Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/2190
Predicate | Object |
---|---|
rdf:type | |
rdfs:label |
Milrinone Lactate in Dextrose (Injection)
|
dailymed-instance:dosage |
Milrinone should be
administered with a loading dose followed by a continuous infusion
(maintenance dose) according to the following guidelines:<br/>Loading Dose: 50 mcg/kg:
Administer slowly over 10 minutes Note:
Milrinone (200 mcg/mL) in INTRAVIA Plastic Container is for
intravenous infusion only. Dosage
recommendations using a 1 mg/mL concentration of milrinone are
included for informational purposes only. The table
below shows the loading dose in milliliters (mL) of milrinone
(1mg/mL) by patient body weight (kg). The loading
dose may be given undiluted, but diluting to a rounded total
volume of 10 or 20 mL (see appropriate package insert for
diluents) may simplify the visualization of the injection
rate.<br/>Maintenance Dose: The
infusion rate should be adjusted according to hemodynamic and
clinical response. Patients should be closely monitored. In
controlled clinical studies, most patients showed an improvement
in hemodynamic status as evidenced by increases in cardiac
output and reductions in pulmonary capillary wedge pressure. Note: See
"Dosage Adjustment in Renally
Impaired Patients." Dosage may be titrated to the
maximum hemodynamic effect and should not exceed 1.13 mg/kg/day.
Duration of therapy should depend upon patient responsiveness. The
maintenance dose in mL/hr by patient body weight (kg) may be
determined by reference to the following table<br/>Dosage Adjustment
in Renally Impaired Patients: Data
obtained from patients with severe renal impairment (creatinine
clearance = 0 to 30 mL/min) but without congestive heart failure
have demonstrated that the presence of renal impairment
significantly increases the terminal elimination half-life of
milrinone. Reductions in infusion rate may be necessary in
patients with renal impairment. For patients with clinical
evidence of renal impairment, the recommended infusion rate can
be obtained from the following table: Parenteral
drug products should be inspected visually for particulate
matter and discoloration prior to administration, whenever
solution and container permit. Milrinone Lactate in 5% Dextrose
Injection is a clear, colorless to pale yellow
solution.
|
dailymed-instance:descripti... |
Milrinone lactate
is a member of a new class of bipyridine inotropic/vasodilator agents
with phosphodiesterase inhibitor activity, distinct from digitalis
glycosides or catecholamines. Milrinone lactate is designated chemically
as 1,6-dihydro-2-methyl-6-oxo-[3,4'-bipyridine]-5-carbonitrile
lactate and has the following structure: Milrinone is an
off-white to tan crystalline compound with a molecular weight of 211.2
and a molecular formula of CHNO. It is slightly soluble in methanol,
and very slightly soluble in chloroform and in water. As the lactate
salt, it is stable and colorless to pale yellow in solution. Milrinone
is available as sterile aqueous solutions of the lactate salt of
milrinone for infusion intravenously. The flexible containers provide
two ready-to-use dilutions of milrinone in volumes of 100 mL and 200 mL
of 5% Dextrose Injection. Each mL contains milrinone lactate equivalent
to 200 mcg milrinone. The nominal concentration of lactic acid is 0.282
mg/mL. Each mL also contains 54.3 mg Dextrose Hydrous, USP. The pH is
adjusted with lactic acid and/or sodium hydroxide pH 3.5 (3.2 - 4.0).
The flexible container is manufactured from a specially designed
multilayer plastic (PL 2408). Solutions in contact with the plastic
container leach out certain chemical components from the plastic in very
small amounts; however, biological testing was supportive of the safety
of the plastic container materials. The flexible container has a foil
overwrap. Water can permeate the plastic into the overwrap, but theamount is insufficient to significantly affect the premixed
solution.
