Hyaluronidase for Dissolving Filler: Reverse the Damage

Last Updated On: April 17, 2025

Dermal fillers have exploded in popularity over the last two decades, but so have filler removals. Studies show that swelling prompts 52% of filler dissolutions, 20% are caused by lumpiness, and 17% have to be done before surgical procedures like blepharoplasty. ^[1]

That’s where hyaluronidase comes in.

As an enzyme capable of breaking down hyaluronic acid (HA), hyaluronidase is used in both elective corrections and urgent filler removal interventions. 

But dosing isn’t one-size-fits-all. It depends on factors like the filler’s structure and placement depth. Keep reading to learn how much to use in different situations and how to use the product safely.

Key Takeaways

1. Hyaluronidase is an enzyme used to dissolve HA-based dermal fillers in both elective and emergency complications.
2. Dosing depends on several factors, including filler type, depth of placement, time since injection, and patient-specific variables.
3. In urgent cases like vascular compromise, high-dose, pulsed protocols are often required to restore tissue perfusion and prevent complications.

What Is Hyaluronidase?

Hyaluronidase is an enzyme that breaks down hyaluronic acid. In aesthetics, it’s used to dissolve HA-based dermal fillers either to correct poor outcomes or to address complications like nodules or vascular occlusion. ^[2]

There are six known human isoforms of hyaluronidase, but HYAL1 and HYAL2 are the most physiologically relevant. These work together to degrade HA in the extracellular matrix. HYAL2 first breaks it into intermediate fragments, which HYAL1 further reduces into small sugar units cleared by the body. ^[3]

The forms of hyaluronidase used in aesthetic medicine are typically derived from three sources:

1. Bovine (cattle-derived) enzymes
2. Ovine (sheep-derived) enzymes
3. Recombinant human hyaluronidase ^[2]

Although these forms of hyaluronidase degrade both native and cross-linked HA, the body replenishes native HA within 15 to 20 hours. This means there are no long-term effects on skin quality when used correctly.

How Does Hyaluronidase Work?

Hyaluronidase treatment works by breaking the bonds that hold HA together. Specifically, it breaks the β-1,4 glycosidic linkages between glucuronic acid and N-acetylglucosamine. ^[4]

Once these are broken, the cross-linked HA gel begins to soften and eventually dissolve. This hyaluronidase mechanism of action (MOA) happens primarily on the surface of the filler. That means more enzymatic activity occurs when the surface area is increased through dilution, massage, or proper injection technique. 

Hyaluronidase doesn’t penetrate deep into dense filler masses unless injected directly into them. Here’s how the process will look for the different types of fillers:

• Biphasic fillers. These contain loosely bound particles suspended in gel. Hyaluronidase often softens this filler within 5-15 minutes.
• Monophasic fillers. These have a tightly cross-linked matrix that resists penetration, so they often require more time, usually 1-2 hours or more, to show noticeable softening. They may need higher doses or repeated treatments. ^[3]

Here’s a breakdown of common fillers according to type:

Source

Hyaluronidase’s enzymatic activity is short-lived in the bloodstream, with a plasma half-life of about two minutes. But in tissue, its clinical effects may last up to 24-48 hours. This means it has to be injected repeatedly during emergencies, where it gets degraded quickly by enzymes in the blood. ^[5]

Factors That Influence Hyaluronidase Dosing Decision

The hyaluronidase dose to dissolve filler depends on the filler type, cross-linking, location, and some other factors. Here are more details:

1. Filler Structure and Degree of Cross-Linking

Not all fillers break down the same way. Their internal structure — how tightly the HA chains are cross-linked — affects their resistance to enzymatic action.

Highly cross-linked fillers like Juvederm Voluma or Volux often need multiple injections or doses exceeding 500 IU per mL. In contrast, low-density fillers used for fine lines may respond to much smaller amounts. ^[3]

2. Site of Injection and Depth

Fillers placed close to the bone, like in the midface or chin, last longer because these layers have lower levels of natural hyaluronidase and less blood flow. That makes them harder to reach and slower to dissolve.

But fillers in areas with thinner skin and more movement, like the lips, eyelids, or glabella, tend to soften more easily, though that doesn’t mean they need less attention. These regions are delicate and more prone to bruising, so injections must be precise, and lower doses are often safer. ^[2]

3. Patient-Specific Variables

No two patients respond to hyaluronidase in the same way. Individual factors like medications, allergies, immune conditions, and prior exposure to HA fillers all affect the effectiveness of hyaluronidase.  

For instance, anti-inflammatories, corticosteroids, salicylates, or herbal supplements may decrease a patient’s tissue permeability or increase resistance to hyaluronidase. ^[6]

Similarly, patients with known allergies to bee or wasp venom may have a potential risk of cross-reactivity, especially with animal-derived hyaluronidase. In these cases, recombinant human formulations may be safer to use. ^[7]

4. Clinical Goals

The amount of hyaluronidase used depends on the goal. Lower doses — often as little as 10-75 IU — can improve superficial issues like lumps or asymmetry without wiping out the entire filler effect. ^[2]

But you’ll require higher doses when complete filler degradation is the goal, especially in cases involving deeply placed or highly cross-linked hyaluronidase products. 

