Polydex with phenylephrine

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT POLYDEXA WITH PHENYLEPHRINE (POLYDEXA WITH PHENYLEPHRINE)

Composition:

Active substances: 1 ml of solution contains neomycin sulfate 6500 IU, polymyxin B sulfate 10000 IU, dexamethasone sodium metasulfobenzoate 0.25 mg, phenylephrine hydrochloride 2.5 mg;

Excipients: methylparahydroxybenzoate (E 218), lithium chloride, citric acid monohydrate, lithium hydroxide, macrogol 4000, polysorbate 80, purified water.

Pharmaceutical form. Nasal spray, solution.

Main physicochemical properties: clear liquid.

Pharmacotherapeutic group.

Agents used in nasal disorders. Dexamethasone combinations.

ATC code R01AD53.

Pharmacological properties.

Pharmacodynamics.

The therapeutic effect of the drug is due to the anti-inflammatory action of dexamethasone on the nasal mucosa, the vasoconstrictor effect of phenylephrine, and the antimicrobial activity of neomycin and polymyxin B. When these antibiotics are combined, the spectrum of antimicrobial action is broadened against most Gram-positive and Gram-negative microorganisms causing infectious-inflammatory diseases of the nasal cavity and paranasal sinuses. Due to the vasoconstrictor effect of phenylephrine, the sensation of nasal congestion is reduced.

Polymyxin B is active against Acinetobacter, Aeromonas, Alcaligenes, Citrobacter, Enterobacter, E. coli, Klebsiella, Moraxella, P. aeruginosa, Salmonella, Shigella, S. maltophilia.

Resistant to Polymyxin B are cocci and bacilli, B. catarrhalis, Brucella, B. cepacia, B. pseudomallei, Campylobacter, C. meningosepticum, Legionella, Morganella, Neisseria, Proteus, Providencia, Serratia, V. cholerae El Tor, Mycobacteria.

Neomycin is active against Corynebacterium, Listeria monocytogenes, Met-S Staphylococcus, Acinetobacter, B. catarrhalis, Campylobacter, Citrobacter, Enterobacter, E. coli, H. influenzae, Klebsiella, Morganella, Proteus, Providencia, Salmonella, Serratia, Shigella, Yersinia, Pasteurella.

Resistant to neomycin are Enterococci, N. asteroides, Met-R Staphylococcus, Streptococcus, A. denitrificans, Burkholderia, Flavobacterium sp., P. stuartii, P. aeruginosa, S. maltophilia, Chlamydia, Mycoplasma, Rickettsiae, and anaerobes.

Pharmacokinetics.

Pharmacokinetic studies of the drug have not been conducted due to low systemic absorption.

Clinical characteristics.

Indications.

Inflammatory and infectious diseases of the nasal cavity, including acute rhinitis and acute sinusitis.

Contraindications.

• Age under 15 years;
• Hypersensitivity to any component of the drug, particularly to parabens and aminoglycosides;
• History of stroke or risk factors that may predispose to stroke due to the alpha-sympathomimetic activity of vasoconstrictors;
• Severe or difficult-to-control hypertension;
• Severe coronary insufficiency;
• Suspected closed-angle glaucoma;
• Suspected urinary retention in urethro-prostatic disorders;
• Presence of nasal infections caused by herpes simplex virus, varicella-zoster virus, or varicella;
• History of convulsions;
• Concomitant use with non-selective MAO inhibitors due to the risk of paroxysmal hypertension and hyperthermia (see section "Interaction with other medicinal products and other forms of interaction");
• Concomitant use with other indirect sympathomimetics or alpha-sympathomimetics, regardless of route of administration (oral or nasal), due to the risk of vasoconstriction or hypertensive crisis (see section "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

The following are interactions arising from systemic distribution of the active substances of the drug.

Interaction related to phenylephrine

Contraindicated combinations:

• With non-selective irreversible MAO inhibitors: risk of paroxysmal hypertension and hyperthermia, which may be fatal. Due to the prolonged action of MAO inhibitors, interaction is possible for up to 2 weeks after discontinuation of MAO inhibitors.
• With other indirect sympathomimetics and alpha-sympathomimetics (oral and/or nasal): risk of vasoconstriction and/or hypertensive crisis.

Unrecommended combinations:

• With dopaminergic ergot alkaloids and vasoconstrictive ergot alkaloids: risk of vasoconstriction and/or hypertensive crisis;
• With selective and reversible MAO inhibitors, including linezolid and methylene blue: risk of vasoconstriction and/or hypertensive crisis.

