Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3893
Predicate | Object |
---|---|
rdf:type | |
rdfs:label |
Nitroglycerin (Injection, Solution, Concentrate)
|
dailymed-instance:dosage |
NOT FOR DIRECT INTRAVENOUS INJECTION. NITROGLYCERIN INJECTION, USP IS A CONCENTRATED, POTENT DRUG WHICH
MUST BE DILUTED IN 5% DEXTROSE INJECTION, USP OR 0.9% SODIUM CHLORIDE INJECTION,
USP, PRIOR TO ITS INFUSION. NITROGLYCERIN SHOULD NOT BE MIXED WITH OTHER DRUGS. 1. Initial Dilution: Aseptically transfer the
desired amount of Nitroglycerin Injection, USP (as noted in the table below)
into a glass I.V. bottle containing the stated volume of 5% Dextrose Injection,
USP or 0.9% Sodium Chloride Injection, USP and mix well. This yields a final
concentration of 50 mcg/mL to 400 mcg/mL. Diluting 5 mg nitroglycerin injection
into 100 mL will also yield a final concentration of 50 mcg/mL. 2. Maintenance Dilution: It is important to consider
the fluid requirements of the patient as well as the expected duration of
infusion in selecting the appropriate dilution of nitroglycerin injection. After
the initial dosage titration, the concentration of the admixture may be increased,
if necessary, to limit fluids given to the patient. The concentration of the
infusion solution should not exceed 400 mcg/mL of nitroglycerin. See chart. Note: If the concentration is adjusted, it is imperative
to flush or replace the infusion set before a new concentration is utilized.
If the set is not flushed or replaced, it could take minutes to hours, depending
upon the flow rate and the dead space of the set, for the concentration to
reach the patient. Invert the glass parenteral bottle
several times to assure uniform dilution of nitroglycerin. Dosage
is affected by the type of container and administration set used. See WARNINGS. Although
the usual starting adult dose range reported in clinical studies was 25 mcg/min
or more, these studies used PVC administration sets. THE USE OF NONABSORBING
TUBING WILL RESULT IN THE NEED FOR REDUCED DOSES. If
a peristaltic action infusion pump is used, an appropriate administration
set should be selected with a drip chamber that delivers approximately 60
microdrops/mL. The dilution and administration tables below may be used to
calculate the nitroglycerin dilution and flow rate in microdrops/minute to
achieve the desired nitroglycerin injection administration rate. If
a volumetric infusion pump is used, the dilution and administration table
below may still be used; however, flow rate will be determined directly by
the infusion pump independent of the drop size of the drop chambers. Thus,
the reference to���microdrops/min���is not applicable, and the
corresponding flow rate in the mL/hr should be used to determine pump settings. The
dosage for nitroglycerin should initially be 5 mcg/min delivered through an
infusion pump capable of exact and constant delivery of the drug. Subsequent
titration must be adjusted to the clinical situation, with dose increments
becoming more cautious as partial response is seen. Initial titration should
be in 5 mcg/min increments, with increases every 3 to 5 minutes until some
response is noted. If no response is seen at 20 mcg/min, increments of 10
and later 20 mcg/min can be used. Once a partial blood pressure response is
observed, the dose increase should be reduced and the interval between increments
should be lengthened. Patients with normal or low left
ventricular filling pressure or pulmonary capillary wedge pressure (e.g.,
angina patients without other complications) may be hypersensitive to the
effects of nitroglycerin and may respond fully to doses as small as 5 mcg/min.
These patients require especially careful titration and monitoring. There
is no fixed optimum dose of nitroglycerin. Due to variations in the responsiveness
of individual patients to the drug, each patient must be titrated to the desired
level of hemodynamic function. Therefore, continuous monitoring of physiologic
parameters (i.e., blood pressure and heart rate in all patients, other measurements
such as pulmonary capillary wedge pressure, as appropriate) MUST be performed
to achieve the correct dose. Adequate systemic blood pressure and coronary
perfusion pressure must be maintained. Parenteral drug
products should be inspected visually for particulate matter and discoloration
prior to administration, whenever solution and container permit. Discard unused
portion. 60 microdrops = 1 mL
|
dailymed-instance:descripti... |
Nitroglycerin is 1,2,3-propanetriol trinitrate, an organic
nitrate whose structural formula is: CHNOMol. weight 227.09 The organic nitrates are vasodilators,
active on both arteries and veins. Nitroglycerin Injection,
USP is a clear, practically colorless additive solution for intravenous infusion
after dilution. Each mL contains: 5 mg nitroglycerin, in a vehicle of 50%
v/v dehydrated alcohol and 50% v/v propylene glycol. The
solution is sterile, nonpyrogenic, and nonexplosive.
