Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/108
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COREG CR (Capsule, Extended Release)
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dailymed-instance:dosage |
General: COREG CR is an extended-release capsule intended
for once-daily administration. Patients controlled with immediate-release
carvedilol tablets alone or in combination with other medications
may be switched to COREG CR extended-release capsules based on
the total daily doses shown in Table 6. Subsequent titration to higher
or lower doses may be necessary as clinically warranted. COREG CR should be taken once daily in the
morning with food. COREG CR should be swallowed as a whole capsule.
COREG CR and/or its contents should not be crushed, chewed, or
taken in divided doses.<br/>Alternative Administration: The capsules may be carefully opened and the beads
sprinkled over a spoonful of applesauce. The applesauce should not
be warm because it could affect the modified-release properties of
this formulation. The mixture of drug and applesauce should be consumed
immediately in its entirety. The drug and applesauce mixture shouldnot be stored for future use. Absorption of the beads sprinkled on
other foods has not been tested.<br/>Heart Failure: DOSAGE MUST BE INDIVIDUALIZED AND CLOSELY MONITORED
BY A PHYSICIAN DURING UP-TITRATION. Prior to initiation of COREG CR,
it is recommended that fluid retention be minimized. The recommended
starting dose of COREG CR is 10 mg once daily for 2 weeks.
Patients who tolerate a dose of 10 mg once daily may have their
dose increased to 20, 40, and 80 mg over successive intervals
of at least 2 weeks. Patients should be maintained on lower doses
if higher doses are not tolerated. Patients
should be advised that initiation of treatment and (to a lesser extent)
dosage increases may be associated with transient symptoms of dizziness
or lightheadedness (and rarely syncope) within the first hour after
dosing. Thus during these periods they should avoid situations such
as driving or hazardous tasks, where symptoms could result in injury.
Vasodilatory symptoms often do not require treatment, but it may be
useful to separate the time of dosing of COREG CR from that of
the ACE inhibitor or to reduce temporarily the dose of the ACE inhibitor.
The dose of COREG CR should not be increased until symptoms of
worsening heart failure or vasodilation have been stabilized. Fluid retention (with or without transient worsening
heart failure symptoms) should be treated by an increase in the dose
of diuretics. The dose of COREG CR should
be reduced if patients experience bradycardia (heart rate<55 beats/minute). Episodes of dizziness or fluid retention during initiation
of COREG CR can generally be managed without discontinuation
of treatment and do not preclude subsequent successful titration of,
or a favorable response to, COREG CR.<br/>Left Ventricular Dysfunction Following
Myocardial Infarction: DOSAGE MUST BE INDIVIDUALIZED AND MONITORED DURING
UP-TITRATION. Treatment with COREG CR may be started as an inpatient
or outpatient and should be started after the patient is hemodynamically
stable and fluid retention has been minimized. It is recommended that
COREG CR be started at 20 mg once daily and increased after
3 to 10 days, based on tolerability to 40 mg once daily,
then again to the target dose of 80 mg once daily. A
lower starting dose may be used (10 mg once daily) and/or, the
rate of up-titration may be slowed if clinically indicated (e.g.,
due to low blood pressure or heart rate, or fluid retention). Patients should be maintained on lower doses if higher doses are
not tolerated. The recommended dosing regimen need not be altered
in patients who received treatment with an IV or oral��-blocker
during the acute phase of the myocardial infarction.<br/>Hypertension: DOSAGE MUST BE INDIVIDUALIZED. The recommended starting
dose of COREG CR is 20 mg once daily. If this dose is tolerated,
using standing systolic pressure measured about one hour after
dosing as a guide, the dose should be maintained for 7 to 14 days,
and then increased to 40 mg once daily if needed, based on trough
blood pressure, again using standing systolic pressure one hour after
dosing as a guide for tolerance. This dose should also be maintained
for 7 to 14 days and can then be adjusted upward to 80 mg
once daily if tolerated and needed. Although not specifically studied,
it is anticipated the full antihypertensive effect of COREG CR
would be seen within 7 to 14 days as had been demonstrated with
immediate-release carvedilol. Total daily dose should not exceed 80 mg. Addition of a diuretic to COREG CR, or COREG CR
to a diuretic can be expected to produce additive effects and exaggerate
the orthostatic component of COREG CR action.<br/>Use in Patients with Hepatic Impairment: COREG CR should not be given to patients with
severe hepatic impairment (see CONTRAINDICATIONS).
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dailymed-instance:descripti... |
Carvedilol phosphate is a nonselective��-adrenergic
blocking agent with��-blocking activity. It is (2RS)-1-(9H-Carbazol-4-yloxy)-3-[[2-(2-methoxyphenoxy)ethyl]amino]propan-2-ol
phosphate salt (1:1) hemihydrate. It is a racemic mixture with the
following structure: Carvedilol
phosphate is a white to almost-white solid with a molecular weight
of 513.5 (406.5 carvedilol free base) and a molecular formula of CHNO���HPO���1/2 HO. COREG CR
is available for once-a-day administration as controlled-release oral
capsules containing 10, 20, 40, or 80 mg carvedilol phosphate. COREG CR hard gelatin capsules are filled
with carvedilol phosphate immediate-release and controlled-release microparticles that are drug-layered and then coated
with methacrylic acid copolymers. Inactive ingredients include
crospovidone, hydrogenated castor oil, hydrogenated vegetable oil,
magnesium stearate, methacrylic acid copolymers, microcrystalline
cellulose, and povidone.
