Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/2984
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Tilade (Aerosol, Metered)
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| dailymed-instance:dosage |
The recommended dosage for adult and pediatric patients
6 years of age and older is two inhalations four times a day at regular intervals,
which provides a dose of 14 mg per day. In patients whose asthma is well controlled
on this dosage (e.g., patients who
only need occasional inhaled or oral beta-agonists and who are
not experiencing serious exacerbations), less frequent administration may
be effective. Each Tilade
Inhaler canister must be primed with 3 actuations prior to the
first use. If a canister remains unused for more than 7 days, then it should
be reprimed with 3 actuations. Tilade
Inhaler may be added to the patient's existing treatment
regimen (e.g., bronchodilators). When
a clinical response to Tilade Inhaler
is evident and if the patient's asthma is under good control, an attempt
may be made to decrease concomitant medication usage gradually. Proper
inhalational technique is essential (see Patient Instructions for Use). Patientsshould be advised that the optimal effect of Tilade
therapy depends upon its administration at regular intervals, even
during symptom-free periods.
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| dailymed-instance:descripti... |
Tilade (nedocromil sodium)
is an inhaled anti-inflammatory agent for the preventive management of asthma.
Nedocromil sodium is a pyranoquinoline with the chemical name 4H
-Pyrano[3,2-g]quinoline-2,8-dicarboxylic
acid, 9-ethyl-6,9-dihydro-4,6-dioxo-10- propyl-, disodium salt, and it has
a molecular weight of 415.3. The empirical formula is CHNNaO.
Nedocromil sodium, a yellow powder, is soluble in water. The
molecular structure of nedocromil sodium is: Chemical Class: Pyranoquinoline Tilade Inhaler (nedocromil sodium inhalation aerosol)
is a pressurized metered-dose aerosol suspension for oral inhalation containing
micronized nedocromil sodium and sorbitan trioleate, as well as dichlorotetrafluoro
ethane and dichlorodifluoromethane as propellants. Each Tilade
canister contains 210 mg nedocromil sodium. Each actuation meters
2.00 mg nedocromil sodium from the valve and delivers 1.75 mg nedocromil sodium
from the mouthpiece. Each 16.2 g canister provides at least 104 metered actuations. After 104 metered actuations, the amount delivered per actuation
may not be consistent and the unit should be discarded. Each Tilade Inhaler canister must be primed with 3 actuations
prior to the first use. If a canister remains unused for more than 7 days,
then it should be reprimed with 3 actuations.
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| dailymed-instance:clinicalP... |
General: Nedocromil sodium
has been shown to inhibit the in vitro activation
of, and mediator release from, a variety of inflammatory cell types associated
with asthma, including eosinophils, neutrophils, macrophages, mast cells,
monocytes, and platelets. In vitro studies
on cells obtained by bronchoalveolar lavage from antigen-sensitized macaque
monkeys show that nedocromil sodium inhibits the release of mediators including
histamine, leukotriene C, and prostaglandin D. Similar
studies with human bronchoalveolar cells showed inhibition of histamine release
from mast cells and beta-glucuronidase release from macrophages. Nedocromil
sodium has been tested in experimental models of asthma using allergic animals
and shown to inhibit the development of early and late bronchoconstriction
responses to inhaled antigen. The development of airway hyper-responsiveness
to nonspecific bronchoconstrictors was also inhibited. Nedocromil sodium reduced
antigen-induced increases in airway microvasculature leakage when administered
intravenously in a model system. In humans, nedocromil
sodium has been shown to inhibit acutely the bronchoconstrictor response to
several kinds of challenge. Pretreatment with single doses of nedocromil sodium
inhibited the bronchoconstriction caused by sulfur dioxide, inhaled neurokinin
A, various antigens, exercise, cold air, fog, and adenosine monophosphate. Nedocromil
sodium has no bronchodilator, antihistamine, or corticosteroid activity. Nedocromil
sodium, when delivered by inhalation at the recommended dose, has no known
systemic activity. Pharmacokinetics and Bioavailability:
Systemic bioavailability of nedocromil sodium administered as an
inhaled aerosol is low. In a single dose study involving 20 healthy adult
subjects who were administered a 3.5 mg dose of nedocromil sodium (2 actuations
of 1.75 mg each), the mean AUC was 5.0 ng-hr/mL and the mean Cwas
1.6 ng/mL attained about 28 minutes after dosing. The mean half-life was 3.3
hours. Urinary excretion over 12 hours averaged 3.4% of the administered dose,
of which approximately 75% was excreted in the first six hours of dosing. In
a multiple dose study, six healthy adult volunteers (3 males and 3 females)
received a 3.5 mg single dose followed by 3.5 mg four times a day for seven
consecutive days. Accumulation of the drug was not observed. Following single
and multiple dose inhalations, urinary excretion of nedocromil accounted for
5.6% and 12% of the drug administered, respectively. After intravenous administration
to healthy adults, urinary excretion of nedocromil was approximately 70%.