|
dailymed-instance:clinicalP... |
The principal pharmacological action of nitroglycerin is
relaxation of vascular smooth muscle and consequent dilatation of peripheral
arteries and veins, especially the latter. Dilatation of the veins promotes
peripheral pooling of blood and decreases venous return to the heart, thereby
reducing left ventricular end-diastolic pressure and pulmonary capillary wedge
pressure (preload). Arteriolar relaxation reduces systemic vascular resistance,
systolic arterial pressure, and mean arterial pressure (afterload). Dilatation
of the coronary arteries also occurs. The relative importance of preload reduction,
afterload reduction, and coronary dilatation remains undefined. Dosing
regimens for most chronically used drugs are designed to provide plasma concentrations
that are continuously greater than a minimally effective concentration. This
strategy is inappropriate for organic nitrates. Several well-controlled clinical
trials have used exercise testing to assess the anti-anginal efficacy of continuously-delivered
nitrates. In the large majority of these trials, active agents were indistinguishable
from placebo after 24 hours (or less) of continuous therapy. Attempts to overcome
nitrate tolerance by dose escalation, even to doses far in excess of those
used acutely, have consistently failed. Only after nitrates have been absent
from the body for several hours has their anti-anginal efficacy been restored. Pharmacokinetics: The volume of distribution of
nitroglycerin is about 3 L/kg, and nitroglycerin is cleared from this volume
at extremely rapid rates, with a resulting serum half-life of about 3 minutes.
The observed clearance rates (close to 1 L/kg/min) greatly exceed hepatic
blood flow; known sites of extrahepatic metabolism include red blood cells
and vascular walls. The first products in the metabolism
of nitroglycerin are inorganic nitrate and the 1,2- and 1,3-dinitroglycerols.
The dinitrates are less effective vasodilators than nitroglycerin, but they
are longer-lived in the serum, and their net contribution to the overall effect
of chronic nitroglycerin regimens is not known. The dinitrates are further
metabolized to (nonvasoactive) mononitrates and, ultimately, to glycerol and
carbon dioxide. To avoid development of tolerance to
nitroglycerin, drug-free intervals of 10 to 12 hours are known to be sufficient;
shorter intervals have not been well studied. In one well-controlled clinical
trial, subjects receiving nitroglycerin appeared to exhibit a rebound or withdrawal
effect, so that their exercise tolerance at the end of the daily drug-free
interval was less than that exhibited
by the parallel group receiving placebo. Clinical
Trials: Blinded, placebo-controlled trials of intravenous nitroglycerin
have not been reported, but multiple investigators have reported open-label
studies, and there are scattered reports of studies in which intravenous nitroglycerin
was tested in blinded fashion against sodium nitroprusside. In
each of these studies, therapeutic doses of intravenous nitroglycerin were
found to reduce systolic and diastolic arterial blood pressure. The heart
rate was usually increased, presumably as a reflexive response to the fall
in blood pressure. Coronary perfusion pressure was usually, but not always,
maintained. Intravenous nitroglycerin reduced central
venous pressure (CVP), right atrial pressure (RAP), pulmonary arterial pressure
(PAP), pulmonary-capillary wedge pressure (PCWP), pulmonary vascular resistance
(PVR), and systemic vascular resistance (SVR). When these parameters were
elevated, reducing them toward normal usually caused a rise in cardiac output.
Conversely, intravenous nitroglycerin usually reduced cardiac output when it was given to patients whose CVP, RAP, PAP,
PCWP, PVR, and SVR were all normal. Most clinical trials
of intravenous nitroglycerin have been brief; they have typically followed
hemodynamic parameters during a single surgical procedure. In one careful
study, one of the few that lasted more than a few hours, continuous intravenous
nitroglycerin had lost almost all of its hemodynamic effect after 48 hours.
