Attributes
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- Dosage mg
- Pack
- Description en
- MAXITROL Composition Active ingredients: Dexamethasone, Neomycin sulfate, Polymyxin B sulfate; 1 ml of suspension contains 1 mg of dexamethasone, 3500 IU of neomycin sulfate, 6000 IU of polymyxin B sulfate; Excipients: Benzalkonium chloride, Hypromellose, Polysorbate 20, Sodium chloride, Hydrochloric acid and/or sodium hydroxide (to adjust pH), Purified water. Dosage form Eye drops, suspension. Opaque suspension from white to pale yellow, free of agglomerates. Pharmacotherapeutic group Dexamethasone and anti-infective agents. ATC code: S01CA01. Clinical properties Indications For short-term treatment of inflammatory conditions of the eye sensitive to steroids, when prophylactic antibiotic treatment is also indicated, after exclusion of fungal or viral infections. Contraindications - Hypersensitivity to the active substances or any other component of the preparation. - Herpetic keratitis. - Cowpox, chickenpox and other viral infections of the cornea or conjunctiva. - Fungal diseases of the eye structures or untreated parasitic infections of the eye. - Ocular mycobacterial infection. Method of administration and dosage For topical ophthalmic use. Shake the bottle before use. 1-2 drops into the conjunctival sac of the eye(s) 6 times a day or more frequently if needed. After removing the cap, if the protective ring is loose, remove it before use. To avoid contamination of the dropper tip and the contents of the bottle, care must be taken not to touch the dropper tip of the bottle to the eyelids, surrounding areas or other surfaces. It is recommended to close the nasolacrimal duct or close the eyelids after instillation of the preparation, which can reduce the systemic absorption and side effects of the preparation. If more than one topical ophthalmic preparation is used, an interval of at least 5 minutes should be observed. Ophthalmic ointments should be used last. Children The safety and efficacy of the preparation in pediatric patients have not been established. Elderly patients No dose adjustment is required in elderly patients. Use of the preparation in patients with impaired liver and kidney function The use of the preparation in patients with impaired liver and kidney function has not been studied. However, due to low systemic absorption of the active substances after topical administration, dose adjustment is not required. Side effects In clinical studies of MAXITROL eye drops, the most common side effects were eye discomfort, keratitis, and eye irritation, observed in 0.7-0.9% of patients. The described side reactions are classified by the following 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 unknown frequency (cannot be estimated from available data). Within each frequency group, side effects are presented in decreasing order of severity. Side effects were observed in clinical trials and during post-marketing use of MAXITROL. System organ class | Side effects Immune system disorders | Unknown: Hypersensitivity (systemic or local) Endocrine disorders | Unknown: Cushing's syndrome and/or adrenal suppression Nervous system disorders | Unknown: Headache Eye disorders | Uncommon: Keratitis, increased intraocular pressure, eye itching, eye discomfort, eye irritation. Unknown: Ulcerative keratitis, corneal thinning, blurred vision, photophobia, mydriasis, eyelid ptosis, eye pain, eye swelling, foreign body sensation in the eye, ocular hyperemia, increased lacrimation. Skin and subcutaneous tissue disorders | Unknown: Stevens-Johnson syndrome Description of individual side effects With corticosteroid component, in diseases causing thinning of the cornea or sclera, especially after prolonged treatment, the risk of perforation increases. Use of topical ophthalmic corticosteroids can lead to increased intraocular pressure with optic nerve damage, decreased visual acuity, and visual field defects, as well as posterior subcapsular cataract formation. Some patients may experience sensitivity to topically applied aminoglycosides. With intensive use, systemic side effects may develop. Corticosteroids can reduce glucose tolerance, which can lead to the development or exacerbation of existing diabetes mellitus. Overdose No cases of overdose have been reported. Signs and symptoms of MAXITROL overdose may be similar to side effects observed in some patients (punctate keratitis, redness, increased tearing, eyelid swelling, and itching). Due to the properties of this preparation, toxic effects are not expected with topical administration or accidental ingestion of the contents of one bottle. In case of overdose with ophthalmic use, excess preparation can be washed out of the eyes