Medrolgin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT MEDROLGIN (MEDROLGIN)

Composition:

Active substance: ketorolac;

1 ml of solution contains ketorolac tromethamine 5 mg;

Excipients: octoxynol 40, disodium edetate, sodium chloride, benzalkonium chloride, sodium hydroxide or hydrochloric acid, purified water.

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: clear solution ranging from colorless to pale yellow, practically free from mechanical impurities.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory drugs. Ketorolac. ATC code S01BC05.

Pharmacological properties.

Pharmacodynamics.

Ketorolac is a non-steroidal anti-inflammatory drug (NSAID) that exerts analgesic and anti-inflammatory effects. It acts by inhibiting cyclooxygenase, an enzyme essential for the biosynthesis of prostaglandins. When administered locally into the eye, ketorolac reduces the level of prostaglandins in the aqueous humor of the eye.

After systemic administration, it does not cause pupillary constriction. Ketorolac has no significant effect on intraocular pressure.

Pharmacokinetics.

Ocular drops of ketorolac (0.1% or 0.5%) or placebo were instilled approximately 12 hours and 1 hour before surgery. Ketorolac concentrations in the aqueous humor at the time of surgery were at the lower limit of quantification (40 ng/mL) in 1 patient and below the quantifiable limit in 7 patients who received the 0.1% ketorolac solution. The mean ketorolac concentration in the aqueous humor in patients who received the 0.5% ketorolac solution was 95 ng/mL.

The following shows the concentration of prostaglandin PGE2 in the aqueous humor in patients who received placebo, 0.1% and 0.5% ketorolac solution, respectively.

A 21-day multiple-dose tolerability study of ketorolac (three times daily) in healthy volunteers showed that measurable plasma concentrations of ketorolac were detected in only 1 out of 13 volunteers (0.021 μg/mL). In another group of 13 volunteers, very low plasma concentrations of ketorolac (0.011–0.023 μg/mL) were detected in only 4 subjects, 15 minutes after instillation of the solution.

Thus, the observation of higher ketorolac concentrations in aqueous humor and very low or below the quantifiable limit concentrations in plasma following ophthalmic administration suggests that ketorolac has minimal systemic absorption when used ophthalmically.

Clinical characteristics.

Indications.

Prevention and reduction of ocular tissue inflammation following cataract surgery.

Contraindications.

Hypersensitivity to the active substance and/or to any of the excipients of the medicinal product.

Cross-reactivity with acetylsalicylic acid and other NSAIDs is possible; therefore, the use of this medicinal product is contraindicated in patients who have previously shown hypersensitivity to these drugs.

Interaction with other medicinal products and other forms of interaction.

Interaction studies have not been conducted.

Without apparent risk of intolerance, ketorolac in the form of eye drops has been used concomitantly with systemic and ophthalmic medicinal products such as antibiotics, sedatives, beta-blockers, carbonic anhydrase inhibitors, miotics, mydriatics, local anesthetics, and cycloplegics.

Ketorolac may delay or impair wound healing. Topical corticosteroids are also known to delay or impair wound healing. Concomitant use of topical NSAIDs (including ketorolac) and topical corticosteroids may increase the risk of healing complications (see section "Special precautions for use").

When using ketorolac eye drops together with other ophthalmic medicinal products, an interval of at least 5 minutes between applications should be maintained.

Special precautions for use.

It has been reported that NSAIDs used for the treatment of eye disorders may cause increased bleeding in ocular tissues (including hemorrhage in the anterior chamber of the eye) during ophthalmic surgery. The medicinal product should be used with caution in patients with a tendency to bleeding or in those receiving other medicinal products that may increase bleeding time.

Similar to other NSAIDs, ketorolac may mask the usual signs of infection. Appropriate treatment should be initiated if there is a risk of infection.

All NSAIDs (including ketorolac) may delay or impair wound healing. Concomitant use of topical NSAIDs (including ketorolac) and topical corticosteroids may increase the risk of healing complications. Caution should be exercised in patients receiving concomitant therapy with the medicinal product and topical corticosteroids, particularly in patients with a predisposition to corneal epithelial damage.

Patients should be informed about the possibility of delayed or impaired healing when using the medicinal product.

Use of topical NSAIDs (including ketorolac) may lead to the development of keratitis. In some patients predisposed to the condition, prolonged use of topical NSAIDs (including ketorolac) may result in corneal epithelial breakdown, thinning, erosion, corneal ulceration, and corneal perforation. These events may threaten vision. Patients showing signs of corneal epithelial breakdown should discontinue the medicinal product immediately and undergo corneal evaluation.

The medicinal product should be used with caution in patients who have undergone complicated ocular surgery, patients with corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid arthritis, or patients who have undergone repeated ocular surgeries within a short period, as the risk of corneal adverse reactions, potentially leading to vision loss, is increased.