In the same study, patients who received nitroglycerin infusions for only
12 hours out of each 24 demonstrated no similar attenuation of effect. These
results are consistent with those seen in multiple large, double-blind, placebo-controlled
trials of other formulations of nitroglycerin and other nitrates.
|
dailymed-instance:activeIng... | |
dailymed-instance:contraind... |
Allergic reactions to organic nitrates are extremely rare,
but they do occur. Nitroglycerin Injection is contraindicated in patients
who are allergic to it. In patients with pericardial
tamponade, restrictive cardiomyopathy, or constrictive pericarditis, cardiac
output is dependent upon venous return. Intravenous nitroglycerin is contraindicated
in patients with these conditions.
|
dailymed-instance:supply |
Store at 20 to 25��C (68 to 77��F). [See USP Controlled
Room Temperature.] Do not permit to freeze. Protect from light by retaining product in carton until ready
to use. ��Hospira
2004 EN-0569 Printed in USA HOSPIRA, INC., LAKE FOREST,
IL 60045 USA
|
dailymed-instance:genericDr... | |
dailymed-instance:activeMoi... | |
dailymed-instance:inactiveI... | |
dailymed-instance:possibleD... | |
dailymed-instance:precautio... |
General:: Severe hypotension and shock may occur with even small doses
of nitroglycerin. This drug should therefore be used with caution in patients
who may be volume depleted or who, for whatever reason, are already hypotensive.
Hypotension induced by nitroglycerin may be accompanied by paradoxical bradycardia
and increased angina pectoris. Nitrate therapy may aggravate
the angina caused by hypertrophic cardiomyopathy. As
tolerance to other forms of nitroglycerin develops, the effect of sublingual
nitroglycerin on exercise tolerance, although still observable, is somewhat
blunted. In industrial workers who have had long-term
exposure to unknown (presumably high) doses of organic nitrates, tolerance
clearly occurs. Chest pain, acute myocardial infarction, and even sudden death
have occurred during temporary withdrawal of nitrates from these workers,
demonstrating the existence of true physical dependence. Some
clinical trials in angina patients have provided nitroglycerin for about 12
continuous hours of every 24-hour day. During the nitrate-free intervals in
some of these trials, anginal attacks have been more easily provoked than
before treatment, and patients have demonstrated hemodynamic rebound and decreased exercise tolerance. The importanceof these observations to the routine, clinical use of intravenous nitroglycerin
is not known. Lower concentrations of nitroglycerin
increase the potential precision of dosing, but these concentrations increase
the total fluid volume that must be delivered to the patient. Total fluid
load may be a dominant consideration in patients with compromised function
of the heart, liver, and/or kidneys. Nitroglycerin infusions
should be administered only via a pump that can maintain a constant infusion
rate. Intracoronary injection of nitroglycerin infusions
has not been studied.<br/>Laboratory Tests:: Because of the propylene glycol content of intravenous nitroglycerin,
serum triglyceride assays that rely on glycerol oxidase may give falsely elevated
results in patients receiving this medication.<br/>Drug Interactions:: The vasodilating effects of nitroglycerin may be additive
with those of other vasodilators. Administration of
nitroglycerin infusions through the same infusion set as blood can result
in pseudoagglutination and hemolysis. More generally, nitroglycerin in 5%
dextrose or sodium chloride 0.9% should not be mixed with any other medication
of any kind. Intravenous nitroglycerin interferes, at
least in some patients, with the anticoagulant effect of heparin. In patients
receiving intravenous nitroglycerin, concomitant heparin therapy should be
guided by frequent measurement of the activated partial thromboplastin time.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility:: Animal carcinogenesis studies with injectable nitroglycerin
have not been performed. Rats receiving up to 434 mg/kg/day
of dietary nitroglycerin for 2 years developed dose-related fibrotic and neoplastic
changes in liver, including carcinomas, and interstitial cell tumors in testes.
At high dose, the incidences of hepatocellular carcinomas in both sexes were
52% vs. 0% in controls, and incidences of testicular tumors were 52% vs. 8%
in controls. Lifetime dietary administration of up to 1058 mg/kg/day of nitroglycerin
was not tumorigenic in mice. Nitroglycerin was weakly
mutagenic in Ames tests performed in two different laboratories. There was
no evidence of mutagenicity in an in vivo dominant
lethal assay with male rats treated with doses up to about 363 mg/kg/day,
p.o., or in in vitro cytogenetic tests
in rat and dog tissues. In a three-generation reproduction
study, rats received dietary nitroglycerin at doses up to about 434 mg/kg/day
for six months prior to mating of the Fgeneration with treatment
continuing through successive Fand Fgenerations.
