Indoftalmik

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

Composition:

Active substance: indomethacin;

1 ml of eye drops, solution contains 1 mg of indomethacin;

Excipients: arginine, hydroxypropylbetadex, thimerosal, 1 M hydrochloric acid solution, purified water.

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: greenish-yellow clear solution, practically free from particles.

Pharmacotherapeutic group.

Agents used in ophthalmology. Nonsteroidal anti-inflammatory agents.

ATC Code: S01BC01

Pharmacological properties.

Pharmacodynamics. The drug belongs to the group of non-steroidal anti-inflammatory analgesic agents for topical use.

Indomethacin inhibits prostaglandin synthetase and belongs to the indole group of agents.

Pharmacokinetics. No data available.

Clinical characteristics.

Indications.

• Inhibition of miosis during surgical procedures.
• Prevention of inflammation following cataract surgery or surgery on the anterior chamber of the eye.
• Relief of ocular pain after photorefractive keratectomy during the first few days following surgery.

Contraindications.

• Third trimester of pregnancy (see section "Use during pregnancy or breastfeeding");
• Known hypersensitivity to indomethacin or drugs with similar action, e.g., other nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin;
• History of asthma attacks induced by aspirin or other NSAIDs;
• Active peptic ulcer of the stomach or duodenum;
• Severe hepatic impairment;
• Severe renal insufficiency.

Interaction with other medicinal products and other forms of interaction.

To avoid mixing and interaction of active substances, an interval of 15 minutes should be maintained between instillation of different eye drops.

If necessary, indomethacin eye drops may be combined with eye drops containing corticosteroids.

Although only a minimal amount of indomethacin reaches the systemic circulation after ocular administration, drug interactions may still occur. Therefore, interactions observed with systemic use of NSAIDs should be taken into consideration.

Combinations not recommended

Oral anticoagulants: Increased risk of bleeding due to oral anticoagulant use (platelet function inhibition and gastrointestinal mucosal damage caused by NSAIDs).

If such combination is necessary, close clinical and laboratory monitoring is required.

Other NSAIDs (including salicylates at doses exceeding 3 g/day in adults): Increased risk of gastrointestinal ulceration and bleeding (synergism).

Diffunisal: Fatal gastrointestinal bleeding associated with increased plasma concentration of indomethacin (competitive interaction with glucuronide-conjugating enzymes).

Heparins: Increased risk of bleeding (platelet function inhibition and gastrointestinal mucosal damage caused by NSAIDs).

If such combination is necessary, close clinical monitoring (and laboratory monitoring of unfractionated heparins) should be performed.

Lithium: Lithium blood levels may increase to toxic levels (reduced renal excretion of lithium). If such combination is necessary, careful monitoring of lithium blood levels and dose adjustment during combined treatment and after discontinuation of indomethacin are required.

Methotrexate at doses of 15 mg per week or higher: Hematological toxicity of methotrexate is enhanced due to reduced renal clearance under the influence of anti-inflammatory agents.

Ticlopidine: Increased risk of bleeding (synergism of antiplatelet activity).

If such combination is necessary, careful monitoring of clinical and laboratory parameters, including bleeding time, should be performed.

Combinations requiring caution

Diuretics, angiotensin-converting enzyme (ACE) inhibitors: Acute renal failure in patients with documented dehydration (reduction in glomerular filtration due to inhibition of vasodilatory prostaglandins by NSAIDs). Additionally, attenuation of antihypertensive effect.

Patient hydration and monitoring of renal function at the beginning of treatment are required.

Methotrexate at doses less than 15 mg per week: Hematological toxicity of methotrexate is enhanced due to reduced renal clearance under the influence of anti-inflammatory agents. Complete blood count should be performed weekly during the first few weeks of combined therapy. Close monitoring is required even with minor changes in renal function, especially in elderly patients.

Pentoxifylline: Increased risk of bleeding. Enhanced monitoring of clinical parameters and more frequent assessment of bleeding time are required.

Locally acting gastrointestinal agents (salts, oxides, and hydroxides of magnesium, aluminum, and calcium): Reduced gastrointestinal absorption of indomethacin. Antacids should be administered separately from indomethacin (if possible, with an interval of at least 2 hours).

Zidovudine: Increased risk of erythrocyte toxicity (effect on reticulocytes), accompanied by severe anemia, occurring 8 days after initiation of NSAID therapy.

Complete blood count and reticulocyte count should be performed 8 and 15 days after initiation of NSAID therapy.

Combinations with warnings

Beta-blockers: Reduced antihypertensive effect (NSAIDs inhibit vasodilatory prostaglandins).

Cyclosporine: Risk of enhanced nephrotoxicity, particularly in elderly patients.

Desmopressin: Potentiation of antidiuretic activity.

Intrauterine contraceptive devices (IUDs): Risk of reduced efficacy of IUDs (association not proven).