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dailymed-instance:clinicalP... |
Carvedilol is a racemic mixture in which nonselective��-adrenoreceptor
blocking activity is present in the S(-) enantiomer and��-adrenergic blocking activity is present in both R(+) and
S(-) enantiomers at equal potency. Carvedilol has no intrinsic sympathomimetic
activity.<br/>Pharmacokinetics:<br/>Absorption: Carvedilol is rapidly and extensively absorbed following
oral administration of immediate-release carvedilol tablets, with
an absolute bioavailability of approximately 25% to 35% due to a significant
degree of first-pass metabolism. COREG CR extended-release capsules
have approximately 85% of the bioavailability of immediate-release
carvedilol tablets. For corresponding dosages (see DOSAGE AND ADMINISTRATION),
the exposure (area under the curve [AUC], C, trough
concentration) of carvedilol as COREG CR extended-release capsules
is equivalent to those of immediate-release carvedilol tablets when
both are administered with food. The absorption of carvedilol from
COREG CR is slower and more prolonged compared to the immediate-release
carvedilol tablet with peak concentrations achieved approximately
5 hours after administration. Plasma concentrations of carvedilol
increase in a dose-proportional manner over the dosage range of COREG CR
10 to 80 mg. Within-subject and between-subject variability for
AUC and Cis similar for COREG CR and immediate-release
carvedilol.<br/>Effect of Food: Administration of COREG CR with a high-fat
meal resulted in increases (~20%) in AUC and Ccompared
to COREG CR administered with a standard meal. Decreases in AUC
(27%) and C(43%) were observed when COREG CR was
administered in the fasted state compared to administration after
a standard meal. COREG CR should be taken with food. In a study with adult subjects, sprinkling the contents
of the COREG CR capsule on applesauce did not appear to have
a significant effect on overall exposure (AUC) compared to administration
of the intact capsule following a standard meal but did result in
a decrease in C(18%).<br/>Distribution: Carvedilol is more than 98% bound to plasma proteins,
primarily with albumin. The plasma-protein binding is independent
of concentration over the therapeutic range. Carvedilol is a basic,
lipophilic compound with a steady-state volume of distribution of
approximately 115 L, indicating substantial distribution into
extravascular tissues.<br/>Metabolism and Excretion: Carvedilol is extensively metabolized. Following
oral administration of radiolabelled carvedilol to healthy volunteers,
carvedilol accounted for only about 7% of the total radioactivity
in plasma as measured by AUC. Less than 2% of the dose was excreted
unchanged in the urine. Carvedilol is metabolized primarily by aromatic
ring oxidation and glucuronidation. The oxidative metabolites are
further metabolized by conjugation via glucuronidation and sulfation.
The metabolites of carvedilol are excreted primarily viathe bile
into the feces. Demethylation and hydroxylation at the phenol ring
produce 3 active metabolites with��-receptor blocking activity.
Based on preclinical studies, the 4'-hydroxyphenyl metabolite is approximately
13 times more potent than carvedilol for��-blockade. Compared to carvedilol, the 3 active metabolites exhibit
weak vasodilating activity. Plasma concentrations of the active metabolites
are about one-tenth of those observed for carvedilol and have pharmacokinetics
similar to the parent. Carvedilol undergoes
stereoselective first-pass metabolism with plasma levels of R(+)-carvedilol
approximately 2 to 3 times higher than S(-)-carvedilol following
oral administration of COREG CR in healthy subjects. Apparent
clearance is 90 L/h and 213 L/h for R(+)- and S(-)-carvedilol, respectively. The primary P450 enzymes responsible for the metabolism
of both R(+) and S(-)-carvedilol in human liver microsomes were CYP2D6
and CYP2C9 and to a lesser extent CYP3A4, 2C19, 1A2, and 2E1. CYP2D6
is thought to be the major enzyme in the 4'- and 5'-hydroxylation
of carvedilol, with a potential contribution from 3A4. CYP2C9 is thought
to be of primary importance in the O-methylation pathway of S(-)-carvedilol. Carvedilol is subject to the effects of genetic polymorphism
with poor metabolizers of debrisoquin (a marker for cytochrome P450
2D6) exhibiting 2- to 3-fold higher plasma concentrations of R(+)-carvedilol
compared to extensive metabolizers. In contrast, plasma levels of
S(-)-carvedilol are increased only about 20% to 25% in poor metabolizers,
indicating this enantiomer is metabolized to a lesser extent by cytochrome
P450 2D6 than R(+)-carvedilol. The pharmacokinetics of carvedilol
do not appear to be different in poor metabolizers of S-mephenytoin
(patients deficient in cytochrome P450 2C19).<br/>Heart Failure: Following administration of immediate-release carvedilol
tablets, steady-state plasma concentrations of carvedilol and its
enantiomers increased proportionally over the dose range in patients
with heart failure. Compared to healthy subjects, heart failure patients
had increased mean AUC and Cvalues for carvedilol and
its enantiomers, with up to 50% to 100% higher values observed in
6 patients with NYHA class IV heart failure. The mean apparent terminal
elimination half-life for carvedilol was similar to that observed
in healthy subjects. For corresponding dose
levels (see DOSAGE AND ADMINISTRATION), the steady-state pharmacokinetics
of carvedilol (AUC, C, trough concentrations) observed
after administration of COREG CR to chronic heart failure patients
(mild, moderate, and severe) were similar to those observed after
administration of immediate-release carvedilol tablets.<br/>Hypertension: For corresponding dose levels (see DOSAGE AND ADMINISTRATION),
the pharmacokinetics (AUC, C, and trough concentrations)
observed with administration of COREG CR were equivalent (��20%)
to those observed with immediate-release carvedilol tablets following
repeat dosing in patients with essential hypertension.<br/>Pharmacokinetic Drug-Drug Interactions: Since carvedilol undergoes substantial oxidative
metabolism, the metabolism and pharmacokinetics of carvedilol may
be affected by induction or inhibition of cytochrome P450 enzymes. The following drug interaction studies were performed
with immediate-release carvedilol tablets.<br/>Rifampin: In a pharmacokinetic study conducted in 8 healthy
male subjects, rifampin (600 mg daily for 12 days) decreased
the AUC and Cof carvedilol by about 70%.<br/>Cimetidine: In a pharmacokinetic study conducted in 10 healthy
male subjects, cimetidine (1,000 mg/day) increased the steady-state
AUC of carvedilol by 30% with no change in C.<br/>Glyburide: In 12 healthy subjects, combined administration
of carvedilol (25 mg once daily) and a single dose of glyburide
did not result in a clinically relevant pharmacokinetic interaction
for either compound.<br/>Hydrochlorothiazide: A single oral dose of carvedilol 25 mg did
not alter the pharmacokinetics of a single oral dose of hydrochlorothiazide
25 mg in 12 patients with hypertension. Likewise, hydrochlorothiazide
had no effect on the pharmacokinetics of carvedilol.<br/>Digoxin: Following concomitant administration of carvedilol
(25 mg once daily) and digoxin (0.25 mg once daily) for
14 days, steady-state AUC and trough concentrations of digoxin
were increased by 14% and 16%, respectively, in 12 hypertensive patients
(see PRECAUTIONS, Drug Interactions).<br/>Torsemide: In a study of 12 healthy subjects, combined oral
administration of carvedilol 25 mg once daily and torsemide 5 mg
once daily for 5 days did not result in any significant differences
in their pharmacokinetics compared with administration of the drugs
alone.<br/>Warfarin: Carvedilol (12.5 mg twice daily) did not have
an effect on the steady-state prothrombin time ratios and did not
alter the pharmacokinetics of R(+)- and S(-)-warfarin following concomitant
administration with warfarin in 9 healthy volunteers.<br/>Special Populations:<br/>Elderly: Plasma levels of carvedilol average about 50% higher
in the elderly compared to young subjects after administration of
immediate-release carvedilol.<br/>Hepatic Impairment: No studies have been performed with COREG CR
in patients with hepatic impairment. Compared to healthy subjects,
patients with cirrhotic liver disease exhibit significantly higher
concentrations of carvedilol (approximately 4- to 7-fold) following
single-dose therapy with immediate-release carvedilol.<br/>Renal Insufficiency: No studies have been performed with COREG CR
in patients with renal insufficiency. Although carvedilol is metabolized
primarily by the liver, plasma concentrations of carvedilol have been
reported to be increased in patients with renal impairment after dosing
with immediate-release carvedilol. Based on mean AUC data, approximately
40% to 50% higher plasma concentrations of carvedilol were observed
in hypertensive patients with moderate to severe renal impairment
compared to a control group of hypertensive patients with normal renal
function. However, the ranges of AUC values were similar for both
groups. Changes in mean peak plasma levels were less pronounced, approximately
12% to 26% higher in patients with impaired renal function. Consistent with its high degree of plasma protein binding,
carvedilol does not appear to be cleared significantly by hemodialysis.<br/>Pharmacodynamics:<br/>Heart Failure and Left Ventricular
Dysfunction Following Myocardial Infarction: The basis for the beneficial effects of carvedilol
in patients with heart failure and in patients with left ventricular
dysfunction following an acute myocardial infarction is not known.