Post-marketing experience with topical NSAIDs (including ketorolac) suggests that use earlier than 1 day before or later than 14 days after surgery may increase the risk and severity of corneal adverse reactions.

In the post-marketing period, cases of bronchospasm or asthma exacerbation have been observed in patients with hypersensitivity to acetylsalicylic acid/NSAIDs or a history of asthma when using ketorolac eye drops. The medicinal product should be used with caution in such patients (see section "Adverse reactions").

The bottle should be closed after each use. The dropper tip should not touch the eye or any other surface to prevent contamination of the eye drops or eye injury. Serious eye damage with subsequent vision loss may result from the use of contaminated solutions.

The risk of adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.

The medicinal product contains benzalkonium chloride, which may cause eye irritation and may discolor soft contact lenses. Contact with soft contact lenses should be avoided. Contact lenses must be removed before instillation of eye drops and reinserted only after 15 minutes following instillation.

Use during pregnancy or breastfeeding.

Pregnancy.

There are insufficient data on the use of ketorolac eye drops in pregnant women. Animal studies have shown reproductive toxicity. Inhibition of prostaglandin synthesis may have a negative effect on pregnancy, embryofetal development, and/or postnatal development.

Despite the low systemic exposure following ocular administration of ketorolac eye drops, the medicinal product is not recommended during pregnancy.

Breastfeeding period.

After systemic administration, ketorolac is excreted in breast milk. The medicinal product should not be used during breastfeeding.

Fertility.

There is insufficient data on the effect of ketorolac on human fertility.

Ability to affect reaction speed when driving or operating machinery.

Blurred vision may occur temporarily after instillation of eye drops. Patients should wait until vision clears before driving or operating machinery.

Dosage and Administration

The medicinal product is intended for topical use only in adults.

The recommended dose is 1 drop instilled into the affected eye(s) three times daily. Instillations should begin 24 hours prior to surgical intervention, continued on the day of surgery, and maintained throughout the postoperative period for 3–4 weeks.

The solution should be administered as 1 drop into the conjunctival sac of the affected eye, gently pulling down the lower eyelid and directing the gaze upward.

When using concurrently with other ophthalmic agents, an interval of at least 5 minutes between administrations should be maintained.

Elderly patients

No differences in safety and efficacy have been observed between elderly patients and younger patients.

Children

The safety and efficacy of ketorolac eye drops in children have not been established. The medicinal product should not be used in pediatric practice.

Overdose

There are no reported cases of overdose. Overdose is unlikely to occur with recommended administration.
In case of accidental ingestion of eye drops, drink plenty of fluids.

Side effects

The most commonly reported side effects with ocular ketorolac administration are transient sensations of stinging and burning upon instillation.

Adverse reactions are listed by frequency: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000), and not known (frequency cannot be estimated from available data). Within each frequency category, adverse reactions are presented in order of decreasing severity.

Immune system disorders:

Common – hypersensitivity, including local allergic reactions.

Nervous system disorders:

Common – headache.

Eye disorders:

Very common – eye irritation (including burning sensation), eye pain (including stinging); common – superficial (punctate) keratitis, eye and/or eyelid edema, eye pruritus, conjunctival hyperemia, eye infections, eye inflammation, uveitis, keratic precipitates, retinal hemorrhage, cystoid macular edema, eye injury, increased intraocular pressure, blurred and/or worsened vision; uncommon – corneal ulcer, corneal infiltrate, dry eye, epiphora; not known – corneal damage (thinning, erosion, degradation, and epithelial perforation)*.

Respiratory, thoracic and mediastinal disorders:

Not known – bronchospasm or asthma exacerbation**.

* There have been a small number of spontaneous reports of corneal events including corneal thinning, corneal erosion, epithelial damage, and corneal perforation. These events have mostly occurred in patients concurrently using topical corticosteroids and/or in the presence of risk factors (see section "Special precautions").

** During the post-marketing period, cases of bronchospasm or asthma exacerbation have been reported with ocular ketorolac use in patients with hypersensitivity to acetylsalicylic acid/NSAIDs or with a history of asthma.

When NSAIDs (including ketorolac) are used in ophthalmology at standard doses, systemic adverse reactions have not been observed.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions via the national pharmacovigilance system.

Shelf life

2 years.

After opening the bottle, the medicinal product can be used for up to 4 weeks.

Storage conditions

Store at temperatures not exceeding 25 °C. Keep out of reach and sight of children.

Packaging

5 ml in a dropper bottle; 1 dropper bottle in a cardboard box.

Prescription status

Prescription only.

Manufacturer

C.O. Rompharm Company S.R.L., Romania

S.C. Rompharm Company S.R.L., Romania.

Manufacturer's address and place of business

Otopeni, Eroilor str. No. 1A, 075100, Ilfov county, Romania.

Marketing Authorization Holder

WORLD MEDICINE, LLC, Ukraine.