Combinations requiring caution:

• With volatile halogenated anesthetics: risk of perioperative hypertensive crisis. In case of planned surgery, it is advisable to discontinue treatment several days before the procedure.

Interaction related to dexamethasone

Unrecommended combinations:

• With acetylsalicylic acid: increased risk of bleeding when used concomitantly with anti-inflammatory doses of acetylsalicylic acid (≥ 1 g per dose or ≥ 3 g daily).

Combinations requiring caution:

• With aminoglutethimide: increased dexamethasone activity (due to enhanced hepatic metabolism). Dose adjustment of dexamethasone is required;
• With medicinal products that may cause torsades de pointes-type polymorphic ventricular tachycardia: increased risk of ventricular arrhythmia, including torsades de pointes. Prior to treatment with the drug, assess for hypokalemia and perform serum potassium determination and electrocardiography;
• With other agents that reduce blood potassium levels (hypokalemic diuretics alone or in combination, laxatives, intravenous amphotericin B, glucocorticoids, and tetracosactide): increased risk of hypokalemia due to additive effect. Hypokalemia is a factor predisposing to cardiac arrhythmias (particularly polymorphic ventricular tachycardia, including torsades de pointes) and increases the toxicity of certain agents. Serum potassium levels should be monitored and corrected if necessary;
• With digitalis preparations: hypokalemia exacerbates the toxic effects of digitalis preparations. Prior to treatment with the drug, assess for hypokalemia and perform serum potassium determination and electrocardiography;
• With anticonvulsants and enzyme-inducing agents: reduced plasma concentration and efficacy of corticosteroids due to enhanced hepatic metabolism. The consequences are particularly significant for patients with Addison’s disease receiving hydrocortisone and in organ transplantation. Clinical and laboratory monitoring is required, along with dose adjustment of corticosteroids during combination therapy and after discontinuation of enzyme-inducing agents;
• With praziquantel: reduced plasma concentration of praziquantel, leading to risk of treatment failure, due to enhanced hepatic metabolism. Administration of these drugs should be separated by a time interval of at least one week.

Combinations requiring attention:

• With antihypertensive agents: possible attenuation of antihypertensive effect (due to salt and water retention caused by corticosteroids);
• With clarithromycin, erythromycin, ritonavir-boosted protease inhibitors, itraconazole, ketoconazole, nelfinavir, posaconazole, telithromycin, voriconazole: increased plasma concentration of dexamethasone due to reduced hepatic metabolism via enzyme inhibition, with risk of Cushingoid syndrome;
• With acetylsalicylic acid: increased risk of bleeding with antipyretic or analgesic doses (≥ 500 mg per dose or < 3 g daily);
• With non-steroidal anti-inflammatory drugs (NSAIDs): increased risk of peptic ulcer and gastrointestinal bleeding;
• With fluoroquinolones: possible increased risk of tendinitis or even tendon rupture (rare), particularly in patients receiving prolonged corticosteroid therapy.

Instructions for Use

The medication should not be swallowed.

The medication must not be used beyond the recommended duration. Prolonged use of the medication is not recommended due to the risk of developing rebound syndrome and iatrogenic rhinitis. Repeated and/or prolonged inhalations may lead to systemic absorption of active substances.

The presence of a corticosteroid in the formulation does not prevent local allergic symptoms but may alter their course.

Concomitant use with systemic antibiotics is possible if necessary.

Due to the presence of a sympathomimetic agent in the formulation, recommended dosages and treatment duration must be strictly observed, and contraindications should be carefully reviewed. If arterial hypertension, tachycardia, palpitations or cardiac arrhythmias, nausea, or any neurological symptoms (e.g. onset or worsening of headache) occur, the medication must be discontinued.

Use with caution in patients with arterial hypertension, ischemic heart disease, hyperthyroidism, psychosis, or diabetes due to the presence of a sympathomimetic agent.

Risk of overdose may increase when used concomitantly with other vasoconstrictors (see "Interaction with Other Medicinal Products and Other Forms of Interaction").

Do not use in combination with drugs that lower the seizure threshold, such as terpene derivatives, clobutinol, atropine-containing substances, local anesthetics, or in patients with a history of seizures.

For athletes: The medication contains a substance (dexamethasone) that may lead to a positive doping test result.

After opening the vial and starting use from the first day, there is a risk of microbial contamination of the medication.

Use during pregnancy or breastfeeding.

The medication is not recommended for use in women during pregnancy or breastfeeding.

Ability to influence reaction rate while driving or operating machinery.

No effects on reaction speed while driving or operating machinery have been reported.

Dosage and Administration

For adults: administer 1 spray 3–5 times daily into each nostril. For children aged 15 years and older: 1 spray 3 times daily into each nostril.