The absolute bioavailability of nedocromil was thus 8% (5.6/70) for single
and 17% (12/70) for multiple inhaled doses. Similarly,
in a multiple dose study of 12 asthmatic adult patients, each given a 3.5
mg single dose followed by 3.5 mg four times a day for one month, both single
dose and multiple dose inhalations gave a mean high plasma concentration of
2.8 ng/mL between 5 and 90 minutes, mean AUC of 5.6 ng-hr/mL, and a mean terminal
half-life of 1.5 hours. The mean 24-hour urinary excretion after either single
or multiple dose administration represented approximately 5% of the administered
dose. Studies involving very high oral doses of nedocromil
(600 mg single dose, and subsequently 200 mg three times a day for seven days)
showed an absolute bioavailability of less than 2%. In a radiolabeled (C)
nedocromil intravenous study involving two healthy adult males, urinary excretion
accounted for 64% of the dose, fecal excretion for 36%. Although
minimal pharmacokinetic data are available in children between the ages of
6 and 11 years, the nedocromil sodium levels obtained at 1 hour after chronic
dosing in this age group appear to be similar to those observed in adults. Protein Binding: Nedocromil is approximately
89% protein bound in human plasma over a concentration range of 0.5 to 50��g/mL. This binding is reversible. Metabolism:
Nedocromil is not metabolized after IV administration and is excreted
unchanged.
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Tilade Inhaler is contraindicated
in patients who have shown hypersensitivity to nedocromil sodium or other
ingredients in this preparation.
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| dailymed-instance:supply |
Tilade Inhaler is available
in 16.2 g canisters providing at least 104 metered inhalations. Each Tilade canister contains 210 mg nedocromil sodium.
Each pack is supplied with patient instructions, a tan-colored rubber valve
cover, and white plastic mouthpiece and cover, bearing the Tilade
logo. The Tilade mouthpiece
should not be used with other aerosol medications and the Tilade
canister should not be used with other mouthpieces. Each actuation
meters 2.00 mg nedocromil sodium from the valve and delivers 1.75 mg nedocromil
sodium from the mouthpiece. NDC 60793-120-01 ........................ One
16.2 g Canister (104 Metered Inhalations) The canister
should be discarded after the labeled number of actuations have been used.
The amount of medication in each actuation cannot be assured after this point. Store
between 2��to 30��C (36��to 86��F). Do not freeze. Avoid spraying in eyes. Contents under pressure.
Do not puncture, incinerate, place near sources of heat, or use with other
mouthpieces. Exposure to temperatures above 120��F may cause bursting.
