Which intravenous medication—diphenhydramine, paracetamol, 50% dextrose (D50‑50), or tranexamic acid—is non‑dialyzable and will not be cleared during hemodialysis?

Diphenhydramine is Non-Dialyzable

Among the listed medications, diphenhydramine is the only one that will not be significantly cleared during hemodialysis treatment.

Rationale for Each Medication

Diphenhydramine (Non-Dialyzable)

Diphenhydramine is highly protein-bound to albumin, which severely limits its ability to be removed by hemodialysis 1. This high degree of protein binding prevents the drug from crossing the dialysis membrane effectively, meaning standard hemodialysis sessions will not significantly reduce serum concentrations. This property actually increases the risk of drug accumulation and side effects in patients with end-stage kidney disease, as the medication cannot be cleared through either native kidneys or dialysis 1.

Tranexamic Acid (Dialyzable)

Tranexamic acid is extensively cleared by hemodialysis. The drug undergoes approximately 90% cumulative excretion in urine within 24 hours, with renal clearance being the major elimination mechanism 2. The FDA label explicitly states that reduced doses are indicated in patients with renal dysfunction, with specific dosing adjustments required based on creatinine clearance 3. For patients with serum creatinine >5.66 mg/dL, dosing should be reduced to 10 mg/kg every 48 hours or 5 mg/kg every 24 hours 3. This dialyzability necessitates dose supplementation if the drug is given before dialysis sessions.

Paracetamol/Acetaminophen (Dialyzable)

While specific dialyzability data for paracetamol is limited in the provided evidence, acetaminophen and its metabolites are known to be removed by hemodialysis due to their relatively low molecular weight and limited protein binding.

D50 (Dextrose 50%)

Dextrose is a small molecule that would be dialyzable; however, it is rapidly metabolized in the body, making dialysis clearance clinically irrelevant in most scenarios.

Clinical Implications

The non-dialyzability of diphenhydramine has important clinical consequences:

• No dose adjustment needed for the dialysis session itself
• Increased risk of accumulation and anticholinergic side effects in dialysis patients
• Caution advised when prescribing to patients with end-stage kidney disease due to limited safety data in this population 1

In contrast, tranexamic acid requires careful dose adjustment in renal impairment and dialysis patients to prevent neurotoxicity and ocular toxicity from drug accumulation 2, 3.