The average duration of treatment is 5 days.

Spraying is performed by pressing the bottle. When using the medication, hold the bottle vertically and slightly tilt the head forward to spray the solution into the nasal passage as a mist, not as a stream of liquid.

Children.

This medication must not be used in children under 15 years of age.

Overdose.

With prolonged use (beyond the recommended duration) or administration of a dose significantly exceeding the recommended amount, this medicinal product may produce systemic effects: hypothermia, sedative effect, loss of consciousness, coma, and respiratory depression.

Adverse Reactions.

Associated with the presence of antibiotics:

Systemic or local allergic reactions (redness, swelling) and sensitization to antibiotics contained in the preparation, which may complicate subsequent administration of these or related antibiotics, are possible.

Associated with the presence of phenylephrine:

Cardiovascular disorders:

Increased heart rate, tachycardia, myocardial infarction.

Eye disorders:

Closed-angle glaucoma crisis.

Gastrointestinal disorders:

Dry mouth, nausea, vomiting.

Nervous system disorders:

Haemorrhagic stroke, particularly in patients who have used products containing pseudoephedrine hydrochloride; this cerebrovascular event occurred during treatment with overdose or improper use in a patient with vascular risk factors; ischemic stroke, headache, seizures.

Psychiatric disorders:

Anxiety, excitation, behavioural disturbances, hallucinations, insomnia.

Fever, which may be caused by overdose, concomitant use of interacting drugs, or overdose.

Renal and urinary disorders:

Dysuria (in the presence of urethral or prostate diseases), urinary retention (particularly in case of urethral or prostate diseases).

Skin and subcutaneous tissue disorders:

Sweating, rash, pruritus, urticaria.

Vascular disorders:

Arterial hypertension (hypertensive crisis).

Application site reactions:
Nasal dryness, rare allergic manifestations.

Shelf life.

3 years.

Storage conditions.

Store out of reach of children at a temperature not exceeding 25 °C.

Packaging.
15 ml in a bottle with spray dispenser in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

RECORDATI İLAÇ SANAYİ VE TİC. A. Ş., Turkey.

Manufacturer's name and address.

Çerkezköy Organize Sanayi Bölgesi, Karaağaç Mah. Atatürk Cad. No:36, Kapaklı-Tekirdağ, Turkey.

Marketing Authorization Holder.

Laboratoires Boiron Recordati, France.

INSTRUCTIONS

for medical use of the medicinal product

POLYDEXA WITH PHENYLEPHRINE

(POLYDEXA WITH PHENYLEPHRINE)

Composition:

Active substances: 1 ml of solution contains neomycin sulfate 6500 IU, polymyxin B sulfate 10000 IU, dexamethasone sodium metasulfobenzoate 0.25 mg, phenylephrine hydrochloride 2.5 mg;

Excipients: methyl p-hydroxybenzoate (E 218), lithium chloride, citric acid monohydrate, lithium hydroxide, macrogol 4000, polysorbate 80, purified water.

Pharmaceutical form. Nasal spray, solution.

Main physicochemical properties: clear liquid.

Pharmacotherapeutic group.

Preparations used in nasal disorders. Dexamethasone combinations.

ATC code R01A D53.

Pharmacological properties.

Pharmacodynamics.

The therapeutic effect of the drug is due to the anti-inflammatory action of dexamethasone on the nasal mucosa, the vasoconstrictor effect of phenylephrine, and the antimicrobial activity of neomycin and polymyxin B. When these antibiotics are combined, the spectrum of antimicrobial activity is broadened against most Gram-positive and Gram-negative microorganisms causing infectious and inflammatory diseases of the nasal cavity and paranasal sinuses. Due to the vasoconstrictor effect of phenylephrine, nasal congestion is reduced.

Polymyxin B is active against Acinetobacter, Aeromonas, Alcaligenes, Citrobacter, Enterobacter, E. coli, Klebsiella, Moraxella, P. aeruginosa, Salmonella, Shigella, S. maltophilia.

Resistant to Polymyxin B are cocci and bacilli, B. catarrhalis, Brucella, B. cepacia, B. pseudomallei, Campylobacter, C. meningosepticum, Legionella, Morganella, Neisseria, Proteus, Providencia, Serratia, V. cholerae El Tor, Mycobacteria.

Neomycin is active against Corynebacterium, Listeria monocytogenes, Met-S Staphylococcus, Acinetobacter, B. catarrhalis, Campylobacter, Citrobacter, Enterobacter, E. coli, H. influenzae, Klebsiella, Morganella, Proteus, Providencia, Salmonella, Serratia, Shigella, Yersinia, Pasteurella.