Never throw canister into fire or incinerator. Keep
out of the reach of children. For best results, the canister should
be at room temperature before use. Shake well before
using. Note: The indented statement below is required
by the Federal government's Clean Air Act for all products containing
or manufactured with chlorofluorocarbons (CFCs). WARNING:
Contains CFC-12 and CFC-114, substances which harm public health and the environment
by destroying ozone in the upper atmosphere. A notice
similar to the above WARNING has been placed in the���Patient Instructions
for Use���portion of this package insert under the Environmental Protection
Agency's (EPA's) regulations. The patient's warning states
that the patient should consult his or her physician if there are questions
about alternatives. Rx only Prescribing
Information as of September 2005. Distributed by: King
Pharmaceuticals, Inc., Bristol, TN 37620 Manufactured
by: Aventis Pharma LTD, Holmes Chapel CW48BE, United Kingdom Made
in United Kingdom
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General: The role of Tilade as a corticosteroid-sparing agent in patients
receiving oral or inhaled corticosteroids remains to be defined. If systemic
or inhaled corticosteroid therapy is reduced in patients receiving Tilade, careful monitoring is necessary. Information for Patients: Patients should be told
that: Drug Interactions: In
clinical studies, Tilade has been co-administered
with other anti-asthma medications, including inhaled and oral bronchodilators,
and inhaled corticosteroids, with no evidence of increased frequency of adverse
events or laboratory abnormalities. No formal drug-drug interaction studies,
however, have been conducted. Carcinogenesis, Mutagenesis, Impairment
of Fertility: A two-year inhalation carcinogenicity study of nedocromil
sodium at a dose of 24 mg/kg/day (approximately 8 times the maximum recommended
human daily inhalation dose on a mg/mbasis) in Wistar rats showed
no carcinogenic potential. A 21-month oral dietary carcinogenicity study of
nedocromil sodium performed in B6C3F1 mice with doses up to 180 mg/kg/day
(approximately 30 times the maximum recommended human daily inhalation dose
on a mg/mbasis) showed no carcinogenic potential. Nedocromil
sodium showed no mutagenic potential in the Ames Salmonella/microsome plate
assay, mitotic gene conversion in Saccharomyces
cerevisiae, mouse lymphoma forward mutation, and mouse micronucleus
assays. Reproduction and fertility studies in mice and
rats showed no effects on male and female fertility at a subcutaneous dose
of 100 mg/kg/day (approximately 30 times and 60 times, respectively, the maximum
recommended human daily inhalation dose on a mg/mbasis). Pregnancy:Pregnancy
Category B: Reproduction studies performed in mice, rats, and rabbits
using a subcutaneous dose of 100 mg/kg/day (approximately 30 times, 60 times,
and 116 times, respectively, the maximum recommended human daily inhalation
dose on a mg/mbasis) revealed no evidence of teratogenicity or
harm to the fetus due to nedocromil sodium. There are, however, no adequate
and well-controlled studies in pregnant women. Because animal reproduction
studies are not always predictive of human response, this drug should be used
during pregnancy only if clearly needed. Nursing Mothers: It
is not known whether this drug is excreted in human milk. Because many drugs
are excreted in human milk, caution should be exercised when Tilade
is administered to a nursing woman. Pediatric Use: Safety
data in normal volunteers and asthmatic patients between the ages of 6 and
11 years are available on a total of 311 children from U.S. clinical trials
and 192 children from foreign clinical trials (total = 503) of 4���12
weeks duration. An additional 225 children received Tilade
for 40 weeks and 24 received Tilade
for 52 weeks. The safety and effectiveness
of Tilade in children ages 6 through 11
have been established in adequate and well-controlled clinical trials. (See CLINICAL STUDIES: Pediatric Studies.) Use of Tilade in children ages 6 through 11 years is also
supported by evidence from adequate and well-controlled studies of Tilade in adults. The safety and effectiveness
of Tilade in patients below the age of
6 years have not been established. Geriatric Use: Clinical
studies of Tilade did not include sufficient
numbers of subjects aged 65 and over to determine whether they respond differently
from younger subjects. Other reported clinical experience has not identified
differences in responses between the elderly and younger patients.
