MHRA DSI/2026/014 (October 2026): Delay Caspofungin by at Least 6 Hours With PAN Membrane Filters in CRRT

Event overview

On 13 October 2026, the UK Medicines and Healthcare products Regulatory Agency (MHRA) issued Device Safety Information DSI/2026/014. The notice states that polyacrylonitrile (PAN) membrane filters used in continuous renal replacement therapy (CRRT) can adsorb caspofungin, potentially causing antifungal treatment to fail. The risk is highest when a new membrane or new circuit is first used.

The MHRA advises that echinocandins, including caspofungin, should be administered at least 6 hours after CRRT initiation or after replacement of the filter circuit, where conditions allow. CRRT itself should not be delayed for this reason. The document also notes that this conclusion differs from the position of the EU Pharmacovigilance Risk Assessment Committee (PRAC), which recommends avoiding PAN membranes.

This is not a product recall, and the document does not name any manufacturer or specific model. It addresses an interaction between a class of membrane material and a class of medicines. All institutions using PAN membrane CRRT in intensive care are affected.

Why the risk is concentrated on new filters

CRRT is a slow dialysis modality, typically continuing for approximately 24 hours, that controls fluid balance through a semipermeable membrane. It is often used in haemodynamically unstable critically ill patients. Caspofungin is used in adults and children for invasive fungal infections and for empirical treatment in patients with febrile neutropenia. In critically ill patients, failure of antifungal treatment can have fatal consequences.

Published evidence shows that caspofungin binds to PAN membranes. The MHRA explains that this adsorption is not specific to one medicine, is strongest when a new membrane or new circuit is first used, and decreases as the membrane becomes saturated. The risk window is therefore concentrated in the initial period after treatment starts and after each filter circuit replacement.

The MHRA also states that the same risk cannot be excluded for CRRT membranes made from other materials or for other medicines with similar properties, because comparative studies on other membrane materials have not been conducted and adsorption cannot be conclusively ruled out.

Regulatory advice: delay dosing, not therapy

The core recommendation is a single timing requirement: where conditions allow, antifungal treatment should be administered at least 6 hours after CRRT initiation or after routine replacement of the filter circuit. The document also emphasises that CRRT should continue according to clinical need and should not be delayed or interrupted solely to accommodate medicine administration, unless the responsible clinician considers it necessary.

If a patient is already receiving an echinocandin before starting CRRT, delaying the next dose or delaying CRRT initiation should only be considered where clinically feasible. During periods of overlapping treatment, patients should be monitored for signs of insufficient efficacy.

Related requirements include the following: all personnel involved in CRRT operation and setup, as well as in prescribing, preparing and administering caspofungin, should be aware of the advice; specialist pharmacist, infectious diseases, medical microbiology or mycology advice should be sought when loss of efficacy is a concern; filter adsorption should be considered a possible cause when a patient does not respond or responds insufficiently; and healthcare institutions should review and update local procedures and standard operating procedures to include administration timing.

Difference from the EU PRAC conclusion

The same issue has been handled differently in Europe. DSI/2026/014 explains that the EU Pharmacovigilance Risk Assessment Committee (PRAC), after reviewing the evidence, recommended that CRRT patients receiving antifungal treatment should avoid PAN membranes. This could be achieved by changing the membrane material or switching to another antifungal medicine.

The MHRA reviewed studies published after the PRAC recommendation, together with input from clinicians and the availability of CRRT equipment in UK centres, and considered the PRAC advice not feasible in the UK clinical environment. The reasons are stated directly: echinocandins are first-line treatment for invasive candidiasis, and stopping them could have serious consequences for patients; alternative antifungal medicines are also limited by susceptibility and resistance considerations.

The same body of evidence has led to different operational conclusions in two markets. The difference arises not only from scientific judgement but also from device conditions and clinical practicability.

