Mitraseptin^®-Prolor (Spray) Instructions for Use

Marketing Authorization Holder

Pharmstandard-Lexredstva OJSC (Russia)

ATC Code

R02AX (Other drugs for the treatment of throat diseases)

Active Substances

Flurbiprofen (Rec.INN registered by WHO)

Benzyldimethyl-myristoylamino-propylammonium (Grouping name)

Dosage Form

Mitraseptin®-Prolor

Metered-dose topical spray 0.051 mg+8.75 mg/1 dose: 15 ml (20 doses) or 30 ml (45 doses) bottle

Dosage Form, Packaging, and Composition

Metered-dose spray for topical application in the form of a transparent, colorless or yellowish solution with a characteristic odor; slight opalescence is allowed.

Excipients: betadex – 22.83 mg, sodium phosphate dibasic dodecahydrate – 17.19 mg, hydroxypropyl betadex – 12.09 mg, macrogol glyceryl ricinoleate – 5.1 mg, sodium hydroxide – 1.3 mg, methylparaben – 1.18 mg, citric acid monohydrate – 0.63 mg, sodium saccharin – 0.27 mg, propylparaben – 0.24 mg, eucalyptus oil – 0.09 mg, peppermint oil – 0.045 mg, purified water – up to 510 µl.

15 ml (20 doses) – polyethylene bottles (1) with a metering pump complete with a sprayer – cardboard packs.
15 ml (20 doses) – polyethylene bottles (1) with a metering pump complete with a sprayer with a rotating cannula and a cuff – cardboard packs.
30 ml (45 doses) – polyethylene bottles (1) with a metering pump complete with a sprayer – cardboard packs.
30 ml (45 doses) – polyethylene bottles (1) with a metering pump complete with a sprayer with a rotating cannula and a cuff – cardboard packs.

Clinical-Pharmacological Group

A drug with antimicrobial and anti-inflammatory action for topical use in ENT practice

Pharmacotherapeutic Group

Drugs for the treatment of throat diseases; other drugs for the treatment of throat diseases

Pharmacological Action

Combined medicinal product for topical use.

Flurbiprofen – NSAID, a propionic acid derivative. It has analgesic, anti-inflammatory and antipyretic effects, which is due to the suppression of COX-1 and COX-2 activity, with some selectivity for COX-1; as a result, the production of prostaglandins – mediators of pain, inflammation and hyperthermic reaction – is reduced. It has a local analgesic and anti-inflammatory effect on the mucous membrane of the oral cavity and pharynx: it reduces swelling, difficulty swallowing, pain and a feeling of irritation in the throat. When used in a single dose (3 presses of the dispenser), a decrease in soreness and difficulty in swallowing is noted after 5 minutes, a significant reduction in pain intensity – after 20 minutes, a decrease in swelling 30 minutes after application. The analgesic and decongestant effect of the drug lasts up to 6 hours.

Benzyldimethyl-myristoylamino-propylammonium – has a broad spectrum of antimicrobial action, including hospital strains resistant to antibiotics. It has a pronounced bactericidal effect against gram-positive (Staphylococcus spp., Streptococcus spp., Streptococcus pneumoniae), gram-negative (Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp.), aerobic and anaerobic bacteria, determined as monocultures and microbial associations, including hospital strains with polyresistance to antibiotics.

It has an antifungal effect on ascomycetes of the genus Aspergillus and the genus Penicillium, yeast (Rhodotorula rubra, Torulopsis gabrata), and yeast-like fungi (Candida albicans, Candida tropicalis, Candida krusei, Pityrosporum orbiculare (Malassezia furfur), dermatophytes (Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton verrucosum, Trichophyton schoenleini, Trichophyton violacent, Epidermophyton Kaufman-Wolf, Epidermophyton floccosum, Microsporum gypseum, Microsporum canis), as well as other pathogenic fungi, in the form of monocultures and microbial associations, including fungal microflora with resistance to chemotherapeutic drugs.

