Major
clonidine × Sildenafil
Central α2-adrenergic agonist×Phosphodiesterase type 5 inhibitors (PDE5)
Mechanism
Additive hypotensive effect. Sildenafil vasodilates by blocking phosphodiesterase-5; clonidine lowers blood pressure via central α2-agonism. Combined action can cause symptomatic hypotension.
Symptoms
Sudden blood pressure drop: postural dizziness, syncope. Particularly dangerous in older patients and in ischaemic heart disease.
Management
The combination is acceptable in stable hypertension. Cap sildenafil at 25 mg (instead of 50–100 mg). Warn the patient about orthostatic hypotension; take the first dose lying down.