Thinking about the use of pregabalin for pruritus in advanced CKD (Part 1: Organizing the premises for judgment)

As a hospital pharmacist,
I have encountered many patients with advanced CKD
suffering from "itchiness."

They scratch themselves at night and cannot sleep.
Because they cannot sleep, they cannot fully engage in rehabilitation the next morning.

I have seen such scenes many times on the ward.

Following textbooks and guidelines,
I try all the standard approaches.

Moisturizing, reviewing dialysis conditions,
controlling phosphorus and PTH,
antihistamines,
and in some cases, nalfurafine.

Even so,
"Doctor, it's still itchy and I can't sleep,"when the complaints continue,

both the desire to do something for them
and the feeling of not knowing what else can be done
arise.

Thinking about such things every day,
I have had more opportunities to see information stating that
"pregabalin is effective for intractable pruritus."

This drug, which has a strong image as a "neuropathic pain medication," is being used for CKD-related pruritus.

If the itchiness is relieved and they can sleep even a little,
that must surely be a positive thing for the patient.

But on the other hand,
"Is it really okay for advanced CKD?"
"What if they fall?"
anxieties like these
also come to mind at the same time.

■ Facing a theme with no answer

In my previous notes,
I think many articles had the stance of
"an expert organizing and conveying information."

But for this theme,
honestly, I myself
do not yet have a clear answer.

That is precisely why in this article,
regarding "using pregabalin for pruritus in advanced CKD," I would like you to follow along with the process of where I am currently hesitant
and how I am trying to organize the information.

■ What kind of problem is CKD-related pruritus in the first place?

1. The impact of CKD-related pruritus on patients

CKD- or dialysis-relatedCKD-associated pruritus (CKD-aP)is by no means a rare symptom.

In DOPPS, an international observational study,
it was reported that some form of pruritus was seen in about 40-50% of hemodialysis patients,
and Japanese data also suggests that "moderate or severe itchiness" is recognized in about 30-40%.

It has been shown that "itching" is not merely a source of discomfort, but is also associated with
sleep disorders, depression, anxiety,
and even an increased risk of death, and it ispositioned as "one of the symptoms that significantly impairs quality of life (QOL)."

Even in the clinical setting of convalescent rehabilitation,
I have the impression that patients with severe nighttime itching
have reduced concentration during the day and less motivation
to participate in rehabilitation.

There is not just one cause for itching.

• Accumulation of uremic toxins

• Calcium and phosphorus metabolic abnormalities

• Dry skin

• Chronic inflammation

• Changes in the peripheral and central nervous systems

• Involvement of the opioid system

It is believed that multiple factors such as these
are intertwined.

Therefore, measures against itching are not
simple enough to be solved by doing just one thing,
and it is necessary to consider a combination of approaches,
from lifestyle guidance to dialysis conditions and pharmacotherapy.

② "Standard Options" Tested in Clinical Practice

The "standard options" frequently used in clinical practice
include the following:

• Measures for dry skin (such as the use of moisturizers)

• Adjustments to dialysis conditions, such as ensuring adequate dialysis dosage, membrane type, and duration

• Optimization of CKD-MBD management, including phosphorus, calcium, and PTH

• Antihistamines and anti-allergic drugs

• Phototherapy such as narrow-band UVB irradiation

• Antipruritic drugs such as nalfurafine hydrochloride (Remitch)

By combining these standard treatments,
the itching of many patients may be controlled to some extent.

Even so, there are patients who say it is "ineffective"
and suffer from itching every day.

This article is also a record of my thoughts as a ward pharmacist regarding the gray zone that exists "after standard treatments have been exhausted."

■ Why is pregabalin a topic of discussion?

When I looked into it,

as mentioned above.

For example, there are reports that for patients with intractable pruritus,
pregabalin was started at a low dose,
and the itch score improved within days to weeks.

In the Japanese Dermatological Association's "Clinical Practice Guidelines for Pruritus 2020,"
gabapentin is given a C1 recommendation (consideration for use is permitted)
for treatment-resistant pruritus.

