DECATILEN FLU

INSTRUCTION for medical use of the medicinal product Decatylen Flu (Decatylen Flu)

Composition:

Active substance: flurbiprofen;

1 lozenge contains flurbiprofen 8.75 mg;

Excipients: isomalt (E 953), maltitol (E 965), polyethylene glycol 300, peppermint oil, honey flavor, lemon flavor.

Pharmaceutical form. Lozenges.

Main physicochemical characteristics: round lozenges, transparent to slightly yellow, with a diameter of 19 ± 1 mm.

Pharmacotherapeutic group. Preparations used in throat disorders. Flurbiprofen. ATC code R02AX01.

Pharmacological Properties.

Mechanism of action.

Flurbiprofen is a non-steroidal anti-inflammatory drug (NSAID), a derivative of propionic acid, which acts by inhibiting the synthesis of prostaglandins.

Pharmacodynamics.

In humans, flurbiprofen exerts potent anti-inflammatory, analgesic, and antipyretic effects. In studies on cultured human respiratory cells, flurbiprofen at a dose of 8.75 mg dissolved in artificial saliva was shown to reduce prostaglandin synthesis. According to whole blood assay studies, flurbiprofen is a mixed inhibitor of COX-1/COX-2 with some selectivity towards COX-1.

Preclinical studies suggest that the R(-) enantiomer of flurbiprofen and related NSAIDs may affect the central nervous system (CNS); the likely mechanism involves inhibition of COX-2 induction at the spinal cord level.

Clinical efficacy and safety.

A single 8.75 mg dose of flurbiprofen in the form of a lozenge has been shown to relieve sore throat pain, including swelling and inflammation of the throat mucosa, by significantly reducing (least squares mean difference) throat pain intensity starting from 22 minutes (-5.5 mm), reaching maximum effect at 70 minutes (-13.7 mm), and remaining significant up to 240 minutes (-3.5 mm), including patients with streptococcal and non-streptococcal infections; difficulty in swallowing improved from 20 minutes (-6.7 mm), reaching maximum at 110 minutes (-13.9 mm) and persisting up to 240 minutes (-3.5 mm); and reduction in the sensation of throat swelling was observed from 60 minutes (-9.9 mm), peaking at 120 minutes (-11.4 mm) and lasting up to 210 minutes (-5.1 mm).

The efficacy of multiple doses, measured as the sum of pain intensity differences (SPID) over 24 hours, demonstrated significant reduction in throat pain intensity (from -473.7 mm*hr to -529.1 mm*hr), difficulty in swallowing (from -458.4 mm*hr to -575.0 mm*hr), and throat swelling (-482.4 mm*hr to -549.9 mm*hr), with statistically significant greater total pain relief at each time interval over 23 hours for all three parameters and statistically significant hourly improvement in throat pain relief over 6 hours of assessment. Efficacy of multiple doses was also demonstrated at 24 hours and over 3 days. In patients receiving antibiotics for streptococcal infection, statistically significant greater reduction in throat pain intensity was observed with 8.75 mg flurbiprofen starting at 7 hours and beyond after antibiotic administration. The analgesic effect of 8.75 mg flurbiprofen was not diminished when antibiotics were used to treat patients with streptococcal throat infection. Two hours after the first dose of 8.75 mg flurbiprofen lozenges, significant relief of certain baseline accompanying symptoms of sore throat was observed, including cough (50% vs. 4%), reduced appetite (84% vs. 57%), and fever (68% vs. 29%). The lozenge dissolves in the mouth within 5–12 minutes and provides a noticeable soothing and coating effect within 2 minutes of administration.

Children. No specific studies involving children have been conducted. Studies on the efficacy and safety of 8.75 mg flurbiprofen lozenges included children aged 12–17 years; however, due to the small sample size, statistically significant conclusions cannot be drawn.

Pharmacokinetics.

Absorption. Lozenges dissolve within 5–12 minutes, and flurbiprofen is readily absorbed, detectable in the blood within 5 minutes, with peak plasma concentrations reached within 40–45 minutes after administration, but remaining on average at a low level of 1.4 µg/mL, approximately 4.4 times lower than after a 50 mg tablet. Absorption of flurbiprofen may occur from the oral cavity via passive diffusion. The rate of absorption depends on the dosage form; peak concentrations of flurbiprofen are achieved faster after lozenge administration than after swallowing an equivalent dose, although plasma concentration levels are similar in both cases.

