Oftachrom

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

Composition:

Active substances: cytochrome C, adenosine, nicotinamide;

1 ml of the preparation contains cytochrome C 0.675 mg, adenosine 2 mg, nicotinamide 20 mg;

Excipients: succinic acid, sodium hydroxide, benzalkonium chloride, sorbitol (E 420), anhydrous sodium dihydrogen phosphate, anhydrous sodium hydrogen phosphate, water for injections.

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: transparent solution of red color with shades ranging from yellow to brown.

Pharmacotherapeutic group. Ophthalmological agents. ATC code S01X A.

Pharmacological Properties.

Pharmacodynamics.

Mechanism of action. The use of the medicinal product in cataract is primarily based on the antioxidant and nutritive effects of its active components. It has been demonstrated that the medicinal product exerts a beneficial effect on non-specific, non-infectious inflammatory processes of the anterior segment of the eye.

Cytochrome C is an iron-porphyrin-like compound with high molecular weight bound to a complex protein, the structure of which is similar to hemoglobin. It plays an important role in biochemical redox processes of almost all aerobic organisms.

Pharmacodynamic effect. Cytochrome C in ophthalmic drops has the potential to directly neutralize oxygen radicals in the cornea and is cleaved into heme-peptide within the intraocular fluid and lens epithelium. Cytochrome C may also act indirectly as an antioxidant by inhibiting cytochrome oxidase in the lens epithelium, thereby preventing radical-induced cataract formation.

Adenosine plays multiple roles in ophthalmic drops. It promotes vasodilation and increases ocular blood perfusion. Adenosine nourishes the lens and cornea, while facilitating the removal of toxic catabolites and improving the metabolism of intraocular fluid. Adenosine suppresses inflammation of the conjunctiva, cornea, and other anterior eye segments. It is a physiologically active substance and endogenous molecule that inhibits inflammation by stimulating A2-receptors on the cell membrane surface. In addition, adenosine reduces the release of inflammatory mediators such as calcitonin gene-related peptide.

Adenosine serves as a nutritive substance and a key component in DNA repair and energy metabolism. It plays an indirect role in glutathione regeneration in the ocular lens, as it is a structural component of the enzyme glutathione reductase and of NADP (nicotinamide-adenine-dinucleotide phosphate).

Nicotinamide is a structural component of the vital coenzymes NAD (nicotinamide-adenine-dinucleotide) and NADP (nicotinamide-adenine-dinucleotide phosphate). The inclusion of nicotinamide in the medicinal product is based on the assumption that cataract development can be prevented by enhancing the regenerative capacity of lens epithelial cells through metabolic nutrients essential for DNA repair and glutathione system enzyme activity.

Oftahrom is intended to halt the progression of cataract. Due to its low toxicity, it can also be used prophylactically. Treatment is usually long-term to achieve a significant effect in preventing lens opacification. Data indicate that lens clouding was halted after at least 6–12 months of using the medicinal product in cases of senile cataract. It is also known to be effective when used for less than 6 months.

The action of the medicinal product is not limited exclusively to the ocular lens. Oftahrom also exerts anti-inflammatory, antioxidant, antibacterial, nutritive, disinfectant, and moisturizing effects on the ocular surface. It has been demonstrated to exert a beneficial effect on non-specific, non-infectious inflammatory processes of the anterior eye segment.

Clinical efficacy and safety. It is known that patients with inflammatory, traumatic, and metabolic diseases of the cornea and conjunctiva—such as postherpetic keratopathy, corneal ulcer and dystrophy, dry eye syndrome, chronic keratoconjunctivitis, and chronic blepharoconjunctivitis—experienced shorter recovery times when treated with corticosteroids in combination with ophthalmic drops compared to treatment with corticosteroids alone.

Pharmacokinetics.

The active components of ophthalmic drops are endogenous substances. Cytochrome C consists of heme and one peptide chain (apocytochrome C), while adenosine consists of a purine (adenine) and a sugar (D-ribose). The third active ingredient is nicotinamide.

Absorption. Cytochrome C itself does not penetrate the cornea in large amounts but only after cleavage of the peptide chain; the heme nonapeptide penetrates. Adenosine and nicotinamide readily and rapidly penetrate the cornea.

Distribution. The absolute systemic bioavailability of cytochrome C after topical ocular administration is minimal. After penetration into the cornea, heme is distributed into nearly all ocular tissues. Heme itself is lipophilic and quite hydrophobic, but when bound to a peptide or globin (hemoglobin), it becomes hydrophilic. After local ophthalmic administration, adenosine and nicotinamide are distributed throughout all ocular tissues.

