Carvedilol: Difference between revisions

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Beta blocker (non-selective, with alpha-1 antagonism), Antihypertensive, Heart failure medicine

Carvedilol

Coreg, Coreg CR

Experience

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Problems

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Titration strategies

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Effects

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Summary

Classes

Beta blocker (non-selective, with alpha-1 antagonism), Antihypertensive, Heart failure medicine

Pharmacy

Starting dose

Heart failure: 3.125 mg PO BID, doubling every 2 weeks as tolerated to target 25 mg BID (50 mg BID if >85 kg). Hypertension: 6.25 mg PO BID, titrate to 25 mg BID

Preparations

IR tablets 3.125, 6.25, 12.5, 25 mg; Coreg CR capsules 10, 20, 40, 80 mg (once-daily)

US FDA Max

50 mg BID in heart failure (or once-daily equivalent CR); 25 mg BID in hypertension

Pharmacology

Routes

Oral

Onset

Antihypertensive effect within 1 week; heart-failure mortality benefit accrues over months of titration

Duration

~12 hours (IR); 24 hours (CR)

Half-life

7-10 hours^[1]

Bioavailability

~25-35% (extensive first-pass), increased by food which slows absorption and reduces orthostatic risk^[1]

Pregnancy

Limited human data; β-blocker class effects include fetal growth restriction and neonatal bradycardia/hypoglycemia.^{[citation needed]}

Legal status

Rx-only in US

Purported mechanism

Non-selective β1/β2-adrenergic receptor antagonist with additional α1-adrenergic antagonism, giving combined heart-rate-and-contractility blunting plus peripheral vasodilation. The α1 blockade and ancillary antioxidant activity distinguish carvedilol from cardioselective β-blockers, and explain its strong mortality benefit in heart failure with reduced ejection fraction shown in COPERNICUS, CAPRICORN, and US Carvedilol Heart Failure Trials.0 CYP2D6 metabolism produces stereoselective clearance; CYP2D6 poor metabolizers have higher plasma exposure and may need lower doses^[1].

References

↑ ^1.0 ^1.1 ^1.2 FDA Prescribing Information, Coreg (carvedilol), GSK/Woodward, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020297s039lbl.pdf

[coreg-label-1] 1.0 ^1.1 ^1.2 FDA Prescribing Information, Coreg (carvedilol), GSK/Woodward, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020297s039lbl.pdf

[1]

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-{{Stub}}
 {{MedTemplate
-| generic = Carvedilol
+| generic           = Carvedilol
-| brand   = Coreg
+| brand             = Coreg, Coreg CR
-| classes = Beta blocker
+| structure         =
-| intro   = Carvedilol is a non-selective beta blocker that also has blood-vessel-widening (vasodilating) activity, used in heart failure and other cardiovascular conditions.
+| classes           = [[:Category:Beta blockers|Beta blocker (non-selective, with alpha-1 antagonism)]], [[:Category:Antihypertensives|Antihypertensive]], [[:Category:Heart failure medicines|Heart failure medicine]]
+| uses              = <vote slug="heart-failure-reduced-ef-use">Heart failure with reduced ejection fraction (FDA; foundational guideline-directed medical therapy)</vote>, <vote slug="post-mi-lv-dysfunction-use">Left ventricular dysfunction after myocardial infarction (FDA)</vote>, <vote slug="hypertension-use">Hypertension (FDA)</vote>, <vote slug="angina-use">Stable angina (off-label)</vote>
+| starting_dose     = Heart failure: 3.125 mg PO BID, doubling every 2 weeks as tolerated to target 25 mg BID (50 mg BID if >85 kg). Hypertension: 6.25 mg PO BID, titrate to 25 mg BID
+| preparations      = IR tablets 3.125, 6.25, 12.5, 25 mg; Coreg CR capsules 10, 20, 40, 80 mg (once-daily)
+| fda_max           = 50 mg BID in heart failure (or once-daily equivalent CR); 25 mg BID in hypertension
+| pill_id           =
+| routes            = Oral
+| onset             = Antihypertensive effect within 1 week; heart-failure mortality benefit accrues over months of titration
+| duration          = ~12 hours (IR); 24 hours (CR)
+| halflife          = 7-10 hours<ref name="coreg-label">FDA Prescribing Information, Coreg (carvedilol), GSK/Woodward, current revision. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020297s039lbl.pdf</ref>
+| bioavailability   = ~25-35% (extensive first-pass), increased by food which slows absorption and reduces orthostatic risk<ref name="coreg-label" />
+| pregnancy         = Limited human data; β-blocker class effects include fetal growth restriction and neonatal bradycardia/hypoglycemia.{{citation needed}}
+| legal             = [[USLegal:Prescription only|Rx-only]] in US
+| mechanism         = <vote slug="carvedilol-mech-claim">Non-selective β1/β2-adrenergic receptor antagonist with additional α1-adrenergic antagonism, giving combined heart-rate-and-contractility blunting plus peripheral vasodilation. The α1 blockade and ancillary antioxidant activity distinguish carvedilol from cardioselective β-blockers, and explain its strong mortality benefit in heart failure with reduced ejection fraction shown in COPERNICUS, CAPRICORN, and US Carvedilol Heart Failure Trials.</vote> CYP2D6 metabolism produces stereoselective clearance; CYP2D6 poor metabolizers have higher plasma exposure and may need lower doses<ref name="coreg-label" />.
 }}
+== References ==
+<references />
+[[Category:Beta blockers]]
+[[Category:Antihypertensives]]
+[[Category:Heart failure medicines]]

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