Hyaluronidase in 2026: A Review of Safety and Practice

Hyaluronidase is the enzyme used to dissolve hyaluronic acid filler, both for cosmetic corrections and for emergencies. A 2026 review by a group of Italian clinicians pulls together recent reports on how it is made, how safe it is and how it is used. Its overall message is that the enzyme is an essential and generally safe tool, but that allergy is possible, practice varies widely and better standards are still needed.

Why this review was written

As filler use has grown, so has the use of hyaluronidase. Yet the enzyme comes in many forms, doses are not standardized and experts disagree on questions such as whether to skin-test before using it. The authors set out to summarize what has been published, mostly since 2020, and to highlight where guidance agrees and where it does not.

What the researchers did

This is a narrative review. The authors searched a major medical database and selected 86 representative articles, many of them case reports and case series. They did not use strict inclusion rules or pool results statistically, so the review reflects expert summary rather than a formal analysis.

What they found

Where the enzyme comes from. Most hyaluronidase used worldwide comes from animal sources. A human version made in the laboratory is purer but available in only a few countries. Products differ in strength and ingredients, and in some places, including parts of Europe, the enzyme is prepared by compounding pharmacies. The review notes that in Canada, using hyaluronidase for filler problems is off-label, and some practitioners use compounded preparations.

Allergy risk. The review estimates that allergic reactions occur in roughly 0.05% to 0.7% of uses. Most concern is around fast, immediate reactions, but delayed reactions also happen. People allergic to bee or especially wasp stings appear to be at higher risk. Some medications, such as certain blood pressure drugs, and some rare conditions may make a reaction more severe.

The skin-testing debate. Guidance conflicts. Some clinicians test a small amount in the skin first; others feel testing is unreliable and may delay urgent care. The review describes expert advice against routine testing in people with no allergy history, with referral to an allergist for anyone who has had a serious reaction before. In an emergency, delaying treatment for a test is generally not advised.

Uses. The enzyme is used to correct lumps, unevenness, overfilling and a bluish tint from filler placed too close to the surface, and to help manage some swelling and certain lumps that appear later. In blood-flow emergencies, larger doses are given repeatedly. Vision changes after filler require urgent referral, as time is critical.

The review also notes that firmer, more tightly cross-linked fillers may need more enzyme and more than one session.

How strong is this evidence?

A narrative review is useful for an overview but does not carry the weight of a systematic review or controlled trial. Much of the underlying evidence is from individual case reports, which tend to describe unusual events. Dosing advice varies between sources, and the review leans heavily on Italian practice. There are also some internal inconsistencies, for example on how long the enzyme stays active in the body. The authors themselves call for standardized protocols and controlled trials.

What it means for you

If you have filler, or are considering it, it is reassuring to know that hyaluronic acid filler can usually be dissolved. A physician-led clinic should keep hyaluronidase on hand and have an emergency plan before treatment starts. Our article on dissolving filler explains what the appointment is like.

Tell your clinician before any filler or dissolving treatment if you have:

• Any past reaction to hyaluronidase
• An allergy to bee or wasp stings
• A history of severe allergic reactions or angioedema
• A list of current medications, including blood pressure medicines

Never stop a prescribed medication on your own to prepare for treatment; your clinician and family doctor can advise.

For cosmetic corrections, many clinicians start with a smaller dose, since the enzyme can also break down some of the body's own hyaluronic acid. A temporary hollow can occur, and more than one session may be needed. Common side effects include short-lived swelling, redness and tenderness. Signs of an allergic reaction, such as hives, spreading swelling, wheezing or feeling faint, need immediate attention.

People who are pregnant or breastfeeding are usually advised to postpone non-urgent dissolving. In a true emergency, the balance of risks is different and will be discussed with you.

Questions to ask at your consultation

• Do you keep hyaluronidase on site, and what is your emergency plan?
• Given my allergy history, would you recommend testing or an allergist's opinion?
• How many sessions might I need to dissolve my filler?

Our article on delayed filler reactions also covers when the enzyme may be used for later lumps.

Why standards still vary

Part of the reason practice differs is that hyaluronidase is regulated differently from country to country, and the products available are not identical. A dose that suits one product may not translate directly to another. Until larger studies are done, clinicians rely on consensus guidance, their training and the specific product they have, which is why it is reasonable to ask your clinician how they approach dosing and safety.

Frequently asked questions

Is hyaluronidase approved for dissolving filler in Canada?

The review notes that this use is off-label in Canada, as in many places. Off-label use is common in medicine when supported by clinical experience, and it should be explained to you as part of consent.

Will I be skin-tested first?

Practice varies. Your clinician will consider your allergy history. In an emergency, treatment usually goes ahead without delay.

Can it dissolve other fillers?

No. It works only on hyaluronic acid filler, not on calcium hydroxylapatite or PLLA.

If you would like to understand your options for correcting filler, or how a clinic prepares for complications, a consultation is a good place to start.

Source

Arrigoni F, Belletti S, Caboni S, Cavallini M, Cordovana A, Lazzari R, Papagni MF. Hyaluronidase use in aesthetic medicine: formulations, safety, and clinical practice. Journal of Clinical Medicine, 2026. Read the study