Ofloxacin stuln ud

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT OFLOXACIN-STULLN® UD (Ofloxacin)

Composition:

Active substance: ofloxacin;

1 ml of eye drops contains 3.0 mg of ofloxacin;

Excipients: sodium chloride, hydrochloric acid and sodium hydroxide, water for injections.

Pharmaceutical form. Eye drops.

Main physicochemical properties: clear, colorless solution.

Pharmacotherapeutic group.

Agents used in ophthalmology. Antimicrobial agents. Ofloxacin.

ATC code S01AE01.

Pharmacological properties.

Pharmacodynamics.

Ofloxacin, a derivative of quinolonic acid, is a fluoroquinolone (gyrase inhibitor) antibiotic with bactericidal activity.

Breakpoints

Ofloxacin testing was performed using a dilution series. Minimum inhibitory concentrations were determined for susceptible and resistant bacteria (see table).

EUCAST (European Committee on Antimicrobial Susceptibility Testing) breakpoints

*Primarily determined based on serum pharmacokinetics.

Antibacterial spectrum

The spectrum of activity of ofloxacin includes obligate anaerobes, facultative anaerobes, aerobes, and other microorganisms such as Chlamydia. The prevalence of acquired resistance among individual species may vary depending on geographic location and over time. Therefore, obtaining local resistance data is essential for appropriate treatment of severe infections.

Microbiological identification of the causative pathogen and its susceptibility to ofloxacin is mandatory in cases of severe infections or lack of therapeutic response. Cross-resistance between ofloxacin and other fluoroquinolones is possible.

The information provided below is derived from a resistance study conducted using 1391 isolates from examined eyes (mainly external washings) across 31 centers in Germany.

This study provides representative data on aerobes causing ocular infections in Germany. It may be assumed that the frequency of bacteria capable of causing ophthalmological diseases in other countries will not be identical but similar; therefore, the bacteria listed below are the most common causative agents of bacterial infections of the external eye.

Resistance data refer to systemic use. When applied topically to the eye, significantly higher antibiotic concentrations are achieved; thus, clinical efficacy may be observed even against pathogens identified as resistant in laboratory testing. Such an effect, for example, has been observed with Enterococcus species.

Typically susceptible species

Gram-positive aerobes: Bacillus spp., methicillin-susceptible Staphylococcus aureus.

Gram-negative aerobes: Acinetobacter baumannii, Acinetobacter lwoffi, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis, Proteus mirabilis, Serratia marcescens.

Species that may be resistant due to acquired resistance when using the drug

Gram-positive aerobes: Corynebacterium spp., Enterococcus faecalis, methicillin-resistant Staphylococcus aureus¹, Staphylococcus epidermidis, Streptococcus pneumoniae², Streptococci (except Streptococcus pneumoniae)².

Gram-negative aerobes: Pseudomonas aeruginosa, Stenotrophomonas maltophilia.

Species with intrinsic resistance to the drug

Gram-positive aerobes: Enterococcus spp.

¹ Resistance levels exceed 50% in at least one region.
² The natural susceptibility of most individual species lies within intermediate ranges. However, in tear fluid, concentrations of at least 4 mg/L are achieved after a single instillation and maintained for 4 hours, which is sufficient to eliminate 100% of microorganisms.

Pharmacokinetics.

Efficacy largely depends on the ratio between maximum tissue concentration (C_max) and the minimum inhibitory concentration (MIC) of the pathogen.

Animal experiments have shown that after topical administration, ofloxacin can be detected in the cornea, conjunctiva, ocular muscle, sclera, iris, ciliary body, and anterior chamber of the eye. With repeated administration, the drug accumulates in therapeutic concentrations in the vitreous body.

After administration of Ofloxacin Stulln UD, eye drops, five times daily at 5-minute intervals, ofloxacin concentrations in human intraocular fluid reach 1.2–1.7 µg/mL within 60–120 minutes. After 3 hours, this value decreases to 0.8 µg/mL. Depending on the frequency of instillation, ofloxacin concentrations in intraocular fluid decrease to zero within 5–6 hours.

