GLYCERYL TRINITRATE 1MG/ML SOLUTION FOR INFUSION
Active substance(s): GLYCERYL TRINITRATE
PACKAGE LEAFLET: INFORMATION FOR THE PATIENT
Glyceryl Trinitrate 1 mg/ml solution for infusion
Read all of this leaflet carefully before you receive this medicine because it contains important information for you.
• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.
See section 4
The name of your medicine is Glyceryl Trinitrate 1 mg/ml solution for infusion, which will be referred to as Glyceryl Trinitrate throughout
WHAT IS IN THIS LEAFLET:
accompanied by increased pressure on the brain
• If you have or had heart conditions
1. What Glyceryl Trinitrate is and what it is used for
What you need to know before you receive Glyceryl Trinitrate
How to use Glyceryl Trinitrate
Possible side effects
How to store Glyceryl Trinitrate
Contents of the pack and other information
WHAT GLYCERYL TRINITRATE IS AND WHAT IT IS
Glyceryl Trinitrate belongs to a group of drugs called nitrates. This
medicine is used to prevent and relieve the pain or discomfort of
an angina attack (chest pain). It relaxes the muscle around blood
vessels and makes the heart’s work easier.
This solution is only used in hospitals and is given to you by a
doctor or nurse. It is used in the following conditions:
• heart failure and acute myocardial infarction (heart attack)
• angina attack
• to lower blood pressure during surgery
• to control blood pressure during and after cardiac surgery
WHAT YOU NEED TO KNOW BEFORE YOU RECEIVE
Do not use Glyceryl Trinitrate:
• if you are allergic (hypersensitive) to nitrate medicines or to
any of the other ingredients in Glyceryl Trinitrate (See section
• if you are taking a medicine for the treatment of erectile
dysfunction (e.g. sildenafil vardenafil, tadalafil). If you take
Glyceryl Trinitrate concomitantly with such medicines a severe
and possibly dangerous fall in blood pressure can occur. This
would result in collapse, unconsciousness and could be fatal.
You should not take such medicines whilst on Glyceryl Trinitrate
• if you are in shock (a life-threatening medical condition where
insufficient blood flow reaches the body tissues)
• if you have severe anaemia (lack of red blood cells)
• if you have low blood pressure
• if you have low blood volume
• if you have low blood oxygen (this can make you feel fatigued
and short of breath) and angina caused by a heart disease
where the muscle mass of the left heart ventricle is enlarged
• if you have severe blood loss
• if you have fluid accumulation in the lung
• if you have ever had a serious head injury, cerebral
haemorrhage (bleeding in the brain) or a disease which is
Warnings and precautions
Talk to your doctor or pharmacist before using Glyceryl Trinitrate if:
• you have acute left-sided heart failure - providing that
systolic blood pressure (the blood pressure when the heart is
contracting) is over 90 mmHg
• you have had an acute myocardial infarction (heart attack) providing that systolic blood pressure is over 90 mmHg
• you have severe liver or kidney problems
• you have an under active thyroid
• your body temperature is lower than normal (hypothermia)
• you are pregnant or breastfeeding.
This medicine is not recommended in children.
Other medicines and Glyceryl Trinitrate
Tell your doctor or pharmacist if you are taking, have recently
taken or might take any other medicines. This is especially
important with the following medicines as they may interact with
your Glyceryl Trinitrate:
• Medicines which lower blood pressure (e.g. other vasodilators,
beta-blockers, calcium channel blockers)
• Medicines for the treatment of erectile dysfunction (e.g.
sildenafil, vardenafil, tadalafil)
• Certain antidepressants (tricyclics e.g. amitriptyline,
nortiptyline, clomipramine, imipramine)
• Certain very strong pain killers which are similar to morphine
(opioids e.g. alfentanil)
• Medicines used to treat anxiety (neuroleptics)
• Sapropterine containing medicines
• Non-steroidal anti-inflammatory drugs (NSAIDs) except acetyl
Pregnancy and breast-feeding
If you are pregnant or breast-feeding, think you may be pregnant
or are planning to have a baby, ask your doctor or pharmacist for
advice before taking this medicine
Driving and using machines
This medicine is used in hospitalised patients. Therefore if you
have any concerns ask your doctor or pharmacist.
