Amlodipine Seasonal Use Considerations: A Clinical Guide

How much does blood pressure change with the seasons?

A study of 506,673 adults aged 30 to 79 across 10 regions of China measured blood pressure and local outdoor temperature together [2]. Mean systolic pressure was 10 mmHg higher in December to February than in June to August, and the gap was larger in rural areas (12 mmHg) than urban ones (8 mmHg) [2]. Above 5°C, systolic pressure was 5.7 mmHg higher for every 10°C drop in outdoor temperature, and the relationship was stronger in older people and in people with a lower body mass index [2]. At lower temperatures, participants who reported central heating at home showed no evidence of an association [2].

A second study measured temperature at the person rather than the region. In 1,897 patients referred for ambulatory blood pressure monitoring, each monitor carried a temperature logger [3]. Daytime systolic pressure was inversely related to the personal environmental temperature (coefficient -0.14, 95% CI -0.25 to -0.02), while nighttime pressure was positively related to daylight hours (0.63, 95% CI 0.37 to 0.90) and morning blood pressure surge was inversely related to daylight hours (-0.54, 95% CI -0.87 to -0.21) [3]. Temperature and day length each predicted ambulatory pressure independently of the other [3].

These are population-wide patterns. An average difference between seasons does not tell you how much one person's readings will change.

Does the Norvasc label adjust anything for season?

No. The labeled regimen is a starting dose of 5 mg once daily and a maximum of 10 mg once daily. A 2.5 mg starting dose is allowed for small, fragile or elderly patients, for patients with hepatic insufficiency, or when amlodipine is added to other antihypertensive therapy, with adjustment according to blood pressure goals [1]. The label says to wait 7 to 14 days between titration steps unless faster titration is clinically warranted with frequent assessment [1]. There is no winter dose, no summer dose, and no instruction to change the dose with temperature.

What the half-life means for the timing of any change

Peak plasma concentration occurs 6 to 12 hours after a dose, absolute bioavailability is 64% to 90% and is not altered by food, and steady state is reached after 7 to 8 days of once-daily dosing [1]. Terminal half-life is about 30 to 50 hours [1]. Elderly patients and patients with hepatic insufficiency clear amlodipine more slowly, with an AUC about 40% to 60% higher, so a lower starting dose may be needed; the plasma half-life is 56 hours in impaired hepatic function [1]. Renal impairment does not significantly change pharmacokinetics, so patients with renal failure may take the usual starting dose [1].

Edema and dizziness: what the label reports

Edema is the most common adverse reaction and is dose related: 1.8% at 2.5 mg, 3.0% at 5 mg and 10.8% at 10 mg, against 0.6% on placebo [1]. It is reported more often in women: 14.6% versus 5.1% on placebo among women (N=512), and 5.6% versus 1.4% among men (N=1218) [1]. Dizziness occurred in 1.1% at 2.5 mg, 3.4% at 5 mg and 3.4% at 10 mg versus 1.5% on placebo; flushing in 0.7%, 1.4% and 2.6% versus 0.0%; palpitation in 0.7%, 1.4% and 4.5% versus 0.6% [1].

The label reports these rates by dose, not by month or outdoor temperature. Two other label statements are relevant when doses change: symptomatic hypotension is possible, particularly in severe aortic stenosis, but acute hypotension is unlikely because onset is gradual, and worsening angina or acute myocardial infarction can develop after starting or increasing the dose, particularly in severe obstructive coronary artery disease [1].

Winter: higher readings in the population

In the China study, average systolic pressure for the group was 10 mmHg higher in winter than in summer, and the effect was weaker where participants had central heating at home [2]. The label's framework for changing an amlodipine dose is titration toward blood pressure goals, with 7 to 14 days between steps unless faster titration is clinically warranted [1].