Regarding pregabalin,
although its effectiveness at the case report level is suggested, high-level evidence such as RCTs is scarce,
placing it in a position where "it can be considered as an option, but the recommendation level is not high."

The original indication for pregabalin is neuropathic pain, and since it has been pointed out that peripheral and central nervous system sensitization may also be involved in some CKD-associated pruritus, the idea that "it might work" seems to have emerged from that commonality (details of the pharmacology will be in Part 2).

Looking at literature and guidelines,

"The logic makes sense"
"It seems to work at the case level"

I understood up to that point.

But inside me,
an inescapable
"unease" began to grow.

■ The "three points of unease" I am feeling

1. Is it really okay to administer the "effective dose" for itching?

When reading reports on the use of pregabalin for CKD-associated pruritus,
I often see descriptions like, "Started at a low dose and gradually increased while monitoring for effects."

In fact, even for neuropathic pain,
I have experienced on the wards that
it is not uncommon to feel that it has "started to work"
as the dose approaches the standard dosage listed in the package insert.

On the other hand, for patients with advanced CKD,
I cannot help but be cautious about
increasing the pregabalin dose
to a level that "might be effective" for pruritus.

It is a renally excreted drug,
and the fact that dose adjustment according to renal function decline is
necessary
is written in various materials,
including the package insert,
and there is also data showing that even within the recommended doses considering renal function,
adverse events such as drowsiness, dizziness, and unsteadiness are
not uncommon.

What makes it even more complicated is
the point that the "effective dose" of pregabalin for pruritus
is not necessarily the same as for neuropathic pain,
.

• "How much should I increase it before I can say I have 'tried' it?"

• "Is the current dose 'too safe, to the point where it couldn't possibly be effective'?"

These doubts continue to smolder in my mind.

At the same time, reports of patients who fell and fractured their femurs due to drowsiness and unsteadiness caused by pregabalin, as well as cases where excessive sedation made rehabilitation impossible, also cross my mind.

"What if the move to relieve the itching ends up worsening their ADLs or life prognosis?"

This anxiety simply will not go away.

• "A certain dosage" that can be expected to improve pruritus

• A "safe dosage" that is tolerable for advanced CKD, elderly, or frail patients

I am not sure how much these two overlapping zones
actually have in common,
and it feels like I am groping in the dark for that narrow zone.

And literature and guidelines do not fully answer
this sense of unease I have.

② Nalfurafine, Adopted Drugs, and the Barrier of Comprehensive Medical Care

When considering treatment for CKD-associated pruritus,
"Start with standard treatment" is a premise
shared by most medical professionals.

However, when actually facing a patient,
"How far should I go to say I have 'exhausted standard treatment'?"feels more gray than I imagined.

For example, the κ-opioid receptor agonist nalfurafine (Remitch) has been reported to be effective for pruritus in dialysis patients and is considered one of the standard options for CKD-associated pruritus in Japan as well.

But in reality,

• It is not adopted at my facility

• It is difficult to use in convalescent rehabilitation wards due to the comprehensive payment system

• It is off-label for non-dialysis CKD, making insurance and cost hurdles high

You may encounter such barriers of
“systems, adoption, and costs.”

Even if you understand intellectually that “textbook-wise, you should first do as much standard treatment as possible, including nalfurafine,”
when you layer on the conditions of the clinical setting,

• How far can we go within the range of adopted drugs?

• Within the framework of comprehensive medical care, how much “out-of-pocket” cost can we tolerate?

• To what extent can we consider off-label nalfurafine for patients with non-dialysis CKD?

There is the issue of,
“Nalfurafine is realistically unusable. Even so, can we say we have ‘exhausted all standard treatments’?” This creates a question that I myself struggle to answer.

And here, a thought suddenly comes to mind:

This is the question.

In a situation where standard treatments have not been fully exhausted,
how far is it permissible to step into using a drug that is off-label?