By analogy with animal study results, it can be assumed that other ocular tissues contain higher concentrations of the drug than intraocular fluid. Since ofloxacin may bind to melanin-containing tissues, a slower elimination of the substance from these tissues is expected. The elimination half-life of ofloxacin in plasma during systemic administration ranges from 3.5 to 6.7 hours.

Clinical characteristics.

Indications.

Infections of the anterior eye segments caused by pathogenic microorganisms sensitive to ofloxacin, such as bacterial inflammation of the conjunctiva, cornea, eyelid margins, and lacrimal sac; hordeolum and corneal ulcer.

Contraindications.

Hypersensitivity to any component of the drug or to other quinolones.

Interaction with other medicinal products and other forms of interaction.

Not known so far. Drug interaction studies conducted with systemic administration of ofloxacin have shown that the clearance of metabolites of caffeine and theophylline is slightly affected by ofloxacin.

Special precautions for use.

Safety and efficacy in children under 1 year of age have not been established.

There is only limited evidence of the efficacy and safety of 0.3% ophthalmic drops containing ofloxacin in the treatment of conjunctivitis in newborns.

The use of ophthalmic drops containing ofloxacin in newborns for the treatment of ophthalmia neonatorum caused by Neisseria gonorrhoeae or Chlamydia trachomatis is not recommended, as administration to this age group has not been studied.

If an allergic reaction to the drug occurs, its use must be discontinued.

Prior to initial administration, microbiological examination of conjunctival swabs is advisable to determine bacterial strain sensitivity to the drug.

With prolonged use, development of bacterial resistance and emergence of microorganisms insensitive to the antibacterial agent may occur. If symptoms worsen or no clinical improvement is observed, treatment should be discontinued and alternative therapy initiated.

Cases of corneal perforation have been reported in patients with corneal epithelial defects or corneal ulcers treated with topical fluoroquinolone antibiotics. However, in many cases, risk factors were present, such as advanced age, presence of large ulcers, concomitant ocular diseases (e.g., severe dry eye), systemic inflammatory conditions (e.g., rheumatoid arthritis), or concomitant use of corticosteroids or nonsteroidal anti-inflammatory drugs. Nevertheless, due to the risk of corneal perforation, caution should be exercised when using this medicinal product in patients with existing corneal epithelial defects or corneal ulcers.

During treatment with ofloxacin, excessive sun exposure or ultraviolet irradiation (e.g., tanning beds, sunlamps, etc.) should be avoided, as photosensitivity may occur.

During treatment, rigid contact lenses should not be worn. Therefore, it is recommended to remove rigid lenses before applying the medication and not to reinsert them earlier than 20 minutes after instillation.

When using this product together with other ophthalmic drops/ointments, medicinal products should be administered at intervals of at least 15 minutes. In any case, ophthalmic ointment should be applied last.

With systemic use of fluoroquinolones, caution is advised in patients at risk of QT interval prolongation, namely: those with congenital long QT syndrome, those receiving concomitant medications that prolong the QT interval (e.g., class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics), those with uncorrected electrolyte imbalances (e.g., hypokalemia, hypomagnesemia), elderly patients, and patients with cardiac conditions (e.g., heart failure, myocardial infarction, bradycardia).

Tendon inflammation and rupture may occur during systemic fluoroquinolone therapy, including ofloxacin, particularly in elderly patients and in patients receiving concomitant corticosteroids. Therefore, caution should be exercised, and if early signs of tendon inflammation occur, treatment with ophthalmic drops should be discontinued.

Use during pregnancy or breastfeeding.

Despite the lack of evidence for any embryotoxic effects, ophthalmic drops should not be used during pregnancy or breastfeeding if possible.

Ability to influence reaction speed when driving or operating machinery.

The use of ophthalmic drops does not affect the patient's reaction speed.

After instillation of the drug into the conjunctival sac of the eye, blurred vision may occur for several minutes. During this time, patients should refrain from driving or operating machinery.

Dosage and Administration

The dosage and duration of treatment are always determined by a physician, depending on the severity of the disease and the patient's age.