with warm water. Use during pregnancy or breastfeeding Pregnancy Data on the use of MAXITROL eye drops in pregnant women are absent or limited. After intravenous administration in pregnant women, aminoglycoside antibiotics, such as neomycin, cross the placenta. Aminoglycosides have been shown to induce ototoxicity and nephrotoxicity through non-clinical and clinical systemic effects. Neomycin, after topical administration of low doses, should not cause ototoxicity or nephrotoxicity in the fetus. Prolonged or repeated use of corticosteroids during pregnancy has been associated with an increased risk of fetal growth retardation. Newborns whose mothers received significant doses of corticosteroids during pregnancy require careful observation for timely detection of signs of hypoadrenalism. Studies of some active ingredients of MAXITROL in animals have shown reproductive toxicity. Use of MAXITROL during pregnancy is not recommended. Breastfeeding It is unknown whether dexamethasone, neomycin, or polymyxin B are excreted in breast milk after topical administration. Since systemically administered corticosteroids and aminoglycosides can be excreted in breast milk, the risk to breastfed infants cannot be excluded. In such cases, a decision should be made on discontinuing/stopping breastfeeding or discontinuing treatment, taking into account the benefits of breastfeeding for the child and the benefits of treatment for the mother. Fertility There is no data on the effect of this preparation on male or female fertility. There is limited clinical data assessing the effect of dexamethasone on male or female fertility. Dexamethasone did not show adverse effects on fertility in a model studying chorionic gonadotropin secretion in primed rats. Special precautions for use Prolonged use of any antibacterial preparation may lead to overgrowth of resistant bacterial strains or fungi. In case of superinfection, appropriate treatment should be initiated. Some patients may experience sensitivity to topically administered aminoglycosides, such as neomycin. Cross-sensitization to other aminoglycosides may also occur. The severity of hypersensitivity reactions can range from local effects to generalized reactions such as erythema, itching, urticaria, rash, anaphylaxis, anaphylactoid or bullous reactions. If hypersensitivity occurs during the use of the preparation, treatment should be discontinued. When using ophthalmic preparations containing neomycin sulfate, patients should be advised to consult a doctor if eye pain, redness, swelling, or irritation persists or worsens. Serious adverse reactions, including neurotoxicity, ototoxicity, and nephrotoxicity, have been observed in patients receiving neomycin systemically or topically on open wounds or damaged skin. Nephrotoxic and neurotoxic reactions have also been observed with systemic administration of polymyxin B. Although no reports of these effects have been documented after topical use, caution is recommended with concomitant systemic use of aminoglycosides or polymyxin B. Prolonged use of ophthalmic corticosteroids can cause ocular hypertension and/or glaucoma, optic nerve damage, decreased visual acuity, and visual field defects, as well as posterior subcapsular cataract formation. In patients undergoing long-term ophthalmic treatment with corticosteroids, intraocular pressure should be checked regularly and frequently. This is especially important in pediatric patients, as the risk of developing corticosteroid-induced ocular hypertension may be higher in children and may occur earlier than in adults. The risk of developing corticosteroid-induced increased intraocular pressure and/or cataract formation is increased in predisposed patients (e.g., patients with diabetes mellitus). Cushing's syndrome and/or adrenal suppression associated with systemic absorption of ophthalmic dexamethasone may occur after intensive or prolonged continuous treatment in predisposed patients, including children and patients receiving CYP3A4 inhibitors (including ritonavir and cobicistat). In such cases, abrupt discontinuation of treatment is not allowed; treatment should be gradually discontinued. In cases of diseases that cause thinning of the cornea or sclera, perforation has been described with the use of topical corticosteroids. Corticosteroids can reduce resistance and promote the development of non-susceptible bacterial, fungal, parasitic, or viral infections, and can mask clinical signs of infection, suppress hypersensitivity reactions to MAXITROL drops. Suspicion of fungal infection may arise in patients with prolonged, unhealed corneal ulcers if treated with corticosteroids. In case of fungal infection, corticosteroid treatment should be discontinued. To