Biotransformation. Cytochrome C is completely metabolized in the body. Apocytochrome C is degraded via amino acid metabolism, and heme is catabolized into bilirubin, which is excreted via bile. Adenosine is metabolized in nearly all body tissues. Its metabolites include inosine, xanthine, and finally urates, which are excreted by the kidneys. Ribose is metabolized via transketolase into glyceraldehyde-3-phosphate and ultimately into pyruvate. Nicotinamide is partially metabolized in the body by nicotinamidase into nicotinic acid (niacin). Both components are converted into N-methylnicotinamide, which is further degraded in the liver.

Elimination. Heme from cytochrome C is excreted from the body via bile. Adenosine metabolites are excreted in urine, as are unchanged nicotinamide and its metabolites. The plasma half-life of adenosine is less than 1 minute, while that of nicotinic acid is highly variable, typically several hours.

Clinical characteristics.

Indications.

Cataract.

Contraindications.

Hypersensitivity to the active substances or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

No studies on drug interactions have been conducted. No significant interactions with other medicinal products are known when the preparations are administered simultaneously by topical instillation into the eye.

Special precautions for use

Ophthachrom eye drops are intended for topical ophthalmic use only and must not be used for injection or oral administration.

Benzalkonium chloride

Benzalkonium chloride, an ingredient of this medicinal product, may cause eye irritation, symptoms of dry eye, and may affect the tear film and corneal surface. Ophthachrom should be used with caution in patients with dry eye syndrome and in patients in whom the cornea may be damaged. Patients should be monitored during prolonged use.

Use of contact lenses

Since Ophthachrom eye drops contain the preservative benzalkonium chloride, contact lenses must be removed before administration of the eye drops. Lenses may be reinserted 15 minutes after instillation. It is known that benzalkonium chloride may discolor soft contact lenses.

Any remaining solution should be discarded 4 weeks after first opening the bottle.

To avoid contamination of the dropper and solution, the tip of the dropper must not touch the eyelids, surrounding areas, or any other surface of the eye.

The bottle should be kept tightly closed when not in use.

The eye drops contain phosphates: sodium hydrogen phosphate anhydrous (2.27 mg/mL) and sodium dihydrogen phosphate anhydrous (3.40 mg/mL).

No special requirements for disposal.

Any unused medicinal product or waste material should be disposed of in accordance with local regulations.

Use during pregnancy or breastfeeding

The effects of the eye drops during pregnancy or breastfeeding have not been studied. Therefore, the use of this medicinal product is not recommended during these periods.

Effect on ability to drive or operate machinery

The medicinal product does not have any effect on the ability to drive or operate machinery. However, as with any ophthalmic medication, if transient blurred vision occurs after instillation, patients should wait until vision clears before driving or operating machinery.

Dosage and Administration.

Dosage: instill 1–2 drops locally into the eye (eyes) 3 times daily.

Route of administration: ophthalmic use.

When using other ophthalmic medications simultaneously, an interval of 5–15 minutes between instillation of each medication should be maintained.

Children.

There are no adequate data on the use of the medicinal product in children.

Overdose.

The medicinal product is safe for ophthalmic use. Cases of accidental or intentional oral overdose are unknown. In the event of overdose with eye drops, symptomatic therapy should be administered.

Adverse reactions.

Below is a list of adverse reactions reported during clinical trials and post-marketing surveillance with the use of ophthalmic drops.

The frequency of adverse reactions is defined according to the following categories: 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); frequency not known (cannot be estimated from the available data). Within each frequency category, adverse reactions are listed in order of decreasing severity.

Ophthalmological:

Common: transient eye pain and eye irritation.

Rare: hypersensitivity reactions including skin rash, pruritus, facial skin hyperemia and swelling; allergic conjunctivitis, including eye pain, ocular hyperemia, and ocular pruritus; contact dermatitis.

Non-ophthalmological:

Very rare: adenosine: very transient nausea, dizziness, arterial hypotension, and dyspnea.

Nicotinic acid: flushing, hot flashes, syncope, and headache.

Frequency not known: lacrimation, transient eye irritation associated with benzalkonium chloride (preservative).

Very rare cases of corneal deposits have been reported in some patients with significantly damaged corneas, related to the phosphate content in the ophthalmic drops.

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

Shelf life. 2 years.

The shelf life of the medicinal product after opening the bottle is no more than 1 month.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Packaging. 5 mL in a bottle with a dropper cap in a box.

Prescription status. Prescription only.

Manufacturer. Limited Liability Company "FARMEKS GROUP".

Manufacturer's address and location of business activity.

100, Shevchenka Street, Boryspil, Kyiv Oblast, Ukraine, 08301.