HOW TO USE GLYCERYL TRINITRATE
Usually Glyceryl Trinitrate will be given to you by your doctor or a
nurse and you will be monitored very carefully.
• This solution is always given slowly into the blood stream as a
diluted solution for (intravenous) infusion.
SUMMARY OF PRODUCT CHARACTERISTICS
Glyceryl Trinitrate 1 mg/ml solution for infusion
NAME OF THE MEDICINAL PRODUCT
Glyceryl Trinitrate 1 mg/ml solution for infusion
QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml solution contains 1 mg glyceryl trinitrate.
Amount of active substance per pack size:
Total GTN Content
For the full list of excipients, see section 6.1.
Solution for infusion
The product is a clear and colourless solution.
4.1 Therapeutic indications
The following indications exist for Glyceryl Trinitrate:
• Unresponsive congestive heart failure, including that secondary
to acute myocardial infarction; acute left-sided heart failure and
acute myocardial infarction,
• Refractory unstable angina pectoris and coronary insufficiency,
including Prinzmetal‘s angina,
• Control of hypertensive episodes and/or myocardial ischaemia
during and after cardiac surgery,
• Induction of controlled hypotension for surgery.
4.2 Posology and method of administration
For intravenous use. Glyceryl Trinitrate should be administered by
means of a micro-drip set infusion pump or similar device which
permits maintenance of constant infusion rate.
Recommendations on the dilution of the product are presented
in this section. For further instructions on dilution of the product
before administration, see section 6.6.
The dose of Glyceryl Trinitrate should be adjusted to meet the
individual needs of the patient.
The recommended dosage range is 10-200 mcg/min but up to
400 mcg/min may be necessary during some surgical procedures.
The safety and efficacy of Glyceryl Trinitrate has not yet been
established in children.
There is no evidence that a posology adjustment is required in
Use in surgery
A starting dose of 25 mcg/min is recommended for the control of
hypertension, or to produce hypotension during surgery. This may
be increased by increments of 25 mcg/min at 5 minute intervals
until the blood pressure is stabilised. Doses between 10-200 mcg/
min are usually sufficient during surgery, although doses of up to
400 mcg/min have been required in some cases.
The treatment of perioperative myocardial ischaemia may be
started with a dose of 15-20 mcg/min, with subsequent increments
of 10-15 mcg/min until the required effect is obtained.
Unresponsive congestive heart failure:
The recommended starting dose is 20-25 mcg/min. This may be
decreased to 10 mcg/min, or increased in steps of 20-25 mcg/min
every 15-30 minutes until the desired effect is obtained.
An initial dose of 10 mcg/min is recommended with increments
of 10 mcg/min being made at approximately 30 minute intervals
according to the needs of the patient.
Method of administration
Glyceryl Trinitrate can be administered undiluted by slow
intravenous infusion using a syringe pump incorporating a glass
or rigid plastic syringe.
Alternatively, Glyceryl Trinitrate may be administered intravenously
as an admixture using a suitable vehicle such as Sodium Chloride
Injection B.P. or Dextrose Injection B.P. In case of dilution, Glyceryl
Trinitrate must be mixed under aseptic conditions immediately
Prepared admixtures should be given by intravenous infusion or
with the aid of a syringe pump to ensure a constant rate of infusion.
During Glyceryl Trinitrate administration there should be close
haemodynamic monitoring of the patient.
The posology of Glyceryl Trinitrate i.v. should be adjusted to
achieve the desired clinical response. Additional dose adjustments
in patients with severe hepatic insufficiency or severe renal failure
may be necessary and require additional monitoring.
Example of admixture preparation
To obtain an admixture of Glyceryl Trinitrate at a concentration
of 100 mcg/ml, add 50 ml Glyceryl Trinitrate solution (containing
50 mg glyceryl trinitrate) to 450 ml of infusion vehicle to give a final
volume of 500 ml.