prevent exacerbation of herpes virus-induced corneal disease, frequent examination with a slit lamp is necessary. Topical ophthalmic corticosteroids may slow down corneal wound healing. Topical non-steroidal anti-inflammatory drugs (NSAIDs) are known to slow down or inhibit wound healing. Concomitant use of topical NSAIDs and topical steroids may increase the risk of delayed healing. Visual disturbances Visual disturbances can occur with systemic and topical use of corticosteroids. If a patient experiences symptoms such as blurred vision or other visual disturbances, an ophthalmologist consultation is required to assess possible causes, which may include cataracts, glaucoma, or rare diseases (e.g., central serous chorioretinopathy) described after systemic and topical use of corticosteroids. Wearing contact lenses is not recommended during the treatment of eye infections. Therefore, patients are advised not to wear contact lenses during treatment with MAXITROL. MAXITROL eye drops 5 ml contain 0.2 mg of benzalkonium chloride, which is equivalent to 0.04 mg/ml. Benzalkonium chloride can be absorbed by soft contact lenses and change their color. If contact lenses are allowed for patients, contact lenses should be removed before using the preparation, and at least 15 minutes should pass before reinsertion. Based on limited available data, no differences in the side effect profile between children and adults are observed. However, in general, the eye's reaction to irritants is usually stronger in children than in adults. Irritation can affect adherence to the treatment regimen in children. There is information that benzalkonium chloride can cause eye irritation, dry eye symptoms, affect the tear film and corneal surface. Caution is needed in patients with dry eye syndrome and in patients with possible corneal damage. Patients should be monitored during long-term treatment. New onset or exacerbation of diabetes mellitus may occur with systemic corticosteroid therapy. Due to the possibility of decreased glucose tolerance/diabetes mellitus with the use of topical ophthalmic corticosteroids, caution is recommended when prescribing MAXITROL to patients with a family or personal history of diabetes. Ability to influence reaction speed when driving or operating machinery. MAXITROL eye drops have no or negligible effect on the ability to drive or operate machinery. As with other eye drops, temporary blurred vision or other visual disturbances may affect the ability to drive or operate machinery. If temporary blurred vision occurs after instillation of the preparation, the patient should wait for vision to recover before driving or operating machinery. Interactions with other drugs and other types of interactions Interaction studies have not been conducted. Concomitant use of topical steroids and NSAIDs may increase the potential risk of delayed corneal wound healing. Use of CYP3A4 inhibitors, including ritonavir and cobicistat, may reduce dexamethasone clearance, increase exposure, and increase the risk of adrenal suppression/Cushing's syndrome. Concomitant use of the preparations should be avoided, unless the benefit outweighs the risk of developing systemic side effects of corticosteroids. In this case, the patient should be monitored for signs of systemic effects of corticosteroids. If possible, concomitant and/or sequential use of aminoglycosides (neomycin) and other systemic, oral or topical preparations with neurotoxic, ototoxic, or nephrotoxic effects should be avoided, as this may lead to additional toxicity. If more than one ophthalmic preparation is used, an interval of 5 minutes should be observed between administrations. Eye ointments are used last. In patients with diabetes mellitus, it should be considered that the need for hypoglycemic drugs may be higher, as the hypoglycemic effect of these preparations may be reduced. Pharmacological properties Pharmacodynamics Mechanism of action MAXITROL eye drops have a dual mechanism of action: suppression of inflammatory symptoms due to the corticosteroid component, dexamethasone, and anti-infective effect due to the presence of two antibiotics, polymyxin B and neomycin. Dexamethasone is a synthetic glucocorticoid with potent anti-inflammatory activity. Polymyxin B is a cyclic lipopeptide that penetrates the cell wall of Gram-negative bacteria and destabilizes the cytoplasmic membrane. It is generally less active against Gram-positive bacteria. Neomycin is an antibiotic of the aminoglycoside group that primarily affects bacterial cells by inhibiting the assembly and synthesis of polypeptides on the ribosome. Mechanism of resistance Bacterial resistance to polymyxin B is chromosomal in origin and rare. Modification of cytoplasmic