angiography of the retina and choroid).

5.2

Pharmacokinetic properties
Distribution:
Within 7 to 14 seconds after intravenous administration into antecubital vein,
fluorescein usually appears in the central artery of the eye. Within a few minutes of
intravenous administration of fluorescein, a yellowish discoloration of the skin
occurs, which begins to fade 6 to 12 hours after dosing. Various estimates of volume
of distribution indicate that fluorescein distributes well into interstitial space (0.5
L/kg).
Metabolism:
Fluorescein undergoes rapid metabolism to fluorescein monoglucuronide. After
intravenous administration of fluorescein sodium (14 mg/kg) to 7 healthy subjects,
approximately 80% of fluorescein in plasma was converted to glucuronide conjugate
after a period of 1 hour post dose, indicating relatively rapid conjugation.
Excretion:
Fluorescein and its metabolites are mainly eliminated via renal excretion. After
intravenous administration, the urine remains slightly fluorescent for 24 to 36 hours.
A renal clearance of 1.75 ml/min/kg and a hepatic clearance (due to conjugation) of
1.50 ml/min/kg have been estimated. The systemic clearance of fluorescein is
essentially complete by 48 to 72 hours after administration of 500 mg fluorescein.
Although a longer excretion rate in patients with renal impairment is possible, limited
experience in renally impaired subjects (glomerular filtration rate below 20 ml/min)
suggests that, in general, no dose adjustment is required.

5.3

Preclinical safety data
Non-clinical data for sodium fluorescein reveal no special hazard for humans based
on studies of single dose toxicity.
Fluorescein did not show teratogenic effects in rats and rabbits. Fluorescein crosses
the placental barrier. After the intravenous application of 500 mg/kg intense
fluorescence was detectable both in the fetus and the amniotic fluid.
Studies on mutagenicity did not show any mutagenic effects of fluorescein sodium

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Sodium hydroxide (for pH-adjustment)
Hydrochloric acid (for pH-adjustment)
Water for injections

6.2

Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed
with other medicinal products.
To avoid physical incompatibilities, this product must not be administered
simultaneously with other solutions for injection with acid pH (especially
antihistamines) by the same intravenous route (see section 4.2 for information about
cannulas).
Once opened the vial must be immediately used.

6.3

Shelf life
2 years

6.4

Special precautions for storage
Do not store above 25°C.
Do not freeze.
Keep the vial in the outer carton in order to protect from light.

6.5

Nature and contents of container
Glass (type I) vial with grey chlorobutyl coated rubber stopper and aluminum seal
with polypropylene flip-off cap.
Pack containing 12 vials of 5 ml injection solution

6.6

Special precautions for disposal and other handling
The solution is to be inspected visually for particulate matter and discoloration prior
to administration. The solution should only be used if the solution is clear and free
from particles. For single use only. Any unused product or waste material should be

disposed of in accordance with local requirements. Do not use Anatera 100 mg/ml
solution for injection if the vial is cracked or damaged in any way.

7

MARKETING AUTHORISATION HOLDER

Alcon Laboratories (UK) Ltd
Frimley Business Park,
Frimley, Camberley,
Surrey, GU16 7SR,
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 00649/0377

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
24/04/2008

10

/

25/04/2012

DATE OF REVISION OF THE TEXT
30/04/2014

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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