Distribution. Flurbiprofen is rapidly distributed throughout the body and binds to plasma proteins.

Biotransformation/elimination. Flurbiprofen is metabolized via hydroxylation and excreted by the kidneys. The elimination half-life ranges from 3 to 6 hours.

Flurbiprofen passes into human milk in very small amounts (less than 0.05 µg/mL). Approximately 20–25% of an oral dose of flurbiprofen is excreted unchanged.

Elderly patients and children. No differences in pharmacokinetic parameters were observed between elderly patients and young adult volunteers after oral administration of flurbiprofen tablets. Pharmacokinetic data are not available in children under 12 years after administration of 8.75 mg flurbiprofen; however, administration of flurbiprofen syrup and suppositories does not indicate significant differences in pharmacokinetic parameters compared to adults.

Clinical characteristics.

Indications. For short-term symptomatic relief of sore throat pain in adults and children aged 12 years and older.

Contraindications.

• Hypersensitivity to flurbiprofen or to any of the excipients of the medicinal product.
• History of hypersensitivity reactions (e.g. bronchial asthma, bronchospasm, rhinitis, angioedema, or urticaria) after taking acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs).
• Recurrent peptic ulcer/bleeding in history or in acute phase, or intestinal ulcers (two or more episodes confirmed by characteristic clinical manifestations).
• Gastrointestinal bleeding or perforation in history, severe colitis, hemorrhagic or hemopoietic disorders associated with previous NSAID therapy.
• Third trimester of pregnancy.
• Severe heart failure, severe renal failure, or severe hepatic failure.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of flurbiprofen with the following should be avoided:

other NSAIDs, including selective COX-2 inhibitors: concomitant use of two or more NSAIDs should be avoided, as this may increase the risk of adverse reactions, particularly gastrointestinal (e.g. ulcers and bleeding);

acetylsalicylic acid (at low doses): unless prescribed by a physician at low doses (not exceeding 75 mg/day), as this may increase the risk of adverse reactions.

Flurbiprofen should be used with caution in combination with the following medicinal products:

anticoagulants: NSAIDs may enhance the effect of anticoagulants (e.g. warfarin);

antiplatelet agents: increased risk of gastrointestinal ulceration or bleeding;

antihypertensive agents, diuretics, ACE inhibitors, and angiotensin II antagonists: NSAIDs may reduce the efficacy of diuretics and other antihypertensive agents and may enhance nephrotoxicity due to cyclooxygenase inhibition, particularly in patients with impaired renal function (patients should receive adequate hydration);

alcohol: increases the risk of adverse reactions, particularly gastrointestinal bleeding;

cardiac glycosides: NSAIDs may exacerbate heart failure, reduce glomerular filtration rate, and increase plasma levels of glycosides. Monitoring of the patient is recommended, and dose adjustment if necessary;

cyclosporine: increased risk of nephrotoxicity;

corticosteroids: possible increased risk of adverse reactions, particularly gastrointestinal;

lithium: possible increase in serum lithium concentration; appropriate monitoring is recommended, and dose adjustment if necessary;

methotrexate: use of NSAIDs within 24 hours before or after methotrexate administration may lead to elevated methotrexate concentrations and increased toxicity;

mifepristone: NSAIDs should not be taken within 8–12 days after mifepristone administration, as NSAIDs may reduce the efficacy of mifepristone;

oral antidiabetic agents: changes in blood glucose levels have been reported (increased monitoring of blood glucose levels is recommended);

phenytoin: possible increase in plasma phenytoin levels; appropriate monitoring is recommended, and dose adjustment if necessary;

potassium-sparing diuretics: concomitant use may lead to hyperkalemia;

probenecid, sulfinpyrazone: medicinal products containing probenecid or sulfinpyrazone may delay the elimination of flurbiprofen;

quinolone antibiotics: animal studies indicate that NSAIDs increase the risk of seizures associated with quinolone antibiotics. Patients receiving NSAIDs and quinolones may have an increased risk of developing seizures;

selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal ulceration or bleeding;

tacrolimus: possible increased risk of nephrotoxicity when used concomitantly with NSAIDs;

zidovudine: increased risk of hematological toxicity when used concomitantly with NSAIDs.