membrane phospholipids plays an important role in this process. Resistance to neomycin develops through several different mechanisms, including: (1) changes in ribosomal subunits in the bacterial cell; (2) inhibition of neomycin transport into the cell; and (3) inactivation by adenylating, phosphorylating, and acetylating enzymes. Genetic information for the production of inactivating enzymes can be transferred to the bacterial chromosome or plasmids. Breakpoints of minimum inhibitory concentrations of antibacterial agents Each gram of MAXITROL eye drops contains 6000 IU of polymyxin B sulfate and 3500 IU of neomycin sulfate. The breakpoints of minimum inhibitory concentrations and in vitro spectrum, as mentioned below, consider the dual component activity of both polymyxin B and neomycin. The breakpoints of minimum inhibitory concentrations listed here are based on acquired resistance to specific species isolated from ocular infections and the ratio of neomycin and polymyxin B in the preparation in international units (IU): Breakpoints of minimum inhibitory concentrations: >5 : 2.5 - >40 : 20 by bacterial species. Susceptibility Below is information on the approximate probabilities of microorganism susceptibility to polymyxin B or neomycin. Bacterial species isolated from external eye infections are listed. The prevalence of acquired resistance may vary geographically and over time for individual species; it is desirable to have local information on resistance, especially when treating acute infections. If necessary, expert recommendations can be sought when local information suggests resistance such that the effectiveness of the combination of polymyxin B and neomycin, as well as MAXITROL eye drops, is questionable for at least some species of infections. Susceptible species Aerobic Gram-positive: Bacillus cereus; Bacillus megaterium; Bacillus pumilus; Bacillus simplex; Corynebacterium accolens; Corynebacterium bovis; Corynebacterium macginleyi; Corynebacterium propinquum; Corynebacterium pseudodiphtheriticum; Staphylococcus aureus (methicillin-susceptible - MSSA); Staphylococcus capitis; Staphylococcus epidermidis (methicillin-susceptible - MSSE); Staphylococcus pasteuri; Staphylococcus warneri; Streptococcus mutans. Aerobic Gram-negative: Haemophilus influenzae; Klebsiella pneumoniae; Moraxella catarrhalis; Moraxella lacunata; Pseudomonas aeruginosa; Serratia species. Species for which acquired resistance may be a problem: Staphylococcus epidermidis (methicillin-resistant - MRSE); Staphylococcus hominis; Staphylococcus lugdunensis. Highly resistant organisms Aerobic Gram-positive: Enterococcus faecalis; Staphylococcus aureus (methicillin-resistant - MRSA); Streptococcus mitis; Streptococcus pneumoniae. Anaerobic microorganisms: Propionibacterium acnes. Dexamethasone is a moderately potent corticosteroid that penetrates ocular tissues well. Corticosteroids have anti-inflammatory and vasoconstrictive effects. They suppress inflammatory reactions and symptoms in various diseases without affecting the cause of the disease. Pharmacokinetic properties Dexamethasone, like other corticosteroids, is rapidly absorbed after oral administration. Its biological half-life is approximately 190 minutes. After topical application to the skin and eyes, adequate absorption can occur to achieve systemic effects. Dexamethasone penetrates ocular tissues in significant amounts, making it effective in inflammatory diseases of the anterior segment of the eye. Polymyxin B sulfate is not absorbed from the gastrointestinal tract or intact skin. Although intact corneal epithelium prevents penetration into the corneal stroma, therapeutic concentrations still reach the stroma after epithelial damage. Good penetration into the stroma is achieved after epithelial abrasion, following topical instillation, subconjunctival injection, or corneal bath. Significant penetration of polymyxin B into the vitreous humor is not observed after parenteral or topical administration of the preparation. Neomycin is poorly absorbed from the gastrointestinal tract and, after topical administration, is absorbed in insufficient amounts to cause systemic effects. Absorption from wound surfaces and inflamed skin surfaces has been described. After absorption, neomycin is rapidly excreted by the kidneys in active form. Shelf life 2 years. Use within 4 weeks after first opening the package. Storage conditions Store at a temperature of 8-30 °C. Keep out of reach of children. Packaging In a 5 ml bottle, 1 bottle in a carton. Dispensing regime: Pharmaceutical product group - III, available without a prescription. See also: MAXITROL - Maxitrol 3.5 Ophthalmic Ointment
- Active
- dexamethasone+neomycin+polymyxin b
What is it?