|
dailymed-instance:clinicalP... |
Milrinone is a
positive inotrope and vasodilator, with little chronotropic activity
different in structure and mode of action from either the digitalis
glycosides or catecholamines. Milrinone, at relevant inotropic and
vasorelaxant concentrations, is a selective inhibitor of peak III cAMP
phosphodiesterase isozyme in cardiac and vascular muscle. This
inhibitory action is consistent with cAMP mediated increases in
intracellular ionized calcium and contractile force in cardiac muscle,
as well as with cAMP dependent contractile protein phosphorylation and
relaxation in vascular muscle. Additional experimental evidence also
indicates that milrinone is not a beta-adrenergic agonist nor does it
inhibit sodium-potassium adenosine triphosphatase activity as do the
digitalis glycosides. Clinical studies in
patients with congestive heart failure have shown that milrinone
produces dose-related and plasma drug concentration-related increases in
the maximum rate of increase of left ventricular pressure. Studies in
normal subjects have shown that milrinone produces increases in the
slope of the left ventricular pressure-dimension relationship,
indicating a direct inotropic effect of the drug. Milrinone also
produces dose-related and plasma concentration-related increases in
forearm blood flow in patients with congestive heart failure, indicating
a direct arterial vasodilator activity of the drug. Both the inotropic
and vasodilatory effects have been observed over the therapeutic range
of plasma milrinone concentrations of 100 ng/mL to 300 ng/mL. In addition to
increasing myocardial contractility, milrinone improves diastolic
function as evidenced by improvements in left ventricular diastolic
relaxation. The acute
administration of intravenous milrinone has also been evaluated in
clinical trials in excess of 1600 patients, with chronic heart failure,
heart failure associated with cardiac surgery, and heart failure
associated with myocardial infarction. The total number of deaths,
either on therapy or shortly thereafter (24 hours) was 15, less than
0.9%, few of which were thought to be drug-related.
|
dailymed-instance:activeIng... | |
dailymed-instance:contraind... |
Milrinone is
contraindicated in patients who are hypersensitive to it. Solutions
containing dextrose may be contraindicated in patients with known
allergy to corn or corn products.
|
dailymed-instance:supply |
Baxter's
Milrinone Lactate in 5% Dextrose Injection is supplied in INTRAVIA
Plastic Container as follows: Exposure of
pharmaceutical products to heat should be minimized. Avoid excessive
heat. Protect from freezing. It is recommended that the product be
stored at room temperature, 25��C (77��F); however,
brief exposure up to 40��C (104��F) does not adversely
affect the product. Baxter Healthcare Corporation Deerfield, IL 60015
USA Printed in USA BAXTER and INTRAVIA
are trademarks of Baxter International Inc. 07-19-54-485,
September 2007
|
dailymed-instance:activeMoi... | |
dailymed-instance:inactiveI... | |
dailymed-instance:precautio... |
General: Milrinone
should not be used in patients with severe obstructive aortic or
pulmonic valvular disease in lieu of surgical relief of the
obstruction. Like other inotropic agents, it may aggravate
outflow tract obstruction in hypertrophic subaortic stenosis. Supraventricular and ventricular arrhythmias have been observed
in the high-risk population treated. In some patients,
injections of milrinone and oral milrinone have been shown to
increase ventricular ectopy, including nonsustained ventricular
tachycardia. The potential for arrhythmia, present in congestive
heart failure itself, may be increased by many drugs or
combinations of drugs. Patients receiving milrinone should be
closely monitored during infusion. Milrinone
produces a slight shortening of AV node conduction time,
indicating a potential for an increased ventricular response
rate in patients with atrial flutter/fibrillation which is not
controlled with digitalis therapy. During
therapy with milrinone, blood pressure and heart rate should be
monitored and the rate of infusion slowed or stopped in patients
showing excessive decreases in blood pressure. If prior vigorous
diuretic therapy is suspected to have caused significant
decreases in cardiac filling pressure, milrinone should be
cautiously administered with monitoring of blood pressure, heart
rate, and clinical symptomatology. There is no
experience in controlled trials with infusions of milrinone for
periods exceeding 48 hours. Cases of infusion site reaction have
been reported with intravenous milrinone therapy (see ADVERSE
