Usage
Hyaluronidase is used to increase the absorption and dispersion of other injected drugs, for subcutaneous urography to improve resorption of radiopaque agents, and to promote resorption of excess fluids and blood in the tissues. It is also used in ophthalmology to facilitate surgery and in the management of extravasation. Its pharmacological classification is an enzyme, specifically a glycosaminoglycan hydrolase. It works by temporarily breaking down hyaluronic acid, a component of the extracellular matrix that holds tissues together and resists the diffusion of fluids. This allows injected fluids or medications to spread and be absorbed more easily.
Alternate Names
Hyaluronidase is also known as hyaluronidase human injection or recombinant human hyaluronidase (rHuPH20). Brand names include Amphadase, Hylenex, Vitrase, and Hydase. Hyalase is another recognized name for hyaluronidase.
How It Works
Pharmacodynamics: Hyaluronidase hydrolyzes hyaluronic acid, increasing tissue permeability and facilitating the diffusion of injected fluids and medications.
Pharmacokinetics: Hyaluronidase is administered subcutaneously, intradermally, or intramuscularly. It is not effective intravenously as it is rapidly degraded in the bloodstream. Absorption is rapid following subcutaneous or intramuscular injection. Metabolism and elimination pathways are not fully characterized but likely involve widespread enzymatic degradation.
Mode of Action: Hyaluronidase acts by cleaving the glycosidic linkages between N-acetyl-D-glucosamine and D-glucuronic acid residues in hyaluronic acid, resulting in depolymerization. This reduces the viscosity of hyaluronic acid and increases tissue permeability, promoting absorption and dispersion.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Hyaluronidase exerts its effects by enzymatic activity directly on hyaluronic acid rather than through receptor binding, enzyme inhibition, or neurotransmitter modulation.
Elimination Pathways: Elimination pathways have not been fully elucidated but involve rapid breakdown by ubiquitous enzymes.
Dosage
Standard Dosage
Adults:
Doses range from 150-1500 IU depending on the indication. For hypodermoclysis, 1500 IU are added to facilitate absorption of 500-1000ml. For subcutaneous or intramuscular injections or to enhance local anesthetics, 1500 IU may be directly mixed with the injection solution.
Children:
Pediatric dosing varies depending on the indication. Skin testing: 0.02 mL of a 150 units/mL or 200 units/mL solution is given intradermally. In subcutaneous urography, 75 units are administered over each scapula. For other subcutaneous injections, 50-300 units may be added to the injection solution (up to 200 mL). In neonates and infants under 3 years, fluid volume for hypodermoclysis should be limited to 200mL. Premature/neonatal hypodermoclysis should not exceed 25 mL/kg/day with a rate no greater than 2 mL/minute.
Special Cases:
- Elderly Patients: Adjust dosage as needed, especially in those with renal impairment.
- Patients with Renal Impairment: Use with caution and reduce dosage as necessary.
- Patients with Hepatic Dysfunction: Exercise caution.
- Patients with Comorbid Conditions: Consider individual patient factors when determining dosage.
Clinical Use Cases
Dosage recommendations vary widely for each clinical situation:
- Extravasation: Doses range from 15 units/mL (for smaller volumes <100 mL) up to 150 units/mL. 1 mL of hyaluronidase (150 units/mL) is usually given per each 1 mL of extravasated drug.
- Subcutaneous Urography: 75 units over each scapula.
- Absorption/Dispersion of Injected Drugs: 50-300 units added to the injection solution.
- Hypodermoclysis: 1500 IU to facilitate 500-1000 mL of fluid.
- Ophthalmologic Procedures: 15 IU per mL of solution.
Dosage Adjustments
Adjust dosage based on patient-specific factors, such as renal or hepatic dysfunction and co-administered medications.
Side Effects
Common Side Effects
Injection site reactions (pain, swelling, itching, redness).
