Celistar® for sore throat

INSTRUCTIONS for medical use of the medicinal product Celista® From a sore throat (Celista From a sore throat)

Composition:

Active substance: flurbiprofen;

1 lozenge contains flurbiprofen 8.75 mg;

Excipients: sucrose, glucose syrup, macrogol 300, peppermint oil, levomenthol, potassium hydroxide.

Pharmaceutical form. Lozenges.

Main physicochemical properties: round-shaped lozenges, 19 mm ± 1 mm in size, from pale yellow to brown in color.

Pharmacotherapeutic group. Preparations used in throat diseases. Flurbiprofen. ATC code R02A X01.

Pharmacological properties.

Pharmacodynamics.

Flurbiprofen is a nonsteroidal anti-inflammatory agent that exerts potent anti-inflammatory, analgesic, and antipyretic effects due to its ability to inhibit the synthesis of prostaglandins.

Pain reduction, decreased pain sensations in the throat area, and reduction of throat swelling are observed within 30 minutes after taking the lozenge; the duration of action lasts 2−3 hours.

Analgesic and anti-inflammatory activity is due to inhibition of the cyclooxygenase enzyme and suppression of prostaglandin synthesis. The drug exerts a local effect. It equally inhibits the activity of PGE2 and PGE2a by inhibiting endoperoxidase, which catalyzes the conversion of arachidonic acid into cyclic endoperoxide.

Pharmacokinetics.

Maximum plasma concentration of flurbiprofen is observed within 30−40 minutes after dissolving the lozenge in the oral cavity. Peak concentrations of flurbiprofen are achieved faster after administration of the lozenge than after swallowing an equivalent dose, although the concentration levels in both cases are similar. Flurbiprofen is rapidly distributed throughout the body. The drug is actively metabolized via methylation and hydroxylation, followed by renal elimination. The main metabolites of the drug are 4’-hydroxy-flurbiprofen and 3’-hydroxy-4’-methoxy-flurbiprofen. Approximately 70% of each dose is excreted in the urine within 24 hours. The elimination half-life is 3–6 hours.

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) following intake of acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (NSAIDs).
• Recurrent peptic ulcer/bleeding in history or in the acute phase (two or more episodes confirmed by characteristic clinical manifestations) and intestinal ulcers.
• History of gastrointestinal bleeding or perforation, severe colitis, hemorrhagic or hematopoietic disorders associated with previous NSAID therapy.
• Third trimester of pregnancy.
• Severe heart failure, severe renal impairment, or severe hepatic impairment.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of flurbiprofen with the following should be avoided:

Other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors: concomitant use of two or more NSAIDs should be avoided, as this increases the risk of adverse effects (particularly gastrointestinal side effects such as ulcers and bleeding);

Acetylsalicylic acid (at low doses), except when low-dose aspirin (not exceeding 75 mg per day) has been prescribed by a physician, as this increases the risk of adverse reactions.

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

Anticoagulants: NSAIDs may enhance the effects of anticoagulants such as 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 also enhance nephrotoxicity caused by cyclooxygenase inhibition, particularly in patients with impaired renal function (patients should receive adequate fluid intake);

Alcohol: increases the risk of adverse reactions, especially 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, with dose adjustment if necessary;

Cyclosporine: increased risk of nephrotoxicity;

Corticosteroids: increased risk of adverse reactions, particularly in the gastrointestinal tract;

Lithium: possible increase in serum lithium levels; appropriate monitoring and, if necessary, dose adjustment are recommended;

Methotrexate: administration of NSAIDs within 24 hours before or after methotrexate may lead to increased methotrexate concentrations and enhanced 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: blood glucose levels may change (increased monitoring of blood glucose levels is recommended);

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

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

Probenecid, sulfinpyrazone, medicinal products containing probenecid or sulfinpyrazone: may cause delayed elimination of flurbiprofen;

Quinolone antibiotics: animal studies indicate that NSAIDs increase the risk of seizures associated with quinolone antibiotics. Patients receiving NSAIDs and quinolones 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 NSAIDs are used concomitantly with tacrolimus;

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

Studies conducted to date have not revealed any interaction 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 duration necessary.

Elderly patients have an increased frequency of adverse reactions associated with NSAID use, particularly gastrointestinal bleeding or perforation, which may be fatal.

Respiratory effects. Bronchospasm may occur in patients suffering from bronchial asthma or allergic diseases, or in those with a history of these conditions. Such patients should use flurbiprofen lozenges with caution.