What this means for device companies

For manufacturers of CRRT filters and circuits, this document moves medicine adsorption from a literature topic to the level of instructions for use and risk management. The questions to answer become specific: do the instructions for use for PAN membrane products mention the risk of adsorption of medicines such as caspofungin; does the risk management file identify medicine adsorption as a foreseeable hazard; does post-market surveillance collect feedback on treatment non-response; and do hospital training materials include administration timing, not only filter life and transmembrane pressure.

The MHRA has issued a Dear Healthcare Professional Communication (DHPC) with the DSI to communicate key safety information. Companies selling in the UK need to confirm that this letter has reached customers through their own channels. The DSI does not impose additional requirements on distributors, but distributors are often the first point of contact for hospitals. If information stops there, clinicians will not receive it.

Recommended next steps

• Review the instructions for use and promotional materials for PAN membrane products and remove statements such as no effect on medicine concentrations where these are not supported by evidence.
• Include medicine adsorption in the update plan for risk management and clinical evaluation, with a focus on intensive care and CRRT settings.
• Add administration timing to customer training and present it together with the filter replacement procedure.
• Establish a route for collecting feedback on abnormal efficacy, separate from formal adverse event reporting.
• Monitor whether the MHRA and EMA subsequently converge in their positions. At present, the two markets handle PAN membranes differently, and one approach cannot be directly applied to the other.

AIMEILI regulatory interpretation

From a regulatory affairs perspective, DSI/2026/014 is a device safety communication rather than a recall, but it creates clear expectations for labelling, risk management, post-market surveillance and customer training. For PAN membrane CRRT filters and circuits, manufacturers should be able to show that the interaction with caspofungin and other echinocandins has been considered in the risk management process and that residual risks are communicated appropriately. The UK and EU positions currently diverge: the UK MHRA accepts delayed administration with continued use of PAN membranes where clinically appropriate, while the EU PRAC recommends avoiding PAN membranes in patients receiving antifungal treatment. This means that global manufacturers may need market-specific instructions for use, training materials and regulatory responses rather than a single global statement.

Business impact

The immediate business impact is likely to be seen in hospital procurement, distributor support and post-market surveillance. Hospital customers may ask manufacturers whether their PAN membrane products adsorb caspofungin, whether administration timing is addressed in training, and what evidence supports statements about medicine compatibility. Distributors in the UK may need updated FAQs and training to ensure that the DHPC and DSI reach clinical teams. Manufacturers should also assess whether existing complaint categories capture reports of antifungal treatment non-response, because such reports may be relevant to device performance and risk management even when they do not meet the threshold for a formal adverse event report. Finally, companies operating in both the UK and EU should monitor further MHRA and EMA communications and prepare to update regulatory documentation if either position changes.

Sources and scope

• MHRA, Continuous renal replacement therapy (CRRT): Consider delayed administration of concurrent echinocandins, such as caspofungin, to reduce the risk of adsorption onto new polyacrylonitrile (PAN)-based filter membranes, DSI/2026/014, published 13 October 2026: https://www.gov.uk/drug-device-alerts/continuous-renal-replacement-therapy-crrt-consider-delayed-administration-of-concurrent-echinocandins-such-as-caspofungin-to-reduce-the-risk-of-adsorption-onto-new-polyacrylonitrile-pan-based-filter-membranes-dsi-slash-2026-slash-
• MHRA / Medicines UK, Caspofungin DHPC: https://assets.publishing.service.gov.uk/media/6accbbdab8542d3693fd430a/Medicines_UK_Draft_Caspofungin_DHPC_-_final_07_10_26.pdf
• MHRA Drug Device Alerts, device safety information list: https://www.gov.uk/drug-device-alerts?alert_type%5B%5D=device-safety-information

Verification scope and access date: the above pages were accessed on 18 October 2026 to check the document number, publication date, adsorption mechanism, 6-hour dosing recommendation, requirements for clinicians and distributors, and the difference from PRAC advice. This article does not make judgements on specific product models or companies.

Applicability: this article interprets public regulatory information and does not constitute a compliance conclusion for any specific product, company or registration application. Clinical practice should follow the original MHRA text, the DHPC and local institutional procedures; regulatory positions may change with official updates.