A dosage of 100 mcg/min. can be obtained by giving 60 ml of the
admixture per hour.
Vials of Glyceryl Trinitrate are for single use only and should not be
regarded as multi-dose containers.
Glyceryl Trinitrate should not be used in the following cases:
• Hypersensitivity to the active substance, other nitrates or any of
the excipients listed in Section 6.1
• Acute circulatory failure (shock, collapse)
• Cardiogenic shock (unless a sufficient end-diastolic pressure is
maintained by appropriate measures)
• Severe anaemia,
• Severe cerebral haemorrhage
• Head trauma
• Uncorrected hypovolaemia and hypotensive shock
• Arterial hypoxaemia and angina caused by hypertrophic
• Constrictive pericarditis
• Pericardial tamponade
• Toxic pulmonary oedema.
• During nitrate therapy, phosphodiesterase inhibitors type
5 (PDE5) (e. g. sildenafil, vardenafil, tadalafil) must not be used
because PDE5 inhibitors may amplify the vasodilatory effects
of Glyceryl Trinitrate resulting in severe hypotension (see
sections 4.4 and 4.5).
• Conditions associated with an increased intracranial pressure.
• Myocardial insufficiency due to obstruction, aortic or mitral
stenosis, hypertrophic obstructive cardiomyopathy or
4.4 Special warnings and precautions for use
Caution should be exercised in patients with severe liver or renal
disease, hypothermia, hypothyroidism.
Glyceryl Trinitrate should not be given by bolus injection.
Glyceryl Trinitrate must be used only with particular caution and
under medical supervision in:
Low filling pressures e.g. in acute myocardial infarction,
impaired left ventricular function (left ventricular failure).
Reducing systolic blood-pressure below 90 mmHg must be
• Orthostatic dysfunction
The development of tolerance and cross tolerance to other nitro
compounds has been described.
Glyceryl Trinitrate must not be used in patients known to be taking
phosphodiesterase inhibitor-containing products (e. g. sildenafil,
vardenafil, tadalafil). Patients who receive Glyceryl Trinitrate
solution therapy must be warned not to take phosphodiesterase
inhibitor-containing products (e.g. sildenafil, vardenafil, tadalafil)
(see sections 4.3 and 4.5).
Materials made of polyethylene (PE), polypropylene (PP) or
polytetrafluorethylene (PTFE) have proven to be suitable for
infusing Glyceryl Trinitrate solution. However, infusion material
made of polyvinyl chloride (PVC) or polyurethane (PU) has been
shown to induce a loss of the active substance due to adsorption.
If these materials are used the dose must be adjusted to suit
patient‘s needs (see also section 6.2).
The solution contains glucose; this should be taken into account in
patients with diabetes mellitus.
Caution should be exercised in patients with arterial hypoxaemia
due to severe anaemia (including G6PD deficiency induced forms),
because in such patients the biotransformation of nitroglycerin is
Similarly, caution is called for in patients with hypoxaemia and
ventilation/perfusion imbalance due to lung disease or ischaemic
Patients with angina pectoris, myocardial infarction, or cerebral
ischaemia frequently suffer from abnormalities of the small
airways (especially alveolar hypoxia).
Under these circumstances vasoconstriction occurs within the lung
to shift perfusion from areas of alveolar hypoxia to better ventilated
regions of the lung (see also section 4.8). As a potent vasodilator,
nitroglycerin could reverse this protective vasoconstriction and
thus result in increased perfusion of poorly ventilated areas,
worsening of the ventilation/perfusion imbalance, and a further
decrease in the arterial partial pressure of oxygen.
Following treatment with Glyceryl Trinitrate, methaemoglobinaemia
has been reported. Treatment of methaemoglobinaemia with
methylene blue is contraindicated in patients with glucose-6phosphate deficiency or methaemoglobin-reductase deficiency
(see also section 4.9).
