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INDIGO CARMINE 40 MG/5 ML SOLUTION FOR INJECTION

Active substance(s): INDIGOTINE / INDIGOTINE

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Indigo carmine 40 mg/5 mL solution for injection

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Indigotin (indigo carmine)…………………………………………………...40 mg
For 5 mL of solution for injection.
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Solution for injection.
pH: 3.0 to 5.9
Osmolarity: 0.05 osmol/L.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
This medicinal product is for diagnostic use only.
Indigo carmine is indicated for the intra-operative detection of suspected ureteral
injuries during abdominal and pelvic surgery.

4.2

Posology and method of administration
Posology
This medicinal product is to be injected by intravenous route. The recommended
initial dosage is 1 ampoule of 5 mL by slow intravenous injection.
A second ampoule may be injected 20 to 30 minutes after the first injection if
necessary.
Paediatric population

The efficacy and safety of Indigo carmine in children has not been established (see
section 4.4).
Patients with renal impairement
In patients with a clearance of creatinine ≥ 10 mL/min, indigotin (indigo carmine)
may be administered.
In patients with a clearance of creatinine < 10 mL/min, Indigo carmine should not be
used (see section 4.4).
Elderly
No dosage adjustment is necessary.
Patients with liver impairement
The excretion of Indigo carmine is mainly renal. There is no data in patients with
liver impairement, however no dosage adjustment is necessary.
Method of administration
Slow intravenous injection under monitoring of arterial pressure and heart rate.
Precautions to be taken before administering the medicinal product
Considering the dark blue colour of Indigo carmine, a filtration is recommended
during the intravenous administration (for example a filter of 0.45 µm, with a filtering
surface of at least 2.8 cm², composed of a hydrophilic polyethersulfone membrane).

4.3

Contraindications
Hypersensitivity to the active substance or to dyes.

4.4

Special warnings and precautions for use
Special warnings
Indigotin (indigo carmine) may cause a transient elevation of blood pressure and
reflex bradycardia especially in patients under general anaesthesia or under spinal
anaesthesia. Rare idiosyncratic reactions with bradycardia and hypotension have also
been reported. It is therefore necessary to monitor heart rate and blood pressure
during and a few minutes after the injection.
Intravenous injection should be stopped if the following symptoms occur:
bradycardia, tachycardia, hypotension, hypertension, rash or erythema, respiratory
symptoms such as dyspnea or bronchospasm.
The efficacy and safety of Indigo carmine in children has not been established.

In patients with a clearance of creatinine < 10 mL/min, the time to onset of indigotin
(indigo carmine) in urines may be delayed for several minutes. Therefore, it should
not be used in patients with clearance of creatinine < 10 mL/min.
Indigotin (indigo carmine) may interfere with pulse oxymetric methods.
A discolouration of urine may be observed following administration of indigotin
(indigo carmine).
Precautions for use
Indigotin (indigo carmine) should be used with caution in case of:

concomitant use of medicines inducing bradycardia,

heart rate and conduction disorders,

high blood pressure,

low heart rate,

coronary disorders due to its peripheral vasoconstrictor effect.
The use of indigotin (indigo carmine) should be avoided in patients with:

uncontrolled heart failure,

history of allergic reactions,

hemodynamic instability.

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 no or limited amount of data from the use of indigotin (indigo carmine) in
pregnant women. Animal studies are insufficient with respect to reproductive toxicity
(see section 5.3). Indigo carmine is not recommended during pregnancy and in
women of childbearing potential not using contraception.
Breast-feeding
It is unknown whether indigotin (indigo carmine) or its metabolites are excreted in
human milk. A risk to the suckling child cannot be excluded. A decision must be
made whether to discontinue breast-feeding or to abstain from indigotin (indigo
carmine) administration taking into account the benefit of breastfeeding for the child
and the benefit of therapy for the woman.

4.7

Effects on ability to drive and use machines
Not relevant.

