NITROGLYCERIN INJECTION USP 0.05%W/V 10ML

Active substance: GLYCERYL TRINITRATE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Nitroglycerin Injection USP 0.05%W/V 10ml

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each 10ml contains 5mg of Nitroglycerin U.S.P.

3.

PHARMACEUTICAL FORM
Clear, colourless or pale yellow sterile solution intended for parenteral
administration to human beings after dilution in either Sodium Chloride
Injection B.P. or Glucose Injection B.P.

4.

CLINICAL PARTICULARS

4.1.

Therapeutic Indications
a) Control of blood pressure in perioperative hypertension, i.e. hypertension
associated with surgical procedures, especially cardiovascular procedures
and in the immediate post-surgical period.
b) Unresponsive congestive cardiac failure secondary to acute myocardial
infarction.
c) Treatment of angina pectoris in patients who have not responded to
recommended doses of organic nitrates and/or beta-adrenoceptor blocking
agents.
d) Production of elective hypotension and maintenance of controlled
hypotension during surgical procedures.

4.2.

Posology and Method of Administration

Route of administration: Intravenous infusion after dilution.
Nitroglycerin Injection is a concentrated potent drug which must be diluted in
either Sodium Chloride Injection B.P. or Glucose Injection B.P. prior to its
infusion.
Nitroglycerin Injection should not be mixed with other drugs. It is
recommended that the drug is diluted to give a final concentration of 400
micrograms/ml or less, according to the dosage requirements of the patient.
Most patients respond to doses between 10 - 200 micrograms/minute, although
doses up to 400 micrograms/minute may be required during some surgical
procedures.
Dosage: The usual recommended dose range is 10 - 200 micrograms/minute.
Doses in excess of these have been used and up to 400 micrograms/minute
may be required during some surgical procedures. Careful clinical assessment
and frequent monitoring of blood pressure and heart rate are essential to
maintain the appropriate rate of infusion. Where available, monitoring of
pulmonary capillary wedge pressure and cardiac output can be used to titrate
dosage to response.
Surgery: For the control of hypertensive episodes, the recommended starting
dose is 25 micrograms/minute increasing in steps of 25 micrograms/minute at
5 minute intervals until the desired reduction in blood pressure is achieved.
Although most patients respond to doses between 10 to 200
micrograms/minute, doses up to 400 micrograms/minute have been required
during some surgical procedures. In the treatment of perioperative myocardial
ischaemia, the recommended starting dose is 15 to 20 micrograms/minute
increasing in steps of 10 to 15 micrograms/minute until the desired effect is
achieved.
Unresponsive congestive cardiac failure secondary to acute myocardial
infarction : The recommended starting dose is 20 to 25 micrograms/minute
which can be decreased to 10 micrograms/minute or increased in steps of 20 to
25 micrograms/minute at 15 to 30 minute intervals until the desired effect is
achieved.
Unstable angina : The recommended starting dose is 10 micrograms/minute
increasing in steps of 5 to 10 micrograms/minute at approximately 30 minute
intervals.
Children: The safety and effectiveness of nitroglycerin in children have not
been established.
Use in the elderly : Special care in dose titration and monitoring is required
in elderly patients, as there is an increased risk of a fall in perfusion pressure
owing to a higher prevalence of coronary or cerebral artery disease in the
elderly.

4.3. Contra-Indications
Known hypersensitivity to organic nitrates. Marked anaemia, raised intracranial
pressure (e.g. due to head trauma or cerebral haemorrhage), arterial hypoxaemia,
uncorrected hypovolaemia or severe hypotension. Constrictive pericarditis,
pericardiac tamponade, hypertrophic obstructive cardiomyopathy, aortic stenosis and
mitral stenosis.
Phosphodiesterase type-5 inhibitors (e.g. sildenafil, tadalafil, vardenafil) have been
shown to potentiate the hypotensive effects of nitrates, and their co-administration
with nitrates or nitric oxide donors is therefore contra-indicated.
4.4.

