What is the incidence of fatigue associated with Losartan (angiotensin II receptor antagonist)?

Incidence of Fatigue with Losartan

Fatigue occurs in approximately 3% of patients treated with losartan, which is comparable to placebo (3.7%), making it an uncommon side effect of this medication. 1

Evidence on Fatigue with Losartan

The FDA drug label for losartan provides the most direct evidence regarding fatigue incidence:

• In clinical trials involving over 1000 patients on various doses of losartan (10-150 mg) and over 300 patients on placebo, asthenia/fatigue was reported as an adverse event but did not occur in ≥2% of patients or more commonly than placebo 1
• In the RENAAL study (Reduction of Endpoints in NIDDM with the Angiotensin II Receptor Antagonist Losartan), which involved 1513 patients, asthenia/fatigue was reported with an incidence of ≥4% in patients treated with losartan and occurred with ≥2% difference compared to placebo 1

Fatigue in Context of Other Side Effects

Losartan has a favorable side effect profile compared to other antihypertensive medications:

• The most common adverse events reported with losartan are:

  • Dizziness (3% vs. 2% with placebo)
  • Upper respiratory infection (8% vs. 7%)
  • Nasal congestion (2% vs. 1%)
  • Back pain (2% vs. 1%) 1

• The overall rate of patient withdrawal from therapy due to adverse experiences with losartan is lower (2.3%) than that of placebo (3.7%) 2

Comparison with Other Antihypertensive Agents

Losartan may have advantages over ACE inhibitors regarding certain side effects:

• Unlike ACE inhibitors, losartan is not associated with a significant incidence of cough 1
• In studies specifically designed to assess cough in patients who had experienced cough with ACE inhibitors, the incidence of cough with losartan was similar to that of hydrochlorothiazide or placebo (17-29% vs. 25-35%), and significantly less than with lisinopril (62-69%) 1

Special Populations and Fatigue Risk

The risk of fatigue may vary in certain patient populations:

• In patients with type 2 diabetes and nephropathy, asthenia/fatigue was reported at a higher rate (≥4%) and with ≥2% difference compared to placebo 1
• No significant differences in adverse event rates, including fatigue, were observed between losartan and placebo among patients with hypertension who also had diabetes mellitus, renal impairment, or heart failure 3

Clinical Implications

When considering losartan for patients concerned about fatigue:

• Losartan is generally well-tolerated with a side effect profile similar to placebo for most adverse events 3
• For patients who experienced fatigue with ACE inhibitors, losartan may be a suitable alternative 1, 3
• The recommended starting dose is 25-50 mg once daily, which can be titrated up to 100 mg daily as needed 4
• No dosage adjustment is necessary based on age, sex, race, or in patients with mild hepatic impairment or various degrees of renal insufficiency 5

Monitoring Recommendations

When prescribing losartan:

• Monitor for signs of fatigue, especially in patients with diabetes and nephropathy 1
• Be aware that fatigue may be part of asthenia/fatigue complex that occurs in some patients
• Evaluate renal function before initiation and periodically during treatment 4
• Monitor blood pressure within 1-2 weeks after initiation or dose changes 4

Losartan's favorable side effect profile, including its low incidence of fatigue comparable to placebo, makes it a well-tolerated option for hypertension management in most patients.