The concentration-response relationship for��-blockade
following administration of COREG CR is equivalent (��20%)
to immediate-release carvedilol tablets.<br/>Hypertension: The mechanism by which��-blockade produces
an antihypertensive effect has not been established. ��-adrenoreceptor blocking activity has been demonstrated in
animal and human studies showing that carvedilol (1) reduces cardiac
output in normal subjects; (2) reduces exercise- and/or isoproterenol-induced
tachycardia; and (3) reduces reflex orthostatic tachycardia. Significant��-adrenoreceptor blocking effect is usually seen within 1 hour
of drug administration. ��-adrenoreceptor
blocking activity has been demonstrated in human and animal studies,
showing that carvedilol (1) attenuates the pressor effects of
phenylephrine; (2) causes vasodilation; and (3) reduces
peripheral vascular resistance. These effects contribute to the reduction
of blood pressure and usually are seen within 30 minutes of drug
administration. Due to the��-receptor blocking activity of carvedilol, blood pressure is lowered
more in the standing than in the supine position, and symptoms of
postural hypotension (1.8%), including rare instances of syncope,
can occur. Following oral administration, when postural hypotension
has occurred, it has been transient and is uncommon when immediate-release
carvedilol is administered with food at the recommended starting dose
and titration increments are closely followed (see DOSAGE AND ADMINISTRATION). In a randomized, double-blind, placebo-controlled trial,
the��-blocking effect of COREG CR, as measured
by heart rate response to submaximal bicycle ergometry, was shown
to be equivalent to that observed with immediate-release carvedilol
at steady state in adult patients with essential hypertension. In hypertensive patients with normal renal function,
therapeutic doses of carvedilol decreased renal vascular resistance
with no change in glomerular filtration rate or renal plasma flow.
Changes in excretion of sodium, potassium, uric acid, and phosphorus
in hypertensive patients with normal renal function were similar after
carvedilol and placebo. Carvedilol has little
effect on plasma catecholamines, plasma aldosterone, or electrolyte
levels, but it does significantly reduce plasma renin activity when
given for at least 4 weeks. It also increases levels of atrial
natriuretic peptide.
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dailymed-instance:activeIng... | |
dailymed-instance:contraind... |
COREG CR is contraindicated in patients with
bronchial asthma (2 cases of death from status asthmaticus have been
reported in patients receiving single doses of immediate-release carvedilol)
or related bronchospastic conditions, second- or third-degree AV block,
sick sinus syndrome or severe bradycardia (unless a permanent pacemaker
is in place), or in patients with cardiogenic shock or who have decompensated
heart failure requiring the use of intravenous inotropic therapy.
Such patients should first be weaned from intravenous therapy before
initiating COREG CR. Use of COREG CR
in patients with clinically manifest hepatic impairment is not recommended. COREG CR is contraindicated in patients with a history
of a serious hypersensitivity reaction (e.g., Stevens-Johnson syndrome,
anaphylactic reaction, angioedema) to carvedilol or any of the components
of COREG CR.