4.5 Interaction with other medicinal products and other
forms of interaction
Concomitant treatment with other vasodilators, calcium
antihypertensives, tricyclic antidepressants and neuroleptics, as
well as the consumption of alcohol, may potentiate the hypotensive
effect of the preparation.
The blood pressure lowering effect of Glyceryl Trinitrate will be
increased if used together with phosphodiesterase inhibitors
(e.g. sildenafil, vardenafil, tadalafil) which are used for erectile
dysfunction (see Section 4.3). This might lead to life threatening
cardiovascular complications. Patients who are on nitrate therapy
must not use phosphodiesterase inhibitors (e.g. sildenafil,
Simultaneous intravenous infusions of tissue plasminogen
activator (tPA) and glyceryl trinitrate may accelerate plasma
clearance of tPA by increasing hepatic blood flow.
Reports suggest that, when administered concomitantly, Glyceryl
Trinitrate may increase the blood level of dihydroergotamine and
its effect. This warrants special attention in patients with coronary
artery disease, because dihydroergotamine antagonises the effect
of Glyceryl Trinitrate and may lead to coronary vasoconstriction.
The use of heparin and Glyceryl Trinitrate solution can lead
to a partial loss of action of heparin when both drugs are given
simultaneously by intravenous route.
Concurrent administration of Glyceryl Trinitrate with acetyl salicylic
acid may potentiate the blood pressure lowering effects of Glyceryl
The non-steroidal anti-inflammatory drugs except acetyl salicylic
acid may diminish the therapeutic response of Glyceryl Trinitrate.
Sapropterine (Tetrahydrobiopterine, BH4) is a cofactor for nitric
oxide synthetase. Caution is recommended during concomitant
use of sapropterine-containing medicine with all agents that cause
vasodilation by affecting nitric oxide (NO) metabolism or action,
including classical NO donors (e.g. glyceryl trinitrate (GTN),
isosorbide dinitrate (ISDN), isosorbide 5-mononitrate (5-ISMN)
4.6 Fertility, pregnancy and lactation
Reproduction toxicity studies performed in
various routes of administration did not
mating, fertility and general reproductive
no data available on the effect of Glyceryl
rats and rabbits using
reveal any effect on
parameters. There is
Trinitrate on fertility in
Developmental toxicity studies performed in rats and rabbits using
various routes of administration did not reveal any effect on the
embryos, fetuses or the young animals even at toxic doses for
Available evidence is inconclusive or inadequate for
determining infant risk when used during breastfeeding. There
is data that nitrates are excreted in breast milk and may cause
methaemoglobinaemia in infants. The extent of excretion of
nitroglycerin in human breast milk has not been determined. A risk
to the suckling child cannot be excluded.
A decision must be made whether to discontinue breast-feeding or
to discontinue/abstain from Glyceryl Trinitrate therapy taking into
account the benefit of breast feeding for the child and the benefit
of therapy for the woman.
4.7 Effects on ability to drive and use machines
Glyceryl Trinitrate may affect the patient‘s reactivity to an extent
that her/his ability to drive or to operate machinery is impaired.
This effect is increased in combination with alcohol
4.8 Undesirable effects
Undesirable effects frequencies are defined as: very common
(≥1/10), common (≥1/100 <1/10), uncommon (≥1/1,000 <1/100),
rare (≥1/10,000 <1/1,000) or very rare (<1/10,000), not known
(cannot be estimated from the available data).
During administration of Glyceryl Trinitrate the following
undesirable effects may be observed
The dose depends on the condition. Your doctor will decide the
correct dose and duration of therapy for you, while carefully
monitoring the effects of the drug.
Dosage in adults and the elderly:
• unresponsive congestive heart failure (a condition in which
the heart is not able to pump enough blood to meet the oxygen
demands of the body), acute myocardial infarction (heart
attack) and left-sided heart failure
- The usual doses are: 10-100 micrograms per minute
administered as a continuous intravenous infusion with
frequent monitoring of blood pressure and heart rate.