If not otherwise prescribed, instill 1 drop of ophthalmic drops into the conjunctival sac of the affected eye 4 times daily. The duration of treatment with ophthalmic drops should not exceed 2 weeks.

Instructions for Use

1. Open the aluminum foil pouch and remove the unit containing single-dose vials.
2. Separate one single-dose vial from the unit.
3. Place the remaining single-dose vials back into the pouch and close it by folding the edge. Store the pouch in the carton.
4. Gently pull down the lower eyelid and, by slightly squeezing the vial, instill 1 drop into the conjunctival sac of the affected eye. The contents of a single-dose vial are sufficient for both eyes.
5. Discard the vial after use.

Children

Ofloxacin Stulln UD, ophthalmic drops, can be prescribed to children aged 1 year and older.

Overdose

There have been no reports of overdose to date.

Treatment is symptomatic; immediately rinse the eye(s) with water.

Side effects.

Immediately after instillation of the medication, blurred vision may occur for several minutes.

General manifestations.

Serious reactions following systemic administration of ofloxacin are rare, and most symptoms are reversible. Although only a small amount of ofloxacin is absorbed into the systemic circulation with topical use, the possibility of adverse effects reported with systemic use cannot be excluded.

Immune system side effects: occasionally – conjunctival hyperemia and/or mild eye burning sensation. In most cases, these symptoms are transient.

In very rare cases (<1/10,000): hypersensitivity reactions, including angioneurotic edema, dyspnea, anaphylactic reactions/shock, swelling of the mouth, pharynx and tongue, eye and eyelid itching.

Nervous system side effects: in isolated cases – dizziness.

Eye-related side effects: frequently: eye discomfort, eye irritation.

Occasionally: keratitis, conjunctivitis, blurred vision, photophobia, eye swelling, eye redness, foreign body sensation, increased lacrimation, dry eyes, eye pain, itching, eyelid swelling.

In rare cases (from 1/10,000 to 1/1,000), corneal deposits may occur, particularly in patients with a history of corneal disease.

There have been reports of very rare reactions following topical administration such as toxic epidermal necrolysis and Stevens–Johnson syndrome. A causal relationship between these events and the use of ophthalmic drops has not been established.

Gastrointestinal side effects: in isolated cases – nausea.

Skin and subcutaneous tissue side effects: in isolated cases – facial swelling, periorbital edema.

Serious, sometimes fatal, hypersensitivity reactions, occasionally after the first dose, have been observed with systemic administration of quinolones.

In patients receiving systemic fluoroquinolones, cases of shoulder, hand, or Achilles tendon rupture have been reported, which required surgical repair or resulted in prolonged disability. Clinical studies and post-marketing experience with systemic quinolones indicate that the risk of such tendon ruptures may be increased in patients receiving corticosteroids, particularly in elderly patients. This risk primarily affects tendons under high stress, including the Achilles tendon.

Shelf life.

The shelf life of the product, when stored in undamaged packaging, is 3 years. Do not use the medication after the expiry date stated on the packaging and on the single-dose vial.

Ofloxacin Stulln UD does not contain preservatives. Once opened, the single-dose vial must not be stored. Any unused portion remaining in the single-dose vial after use must be discarded.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C, in a place inaccessible to children. Protect from light.

After opening, the contents of the single-dose vial should be used immediately.

After opening the aluminum foil pouch, the medicinal product should be used within 4 weeks. If the single-dose vials are stored in the cardboard box after opening the aluminum foil pouch, the product remains stable for 3 months.

Packaging.

0.5 mL in a single-dose dropper tube containing one dose of Ofloxacin Stulln UD eye drops.

5 dropper tubes connected into one block; 1 block (No. 5) or 2 blocks (No. 10) in an aluminum package, or 6 blocks (No. 30, with every 2 blocks in an aluminum package) of dropper tubes in a cardboard box.

Prescription category.

Prescription only.

Manufacturer. Pharma Stulln GmbH.

Manufacturer's address and place of business.

Werksstrasse 3, 92551 Stulln, Germany.