“Because it is an adopted drug”
“Because it is within the scope of comprehensive care”

Because of these reasons, are the choices
becoming biased toward pregabalin?

This is one of the areas that I still
have not been able to fully verbalize.

3. Who in the team gives the go-ahead?

Another major source of unease is the issue unique to team medicine:
“Who gives the ‘go-ahead’ and how?”

Whether or not to use pregabalin (or off-label nalfurafine) for pruritus in patients with advanced CKD
inevitably becomes a judgment call in a gray zone.

At this time,

• The attending physician feels a desire to do something about the itching and sleep issues.

• The nurse is in a position to feel firsthand the distress of nighttime itching, scratching, and insomnia.

• The rehabilitation staff is in a position to be strongly aware of daytime sleepiness, unsteadiness, and the risk of falls.

• The pharmacist is in a position to consider the balance between renal function, pharmacokinetics, and evidence.

In this way,
the perspective each person has is slightly different.

When discussing in a conference,

• “They are suffering so much from the itching, isn't there something we can do?”

• “But considering this renal function, age, and ADL, the damage from a fall would be too great.”

As someone in a position to propose dosages and discontinuation criteria,
I understand intellectually that the final decision rests with the attending physician.

These two voices
emerge with equal weight.

In that situation, the moment I say, “Let’s try a low dose of pregabalin,” I feel the weight of that decision suddenly pressing down on me.

Even so, “Is the information or comment I provided acting as the trigger for the go-ahead?” is a feeling that inevitably follows me.

“Who bears responsibility and to what extent?”
“What level of risk do we share as a team premise?”
—These questions were not taught in school,
nor are they written in the guidelines.

That is precisely why, for every case,
I continue to look back and ask, “Was this the right thing to do?”
which is the honest truth.

■ Toward Part 2: Returning to the “Facts”

What I have written so far
has been,
if anything, centered on my own “hesitation.”

On the other hand, regarding the drug pregabalin,
there are many “points that should be grasped as facts,”
such as pharmacology, pharmacokinetics, dosage by renal function, adverse events,
and evidence regarding pruritus.

In Part 2,
after re-organizing the textbook understanding of pregabalin,

• I will discuss a case I actually experienced in a convalescent rehabilitation ward.

• A 'virtual case' assuming a similar scenario

Through this, I would like to put into my own words, as I currently understand them, 'under what conditions and with what prerequisites pregabalin might be considered.'

▶ Continue to [Part 2] A 'cautious step' considered through clinical cases

■ References

1. Pisoni RL, et al. Pruritus in haemodialysis patients:
   International results from the Dialysis Outcomes and Practice Patterns Study (DOPPS).
   Nephrol Dial Transplant. 2006;21(12):3495-505.
   https://pubmed.ncbi.nlm.nih.gov/16968725/

2. Sato Takahiro, Yokozeki Hiroo, Murota Hiroyuki, et al.
   Japanese Dermatological Association Guidelines: Clinical Practice Guidelines for Pruritus 2020.
   The Journal of the Japanese Dermatological Association. 2020;130(7):1589-1606.
   https://www.jstage.jst.go.jp/article/dermatol/130/7/130_1589/_article/-char/ja

3. Solak Y, et al. Pregabalin versus placebo in treatment of uraemic pruritus
   in haemodialysis patients. Nephrology (Carlton). 2012;17(8):710-7.
   https://pubmed.ncbi.nlm.nih.gov/22819436/

4. Lyrica Capsules 25mg/75mg/150mg, Lyrica OD Tablets Package Insert.
   Viatris Inc./PMDA.
   https://www.pmda.go.jp/PmdaSearch/rdSearch/02/1190017M2024?user=1

5. Request for Proper Use of Lyrica Capsules
   'Regarding dizziness, somnolence, and loss of consciousness in the elderly.' Pfizer (at the time)/PMDA.
   https://www.pmda.go.jp/files/000144302.pdf

*This article is based on information as of May 2026.