Resistant to neomycin are Enterococci, N. asteroides, Met-R Staphylococcus, Streptococcus, A. denitrificans, Burkholderia, Flavobacterium sp., P. stuartii, P. aeruginosa, S. maltophilia, Chlamydia, Mycoplasma, Rickettsiae, and anaerobes.

Pharmacokinetics.

Pharmacokinetic studies of the drug have not been conducted due to low systemic absorption.

Clinical characteristics.

Indications.

Inflammatory and infectious diseases of the nasal cavity, including acute rhinitis and acute sinusitis.

Contraindications.

• Children under 15 years of age;
• Hypersensitivity to any component of the medicinal product, particularly to parabens and aminoglycosides;
• History of stroke or risk factors predisposing to stroke due to the alpha-sympathomimetic activity of vasoconstrictors;
• Severe or difficult-to-treat hypertension;
• Severe coronary insufficiency;
• Suspected closed-angle glaucoma;
• Suspected urinary retention in urethro-prostatic disorders;
• Presence of nasal infections caused by herpes simplex virus, varicella-zoster virus, or varicella;
• History of convulsions;
• Concomitant use with non-selective MAO inhibitors due to the risk of paroxysmal hypertension and hyperthermia (see section "Interaction with other medicinal products and other forms of interaction");
• Concomitant use with other indirect sympathomimetics or alpha-sympathomimetics, regardless of route of administration (oral or nasal), due to the risk of vasoconstriction or hypertensive crisis (see section "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

The interactions listed below occur due to systemic distribution of the active substances of the medicinal product.

Interaction related to phenylephrine

Contraindicated combinations:

• With non-selective irreversible MAO inhibitors: risk of paroxysmal hypertension and hyperthermia, which may be fatal. Due to the prolonged action of MAO inhibitors, interaction may occur for up to 2 weeks after discontinuation of MAO inhibitors.
• With other indirect sympathomimetics and alpha-sympathomimetics (oral and/or nasal): risk of vasoconstriction and/or hypertensive crisis.

Unrecommended combinations:

• With dopamine receptor agonist ergot alkaloids and vasoconstrictive-type ergot alkaloids: risk of vasoconstriction and/or hypertensive crisis;
• With selective and reversible MAO inhibitors, including linezolid and methylene blue: risk of vasoconstriction and/or hypertensive crisis.

Combinations requiring caution:

• With volatile halogenated anesthetics: perioperative hypertensive crisis. In case of planned surgery, it is advisable to discontinue treatment several days before the procedure.

Interaction related to dexamethasone

Unrecommended combinations:

• With acetylsalicylic acid: increased risk of bleeding when used concomitantly with anti-inflammatory doses of acetylsalicylic acid (≥ 1 g per dose or ≥ 3 g per day).

Combinations requiring caution:

• With aminoglutethimide: increased activity of dexamethasone (due to enhanced hepatic metabolism). Dose adjustment of dexamethasone is required;
• With medicinal products that may cause torsades de pointes: increased risk of ventricular arrhythmias, including torsades de pointes. Prior to treatment with the medicinal product, assess for hypokalemia, measure serum potassium levels, and perform electrocardiography;
• With other medicinal products that reduce blood potassium levels (hypokalemic diuretics alone or in combination, laxatives, intravenous amphotericin B, glucocorticoids, and tetracosactide): increased risk of hypokalemia due to additive effects. Hypokalemia is a factor predisposing to cardiac arrhythmias (particularly polymorphic ventricular tachycardia such as torsades de pointes) and increases the toxicity of certain agents. Serum potassium levels should be monitored and corrected if necessary;
• With digitalis preparations: hypokalemia exacerbates the toxic effects of digitalis preparations. Prior to treatment with the medicinal product, assess for hypokalemia, measure serum potassium levels, and perform electrocardiography;
• With anticonvulsants and enzyme-inducing agents: reduced plasma concentration and efficacy of corticosteroids due to enhanced hepatic metabolism. The consequences are particularly significant for patients with Addison's disease receiving hydrocortisone and in organ transplantation. Clinical and laboratory monitoring is required, and corticosteroid dosage adjustment may be necessary during and after combined therapy with enzyme inducers;
• With praziquantel: reduced plasma concentration of praziquantel, leading to potential treatment failure, due to enhanced hepatic metabolism. Administration of these drugs should be separated in time by at least one week.