• refractory unstable angina pectoris (angina attack with chest
- An initial infusion rate of 10-15 micrograms per minute is
• use in surgery
- An initial infusion rate of 25 micrograms per minute is
recommended; this may be increased by 25 micrograms
per minute at 5 minute intervals until your blood pressure
is stabilised. Doses up to 400 micrograms per minute may
occasionally be needed.
If you receive more Glyceryl Trinitrate than you should
Since Glyceryl Trinitrate will be administered to you by a doctor or
nurse, it is unlikely that you will be given too much. In the event
of overdose following signs or symptoms can occur vomiting,
restlessness, fall in blood pressure, coldness of the skin, breathing
difficulties, mental illness, blue discolouration of the skin, slow
heart rate of less than 60 beats per minute, a temporary loss of
consciousness and posture and a very rare blood disorder where
the blood is unable to carry oxygen to cells in the body.
These symptoms may be readily reversed by discontinuing your
treatment, therefore please tell your doctor or nurse immediately if
one or more of these symptoms occur.
POSSIBLE SIDE EFFECTS
Like all medicines, Glyceryl Trinitrate can cause side effects,
although not everybody gets them. These side effects require
special management to minimise the risk of complications. Your
doctor will discuss these side effects with you and explain the risks
and benefits of your treatment.
Tell your doctor immediately if you experience the following:
• An allergic skin reaction – this occurs uncommonly. Symptoms
may include skin rash, redness, itch, burning sensation,
The following side effects have been reported:
Very common (may affect more than 1 in 10 people):
Common (may affect up to 1 in 10 people):
• dizziness, light-headedness
• fast or irregular heart beat
• dizziness when standing up suddenly
Uncommon (may affect up to 1 in 100 people):
• chest pain
• heart failure
Very rare (may affect up to 1 in 10,000 people):
Not known (frequency cannot be estimated from the available
• irregular heart beat (palpitations)
• low blood pressure
Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse.
This includes any possible side effects not listed in this leaflet. You
can also report side effects directly via the Yellow Card Scheme at:
By reporting side effects you can help provide more information on
the safety of this medicine.
HOW TO STORE GLYCERYL TRINITRATE
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on
the label and carton after “Exp”. The expiry date refers to the last
day of that month.
Glyceryl Trinitrate ampoules and vials will be stored below 25°C in
the outer carton to protect the medicine from light.
This medicine should not be given to you if the solution for infusion
shows any discolouration, precipitation or any other visible
Do not throw away any medicines via wastewater or household
waste. Ask your pharmacist how to dispose of medicines no longer
required. These measures will help to protect the environment.
CONTENTS OF THE PACK AND OTHER INFORMATION
What Glyceryl Trinitrate contains:
• The active substance is glyceryl trinitrate.
1 ml solution for infusion contains 1 mg glyceryl trinitrate.
• The other ingredients are water for injections, glucose
monohydrate and hydrochloric acid.
What Glyceryl Trinitrate looks like and the contents of the
The product is a clear and colourless solution for infusion. This
solution is packed in boxes containing:
- 10 ampoules with 5 ml
1 vial with 50 ml
- 10 ampoules with 10 ml
- 10 vials with 50 ml
- 10 ampoules with 25 ml
- 25 vials with 50 ml
Vials are closed with bromobutyl rubber stoppers.
Not all pack sizes may be marketed.
Marketing Authorisation Holder:
hameln pharma plus gmbh,
Langes Feld 13, 31789 Hameln, Germany
hameln pharmaceuticals gmbh,
Langes Feld 13, 31789 Hameln, Germany
hameln pharmaceuticals ltd,
Gloucester, United Kingdom
This package leaflet was last revised in June 2016.
--------------------------------------------------------------------------------------------------------------------Nervous system Very Common: Headache
Heart rate increase
Severe hypotensive responses have been reported for organic
nitrates and include nausea, vomiting, restlessness, pallor, and
During treatment with Glyceryl Trinitrate, a temporary hypoxemia
may occur due to a relative redistribution of the blood flow
in hypoventilated alveolar areas. Particularly in patients with
coronary artery disease this may lead to a myocardial hypoxia.
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.
