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Mancano
cumulative dose of TMP-SMX. Patients who were African
American were also identified as at an increased risk for
hyponatremia. The authors note, "since they excluded patients
who had comorbid conditions and those on medications that
could lower serum sodium concentrations, therefore the incidence of hyponatremia among hospitalized patients secondary to high-dose TMP-SMX is likely even higher." Additional
findings include an elevated urine osmolality and a relatively
low fraction excreted of sodium which suggests volume
depletion in patients receiving high-dose TMP-SMX. The
authors state that "The findings of a high incidence of hyponatremia upon reexposure suggest the possibility of hyponatremia from TMP-SMX-induced renal salt wasting."
Tsapepas et al point out that trimethoprim is structurally
related to the potassium-sparing diuretic amiloride and has
been known to interfere with reabsorption of sodium in the
kidney. Trimethoprim blocks the reabsorption of sodium at
the epithelial sodium channel in the distal nephron and
leads to hyponatremia, hyperkalemia, and metabolic acidosis. While hyperkalemia related to trimethoprim is widely
recognized, hyponatremia due to trimethoprim use is often
overlooked.
In closing, the authors state,
This study underscores the need for close monitoring of serum
sodium levels among patients receiving high doses of TMPSMX, particularly among African American patients. Strategies
such as liberalization of dietary sodium and intravenous saline
infusions while on TMP-SMX therapy may be necessary to
attenuate the risk of hyponatremia.

Lithium Carbonate-Induced
Hypersalivation
A 50-year-old female was admitted to the hospital for symptoms of a manic episode. She had a 4-year history of bipolar
disorder and had been receiving outpatient treatment. Prior
to her admission, she was receiving escitalopram 10 mg
daily, quetiapine 300 mg daily, levothyroxine 100 µg daily,
and valsartan 160 mg daily. The patient had stopped all of her
medications 2 months before her hospitalization. After
admission, the patient received lithium carbonate controlled
release 400 mg daily for 3 days and increased to 800 mg
daily. Olanzapine and diazepam were also added to her medication regimen. Her levothyroxine and valsartan were also
continued, and the patient had been taking these 2 medications for the past 5 years without adverse effect.
The patient described having hypersalivation on the third
day of inpatient lithium carbonate therapy along with a constant salty taste and polyuria. The patient's symptoms increased
when the lithium carbonate dosage was increased to 800 mg
daily. A trough lithium serum level was drawn 12 hours after a
dose of lithium carbonate extended release and the level was
0.9 mEq/L (normal range, 0.6-1.2 mEq/L). One week later,
a subsequent lithium trough level was 0.7 mEq/L, and her
physical and laboratory findings were normal. The patient's

hypersalivation continued, and she described excessive saliva
on her lower lip which she constantly had to hold a tissue to
wipe the excess saliva from her lip. She did not describe nocturnal hypersalivation. The patient did not manifest any signs
or symptoms of lithium toxicity during her admission.
The patient was discharged on a regimen of lithium carbonate extended release 800 mg daily, olanzapine 5 mg daily,
levothyroxine 100 µg daily, and valsartan 160 mg daily. After
discharge, the patient was scheduled for a follow-up appointment in 10 days. A few days before her scheduled appointment, the patient acutely had nausea and vomiting and went
to her family physician. Her physician asked her to stop all of
her medications and have her laboratory parameters evaluated at her scheduled 10-day follow-up appointment. Her
lithium serum level was 0.4 mEq/L at her scheduled appointment. The patient had not taken any of her psychotropic
medications since her visit to her family physician a few
days prior to her scheduled appointment. During the time
when she was not taking her lithium, the patient noticed that
her hypersalivation was progressively decreasing. Upon further questioning, the patient reported that she had hypersalivation 1 year ago when she was receiving lithium 600 mg
daily which resolved after discontinuation. She reported she
had not had any other episodes of hypersalivation.
Khalil et al4 speculate, "low aldosterone/angiotensin II
due to angiotensin receptor blocker intake along with lithium
carbonate could have induced lithium accumulation in the
intracellular compartment and in the saliva of our patient,
manifesting clinically with hypersalivation along with salty
taste." The authors also note that case reports have been published of patients manifesting with signs and symptoms of
lithium toxicity without a high lithium serum level. They
suggest that intra-red blood cell concentration of lithium
may better reflect lithium intoxication when lithium serum
levels are in the therapeutic range. In closing, Khalil et al
warn that
lithium toxicity should be considered even with lithium serum
levels within the normal range. Potential interacting drugs that
are being concomitantly taken such as ARBs or ACE inhibitors
should warrant particular attention because of their ability to
increase lithium serum levels.

Persistent Hemorrhage After
Idarucizumab Administration
Alhasham et al5 report a 65-year-old male who was seen in an
emergency department with complaints of generalized weakness and shortness of breath. The patient reported a 3-day history of black stools, and he had recently initiated treatment
with dabigatran (Pradaxa) due to atrial fibrillation. The patient
had no prior history of gastrointestinal hemorrhage. His initial vital signs included a blood pressure of 74/52 mm Hg, an
irregular heart rate of 122 bpm, and a respiratory rate of 22
bpm. A nasogastric tube was placed and yielded an immediate
return of 300 mL of bright red blood which failed to clear

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