carvedilol 3.125 MG Oral Tablet
Generic Name: CARVEDILOL
Brand Name: Carvedilol
- Substance Name(s):
• CYP P450 2D6 enzyme inhibitors may increase and rifampin may decrease carvedilol levels.
( 7.1 , 7.5 ) • Hypotensive agents (e.g., reserpine, MAO inhibitors, clonidine) may increase the risk of hypotension and/or severe bradycardia.
( 7.2 ) • Cyclosporine or digoxin levels may increase.
( 7.3 , 7.4 ) • Both digitalis glycosides and β-blockers slow atrioventricular conduction and decrease heart rate.
Concomitant use can increase the risk of bradycardia.
( 7.4 ) • Amiodarone may increase carvedilol levels resulting in further slowing of the heart rate or cardiac conduction.
( 7.6 ) • Verapamil- or diltiazem-type calcium channel blockers may affect ECG and/or blood pressure.
(7.6) • Insulin and oral hypoglycemics action may be enhanced.
(7.7) 7.1 CYP2D6 Inhibitors and Poor Metabolizers Interactions of carvedilol with potent inhibitors of CYP2D6 isoenzyme (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 (12.3)].
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 α-blocking R(+) enantiomer.
7.2 Hypotensive Agents Patients taking both agents with β-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.
Concomitant administration of clonidine with agents with β-blocking properties may potentiate blood-pressure and heart-rate-lowering effects.
When concomitant treatment with agents with β-blocking properties and clonidine is to be terminated, the β-blocking agent should be discontinued first.
Clonidine therapy can then be discontinued several days later by gradually decreasing the dosage.
7.3 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.
7.4 Digitalis Glycosides Both digitalis glycosides and β-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 Carvedilol tablets [see CLINICAL PHARMACOLOGY (12.5) ].
7.5 Inducers/Inhibitors of Hepatic Metabolism Rifampin reduced plasma concentrations of carvedilol by about 70% [see CLINICAL PHARMACOLOGY (12.5) ].
Cimetidine increased AUC by about 30% but caused no change in C max [see CLINICAL PHARMACOLOGY (12.5) ].
7.6 Amiodarone Amiodarone, and its metabolite desethyl amiodarone, inhibitors of CYP2C9 and P385 glycoprotein, increased concentrations of the S(-) enantiomer of carvedilol by at least 2-fold [see CLINICAL PHARMACOLOGY (12.5)].
The concomitant administration of amiodarone or other CYP2C9 inhibitors such as fluconazole with carvedilol may enhance the β-blocking properties of carvedilol resulting in further slowing of the heart rate or cardiac conduction.
Patients should be observed for signs of bradycardia or heart block, particularly when one agent is added to pre-existing treatment with the other.
7.7 Calcium Channel Blockers Conduction disturbance (rarely with hemodynamic compromise) has been observed when carvedilol tablet is co-administered with diltiazem.
As with other agents with β-blocking properties, if carvedilol tablet is to be administered with calcium channel blockers of the verapamil or diltiazem type, it is recommended that ECG and blood pressure be monitored.
7.8 Insulin or Oral Hypoglycemics Agents with β-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 [see WARNINGS AND PRECAUTIONS (5.6)].
7.9 Anesthesia If treatment with carvedilol extended-release capsules 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 (10) ].
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, β-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.
Cases of overdosage with carvedilol tablets 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.
Carvedilol is a nonselective β-adrenergic blocking agent with α 1 -blocking activity.
It is (±)-1-(Carbazol-4-yloxy)-3-[[2-(o-methoxyphenoxy)ethyl]amino]-2-propanol.
Carvedilol is a racemic mixture with the following structure: Carvedilol, USP is a white to almost white crystalline powder with a molecular weight of 406.5 and a molecular formula of C 24 H 26 N 2 O 4 .
It is freely soluble in dimethylsulfoxide; soluble in methylene chloride and methanol; sparingly soluble in 95% ethanol and isopropanol; slightly soluble in ethyl ether; and practically insoluble in water, gastric fluid (simulated, TS, pH 1.1), and intestinal fluid (simulated, TS without pancreatin, pH 7.5).
Each carvedilol tablet, USP intended for oral administration contains 3.125 mg or 6.25 mg or 12.5 mg or 25 mg of carvedilol.
In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, crospovidone, hypromellose, lactose monohydrate, magnesium stearate, polyethylene glycol, povidone, talc, and titanium dioxide.
The product meets USP Dissolution Test 3.
structured formula for carvedilol
14.1 Left Ventricular Dysfunction Following Myocardial Infarction CAPRICORN was a double-blind study comparing carvedilol and placebo in 1,959 patients with a recent myocardial infarction (within 21 days) and left ventricular ejection fraction of ≤40%, with (47%) or without symptoms of heart failure.
