Rubrodex (Drops) Instructions for Use

Marketing Authorization Holder

Sun Pharmaceutical Industries, Ltd. (India)

Manufactured By

Sun Pharmaceutical Medicare Ltd. (India)

ATC Code

S01CA01 (Dexamethasone and antimicrobial drugs)

Active Substances

Dexamethasone (Rec.INN registered by WHO)

Tobramycin (Rec.INN registered by WHO)

Dosage Form

Rubrodex

Eye drops 1 mg+3 mg/1 ml: 5 ml dropper bottle

Dosage Form, Packaging, and Composition

Eye drops as a suspension from white to almost white in color.

Excipients: hyetellose (hydroxyethylcellulose) – 2.5 mg, sodium chloride – 3 mg, disodium edetate – 0.1 mg, sodium sulfate – 12 mg, tyloxapol – 0.5 mg, benzalkonium chloride (50% w/w) – 0.2 mg, water for injections – up to 1 ml, sodium hydroxide – sufficient quantity to adjust pH to 5.5±0.5, sulfuric acid – sufficient quantity to adjust pH to 5.5±0.5.

5 ml – polyethylene dropper bottles (1) – cardboard packs.

Clinical-Pharmacological Group

A drug with antibacterial and anti-inflammatory action for topical application in ophthalmology

Pharmacotherapeutic Group

Topical glucocorticosteroid + aminoglycoside antibiotic

Pharmacological Action

A combined medicinal product with antibacterial and anti-inflammatory action for topical use in ophthalmology.

Dexamethasone is a glucocorticosteroid. It has a pronounced anti-inflammatory, anti-allergic, and desensitizing effect. Dexamethasone actively suppresses inflammatory processes by inhibiting the release of inflammatory mediators by eosinophils, the migration of mast cells, and by reducing capillary permeability. It does not possess mineralocorticoid activity.

Tobramycin is a broad-spectrum antibiotic from the aminoglycoside group. It disrupts protein synthesis and the permeability of the cytoplasmic membrane of the microbial cell. Active against gram-positive and gram-negative microorganisms: Staphylococcus spp. (including Staphylococcus aureus, Staphylococcus epidermidis, including strains resistant to penicillin); Streptococcus spp. (including some beta-hemolytic species of group A, some non-hemolytic species, and some strains of Streptococcus pneumoniae), Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Proteus mirabilis, Morganella morganii, Citrobacter spp., Haemophilus influenzae, Moraxella spp., Acinetobacter spp., Serratia marcescens.

The combination of dexamethasone with the antibiotic tobramycin allows to reduce the risk of an infectious process.

Pharmacokinetics

With topical application, the systemic absorption of dexamethasone is low. After instillation into the eye, it penetrates well into the corneal epithelium and conjunctiva, and the aqueous humor of the eye. About 77-84% of dexamethasone entering the systemic circulation binds to plasma proteins. It undergoes metabolism. About 60% is excreted in the urine as the metabolite 6-beta-hydroxydexamethasone.

After topical application, Tobramycin is absorbed through the cornea and conjunctiva. A very small amount reaches the aqueous humor. Tobramycin reaches the systemic circulation in very low concentrations. The C_max of tobramycin in blood plasma was 247 ng/ml, which is 8 times lower than the threshold concentration associated with nephrotoxicity. It is excreted by the kidneys, mainly unchanged.

Indications

Inflammatory diseases of the eye and its appendages caused by susceptible pathogens: blepharitis, conjunctivitis, blepharoconjunctivitis, keratoconjunctivitis, keratitis, iridocyclitis.

Prevention and treatment of inflammatory phenomena in the postoperative period after cataract extraction.

ICD codes

Dosage Regimen

Instill one to two drops into the conjunctival sac of the affected eye(s) every four to six hours.

For severe infections, increase the frequency to one to two drops every two hours during the initial 24 to 48 hours.

Gradually reduce the dosage frequency as the clinical response warrants.

Do not discontinue therapy prematurely. Taper the dosage frequency to avoid a recurrence of the inflammatory or infectious condition.

Shake the bottle well before each use to ensure a uniform suspension.

The maximum recommended treatment duration is 24 days. Prolonged use increases the risk of elevated intraocular pressure, cataract formation, and secondary ocular infections.

In postoperative treatment, follow the specific regimen prescribed by the ophthalmologist.

Do not allow the dropper tip to contact any surface, including the eye, to prevent contamination of the suspension.

Adverse Reactions

Immune system disorders frequency unknown – anaphylactic reactions.

Nervous system disorders uncommon – headache; frequency unknown – dizziness.

Eye disorders uncommon – eye pain, eye itching, increased intraocular pressure, conjunctival edema, eye irritation; rare – keratitis, allergic eye manifestations, blurred vision, dry eye syndrome, conjunctival injection; frequency unknown – eyelid edema, eyelid erythema, mydriasis, lacrimation.

Respiratory system disorders uncommon – rhinorrhea, laryngospasm.

Gastrointestinal disorders rare – dysgeusia; frequency unknown – nausea, stomach discomfort.

Skin and subcutaneous tissue disorders frequency unknown – erythema multiforme, rash, facial edema.

Contraindications

Hypersensitivity to the active substances of the combination; viral diseases of the cornea and conjunctiva, including superficial forms of keratitis caused by Herpes simplex (in particular, dendritic keratitis); vaccinia, varicella; mycobacterial eye infections; fungal eye diseases; previously untreated parasitic eye infections; acute purulent eye diseases without concomitant antimicrobial therapy; conditions after removal of a foreign body from the cornea.