Thrombolytics: Increased risk of bleeding.

Special precautions for use.

This product contains an organic mercury compound that may cause an allergic reaction.

• If symptoms of hypersensitivity develop, treatment with the drug should be discontinued.
• If there is a risk of eye infection, appropriate treatment should be prescribed.
• NSAIDs may slow or delay corneal healing. Topical corticosteroids are also known to slow or delay corneal healing. The use of topical NSAIDs and corticosteroids increases this risk. Therefore, indomethacin eye drops should be used with particular caution and care when co-administered with corticosteroids, especially in patients at increased risk of corneal adverse effects described below. Post-marketing experience with topical NSAIDs indicates that the risk of sight-threatening corneal adverse effects is increased in cases of complicated ocular surgery, corneal denervation, corneal epithelial defects, diabetes mellitus, ocular surface diseases (e.g., dry eye syndrome), rheumatoid arthritis, or repeated ophthalmic surgeries within a short period of time. Topical NSAIDs should be used cautiously in such patients. Prolonged use of topical NSAIDs may increase their negative impact on the cornea.
• In patients sensitive to nonsteroidal anti-inflammatory analgesics, the use of topical NSAIDs may cause keratitis. Prolonged use of topical NSAIDs in such patients may lead to corneal epithelial defects, corneal thinning, corneal erosion, corneal ulceration, or corneal perforation. These events may be sight-threatening. Patients who develop a corneal epithelial defect should immediately discontinue use of indomethacin eye drops and undergo careful monitoring of corneal status.
• NSAIDs may prolong bleeding in ocular tissues during surgery, particularly in patients with bleeding tendencies or in patients receiving other medications that may prolong bleeding.
• It is not recommended to wear contact lenses during treatment with this medication.
• If other eye drops are used concurrently with Indoftalmik, the interval between instillations should be at least 15 minutes.
• During instillation, avoid touching the eye with the dropper tip.

Use during pregnancy or breastfeeding.

Pregnancy

There have been no reports of teratogenic effects of the drug in humans. However, additional epidemiological studies are needed to confirm the absence of any risk.

During the third trimester of pregnancy, the use of prostaglandin synthesis inhibitors may have the following effects on the fetus:

• Toxic effects on the cardiovascular and pulmonary systems (pulmonary hypertension with premature closure of the ductus arteriosus);
• Impaired renal function, which may lead to renal failure associated with oligohydramnios.

Near the end of pregnancy, prolonged bleeding time may occur in both mother and child.

Therefore, indomethacin may be used during the first 5 months of pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus.

From the 6th month of pregnancy onwards, the use of indomethacin is contraindicated.

Breastfeeding period

NSAIDs are known to pass into breast milk; therefore, their use in breastfeeding women should be avoided.

Ability to affect reaction speed when driving or operating machinery.

Patients who experience blurred vision immediately after instillation should temporarily refrain from driving or operating machinery.

Method of Administration and Dosage

The medicinal product is intended for topical ophthalmic use in adults. The dose, frequency, and duration of administration are determined individually by a physician.

Inhibition of miosis during surgery:

administer 1 drop 4 times daily the day before surgery and 4 times 1 drop 3 hours before surgery.

Prevention of inflammation following cataract surgery or surgery on the anterior chamber of the eye:

1 drop 4–6 times daily until complete resolution of disease symptoms, starting instillation 24 hours before surgery.

Relief of ocular pain after photorefractive keratectomy:

1 drop 4 times daily for the first few days after surgery.

Instructions for use

To instill the solution, gently pull down the lower eyelid of the eye and administer 1 drop into the conjunctival sac while the patient looks upward.

Children

Specific studies in pediatric populations have not been conducted; therefore, the drug is not recommended for use in pediatric practice.

Overdose

In case of overdose, an intensification of adverse effects may occur.

In the event of local overdose, rinse the eyes with sterile 0.9% sodium chloride solution.

Adverse reactions

Adverse reactions observed during clinical trials or post-marketing use are listed below according to frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000), and not known (cannot be estimated from the available data).

* Adverse reactions such as keratitis or corneal ulceration, which may lead to corneal perforation, have been reported. In particular, this risk exists in patients who have been treated with topical corticosteroids for ophthalmic use and in patients with weakened corneas.

Reporting of suspected adverse reactions

Reporting of suspected adverse reactions after authorization of the medicinal product is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical personnel, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life.

18 months.

The shelf life of the product after first opening of the container is 28 days.

Storage conditions.

Store at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Incompatibilities.

Not applicable.

Packaging.

5 ml in a bottle with a dropper cap, with a cardboard carton.

Prescription status.

Prescription only.

Manufacturer.

C.T. ROMPHARM COMPANY S.R.L.

Manufacturer's address and location of its business operations.

Strada Eroilor No. 1A, Otopeni, 075100, Ilfov County – Rompharm 1 and Rompharm 2 buildings, Romania.