Can amlodipine cause fatigue and lethargy?

Does Amlodipine Cause Fatigue and Lethargy?

Yes, amlodipine can cause fatigue as a side effect, with clinical trials showing fatigue occurring in 4.5% of patients taking amlodipine compared to 2.8% in placebo groups. 1

Evidence on Amlodipine and Fatigue

FDA Drug Label Evidence

According to the FDA drug label for amlodipine, fatigue is one of the most commonly reported adverse reactions:

• Fatigue occurs in 4.5% of patients taking amlodipine versus 2.8% in placebo groups 1
• Somnolence (extreme sleepiness) is reported in 1.4% of amlodipine patients versus 0.6% in placebo 1
• These side effects are listed among the most common adverse reactions that occurred with an incidence greater than 1.0% in placebo-controlled clinical trials 1

Calcium Channel Blockers and Fatigue

Calcium channel blockers as a class can cause several side effects that may contribute to feelings of fatigue or lethargy:

• Dihydropyridines like amlodipine can cause peripheral edema, headache, flushing, and hypotension 2
• These effects are due to the vasodilatory properties of the medication
• Side effects are often dose-dependent, with higher incidence at the 10 mg dose compared to lower doses 1, 3

Fatigue in Specific Populations

Pediatric Population

Even in pediatric patients, fatigue has been documented as an adverse effect:

• In a study of 32 pediatric patients, fatigue was reported in 2 patients (6.25%) 4
• Only one patient discontinued amlodipine due to side effects (ankle edema), suggesting that fatigue, while present, was generally tolerable 4

Elderly Patients

Elderly patients may be more susceptible to side effects:

• Older adults experience greater antihypertensive effects due to decreased baroreceptor response and age-related increase in drug exposure 2
• This increased sensitivity may contribute to hypotension-related fatigue

Mechanisms of Fatigue with Amlodipine

Several mechanisms may explain why amlodipine causes fatigue:

1. Hypotension: Excessive blood pressure reduction can lead to reduced cerebral perfusion, causing fatigue and lethargy 2

2. Vasodilation: Amlodipine's primary mechanism of action involves vasodilation, which can lead to peripheral edema and reduced effective circulating volume 1

3. Neurohormonal effects: Amlodipine has been shown to raise basal and stress-related plasma catecholamines, which may affect energy levels 5

Management of Amlodipine-Related Fatigue

If a patient experiences fatigue while taking amlodipine, consider these approaches:

1. Dose adjustment: Lower doses (2.5-5 mg) are associated with fewer side effects than higher doses (10 mg) 1, 3

2. Timing of administration: Taking amlodipine at bedtime may help minimize daytime fatigue

3. Alternative medications: Consider switching to another antihypertensive class if fatigue is intolerable

4. Combination therapy: Using lower doses of amlodipine in combination with other antihypertensive medications may provide blood pressure control with fewer side effects

Clinical Pearls and Caveats

• Fatigue may be more common in women than men, as several amlodipine side effects show gender differences in incidence 1
• Fatigue typically appears early in therapy and may diminish over time as the body adjusts to the medication
• Rule out other causes of fatigue (anemia, hypothyroidism, depression, sleep apnea) before attributing it solely to amlodipine
• Beta-blockers, which are sometimes combined with calcium channel blockers, may also cause fatigue (reported in 0.4% of patients) 2, potentially compounding this side effect

In conclusion, fatigue is a recognized side effect of amlodipine that occurs more frequently than with placebo. While not among the most common side effects (like edema), it is still clinically significant and should be considered when patients report new-onset fatigue after starting this medication.