REACTIONS). Consequently, careful monitoring of
the infusion site should be maintained to avoid possible
extravasation.<br/>Use in Acute
Myocardial Infarction: No clinical
studies have been conducted in patients in the acute phase of
post myocardial infarction. Until further clinical experience
with this class of drugs is gained, milrinone is not recommended
in these patients.<br/>Laboratory Tests: Fluid and electrolytes: Fluid and
electrolyte changes and renal function should be carefully
monitored during therapy with milrinone. Improvement in cardiac
output with resultant diuresis may necessitate a reduction in
the dose of diuretic. Potassium loss due to excessive diuresis
may predispose digitalized patients to arrhythmias. Therefore,
hypokalemia should be corrected by potassium supplementation in
advance of or during use of milrinone.<br/>Drug Interactions: No untoward
clinical manifestations have been observed in limited experience
with patients in whom milrinone was used concurrently with the
following drugs: digitalis glycosides; lidocaine, quinidine;
hydralazine, prazosin; isosorbide dinitrate, nitroglycerin;
chlorthalidone, furosemide, hydrochlorothiazide, spironolactone;
captopril; heparin, warfarin, diazepam, insulin; and potassium
supplements.<br/>Chemical
Interactions: There is an
immediate chemical interaction which is evidenced by the
formation of a precipitate when furosemide is injected into an
intravenous line of an infusion of milrinone. Therefore,
furosemide should not be administered in intravenous lines
containing milrinone<br/>Carcinogenesis and
Mutagenesis and Impairment of Fertility: Twenty-four
months of oral administration of milrinone to mice at doses up
to 40 mg/kg/day (about 50 times the human oral therapeutic dose
in a 50 kg patient) was unassociated with evidence of
carcinogenic potential. Neither was there evidence of
carcinogenic potential when milrinone was orally administered to
rats at doses up to 5 mg/kg/day (about 6 times the human oral
therapeutic dose) for twenty-four months or at 25 mg/kg/day
(about 30 times the human oral therapeutic dose) for up to 18
months in males and 20 months in females. Whereas the Chinese
Hamster Ovary Chromosome Aberration Assay was positive in the
presence of a metabolic activation system, results from the Ames
Test, the Mouse Lymphoma Assay, the Micronucleus Test, and the
in vivo Rat Bone Marrow Metaphase Analysis indicated an absence
of mutagenic potential. In reproductive performance studies in
rats, milrinone had no effect on male or female fertility at
oral doses up to 32 mg/kg/day.<br/>Animal Toxicity: Oral and
intravenous administration of toxic dosages of milrinone to rats
and dogs resulted in myocardial degeneration/fibrosis and
endocardial hemorrhage, principally affecting the left
ventricular papillary muscles. Coronary vascular lesions
characterized by periarterial edema and inflammation have been
observed in dogs only. The myocardial/endocardial changes are
similar to those produced by beta-adrenergic receptor agonists
such as isoproterenol, while the vascular changes are similar to
those produced by minoxidil and hydralazine. Doses within the
recommended clinical dose range (up to 1.13 mg/kg/day) for
congestive heart failure patients have not produced significant
adverse effects in animals.<br/>Pregnancy Category
C: Oral
administration of milrinone to pregnant rats and rabbits during
organogenesis produced no evidence of teratogenicity at dose
levels up to 40 mg/kg/day and 12 mg/kg/day, respectively.
Milrinone did not appear to be teratogenic when administered
intravenously to pregnant rats at doses up to 3 mg/kg/day (about
2.5 times the maximum recommended clinical intravenous dose) or
pregnant rabbits at doses up to 12 mg/kg/day, although an
increased resorption rate was apparent at both 8 mg/kg/day and
12 mg/kg/day (intravenous) in the latter species. There are no
adequate and well-controlled studies in pregnant women.
Milrinone should be used during pregnancy only if the potential
benefit justifies the potential risk to the fetus.<br/>Nursing Mothers: Caution
should be exercised when milrinone is administered to nursing
women, since it is not known whether it is excreted in human
milk.<br/>Pediatric Use: Safety and
effectiveness in pediatric patients have not been
established.<br/>Use in Elderly
Patients: There are
no special dosage recommendations for the elderly patient.
Ninety percent of all patients administered milrinone in
clinical studies were within the age range of 45 to 70 years,
with a mean age of 61 years. Patients in all age groups
demonstrated clinically and statistically significant responses.