MAXITROL Composition Active ingredients: Dexamethasone, Neomycin sulfate, Polymyxin B sulfate; 1 ml of suspension contains 1 mg of dexamethasone, 3500 IU of neomycin sulfate, 6000 IU of polymyxin B sulfate; Excipients: Benzalkonium chloride, Hypromellose, Polysorbate 20, Sodium chloride, Hydrochloric acid and/or sodium hydroxide (to adjust pH), Purified water. Dosage form Eye drops, suspension. Opaque suspension from white to pale yellow, free of agglomerates. Pharmacotherapeutic group Dexamethasone and anti-infective agents. ATC code: S01CA01. Clinical properties Indications For short-term treatment of inflammatory conditions of the eye sensitive to steroids, when prophylactic antibiotic treatment is also indicated, after exclusion of fungal or viral infections. Contraindications - Hypersensitivity to the active substances or any other component of the preparation. - Herpetic keratitis. - Cowpox, chickenpox and other viral infections of the cornea or conjunctiva. - Fungal diseases of the eye structures or untreated parasitic infections of the eye. - Ocular mycobacterial infection. Method of administration and dosage For topical ophthalmic use. Shake the bottle before use. 1-2 drops into the conjunctival sac of the eye(s) 6 times a day or more frequently if needed. After removing the cap, if the protective ring is loose, remove it before use. To avoid contamination of the dropper tip and the contents of the bottle, care must be taken not to touch the dropper tip of the bottle to the eyelids, surrounding areas or other surfaces. It is recommended to close the nasolacrimal duct or close the eyelids after instillation of the preparation, which can reduce the systemic absorption and side effects of the preparation. If more than one topical ophthalmic preparation is used, an interval of at least 5 minutes should be observed. Ophthalmic ointments should be used last. Children The safety and efficacy of the preparation in pediatric patients have not been established. Elderly patients No dose adjustment is required in elderly patients. Use of the preparation in patients with impaired liver and kidney function The use of the preparation in patients with impaired liver and kidney function has not been studied. However, due to low systemic absorption of the active substances after topical administration, dose adjustment is not required. Side effects In clinical studies of MAXITROL eye drops, the most common side effects were eye discomfort, keratitis, and eye irritation, observed in 0.7-0.9% of patients. The described side reactions are classified by the following 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 unknown frequency (cannot be estimated from available data). Within each frequency group, side effects are presented in decreasing order of severity. Side effects were observed in clinical trials and during post-marketing use of MAXITROL. System organ class | Side effects Immune system disorders | Unknown: Hypersensitivity (systemic or local) Endocrine disorders | Unknown: Cushing's syndrome and/or adrenal suppression Nervous system disorders | Unknown: Headache Eye disorders | Uncommon: Keratitis, increased intraocular pressure, eye itching, eye discomfort, eye irritation. Unknown: Ulcerative keratitis, corneal thinning, blurred vision, photophobia, mydriasis, eyelid ptosis, eye pain, eye swelling, foreign body sensation in the eye, ocular hyperemia, increased lacrimation. Skin and subcutaneous tissue disorders | Unknown: Stevens-Johnson syndrome Description of individual side effects With corticosteroid component, in diseases causing thinning of the cornea or sclera, especially after prolonged treatment, the risk of perforation increases. Use of topical ophthalmic corticosteroids can lead to increased intraocular pressure with optic nerve damage, decreased visual acuity, and visual field defects, as well as posterior subcapsular cataract formation. Some patients may experience sensitivity to topically applied aminoglycosides. With intensive use, systemic side effects may develop. Corticosteroids can reduce glucose tolerance, which can lead to the development or exacerbation of existing diabetes mellitus. Overdose No cases of overdose have been reported. Signs and symptoms of MAXITROL overdose may be similar to side effects observed in some patients (punctate keratitis, redness, increased tearing, eyelid swelling, and itching). Due to the properties of this preparation, toxic effects are not expected with topical administration or accidental ingestion of the contents of one bottle. In case of overdose with ophthalmic use, excess preparation can be washed out of the eyes with warm water. Use during pregnancy or breastfeeding