Can Losartan Cause Hyponatremia?
Yes, losartan can cause hyponatremia, though it is rare when used as monotherapy, and the risk increases substantially when combined with thiazide diuretics like hydrochlorothiazide.
Mechanism and Risk Profile
Losartan as a single agent has been associated with rare cases of severe hyponatremia. A case report documented a 73-year-old diabetic patient who developed severe hyponatremia (serum sodium 123 mEq/L) after 3.5 months of losartan 50 mg monotherapy, with no other identifiable causes 1. The Naranjo adverse drug reaction probability scale rated this as "probable" causation 1.
However, the risk of hyponatremia is dramatically higher when losartan is combined with hydrochlorothiazide 2. In a case series of 40 patients taking losartan/hydrochlorothiazide combination therapy, hyponatremia was identified as a primary adverse effect, with the lowest recorded sodium level being 114.4 mEq/L (range 99-133 mEq/L) 2. The median time to development of hyponatremia was 24 days, though the range extended from 2 to 207 days 2.
Clinical Presentation Patterns
Two distinct clinical patterns emerge:
- Early-onset (<50 days): Patients typically present with progressive symptoms including drowsiness, severe generalized weakness, and occasional palpitations 1, 2
- Late-onset (>50 days): Patients often remain asymptomatic until a precipitating event such as fever or appetite loss triggers symptoms 2
Your Specific Situation
With your normal baseline sodium of 141 mmol/L, you are not currently hyponatremic. However, you should be aware of this potential adverse effect, particularly if losartan is ever combined with a thiazide diuretic 2.
Monitoring Recommendations
- If on losartan monotherapy: Periodic sodium monitoring is prudent, especially during the first 3-6 months of therapy 1
- If losartan is combined with hydrochlorothiazide: More vigilant monitoring is essential, with sodium checks at baseline, 2-4 weeks, and then periodically, as 90% of affected patients in the case series achieved full recovery after drug discontinuation 2
Important Safety Considerations
Serious outcomes are possible but uncommon. In the case series of 40 patients with losartan/hydrochlorothiazide-induced hyponatremia, 90% achieved full recovery, but one patient developed central pontine myelinolysis and one died 2. Recovery typically occurred within a median of 5 days for early improvement and 7.5 days for complete recovery after drug discontinuation 2.
Hyponatremia was observed as a primary adverse effect across all angiotensin II receptor blocker (ARB)/thiazide combinations, not just losartan 2. This suggests a class effect when ARBs are combined with diuretics 2.
Counterbalancing Effect on Uric Acid
Interestingly, losartan has a unique property among ARBs: it increases uric acid secretion and lowers plasma uric acid levels 3, 4. When combined with hydrochlorothiazide (which typically raises uric acid), losartan significantly decreased serum uric acid by -0.44 mg/dL compared to other ARBs (+0.10 mg/dL) 4. This uricosuric effect may be beneficial but could theoretically lead to uric acid stone formation 3.
Common Pitfalls to Avoid
- Do not dismiss mild symptoms such as nausea, weakness, or confusion in patients on losartan, especially when combined with diuretics, as these may herald developing hyponatremia 1, 2
- Do not assume safety based on duration of therapy alone—hyponatremia can develop anywhere from 2 days to 7 months after initiation 2
- Do not overlook precipitating factors such as fever, decreased oral intake, or volume depletion in patients on chronic losartan/diuretic therapy 2