It has an antiviral effect, is active against complex viruses (herpes viruses, human immunodeficiency virus).

Benzyldimethyl-myristoylamino-propylammonium acts on the causative agents of sexually transmitted diseases (Chlamydia spp., Treponema spp., Trichomonas vaginalis, Neisseria gonorrhoeae).

Effectively prevents infection of wounds and burns. Activates regeneration processes. Stimulates protective reactions at the site of application, by activating the absorptive and digestive function of phagocytes, potentiates the activity of the monocyte-macrophage system. It has a pronounced hyperosmolar activity, as a result of which it relieves wound and perifocal inflammation, absorbs purulent exudate, contributing to the formation of a dry scab. It does not damage granulations and viable skin cells, does not inhibit marginal epithelialization.

It does not have a local irritant effect or allergenic properties.

Pharmacokinetics

Flurbiprofen – when a single dose (3 presses of the dispenser) is applied to the oropharyngeal mucosa, it is rapidly absorbed and detected in blood plasma after 2-5 minutes. C_max of flurbiprofen in blood plasma is reached 30 minutes after application and is 1.6 µg/ml, which is 4 times lower than when taking 50 mg of flurbiprofen orally. Flurbiprofen is rapidly bound to blood plasma proteins and distributed throughout the body. It is metabolized mainly by hydroxylation and excreted by the kidneys, the elimination half-life T_1/2 is 3-6 hours. Approximately 20-25% of the oral dose of flurbiprofen is excreted by the kidneys unchanged.

Benzyldimethyl-myristoylamino-propylammonium – when applied topically, it is not able to be absorbed through the skin and mucous membranes.

Indications

As a symptomatic agent to relieve sore throat in infectious and inflammatory diseases of the upper respiratory tract.

ICD codes

Dosage Regimen

Administer the spray topically into the oropharyngeal cavity.

Perform one to two sprays per application.

Repeat administration every 3 to 6 hours as needed for pain relief.

Do not exceed five doses within a 24-hour period.

The total duration of self-treatment must not exceed three consecutive days.

If symptoms persist or worsen after three days, discontinue use and consult a physician.

Before first use, prime the pump by spraying several times into the air until a fine mist is produced.

Direct the spray nozzle toward the affected area of the throat.

Avoid contact with eyes.

Do not eat or drink for several minutes after application to enhance local effect.

Adverse Reactions

Blood and lymphatic system disorders frequency unknown – impaired hematopoiesis (anemia, thrombocytopenia).

Immune system disorders rare – anaphylactic reactions; very rare – allergic reactions, mild burning sensation.

Psychiatric disorders uncommon – insomnia.

Nervous system disorders common – dizziness, headache, paresthesia; uncommon – drowsiness.

Cardiac disorders frequency unknown – heart failure, edema, increased blood pressure.

Respiratory, thoracic and mediastinal disorders common – feeling of irritation in the throat; uncommon – exacerbation of asthma and bronchospasm, dyspnea, wheezing, blisters in the oral cavity and pharynx, pharyngeal hypesthesia (decreased sensitivity in the oral cavity and pharynx).

Gastrointestinal disorders common – diarrhea, ulceration of the oral cavity, nausea, pain in the oral cavity, paresthesia of the oral cavity, pain in the oral cavity and pharynx, discomfort in the oral cavity (feeling of warmth, burning or tingling in the mouth); uncommon – abdominal distension, abdominal pain, constipation, dry mouth, dyspepsia, flatulence, glossalgia (burning mouth syndrome), dysgeusia (change in taste perception), oral dysesthesia, vomiting.

Hepatobiliary disorders frequency unknown – hepatitis.

Skin and subcutaneous tissue disorders uncommon – skin rash, pruritus; very rare – hypersensitivity reactions, including irritation and skin rash; frequency unknown – severe skin reactions such as bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell’s syndrome).

General disorders and administration site conditions: uncommon – fever, pain.