Patients given carvedilol received 6.25 mg twice daily, titrated as tolerated to 25 mg twice daily.
Patients had to have a systolic blood pressure >90 mm Hg, a sitting heart rate >60 beats/minute, and no contraindication to β-blocker use.
Treatment of the index infarction included aspirin (85%), IV or oral β-blockers (37%), nitrates (73%), heparin (64%), thrombolytics (40%), and acute angioplasty (12%).
Background treatment included ACE inhibitors or angiotensin receptor blockers (97%), anticoagulants (20%), lipid-lowering agents (23%), and diuretics (34%).
Baseline population characteristics included an average age of 63 years, 74% male, 95% Caucasian, mean blood pressure 121/74 mm Hg, 22% with diabetes, and 54% with a history of hypertension.
Mean dosage achieved of carvedilol was 20 mg twice daily; mean duration of follow-up was 15 months.
All-cause mortality was 15% in the placebo group and 12% in the carvedilol group, indicating a 23% risk reduction in patients treated with carvedilol (95% CI 2-40%, p = 0.03), as shown in Figure 1.
The effects on mortality in various subgroups are shown in Figure 2.
Nearly all deaths were cardiovascular (which were reduced by 25% by carvedilol), and most of these deaths were sudden or related to pump failure (both types of death were reduced by carvedilol).
Another study end point, total mortality and all-cause hospitalization, did not show a significant improvement.
There was also a significant 40% reduction in fatal or non-fatal myocardial infarction observed in the group treated with carvedilol (95% CI 11% to 60%, p = 0.01).
A similar reduction in the risk of myocardial infarction was also observed in a meta-analysis of placebo-controlled trials of carvedilol in heart failure.
Figure 1 Survival Analysis for CAPRICORN (intent-to-treat) Figure 2.
Effects on Mortality for Subgroups in CAPRICORN structured formula for carvedilol structured formula for carvedilol 14.2 Hypertension Carvedilol tablets were studied in 2 placebo-controlled trials that utilized twice-daily dosing, at total daily doses of 12.5 to 50 mg.
In these and other studies, the starting dose did not exceed 12.5 mg.
At 50 mg/day, carvedilol tablets reduced sitting trough (12-hour) blood pressure by about 9/5.5 mm Hg; at 25 mg/day the effect was about 7.5/3.5 mm Hg.
Comparisons of trough to peak blood pressure showed a trough to peak ratio for blood pressure response of about 65%.
Heart rate fell by about 7.5 beats/minute at 50 mg/day.
In general, as is true for other β-blockers, responses were smaller in black than non-black patients.
There were no age- or gender-related differences in response.
The peak antihypertensive effect occurred 1 to 2 hours after a dose.
The dose-related blood pressure response was accompanied by a dose-related increase in adverse effects [see ADVERSE REACTIONS (6)].
14.3 Hypertension With Type 2 Diabetes Mellitus In a double-blind study (GEMINI), carvedilol, added to an ACE inhibitor or angiotensin receptor blocker, was evaluated in a population with mild-to-moderate hypertension and well controlled type 2 diabetes mellitus.
The mean HbA1c at baseline was 7.2%.
carvedilol was titrated to a mean dose of 17.5 mg twice daily and maintained for 5 months.
Carvedilol had no adverse effect on glycemic control, based on HbA1c measurements (mean change from baseline of 0.02%, 95% CI -0.06 to 0.10, p = NS) [see WARNINGS AND PRECAUTIONS (5.6)].
/STORAGE AND HANDLING Carvedilol Tablets USP, 3.125 mg are white to off-white, round, biconvex, film-coated tablets debossed with ‘Z’ on one side and ‘1’ on other side and are supplied as follows: NDC-63187-570-30 in bottles of 30 tablets NDC-63187-570-60 in bottles of 60 tablets NDC-63187-570-90 in bottles of 90 tablets Storage: Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature].
Protect from moisture.
Dispense in a tight, light-resistant container.
RECENT MAJOR CHANGES
Warnings and Precautions, Major Surgery (5.9) October 2010 Warnings and Precautions, Intraoperative Floppy Iris Syndrome January 2011 (5.14)
8.5 Geriatric Use Of the 975 myocardial infarction patients randomized to carvedilol tablets 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 treated with carvedilol tablets, 21% (436) were 65 years of age or older.
Of 3,722 patients receiving carvedilol tablets 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 versus 6% in younger patients), no overall differences in the safety or effectiveness (see Figure 2 ) 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.
DOSAGE FORMS AND STRENGTHS
Tablets: 3.125, 6.25, 12.5, 25 mg ( 3 ) The white to off-white, round, film-coated tablets are available in the following strengths: 3.125 mg– debossed with Z and 1, 6.25 mg–debossed with ZC40, 12.5 mg–debossed with ZC41 and 25 mg–debossed with ZC42.
