Major
carvedilol × clonidine
Alpha and beta blocker (non-selective β + α1)×Central α2-adrenergic agonist
Mechanism
Clonidine is an α2-agonist that reduces sympathetic tone. Carvedilol blocks β-receptors plus α1-receptors. On abrupt clonidine withdrawal, the α2 effect is lost while carvedilol's β-blockade persists – an 'unopposed' α1 effect develops with a sharp blood pressure rise.
Symptoms
Abrupt clonidine withdrawal causes hypertensive crisis: sharp blood pressure rise, headache, tachycardia, anxiety, sweating. Symptoms appear 18–24 hours after a missed clonidine dose.
Management
For planned clonidine withdrawal, stop carvedilol 3–7 days beforehand, then taper clonidine over 1–2 weeks. Alternative antihypertensive therapy: an ACE-I (enalapril) plus a calcium channel blocker (amlodipine) without clonidine.