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dailymed-instance:supply |
Capsules: The
hard gelatin capsules are filled with white to off-white microparticles
and are available in the following strengths: 10 mg���white and green capsule shell printed with GSK
COREG CR and 10 mg 20 mg���white and yellow capsule shell printed with GSK
COREG CR and 20 mg 40 mg���yellow and green capsule shell printed with GSK
COREG CR and 40 mg 80 mg���white capsule shell printed with GSK COREG CR and 80 mg 10 mg
30's: NDC 0007-3370-13 10 mg 90's:
NDC 0007-3370-59 20 mg 30's: NDC
0007-3371-13 20 mg 90's: NDC 0007-3371-59 40 mg 30's: NDC 0007-3372-13 40 mg 90's: NDC 0007-3372-59 80 mg
30's: NDC 0007-3373-13 80 mg 90's:
NDC 0007-3373-59
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dailymed-instance:genericDr... | |
dailymed-instance:activeMoi... | |
dailymed-instance:inactiveI... |
dailymed-ingredient:crospovidone,
dailymed-ingredient:hydrogenated_castor_oil,
dailymed-ingredient:hydrogenated_vegetable_oil,
dailymed-ingredient:magnesium_stearate,
dailymed-ingredient:methacrylic_acid_copolymer_dispersion,
dailymed-ingredient:microcrystalline_cellulose,
dailymed-ingredient:povidone
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dailymed-instance:possibleD... |
diseasome-diseases:1112,
diseasome-diseases:116,
diseasome-diseases:1235,
diseasome-diseases:126,
diseasome-diseases:1313,
diseasome-diseases:149,
diseasome-diseases:1499,
diseasome-diseases:1533,
diseasome-diseases:1598,
diseasome-diseases:1907,
diseasome-diseases:1984,
diseasome-diseases:2175,
diseasome-diseases:24,
diseasome-diseases:251,
diseasome-diseases:261,
diseasome-diseases:2759,
diseasome-diseases:2989,
diseasome-diseases:319,
diseasome-diseases:3413,
diseasome-diseases:3428,
diseasome-diseases:3734,
diseasome-diseases:4003,
diseasome-diseases:691,
diseasome-diseases:851,
diseasome-diseases:855,
diseasome-diseases:989
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dailymed-instance:precautio... |
General: In clinical trials of COREG CR in patients
with hypertension (338 subjects) and in patients with left ventricular
dysfunction following a myocardial infarction or heart failure (187 subjects),
the profile of adverse events observed with carvedilol phosphate was
generally similar to that observed with the administration of immediate-release
carvedilol. Therefore, the information included within this section
is based on data from controlled clinical trials with COREG CR
as well as immediate-release carvedilol. In
clinical trials with immediate-release carvedilol, bradycardia was
reported in about 2% of hypertensive patients, 9% of heart failure
patients, and 6.5% of myocardial infarction patients with left ventricular
dysfunction. Bradycardia was reported in 0.5% of patients receiving
COREG CR in a study of heart failure patients and myocardial
infarction patients with left ventricular dysfunction. There were
no reports of bradycardia in the clinical trial of COREG CR in
hypertension. However, if pulse rate drops below 55 beats/minute,
the dosage of COREG CR should be reduced. In clinical trials of primarily mild-to-moderate heart failure with
immediate-release carvedilol, hypotension and postural hypotension
occurred in 9.7% and syncope in 3.4% of patients receiving carvedilol
compared to 3.6% and 2.5% of placebo patients, respectively. The risk
for these events was highest during the first 30 days of dosing,
corresponding to the up-titration period and was a cause for discontinuation
of therapy in 0.7% of carvedilol patients, compared to 0.4% of placebo
patients. In a long-term, placebo-controlled trial in severe heart
failure (COPERNICUS), hypotension and postural hypotension occurred
in 15.1% and syncope in 2.9% of heart failure patients receiving carvedilol
compared to 8.7% and 2.3% of placebo patients, respectively. These
events were a cause for discontinuation of therapy in 1.1% of carvedilol
patients, compared to 0.8% of placebo patients. In the clinical trial of COREG CR in hypertensive patients,
syncope was reported in 0.3% of patients receiving COREG CR compared
to 0% of patients receiving placebo. There were no reports of postural
hypotension in this trial. Postural hypotension occurred in 1.8% and
syncope in 0.1% of hypertensive patients receiving immediate-release
carvedilol, primarily following the initial dose or at the time of
dose increase and was a cause for discontinuation of therapy in 1%
of patients. In the CAPRICORN study of survivors
of an acute myocardial infarction with left ventricular dysfunction,
hypotension or postural hypotension occurred in 20.2% of patients
receiving carvedilol compared to 12.6% of placebo patients. Syncope
was reported in 3.9% and 1.9% of patients, respectively. These events
were a cause for discontinuation of therapy in 2.5% of patients receiving
carvedilol, compared to 0.2% of placebo patients. To decrease the likelihood of syncope or excessive hypotension,
treatment with COREG CR should be initiated with 10 mg once
daily for heart failure patients, and at 20 mg once daily for
hypertensive patients and survivors of an acute myocardial infarction
with left ventricular dysfunction. Dosage should then be increased
slowly, according to recommendations in the DOSAGEAND ADMINISTRATION
section, and the drug should be taken with food. During initiation
of therapy, the patient should be cautioned to avoid situations such
as driving or hazardous tasks, where injury could result should syncope
occur. Rarely, use of carvedilol in patients
with heart failure has resulted in deterioration of renal function.
Patients at risk appear to be those with low blood pressure (systolic
blood pressure<100 mm Hg), ischemic heart disease and diffuse
vascular disease, and/or underlying renal insufficiency. Renal function
has returned to baseline when carvedilol was stopped. In patients
with these risk factors it is recommended that renal function be monitored
during up-titration of COREG CR and the drug discontinued or
dosage reduced if worsening of renal function occurs. Worsening heart failure or fluid retention may occur during up-titration
of carvedilol. If such symptoms occur, diuretics should be increased
and the dose of COREG CR should not be advanced until clinical
stability resumes (see DOSAGE AND ADMINISTRATION). Occasionally it
is necessary to lower the dose of COREG CR or temporarily discontinue
it. Such episodes do not preclude subsequent successful titration
of, or a favorable response to, COREG CR. In a placebo-controlled
trial of patients with severe heart failure, worsening heart failure
during the first 3 months was reported to a similar degree with
immediate-release carvedilol and with placebo. When treatment was
maintained beyond 3 months, worsening heart failure was reported
less frequently in patients treated with carvedilol than with placebo.
Worsening heart failure observed during long-term therapy is more
likely to be related to the patients' underlying disease than
to treatment with carvedilol. In patients with
pheochromocytoma, an��-blocking agent should be initiated prior
to the use of any��-blocking agent. Although carvedilol has
both��- and��-blocking pharmacologic activities, there
has been no experience with its use in this condition. Therefore,
caution should be taken in the administration of carvedilol to patients
suspected of having pheochromocytoma. Agents
with non-selective��-blocking activity may provoke chest pain
in patients with Prinzmetal's variant angina. There has been
no clinical experience with carvedilol in these patients although
the��-blocking activity may prevent such symptoms. However,
caution should be taken in the administration of COREG CR to
patients suspected of having Prinzmetal's variant angina.<br/>Effects on Glycemic Control in Type
2 Diabetic Patients: In heart failure patients with diabetes,
carvedilol therapy may lead to worsening hyperglycemia, which responds
to intensification of hypoglycemic therapy. It is recommended that
blood glucose be monitored when dosing with COREG CR is initiated,
adjusted, or discontinued. Studies designed to examine the
effects of carvedilol on glycemic control in patients with diabetes
and heart failure have not been conducted. In a study designed to examine the effects of immediate-release carvedilol on glycemic control in a population
with mild-to-moderate hypertension and well-controlled
type 2 diabetes mellitus, carvedilol had no adverse effect on glycemic
control, based on HbA1c measurements (see CLINICAL TRIALS, Hypertensive
Patients with Type 2 Diabetes Mellitus [GEMINI]).<br/>Risk of Anaphylactic Reaction: While taking��-blockers, patients with a history
of severe anaphylactic reaction 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.<br/>Nonallergic Bronchospasm (e.g., chronic
bronchitis and emphysema): Patients with bronchospastic disease should, in
general, not receive��-blockers. COREG CR may be used with
caution, however, in patients who do not respond to, or cannot tolerate,
other antihypertensive agents. It is prudent, if COREG CR is
used, to use the smallest effective dose, so that inhibition of endogenous
or exogenous��-agonists is minimized. In clinical trials of patients with heart failure, patients with
bronchospastic disease were enrolled if they did not require oral
or inhaled medication to treat their bronchospastic disease. In such
patients, it is recommended that COREG CR be used with caution.