MECHANISM OF ACTION
12.1 Mechanism of Action Carvedilol is a racemic mixture in which nonselective β-adrenoreceptor blocking activity is present in the S(-) enantiomer and α 1 -adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency.
carvedilol has no intrinsic sympathomimetic activity.
INDICATIONS AND USAGE
Carvedilol tablets, USP is an alpha/beta-adrenergic blocking agent indicated for the treatment of: • Left ventricular dysfunction following myocardial infarction in clinically stable patients( 1.1 ) • Hypertension( 1.2 ) 1.1 Left Ventricular Dysfunction Following Myocardial Infarction Carvedilol tablets, USP are 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 Studies (14.1)].
1.2 Hypertension Carvedilol tablets, USP are indicated for the management of essential hypertension [see Clinical Studies (14.2)] .
It can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics [see Drug Interactions (7.2)].
8.4 Pediatric Use Effectiveness of carvedilol tablets 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 β-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 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%).
8.1 Pregnancy 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 maximum recommended human dose [MRHD] as mg/m 2 ) and in rabbits at doses of 75 mg/kg/day (25 times the MRHD as mg/m 2 ).
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 2 ), 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 2 ); in rabbits it was 15 mg/kg/day (5 times the MRHD as mg/m 2 ).
There are no adequate and well-controlled studies in pregnant women.
Carvedilol tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
8.3 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 β-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 2 ) 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 β-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 α- and β-blocking agents have included perinatal and neonatal distress.
WARNING AND CAUTIONS
WARNINGS AND PRECAUTIONS • Acute exacerbation of coronary artery disease upon cessation of therapy: Do not abruptly discontinue.
( 5.1 ) • Bradycardia, hypotension, worsening heart failure/fluid retention may occur.
Reduce the dose as needed.
( 5.2 , 5.3 , 5.4 ) • Non-allergic bronchospasm (e.g., chronic bronchitis and emphysema): Avoid β-blockers.
( 4 ) However, if deemed necessary, use with caution and at lowest effective dose.
( 5.5 ) • Diabetes: Monitor glucose as β-blockers may mask symptoms of hypoglycemia or worsen hyperglycemia.
( 5.6 ) 5.1 Cessation of Therapy Patients with coronary artery disease, who are being treated with carvedilol tablets, 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 β-blockers.
The last 2 complications may occur with or without preceding exacerbation of the angina pectoris.
As with other β-blockers, when discontinuation of carvedilol tablets is planned, the patients should be carefully observed and advised to limit physical activity to a minimum.
Carvedilol tablets should be discontinued over 1 to 2 weeks whenever possible.
If the angina worsens or acute coronary insufficiency develops, it is recommended that carvedilol tablets be promptly reinstituted, at least temporarily.
Because coronary artery disease is common and may be unrecognized, it may be prudent not to discontinue therapy with carvedilol abruptly even in patients treated only for hypertension or heart failure.
5.2 Bradycardia In clinical trials, carvedilol tablets caused bradycardia in about 2% of hypertensive patients, and 6.5% of myocardial infarction patients with left ventricular dysfunction.
If pulse rate drops below 55 beats/minute, the dosage should be reduced.
5.3 Hypotension Postural hypotension occurred in 1.8% and syncope in 0.1% of hypertensive patients, 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, hypotension or postural hypotension occurred in 20.2% of patients receiving carvedilol tablets 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 tablets, compared to 0.2% of placebo patients.
Starting with a low dose, administration with food, and gradual up-titration should decrease the likelihood of syncope or excessive hypotension [see DOSAGE AND ADMINISTRATION (2.1, 2.2)].
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.
5.4 Heart Failure/Fluid Retention Worsening heart failure or fluid retention may occur during up-titration of carvedilol.
If such symptoms occur, diuretics should be increased and the carvedilol dose should not be advanced until clinical stability resumes [see DOSAGE AND ADMINISTRATION ( 2 ) ].
Occasionally it is necessary to lower the carvedilol dose or temporarily discontinue it.
Such episodes do not preclude subsequent successful titration of, or a favorable response to, carvedilol.
5.5 Non-allergic Bronchospasm Patients with bronchospastic disease (e.g., chronic bronchitis and emphysema) should, in general, not receive β-blockers.
Carvedilol tablets may be used with caution, however, in patients who do not respond to, or cannot tolerate, other antihypertensive agents.
It is prudent, if carvedilol tablets are used, to use the smallest effective dose, so that inhibition of endogenous or exogenous β-agonists is minimized.
In clinical trials, 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 carvedilol 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.
5.6 Glycemic Control in Type 2 Diabetes In general, β-blockers may mask some of the manifestations of hypoglycemia, particularly tachycardia.
Nonselective β-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.