The high-dose was associated with decreased feed intake and body weight gain
in both sexes at all matings. No specific effect on the fertility of the Fgeneration
was seen. Infertility noted in subsequent generations, however, was attributed
to increased interstitial cell tissue and aspermatogenesis in the high dose
males. In this three-generation study there was no clear evidence of teratogenicity.<br/>Pregnancy:: Pregnancy Category C: Animal
teratology studies have not been conducted with nitroglycerin injection. Teratology
studies in rats and rabbits, however, were conducted with topically applied
nitroglycerin ointment at doses up to 80 mg/kg/day and 240 mg/kg/day, respectively.
No toxic effects on dams or fetuses were seen at any dose tested. There are
no adequate and well-controlled studies in pregnant women. Nitroglycerin should
be given to a pregnant woman only if clearly needed.<br/>Nursing Mothers:: It is not known whether nitroglycerin is excreted in human
milk. Because many drugs are excreted in human milk, caution should be exercised
when nitroglycerin injection is administered to a nursing woman.<br/>Pediatric Use:: The safety and effectiveness of nitroglycerin injection in
pediatric patients have not been established.
|
dailymed-instance:overdosag... |
Hemodynamic Effects: The
ill effects of nitroglycerin overdose are generally the results of nitroglycerin's
capacity to induce vasodilatation, venous pooling, reduced cardiac output,
and hypotension. These hemodynamic changes may have protean manifestations,
including increased intracranial pressure, with any or all of persistent throbbing
headache, confusion, and moderate fever; vertigo; palpitation; visual disturbances;
nausea and vomiting (possibly with colic and even bloody diarrhea); syncope
(especially in the upright posture); air hunger and dyspnea,later followed
by reduced ventilatory effort; diaphoresis, with the skin either flushed or
cold and clammy; heart block and bradycardia; paralysis; coma; seizures; and
death. Laboratory determinations of serum levels of
nitroglycerin and its metabolites are not widely available, and such determinations
have, in any event, no established role in the management of nitroglycerin
overdose. No data are available to suggest physiological
maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate
elimination of nitroglycerin and its active metabolites. Similarly, it is
not known which���if any���of these substances can usefully be removed
from the body by hemodialysis. No specific antagonist
to the vasodilator effects of nitroglycerin is known, and no intervention
has been subject to controlled study as a therapy of nitroglycerin overdose.
Because the hypotension associated with nitroglycerin overdose is the result
of venodilatation and arterial hypovolemia, prudent therapy in this situation
should be directed toward increase in central fluid volume. Passive elevation
of the patient's legs may be sufficient, but intravenous infusion of
normal saline or similar fluid may also be necessary. The
use of epinephrine or other arterial vasoconstrictors in this setting is likely
to do more harm than good. In patients with renal disease
or congestive heart failure, therapy resulting in central volume expansion
is not without hazard. Treatment of nitroglycerin overdose in these patients
may be subtle and difficult, and invasive monitoring may be required. Methemoglobinemia: Nitrate ions liberated during
metabolism of nitroglycerin can oxidize hemoglobin into methemoglobin. Even
in patients totally without cytochrome breductase activity, however,
and even assuming that the nitrate moieties of nitroglycerin are quantitatively
applied to oxidation of hemoglobin, about 1 mg/kg of nitroglycerin should
be required before any of these patients manifests clinically significant
(���10%) methemoglobinemia. In patients with normal reductase function,
significant production of methemoglobin should require even larger doses of
nitroglycerin. In one study in which 36 patients received 2 to 4 weeks of
continuous nitroglycerin therapy at 3.1 to 4.4 mg/hr, the average methemoglobin
level measured was 0.2%; this was comparable to that observed in parallel
patients who received placebo. Notwithstanding these
observations, there are case reports of significant methemoglobinemia in association
with moderate overdoses of organic nitrates. None of the affected patients
have been thought to be unusually susceptible. Methemoglobin
levels are available from most clinical laboratories. The diagnosis should
be suspected in patients who exhibit signs of impaired oxygen delivery despite
adequate cardiac output and adequate arterial pO. Classically,
methemoglobinemic blood is described as chocolate brown, without color change
on exposure to air. When methemoglobinemia is diagnosed,
the treatment of choice is methylene blue, 1 to 2 mg/kg intravenously.