Rare but Serious Side Effects
Allergic reactions (including anaphylaxis), breathing difficulties, dizziness.
Long-Term Effects
Data on chronic complications is limited.
Adverse Drug Reactions (ADR)
Thrombosis (especially in patients with risk factors).
Contraindications
Hypersensitivity to hyaluronidase, active infections at the injection site, not to be used for intravenous injections. Use caution in pregnancy and breastfeeding.
Drug Interactions
Incompatible with furosemide, benzodiazepines, and phenytoin. Do not use with dopamine or alpha-agonist drugs. Salicylates, cortisone, ACTH, estrogens, and antihistamines may require higher doses of hyaluronidase. May interact with several other medications; refer to a comprehensive drug interaction resource before co-administration.
Pregnancy and Breastfeeding
Use with caution. Safety profiles for pregnancy and breastfeeding are not well-established. Avoid use unless no safer alternative exists. It is not known whether hyaluronidase is excreted in human milk.
Drug Profile Summary
- Mechanism of Action: Hydrolyzes hyaluronic acid, increasing tissue permeability.
- Side Effects: Injection site reactions, allergic reactions, thrombosis.
- Contraindications: Hypersensitivity, active infections at injection site, intravenous use.
- Drug Interactions: Furosemide, benzodiazepines, phenytoin, dopamine, alpha-agonist drugs.
- Pregnancy & Breastfeeding: Use with caution; safety not established.
- Dosage: Varies depending on the indication and patient-specific factors.
- Monitoring Parameters: Observe injection site, monitor for allergic reactions and signs of thrombosis.
Popular Combinations
Used with local anesthetics to improve diffusion, and with subcutaneous fluids for hypodermoclysis.
Precautions
- General Precautions: Perform skin testing before administration if hypersensitivity is suspected.
- Specific Populations: Use with caution in pregnant women, breastfeeding mothers, children, and elderly patients.
- Lifestyle Considerations: No specific lifestyle considerations generally apply.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Hyaluronidase?
A: The dosage varies widely depending on the clinical indication and the patient’s specific characteristics (age, weight, renal/hepatic function). Consult dosage guidelines provided above and refer to a comprehensive drug information resource for detailed and situation-specific recommendations.
Q2: How is Hyaluronidase administered?
A: It can be administered subcutaneously, intramuscularly, or intradermally, depending on the indication. Never administer intravenously.
Q3: Can Hyaluronidase be used in pregnant or breastfeeding women?
A: It should be used with caution in pregnant or breastfeeding women, and only when the benefits outweigh the potential risks. Safety in pregnancy and breastfeeding is not fully established.
Q4: What are the most common side effects of Hyaluronidase?
A: The most common side effects are injection site reactions, including pain, swelling, itching, and redness.
Q5: What should be done in case of a suspected allergic reaction?
A: Discontinue the injection immediately and provide appropriate medical care, such as administering antihistamines, corticosteroids, or epinephrine as needed.
Q6: Are there any drug interactions I should be aware of?
A: Yes, hyaluronidase is incompatible with several drugs, including furosemide, benzodiazepines, and phenytoin. It can also interact with other medications. Always check for potential drug interactions before administering hyaluronidase.
A: While effective for many medications, it is not universally effective for all extravasations. It primarily works by breaking down hyaluronic acid; therefore, it may not be effective in dispersing drugs that do not interact significantly with this substance.
Q8: Can hyaluronidase be used with dopamine or alpha-agonist drugs?
A: No, hyaluronidase should not be used to enhance dispersion and absorption of dopamine and/or alpha agonist drugs.
Q9: What is the role of hyaluronidase in ophthalmology?
A: In ophthalmology, hyaluronidase is used to facilitate certain surgical procedures by increasing the dispersion of other injected substances.
Q10: How does the concentration of hyaluronidase impact its efficacy?
A: Higher concentrations are typically associated with more pronounced effects. The appropriate concentration should be selected based on the indication and desired clinical outcome.
