From the Guidelines
Amlodipine is not well tolerated by older adults due to its tendency to cause peripheral edema, dizziness, and hypotension, as evidenced by the adverse effects associated with calcium-channel blockers, including dizziness, headache, edema, and constipation 1.
Reasons for Poor Tolerance
- Peripheral edema: Amlodipine can cause fluid retention in the lower extremities, affecting up to 30% of elderly patients.
- Dizziness and hypotension: The vasodilatory effects of amlodipine can lead to these side effects, which are particularly problematic in older adults with age-related changes in cardiovascular function, decreased baroreceptor sensitivity, and reduced kidney function.
- Orthostatic hypotension: Elderly patients may experience more pronounced orthostatic hypotension, increasing fall risk.
- Polypharmacy: Older adults often take multiple medications that can interact with amlodipine, exacerbating side effects.
Recommendations for Use in Older Adults
- Start with a lower dose (2.5 mg daily) and monitor carefully for edema, dizziness, and blood pressure changes.
- Consider alternative antihypertensives like ACE inhibitors or ARBs, which may be better tolerated in this population if amlodipine side effects become problematic.
- Non-pharmacologic approaches, such as lifestyle modifications, may be recommended as initial therapy to avoid or reduce the need for pharmacologic therapy and its potential adverse effects 1.
From the FDA Drug Label
Elderly patients and patients with hepatic insufficiency have decreased clearance of amlodipine with a resulting increase in AUC of approximately 40 to 60%, and a lower initial dose may be required.
Amlodipine is not well tolerated by older adults because decreased clearance and increased AUC may lead to higher plasma concentrations, potentially causing adverse effects.
- Key factors contributing to this issue include:
- Decreased clearance: Older adults may have reduced ability to eliminate the drug from their system.
- Increased AUC: The area under the concentration-time curve (AUC) is increased by approximately 40 to 60% in elderly patients, which may lead to higher plasma concentrations of the drug.
- Lower initial dose required: Due to these changes, a lower initial dose of amlodipine may be necessary for older adults to minimize the risk of adverse effects 2.
From the Research
Amlodipine Tolerability in Older Adults
- Amlodipine is generally considered effective in treating hypertension in older adults, with studies showing significant reductions in blood pressure 3, 4, 5.
- However, older adults may experience more frequent adverse reactions to amlodipine, such as edema, palpitations, dizziness, and flushing, particularly at higher doses 6, 7.
- The incidence of adverse events in older adults taking amlodipine is similar to that in younger adults, with no statistically significant differences between groups 5.
- Some studies suggest that older adults may be more susceptible to the hypotensive effects of amlodipine, with greater decreases in systolic and diastolic blood pressure compared to younger adults 4.
Factors Affecting Amlodipine Tolerability
- Age-related changes in pharmacokinetics, such as decreased renal clearance and prolonged elimination half-life, may contribute to increased sensitivity to amlodipine in older adults 4.
- The presence of comorbidities, such as diabetes or chronic kidney disease, may also affect the tolerability of amlodipine in older adults 6.
- Dose and dosing schedule may impact tolerability, with lower doses and morning dosing potentially conferring a slight advantage in terms of adverse event profile 5.
Comparison with Other Calcium Channel Blockers
- Manidipine, another calcium channel blocker, has been shown to have similar antihypertensive efficacy and safety to amlodipine in elderly subjects with isolated systolic hypertension 7.
- However, manidipine may have a lower incidence of edema compared to amlodipine, which could impact tolerability in older adults 7.