Prednisolone acetate: ester prodrug of prednisolone with depot effect
Prednisolone acetate is a poorly water-soluble acetate ester of prednisolone, a moderately potent synthetic glucocorticoid. The esterification changes the physicochemical properties: prednisolone acetate is formulated as a crystalline suspension and provides a delayed, depot-like release. It is mainly used as eye drops and for intra-articular, intramuscular or local infiltrative applications.
In contrast to free prednisolone base, which is rapidly absorbed, prednisolone acetate has a particularly long duration of action at the site of application. In the eye, this delivers effective anti-inflammatory therapy for the anterior segments.
Mechanism of action
After application, prednisolone acetate is cleaved by esterases to release free prednisolone, which binds to the intracellular glucocorticoid receptor. Through transcription-dependent and -independent actions:
- Inhibition of phospholipase A2 with reduced production of prostaglandins, leukotrienes and platelet-activating factor
- Reduction of cytokine release and inhibition of inflammatory cell migration
- Stabilisation of lysosomal membranes
- Reduction of vascular permeability
The potency is about 4 times that of hydrocortisone with moderate mineralocorticoid activity. The biological half-life is 18 to 36 hours; the depot property of the acetate ester markedly prolongs the effect at the site of application.
Indications
- Ophthalmology: prednisolone acetate 1 % eye drops (e.g. Pred Forte) for non-infectious uveitis, postoperative inflammation after cataract surgery, severe allergic conjunctivitis, episcleritic and scleritic irritation
- Intra-articular use: acute flares of rheumatic disease, tendinitis, bursitis, post-traumatic irritation
- Intramuscular depot therapy: acute flares of inflammatory disease, severe hay fever (used cautiously due to non-controllable pharmacokinetics)
- Local infiltrations: inflammatory skin lesions, tenosynovitis
Prednisolone acetate eye drops are not suitable for treating infectious eye disease, since steroids can favour pathogen spread and mask the course of healing. Before use in red eye of unclear cause, ophthalmological evaluation is necessary.
Dosing and administration
Eye drops prednisolone acetate 1 %: 1 to 2 drops four to six times daily, more often in acute phases. Shake suspension well before use, as the substance is in microcrystals.
Intra-articular use: 5 to 50 mg depending on joint and severity, no more than 3 to 4 repetitions per year in the same joint.
Intramuscular use: 25 to 100 mg, repeat every 2 to 4 weeks. Due to poorly controllable duration of action, oral therapy is usually preferable.
Eye drops are placed in the conjunctival sac; afterwards close the lower lid briefly or press the tear duct for 1 to 2 minutes to reduce systemic uptake.
Side effects
Eye drops, common: burning or stinging immediately after instillation, briefly blurred vision.
Eye drops with prolonged use: raised intraocular pressure (steroid glaucoma), cataract (posterior subcapsular cataract), delayed wound healing, secondary fungal infections (especially in contact lens wearers), reactivation of ocular herpes infections.
Intra-articular: pain at injection site, transient flush symptoms, in rare cases cartilage damage with repeated injections in the same joint, infections, periarticular skin atrophy.
Systemic: as with all glucocorticoids; with repeated depot injection or local high doses, Cushing's syndrome, weight gain, hyperglycaemia and adrenal insufficiency are possible.
Important: prednisolone acetate eye drops should not be used over long periods without medical supervision. Regular ophthalmological checks including intraocular pressure measurement are standard.
Interactions
- Other ophthalmic substances: apply with a time interval to avoid wash-out
- Antiglaucoma drugs: in steroid glaucoma as concurrent therapy
- Live vaccines: contraindicated after high-dose systemic use; topical ophthalmological use usually unproblematic clinically
- NSAIDs: additive effects on ocular wound healing
- CYP3A4 inhibitors and inducers: relevant with systemic effect, mostly not clinically relevant topically
Special considerations
Pregnancy: ophthalmic use with low absorption is acceptable; intra-articular or intramuscular after individual judgement.
Breastfeeding: usually no impact on the infant with local use.
Children: ophthalmic use with caution and close intraocular pressure monitoring.
Contact lenses: soft lenses should be removed during eye-drop use, as preservatives can accumulate in the lens. Reinsert at the earliest 15 minutes after instillation.
Steroid glaucoma: with family history of glaucoma or known steroid sensitivity, close intraocular pressure monitoring.
Infectious eye disease: exclude before therapy. In herpes simplex keratitis, steroids are contraindicated without antiviral cover.
Patient communication: instructions on correct technique, the need for ophthalmological monitoring and early warning signs such as worsening vision or eye pain.
Related substances
- Betamethasone, highly potent glucocorticoid
- Betamethasone valerate, mid-potency ester
- Fluticasone, highly potent inhaled and topical steroid
- Fluocinolone, another potent topical glucocorticoid
Frequently asked questions
Why must I shake the eye drops?
Prednisolone acetate is poorly water-soluble and exists as a microcrystal suspension. On standing, the crystals settle. Shaking before each use ensures homogeneous distribution and a uniform dose. Without shaking, the first drops can be underdosed and the last overdosed.
How long can I use prednisolone acetate eye drops?
Treatment duration depends on indication. Postoperatively after cataract surgery usually 4 to 6 weeks. In uveitis individual control with gradual reduction. Long-term use over several weeks should always be under ophthalmological supervision to detect steroid glaucoma and cataract early.
Are the eye drops an option for red conjunctiva?
Not without diagnostics. Red conjunctiva can have many causes, including viral, bacterial and allergic conjunctivitis as well as herpes keratitis. With infectious cause, steroids can worsen the course. Ophthalmological evaluation before therapy is therefore mandatory.
What is steroid glaucoma?
In genetically predisposed patients, prolonged steroid therapy can considerably raise intraocular pressure, with risk of glaucoma damage. Early signs are often unnoticeable, hence regular intraocular pressure measurements during steroid therapy are recommended.
Sources
- EMA European Medicines Agency
- BfArM Federal Institute for Drugs and Medical Devices
- AWMF guidelines uveitis and postoperative ocular surgery
- Gelbe Liste prednisolone acetate monograph
Legal notice and disclaimer
The information on this page is provided for general information purposes only and does not constitute medical advice, diagnosis or treatment recommendation. It does not replace the advice of a licensed physician or pharmacist. Medicines should only be used after a doctor's prescription or pharmacy supply. All information is based on summaries of product characteristics and accepted scientific sources at the time of writing; the current SmPC of the manufacturer is always decisive. Sanoliste accepts no liability for completeness, timeliness or accuracy. In a medical emergency, dial the emergency number 112.