Pregnancy Data on the use of MAXITROL eye drops in pregnant women are absent or limited. After intravenous administration in pregnant women, aminoglycoside antibiotics, such as neomycin, cross the placenta. Aminoglycosides have been shown to induce ototoxicity and nephrotoxicity through non-clinical and clinical systemic effects. Neomycin, after topical administration of low doses, should not cause ototoxicity or nephrotoxicity in the fetus. Prolonged or repeated use of corticosteroids during pregnancy has been associated with an increased risk of fetal growth retardation. Newborns whose mothers received significant doses of corticosteroids during pregnancy require careful observation for timely detection of signs of hypoadrenalism. Studies of some active ingredients of MAXITROL in animals have shown reproductive toxicity. Use of MAXITROL during pregnancy is not recommended. Breastfeeding It is unknown whether dexamethasone, neomycin, or polymyxin B are excreted in breast milk after topical administration. Since systemically administered corticosteroids and aminoglycosides can be excreted in breast milk, the risk to breastfed infants cannot be excluded. In such cases, a decision should be made on discontinuing/stopping breastfeeding or discontinuing treatment, taking into account the benefits of breastfeeding for the child and the benefits of treatment for the mother. Fertility There is no data on the effect of this preparation on male or female fertility. There is limited clinical data assessing the effect of dexamethasone on male or female fertility. Dexamethasone did not show adverse effects on fertility in a model studying chorionic gonadotropin secretion in primed rats. Special precautions for use Prolonged use of any antibacterial preparation may lead to overgrowth of resistant bacterial strains or fungi. In case of superinfection, appropriate treatment should be initiated. Some patients may experience sensitivity to topically administered aminoglycosides, such as neomycin. Cross-sensitization to other aminoglycosides may also occur. The severity of hypersensitivity reactions can range from local effects to generalized reactions such as erythema, itching, urticaria, rash, anaphylaxis, anaphylactoid or bullous reactions. If hypersensitivity occurs during the use of the preparation, treatment should be discontinued. When using ophthalmic preparations containing neomycin sulfate, patients should be advised to consult a doctor if eye pain, redness, swelling, or irritation persists or worsens. Serious adverse reactions, including neurotoxicity, ototoxicity, and nephrotoxicity, have been observed in patients receiving neomycin systemically or topically on open wounds or damaged skin. Nephrotoxic and neurotoxic reactions have also been observed with systemic administration of polymyxin B. Although no reports of these effects have been documented after topical use, caution is recommended with concomitant systemic use of aminoglycosides or polymyxin B. Prolonged use of ophthalmic corticosteroids can cause ocular hypertension and/or glaucoma, optic nerve damage, decreased visual acuity, and visual field defects, as well as posterior subcapsular cataract formation. In patients undergoing long-term ophthalmic treatment with corticosteroids, intraocular pressure should be checked regularly and frequently. This is especially important in pediatric patients, as the risk of developing corticosteroid-induced ocular hypertension may be higher in children and may occur earlier than in adults. The risk of developing corticosteroid-induced increased intraocular pressure and/or cataract formation is increased in predisposed patients (e.g., patients with diabetes mellitus). Cushing's syndrome and/or adrenal suppression associated with systemic absorption of ophthalmic dexamethasone may occur after intensive or prolonged continuous treatment in predisposed patients, including children and patients receiving CYP3A4 inhibitors (including ritonavir and cobicistat). In such cases, abrupt discontinuation of treatment is not allowed; treatment should be gradually discontinued. In cases of diseases that cause thinning of the cornea or sclera, perforation has been described with the use of topical corticosteroids. Corticosteroids can reduce resistance and promote the development of non-susceptible bacterial, fungal, parasitic, or viral infections, and can mask clinical signs of infection, suppress hypersensitivity reactions to MAXITROL drops. Suspicion of fungal infection may arise in patients with prolonged, unhealed corneal ulcers if treated with corticosteroids. In case of fungal infection, corticosteroid treatment should be discontinued. To prevent exacerbation