No age-related effects on the incidence of adverse reactions
have been observed. Controlled pharmacokinetic studies have not
disclosed any age-related effects on the distribution and
elimination of milrinone.
|
dailymed-instance:overdosag... |
Doses of milrinone
may produce hypotension because of its vasodilator effect. If this
occurs, administration of milrinone should be reduced or temporarily
discontinued until the patient's condition stabilizes. No
specific antidote is known, but general measures for circulatory supportshould be taken.
|
dailymed-instance:genericMe... |
Milrinone Lactate
|
dailymed-instance:fullName |
Milrinone Lactate in Dextrose (Injection)
|
dailymed-instance:adverseRe... |
Cardiovascular
Effects: In patients
receiving milrinone in Phase II and III clinical trials,
ventricular arrhythmias were reported in 12.1%: Ventricular
ectopic activity, 8.5%; nonsustained ventricular tachycardia,
2.8%; sustained ventricular tachycardia, 1% and ventricular
fibrillation, 0.2% (2 patients experienced more than one type of
arrhythmia). Holter recordings demonstrated that in some
patients injection of milrinone increased ventricular ectopy,
including nonsustained ventricular tachycardia. Life-threatening
arrhythmias were infrequent and when present have been
associated with certain underlying factors such as preexisting
arrhythmias, metabolic abnormalities (e.g. hypokalemia),
abnormal digoxin levels and catheter insertion. Milrinone was
not shown to be arrhythmogenic in an electrophysiology study.
Supraventricular arrhythmias were reported in 3.8% of the
patients receivingmilrinone. The incidence of both
supraventricular and ventricular arrhythmias has not been
related to the dose or plasma milrinone concentration. Other
cardiovascular adverse reactions include hypotension, 2.9% and
angina/chest pain, 1.2%. In the
post-marketing experience, there have been rare cases of���torsades de pointes���reported.<br/>CNS Effects: Headaches,
usually mild to moderate in severity, have been reported in 2.9%
of patients receiving milrinone.<br/>Other Effects: Other
adverse reactions reported, but not definitely related to the
administration of milrinone include hypokalemia, 0.6%; tremor,
0.4%; and thrombocytopenia, 0.4%.<br/>Post-Marketing
Adverse Event Reports: In addition
to adverse events reported from clinical trials, the following
events have been reported from worldwide post-marketing
experience with Milrinone: Isolated
spontaneous reports of bronchospasm and anaphylactic shock. Liver
function test abnormalities and skin reactions such as rash. Administration site conditions: Infusion site
reaction.
|
dailymed-instance:warning |
Whether given orally or by continuous or
intermittent intravenous infusion, milrinone has not been shown to
be safe or effective in the longer (greater than 48 hours) treatment
of patients with heart failure. In a multicenter trial of 1088
patients with Class III and IV heart failure, long-term oral
treatment with milrinone was associated with no improvement in
symptoms and an increased risk of hospitalization and death. In this
study, patients with Class IV symptoms appeared to be at particular
risk of life-threatening cardiovascular reactions. There is no
evidence that milrinone given by long-term continuous or
intermittent infusion does not carry a similar risk. The use of milrinone both intravenously and
orally has been associated with increased frequency of ventricular
arrhythmias, including nonsustained ventricular tachycardia.
Long-term oral use has been associated with an increased risk of
sudden death. Hence, patients receiving milrinone should be observed
closely with the use of continuous electrocardiographic monitoring
to allow the prompt detection and management of ventricular
arrhythmias.
|
dailymed-instance:indicatio... |
Milrinone is
indicated for the short-term intravenous treatment of patients with
acute decompensated heart failure. Patients receiving milrinone should
be observed closely with appropriate electrocardiographic equipment. The
facility for immediate treatment of potential cardiac events, which may
include life-threatening ventricular arrythmias, must be available. The
majority of experience with intravenous milrinone has been in patients
receiving digoxin and diuretics. There is no experience in controlledtrials with infusions of milrinone for periods exceeding 48
hours.
|
dailymed-instance:represent... | |
dailymed-instance:routeOfAd... | |
dailymed-instance:name |
Milrinone Lactate in Dextrose
|