The dosing recommendations should be followed closely and the dose
should be lowered if any evidence of bronchospasm is observed during
up-titration.<br/>Information for Patients: Patients taking COREG CR should be advised
of the following:<br/>Drug Interactions: (Also see CLINICAL PHARMACOLOGY, Pharmacokinetic
Drug-Drug Interactions.)<br/>Inhibitors of CYP2D6: poor metabolizers of debrisoquin: Interactions of
carvedilol with strong inhibitors of CYP2D6 (such as quinidine, fluoxetine,
paroxetine, and propafenone) have not been studied, but these drugs
would be expected to increase blood levels of the R(+) enantiomer
of carvedilol (see CLINICAL PHARMACOLOGY). Retrospective analysis
of side effects in clinical trials showed that poor 2D6 metabolizers
had a higher rate of dizziness during up-titration, presumably resulting
from vasodilating effects of the higher concentrations of the��-blocking
R(+) enantiomer.<br/>Catecholamine-depleting agents: Patients taking both agents with��-blocking
properties and a drug that can deplete catecholamines (e.g., reserpine
and monoamine oxidase inhibitors) should be observed closely for signs
of hypotension and/or severe bradycardia.<br/>Clonidine: Concomitant administration of clonidine with agents
with��-blocking properties may potentiate blood-pressure- andheart-rate-lowering effects. When concomitant treatment with agents
with��-blocking properties and clonidine is to be terminated,
the��-blocking agent should be discontinued first. Clonidine
therapy can then be discontinued several days later by gradually decreasing
the dosage.<br/>Cyclosporine: Modest increases in mean trough cyclosporine concentrations
were observed following initiation of carvedilol treatment in 21 renal
transplant patients suffering from chronic vascular rejection. In
about 30% of patients, the dose of cyclosporine had to be reduced
in order to maintain cyclosporine concentrations within the therapeutic
range, while in the remainder no adjustment was needed. On the average
for the group, the dose of cyclosporine was reduced about 20% in these
patients. Due to wide interindividual variability in the dose adjustment
required, it is recommended that cyclosporine concentrations be monitored
closely after initiation of carvedilol therapy and that the dose of
cyclosporine be adjusted as appropriate.<br/>Digitalis Glycosides: Both digitalis glycosides and��-blockers slow
atrioventricular conduction and decrease heart rate. Concomitant use
can increase the risk of bradycardia. Digoxin concentrations are increased
by about 15% when digoxin and carvedilol are administered concomitantly.
Therefore, increased monitoring of digoxin is recommended when initiating,
adjusting, or discontinuing COREG CR (see CLINICAL PHARMACOLOGY,
Pharmacokinetic Drug-Drug Interactions).<br/>Inducers and inhibitors of
hepatic metabolism: Rifampin reduced plasma concentrations of carvedilol
by about 70%. Cimetidine increased AUC by about 30% but caused no
change in C.<br/>Calcium channel blockers: Isolated cases of conduction disturbance (rarely
with hemodynamic compromise) have been observed when carvedilol is
co-administered with diltiazem. As with other agents with��-blocking
properties, if COREG CR is to be administered orally with calcium
channel blockers of the verapamil or diltiazem type, it is recommended
that ECG and blood pressure be monitored.<br/>Insulin or oral hypoglycemics: Agents with��-blocking properties may enhance
the blood-sugar-reducing effect of insulin and oral hypoglycemics.
Therefore, in patients taking insulin or oral hypoglycemics, regular
monitoring of blood glucose is recommended.<br/>Proton Pump Inhibitors: There is no clinically meaningful increase in AUC
and Cwith concomitant administration of carvedilol
extended-release capsules with pantoprazole.<br/>Carcinogenesis, Mutagenesis, Impairment
of Fertility: In 2-year studies conducted in rats given carvedilol
at doses up to 75 mg/kg/day (12 times the maximum recommended
human dose [MRHD] when compared on a mg/mbasis) or in
mice given up to 200 mg/kg/day (16 times the MRHD on a mg/mbasis), carvedilol had no carcinogenic effect. Carvedilol was negative when tested in a battery of genotoxicity
assays, including the Ames and the CHO/HGPRT assays for mutagenicity
and the in vitro hamster micronucleus and in vivo human lymphocyte
cell tests for clastogenicity. At doses���200 mg/kg/day
(���32 times the MRHD as mg/m) carvedilol was
toxic to adult rats (sedation, reduced weight gain) and was associated
with a reduced number of successful matings, prolonged mating time,
significantly fewer corpora lutea and implants per dam, and complete
resorption of 18% of the litters. The no-observed-effect dose level
for overt toxicity and impairment of fertility was 60 mg/kg/day
(10 times the MRHD as mg/m).<br/>Pregnancy:<br/>Teratogenic Effects: Pregnancy Category C. Studies performed in pregnant
rats and rabbits given carvedilol revealed increased post-implantation
loss in rats at doses of 300 mg/kg/day (50 times the MRHD
as mg/m) and in rabbits at doses of 75 mg/kg/day
(25 times the MRHD as mg/m). In the rats, there was
also a decrease in fetal body weight at the maternally toxic dose
of 300 mg/kg/day (50 times the MRHD as mg/m),
which was accompanied by an elevation in the frequency of fetuses
with delayed skeletal development (missing or stunted 13th rib). In
rats the no-observed-effect level for developmental toxicity was 60 mg/kg/day
(10 times the MRHD as mg/m); in rabbits it was 15 mg/kg/day
(5 times the MRHD as mg/m). There are no adequate
and well-controlled studies in pregnant women. COREG CR should
be used during pregnancy only if the potential benefit justifies the
potential risk to the fetus.<br/>Nursing Mothers: It is not known whether this drug is excreted in
human milk. Studies in rats have shown that carvedilol and/or its
metabolites (as well as other��-blockers) cross the placental
barrier and are excreted in breast milk. There was increased mortality
at one week post partum in neonates from rats treated with 60 mg/kg/day
(10 times the MRHD as mg/m) and above during the
last trimester through day 22 of lactation. Because many drugs
are excreted in human milk and because of the potential for serious
adverse reactions in nursing infants from��-blockers, especially
bradycardia, a decision should be made whether to discontinue nursing
or to discontinue the drug, taking into account the importance of
the drug to the mother. The effects of other��- and��-blocking
agents have included perinatal and neonatal distress.<br/>Pediatric Use: Effectiveness of carvedilol in patients younger
than 18 years of age has not been established. In a double-blind trial, 161 children (mean age 6 years, range 2
months to 17 years; 45% less than 2 years old) with chronic heart
failure [NYHA class II-IV, left ventricular ejection fraction<40%
for children with a systemic left ventricle (LV), and moderate-severe
ventricular dysfunction qualitatively by echo for those with a systemic
ventricle that was not an LV] who were receiving standard background
treatment were randomized to placebo or to 2 dose levels of carvedilol.