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 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 STUDIES (14.4) ].
5.7 Peripheral Vascular Disease β-blockers can precipitate or aggravate symptoms of arterial insufficiency in patients with peripheral vascular disease.
Caution should be exercised in such individuals.
5.8 Deterioration of Renal Function 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 carvedilol and the drug discontinued or dosage reduced if worsening of renal function occurs.
5.9 Major Surgery Chronically administered beta-blocking therapy should not be routinely withdrawn prior to major surgery; however, the impaired ability of the heart to respond to reflex adrenergic stimuli may augment the risks of general anesthesia and surgical procedures.
5.10 Thyrotoxicosis β-adrenergic blockade may mask clinical signs of hyperthyroidism, such as tachycardia.
Abrupt withdrawal of β-blockade may be followed by an exacerbation of the symptoms of hyperthyroidism or may precipitate thyroid storm.
5.11 Pheochromocytoma In patients with pheochromocytoma, an α-blocking agent should be initiated prior to the use of any β-blocking agent.
Although carvedilol has both α- and β-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.
5.12 Prinzmetal’s Variant Angina Agents with non-selective β-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 α-blocking activity may prevent such symptoms.
However, caution should be taken in the administration of carvedilol to patients suspected of having Prinzmetal’s variant angina.
5.13 Risk of Anaphylactic Reaction While taking β-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.
5.14 Intraoperative Floppy Iris Syndrome Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in some patients treated with alpha-1 blockers (carvedilol is an alpha/beta blocker).
This variant of small pupil syndrome is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs, and potential prolapse of the iris toward the phacoemulsification incisions.
The patient’s ophthalmologist should be prepared for possible modifications to the surgical technique, such as utilization of iris hooks, iris dilator rings, or viscoelastic substances.
There does not appear to be a benefit of stopping alpha-1 blocker therapy prior to cataract surgery.
INFORMATION FOR PATIENTS
PATIENT COUNSELING INFORMATION See FDA-Approved Patient Labeling [ 17.2 ] 17.1 Patient Advice Patients taking carvedilol tablets should be advised of the following: • Patients should take carvedilol tablets with food.
• Patients should not interrupt or discontinue using carvedilol tablets without a physician’s advice.
• Patients should consult their physician if they experience signs or symptoms of worsening heart failure such as weight gain or increasing shortness of breath.
• Patients may experience a drop in blood pressure when standing, resulting in dizziness and, rarely, fainting.
Patients should sit or lie down when these symptoms of lowered blood pressure occur.
• If experiencing dizziness or fatigue, patients should avoid driving or hazardous tasks.
• Patients should consult a physician if they experience dizziness or faintness, in case the dosage should be adjusted.
• Diabetic patients should report any changes in blood sugar levels to their physician.
• Contact lens wearers may experience decreased lacrimation.
17.2 FDA-Approved Patient Labeling Patient labeling is provided separately.
DOSAGE AND ADMINISTRATION
Take with food.
Individualize dosage and monitor during up-titration.
( 2 ) • Left ventricular dysfunction following myocardial infarction: Start at 6.25 mg twice daily and increase to 12.5 mg then 25 mg twice daily after intervals of 3 to 10 days.
A lower starting dose or slower titration may be used.( 2.1 ) • Hypertension: Start at 6.25 mg twice daily and increase if needed for blood pressure control to 12.5 mg then 25 mg twice daily over intervals of 1 to 2 weeks.( 2.2 ) Carvedilol should be taken with food to slow the rate of absorption and reduce the incidence of orthostatic effects.
2.1 Left Ventricular Dysfunction Following Myocardial Infarction DOSAGE MUST BE INDIVIDUALIZED AND MONITORED DURING UP-TITRATION.
Treatment with carvedilol tablets 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 carvedilol tablets be started at 6.25 mg twice daily and increased after 3 to 10 days, based on tolerability, to 12.5 mg twice daily, then again to the target dose of 25 mg twice daily.
A lower starting dose may be used (3.125 mg twice 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 β-blocker during the acute phase of the myocardial infarction.
2.2 Hypertension DOSAGE MUST BE INDIVIDUALIZED.
The recommended starting dose of carvedilol tablets is 6.25 mg twice daily.
If this dose is tolerated, using standing systolic pressure measured about 1 hour after dosing as a guide, the dose should be maintained for 7 to 14 days, and then increased to 12.5 mg twice 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 25 mg twice daily if tolerated and needed.
The full antihypertensive effect of carvedilol tablet is seen within 7 to 14 days.
Total daily dose should not exceed 50 mg.
Concomitant administration with a diuretic can be expected to produce additive effects and exaggerate the orthostatic component of carvedilol action.
2.3 Hepatic Impairment Carvedilol tablets should not be given to patients with severe hepatic impairment [see CONTRAINDICATIONS (4)].