With caution

Deep stromal keratitis caused by Herpes simplex, pregnancy.

Use in Pregnancy and Lactation

High systemic doses of aminoglycosides have been associated with the development of ototoxicity. However, after application in the form of eye drops, the systemic concentration of tobramycin is expected to be very low and it should not cause direct or indirect effects on reproductive function. Topical application of glucocorticosteroids in pregnant animals can cause abnormalities in fetal development, including cleft palate. The clinical significance is unknown. Animal studies have shown that the administration of glucocorticosteroids in recommended doses during pregnancy may increase the risk of impaired intrauterine fetal development, the development of cardiovascular diseases and/or metabolic disorders and/or psychophysiological development disorders. Currently, there are no data on the embryotoxic effect of the Dexamethasone + Tobramycin combination when used during human pregnancy. However, the danger to the fetus cannot be excluded. Use during pregnancy, especially in the first trimester, is possible only after a thorough assessment of the expected benefit to potential risk ratio. Treatment with glucocorticosteroids in the third trimester of pregnancy may cause inhibition of the production of the body’s own glucocorticosteroids, requiring treatment after birth. Thus, the drug containing this combination should be used during pregnancy only in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

Data on the penetration of dexamethasone into breast milk are absent. Tobramycin penetrates into milk when taken systemically. Data on whether Tobramycin and Dexamethasone penetrate into breast milk after topical application in ophthalmic dosage forms are absent. It is unlikely that Tobramycin and Dexamethasone, when applied topically as eye drops, are able to accumulate in detectable concentrations or cause clinical effects in newborns. However, the risk to the child cannot be completely ruled out. A decision should be made to discontinue breastfeeding or to suspend or discontinue therapy, taking into account the benefit of breastfeeding for the child and the expected benefit of therapy for the mother.

Pediatric Use

Can be used in children aged 2 years and older in the same doses as in adults. The efficacy and safety of use in children under 2 years of age have not been established. Data are absent.

Geriatric Use

In elderly patients, dose reduction is not required.

Special Precautions

If hypersensitivity develops during the use of the drug, treatment should be discontinued.

The development of cross-hypersensitivity to other aminoglycosides is possible. Furthermore, it should be taken into account that patients with hypersensitivity to topical tobramycin may also be sensitive to other topical or systemic aminoglycosides.

Caution is required when using the drug in the therapy of deep stromal keratitis caused by Herpes simplex, and with this type of herpetic eye lesion, frequent biomicroscopy should be performed.

Long-term use of glucocorticosteroids in ophthalmology (exceeding the maximum recommended duration of therapy – 24 days) may lead to an increase in intraocular pressure and the development of a symptom complex of glaucoma, including damage to the optic nerve, decreased visual acuity and narrowing of the visual fields, and the formation of posterior subcapsular cataract. Therefore, in patients using glucocorticosteroid-containing drugs for a long time, intraocular pressure should be measured regularly and frequently. This is especially important when using glucocorticosteroid-containing medicines in patients under 6 years of age, since patients in this age category are more susceptible to steroid-induced intraocular pressure elevation, and these changes develop faster than in adults.

The risk of increased intraocular pressure and/or cataract formation due to glucocorticosteroid use is higher in predisposed patients (for example, with diabetes mellitus).

In predisposed patients, including children and patients receiving ritonavir, after intensive therapy or continuous long-term therapy, Cushing’s syndrome and/or suppression of adrenal function may occur, caused by the systemic absorption of ophthalmic dexamethasone. In such cases, this combination should be discontinued not abruptly, but gradually.

Glucocorticosteroids can reduce resistance to bacterial, viral, or fungal infections and promote their development, as well as mask the clinical signs of infection.

The appearance of non-healing ulcers on the cornea may indicate the development of fungal invasion. If fungal invasion occurs, glucocorticosteroid therapy must be discontinued.

Long-term use of antibiotics such as Tobramycin can lead to the increased growth of resistant microorganisms, including fungi. If superinfection develops, the use of this combination should be discontinued and appropriate therapy initiated.

The use of the fixed combination of dexamethasone and tobramycin in the therapy of acute purulent eye infections is possible only in case of previously conducted local antibiotic therapy, because the use of dexamethasone during this period may worsen the course of the infectious process.

Abrupt discontinuation of therapy is undesirable due to the possibility of recurrence of symptoms of infectious inflammation or eye damage. Glucocorticosteroids with topical application can slow down the process of corneal healing. It is known that topical NSAIDs also slow down or delay healing.

It is known that in diseases that cause thinning of the cornea or sclera, perforations may occur as a result of the use of topical glucocorticosteroids. With therapy duration of more than 2 weeks, the condition of the cornea should be monitored.

In case of topical application of tobramycin simultaneously with systemic aminoglycoside antibiotics, the overall blood picture should be monitored.

When treating inflammatory or infectious eye diseases, it is not recommended to wear contact lenses.

Effect on ability to drive vehicles and operate machinery

Temporary blurred vision or other visual disturbances after using this product may affect the ability to drive vehicles and operate machinery. If blurred vision occurs after instillation, the patient should wait for vision clarity to be restored before driving vehicles and operating machinery.

Drug Interactions

With the concomitant use of topical NSAIDs in ophthalmology and topical glucocorticosteroids in ophthalmology, a potentiation of the negative influence of both groups of drugs on corneal healing processes is possible.

In patients receiving ritonavir, the plasma concentration of dexamethasone may increase.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.