Hypokalemia secondary to capecitabine: A hidden toxicity?

Muhammad Wasif Saif, Mohammad Houman Fekrazad, Leslie Ledbetter, Robert B Diasio

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Background: Hyopkalemia is a listed toxicity in the capecitabine (Xeloda®;Roche, Nutley, NJ) package insert. However, the incidence and severity of this toxicity is not known. Methods: We performed a retrospective evaluation of hypokalemia in 77 patients, who received capecitabine for gastrointestinal malignancies between April 2002 and November 2004. Hypokalemia was defined as K+ level <3.2 mEq/L. Patients with documented ≥grade 2 vomiting or diarrhea, diuretics, hypomagnesemia, hypokalemia, renal insufficiency, endocrine dysfunction (thyroid, adrenal, diabetic) were excluded. Hypokalemic patients were graded as: mild (grade 1: 3.0-3.2 mEq/L), moderate (grade 3: 2.5-2.9 mEq/L) and severe (grade 4: <2.5 mEq/L). We also reviewed the literature. Results: Fifty-four patients met the above criteria. The most common cause of exclusion was ≥ grade 2 diarrhea (23 patients; 3 0%). Overall, hypokalemia was encountered in 11 patients (20.4%). Among hypokalemic patients, 8 patients (73%) presented with mild/grade 1 hypokalemia (3.0-3.2 mEq/L), 2 patients (18.18%) with moderate/grade 3 hypokalemia (2.5-2.9 mEq/L) and 1 patient (9.09%) with severe/grade 4 hypokalemia (<2.5 mEq/L) 8 (73%). Dose of capecitabine ranged between 1000-2000 mg/ m2. Hypokalemia occurred after an average of 83.7 days of capecitabine administration. No cardiac or neuromuscular complications were noticed. Replacement of K+ was required in 6 patients (2 intravenous and 4 oral), while 2 patients (3.7%) required oral supplements >4 weeks. No patient had to stop capecitabine due to hypokalemia. One patient had persistent hypokalemia even after stopping capecitabine. Normalization of K+ levels was achieved in 91% of patients. Four patients were on K+ sparing diuretics for ascites and never presented with hypokalemia. Mean urine K+ was 28 mEq/L. Only 5.5% patients had ≥grade 3 hypokalemia in our study compared with 2% and 14% in two other studies. Conclusions: Although diarrhea being the most common cause of hypokalemia in patients on capecitabine, we postulate that hypokalemia may also be related to the effect of capecitabine on renal tubules suggested by the urine K+ in some patients. Due to potential complications, hypokalemia inpatients on capecitabine deserves special diagnostic and therapeutic attention.

Original languageEnglish (US)
Pages (from-to)177-180
Number of pages4
JournalTherapeutics and Clinical Risk Management
Volume3
Issue number1
DOIs
StatePublished - 2007
Externally publishedYes

Fingerprint

Hypokalemia
normalization
Toxicity
diagnostic
incidence
school grade
cause
evaluation
Urine
Product Labeling
Capecitabine
Diuretics
Ascites
Inpatients
Diarrhea
Kidney
Incidence

Keywords

  • 5-FU
  • Capecitabine (Xeloda)
  • Colon cancer
  • Hypokalemia
  • Potassium
  • Renal loss

ASJC Scopus subject areas

  • Chemical Health and Safety
  • Medicine(all)
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Safety Research

Cite this

Hypokalemia secondary to capecitabine : A hidden toxicity? / Wasif Saif, Muhammad; Fekrazad, Mohammad Houman; Ledbetter, Leslie; Diasio, Robert B.

In: Therapeutics and Clinical Risk Management, Vol. 3, No. 1, 2007, p. 177-180.

