What is the safest antihistamine in patients with End-Stage Renal Disease (ESRD) undergoing dialysis?

From the Guidelines

Loratadine and fexofenadine are the safest antihistamines for dialysis patients due to their minimal renal elimination and lack of significant central nervous system depression or anticholinergic effects. These second-generation antihistamines are preferred in patients with kidney disease because they do not require dose adjustments in renal impairment, unlike other antihistamines such as cetirizine, which requires dose reduction in renal impairment (5mg daily) and may accumulate between dialysis sessions 1.

Key Considerations

• Loratadine is typically dosed at 10mg once daily, while fexofenadine is usually given at 60mg twice daily or 180mg once daily.
• First-generation antihistamines like diphenhydramine should be avoided in dialysis patients as they can cause excessive sedation, confusion, and anticholinergic side effects, which may be more pronounced due to reduced clearance 1.
• Sedative antihistamines long term may predispose to dementia and should be avoided, except in palliative care, as stated in the British Association of Dermatologists' guidelines 1.
• The safety profile of loratadine and fexofenadine relates to their metabolism pathways, with loratadine being primarily metabolized by the liver through CYP3A4 and CYP2D6 enzymes, while fexofenadine undergoes minimal metabolism and is eliminated through biliary excretion.

Monitoring and Precautions

• When administering antihistamines to dialysis patients, it's essential to monitor for side effects such as drowsiness, dry mouth, and urinary retention, even with the safer options.
• Acrivastine should be avoided in moderate renal impairment (creatinine clearance 10–20 mL min) 1.
• Cetirizine is not an effective antihistamine in uraemic pruritus, as stated in the British Association of Dermatologists' guidelines 1.

From the FDA Drug Label

Reports of fexofenadine hydrochloride overdose have been infrequent and contain limited information. However, dizziness, drowsiness, and dry mouth have been reported Single doses of fexofenadine hydrochloride up to 800 mg (6 healthy volunteers at this dose level), and doses up to 690 mg twice daily for 1 month (3 healthy volunteers at this dose level) or 240 mg once daily for 1 year (234 healthy volunteers at this dose level) were administered without the development of clinically significant adverse events as compared to placebo In the event of overdose, consider standard measures to remove any unabsorbed drug. Symptomatic and supportive treatment is recommended. Following administration of terfenadine, hemodialysis did not effectively remove fexofenadine, the major active metabolite of terfenadine, from blood (up to 1. 7% removed) Consumers with liver or kidney diseaseAsk a doctor

The safest antihistamine in dialysis patients is not explicitly stated in the provided drug labels. However, fexofenadine may be a safer option since it is not significantly removed by hemodialysis, as stated in the label 2. On the other hand, cetirizine label 3 advises to "Ask a doctor" for consumers with kidney disease, which may indicate a need for caution or dose adjustment.

• Key points:
  • Fexofenadine is not significantly removed by hemodialysis.
  • Cetirizine label advises caution in patients with kidney disease. Given the limited information, it is recommended to consult a doctor or a clinical expert to determine the safest antihistamine for dialysis patients.

From the Research

Safety of Antihistamines in Dialysis Patients

• The safety of antihistamines in dialysis patients is a concern due to the potential for adverse effects and interactions with other medications 4.
• Diphenhydramine, a commonly used antihistamine, has a high binding affinity to albumin, which may limit its ability to be dialyzed and increase the risk of side effects in patients with end-stage kidney disease (ESKD) 4.
• Loratadine, another antihistamine, has been studied in patients with renal insufficiency and was found to have a similar pharmacokinetic profile to that of patients with normal renal function, suggesting that it may be a safer option for dialysis patients 5.

Pharmacokinetics of Antihistamines in Dialysis Patients

• The pharmacokinetics of loratadine were not significantly altered in patients with severe renal insufficiency, and hemodialysis was not an effective means of removing the drug or its metabolite from the body 5.
• The disposition of diphenhydramine in ESKD patients is not well understood, and there is a lack of studies on its safety and dosing in this population 4.

Medication Management in Dialysis Patients

• Medication management in dialysis patients is complex and requires careful consideration of the patient's individual needs and health status 6.
• The choice of medication should take into account the patient's renal function, as well as the potential for drug interactions and adverse effects 7.
• A thorough review of the patient's medication regimen and regular monitoring of their health status are essential to ensure safe and effective medication use in dialysis patients 6, 7.