These dose levels produced placebo-corrected heart rate reduction
of 4-6 heart beats per minute, indicative of��-blockade activity.
Exposure appeared to be lower in pediatric subjects than adults. After
8 months of follow-up, there was no significant effect of treatment
on clinical outcomes. Adverse reactions in this trial that occurred
in greater than 10% of patients treated with immediate-release carvedilol
and at twice the rate of placebo-treated patients included chest pain
(17% versus 6%), dizziness (13% versus 2%), and dyspnea (11% versus
0%).<br/>Geriatric Use: The clinical studies of COREG CR in patients with
hypertension, heart failure, and left ventricular dysfunction following
myocardial infarction did not include sufficient numbers of subjects
65 years of age or older to determine whether they respond differently
from younger patients. The following information
is available for trials with immediate-release carvedilol. Of the
765 patients with heart failure randomized to carvedilol in US
clinical trials, 31% (235) were 65 years of age or older, and
7.3% (56) were 75 years of age or older. Of the 1,156 patients
randomized to carvedilol in a long-term, placebo-controlled trial
in severe heart failure, 47% (547) were 65 years of age or older,
and 15% (174) were 75 years of age or older. Of 3,025 patients
receiving carvedilol in heart failure trials worldwide, 42% were 65 years
of age or older. Of the 975 myocardial infarction patients randomized
to carvedilol in the CAPRICORN trial, 48% (468) were 65 years
of age or older, and 11% (111) were 75 years of age or older.
Of the 2,065 hypertensive patients in US clinical trials of efficacy
or safety who were treatedwith carvedilol, 21% (436) were 65 years
of age or older. Of 3,722 patients receiving immediate-release carvedilol
in hypertension clinical trials conducted worldwide, 24% were 65 years
of age or older. With the exception of dizziness
in hypertensive patients (incidence 8.8% in the elderly vs. 6% in
younger patients), no overall differences in the safety or effectiveness
(see Figures 2 and 4) were observed between the older subjects and
younger subjects in each of these populations. Similarly, other reported
clinical experience has not identified differences in responses between
the elderly and younger subjects, but greater sensitivity of some
older individuals cannot be ruled out.
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dailymed-instance:overdosag... |
The acute oral LD50 doses in male and female mice
and male and female rats are over 8,000 mg/kg. Overdosage may
cause severe hypotension, bradycardia, cardiac insufficiency, cardiogenic
shock, and cardiac arrest. Respiratory problems, bronchospasms, vomiting,
lapses of consciousness, and generalized seizures may also occur. The patient should be placed in a supine position and,
where necessary, kept under observation and treated under intensive-care
conditions. Gastric lavage or pharmacologically induced emesis may
be used shortly after ingestion. The following agents may be administered: For excessive bradycardia: atropine, 2 mg IV. To support cardiovascular function: glucagon,
5 to 10 mg IV rapidly over 30 seconds, followed by a continuous
infusion of 5 mg/hour; sympathomimetics (dobutamine, isoprenaline,
adrenaline) at doses according to body weight and effect. If peripheral vasodilation dominates, it may be necessary
to administer adrenaline or noradrenaline with continuous monitoring
of circulatory conditions. For therapy-resistant bradycardia, pacemaker
therapy should be performed. For bronchospasm,��-sympathomimetics
(as aerosol or IV) or aminophylline IV should be given. In the event
of seizures, slow IV injection of diazepam or clonazepam is recommended. NOTE: In the event of severe intoxication where there
are symptoms of shock, treatment with antidotes must be continued
for a sufficiently long period of time consistent with the 7- to 10-hour
half-life of carvedilol. There is no experience
of overdosage with COREG CR. Cases of overdosage with carvedilol
alone or in combination with other drugs have been reported. Quantities
ingested in some cases exceeded 1,000 milligrams. Symptoms experienced
included low blood pressure and heart rate. Standard supportive treatment
was provided and individuals recovered.
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dailymed-instance:genericMe... |
carvedilol
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dailymed-instance:fullName |
COREG CR (Capsule, Extended Release)
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dailymed-instance:adverseRe... |
Carvedilol has been evaluated for safety in patients
with heart failure (mild, moderate, and severe heart failure), in
patients with left ventricular dysfunction following myocardial infarction,
and in hypertensive patients. The observed adverse event profile was
consistent with the pharmacology of the drug and the health status
of the patients in the clinical trials. Adverse events reported for
each of these patient populations reflecting the use of either COREG CR
or immediate-release carvedilol are provided below. Excluded are adverse
events considered too general to be informative, and those not reasonably
associated with the use of the drug because they were associated with
the condition being treated or are very common in the treated population.
Rates of adverse events were generally similar across demographic
subsets (men and women, elderly and non-elderly, blacks and non-blacks).