Research output: Contribution to journalArticle

Wasif Saif, Muhammad ; Fekrazad, Mohammad Houman ; Ledbetter, Leslie ; Diasio, Robert B. / Hypokalemia secondary to capecitabine : A hidden toxicity?. In: Therapeutics and Clinical Risk Management. 2007 ; Vol. 3, No. 1. pp. 177-180.
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title = "Hypokalemia secondary to capecitabine: A hidden toxicity?",
abstract = "Background: Hyopkalemia is a listed toxicity in the capecitabine (Xeloda{\circledR};Roche, Nutley, NJ) package insert. However, the incidence and severity of this toxicity is not known. Methods: We performed a retrospective evaluation of hypokalemia in 77 patients, who received capecitabine for gastrointestinal malignancies between April 2002 and November 2004. Hypokalemia was defined as K+ level <3.2 mEq/L. Patients with documented ≥grade 2 vomiting or diarrhea, diuretics, hypomagnesemia, hypokalemia, renal insufficiency, endocrine dysfunction (thyroid, adrenal, diabetic) were excluded. Hypokalemic patients were graded as: mild (grade 1: 3.0-3.2 mEq/L), moderate (grade 3: 2.5-2.9 mEq/L) and severe (grade 4: <2.5 mEq/L). We also reviewed the literature. Results: Fifty-four patients met the above criteria. The most common cause of exclusion was ≥ grade 2 diarrhea (23 patients; 3 0{\%}). Overall, hypokalemia was encountered in 11 patients (20.4{\%}). Among hypokalemic patients, 8 patients (73{\%}) presented with mild/grade 1 hypokalemia (3.0-3.2 mEq/L), 2 patients (18.18{\%}) with moderate/grade 3 hypokalemia (2.5-2.9 mEq/L) and 1 patient (9.09{\%}) with severe/grade 4 hypokalemia (<2.5 mEq/L) 8 (73{\%}). Dose of capecitabine ranged between 1000-2000 mg/ m2. Hypokalemia occurred after an average of 83.7 days of capecitabine administration. No cardiac or neuromuscular complications were noticed. Replacement of K+ was required in 6 patients (2 intravenous and 4 oral), while 2 patients (3.7{\%}) required oral supplements >4 weeks. No patient had to stop capecitabine due to hypokalemia. One patient had persistent hypokalemia even after stopping capecitabine. Normalization of K+ levels was achieved in 91{\%} of patients. Four patients were on K+ sparing diuretics for ascites and never presented with hypokalemia. Mean urine K+ was 28 mEq/L. Only 5.5{\%} patients had ≥grade 3 hypokalemia in our study compared with 2{\%} and 14{\%} in two other studies. Conclusions: Although diarrhea being the most common cause of hypokalemia in patients on capecitabine, we postulate that hypokalemia may also be related to the effect of capecitabine on renal tubules suggested by the urine K+ in some patients. Due to potential complications, hypokalemia inpatients on capecitabine deserves special diagnostic and therapeutic attention.",
keywords = "5-FU, Capecitabine (Xeloda), Colon cancer, Hypokalemia, Potassium, Renal loss",
author = "{Wasif Saif}, Muhammad and Fekrazad, {Mohammad Houman} and Leslie Ledbetter and Diasio, {Robert B}",
year = "2007",
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volume = "3",
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journal = "Therapeutics and Clinical Risk Management",
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T1 - Hypokalemia secondary to capecitabine

T2 - A hidden toxicity?