Contraindications

Hypersensitivity to the components of the combination; history of hypersensitivity reactions (bronchial asthma, bronchospasm, rhinitis, angioedema, urticaria, recurrent nasal or paranasal sinus polyposis) in response to the use of acetylsalicylic acid or other NSAIDs; erosive and ulcerative lesions of the gastrointestinal tract (including peptic ulcer of the stomach and duodenum, Crohn’s disease, ulcerative colitis) or ulcer bleeding in the acute phase or in the history (2 or more confirmed episodes of peptic ulcer or ulcer bleeding); history of gastrointestinal ulcer bleeding or perforation provoked by the use of NSAIDs; hemophilia and other blood clotting disorders (including hypocoagulation), hemorrhagic diatheses; severe hepatic failure or active liver disease; severe renal failure (creatinine clearance <30 ml/min); decompensated heart failure; period after coronary artery bypass surgery; third trimester of pregnancy, breastfeeding period; confirmed hyperkalemia; glucose-6-phosphate dehydrogenase deficiency; children under 18 years of age.

With caution

When taking other NSAIDs simultaneously; history of a single episode of gastric ulcer or gastrointestinal ulcer bleeding; history of gastrointestinal diseases (ulcerative colitis, Crohn’s disease), gastritis, enteritis, colitis, presence of Helicobacter pylori infection, bronchial asthma or allergic diseases in the acute phase or in the history (possible development of bronchospasm); systemic lupus erythematosus and other systemic autoimmune connective tissue diseases (increased risk of aseptic meningitis) – with short-term use of flurbiprofen, the risk is insignificant; in renal failure, including dehydration (creatinine clearance less than 60 ml/min), nephrotic syndrome; hepatic failure; liver cirrhosis with portal hypertension; hyperbilirubinemia (with short-term use of flurbiprofen, the risk is insignificant); arterial hypertension and/or heart failure, edema; simultaneous use of drugs that may increase the risk of ulcers or bleeding, in particular oral corticosteroids (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), SSRIs (including citalopram, fluoxetine, paroxetine, sertraline); in the first and second trimesters of pregnancy; elderly patients; when consuming alcohol.

Use in Pregnancy and Lactation

The use of flurbiprofen in the first and second trimesters of pregnancy should be avoided. Epidemiological data confirm an increased risk of spontaneous abortion, heart defects and gastroschisis when using prostaglandin synthesis inhibitors in early pregnancy. The use of any prostaglandin synthesis inhibitors in the third trimester of pregnancy can lead to the following negative consequences for the fetus: cardiopulmonary toxicity (with premature closure of the ductus arteriosus and the development of pulmonary hypertension); renal dysfunction progressing to renal failure, and oligohydramnios; possible increase in bleeding time, antiplatelet effect even at very low doses; inhibition of uterine muscle contractions, leading to delayed onset of labor and increased duration of labor. Contraindicated for use in the third trimester of pregnancy and during breastfeeding.

The drug inhibits COX and prostaglandin synthesis and may affect ovulation, impairing female reproductive function (reversible after discontinuation of treatment), which should be taken into account when planning pregnancy.

Use in Hepatic Impairment

Contraindication: severe hepatic failure or active liver disease.

Use in Renal Impairment

Contraindication: severe renal failure (creatinine clearance <30 ml/min).

Pediatric Use

Contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

This combination should be taken for the shortest possible course and at the minimum effective dose necessary to relieve symptoms.

If symptoms of gastropathy appear, careful monitoring is indicated, including esophagogastroduodenoscopy, complete blood count (hemoglobin determination), fecal occult blood test.

If it is necessary to determine 17-ketosteroids, the drug should be discontinued 48 hours before the study.

Patients with renal or hepatic insufficiency, as well as elderly patients and patients taking diuretics, should consult a doctor before using the drug, as there is a risk of deterioration in renal function. With short-term use of this combination, the risk is insignificant.

Patients with arterial hypertension, including in the history and/or chronic heart failure, should consult a doctor before using this remedy, since Flurbiprofen can cause fluid retention, increased blood pressure and edema.

