Trade name(s): Carvedilol Sandoz Drug Class: Adrenoreceptor Blocker
Pharmacological action:
Carvedilol is a competitive antagonist at alpha and beta-1,2,3 adrenoreceptors in the heart, vasculature, pancreas, liver, brain, and lungs. It reduces HTN by vasodilation of peripheral vessels (via a1) which indirectly reduces work on the heart. Carvedilol also directly lessens heart work and oxygen consumption as a result.
Pharmacokinetics:
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Absorption: Following oral administration of 25mg capsule to healthy subjects peak Plasma conc of 21mg/L reached after 1.5 hours. Cmax related to dose linearly. Bioavailability seems to be 25% in healthy male subjects.
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Distribution: Plasma protein binding of 95% Distribution volume ranges from 1.5-2 L/kg body weight
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Metabolism: Metabolised to 4 compound (3 acting weakly and one being 13 times as potent) in the liver and secreted through the bile. Main p450 isoforms involved with metabolisation are the CYP2d6 (R- and S-enantiomer) and CYP2C9 (S-enantiomer) Half life = 6.5 hours (this is unclear in the MEDSAFE documents IMO)
Substrate of P-glycoprotein.
- Excretion: 60% secreted into bile and 16% excreted through the urinary system
Indications:
Hypertension, angina, chronic heart failure, left ventricular struggle after an MI, Afib for vent rate control (unapproved), prevention of bleeding from large or medial oesophagal varices in individuals with liver cirrhosis and portal hypertension
Contraindications/precautions:
Asthma due to parasympathetic bronchospasm, acute heart failure due to reducing heart function, Prinzmetals angina. bradycardia, hypotension, sick sinus syndrome, 2nd or 3rd degree AV block. cardiogenic shock metabolic acidosis severe peripheral arterial disease
Adverse reactions: ≥10%: Cardiac failure, fatigue, dizziness, headache, hypotension. ≥1%-≤10%: GI disturbances, eye disorders, bradycardia, hypovolaemia. ≤1: AV block, angina, constipation, paraethesia, sleep disorders, erectile dysfunction, skin reactions.
Interactions: Do not use with any asthma medication because people with asthma may experience fatal bronchospasm. Do not use with the anaesthetic methoylflurane as this can synergise with carvedilol in slowing the heart, to a fatal amount.
In general caution mixing with other medication which cause bradycardia and or proparasympathetic action as these can over-shoot
Dosing/Current guidelines: Generally the target dose is 25 mg twice daily however it is reccomended that dosing be slowly increased until target is reached. Dose increase speed depends on disease. 50mg is max daily dose recommended.
Oral tablets is the only subsidised formulation and is available in 6.25mg, 12.5mg and 25mg oral tablet doses.
When getting patients off medication it is important to gradually reduce the dose to stop sudden withdrawal.
Overdose: Signs: severe hypotension, bradycardia, heart failure, cardiogenic shock and cardiac arrest.
Treatment: monitor for above signs and manage according to best practice on ß-blocker overdose (for example: β-sympathomimetics, glucagon and phosphodiesterase inhibitors)
Monitoring:
Pregnancy: Studies suggest risk in 2nd and 3rd trimesters. Breastfeeding: Manufacturer says avoid but also amount in milk unlikely to affect child.
Subsidisation: Fully subsidised in oral tablet form.
What to tell patients: Use caution when driving or operating machinery. Seek medical advice if you develop any adverse effects.
Comments/Observations/notes:
Pill contains lactose so may be unsuitable for lactose intolerant patients.