Amlodipine Pre-Surgery Hold Window: What Clinicians Need to Know

Does the amlodipine label give a pre-surgery hold window?

No. The dosing and warnings sections of the Norvasc label contain no pre-surgery hold window. The dosing section gives a usual adult starting dose of 5 mg once daily and a maximum of 10 mg once daily; small, fragile or elderly patients and patients with hepatic insufficiency may start at 2.5 mg once daily, and the label says that in general 7 to 14 days should pass between titration steps [1]. The warnings section covers symptomatic hypotension, worsening angina or myocardial infarction after starting or increasing the dose, and slow titration in severe hepatic impairment [1].

The label statement closest to the day of surgery is the hypotension warning: symptomatic hypotension is possible, particularly in severe aortic stenosis, but acute hypotension is unlikely because amlodipine's onset of effect is gradual [1]. Amlodipine is a peripheral arterial vasodilator, it has no boxed warning, and known sensitivity to amlodipine is its only contraindication [1].

What 24 hours off amlodipine does to blood levels

Amlodipine peaks in plasma 6 to 12 hours after a dose, reaches steady state after 7 to 8 days of once-daily dosing, and has absolute bioavailability of 64% to 90%, unchanged by food [1]. Its terminal half-life is about 30 to 50 hours, so a substantial amount can remain 24 hours after a dose [1].

In 12 healthy volunteers, mean half-life was 34 hours after a 10 mg intravenous dose and 36 hours after a 10 mg oral dose [3]. In a second study reported in the same paper, 28 volunteers taking 15 mg once daily for 14 days had a mean half-life of 45 hours [3].

Liver function and age move these numbers. In impaired hepatic function the label gives a plasma elimination half-life of 56 hours, and elderly patients and patients with hepatic insufficiency have about 40% to 60% higher exposure (AUC) [1]. The label says these patients may start at 2.5 mg once daily, and it calls for slow titration in severe hepatic impairment [1].

Medicines that change amlodipine exposure

Diltiazem 180 mg daily with amlodipine 5 mg raised amlodipine exposure by 60% in elderly hypertensive patients; strong CYP3A inhibitors such as itraconazole and clarithromycin may raise concentrations further, while erythromycin did not significantly change exposure [1]. The label says to monitor for symptoms of hypotension and edema when amlodipine is co-administered with a CYP3A inhibitor [1].

In a cohort of older adults taking calcium-channel blockers (amlodipine in more than half), a new clarithromycin prescription compared with azithromycin was associated within 30 days with more hospitalizations for acute kidney injury, more hospitalizations for hypotension and higher all-cause mortality [4].

For CYP3A inducers the label gives no quantitative information and says blood pressure should be closely monitored [1].