AU - Wasif Saif, Muhammad

AU - Fekrazad, Mohammad Houman

AU - Ledbetter, Leslie

AU - Diasio, Robert B

PY - 2007

Y1 - 2007

N2 - Background: Hyopkalemia is a listed toxicity in the capecitabine (Xeloda®;Roche, Nutley, NJ) package insert. However, the incidence and severity of this toxicity is not known. Methods: We performed a retrospective evaluation of hypokalemia in 77 patients, who received capecitabine for gastrointestinal malignancies between April 2002 and November 2004. Hypokalemia was defined as K+ level <3.2 mEq/L. Patients with documented ≥grade 2 vomiting or diarrhea, diuretics, hypomagnesemia, hypokalemia, renal insufficiency, endocrine dysfunction (thyroid, adrenal, diabetic) were excluded. Hypokalemic patients were graded as: mild (grade 1: 3.0-3.2 mEq/L), moderate (grade 3: 2.5-2.9 mEq/L) and severe (grade 4: <2.5 mEq/L). We also reviewed the literature. Results: Fifty-four patients met the above criteria. The most common cause of exclusion was ≥ grade 2 diarrhea (23 patients; 3 0%). Overall, hypokalemia was encountered in 11 patients (20.4%). Among hypokalemic patients, 8 patients (73%) presented with mild/grade 1 hypokalemia (3.0-3.2 mEq/L), 2 patients (18.18%) with moderate/grade 3 hypokalemia (2.5-2.9 mEq/L) and 1 patient (9.09%) with severe/grade 4 hypokalemia (<2.5 mEq/L) 8 (73%). Dose of capecitabine ranged between 1000-2000 mg/ m2. Hypokalemia occurred after an average of 83.7 days of capecitabine administration. No cardiac or neuromuscular complications were noticed. Replacement of K+ was required in 6 patients (2 intravenous and 4 oral), while 2 patients (3.7%) required oral supplements >4 weeks. No patient had to stop capecitabine due to hypokalemia. One patient had persistent hypokalemia even after stopping capecitabine. Normalization of K+ levels was achieved in 91% of patients. Four patients were on K+ sparing diuretics for ascites and never presented with hypokalemia. Mean urine K+ was 28 mEq/L. Only 5.5% patients had ≥grade 3 hypokalemia in our study compared with 2% and 14% in two other studies. Conclusions: Although diarrhea being the most common cause of hypokalemia in patients on capecitabine, we postulate that hypokalemia may also be related to the effect of capecitabine on renal tubules suggested by the urine K+ in some patients. Due to potential complications, hypokalemia inpatients on capecitabine deserves special diagnostic and therapeutic attention.

AB - Background: Hyopkalemia is a listed toxicity in the capecitabine (Xeloda®;Roche, Nutley, NJ) package insert. However, the incidence and severity of this toxicity is not known. Methods: We performed a retrospective evaluation of hypokalemia in 77 patients, who received capecitabine for gastrointestinal malignancies between April 2002 and November 2004. Hypokalemia was defined as K+ level <3.2 mEq/L. Patients with documented ≥grade 2 vomiting or diarrhea, diuretics, hypomagnesemia, hypokalemia, renal insufficiency, endocrine dysfunction (thyroid, adrenal, diabetic) were excluded. Hypokalemic patients were graded as: mild (grade 1: 3.0-3.2 mEq/L), moderate (grade 3: 2.5-2.9 mEq/L) and severe (grade 4: <2.5 mEq/L). We also reviewed the literature. Results: Fifty-four patients met the above criteria. The most common cause of exclusion was ≥ grade 2 diarrhea (23 patients; 3 0%). Overall, hypokalemia was encountered in 11 patients (20.4%). Among hypokalemic patients, 8 patients (73%) presented with mild/grade 1 hypokalemia (3.0-3.2 mEq/L), 2 patients (18.18%) with moderate/grade 3 hypokalemia (2.5-2.9 mEq/L) and 1 patient (9.09%) with severe/grade 4 hypokalemia (<2.5 mEq/L) 8 (73%). Dose of capecitabine ranged between 1000-2000 mg/ m2. Hypokalemia occurred after an average of 83.7 days of capecitabine administration. No cardiac or neuromuscular complications were noticed. Replacement of K+ was required in 6 patients (2 intravenous and 4 oral), while 2 patients (3.7%) required oral supplements >4 weeks. No patient had to stop capecitabine due to hypokalemia. One patient had persistent hypokalemia even after stopping capecitabine. Normalization of K+ levels was achieved in 91% of patients. Four patients were on K+ sparing diuretics for ascites and never presented with hypokalemia. Mean urine K+ was 28 mEq/L. Only 5.5% patients had ≥grade 3 hypokalemia in our study compared with 2% and 14% in two other studies. Conclusions: Although diarrhea being the most common cause of hypokalemia in patients on capecitabine, we postulate that hypokalemia may also be related to the effect of capecitabine on renal tubules suggested by the urine K+ in some patients. Due to potential complications, hypokalemia inpatients on capecitabine deserves special diagnostic and therapeutic attention.

KW - 5-FU

KW - Capecitabine (Xeloda)

KW - Colon cancer

KW - Hypokalemia

KW - Potassium

KW - Renal loss

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