Studies conducted to date have not revealed interactions between flurbiprofen and tolbutamide or antacids.

Special precautions for use

Adverse effects can be minimized by using the lowest effective dose required to control symptoms for the shortest possible duration.

In elderly patients, there is an increased frequency of adverse reactions due to the use of NSAIDs, particularly gastrointestinal bleeding and perforation, which may be fatal.

Patients with respiratory disorders. Bronchospasm may occur in patients suffering from bronchial asthma or allergic diseases, or with a history of these conditions. Such patients should use lozenges containing flurbiprofen with caution.

Other NSAIDs. Concomitant use of flurbiprofen lozenges with other NSAIDs, including selective COX-2 inhibitors, should be avoided.

Systemic lupus erythematosus (SLE) and mixed connective tissue disease. Patients with SLE and mixed connective tissue disease may have an increased risk of developing aseptic meningitis. However, this effect is usually not observed with short-term, limited use of medicinal products such as flurbiprofen lozenges.

Cardiovascular, renal, and hepatic insufficiency. NSAIDs have been reported to cause nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, and renal failure. The use of NSAIDs may lead to dose-dependent reduction in prostaglandin synthesis and may trigger renal failure. The highest risk of this reaction exists in patients with impaired kidney, heart, or liver function, patients taking diuretics, and elderly patients. However, this effect is usually not observed with short-term, limited use of medicinal products such as flurbiprofen lozenges. In patients with impaired renal function, renal function should be monitored, as NSAIDs may worsen it. The medicinal product should be used with caution in patients with mild to moderate hepatic impairment.

Effects on the cardiovascular and cerebrovascular systems. The medicinal product should be initiated with caution (after consultation with a physician) in patients with elevated blood pressure and/or heart failure, as fluid retention, increased blood pressure, and edema have been reported with NSAID use. Clinical studies and epidemiological data suggest that the use of certain NSAIDs (particularly at high doses and for prolonged periods) may be associated with a small increase in the risk of arterial thrombotic events (e.g., myocardial infarction or stroke). There are insufficient data to exclude this risk for flurbiprofen when used at the maximum daily dose of 5 lozenges per day.

Effects on the nervous system. Analgesic-induced headache: prolonged use of analgesics or failure to follow recommendations may lead to headache, which should not be treated with increased doses of the medicinal product. In such cases, NSAID treatment should be discontinued and the patient should consult a physician.

Effects on the gastrointestinal tract. During the use of all NSAIDs at any stage of treatment, gastrointestinal bleeding, ulcers, or perforations—potentially fatal—have been reported, regardless of the presence of warning symptoms or a history of severe gastrointestinal disorders. The risk of gastrointestinal bleeding, ulcers, or perforation increases with higher NSAID doses, in patients with a history of peptic ulcer, especially complicated by bleeding or perforation, and in elderly patients. However, this effect is usually not observed with short-term, limited use of medicinal products such as flurbiprofen lozenges. Patients with a history of gastrointestinal toxicity, particularly elderly patients, should inform their physician about any unusual abdominal symptoms (especially gastrointestinal bleeding). The medicinal product should be used with caution in patients who are concurrently taking medications that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), SSRIs, antiplatelet agents (e.g., acetylsalicylic acid). NSAIDs should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn’s disease), as their condition may worsen. If gastrointestinal bleeding or ulcers occur in patients receiving flurbiprofen, the medicinal product should be discontinued.

Effects on the skin and subcutaneous tissue. Very rarely, severe skin reactions, sometimes even fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, may occur during NSAID use. If early signs of skin rash, mucosal lesions, or any other symptoms of hypersensitivity appear, flurbiprofen lozenges should be discontinued immediately.

