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Toprol Xl Warnings, Precautions, Pregnancy, Nursing, Abuse - Metoprolol Succinate
Toprol Xl Warnings, Precautions, Pregnancy, Nursing, Abuse - Metoprolol Succinate
WARNINGS
Hypertension and Angina
Cardiac Failure: Sympathetic stimulation
is a vital component supporting
circulatory function
in congestive heart failure,
and beta-blockade carries the potential
hazard of further depressing myocardial
contractility and precipitating more severe failure. In
hypertensive and
angina patients who have
congestive heart failure
controlled by digitalis
and diuretics, extended release
metoprolol succinate
should be administered cautiously. Both digitalis
and extended release
metoprolol succinate
AV conduction.
In Patients Without a History of Cardiac Failure:
Continued depression of the myocardium
with beta-blocking agents over a period
of time can, in some cases, lead
to cardiac failure.
At the first sign
or symptom of impending cardiac
failure, patients should be fully digitalized and/or given a diuretic.
The response should
be observed closely. If cardiac failure continues, despite adequate
digitalization
and diuretic therapy,
extended release metoprolol
succinate should be
withdrawn.
| Ischemic Heart Disease: Following abrupt cessation
of therapy with certain beta-blocking agents, exacerbations
of angina pectoris
and, in some cases, myocardial
infarction
have occurred. When discontinuing chronically administered
extended release
metoprolol succinate, particularly in patients with ischemic
heart disease, the
dosage should be
gradually reduced over a period
of 1-2 weeks and the patient
should be carefully monitored. If angina
markedly worsens or acute
coronary insufficiency develops, extended release
metoprolol succinate
administration
should be reinstated promptly, at least temporarily, and other
measures appropriate
for the management of unstable angina
should be taken. Patients should be warned against interruption
or discontinuation of therapy without the physician's advice.
Because coronary artery disease
is common and may be unrecognized, it may be prudent not to
discontinue extended release
metoprolol succinate therapy abruptly even in patients treated
only for hypertension. |
Bronchospastic Diseases: PATIENTS WITH BRONCHOSPASTIC
DISEASES SHOULD, IN GENERAL, NOT RECEIVE BETA-BLOCKERS. Because
of its relative beta1-selectivity, however, extended
release metoprolol succinate
may be used with caution in patients with bronchospastic disease
who do not respond to, or cannot tolerate, other antihypertensive
treatment. Since beta1- selectivity is not absolute,
a beta2-stimulating agent should be administered concomitantly,
and the lowest possible dose of extended release
metoprolol succinate
should be used (see DOSAGE AND ADMINISTRATION.)
Major Surgery: The necessity or desirability of withdrawing
beta-blocking therapy prior to major surgery is controversial; the
impaired ability of the heart
to respond to reflex
adrenergic stimuli
may augment the risks of general anesthesia
and surgical procedures.
Extended release metoprolol
succinate like other
beta-blockers, is a competitive inhibitor
of beta-receptor agonists, and its effects can be reversed by administration
of such agents, e.g., dobutamine or isoproterenol. However, such
patients may be subject
to protracted severe hypotension. Difficulty in restarting and maintaining
the heart beat
has also been reported with beta- blockers.
Diabetes and Hypoglycemia: Extended release
metoprolol succinate should be used with caution in diabetic
patients if a beta-blocking agent is required. Beta- blockers may
mask tachycardia
occurring with hypoglycemia, but other manifestations such as dizziness
and sweating may not
be significantly affected.
Thyrotoxicosis: Beta-adrenergic blockade
may mask certain clinical
signs (e.g., tachycardia) of hyperthyroidism. Patients suspected
of developing thyrotoxicosis
should be managed carefully to avoid abrupt withdrawal
of beta-blockade, which might precipitate
a thyroid storm.
PRECAUTIONS
General
Extended release metoprolol
succinate should be
used with caution in patients with impaired hepatic
function.
Information for the Patient
Patients should be advised to take
extended release metoprolol
succinate regularly and continuously, as directed, preferably with
or immediately following meals. If a dose
should be missed, the patient
should take only the next
scheduled dose (without
doubling it). Patients should not discontinue extended release
metoprolol succinate
without consulting the physician.
Patients should be advised (1) to avoid operating automobiles and
machinery or engaging in other tasks requiring alertness until the
patient's response to therapy with extended release
metoprolol succinate
has been determined; (2) to contact
the physician if any
difficulty in breathing
occurs; (3) to inform the physician
or dentist before any
type of surgery that he
or she is taking Toprol-X
Laboratory Tests
Clinical laboratory findings may include elevated levels of serum
transaminase, alkaline phosphatase, and lactate
dehydrogenase.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
Long-term studies in animals have been conducted to evaluate the
carcinogenic potential of metoprolol tartrate. In
2-year studies in rats at three oral dosage levels of up to 800
mg/kg/day, there was no increase in the development of spontaneously
occurring benign or malignant
neoplasms of any type. The only histologic changes that appeared
to be drug related were
an increased incidence of generally mild focal
accumulation of foamy macrophages in pulmonary alveoli
and a slight increase in biliary hyperplasia. In
a 21-month study in Swiss albino
mice at three oral dosage
levels of up to 750 mg/kg/day, benign lung
tumors (small adenomas) occurred more frequently in female mice
receiving the highest dose
than in untreated control
animals. There was no increase in malignant
or total (benign plus malignant) lung
tumors, nor in the overall incidence
of tumors or malignant
tumors. This 21-month study was repeated in CD-1 mice, and no statistically
or biologically significant differences were observed between treated
and control mice of
either sex for any type
of tumor. All mutagenicity tests performed on metoprolol tartrate
(a dominant lethal
study in mice, chromosome
studies in somatic cells,
a Salmonella/mammalian-microsome mutagenicity test, and a nucleus
anomaly test in somatic
interphase nuclei)
and metoprolol succinate
(a Salmonella/mammalian-microsome mutagenicity test) were negative.
No evidence of impaired
fertility due to metoprolol tartrate
was observed in a study performed in rats at doses up to 55.5 times
the maximum daily human
dose of 450 mg.
Pregnancy Category C
Metoprolol tartrate
has been shown to increase post-implantation loss and decrease neonatal
survival in rats at
doses up to 55.5 times the maximum daily human
dose of 450 mg. Distribution
studies in mice confirm exposure of the fetus
when metoprolol tartrate
is administered to the pregnant
animal. These studies have revealed no evidence
of impaired fertility or teratogenicity. There are 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
Metoprolol is excreted in breast
milk in very small quantities.
An infant consuming 1 liter
of breast milk
daily would receive a dose
of less than 1 mg of the
drug. Caution should be exercised when extended release
metoprolol succinate is administered to a nursing
woman.
Pediatric Use
Safety and effectiveness
in children have not been established.
Risk Of Anaphylactic REACTIONS
While taking beta-blockers, patients with a history of severe anaphylactic
reactions to a variety of allergens may be more reactive to repeated
challenge, either accidental, diagnostic
or therapeutic. Such patients may be unresponsive to the usual doses
of epinephrine used
to treat allergic reaction.
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