Nitroglycerine

Nitroglycerine
50 mg/10 mL - Injectable Solution
50 mg/10 mL - Injectable Solution

Route of administration:
Intravenous

Net Content: 5 Ampoules

Nitroglycerine
50 mg/10 mL - Injectable Solution

Composition:
Each ml contains:
Nitroglycerin USP
Water for Injection BP
HOSPITAL USE
DOSAGE INDICATIONS: At the discretion of the physician.
WARNINGS: Delicate use product that must be administered
to
Nitroglycerine
50 mg/10 mL - Injectable Solution

hospitalized patients, preferably in intensive care units and

under
strict and continuous medical supervision. The solution
should not be injected directly into a vein. It is administered by
appropriately diluted infusion. Discard the portion that is not
used.
Before using this product, read the internal leaflet.
KEEP OUT OF REACH OF CHILDREN.
STORAGE: Store in a cool and dry place at a temperature
below 30°C. Do not refrigerate. Protect yourself from light.
SALE WITH PHYSICIAN PRESCRIPTION
Manufactured by: Zenith Healthcare LTD, India.
Imported and Distributed by: Casa de Representaciones
JMW, C.A. Fixed Point - Venezuela.

website:

AUTHORIZED BY M.P.P.S UNDER SANITARY

PERMIT No.

Nitroglycerine
50 mg/10 mL - Injectable Solution
 For IV
Nitroglycerine
50 mg/10 mL - Net Content:
Injectable Solution 5 Ampoules

STORAGE: Store in a cool and

Composition: dry place at a temperature below
30°C. Do not refrigerate.
Each ml contains: Protect yourself from light.
Nitroglycerin USP
Water for Injection BP
Batch No. :
Mfg Date :
Manufactured by: Zenith Exp Date.:
Healthcare LTD, India.
Imported and Distributed by: Casa de
Representaciones
JMW, C.A. Fixed Point - Venezuela.
RIF: J-41236117-1
 Nitroglycerine
50 mg/10 mL - Injectable Solution