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| dailymed-instance:overdosag... |
There is no experience to date with overdose of Tilade in
humans. There were no deaths in rodents at an oral dose of 4,000 mg/kg (approximately
690 times [for mice] and 1,370 times [for rats] the maximum recommended human
daily inhalation dose on a mg/mbasis). The subcutaneous or intravenous
lethal dose in rats was between 2,000 and 4,000 mg/kg (approximately 690 and
1,370 times, respectively, the maximum recommended human daily inhalation
dose on a mg/mbasis). No deaths occurred in mice at a subcutaneous
dose of 4,000 mg/kg (approximately 690 times the maximum recommended human
daily inhalation dose on a mg/mbasis), and the intravenous lethal
dose in mice was between 2,000 and 4,000 mg/kg (approximately 345 and 690
times, respectively, the maximum recommended human daily inhalation dose on
a mg/mbasis). An intravenous dose of 240 mg/kg (approximately
110 times the maximum recommended human daily inhalation dose on a mg/mbasis)
did not produce any deaths in cats. Head shaking/tremor and salivation were
observed in beagle dogs following daily inhalation doses of 5 mg/kg (approximately
6 times the maximum recommended human daily inhalation dose on a mg/mbasis)
and transient hypotension was detected following daily subcutaneous doses
of 8 mg/kg (approximately 9 times the maximum recommended human daily inhalation
dose on a mg/mbasis). In addition, clonic convulsions were observed
in dogs following daily inhalation doses of 20 mg/kg plus subcutaneous doses
of 20 mg/kg giving peak plasma nedocromil levels of 7.6��g/mL, some three
orders of magnitude greater than peak plasma levels (2.5 ng/mL) of the maximum
recommended human daily inhalation dose. Specific tests designed to evaluate
CNS activity demonstrated no effects due to nedocromil sodium, and nedocromil
sodium does not pass the blood brain barrier. Therefore, overdosage is unlikely
to result in clinical manifestations requiring more than observation and discontinuation
of the drug where appropriate.
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nedocromil sodium
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Tilade (Aerosol, Metered)
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| dailymed-instance:adverseRe... |
Tilade is generally
well tolerated. Adverse event information was derived from 6,469 patients
receiving Tilade in controlled and open-label
clinical trials of 1���52 weeks in duration. A total of 4,400 patients
received two inhalations four times a day. An additional 2,069 patients received
two inhalations twice daily or another dose regimen. Seventy-seven percent
of patients were treated with Tilade for
eight weeks or longer. Of the 4,400 patients who received
two inhalations of Tilade four times a
day, 2,632 were in placebo-controlled, parallel trials and of these 6.0% withdrew
from the trials due to adverse events, compared to 5.7% of the 2,446 patients
who received placebo. The reasons for withdrawal were
generally similar in the Tilade and placebo-treated
groups, except that patients withdrew due to bad taste statistically more
frequently on Tilade than on placebo.
Headache reported as severe or very severe, some with nausea and ill feeling,
was experienced by 1.0% of Tilade patients
and 0.7% of placebo patients. The events reported with
a frequency of 1% or greater across all placebo-controlled studies are displayed
for all patients ages 6 years and older who received Tilade
or placebo at two inhalations four times daily. The
adverse event profile observed in children ages 6 through 11 was similar to
that observed in adults. Other adverse events present at less than the 1% level
of occurrence, but that might be related to Tilade
administration, include arthritis, tremor, and a sensation of
warmth. In clinical trials with 2,632 patients receiving Tilade , 2 patients (0.08%) developed neutropenia
and 3 patients (0.11%) developed leukopenia. Although it is unclear if these
reactions were caused by Tilade, in several
cases these abnormal laboratory tests returned to normal when Tilade
was discontinued. There have been reports
of clinically significant elevation of hepatic transaminases (ALT and AST
greater than 10 times the upper limit of the normal reference range in one
patient) associated with the administration of Tilade
. It is unclear if these abnormal laboratory tests in asymptomatic
patients were caused by Tilade. Cases
of bronchospasm immediately following dosing with Tilade
have been reported from postmarketing experience. (See WARNINGS.) Isolated cases of pneumonitis with eosinophilia
(PIE syndrome) and anaphylaxis have also been reported in which a relationship
to drug is undetermined.
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| dailymed-instance:warning |
Tilade Inhaler
(nedocromil sodium inhalation aerosol) is not a bronchodilator and, therefore,
should not be used for the reversal of acute bronchospasm, particularly status
asthmaticus. Tilade should ordinarily
be continued during acute exacerbations, unless the patient becomes intolerant
to the use of inhaled dosage forms. As with other inhaled
asthma medications, bronchospasm, which can be life-threatening, may occur
immediately after administration. If this occurs, Tilade should be discontinued and alternative therapy instituted.
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| dailymed-instance:indicatio... |
Tilade Inhaler is indicated
for maintenance therapy in the management of adult and pediatric patients
6 years and older with mild to moderate asthma. Tilade is not indicated for the reversal of acute
bronchospasm.
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Tilade
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