Instructions for Celista sugar-free sore throat lozenges 8.75 mg No. 12
Composition
active ingredient: flurbiprofen;
1 lollipop contains 8.75 mg of flurbiprofen;
excipients: isomalt (E 953), maltitol (E 965), cochineal red A (E 124), sunset yellow (E 110), acesulfame potassium, macrogol 300, orange flavoring, potassium hydroxide, levomenthol.
Dosage form
Lollipops.
Main physical and chemical properties: Round orange-colored lollipops with orange flavor.
Pharmacotherapeutic group
Drugs used in throat diseases. Flurbiprofen. ATX code R02A X01.
Pharmacological properties
Pharmacodynamics.
Flurbiprofen is a propionic acid derivative from the group of nonsteroidal anti-inflammatory drugs (NSAIDs), which acts by inhibiting prostaglandin synthesis.
In humans, flurbiprofen has potent analgesic, antipyretic, and anti-inflammatory effects. A dose of 8.75 mg dissolved in artificial saliva has been shown to inhibit prostaglandin synthesis in cultured human airway cells. Flurbiprofen is a mixed inhibitor of COX-1 and COX-2 with some selectivity for COX-1, according to whole blood assay data.
Preclinical data suggest that the R(-)-enantiomer of flurbiprofen and other NSAIDs may have effects on the central nervous system; the proposed mechanism of action is inhibition of induced COX-2 at the spinal cord level.
It has been demonstrated that relief of sore throat, including swelling and inflammation of the throat mucosa, occurs through significant reduction (least squares mean difference) in sore throat starting at 22 minutes (-5.5 mm), reaching a maximum at 70 minutes (-13.7 mm) and remaining significant for 240 minutes (-3.5 mm), particularly in patients with streptococcal and non-streptococcal infections; reduction in difficulty swallowing starting at 20 minutes (-6.7 mm), reaching a maximum at 110 minutes (-13.9 mm) and lasting for 240 minutes (-3.5 mm), and reduction in the sensation of throat swelling at 60 minutes (-9.9 mm), reaching a maximum at 120 minutes (-11.4 mm) and lasting for 210 minutes (-5.1 mm).
The efficacy of multiple doses, measured as the sum of pain intensity differences (SPID) over 24 hours, demonstrated significant reductions in the intensity of throat pain (from -473.7 mm*h to -529.1 mm*h), difficulty swallowing (from -458.4 mm*h to -575.0 mm*h), and throat swelling (from -482.4 mm*h to -549.9 mm*h) with statistically greater total pain reduction at each time point over 23 hours for all three measures and statistically significant greater relief of throat pain at each hour over the 6-hour assessment period. Efficacy of multiple doses was also demonstrated at 24 hours and for 3 days.
In patients taking antibiotics for streptococcal infection, statistically significant greater relief of sore throat was observed with flurbiprofen 8.75 mg 7 hours and longer after taking antibiotics. The analgesic effect of flurbiprofen 8.75 mg was not reduced when patients were taking antibiotics for streptococcal sore throat.
Two hours after the first dose of flurbiprofen 8.75 mg lozenges, there was significant relief of some of the associated symptoms of sore throat that were present before the start of therapy, including cough (50% vs. 4%), loss of appetite (84% vs. 57%), and fever (68% vs. 29%).
The lollipop dissolves in the mouth within 5–12 minutes and provides a significant calming and enveloping effect 2 minutes after application.
Children
No specific studies have been conducted in children. Studies of the efficacy and safety of flurbiprofen 8.75 mg lozenges have been conducted in children aged 12–17 years, however the small sample size used suggests that it is not possible to draw statistically significant conclusions.
Pharmacokinetics.
Absorption
Flurbiprofen 8.75 mg lozenges dissolve within 5-12 minutes, flurbiprofen is readily absorbed and is detected in the blood after 5 minutes, and the maximum plasma concentration is observed 40-45 minutes after administration, but remains at a low average level of 1.4 μg/ml, which is approximately 4.4 times lower than in a 50 mg tablet. Flurbiprofen is absorbed in the oral cavity by passive diffusion. The rate of absorption depends on the dosage form, with peak concentrations being reached more quickly after use of the lozenges than after an equivalent dose taken orally.