Symptoms of overdose
Symptoms could include the following:
• Fall in blood pressure ≤ 90 mmHg
• Weak pulse
• Reflex tachycardia
• Dizziness postural
• Methaemoglobinaemia has been reported in patients
receiving other organic nitrates. During glyceryl trinitrate
biotransformation nitrite ions are released, which may induce
methaemoglobinaemia and cyanosis with subsequent
tachypnoea, anxiety, loss of consciousness and cardiac arrest.
It can not be excluded that an overdose of glyceryl trinitrate
may cause this adverse reaction
• In very high doses the intracranial pressure may be increased.
This might lead to cerebral symptoms
Treatment of overdose
• Stop delivery of the drug.
• General procedures in the event of nitrate-related hypotension:
- Patient should be kept horizontal with the head lowered and
legs raised or, if necessary, compression bandaging of the
- Supply oxygen
- Expand plasma volume
- For specific shock treatment admit patient to intensive care
• Raising the blood pressure if the blood pressure is very low
• Treatment of methaemoglobinaemia:
Treatment with intravenous methylene blue
- Initially 1 to 2 mg/kg, not exceeding 4 mg/kg of a 1% solution
over 5 minutes.
- Repeat dose in 60 minutes if there is no response.
- Administer oxygen (if necessary)
- Initiate artificial ventilation
Treatment of methaemoglobinaemia with methylene blue
is contraindicated in patients with glucose-6-phosphate
dehydrogenase (G-6-PD) deficiency or methaemaglobin
reductase deficiency (see also section 4.4).
Where treatment with methylene blue is contraindicated or is not
effective, exchange transfusion and/or transfusion of packed red
blood cells is recommended.
In case of signs of respiratory and circulatory arrest, initiate
resuscitation measures immediately.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: vasodilators used in cardiac diseases
ATC-Code: C01DA02 Organic nitrates
Glyceryl trinitrate exerts a spasmolytic action on smooth muscle,
particularly in the vascular system. This action is more marked
on the venous capacitance vessels than the arterial vessels; the
predominant increase in venous capacitance results in marked
diminution of both the left ventricular filling pressure and volume
(preload). The moderate dilation of the arteriolar resistance vessels
results in a reduction in afterload. These haemodynamic changes
(reductions) in preload and afterload lower the myocardial oxygen
demand. In addition, by direct action and through the reduction
of myocardial wall tension glyceryl trinitrate also lowers the
resistance to flow in the coronary collateral channels and allows
re-distribution of blood flow to ischaemic areas of the myocardium.
Administration of glyceryl trinitrate by intravenous infusion
to patients with congestive heart failure results in a marked
improvement in haemodynamics, reduction of elevated left
ventricular filling pressure and systolic wall tension, and an
increase in the depressed cardiac output. It reduces the
imbalance that exists between myocardial oxygen demand and
delivery, thereby diminishing myocardial ischaemia and controlling
ischaemia-induced ventricular arrhythmias.
Glyceryl trinitrate relaxes smooth muscles cells in other organs
to some extent. The cellular molecular mechanism of action is
a synthesis of nitric oxide and cyclic guanosyl monophosphate
which acts as a mediator for muscle relaxation.
5.2 Pharmacokinetic properties
After intravenous administration, glyceryl trinitrate is widely
distributed in the body with an estimated apparent volume of
distribution of approximately 200 litres. It is strongly bound to
erythrocytes and vessel walls; the plasma protein binding is
approx. 60%. The therapeutic plasma concentration range is
0.1 to 3 ng/ml (up to 5 ng/ml).
Glyceryl trinitrate is rapidly metabolised to dinitrate and
mononitrate and further metabolised by glucuronidation in the
liver, showing a marked first-pass effect.
Spontaneous hydrolysis occurs in plasma. The estimated
plasma half-life of glyceryl trinitrate is 1 to 4 minutes. The rapid
disappearance from plasma is consistent with the high systemic
clearance values (up to 3270 litres per hour). The less active
metabolites resulting from biotransformation can be recovered
from the urine within 24 hours.