Infections. Isolated cases of exacerbation of infectious inflammation (e.g., development of necrotizing fasciitis) have been observed in temporal association with systemic NSAID use as a class. Patients are advised to seek immediate medical attention if signs of bacterial infection occur or if their condition worsens during treatment with flurbiprofen lozenges. Anti-infective antibiotic therapy should be considered. If symptoms worsen or new symptoms arise, treatment should be re-evaluated. When sucking the lozenge, it should be moved around the entire oral cavity; if irritation in the mouth occurs, treatment should be discontinued.

Masking symptoms of underlying infections. Epidemiological studies indicate that systemic NSAIDs may mask symptoms of infection, potentially delaying appropriate treatment and thereby worsening infection outcomes. This has been observed in community-acquired bacterial pneumonia and bacterial complications of varicella. When flurbiprofen is used in patients with fever or pain related to infection, monitoring for infection is recommended.

Excipients. This medicinal product contains isomalt (E 953) and maltitol (E 965). Patients with rare hereditary fructose intolerance should not use this medicinal product. It may have a mild laxative effect. The caloric value of maltitol and isomalt is 2.3 kcal/g.

Use during pregnancy or breastfeeding.

Pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic/fetal development. Epidemiological data indicate an increased risk of miscarriage, congenital heart defects, and gastroschisis following use of prostaglandin synthesis inhibitors in early pregnancy. The absolute risk of heart defects increased from less than 1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of therapy.

In animal studies, prostaglandin synthesis inhibitors caused increased pre- and post-implantation loss and embryonic/fetal mortality. Furthermore, administration of prostaglandin synthesis inhibitors during organogenesis in animals was associated with increased incidence of various developmental abnormalities, particularly of the cardiovascular system.

From the 20th week of pregnancy, use of flurbiprofen may cause oligohydramnios due to fetal renal dysfunction. This may occur soon after initiation of treatment and is usually reversible upon discontinuation. Additionally, there have been reports of arterial duct constriction after treatment in the second trimester, most of which resolved after treatment cessation. Therefore, flurbiprofen should not be used during the first two trimesters of pregnancy, except when absolutely necessary. If flurbiprofen is used by women attempting to conceive or during the first and second trimesters of pregnancy, the lowest possible dose for the shortest possible duration should be used. Antenatal monitoring for oligohydramnios and arterial duct constriction should be considered after flurbiprofen use for several days starting from the 20th week of pregnancy. Flurbiprofen use should be discontinued if oligohydramnios or arterial duct constriction is detected. During the third trimester, all prostaglandin synthesis inhibitors may pose the following risks: for the fetus – cardiopulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension); renal dysfunction (see above); for the mother near term and the newborn – prolonged bleeding time, antiplatelet effect (which may occur even at very low doses); inhibition of uterine contractions, leading to delayed or prolonged labor.

Flurbiprofen is contraindicated during the third trimester of pregnancy.

Breastfeeding. Flurbiprofen has been detected in breast milk at very low concentrations in some studies. It is unlikely to have a negative effect on the breastfed infant. However, due to the potential for adverse effects of NSAIDs in breastfed infants, the use of Decatilen Flu is not recommended in women who are breastfeeding.

Fertility. There is some evidence that medicinal products which inhibit cyclooxygenase/prostaglandin synthesis may impair female fertility by affecting ovulation. This effect is reversible upon discontinuation of the medicinal product.

Ability to influence reaction speed when driving or operating machinery.

No studies on the ability to influence reaction speed when driving or operating machinery have been conducted.

Method of Administration and Dosage.

The lowest effective dose for the shortest duration necessary to relieve symptoms should be used. It is not recommended to use the medicinal product for longer than 3 days. Lozenges should be sucked until completely dissolved. While sucking, the lozenge should be moved around the entire oral cavity to prevent irritation of the mucous membrane at the site of dissolution.

Adults and children aged 12 years and older: Take 1 lozenge every 3–6 hours as needed for pain relief. The maximum daily dose is 5 lozenges.

Elderly patients. Due to limited clinical experience, general dosage recommendations cannot currently be provided for elderly patients. Elderly patients are at increased risk of severe consequences from adverse reactions.

Patients with renal impairment. Dose adjustment is not required in patients with mild to moderate renal impairment. The medicinal product is contraindicated in patients with severe renal impairment.