Special Warnings and Special Precautions for Use
Nitroglycerin Injection should be used with caution in patients suffering from
severe hepatic or renal disease, hypothyroidism, malnutrition, hypothermia
and in those predisposed to closed angle glaucoma.
In order to achieve and maintain the correct dosage, continuous monitoring of
physiological parameters must be performed, including blood pressure and
heart rate in all patients and other measurements such as capillary wedge
pressure as appropriate. The systemic blood pressure and coronary perfusion
pressure must be maintained adequately at all times.
Nitroglycerin Injection should be administered by means of a micro-drip set
infusion pump or similar device which permits maintenance of a constant
infusion rate. The giving set should be composed of glass or rigid
polyethylene. Infusion systems composed of PVC may absorb up to 50% of
the nitroglycerin from solution, resulting in reduced potency of the infusion
(see incompatibilities).
Excessive hypotension, especially for prolonged periods of time, must be
avoided because of the possible deleterious effects of poor perfusion on body
organs and the consequent risk of ischaemic damage.
Paradoxical
bradycardia and increased angina pectoris may accompany
nitroglycerin-induced hypotension.
Patients with normal or low left ventricular filling pressure or pulmonary
capillary wedge pressure are especially sensitive to the hypotensive effects of
intravenous nitroglycerin and may respond fully to doses as small as 5
micrograms/minute. Where pulmonary capillary wedge pressure is being
monitored, it will be noted that a fall in wedge pressure precedes the onset of
arterial hypotension. Therefore, pulmonary capillary wedge pressure is a
useful guide to titration of the drug in these circumstances.
Nitroglycerin Injection contains both alcohol and propylene glycol. Safety
for intracoronary injection has not been shown.

Propylene glycol can lead to lacticacidosis and it is recommended that the
duration of therapy with this product be restricted to no more than three
successive days.
There are no long-term studies to evaluate the carcinogenic potential of
nitroglycerin

4.5. Interaction with other Medicinal Products and other Forms of Interaction
Concomitant treatment with other vasodilators, calcium antagonists, ACE inhibitors,
beta-blockers, diuretics, antihypertensives, tricyclic antidepressants and major
tranquillisers, as well as the consumption of alcohol, may potentiate the hypotensive
effect of Nitroglycerin Injection.
The blood pressure lowering effect of Nitroglycerin Injection will be increased if used
together with phosphodiesterase inhibitors (e.g. sildenafil) 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 any type of
phosphodiesterase inhibitor (e.g. sildenafil).
If administered concurrently, Nitrogylcerin Injection may increase the blood level of
dihydroergotamine and lead to coronary vasoconstriction.
The possibility that ingestion of acetylsalicylic acid and non-steroidal antiinflammatory drugs might diminish the therapeutic response to Nitroglycerin Injection
cannot be excluded.
4.6.

Pregnancy and Lactation
There is inadequate evidence of the safety of nitroglycerin in pregnancy and
lactation. Nitroglycerin Injection should not be used during pregnancy or
lactation unless considered essential by the physician.

4.7.

Effects on Ability to Drive and Use Machines
The indications for Nitroglycerin Injection limit its use to situations in which
there would not be an opportunity to drive or to operate machinery.

4.8. Undesirable Effects
Frequencies of the adverse reactions are listed according to the following convention:
Very common ( 1/10),
Common ( 1/100, < 1/10),
Uncommon ( 1/1000, < 1/100)
Rare ( 1/10000, < 1/1000),

Very rare (< 1/10000),
Not known (cannot be estimated from the available data).
Cardiac disorders:

Common: Paradoxical Bradycardia
Uncommon: Tachycardia*

Nervous system disorders:

Very Common: Headache*

Gastrointestinal disorders:

Common: Nausea
Not known: Retrosternal discomfort

Vascular disorders:

Very common: Hypotension*
Common: Dizziness*

General disorders and
administration site conditions:

Not known: Diaphoresis, Flushing*, Restlessness,
Abdominal pain

*particularly if the infusion is administered too rapidly.
These symptoms should be readily reversible on reducing the rate of infusion or, if
necessary, discontinuing treatment.
4.9.

Overdose
Accidental overdosage may result in severe hypotension and reflex
tachycardia which can be managed by elevating the lower limbs and
decreasing or temporarily withdrawing the infusion until the condition is
stabilised. In extreme states of hypotension, intravenous administration of an
alpha adrenergic agonist such as methoxamine hydrochloride or phenylephrine
hydrochloride should be considered.

5.

PHARMACOLOGICAL PROPERTIES

5.1.