5.3 Preclinical safety data
The acute toxicity has been reported for rats after intravenous (LD50
17-41 mg/kg body weight), as well as in dogs after intravenous
administration (LD50 19-24 mg/kg body weight). Autopsy did not
reveal any pathological findings.
Subacute studies in rats at doses of 2.5, 5.0 and 10.0 mg/kg per
day, and in dogs at doses of 1.0 and 3.0 mg/kg per day elicited
only minimal reactions. In rats, suppression of body weight gain
and food consumption occurred among treated and vehiclecontrol animals. Mild tissue irritation at injection sites was noted
in treated and vehicle-control groups. There were no clearly drugrelated clinical or pathological findings in dogs. Further results of
studies on repeated-dose toxicity in different species revealed no
indication of drug-specific clinically relevant toxicity.
Glyceryl trinitrate is insufficiently tested for a potential mutagenic
action. There are no adequate state-of-the-art long-term studies
on a possible tumourigenic action of glyceryl trinitrate.
There is inadequate experience with glyceryl trinitrate during
human pregnancy, particularly during the first trimester. Sufficient
evidence is available from animal studies with intravenous,
intraperitoneal and topical administration. Studies on fertility and
embryotoxicity did not result in any toxic effect on the embryo or on
reproductive performance. Any indication of a teratogenic potential
of glyceryl trinitrate was not found. Doses in excess of 1 mg/kg/
day (i.p.) or 28 mg/kg/day (topical) reduced the birth weight in rats.
There are no investigations on the passage of glyceryl trinitrate
into breast milk.
6.1 List of excipients
Water for injections
Glyceryl Trinitrate is not compatible with polyvinylchloride (PVC)
and severe losses of glyceryl trinitrate (up to 50%) may occur if
polyvinylchloride is used, resulting in a reduction of delivered dose
and efficacy. Contact of the solution with polyvinylchloride bags
should be avoided.
The product is compatible with glass infusion sets and with rigid
infusion packs made of polyethylene; it may also be infused slowly
using a syringe pump with a glass or plastic syringe.
6.3 Shelf life
Unopened ampoules: 3 years
Unopened vials: 2 years
Opened ampoules or vials:
The product should be used immediately after opening the
Any unused solution from opened containers should be discarded.
Prepared infusion solutions:
Chemical and physical in-use stability has been demonstrated
in glucose solution 5% and sodium chloride solution 0.9% for
24 hours at room temperature.
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°C to 8°C, unless dilution
has taken place in controlled and validated aseptic conditions.
6.4 Special precautions for storage
Keep the container in the outer carton.
Do not store above 25°C.
6.5 Nature and contents of container
5 ml, 10 ml or 25 ml ampoules, made of colourless glass, type I
50 ml vial, made of colourless glass, type I (Ph. Eur.), bromobutyl
Box of 10 ampoules with 5 ml
Box of 10 ampoules with 10 ml
Box of 10 ampoules with 25 ml
Box of 1 vial with 50 ml
Box of 10 vials with 50 ml
Box of 25 vials with 50 ml
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Glyceryl Trinitrate need not be diluted before use but can be
diluted by 1:10 up to 1:40 with 5% glucose solution, 5% glucose
solution and 0.9% sodium chloride solution, or with 0.9% sodium
The solution, whether or not diluted, should be infused slowly and
not given by bolus injection. To ensure a constant infusion rate
of glyceryl trinitrate it is recommended that Glyceryl Trinitrate be
administered by means of a syringe pump or polyethylene infusion
bag with a counter, or with a glass or rigid polyethylene syringe
and polyethylene tubing. Systems made of polyvinyl chloride
(PVC) may absorb up to 50% of the glyceryl trinitrate from the
Vials of 50 ml Glyceryl Trinitrate are for single use only and should
not be regarded as multi-dose containers.
MARKETING AUTHORISATION HOLDER
hameln pharma plus gmbh
Langes Feld 13
MARKETING AUTHORISATION NUMBER
DATE OF FIRST AUTHORISATION/RENEWAL OF THE
10. DATE OF REVISION OF THE TEXT