5. Timing Since Filler Placement

How long the filler has been in place affects how well it responds to hyaluronidase. Fresh filler — within days or weeks of injection — breaks down more easily. This is because it hasn’t integrated into the surrounding tissue, and the HA structure is still soft and accessible.

Older filler is a different challenge. Over time, HA fillers can become covered in fibrous tissue, form chronic nodules, or even harbor biofilms. This makes the filler harder to dissolve, and it often requires higher doses, multiple sessions, or direct injection into the mass.

6. Time to Reaction

Filler response to hyaluronidase varies based on structure. Biphasic fillers begin softening within 5-15 minutes. This helps the enzyme disperse quickly and expose more HA for breakdown.

Monophasic fillers, in contrast, take longer to respond. In some cases, softening may continue up to 24 hours. ^[3]

In urgent cases, you need to know about this delay because if you’re working with monophasic fillers, you may need to administer larger doses upfront, perform earlier re-dosing, or direct injection into the filler plane to make the response faster.

Recommended Doses of Hyaluronidase for Filler Complications

Filler complications fall into two categories: non-emergent and emergent. Let’s walk through the dosages for them below: 

Non-Emergent Complications

Here are the recommended hyaluronidase dosages for these complications: 

Source

Emergent Complications 

Emergent complications involve vascular events like occlusion or skin necrosis, which require immediate action. 

Here are the recommended hyaluronidase dosages for these complications: 

Source

Hyaluronidase Dosage by Filler Type

Hyaluronidase dosage by filler type includes:

Source

How to Dilute Hyaluronidase

Not all hyaluronidase products need to be reformulated. ^[2] Here are the most commonly used types: 

Source

If the formulation you’re using needs to be diluted, your manufacturer’s leaflet will provide the exact steps you need to take. However, here are the general steps.

• Use 5 to 10 mL of normal saline or bacteriostatic saline (0.9% NaCl) for every 1500 IU of hyaluronidase. 
• Draw a small volume of saline (1-10 mL) and add it to the hyaluronidase powder. 
• Swirl gently to reconstitute. Shaking will introduce air and reduce control over your dose.

Get High-Quality Hyaluronidase From Med Supply Solutions

When you’re using hyaluronidase for filler reversal, the dose you inject will depend on the complication you’re treating. It will also depend on the type and purity of the hyaluronidase formulation you’re using. 

At Med Supply Solutions, we provide high-quality 1500 IU Liporase and Hynidase that you can use for filler removal. Each vial meets strict quality standards and gives you the reliability you need when there is no margin for error. Place your order now. 

FAQs 

Can You Use Hyaluronidase on Non-HA Fillers?

No. It only works on HA-based products like Juvederm and Restylane.

Does Hyaluronidase Dissolve Botox?

No, hyaluronidase does not dissolve Botox. Hyaluronidase is an enzyme that specifically breaks down hyaluronic acid.

Botox, however, is a neurotoxin (botulinum toxin type A). Since it’s a completely different substance with a different mechanism of action, hyaluronidase has no effect on it.

When Should You Repeat Hyaluronidase?

In emergencies like vascular occlusion, repeat the injection every 30-60 minutes as needed until perfusion improves.  

For elective corrections like using hyaluronidase for lip filler, wait 1-2 weeks between sessions, since you could overcorrect if there is any residual hyaluronidase still breaking down filler. 

References

1. Wilde CL, Jiang K, Lee S, Ezra DG. The Posthyaluronidase Syndrome: Dosing Strategies for Hyaluronidase in the Dissolving of Facial Filler and Independent Predictors of Poor Outcomes. Plast Reconstr Surg Glob Open. 2024;12(4):e5765. Published 2024 Apr 23. doi:10.1097/GOX.0000000000005765  

2. Kroumpouzos G, Treacy P. Hyaluronidase for Dermal Filler Complications: Review of Applications and Dosage Recommendations. JMIR Dermatol. 2024;7:e50403. Published 2024 Jan 17. doi:10.2196/50403

3. Yi KH, Wan J, Yoon SE. Considerations for Proper Use of Hyaluronidase in the Management of Hyaluronic Acid Fillers. Plast Reconstr Surg Glob Open. 2025;13(3):e6566. Published 2025 Mar 3. doi:10.1097/GOX.0000000000006566

4. Rzany B, Becker-Wegerich P, Bachmann F, Erdmann R, Wollina U. Hyaluronidase in the correction of hyaluronic acid-based fillers: a review and a recommendation for use. J Cosmet Dermatol. 2009;8(4):317-323. doi:10.1111/j.1473-2165.2009.00462.x

5. Papakonstantinou E, Roth M, Karakiulakis G. Hyaluronic acid: A key molecule in skin aging. Dermatoendocrinol. 2012;4(3):253-258. doi:10.4161/derm.21923

6. Murray G, Convery C, Walker L, Davies E. Guideline for the Safe Use of Hyaluronidase in Aesthetic Medicine, Including Modified High-dose Protocol. J Clin Aesthet Dermatol. 2021;14(8):E69-E75. https://pubmed.ncbi.nlm.nih.gov/34840662/

7. Hong GW, Yi KH. Fundamental considerations for the use of hyaluronidase, an enzyme for degrading HA fillers. Skin Res Technol. 2024;30(7):e13839. doi:10.1111/srt.13839