of herpes virus-induced corneal disease, frequent examination with a slit lamp is necessary. Topical ophthalmic corticosteroids may slow down corneal wound healing. Topical non-steroidal anti-inflammatory drugs (NSAIDs) are known to slow down or inhibit wound healing. Concomitant use of topical NSAIDs and topical steroids may increase the risk of delayed healing. Visual disturbances Visual disturbances can occur with systemic and topical use of corticosteroids. If a patient experiences symptoms such as blurred vision or other visual disturbances, an ophthalmologist consultation is required to assess possible causes, which may include cataracts, glaucoma, or rare diseases (e.g., central serous chorioretinopathy) described after systemic and topical use of corticosteroids. Wearing contact lenses is not recommended during the treatment of eye infections. Therefore, patients are advised not to wear contact lenses during treatment with MAXITROL. MAXITROL eye drops 5 ml contain 0.2 mg of benzalkonium chloride, which is equivalent to 0.04 mg/ml. Benzalkonium chloride can be absorbed by soft contact lenses and change their color. If contact lenses are allowed for patients, contact lenses should be removed before using the preparation, and at least 15 minutes should pass before reinsertion. Based on limited available data, no differences in the side effect profile between children and adults are observed. However, in general, the eye's reaction to irritants is usually stronger in children than in adults. Irritation can affect adherence to the treatment regimen in children. There is information that benzalkonium chloride can cause eye irritation, dry eye symptoms, affect the tear film and corneal surface. Caution is needed in patients with dry eye syndrome and in patients with possible corneal damage. Patients should be monitored during long-term treatment. New onset or exacerbation of diabetes mellitus may occur with systemic corticosteroid therapy. Due to the possibility of decreased glucose tolerance/diabetes mellitus with the use of topical ophthalmic corticosteroids, caution is recommended when prescribing MAXITROL to patients with a family or personal history of diabetes. Ability to influence reaction speed when driving or operating machinery. MAXITROL eye drops have no or negligible effect on the ability to drive or operate machinery. As with other eye drops, temporary blurred vision or other visual disturbances may affect the ability to drive or operate machinery. If temporary blurred vision occurs after instillation of the preparation, the patient should wait for vision to recover before driving or operating machinery. Interactions with other drugs and other types of interactions Interaction studies have not been conducted. Concomitant use of topical steroids and NSAIDs may increase the potential risk of delayed corneal wound healing. Use of CYP3A4 inhibitors, including ritonavir and cobicistat, may reduce dexamethasone clearance, increase exposure, and increase the risk of adrenal suppression/Cushing's syndrome. Concomitant use of the preparations should be avoided, unless the benefit outweighs the risk of developing systemic side effects of corticosteroids. In this case, the patient should be monitored for signs of systemic effects of corticosteroids. If possible, concomitant and/or sequential use of aminoglycosides (neomycin) and other systemic, oral or topical preparations with neurotoxic, ototoxic, or nephrotoxic effects should be avoided, as this may lead to additional toxicity. If more than one ophthalmic preparation is used, an interval of 5 minutes should be observed between administrations. Eye ointments are used last. In patients with diabetes mellitus, it should be considered that the need for hypoglycemic drugs may be higher, as the hypoglycemic effect of these preparations may be reduced. Pharmacological properties Pharmacodynamics Mechanism of action MAXITROL eye drops have a dual mechanism of action: suppression of inflammatory symptoms due to the corticosteroid component, dexamethasone, and anti-infective effect due to the presence of two antibiotics, polymyxin B and neomycin. Dexamethasone is a synthetic glucocorticoid with potent anti-inflammatory activity. Polymyxin B is a cyclic lipopeptide that penetrates the cell wall of Gram-negative bacteria and destabilizes the cytoplasmic membrane. It is generally less active against Gram-positive bacteria. Neomycin is an antibiotic of the aminoglycoside group that primarily affects bacterial cells by inhibiting the assembly and synthesis of polypeptides on the ribosome. Mechanism of resistance Bacterial resistance to polymyxin B is chromosomal in origin and rare. Modification