COREG CR has been evaluated for safety in a 4-week (2 weeks of
immediate-release carvedilol and 2 weeks ofCOREG CR) clinical
study (n = 187) which included 157 patients with stable
mild, moderate, or severe chronic heart failure and 30 patients with
left ventricular dysfunction following acute myocardial infarction.The
profile of adverse events observed with COREG CR in this small,
short-term study was generally similar to that observed with immediate-release
carvedilol. Differences in safety would not be expected based on the
similarity in plasma levels for COREG CR and immediate-release
carvedilol.<br/>Heart Failure: The following information describes the safety experience
in heart failure with immediate-release carvedilol. Carvedilol has been evaluated for safety in heart failure in more
than 4,500 patients worldwide of whom more than 2,100 participated
in placebo-controlled clinical trials. Approximately 60% of the total
treated population in placebo-controlled clinical trials received
carvedilol for at least 6 months and 30% received carvedilol
for at least 12 months. In the COMET trial, 1,511 patients with
mild-to-moderate heart failure were treated with carvedilol for up
to 5.9 years (mean 4.8 years). Both in US clinical trials
in mild-to-moderate heart failure that compared carvedilol in daily
doses up to 100 mg (n = 765) to placebo (n = 437),
and in a multinational clinical trial in severe heart failure (COPERNICUS)
thatcompared carvedilol in daily doses up to 50 mg (n = 1,156)
with placebo (n = 1,133), discontinuation rates for adverse
experiences were similar in carvedilol and placebo patients. In placebo-controlled
clinical trials, the only cause of discontinuation>1%, and occurring
more often on carvedilol was dizziness (1.3% on carvedilol, 0.6% on
placebo in the COPERNICUS trial). Table 3 shows
adverse events reported in patients with mild-to-moderate heart failure
enrolled in US placebo-controlled clinical trials, and with severe
heart failure enrolled in the COPERNICUS trial. Shown are adverse
events that occurred more frequently in drug-treated patients than
placebo-treated patients with an incidence of>3% in patients treated
with carvedilol regardless of causality. Median study medication exposure
was 6.3 months for both carvedilol and placebo patients in the
trials of mild-to-moderate heart failure, and 10.4 months in
the trial of severe heart failure patients. The adverse event profile
of carvedilol observed in the long-term COMET study was generally
similar to that observed in the US Heart Failure Trials. Cardiac failure and dyspnea were also reported
in these studies, but the rates were equal or greater in patients
who received placebo. The following adverse
events were reported with a frequency of>1% but���3% and more
frequently with carvedilol in either the US placebo-controlled trials
in patients with mild-to-moderate heart failure, or in patients with
severe heart failure in the COPERNICUS trial. Incidence>1% to���3% Body as a Whole: Allergy,
malaise, hypovolemia, fever, leg edema. Cardiovascular: Fluid overload, postural
hypotension, aggravated angina pectoris, AV block, palpitation, hypertension. Central and Peripheral Nervous
System: Hypesthesia, vertigo, paresthesia. Gastrointestinal: Melena, periodontitis. Liver and Biliary System: SGPT increased, SGOT increased. Metabolic and Nutritional: Hyperuricemia,
hypoglycemia, hyponatremia, increased alkaline phosphatase, glycosuria,
hypervolemia, diabetes mellitus, GGT increased, weight loss, hyperkalemia,
creatinine increased. Musculoskeletal: Muscle cramps. Platelet, Bleeding and Clotting: Prothrombin
decreased, purpura, thrombocytopenia. Psychiatric: Somnolence. Reproductive, male: Impotence. Special Senses: Blurred
vision. Urinary System: Renal insufficiency, albuminuria, hematuria.<br/>Left Ventricular Dysfunction Following
Myocardial Infarction: The following information describes the safety experience
in left ventricular dysfunction following acute myocardial infarction
with immediate-release carvedilol. Carvedilol
has been evaluated for safety in survivors of an acute myocardial
infarction with left ventricular dysfunction in the CAPRICORN trial
which involved 969 patients who received carvedilol and 980 who received
placebo. Approximately 75% of the patients received carvedilol for
at least 6 months and 53% received carvedilol for at least 12 months.
Patients were treated for an average of 12.9 months and 12.8 months
with carvedilol and placebo, respectively. The
most common adverse events reported with carvedilol in the CAPRICORN
trial were consistent with the profile of the drug in the US heart
failure trials and the COPERNICUS trial. The only additional adverse
events reported in CAPRICORN in>3% of the patients and more commonly
on carvedilol were dyspnea, anemia, and lung edema. The following
adverse events were reported with a frequency of>1% but���3%
and more frequently with carvedilol: Flu syndrome, cerebrovascular
accident, peripheral vascular disorder, hypotonia, depression, gastrointestinal
pain, arthritis, and gout. The overall rates of discontinuations due
to adverse events were similar in both groups of patients. In this
database, the only cause of discontinuation>1%, and occurring more
often on carvedilol was hypotension (1.5% on carvedilol, 0.2% on placebo).<br/>Hypertension: COREG CR was evaluated for safety in an 8-week
double-blind trial in 337 subjects with essential hypertension. The
profile of adverse events observed with COREG CR was generally
similar to that observed with immediate-release carvedilol. The overall
rates of discontinuations due to adverse events were similar between
COREG CR and placebo. The following information describes the safety
experience in hypertension with immediate-release carvedilol. Carvedilol has been evaluated for safety in hypertension
in more than 2,193 patients in US clinical trials and in 2,976 patients
in international clinical trials. Approximately 36% of the total treated
population received carvedilol for at least 6 months. In general,
carvedilol was well tolerated at doses up to 50 mg daily. Most
adverse events reported during carvedilol therapy were of mild to
moderate severity. In US controlled clinical trials directly comparing
carvedilol monotherapy in doses up to 50 mg (n = 1,142)
to placebo (n = 462), 4.9% of carvedilol patients discontinued
for adverse events vs. 5.2% of placebo patients. Although there was
no overalldifference in discontinuation rates, discontinuations were
more common in the carvedilol group for postural hypotension (1% vs.