Pharmacodynamic Properties
Nitroglycerin is an organic nitrate. Relaxation of vascular smooth muscle is
the principal pharmacological action of nitroglycerin. Nitroglycerin causes
dilatation of both venous and arterial smooth muscle in a dose-related manner.
Venodilatation predominates at lower infusion rates and, as the infusion rate
increases, nitroglycerin dilates both arterial and venous systems. Pulmonary
vascular resistance, systemic vascular resistance and arterial pressure are all
reduced by administration of intravenous nitroglycerin.
Dilatation of the post-capillary vessels promotes peripheral pooling of blood
and decreases venous return, reducing left ventricular end-diastolic pressure
(pre-load). Relaxation of arterioles reduces systemic vascular resistance and
arterial pressure (after-load).
Myocardial oxygen consumption (as measured by the rate-pressure product
and tension-time index) is decreased by both the venous and arterial effects of
nitroglycerin, and a more favourable supply-demand ratio can be achieved.

Although the predominant clinical benefits result from the peripheral
vasodilating effects and the resultant decrease in myocardial oxygen demand,
some effect on oxygen supply may occur by direct coronary vasodilatation.
Redistribution of blood from normal to ischaemic areas of the myocardium has
been demonstrated.

5.2.

Pharmacokinetic Properties
Pharmacokinetic data for intravenous nitroglycerin are difficult to interpret
due to factors such as the variation in sensitivity of assay procedures for
calculating plasma concentrations of the drug, intersubject variation in plasma
concentrations and adsorption of nitroglycerin by some types of giving sets.
There appears to be no close correlation between the infusion rates of
intravenous nitroglycerin and the blood concentrations achieved.
Nitroglycerin is extensively distributed and is rapidly metabolised in the liver
and erythrocytes by the enzyme glutathione - organic nitrate reductase. The
enzyme converts nitroglycerin to dinitrates, mononitrates and inorganic
nitrites, which have about one tenth of the vasodilating activity of
nitroglycerin and which are excreted in the urine within 24 hours after a single
dose. The elimination half-life of nitroglycerin ranges from less than one
minute to three minutes. Impaired hepatic function may impair the clearance
of the drug.

5.3.

Pre-clinical Safety Data
No further relevant information other than that which is contained in the other
sections of the Summary of Product Characteristics.

6.

PHARMACEUTICAL PARTICULARS

6.1.

List of Excipients
Propylene Glycol B.P.
Ethanol B.P.
Water for Injections B.P.

6.2.

Incompatibilities

Nitroglycerin Injection is compatible with glass infusion bottles. It has been
shown to be compatible with certain rigid infusion packs made of
polyethylene, such as the polyfusor from Kendall or bottlepak and flatpak
from Braun, Dublin. The injection can be administered as an infusion using
one of these recommended infusion bottles/packs.
Nitroglycerin Injection is not compatible with infusion bags made from
polyvinyl chloride (PVC) and over 40% of the nitroglycerin activity can be
lost if contact with PVC is prolonged. Therefore, it is recommended that
contact with PVC bags is avoided. Some loss of activity can also occur
through the infusion sets but the clinical response should be used to determine
the rate of infusion and thus the dosage of the drug required by the patient.
Alternatively, nitroglycerin injection may be infused slowly via a syringe
pump using a glass syringe or rigid plastic syringe (Gillette Sabre syringe,
Brunswick Disposable, B.D. Plastipak syringes).
A high pressure
polyethylene tubing known to be compatible with nitroglycerin is the
Lectrocath tubing, Vygon, Gloucester.

6.3.

Shelf-Life
3 years (36 months).
If only part of an ampoule is used, discard the remaining solution.

6.4.

Special Precautions for Storage
Protect from light.
Store in a cool dry place.

6.5.

Nature and Contents of Container
10ml, clear glass ampoules, glass type 1 Ph. Eur., packed in cardboard cartons
to contain 5 x 10ml or 10 x 10ml ampoules.

6.6.

Instructions for Use, Handling and Disposal
For administration by i.v. infusion only after dilution with a suitable vehicle
such as 5% dextrose in water or 0.9% w/v sodium chloride.
Use as directed by the physician.
Keep out of reach of children.
If only part used, discard the remaining solution.

7

MARKETING AUTHORISATION HOLDER

Mercury Pharma International Ltd
4045, Kingswood Road,
City West Business Park,
Co Dublin, Ireland
8.
MARKETING AUTHORISATION NUMBER(S)
PL 2848/0167.

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
11/06/2003

10

DATE OF REVISION OF THE TEXT
23/08/2012

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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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