Hyaluronidase, often referred to as the "filler dissolver," is a widely used enzyme in medical and aesthetic procedures to break down hyaluronic acid (HA). It is commonly used to correct overfilled dermal fillers, dissolve vascular occlusions, and aid in the diffusion of injected medications. Understanding the timeline of its effects is critical for both practitioners and patients seeking correction of hyaluronic acid-based treatments.

Mechanism of Action: How Hyaluronidase Works?

Hyaluronidase works by enzymatically breaking down the glycosidic bonds of hyaluronic acid, reducing its molecular weight and viscosity. This degradation increases tissue permeability and allows for faster absorption and distribution of HA-based fillers or extravasated fluids.

The enzyme begins to act immediately upon injection, but the complete dissolution process depends on several factors, including enzyme concentration, filler density, and individual patient response.

Expected Timeframe for Results

The action of hyaluronidase can be divided into several phases:

1. Immediate Effects (0-30 minutes post-injection)

• Many patients report a visible reduction in filler volume within 5-15 minutes after administration.
• This rapid action is due to the enzyme's ability to break down the gel-like structure of hyaluronic acid almost immediately.
• However, in cases of high-density or cross-linked fillers, the initial breakdown may not be fully apparent.

2. Primary Dissolution Phase (1-24 hours post-injection)

• The majority of the filler breakdown occurs within 6-12 hours after injection.
• Patients may notice a significant reduction in volume within the first 24 hours, especially in areas with softer, less cross-linked fillers.
• Mild swelling, redness, or irritation at the injection site is common during this period.

3. Progressive Breakdown Phase (24-72 hours post-injection)

• Further breakdown of hyaluronic acid occurs over the next 24-72 hours as hyaluronidase continues to act.
• Heavily cross-linked fillers (e.g., those used in cheek augmentation) may require a longer time to dissolve completely.

4. Final Resolution Phase (3-7 days post-injection)

• Most of the enzymatic breakdown is complete within 3-7 days.
• Any residual filler that remains after this period may indicate that additional hyaluronidase treatments are needed.
• Tissue swelling subsides, and final results become apparent.

Figure 1. Phases of the action of hyaluronidase.

Factors Influencing the Time It Takes for Hyaluronidase to Work

The time required for full dissolution of hyaluronic acid by hyaluronidase varies depending on several factors:

Type of HA Filler Used

Different dermal fillers have different degrees of cross-linking, which affects how long they take to dissolve:

• Low-density, non-cross-linked fillers (e.g., lip fillers, fine line fillers) dissolve within 24 hours.
• Moderately cross-linked fillers (e.g., nasolabial fold fillers, under-eye fillers) take 48-72 hours to fully break down.
• Highly cross-linked fillers (e.g., cheek and jawline fillers) may take up to a week to fully dissolve.

Amount of Filler Present

• A small amount of filler dissolves faster (within 24 hours).
• Larger volumes or heavily injected areas may take multiple sessions and up to a week for complete resolution.

Dosage and Concentration of Hyaluronidase

• Higher concentrations of hyaluronidase lead to faster breakdown, but excessive dosing may cause unintended volume loss in natural tissue.
• Typical dosing ranges from 1.5 to 75 units per mL of HA filler, depending on the type and location.

Individual Patient Response

• Metabolism and enzymatic activity vary between individuals, affecting how quickly the filler breaks down.
• Some patients experience rapid breakdown within a day, while others may require additional treatments.

Injection Technique

• Direct intralesional injection leads to faster results (within hours).
• More superficial injections may take longer due to slower diffusion.

How Long Until Natural HA Is Fully Restored?

Although hyaluronidase specifically targets injected hyaluronic acid, it may also break down natural hyaluronic acid in surrounding tissues. However, natural HA replenishes over time.

• Within 48 hours: Local tissue begins to regenerate natural HA.
• Within 1-2 weeks: Most of the native HA in the treated area is restored.
• Within 3-4 weeks: Skin and connective tissue have fully recovered their hyaluronic acid levels.

For patients experiencing excessive volume loss post-hyaluronidase treatment, re-injection of filler can typically be performed after 7-14 days.

Multiple Sessions: When to Repeat Hyaluronidase Treatment

In cases where the filler is partially dissolved or more correction is needed, follow-up treatments may be required.

• Mild overcorrection: Wait 48-72 hours to assess full effect before deciding on re-injection.
• Persistent filler remnants: A second hyaluronidase treatment may be done 3-7 days after the initial injection.
• Significant overfilling or complications (e.g., vascular occlusion): Higher doses may be administered in multiple sessions within 24-48 hours.

Comparing Hyaluronidase to Natural Filler Breakdown

If left untreated, hyaluronic acid fillers naturally degrade over time due to enzymatic breakdown by endogenous hyaluronidase. The typical timeline for natural degradation is:

• Soft fillers (e.g., lip fillers): 6-9 months
• Moderate fillers (e.g., nasolabial folds, under-eye fillers): 12-18 months
• Firm fillers (e.g., jawline, cheek fillers): 18-24 months

Hyaluronidase accelerates this process to just a few days, making it the preferred choice for rapid correction.

Key Takeaways: Summary of How Long Hyaluronidase Takes to Work

Hyaluronidase is an essential tool in aesthetic and medical practice for dissolving hyaluronic acid-based fillers and correcting complications. While some effects are immediate, full results take 3-7 days, depending on various factors such as the type of filler, dosage, and individual metabolism. Understanding the timeline helps set realistic expectations for both patients and practitioners. If a patient does not see the desired effects after one week, a follow-up hyaluronidase session may be required for optimal results.

Creative Enzymes is a trusted enzyme supplier offering a wide range of hyaluronidases from various sources for medical and cosmetic applications. Contact us today to learn more about our high-quality hyaluronidase products.