Prescription Drug Information: Carvedilol Phosphate

CARVEDILOL PHOSPHATE- carvedilol phosphate capsule, extended release
Woodward Pharma Services LLC

1 INDICATIONS AND USAGE

1.1 Heart Failure

Carvedilol Phosphate extended-release capsules are indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ACE inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization [see Drug Interactions (7.4), Clinical Studies (14.1)].

1.2 Left Ventricular Dysfunction following Myocardial Infarction

Carvedilol Phosphate extended-release capsules 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 less than or equal to 40% (with or without symptomatic heart failure) [see Clinical Studies (14.2)].

1.3 Hypertension

Carvedilol Phosphate extended-release capsules are indicated for the management of essential hypertension [see Clinical Studies (14.3, 14.4)]. They can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics [see Drug Interactions (7.2)].

2 DOSAGE AND ADMINISTRATION

Carvedilol Phosphate extended-release capsules are intended for once-daily administration. Patients controlled with immediate-release carvedilol tablets alone or in combination with other medications may be switched to Carvedilol Phosphate extended-release capsules based on the total daily doses shown in Table 1.

Table 1. Dosing Conversion
Daily Dose of Immediate-Release Carvedilol Tablets Daily Dose of Carvedilol Phosphate extended-release capsules *
*
When switching from carvedilol 12.5 mg or 25 mg twice daily, a starting dose of Carvedilol Phosphate extended-release capsules 20 mg or 40 mg once daily, respectively, may be warranted for elderly patients or those at increased risk of hypotension, dizziness, or syncope. Subsequent titration to higher doses should, as appropriate, be made after an interval of at least 2 weeks.
6.25 mg (3.125 mg twice daily) 10 mg once daily
12.5 mg (6.25 mg twice daily) 20 mg once daily
25 mg (12.5 mg twice daily) 40 mg once daily
50 mg (25 mg twice daily) 80 mg once daily

Carvedilol Phosphate extended-release capsules should be taken once daily in the morning with food. Carvedilol Phosphate extended-release capsules should be swallowed whole. Carvedilol Phosphate extended-release capsules and/or their contents should not be crushed, chewed, or taken in divided doses.

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 should not be stored for future use. Absorption of the beads sprinkled on other foods has not been tested.

2.1 Heart Failure

DOSAGE MUST BE INDIVIDUALIZED AND CLOSELY MONITORED BY A PHYSICIAN DURING UP-TITRATION. Prior to initiation of Carvedilol Phosphate extended-release capsules, it is recommended that fluid retention be minimized. The recommended starting dose of Carvedilol Phosphate extended-release capsules 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 Carvedilol Phosphate extended-release capsules from that of the ACE inhibitor or to reduce temporarily the dose of the ACE inhibitor. The dose of Carvedilol Phosphate extended-release capsules 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 Carvedilol Phosphate extended-release capsules should be reduced if patients experience bradycardia (heart rate less than 55 beats per minute).

Episodes of dizziness or fluid retention during initiation of Carvedilol Phosphate extended-release capsules can generally be managed without discontinuation of treatment and do not preclude subsequent successful titration of, or a favorable response to, Carvedilol Phosphate extended-release capsules.

2.2 Left Ventricular Dysfunction following Myocardial Infarction

DOSAGE MUST BE INDIVIDUALIZED AND MONITORED DURING UP-TITRATION. Treatment with Carvedilol Phosphate extended-release capsules 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 Phosphate extended-release capsules 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 β-blocker during the acute phase of the myocardial infarction.

2.3 Hypertension

DOSAGE MUST BE INDIVIDUALIZED. The recommended starting dose of Carvedilol Phosphate extended-release capsules is 20 mg once 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 40 mg once daily if needed, based on trough blood pressure, again using standing systolic pressure 1 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 Carvedilol Phosphate extended-release capsules would be seen within 7 to 14 days as had been demonstrated with immediate-release carvedilol. Total daily dose should not exceed 80 mg.

Concomitant administration with a diuretic can be expected to produce additive effects and exaggerate the orthostatic component of carvedilol action.

2.4 Hepatic Impairment

Carvedilol Phosphate extended-release capsules should not be given to patients with severe hepatic impairment [see Contraindications (4)].

2.5 Geriatric Use

When switching elderly patients (aged 65 years or older) who are taking the higher doses of immediate-release carvedilol tablets (25 mg twice daily) to Carvedilol Phosphate extended-release capsules, a lower starting dose (40 mg) of Carvedilol Phosphate extended-release capsules is recommended to minimize the potential for dizziness, syncope, or hypotension [see Dosage and Administration (2)]. Patients who have switched and who tolerate Carvedilol Phosphate extended-release capsules should, as appropriate, have their dose increased after an interval of at least 2 weeks [see Use in Specific Populations (8.5)].

3 DOSAGE FORMS AND STRENGTHS

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 “GSLGK” and “10 mg”
  • 20 mg – white and yellow capsule shell printed with “GSMHV” and “20 mg”
  • 40 mg – yellow and green capsule shell printed with “GSETX” and “40 mg”
  • 80 mg – white capsule shell printed with “GSF1L” and “80 mg”

4 CONTRAINDICATIONS

Carvedilol Phosphate extended-release capsules are contraindicated in the following conditions:

  • Bronchial asthma or related bronchospastic conditions. Deaths from status asthmaticus have been reported following single doses of immediate-release carvedilol.
  • Second- or third-degree AV block.
  • Sick sinus syndrome.
  • Severe bradycardia (unless a permanent pacemaker is in place).
  • 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 Carvedilol Phosphate extended-release capsules.
  • Patients with severe hepatic impairment.
  • 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 Carvedilol Phosphate extended-release capsules.

5 WARNINGS AND PRECAUTIONS

In clinical trials of Carvedilol Phosphate extended-release capsules in subjects with hypertension (338 subjects) and in subjects 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 Carvedilol Phosphate extended-release capsules as well as immediate-release carvedilol tablets.

5.1 Cessation of Therapy

Patients with coronary artery disease, who are being treated with Carvedilol Phosphate extended-release capsules, 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 patients with angina 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 Phosphate extended-release capsules is planned, the patients should be carefully observed and advised to limit physical activity to a minimum. Carvedilol Phosphate extended-release capsules should be discontinued over 1 to 2 weeks whenever possible. If the angina worsens or acute coronary insufficiency develops, it is recommended that Carvedilol Phosphate extended-release capsules 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 Phosphate extended-release capsules abruptly even in patients treated only for hypertension or heart failure.

5.2 Bradycardia

In clinical trials with immediate-release carvedilol, bradycardia was reported in about 2% of hypertensive subjects, 9% of subjects with heart failure, and 6.5% of subjects with myocardial infarction with left ventricular dysfunction. Bradycardia was reported in 0.5% of subjects receiving Carvedilol Phosphate extended-release capsules in a trial of subjects with heart failure and subjects with myocardial infarction and left ventricular dysfunction. There were no reports of bradycardia in the clinical trial of Carvedilol Phosphate extended-release capsules in hypertension. However, if pulse rate drops below 55 beats per minute, the dosage of Carvedilol Phosphate extended-release capsules should be reduced.

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