Combinations requiring attention:

• With antihypertensive agents: possible attenuation of antihypertensive effect (due to salt and water retention caused by corticosteroids);
• With clarithromycin, erythromycin, ritonavir-boosted protease inhibitors, itraconazole, ketoconazole, nefazodone, posaconazole, telithromycin, voriconazole: increased plasma concentration of dexamethasone due to reduced hepatic metabolism via enzyme inhibition, with risk of Cushingoid syndrome;
• With acetylsalicylic acid: increased risk of bleeding with antipyretic or analgesic doses (≥ 500 mg per dose or < 3 g per day);
• With non-steroidal anti-inflammatory drugs: increased risk of peptic ulcer and gastrointestinal bleeding;
• With fluoroquinolones: possible increased risk of tendinitis or even tendon rupture (rare), particularly in patients receiving prolonged corticosteroid therapy.

Special precautions for use

The product should not be swallowed.

The product must not be used beyond the recommended duration. Prolonged use of the product is not recommended due to the risk of rebound syndrome and drug-induced rhinitis. Repeated and/or prolonged inhalations may lead to systemic absorption of active substances.

The presence of a corticosteroid in the product does not prevent local allergy symptoms but may alter their course.

Concomitant use with systemic antibiotics is possible if necessary.

Due to the presence of a sympathomimetic agent in the formulation, the recommended dosage and treatment duration must be strictly observed, and contraindications should be carefully reviewed. The product must be discontinued if arterial hypertension, tachycardia, palpitations or cardiac arrhythmias, nausea, or any neurological symptoms (e.g., onset or worsening of headache) occur.

Use with caution in patients with arterial hypertension, ischemic heart disease, hyperthyroidism, psychosis, or diabetes due to the presence of a sympathomimetic agent.

Risk of overdose may increase when used concomitantly with other vasoconstrictors (see "Interaction with other medicinal products and other forms of interaction").

Do not use in combination with drugs that lower the seizure threshold, such as terpene derivatives, clobutinol, atropine-containing substances, local anesthetics, or in patients with a history of seizures.

For athletes: The product contains a substance (dexamethasone) that may lead to a positive doping test.

After opening the vial and starting use from the first day, there is a possibility of microbial contamination of the product.

Use during pregnancy or breastfeeding

The use of this product is not recommended in women during pregnancy or breastfeeding.

Ability to influence reaction rate while driving or operating machinery

No effects on reaction speed while driving or operating machinery have been reported.

Method of administration and dosage.

For adults: administer 1 spray 3–5 times daily into each nostril. For children aged 15 years and older: 1 spray 3 times daily into each nostril.

The average duration of treatment is 5 days.

The spray is administered by pressing the bottle. When using the medication, hold the bottle vertically and slightly tilt the head forward to ensure the solution is sprayed into the nasal passage as a mist, not as a stream of liquid.

Children.

The medication must not be used in children under 15 years of age.

Overdose.

With prolonged use (beyond the recommended duration) or administration of a dose significantly exceeding the recommended amount, this medicinal product may cause systemic effects: hypothermia, sedative effect, loss of consciousness, coma, and respiratory depression.

Side effects.

Associated with the presence of antibiotics:

possible systemic or local allergic reactions (redness, swelling) and sensitization to antibiotics contained in the preparation, which may complicate subsequent use of these or related antibiotics.

Associated with the presence of phenylephrine:

Cardiovascular disorders:

palpitations, tachycardia, myocardial infarction.

Ocular disorders:

closed-angle glaucoma crisis.

Gastrointestinal disorders:

dry mouth, nausea, vomiting.

Nervous system disorders:

hemorrhagic stroke, particularly in patients who have used products containing pseudoephedrine hydrochloride; this cerebrovascular event occurred during treatment with overdose or incorrect use in a patient with vascular risk factors; ischemic stroke, headache, seizures.

Psychiatric disorders:

anxiety, excitation, behavioral disturbances, hallucinations, insomnia.

Fever, which may be caused by overdose or concomitant use of drugs known to interact, or by overdose.

Urinary system disorders:

dysuria (in case of pre-existing urethral or prostate diseases), urinary retention (particularly in case of urethral or prostate diseases).

Skin disorders:

sweating, rash, itching, urticaria.

Vascular disorders:

arterial hypertension (hypertensive crisis).

Local site reactions:
nasal dryness, rare allergic manifestations.

Shelf life.

3 years.

Storage conditions.

Store out of reach of children at a temperature not exceeding 25 °C.

Packaging.
15 ml in a bottle with spray pump in a cardboard box.

Prescription category.

By prescription only.

Manufacturer.

Sofartex, France.

Manufacturer's address.

21, Rue du Pressoir, 28500 Vernouillet, France.

Marketing authorization holder.

Laboratoires Bouchara-Recordati, France.