1. NAME OF THE ACTIVE SUBSTANCE (INN) n nyec a It is Concomitant treatment with calcium channel blockers, calcium converting enzyme inhibitors,
NITROGLYCERINE angiotensin (ACE) inhibitors, beta-blockers, diuretics, antihypertensives, tricyclic antidepressants and
neuroleptics,
2. ROUTE OF ADMINISTRATION
as well as alcohol consumption, can potentiate the hypotensive effect of Nitroglycerin.) The administration
INTRAVENOUS
Simultaneous use of nitroglycerin with dihydroergotamine may increase the bioavailability of the
3. PHARMACOLOGICAL PROPERTIES dihydroergotamine and therefore increase its plasmatic levels. This is especially important in
Pharmacotherapeutic group: Vasodilators used in cardiac diseases. patients with coronary artery disease, since dihydroergotamine antagonizes the effect of nitroglycerin
ATC code: C01DA02. and may lead to coronary vasoconstriction. Nonsteroidal anti-inflammatory drugs (NSAIDs), with the
exception of acetylsalicylic acid, may decrease the therapeutic response to nitroglycerin. The
3.1.pharmacodynamics
Concomitant administration of nitroglycerin with amifostine and acetylsalicylic acid may potentiate the
In the vascular system, nitroglycerin acts mainly on the systemic veins and secondarily on the
hypotensive effects of nitroglycerin. Alcohol intake should be avoided during treatment with
large coronary arteries, relaxing smooth muscle. At low doses, nitroglycerin is activated by
nitroglycerine.
mitochondrial aldehyde dehydrogenase and converted to nitrites and denitrated metabolites (1,2-
diglyceryl dinitrate, 1,3-diglyceryl dinitrate) by glutathione-dependent organic nitrate reductase. 8. WARNINGS AND PRECAUTIONS
activated by cytochrome oxidase or by acid imbalance in the intermembrane space (H+), finally giving 8.1. generals
nitric oxide (NO) or related compounds, which activate soluble guanylyl cyclase and trigger the During administration of this product, pulmonary capillary pressure should be controlled whenever
cyclic guanosine monophosphate (cGMP) signaling system through the protein CCMP- possible, or at least continuous monitoring of blood pressure and heart rate is necessary. Patients
dependent kinase, which with hepatic and/or renal insufficiency. Seniors. In myocardial infarction. As with other nitrate
causes relaxation. Glyceryl dinitrates, mononitrates, and nitroglycerin at high doses are activated through the medications, when chronic nitrate therapy is replaced by another form of medication,
cytochrome P450 from the smooth endoplasmic reticulum, releasing NO directly and causing smooth nitroglycerin should be withdrawn gradually, and should overlap with the new therapy, to
muscle relaxation. The fundamental mechanism of action of nitroglycerin in angina pectoris avoid a potential nitrate withdrawal reaction. postural hypotension and it is therefore advisable
is an increase in venous capacitance leading to decreased venous return. This decreases the drug to warn the patient of this possibility, to avoid sudden changes in posture, when starting
and produces a redistribution of coronary blood flow to the ischemic subendocardium treatment. Caution should be exercised in patients with arterial hypoxemia due to severe anemia
through selective dilation of the great epicardial vessels. It is also capable of dilating strictures caused (including induced forms of G6PD deficiency), since nitroglycerin biotransformation is reduced in
by eccentric atheroma. In addition, nitroglycerin produces relaxation of vasospasm, both dose- these patients. Treatment with nitrates can worsen angina secondary to hypertrophic
dependent, thereby decreasing systemic vascular resistance (afterload) and systolic blood pressure. cardiomyopathy.
left ventricular end-diastolic pressure (preload) and, consequently, left ventricular
8.2. Pregnancy
filling volume, resulting in decreased resting myocardial oxygen demand and,
There are no adequate and well-controlled studies in pregnant women. It should only be given to
especially, in exercise, with an improvement in exercise capacity. On the other hand, nitrates
pregnant women if the potential benefits to the mother clearly outweigh the potential risks to the fetus.
are potent vasodilators of extramural coronary arteries and collateral coronary vessels. He
Do not administer during pregnancy or when its existence is suspected unless at the discretion of a doctor
spontaneous and ergonovine-induced. Nitroglycerin dilates the arteriolar vascular bed
the risk/benefit balance is favourable.
left ventricle, thus reducing myocardial oxygen consumption.
8.3. Lactation
3.2. Pharmacokinetics
There is insufficient information regarding the excretion of the active substance in human or animal milk. A
After I.V. administration, the achieved bioavailability is around 70%. Distribution
decision should be made whether to discontinue breast-feeding or to discontinue nitroglycerin treatment
The fraction of nitroglycerin that is bound to plasma proteins is 61-64% for nitroglycerin, and 23% and
after considering the benefit of breast-feeding for the child and the benefit of treatment for the mother. If its
11% for 1,2-glyceryl dinitrate and 1,3-glyceryl dinitrate, respectively.
use is essential because there is no other therapeutic alternative, stop breastfeeding for the duration of
Metabolism
the treatment.
Nitroglycerin is rapidly metabolized in the liver to glyceryl dinitrates and mononitrates by a
sulfhydryl-dependent enzymatic process and by reduced interaction with hemoglobin. In human 9. CONTRAINDICATIONS
erythrocytes, the reduced level of hemoglobin appears to play an important role in metabolic Known hypersensitivity to nitroglycerin, organic nitrates or any of the excipients of the
activity and caution should therefore be exercised in patients with anemia. In animal studies, formula.
extrahepatic vascular tissues (femoral vein, inferior vena cava, aorta) have been shown to play - Hypersensitivity to nitroderivatives.
organic nitrate reductase, glutathione dependent. In addition, and probably more importantly, in - States of accentuated hypotension.
vitro studies have shown that the human erythrocyte is also a site of biotransformation, through - Glaucoma.