0). The overall incidence of adverse events in US placebo-controlled
trials was found to increase with increasing dose of carvedilol. For
individual adverse events this could only be distinguished for dizziness,
which increased in frequency from 2% to 5% as total daily dose increased
from 6.25 mg to 50 mg as single or divided doses. Table 5 shows adverse events in US placebo-controlled
clinical trials for hypertension that occurred with an incidence of���1% regardless of causality, and that were more frequent in
drug-treated patients than placebo-treated patients. Dyspnea and fatigue were also reported in these
studies, but the rates were equal or greater in patients who received
placebo. The following adverse events not
described above were reported as possibly or probably related to carvedilol
in worldwide open or controlled trials with carvedilol in patients
with hypertension or heart failure. Incidence>0.1% to���1% Cardiovascular: Peripheral
ischemia, tachycardia. Central and Peripheral Nervous System: Hypokinesia. Gastrointestinal: Bilirubinemia,
increased hepatic enzymes (0.2% of hypertension patients and 0.4%
of heart failure patients were discontinued from therapy because of
increases in hepatic enzymes; see Laboratory Abnormalities.) Psychiatric: Nervousness,
sleep disorder, aggravated depression, impaired concentration, abnormal
thinking, paroniria, emotional lability. Respiratory System: Asthma (see CONTRAINDICATIONS). Reproductive: Male:
Decreased libido. Skin and Appendages: Pruritus, rash erythematous, rash
maculopapular, rash psoriaform, photosensitivity reaction. Special Senses: Tinnitus. Urinary System: Micturition
frequency increased. Autonomic Nervous System: Dry mouth, sweating increased. Metabolic and Nutritional: Hypokalemia, hypertriglyceridemia. Hematologic: Anemia, leukopenia. The following events were reported in���0.1% of
patients and are potentially important: Complete AV block, bundle
branch block, myocardial ischemia, cerebrovascular disorder, convulsions,
migraine, neuralgia, paresis, anaphylactoid reaction, alopecia, exfoliative
dermatitis, amnesia, GI hemorrhage, bronchospasm, pulmonary edema,
decreased hearing, respiratory alkalosis, increased BUN, decreased
HDL, pancytopenia, and atypical lymphocytes.<br/>Laboratory Abnormalities: Reversible elevations in serum transaminases (ALT
or AST) have been observed during treatment with carvedilol. Rates
of transaminase elevations (2- to 3-times the upper limit of normal)
observed during controlled clinical trials have generally been similar
between patients treated with carvedilol and those treated with placebo.
However, transaminase elevations, confirmed by rechallenge, have been
observed with carvedilol. In a long-term, placebo-controlled trial
in severe heart failure, patients treated with carvedilol had lower
values for hepatic transaminases than patients treated with placebo,
possibly because carvedilol-induced improvements in cardiac function
led to less hepatic congestion and/or improved hepatic blood flow. Carvedilol therapy has not been associated with clinically
significant changes in serum potassium, total triglycerides, total
cholesterol, HDL cholesterol, uric acid, blood urea nitrogen, or creatinine.
No clinically relevant changes were noted in fasting serum glucose
in hypertensive patients; fasting serum glucose was not evaluated
in the heart failure clinical trials.<br/>Postmarketing Experience: Reports of aplastic anemia and severe skin reactions
(Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema
multiforme) have been rare and received only when carvedilol was administered
concomitantly with other medications associated with such reactions.
Rare reports of hypersensitivity reactions (e.g., anaphylactic reaction,
angioedema, and urticaria) have been received for COREG' and
COREG CR, including cases occurring after the initiation of COREG
CR in patients previously treated with COREG. Urinary incontinence
in women (which resolved upon discontinuation of the medication) and
interstitial pneumonitis have been reported rarely.
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dailymed-instance:warning |
Cessation of Therapy with
COREG CR: Patients with coronary artery disease, who are being
treated with COREG CR, should be advised against abrupt discontinuation
of therapy. Severe exacerbation of angina and the occurrence of myocardial
infarction and ventricular arrhythmias have been reported in angina
patients following the abrupt discontinuation of therapy with��-blockers.
The last 2 complications may occur with or without preceding exacerbation
of the angina pectoris. As with other��-blockers, when discontinuation
of COREG CR is planned, the patients should be carefully observed
and advised to limit physical activity to a minimum. COREG CR
should be discontinued over 1 to 2 weeks whenever possible. If the
angina worsens or acute coronary insufficiency develops, it is recommended
that COREG CR be promptly reinstituted, at least temporarily.
Because coronary artery disease is common and may be unrecognized,
it may be prudent not to discontinue COREG CR therapy abruptly
even in patients treated only for hypertension or heart failure (see
DOSAGE AND ADMINISTRATION).<br/>Peripheral Vascular Disease: ��-blockers can precipitate or aggravate symptoms
of arterial insufficiency in patients with peripheral vascular disease.
Caution should be exercised in such individuals.<br/>Anesthesia and Major Surgery: If treatment with COREG CR is to be continued
perioperatively, particular care should be taken when anesthetic agents
which depress myocardial function, such as ether, cyclopropane, and
trichloroethylene, are used. See OVERDOSAGE for information on treatment
of bradycardia and hypertension.<br/>Diabetes and Hypoglycemia: In general,��-blockers may mask some of the
manifestations of hypoglycemia, particularly tachycardia. Nonselective��-blockers may potentiate insulin-induced hypoglycemia and delay
recovery of serum glucose levels. Patients subject to spontaneous
hypoglycemia, or diabetic patients receiving insulin or oral hypoglycemic
agents, should be cautioned about these possibilities. In heart failure
patients, there is a risk of worsening hyperglycemia (see PRECAUTIONS,
Effects on Glycemic Control in Type 2 Diabetic Patients).<br/>Thyrotoxicosis: ��-adrenergic blockade may mask clinical signs
of hyperthyroidism, such as tachycardia. Abrupt withdrawal of��-blockade
may be followed by an exacerbation of the symptoms of hyperthyroidism
or may precipitate thyroid storm.
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dailymed-instance:indicatio... |
Heart Failure: COREG CR is indicated for the treatment of
mild-to-severe heart failure of ischemic or cardiomyopathic origin,
usually in addition to diuretics, ACE inhibitor, and digitalis, to
increase survival and, also, to reduce the risk of hospitalization
(see CLINICAL TRIALS and PRECAUTIONS, Drug Interactions).<br/>Left Ventricular Dysfunction Following
Myocardial Infarction: COREG CR is indicated to reduce cardiovascular
mortality in clinically stable patients who have survived the acute
phase of a myocardial infarction and have a left ventricular ejection
fraction of���40% (with or without symptomatic heart failure)
(see CLINICAL TRIALS).<br/>Hypertension: COREG CR is indicated for the treatment of
essential hypertension. It can be used alone or in combination with
other antihypertensive agents, especially thiazide-type diuretics
(see PRECAUTIONS, Drug Interactions).
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dailymed-instance:represent... | |
dailymed-instance:routeOfAd... | |
dailymed-instance:name |
COREG CR
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