Indapamide-Induced Rhabdomyolysis: An Evaluation of Case Reports in VigiBase Using the Bradford Hill Criteria
Qun-Ying Yue1, Pia Caduff-Janosa2
1Uppsala Monitoring Centre, Box 1051, 75140, Uppsala, Sweden. qun-ying.yue@who-umc.org.
Background:
Indapamide can cause hypokalaemia and hyponatraemia. Rhabdomyolysis associated with these electrolyte abnormalities has been reported.
Objective:
The aim of this study was to assess causal association between the use of indapamide and the occurrence of rhabdomyolysis using the Bradford Hill criteria.
Methods:
Variables in the rhabdomyolysis case reports and literature were reviewed. Bradford Hill criteria were used in the assessment of causal association.
Results:
Up to 11 November 2020, there were 28 unique cases in VigiBase from 13 countries reporting indapamide-associated rhabdomyolysis. In 18 of these cases, hypokalaemia (n = 14) or hyponatremia (n = 8) was a co-reported event, including four cases where both of these events were reported. Indapamide was the only suspected drug in nine of these 18 cases and positive dechallenge was mentioned in 13 of them. In addition, there were risk factors such as falls, concomitant drugs with risk of hypokalaemia, or muscle injury. In two cases, liquorice (containing glycyrrhizin) was concomitantly used with indapamide before hypokalaemia and rhabdomyolysis occurred. Thiazide diuretics, known to cause hypokalaemia, showed similar disproportionality patterns as indapamide regarding rhabdomyolysis and myopathy, while calcium channel blockers (not causing hypokalaemia), had lower disproportionality values than indapamide.
Conclusions:
Based on the review of case series and causality assessment using Bradford Hill criteria, indapamide may cause rhabdomyolysis due to hypokalaemia or hyponatremia. Considering the seriousness of the reported cases, health care professionals should be aware of this potential risk following indapamide intake, particularly when there are risk factors for hypokalaemia and hyponatremia such as excessive liquorice consumption. A similar risk of muscle injuries may apply to thiazide diuretics as well.
Insights
Indapamide may cause rhabdomyolysis, a serious muscle condition, linked to electrolyte imbalances like hypokalaemia and hyponatraemia. Healthcare providers should monitor patients for this risk, especially with contributing factors.
Area of Science:
- Pharmacovigilance and Drug Safety
- Clinical Pharmacology
- Nephrology and Endocrinology
Background:
- Indapamide is associated with electrolyte disturbances, specifically hypokalaemia and hyponatraemia.
- Previous reports have linked these electrolyte abnormalities to the development of rhabdomyolysis.
Purpose of the Study:
- To evaluate the causal association between indapamide use and the occurrence of rhabdomyolysis.
- Utilized the Bradford Hill criteria for causality assessment.
Main Methods:
- Reviewed case reports and literature data on indapamide and rhabdomyolysis.
- Applied Bradford Hill criteria to establish causality.
Main Results:
- Identified 28 unique cases of indapamide-associated rhabdomyolysis globally.
- Hypokalaemia or hyponatraemia were co-reported in 18 cases; indapamide was the sole suspected drug in nine.
- Risk factors included falls, concomitant medications, muscle injury, and liquorice consumption; thiazide diuretics showed similar patterns, while CCBs did not.
Conclusions:
- Indapamide may cause rhabdomyolysis, potentially mediated by hypokalaemia or hyponatraemia.
- Healthcare professionals must be aware of this risk, particularly in patients with risk factors like excessive liquorice intake.
- Thiazide diuretics may carry a similar risk of muscle injury.
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