If irritation in the oral cavity, skin rash, damage to the mucous membrane and other manifestations of an allergic reaction occur, the use of this remedy should be discontinued.

If there is no effect after 3 days of therapy, as well as in case of worsening of existing symptoms or the appearance of new ones, including the appearance of signs of a bacterial infection, it is necessary to immediately consult a doctor to review the therapy.

Patients with gastrointestinal diseases (ulcerative colitis, Crohn’s disease) should be prescribed NSAIDs with caution due to the possible exacerbation of these diseases. If symptoms of bleeding or ulceration appear, patients should stop taking the drug.

It is recommended to use with caution in patients at risk of bleeding.

It is not recommended to consume alcohol during treatment.

Effect on ability to drive vehicles and mechanisms

If dizziness, drowsiness, lethargy or visual impairment occurs when taking this remedy, patients should avoid driving vehicles or mechanisms.

Drug Interactions

Flurbiprofen

Concomitant use with acetylsalicylic acid should be avoided (except for low doses of acetylsalicylic acid – no more than 75 mg/day, since concomitant use may increase the risk of side effects; with other NSAIDs, including ibuprofen and selective COX-2 inhibitors; simultaneous use of two or more drugs from the NSAID group should be avoided due to a possible increase in the risk of side effects.

Use with caution with the following medicinal products.

Anticoagulants: NSAIDs may enhance the effect of anticoagulants, in particular, warfarin.

Antiplatelet agents and selective serotonin reuptake inhibitors: increased risk of gastrointestinal bleeding.

Antihypertensive agents (ACE inhibitors and angiotensin II antagonists) and diuretics: NSAIDs may reduce the effectiveness of drugs of these groups and may increase nephrotoxicity due to COX inhibition, especially in patients with impaired renal function (adequate fluid replacement should be provided in such patients).

Cardiac glycosides: simultaneous use with NSAIDs may lead to worsening of heart failure, decreased glomerular filtration rate and increased plasma concentration of cardiac glycosides.

Cyclosporine: increased risk of nephrotoxicity when used concomitantly with NSAIDs.

Corticosteroids: increased risk of gastrointestinal ulcers and gastrointestinal bleeding.

Lithium preparations: there is a risk of increased plasma lithium concentration against the background of NSAID use.

Methotrexate: there is a risk of increased plasma methotrexate concentration against the background of NSAID use.

Mifepristone: NSAIDs should be started no earlier than 8-12 days after the end of mifepristone use, since NSAIDs may reduce the effectiveness of mifepristone.

Quinolone antibiotics: when used concomitantly with NSAIDs, an increased risk of seizures is possible.

SSRIs: increased risk of gastrointestinal ulcers and gastrointestinal bleeding.

Tacrolimus: when used concomitantly with NSAIDs, an increased risk of nephrotoxicity is possible.

Zidovudine: simultaneous use with NSAIDs may lead to increased hematotoxicity.

Oral hypoglycemic drugs: possible change in blood glucose levels (it is recommended to increase the frequency of blood glucose monitoring).

Phenytoin: possible increase in plasma phenytoin concentration (monitoring of plasma phenytoin concentration and, if necessary, dose adjustment is recommended).

Potassium-sparing diuretics: concomitant use with flurbiprofen may lead to hyperkalemia.

Probenecid and sulfinpyrazone: may delay the excretion of flurbiprofen.

Tolbutamide and antacids: to date, studies have not revealed interactions between flurbiprofen and tolbutamide or antacids.

Ethanol: possible increase in the risk of adverse reactions, especially gastrointestinal bleeding.

Benzyldimethyl-myristoylamino-propylammonium

When used concomitantly with antibiotics, an enhancement of their antibacterial and antifungal properties has been noted.

Storage Conditions

Store at 15°C (59°F) to 25°C (77°F).

Keep in original packaging, protected from light.

Keep out of reach of children.

Dispensing Status

Over-the-Counter

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.