4.8

Undesirable effects
The most common adverse reactions of indigotin (indigo carmine) are mainly related
to its alpha-adrenergic activity and are of cardiovascular origin.
Other idiosyncratic reactions such as changes in blood pressure or heart rate or
anaphylactoid reactions have also been described. Serious adverse reactions of
indigotin (indigo carmine) are very rare.
Cardiac disorders
Very common:

Hypertension (transient)

Bradycardia
Very rare:

Tachycardia

Hypotension

Atrioventricular block
Respiratory, thoracic and mediastinal disorders
Very rare:

Dyspnea

Bronchial hyperreactivity
Skin and subcutaneous tissue disorders
Very rare:

Rash and erythema

Skin discolouration
Immune system disorders
Very rare:

Anaphylactoid reactions.
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 reactions
via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.

4.9

Overdose
No case of overdose has been reported in the literature for doses up to 80 mg of
indigotin (indigo carmine) administered intravenously.
Symptoms
An overdose could induce a hypertensive crisis and severe bradycardia.
Management
In case of overdose, a peripheral vasodilator therapy may be considered.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic class: DIAGNOSTIC AGENTS, ATC Code: V04CH02
Indigotin (indigo carmine) is a dye clinically used for diagnostic purposes. When it is
intravenously administered, it causes dark blue discolouration of urine within 5-15
minutes of injection. This intense coloration enables the detection of any lesions of
the urinary tract.
No clinical study has been conducted. However, a meta-analysis of published studies
was used to evaluate the diagnostic performance of indigotin (indigo carmine) in the
detection of ureteral injury in abdominal and pelvic surgery. This meta-analysis
showed that the sensitivity and specificity of the test with indigotin (indigo carmine)
were high (respectively 96% and 100%) as well as the impact on the diagnosis
process (positive predictive value of 86% and negative predictive value of 99.9% in a
population with an incidence of ureteral lesions of 2.5%).
Indigotin (indigo carmine) with its alpha-adrenergic properties triggers an increase of
peripheral vascular resistance, resulting in moderate and transient increase of blood
pressure and a probably reactional moderate decrease of heart rate.

5.2

Pharmacokinetic properties
Pharmacokinetic data are rare. Indigotin (indigo carmine) has a plasma half-life of 4.5
minutes. Indigo carmine is largely bound to protein plasma. It is quickly eliminated
from the plasma compartment and it is easily and largely eliminated by the kidney. A
small amount is excreted in the bile.
In case of renal function impairment, the average time of excretion can be extended
for several minutes.

5.3

Preclinical safety data
Acute toxicity data for indigotin (indigo carmine) are available from rat and mouse
studies. In rats, the LD50 (median lethal single dose) is 93 mg/kg by intravenous
route while in mice the LD50 is 405 mg/kg by subcutaneous route.
No carcinogenicity study has been conducted by intravenous route with indigotin
(indigo carmine). However, long-term studies in rats (oral) and mice (subcutaneous)
have not revealed any carcinogenic effects.
In oral dosing studies performed in rats and rabbits, doses of indigotin (indigo
carmine) up to 250 mg/kg/day did not produce any teratogenic effects. However oral
availability is approximately 3%.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Water for injections.

6.2

Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed
with other medicinal products.

6.3

Shelf life
2 years.
After opening: this product should be used immediately.

6.4

Special precautions for storage
This product does not require any special storage conditions.
For storage conditions after first opening of the medicinal product, see section 6.3.

6.5

Nature and contents of container
5 mL ampoules in type I brown glass. Box of 10 ampoules.

6.6

Special precautions for disposal
Any unused medicinal product or waste material should be disposed of in accordance
with local requirements.

7

MARKETING AUTHORISATION HOLDER
SERB S.A.
Avenue Louise 480
1050 Brussels
Belgium

8

MARKETING AUTHORISATION NUMBER(S)
PL 43956/0001

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
05/06/2015

10

DATE OF REVISION OF THE TEXT
05/06/2015

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Source: Medicines and Healthcare Products Regulatory Agency

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