Hyaluronic Acid

Approved Indications:

• Osteoarthritis (OA): Intra-articular injection to relieve pain in moderate to severe knee osteoarthritis unresponsive to conservative therapy.
• Ophthalmic Surgery: Used as a surgical aid in cataract extraction, intraocular lens implantation, corneal transplantation, and glaucoma filtration surgery.
• Dry Eye Disease: As artificial tears or ophthalmic gel/drops for treating dry eye syndrome.
• Dermal Filler (Aesthetic Use): Temporary correction of moderate to severe facial wrinkles and folds (e.g., nasolabial folds), lip augmentation, and volume restoration in facial soft tissues.
• Wound Healing: Topical application for chronic wounds, ulcers, and burns to accelerate healing and provide a moist environment.
• Urology: In the treatment of interstitial cystitis/bladder pain syndrome via intravesical instillation.
• ENT Disorders: Treatment of nasal mucosa dryness and atrophic rhinitis.

Off-label / Clinically Accepted Uses:

• Temporomandibular Joint Disorders (TMJ): Intra-articular use for pain and mobility improvement.
• Plantar Fasciitis: Injections for pain relief.
• Tendonitis/Bursitis: Investigational intra-tissue injection to reduce inflammation.

Adults:

• Osteoarthritis (Intra-articular):
• 2–4 mL of 1% sodium hyaluronate once weekly for 3–5 weeks (depending on product).
• Some high-molecular-weight preparations require a single injection (e.g., 6 mL once).
• Dry Eye (Ophthalmic use):
• 1–2 drops in each eye 3–4 times daily or as needed.
• Ophthalmic Surgery (Viscoelastic solution):
• Injected into the anterior chamber during surgery; dose varies by procedure.
• Dermal Filler:
• 0.5–2 mL per treatment site via subcutaneous or intradermal injection, every 6–12 months.
• Wound Care:
• Apply topical gel/cream once or twice daily to clean wounds.
• Bladder Instillation (Interstitial Cystitis):
• 40 mg in 50 mL saline intravesically weekly for 4–6 weeks, then monthly.

Pediatrics:

• Not routinely used, except in select surgical or ophthalmic cases under specialist guidance.

Elderly:

• Same as adult dosing. No specific age-related dose adjustment necessary.

Renal/Hepatic Impairment:

• No dosage adjustment required; not systemically absorbed in relevant formulations.

Route of Administration:

• Intra-articular, ophthalmic, intradermal, topical, intravesical, intraocular.

Hyaluronic acid is a naturally occurring glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It binds to cell surface receptors such as CD44 and RHAMM and exerts anti-inflammatory, viscoelastic, and lubricating properties. In joints, it enhances synovial fluid viscosity, reducing friction and pain. In dermal fillers, it restores volume by retaining water, while in ophthalmic and topical formulations, it maintains hydration and promotes tissue repair. The molecule modulates cell proliferation, migration, and inflammatory mediator activity, contributing to wound healing and tissue regeneration.

• Absorption: Topical and ophthalmic forms are minimally absorbed. Intra-articular and dermal forms remain localized with slow systemic absorption.
• Distribution: Binds to extracellular matrix; localized in joint, skin, or ocular tissues.
• Metabolism: Degraded by hyaluronidases and free radicals into smaller oligosaccharides and excreted by the lymphatic system.
• Elimination Half-life:
• Intra-articular: ~13 hours to several days depending on molecular weight.
• Dermal fillers: 6–12 months (resorption depends on cross-linking).
• Excretion: Primarily via lymphatic and hepatic pathways.

• Pregnancy: Hyaluronic acid is generally considered safe (non-FDA categorized); not systemically absorbed in most forms. Use only if clearly needed in pregnancy, especially for injectable formulations.
• Lactation: Limited data; however, systemic absorption is negligible for ophthalmic, topical, or intra-articular use. Considered safe during breastfeeding.

• Primary Class: Mucopolysaccharide / Biological Response Modifier
• Subclasses:
• Viscosupplement
• Ocular Lubricant
• Dermal Filler (Aesthetic Medicine)
• Topical Wound Agent

• Known hypersensitivity to hyaluronic acid or product components
• Active skin infections at the injection site
• Intra-articular use during joint infections or inflammation
• Intravesical use in patients with urinary tract infections

• Aseptic Technique: Mandatory for all injectable uses to prevent infection.
• Anaphylaxis Risk: Though rare, monitor for hypersensitivity reactions post-injection.
• Joint Effusion: Avoid intra-articular injection if large effusion is present.
• Avoid Intravenous Use: Not intended for systemic administration.
• Post-Injection Monitoring: Patients should avoid strenuous activities for 48 hours post-injection.
• Ocular Use: Do not use ophthalmic products with soft contact lenses unless stated.

Common Side Effects:

• Intra-articular: Local pain, swelling, stiffness, warmth, or joint effusion
• Dermal filler: Redness, bruising, pain, swelling at injection site
• Ophthalmic: Eye irritation, blurred vision, itching, redness
• Topical: Mild skin irritation or rash

Serious or Rare Side Effects:

• Anaphylactic reactions (very rare)
• Infection at injection site
• Granulomatous inflammation with dermal fillers
• Inflammatory joint flares
• Ocular infection (rare)

• Drug–Drug:
• No major systemic drug interactions due to local use
• Avoid concurrent intra-articular steroids unless advised
• Drug–Food/Alcohol: No known interactions
• Metabolism Enzymes: Not significantly metabolized via CYP450; low interaction potential

• Osteoarthritis Guidelines (e.g., ACR, OARSI):
• Viscosupplementation with hyaluronic acid is no longer strongly recommended for routine OA due to modest efficacy; reserved for specific patients.
• Dermal Filler Safety Updates:
• New protocols introduced for early identification and treatment of vascular occlusion.
• Ophthalmic Use:
• Enhanced formulations with cross-linked hyaluronic acid now approved for more sustained relief in dry eye.

• Topical, Ophthalmic, Injectable Solutions:
• Store at 20°C to 25°C (68°F to 77°F)
• Protect from light and moisture
• Do not freeze
• Single-use vials: Discard after opening
• Dermal fillers: Refrigerate some brands at 2°C–8°C if specified; check label
• Viscoelastic surgical agents: May require cold-chain storage