Can Amlodipine or Losartan Cause Headaches?
Yes, both amlodipine and losartan can cause headaches, but the evidence shows they affect headache frequency differently: amlodipine at low-to-medium doses (2.5-5 mg) actually reduces headache incidence compared to placebo, while losartan lists headache as a recognized adverse effect occurring in clinical trials.
Amlodipine and Headaches
Evidence from Clinical Trials
Amlodipine reduces headache incidence overall when compared to placebo (7.9% vs. 10.9%, risk ratio: 0.77), according to a 2019 meta-analysis of 22 randomized controlled trials involving 7,226 patients 1.
The protective effect is dose-dependent: Low-to-medium doses (2.5-5 mg) significantly reduce headache risk (risk ratio: 0.52) compared to placebo, while high doses (10 mg) show no significant difference (risk ratio: 0.92) 1.
Guideline Recognition
The 2018 ACC/AHA hypertension guidelines list amlodipine among dihydropyridine calcium channel blockers, noting these agents are "associated with dose-related pedal edema" but do not specifically highlight headache as a primary concern 2.
The 2022 European Society of Cardiology guidelines acknowledge that dihydropyridines can cause "headache/flushing" along with peripheral edema, reflex tachycardia, and hypotension 2.
Clinical Interpretation
If a patient on amlodipine reports new headaches, consider that approximately 8% will experience headaches, but this is actually lower than the 11% baseline rate in untreated hypertensive patients 1. The headaches may be unrelated to the medication, particularly at lower doses.
Losartan and Headaches
FDA-Approved Drug Label Evidence
The FDA label for losartan explicitly lists headache as an adverse reaction observed in clinical trials, though it occurred in less than 2% of patients and was not significantly more common than placebo in the primary safety analysis 3.
In controlled trials of over 1,000 patients, the most common adverse events occurring in ≥2% of losartan-treated patients were dizziness (3% vs. 2% placebo), upper respiratory infection (8% vs. 7%), nasal congestion (2% vs. 1%), and back pain (2% vs. 1%) 3.
Additional nervous system disorders reported include "somnolence, headache, sleep disorders, paresthesia, migraine" 3.
Clinical Trial Data
A 1997 safety analysis of approximately 2,900 patients treated with losartan found headache among the most frequently reported adverse events, though the incidence was similar to placebo 4.
A 2003 comparative trial in isolated systolic hypertension found dizziness was the most common drug-related adverse event with losartan (6.0%), but headache rates were not specifically differentiated from other adverse events 5.
A 2019 case report documented a patient who developed tremors and dysarthria with losartan, noting that "common side effects of the drug include headaches, dizziness, fatigue, nausea, vomiting, and anemia" 6.
Comparative Context
- In the 2024 Bangladesh comparative study, losartan was noted to cause "angioedema, hyperkalemia, headache, dizziness" as adverse events, though specific incidence rates were not provided 7.
Clinical Management Algorithm
When Headaches Occur on Amlodipine:
Verify the dose: If on 10 mg daily, consider dose reduction to 5 mg, as lower doses are associated with fewer side effects and paradoxically lower headache rates 1, 2.
Assess timing: Dihydropyridine-related headaches typically present as flushing/headache together due to vasodilation 2.
Consider that the headache may be unrelated: Up to 63% of adverse events attributed to amlodipine in clinical practice may actually be unrelated to the drug 1.
When Headaches Occur on Losartan:
Recognize this as a known but uncommon adverse effect documented in the FDA label 3.
Differentiate from more serious neurological symptoms: If accompanied by tremors, dysarthria, or other neurological signs, consider immediate evaluation as these may represent rare but serious reactions 6.
Monitor for angioedema: While headache itself is benign, losartan's only well-documented serious adverse effect is angioedema/anaphylactoid reactions 6, 3.
Important Caveats
Amlodipine's peripheral edema is far more common than headache (16.6% vs. 7.9%), and this should be the primary tolerability concern, particularly at higher doses 1, 2.
Losartan is generally better tolerated than amlodipine in head-to-head trials, with fewer overall adverse events (67.8% vs. 79.8%) and drug-related discontinuations (4.4% vs. 12.9%) 5.
Neither medication should be discontinued for headache alone without first ruling out other causes and attempting dose optimization, as both provide significant cardiovascular mortality and morbidity benefits 2.