of cytoplasmic membrane phospholipids plays an important role in this process. Resistance to neomycin develops through several different mechanisms, including: (1) changes in ribosomal subunits in the bacterial cell; (2) inhibition of neomycin transport into the cell; and (3) inactivation by adenylating, phosphorylating, and acetylating enzymes. Genetic information for the production of inactivating enzymes can be transferred to the bacterial chromosome or plasmids. Breakpoints of minimum inhibitory concentrations of antibacterial agents Each gram of MAXITROL eye drops contains 6000 IU of polymyxin B sulfate and 3500 IU of neomycin sulfate. The breakpoints of minimum inhibitory concentrations and in vitro spectrum, as mentioned below, consider the dual component activity of both polymyxin B and neomycin. The breakpoints of minimum inhibitory concentrations listed here are based on acquired resistance to specific species isolated from ocular infections and the ratio of neomycin and polymyxin B in the preparation in international units (IU): Breakpoints of minimum inhibitory concentrations: >5 : 2.5 - >40 : 20 by bacterial species. Susceptibility Below is information on the approximate probabilities of microorganism susceptibility to polymyxin B or neomycin. Bacterial species isolated from external eye infections are listed. The prevalence of acquired resistance may vary geographically and over time for individual species; it is desirable to have local information on resistance, especially when treating acute infections. If necessary, expert recommendations can be sought when local information suggests resistance such that the effectiveness of the combination of polymyxin B and neomycin, as well as MAXITROL eye drops, is questionable for at least some species of infections. Susceptible species Aerobic Gram-positive: Bacillus cereus; Bacillus megaterium; Bacillus pumilus; Bacillus simplex; Corynebacterium accolens; Corynebacterium bovis; Corynebacterium macginleyi; Corynebacterium propinquum; Corynebacterium pseudodiphtheriticum; Staphylococcus aureus (methicillin-susceptible - MSSA); Staphylococcus capitis; Staphylococcus epidermidis (methicillin-susceptible - MSSE); Staphylococcus pasteuri; Staphylococcus warneri; Streptococcus mutans. Aerobic Gram-negative: Haemophilus influenzae; Klebsiella pneumoniae; Moraxella catarrhalis; Moraxella lacunata; Pseudomonas aeruginosa; Serratia species. Species for which acquired resistance may be a problem: Staphylococcus epidermidis (methicillin-resistant - MRSE); Staphylococcus hominis; Staphylococcus lugdunensis. Highly resistant organisms Aerobic Gram-positive: Enterococcus faecalis; Staphylococcus aureus (methicillin-resistant - MRSA); Streptococcus mitis; Streptococcus pneumoniae. Anaerobic microorganisms: Propionibacterium acnes. Dexamethasone is a moderately potent corticosteroid that penetrates ocular tissues well. Corticosteroids have anti-inflammatory and vasoconstrictive effects. They suppress inflammatory reactions and symptoms in various diseases without affecting the cause of the disease. Pharmacokinetic properties Dexamethasone, like other corticosteroids, is rapidly absorbed after oral administration. Its biological half-life is approximately 190 minutes. After topical application to the skin and eyes, adequate absorption can occur to achieve systemic effects. Dexamethasone penetrates ocular tissues in significant amounts, making it effective in inflammatory diseases of the anterior segment of the eye. Polymyxin B sulfate is not absorbed from the gastrointestinal tract or intact skin. Although intact corneal epithelium prevents penetration into the corneal stroma, therapeutic concentrations still reach the stroma after epithelial damage. Good penetration into the stroma is achieved after epithelial abrasion, following topical instillation, subconjunctival injection, or corneal bath. Significant penetration of polymyxin B into the vitreous humor is not observed after parenteral or topical administration of the preparation. Neomycin is poorly absorbed from the gastrointestinal tract and, after topical administration, is absorbed in insufficient amounts to cause systemic effects. Absorption from wound surfaces and inflamed skin surfaces has been described. After absorption, neomycin is rapidly excreted by the kidneys in active form. Shelf life 2 years. Use within 4 weeks after first opening the package. Storage conditions Store at a temperature of 8-30 °C. Keep out of reach of children. Packaging In a 5 ml bottle, 1 bottle in a carton. Dispensing regime: Pharmaceutical product group - III, available without a prescription. See also: MAXITROL - Maxitrol 3.5 Ophthalmic Ointment