Distribution.
Flurbiprofen is rapidly distributed in the body and binds to plasma proteins.
Metabolism/excretion.
Flurbiprofen is mainly metabolized by hydroxylation and excreted by the kidneys. The half-life is 3 to 6 hours. Flurbiprofen is excreted in breast milk in only minimal amounts (less than 0.05 μg/ml). Approximately 20-25% of flurbiprofen administered orally is excreted unchanged.
Special patient groups.
Pharmacokinetic data in children under 12 years of age after administration of 8.75 mg flurbiprofen were not obtained, however, administration of both flurbiprofen syrup and suppository formulations did not indicate significant differences in pharmacokinetic parameters compared to adults.
Indication
For short-term symptomatic relief of sore throat in adults and children aged 12 years and over.
Contraindication
- Hypersensitivity to flurbiprofen or to any of the excipients of the drug.
- History of hypersensitivity reactions (e.g., bronchial asthma, bronchospasm, rhinitis, angioedema, or urticaria) after taking acetylsalicylic acid or other 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 related to previous NSAID therapy.
- Severe heart failure, severe kidney failure, or severe liver failure.
- The last trimester of pregnancy.
Interaction with other medicinal products and other types of interactions
The concomitant use of flurbiprofen with:
other NSAIDs, including selective cyclooxygenase-2 (COX-2) inhibitors: the simultaneous use of two or more NSAIDs should be avoided, as this increases the risk of side effects (especially gastrointestinal side effects such as ulcers and bleeding);
acetylsalicylic acid (in low doses), except in cases where low-dose aspirin (not higher than 75 mg per day) has been prescribed by a doctor, as this increases the risk of adverse reactions.
Flurbiprofen should be used with caution in combination with the following drugs:
Anticoagulants: NSAIDs may enhance the effect of anticoagulants such as warfarin;
antiplatelet agents: increased risk of gastrointestinal ulceration or bleeding;
Antihypertensives (diuretics, ACE inhibitors and angiotensin II antagonists): NSAIDs may reduce the effect of diuretics and other antihypertensive agents, as well as enhance nephrotoxicity caused by inhibition of cyclooxygenase, especially in patients with impaired renal function (patients should receive sufficient fluid intake);
alcohol: increases the risk of adverse reactions, especially bleeding in the gastrointestinal tract;
Cardiac glycosides: NSAIDs may exacerbate heart failure, reduce glomerular filtration rate and increase plasma glycoside levels. Monitoring of the patient's condition and, if necessary, dose adjustment is recommended;
cyclosporine: increased risk of nephrotoxicity;
corticosteroids: increase the risk of adverse reactions, especially of the gastrointestinal tract;
Lithium: possible increase in serum lithium levels. Monitoring of the patient's condition and, if necessary, dose adjustment is recommended;
Methotrexate: use of NSAIDs within 24 hours before or after the use of methotrexate may lead to an increase in its concentration or toxicity;
Mifepristone: NSAIDs should not be taken for 8-12 days after using mifepristone, as NSAIDs reduce its effectiveness;
Oral antidiabetic agents: blood glucose levels may change (blood glucose monitoring is recommended);
Phenytoin: an increase in phenytoin plasma levels is possible, therefore appropriate monitoring and, if necessary, dose adjustment are recommended;
Potassium-sparing diuretics: simultaneous use may cause hyperkalemia (it is recommended to monitor serum potassium levels);
Probenecid, sulfinpyrazone: medicines containing probenecid or sulfinpyrazone may cause a slow release of flurbiprofen;
Quinolone antibiotics: data from animal studies suggest that NSAIDs increase the risk of seizures associated with the use of quinolone antibiotics;
selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal ulceration or bleeding;
Tacrolimus: there may be an increased risk of nephrotoxicity with the simultaneous use of NSAIDs with tacrolimus;
Zidovudine: increased risk of hematological toxicity with concomitant use of NSAIDs with zidovudine.