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

Systemic lupus erythematosus and mixed connective tissue disease. Patients with systemic lupus erythematosus or mixed connective tissue disease have an increased risk of aseptic meningitis.

Cardiac, renal, and hepatic impairment. Nephrotoxicity. There have been reports that NSAIDs may cause nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome, and renal failure, particularly when multiple analgesic agents are used concomitantly or with prolonged regular use. NSAID use may lead to dose-dependent reduction in prostaglandin production and may provoke renal failure. The greatest risk of this reaction occurs in patients with pre-existing renal impairment, heart failure, hepatic dysfunction, those taking diuretics, and elderly patients. Renal function should be monitored in such patients. However, this effect is usually not observed with short-term, limited use of drugs such as flurbiprofen lozenges.

Cardiovascular and cerebrovascular effects. Caution (after consultation with a physician) should be exercised when initiating treatment in patients with a history of elevated blood pressure and/or heart failure, as fluid retention, increased blood pressure, and edema have been reported during NSAID use.

Clinical trials and epidemiological data suggest that the use of certain NSAIDs (particularly at high doses and for prolonged periods) increases the risk of arterial thrombotic complications (e.g., myocardial infarction or stroke). There is insufficient data to exclude such a risk with the use of 5 lozenges per day.

Hepatic effects. Mild to moderate liver function abnormalities.

Neurological effects. Analgesic-induced headache: prolonged use of analgesics or failure to follow recommendations may result in headache, which should not be treated with increased doses of the drug.

Gastrointestinal effects. During treatment with all NSAIDs, gastrointestinal bleeding, ulcers, or perforations—potentially fatal—have been reported at any stage of therapy, regardless of the presence of warning symptoms or a history of severe gastrointestinal disorders. The risk increases with higher NSAID doses, in patients with a history of peptic ulcer disease (especially complicated by bleeding or perforation), and in elderly patients. These patients should start treatment with the lowest available dose. For such patients, as well as those requiring concomitant use of low-dose acetylsalicylic acid or other drugs that may increase gastrointestinal risk, combination therapy with protective agents (e.g., misoprostol or proton pump inhibitors) is recommended. Patients should consult a physician if they experience any unusual gastrointestinal symptoms (especially gastrointestinal bleeding), particularly at the beginning of treatment. The drug should be used with caution in patients receiving concomitant therapy with medications that increase the risk of peptic ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), SSRIs, or antiplatelet agents such as acetylsalicylic acid. If gastrointestinal bleeding or ulceration occurs in patients receiving flurbiprofen, treatment should be discontinued. NSAIDs should be used cautiously in patients with a history of gastrointestinal disorders (e.g., ulcerative colitis, Crohn’s disease), as their condition may worsen.

Skin and subcutaneous tissue effects. Very rarely, severe skin reactions, which may be fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, may occur during NSAID use. Flurbiprofen lozenges should be discontinued at the first signs of skin rash, mucosal lesions, or any other signs of hypersensitivity.

Infections. Since isolated cases of exacerbation of infectious inflammation (e.g., development of necrotizing fasciitis) have been observed temporally associated with systemic NSAID use, patients should be advised to seek immediate medical attention if signs of bacterial infection occur or if their condition worsens during treatment with flurbiprofen lozenges. Anti-infective therapy with antibiotics should be considered.

Sugar intolerances. This medicinal product is not recommended for patients with rare hereditary fructose intolerance, glucose/galactose malabsorption syndrome, or sucrase-isomaltase deficiency.

May be harmful to teeth.

If symptoms worsen or new symptoms develop, treatment should be re-evaluated.

If oral irritation occurs, treatment should be discontinued.

Fertility impairment in women.

Flurbiprofen use may impair fertility in women; therefore, this medicinal product is not recommended for women attempting to conceive. The discontinuation of this medicinal product should be considered in women experiencing difficulty conceiving or undergoing fertility investigations.

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 and congenital heart defects and gastroschisis following prostaglandin synthesis inhibitor use in early pregnancy. The absolute risk of cardiac malformations increases from less than 1% to approximately 1.5%. The risk is considered to increase with higher doses and longer duration of treatment. In animal studies, prostaglandin synthesis inhibitors administered during organogenesis have been associated with increased incidence of various developmental abnormalities, including cardiovascular malformations. Flurbiprofen should not be used during the first two trimesters of pregnancy, except when absolutely necessary. If flurbiprofen is used by a woman trying to conceive or during the first or second trimester of pregnancy, the lowest possible dose for the shortest duration should be used.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may pose the following risks:

For the fetus: cardiopulmonary toxicity (characterized by premature closure of the ductus arteriosus and pulmonary hypertension); renal dysfunction, which may progress to renal failure associated with oligohydramnios;

For the mother at the end of pregnancy 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.