and also an important role in the metabolism of nitroglycerin, a finding that agrees with the high Patients with cardiac tamponade, heart failure due to obstruction, such as in
systemic clearance observed with nitrates. It has also been shown in vitro that the aortic or mitral stenosis, or constrictive pericarditis.
biotransformation of nitroglycerin occurs concurrently with relaxation of vascular smooth muscle; - Acute circulatory failure associated with marked hypotension (shock).
this observation is in agreement with the hypothesis that the biotransformation of nitroglycerin - Situations associated with elevated intracranial pressure.
it is involved in the vasodilatation mechanism induced by nitroglycerin. Severe hypovolemia.
Excretion - Concomitant use of phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil, vadalafil or tadalafil.
Nitroglycerin is excreted via the kidneys in the form of dinitrates and mononitrates, glucuronide conjugates,
10. OVERDOSE
and
10.1. Signs and symptoms
glycerin. The elimination half-lives of nitroglycerin, 1,2-glyceryl dinitrate and mononitrates of
High doses of nitroglycerin can produce the following symptoms:
glycerylc are 10, 30-60 minutes and 5-6 hours, respectively.
- Severe hypotension ≤ 90 mm Hg
3.3. Preclinical safety information - Paleness
In vitro and in vivo studies have not revealed any apparent mutagenic activity of nitroglycerin. In - Sweating -
rats to which nitroglycerin was administered orally, 363 mg/kg/day to males and 434 mg/kg/day to females. Weak pulse
females for two years, the development of hepatocellular carcinomas and testicular tumors of - Reflex tachycardia -
interstitial cells. Mice that received the compound for the same period of time did not Postural dizziness
presented Sc treatment-related tumors unknown systemic exposures - Headache
equivalents in humans and, therefore, a carcinogenic risk for humans cannot be ruled out. They have - Asthenia
conventional reproduction studies in rats and rabbits using different routes of - Vertigo
administration such as the oral, intravenous, intraperitoneal and cutaneous routes (in the form of an ointment), - Nausea
where the Nitroglycerin did not show teratogenic potential at doses similar to those expected in humans. - Vomiting
- Diarrhea
4. INDICATIONS
- Methemoglobinemia has been reported after accidental overdose. During nitroglycerin
- Treatment of unstable angina pectoris.
biotransformation, nitrite ions are released, which cause methemoglobinemia and cyanosis with the
- Treatment of congestive heart failure associated with acute myocardial
from
infarction. - Management of hypertensive crisis during and after surgery.
consequent tachypnea, anxiety, loss of consciousness, and acute coronary
5. DOSAGE
syndrome. - Intracranial pressure may increase. This could lead to brain symptoms.
5.1. Adult
- Collapse and syncope may occur.
Dose:
Initial dose: 5 µg - 10 µg/minute, dose response, I.V., in infusion pump. Adjust the dose according to the 10.2. Treatment
hemodynamic response of the patient. In the event of an overdose of nitroglycerin or organic nitrates, the following protocol should be
followed: General
5.2. Maximum Dose:
procedure: - Suspend the administration of the drug
20 µg/minute.
- To counteract nitrate-related hypotension, place the patient in a horizontal position
5.3. special populations with legs elevated or if necessary a compression bandage on the patient's legs.
- Elderly patients: There is no evidence that dose adjustment is required in elderly patients. - Oxygen supply
- Pediatric population: Nitroglycerin is not recommended for use in children due to lack of data. - Plasma volume expanders (intravenous fluids)
- Specific treatment for shock (admit the patient to an intensive care unit)
5.4. Directions for use or method of administration
Special procedures:
This medication must be administered by infusion pump, it must not be mixed with other drugs
- Increase blood pressure if it is too low
and must be diluted after having analyzed the patient's fluid requirements taking into account the duration
- Additional administration of a vasoconstrictor, e.g. eg norepinephrine hydrochloride
expected from the infusion.
- Treatment of methemoglobinemia (treatment of choice with vitamin C,
6. ADVERSE REACTIONS methylene blue, or toluidine blue).
Adverse reactions have been classified by frequency as: - Administration of oxygen (if necessary) or Start artificial respiration
- Very common (>1/10) - Hemodialysis (if necessary).
- Common (>1/100, <1/10) - In cases of respiratory and circulatory arrest, initiate resuscitation measures
- Uncommon (>1/1000, <1/100) immediately.
- Rare (>1/10,000, <1/1,000)
- Very rare (<1/10,000)
- Frequency not known (reported during post-marketing use and in
laboratory data
Cardiovascular disorders: Rare: Tachycardia, orthostatic hypotension, flushing. Frequency not known:
Palpitation.
Gastrointestinal disorders: Common: Nausea, vomiting.
Nervous system disorders: Common: Headache, dizziness. Very rare: Dizziness.
Skin and subcutaneous tissue disorders: Uncommon:
Contact dermatitis, skin reactions
allergic type. Frequency not known: Widespread eruption
General disorders and administration site conditions: Uncommon: Application site
erythema, pruritus, burning.
Eye disorders: Uncommon: Increased intraocular pressure.
Complementary investigations: Rare: Increased frequency.
7. INTERACTIONS
7.1. With medicines, food and drinks
Concomitant treatment with other vasodilators, phosphodiesterase type 5 (PDE5) inhibitors such as Manufactured by: Zenith Healthcare LTD, India.
sildenafil, vardenafil or tadalafil, potentiate the hypotensive effect of nitroglycerin. The use of nitrites and Imported and Distributed by: Casa de
nitrates together with phosphodiesterase 5 (PDE5) inhibitors can cause cardiovascular complications
that put the life of the patient at risk. Interrupt treatment with nitroglycerin due to taking Representaciones JMW, C.A. Fixed Point - Venezuela.
Medications containing PDE5 inhibitors increase the risk of an angina episode.
chest. Patients receiving nitroglycerin therapy should not use PDE5 inhibitors. website:
aforementioned.