|
dailymed-instance:genericMe... |
Nitroglycerin
|
dailymed-instance:fullName |
Nitroglycerin (Injection, Solution, Concentrate)
|
dailymed-instance:adverseRe... |
Adverse reactions to nitroglycerin are generally dose-related
and almost all of these reactions are the result of nitroglycerin's
activity as a vasodilator. Headache, which may be severe, is the most commonly
reported side effect. Headache may be recurrent with each daily dose, especially
at higher doses. Transient episodes of lightheadedness, occasionally related
to blood pressure changes, may also occur. Hypotension occurs infrequently,
but in some patients it may be severe enough to warrant discontinuation of
therapy. Syncope, crescendo angina, and rebound hypertension have been reported
but are uncommon. Allergic reactions to nitroglycerin
are also uncommon, and the great majority of those reported have been cases
of contact dermatitis or fixed drug eruptions in patients receiving nitroglycerin
in ointments or patches. There have been a few reports of genuine anaphylactoid
reactions, and these reactions can probably occur in patients receiving nitroglycerin
by any route. Extremely rarely, ordinary doses of organic
nitrates have caused methemoglobinemia in normal-seeming patients. Methemoglobinemia
is so infrequent at these doses that further discussion of its diagnosis and
treatment is deferred (see OVERDOSAGE). Data are not
available to allow estimation of the frequency of adverse reactions during
treatment with nitroglycerin injection.
|
dailymed-instance:warning |
Amplification of the vasodilatory
effects of nitroglycerin by sildenafil can result in severe hypotension. The
time course and dose dependence of this interaction have not been studied.
Appropriate supportive care has not been studied, but it seems reasonable
to treat this as a nitrate overdose, with elevation of the extremities and
with volume expansion. Nitroglycerin readily
migrates into many plastics, including the polyvinyl-chloride (PVC) plastics
commonly used for intravenous administration sets. Nitroglycerin absorption
by PVC tubing is increased when the tubing is long, the flow rates are low,
and the nitroglycerin concentration of the solution is high. The delivered
fraction of the solution's original nitroglycerin content has been
20-60% in published studies using PVC tubing; the fraction varies with time
during a single infusion, and no simple correction factor can be used. PVC
tubing has been used in most published studies of intravenous nitroglycerin,
but the reported doses have been calculated by simply multiplying the flow
rate of the solution by the solution's original concentration of nitroglycerin. The actual doses delivered have been less, sometimes much
less, than those reported. Some in-line intravenous filters also
absorb nitroglycerin; these filters should be avoided. Because
of the absorption problem, Hospira, Inc. non-PVC infusion tubing was developed
to minimize the loss of nitroglycerin. Hospira, Inc. Nitroglycerin I.V. Pump
Set or similar infusion sets are recommended for infusions of nitroglycerin
(see DOSAGE AND ADMINISTRATION). DOSING INSTRUCTIONS
MUST BE FOLLOWED WITH CARE. WHEN THE APPROPRIATE INFUSION SETS ARE USED, THE
CALCULATED DOSE WILL BE DELIVERED TO THE PATIENT, BECAUSE THE LOSS OF NITROGLYCERIN
INJECTION SEEN WITH STANDARD PVC TUBING WILL BE AVOIDED. THE DOSAGES REPORTED
IN PUBLISHED STUDIES UTILIZED GENERAL-USE PVC ADMINISTRATION SETS, AND RECOMMENDED
DOSES BASED ON THIS EXPERIENCE WILL BE TOO HIGH IF THE LOW-ABSORBING INFUSION
SETS ARE USED.
|
dailymed-instance:indicatio... |
Nitroglycerin Injection, USP is indicated for treatment of
perioperative hypertension; for control of congestive heart failure in the
setting of acute myocardial infarction; for treatment of angina pectoris in
patients who have not responded to sublingual nitroglycerin and��-blockers;
and for induction of intraoperative hypotension.
|
dailymed-instance:represent... | |
dailymed-instance:routeOfAd... | |
dailymed-instance:name |
Nitroglycerin
|