Therefore, flurbiprofen is contraindicated during the third trimester of pregnancy.

Breastfeeding.

In some studies, flurbiprofen has been detected in breast milk at very low concentrations. It is unlikely to have a negative effect on the breastfed infant. However, due to the potential adverse effects of NSAIDs on breastfed infants, the use of this medicinal product is not recommended in breastfeeding women.

Fertility.

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

Ability to affect reaction speed when driving or operating machinery.

Studies on the ability to affect reaction speed when driving or operating machinery have not been conducted.

Method of Administration and Dosage.

Lozenges should be sucked until completely dissolved. Adults and children aged 12 years and older should take 1 lozenge every 3–6 hours as needed for pain relief. The maximum daily dose is 5 lozenges.

Use the lowest effective dose for the shortest duration necessary to relieve symptoms. If symptoms do not improve, worsen, or persist for more than 3 days, consult a physician.

It is not recommended to use this medicinal product for more than 3 consecutive days.

While sucking the lozenge, move it around the entire oral cavity to prevent irritation of the mucous membrane at the site of dissolution.

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 adverse reactions.

Children.

Do not use in children under 12 years of age.

Overdose.

Symptoms. In most patients, ingestion of a clinically significant amount of NSAIDs causes only nausea, vomiting, epigastric pain, or less commonly, diarrhea. Other possible symptoms include tinnitus, headache, and gastrointestinal bleeding. In more severe poisoning, toxic effects on the central nervous system may occur, such as drowsiness, occasionally excitement, visual disturbances, disorientation, or coma. Severe poisoning may lead to metabolic acidosis and prolonged prothrombin time, likely due to interaction with circulating blood coagulation factors. Acute renal failure and liver damage may also occur. In patients with bronchial asthma, an exacerbation of asthma symptoms is possible.

Treatment. Treatment should be symptomatic and supportive, including maintaining airway patency and monitoring cardiac function and vital signs until the patient's condition stabilizes. Oral administration of activated charcoal is recommended within 1 hour after ingestion of a potentially toxic dose. For frequent or prolonged muscle spasms, 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, for example: pruritus, urticaria, angioneurotic edema, less frequently – exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).

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

The adverse reactions listed below were observed during short-term use of flurbiprofen at over-the-counter doses.

All adverse reactions are listed by system organ class and 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 available data).

Respiratory, thoracic and mediastinal disorders: common – throat irritation; uncommon – exacerbation of bronchial asthma and bronchospasm, dyspnea, wheezing, mouth and pharyngeal blisters, pharyngeal hypoaesthesia.

Gastrointestinal disorders: common – diarrhea, oral ulcers, nausea, oral pain, oral paraesthesia, 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.

Nervous system disorders: common – dizziness, headache, paraesthesia; uncommon – somnolence.

Psychiatric disorders: uncommon – insomnia.

Cardiovascular disorders: frequency not known – edema, arterial hypertension, heart failure.

Blood and lymphatic system disorders: frequency not known – anemia, thrombocytopenia.

Immune system disorders: rare – anaphylactic reactions.

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

General disorders: uncommon – pyrexia, pain.

If adverse reactions occur, treatment should be discontinued and medical advice should be sought.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after drug authorization is an important procedure. It allows continuous monitoring of the benefit-risk ratio of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions via the national reporting system.

Shelf life. 2 years.

The shelf life is defined as the period of time during which the medicinal product may be used, up to the last day of the stated month.

Storage conditions.

Store in the original packaging at a temperature not exceeding 30 °C. Keep out of reach of children.

Packaging.

12 lozenges in a blister; 1 blister per carton.

Supply category. Over-the-counter.

Manufacturer. LOZIS PHARMACEUTICALS S.L.

Manufacturer's address and location of operations.

Campus Empresarial, Lecaroze, Navarra, 31795, Spain.

Marketing Authorization Holder. JSC "Pharmaceutical Company "Darnitsya".

Address of the Marketing Authorization Holder.

13 Borispilska Street, Kyiv, 02093, Ukraine.