Patients with hepatic impairment. Dose adjustment is not required in patients with mild to moderate hepatic impairment. The medicinal product is contraindicated in patients with severe hepatic impairment.

Children.

Do not use in children under 12 years of age.

Overdose.

Symptoms. In most patients, ingestion of clinically significant amounts of NSAIDs causes only nausea, vomiting, epigastric pain, or less frequently, diarrhea. Tinnitus, headache, and gastrointestinal bleeding may also occur. In more severe poisoning, CNS toxicity may manifest as drowsiness, occasionally excitement, visual disturbances, disorientation, or coma. Seizures may occasionally occur. In severe poisoning, metabolic acidosis and prolonged prothrombin time/INR (International Normalized Ratio) may develop, possibly due to interaction with circulating blood coagulation factors. Acute renal failure and liver damage may occur. In patients with bronchial asthma, an exacerbation of the condition may occur.

Treatment. Treatment should be symptomatic and supportive, including maintaining airway patency and monitoring cardiac function and vital signs until the patient's condition normalizes. Administration of activated charcoal or gastric lavage may be considered, and, if necessary, correction of serum electrolyte imbalances, if less than 1 hour has passed since ingestion of a potentially toxic dose. For frequent or prolonged seizures, treatment should include intravenous administration of diazepam or lorazepam. Bronchodilators should be used in cases of bronchial asthma. There is no specific antidote for flurbiprofen.

Adverse Reactions

Hypersensitivity reactions to NSAIDs have been reported, which may include: non-specific allergic reactions and anaphylaxis; respiratory tract reactivity, for example: bronchial asthma, exacerbation of bronchial asthma, bronchospasm, dyspnea; various skin reactions, such as: pruritus, urticaria, angioedema, and less frequently – exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

Edema, arterial hypertension, and heart failure have been reported in association with the use of NSAIDs. Clinical trials and epidemiological data suggest that the use of certain NSAIDs (particularly long-term use at high doses) is associated with a slightly increased risk of arterial thrombotic complications (e.g., myocardial infarction or stroke). There is insufficient data to exclude such a risk with the use of lozenges containing 8.75 mg of flurbiprofen.

The adverse reactions listed below were observed during short-term use of flurbiprofen at over-the-counter doses, with the following frequency: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000); frequency not known (cannot be estimated from the available data).

Blood and lymphatic system disorders: Frequency not known — anemia, thrombocytopenia.

Immune system disorders: Rare — anaphylactic reactions.

Cardiovascular and cerebrovascular system disorders: Frequency not known — edema, arterial hypertension, heart failure.

Nervous system and psychiatric disorders: Common — dizziness, headache, paresthesia; uncommon — somnolence, insomnia.

Respiratory, thoracic and mediastinal disorders: Common — throat irritation; uncommon — exacerbation of bronchial asthma, bronchospasm, dyspnea, wheezing, oral blisters, pharyngeal hypoaesthesia.

Gastrointestinal disorders: Common — diarrhea, oral ulcers, nausea, oral pain, oral paresthesia, oropharyngeal pain, oral discomfort (sensation of warmth, burning, or tingling in the mouth); uncommon — abdominal distension, abdominal pain, constipation, dry mouth, dyspepsia, flatulence, glossodynia, dysgeusia, oral dysaesthesia, vomiting.

Hepatobiliary disorders: Frequency not known — hepatitis.

Skin and subcutaneous tissue disorders: Uncommon — various skin rashes, pruritus; frequency not known — severe skin reactions, such as bullous-type reactions, including Stevens–Johnson syndrome and toxic epidermal necrolysis.

General disorders and administration site conditions: Uncommon — pyrexia, pain.

Reporting of suspected adverse reactions. All suspected adverse reactions and lack of drug efficacy should be reported via the following link: https://aisf.dec.gov.ua

Shelf life. 2 years.

Storage conditions.

Store at temperatures not exceeding 30 °C. Keep out of reach of children.

Packaging.

12 lozenges per blister, 2 blisters per cardboard box.

Availability category.

Over-the-counter (without prescription).

Manufacturer.

Lozis Pharmaceuticals S.L.

Manufacturer's address and location of its business operations.

Campus Empresarial, Lekaros, Navarra, 31795, Spain.