Studies conducted to date have not revealed any interactions between flurbiprofen and tolbutamide and antacids.
Application features
Side effects can be minimized by using the lowest effective dose necessary to control symptoms for the shortest period of time.
Elderly patients: Elderly patients are at increased risk of adverse reactions to NSAIDs, especially gastrointestinal bleeding or perforation, which may be fatal.
Respiratory effects: Bronchospasm may occur in patients with or a history of bronchial asthma or allergic diseases. Flurbiprofen lozenges should be used with caution in such patients.
Systemic lupus erythematosus and mixed connective tissue disease: Patients with systemic lupus erythematosus and mixed connective tissue disease are at increased risk of aseptic meningitis. However, this effect is not usually seen with short-term, limited use of medications such as flurbiprofen lozenges.
Cardiac, renal and hepatic failure. NSAIDs have been reported to cause nephrotoxicity in various forms, including interstitial nephritis, nephrotic syndrome and renal failure, especially when used in combination with several analgesic drugs and in the case of long-term habitual use. The use of NSAIDs can lead to a dose-dependent decrease in prostaglandin production and may precipitate renal failure. Patients with renal insufficiency, cardiac insufficiency, hepatic dysfunction, patients taking diuretics and elderly patients are at greatest risk of this reaction. In such patients, renal function should be monitored. However, this effect is not usually observed with short-term limited use of drugs such as flurbiprofen lozenges.
Cardiovascular and cerebrovascular effects: Caution should be exercised (after consultation with a physician) when initiating treatment in patients with a history of high blood pressure and/or heart failure, as fluid retention, high blood pressure and oedema have been reported with NSAIDs.
Clinical trial and epidemiological data suggest that the use of some NSAIDs (especially at high doses and over a long period of time) increases the risk of arterial thrombotic events (e.g. myocardial infarction or stroke). There is insufficient evidence to exclude such a risk with the use of 5 lozenges per day.
Liver: Mild to moderate liver dysfunction.
Nervous system disorders: Headache caused by analgesics: with prolonged use of analgesics or if the recommendations are not followed, headache may occur, which should not be treated with increased doses of the drug. In such cases, NSAID treatment should be discontinued and the patient should seek medical attention.
Gastrointestinal effects. NSAIDs should be used with caution in patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's disease) as their condition may be aggravated. Gastrointestinal bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, regardless of the presence of warning symptoms or a history of serious gastrointestinal disorders. The risk increases with increasing NSAID doses, in patients with a history of ulcer disease, particularly 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. In these patients, treatment should be started at the lowest available dose. Also, in patients requiring concomitant use of low doses of acetylsalicylic acid or other drugs that may increase the risk of gastrointestinal events, combination therapy with protective drugs (e.g. misoprostol or proton pump inhibitors) is recommended. Patients should consult a doctor 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 drugs that increase the risk of ulceration or bleeding, in particular oral corticosteroids, anticoagulants such as warfarin, SSRIs or antiplatelet agents such as acetylsalicylic acid. In the event of gastrointestinal bleeding or ulceration in patients receiving flurbiprofen, treatment with the drug should be discontinued.
Skin and subcutaneous tissue disorders: Very rarely, severe skin reactions, which can be fatal, including exfoliative dermatitis, Stevens-Johnson syndrome and toxic epidermal necrolysis, may occur in association with the use of NSAIDs. Flurbiprofen lozenges should be discontinued at the first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity.
Infections: Since there have been isolated cases of exacerbation of infectious inflammations (e.g. development of necrotizing fasciitis) observed in temporal association with the use of systemic NSAIDs, the patient is advised to consult a doctor immediately if signs of bacterial infection or deterioration of the condition occur during treatment with flurbiprofen lozenges. The need for anti-infective antibiotic therapy should be considered. Treatment should be reviewed if symptoms worsen or new symptoms appear. Treatment should be discontinued if irritation of the oral cavity occurs.
This medicinal product contains isomalt (E 953) and maltitol (E 965). Patients with rare hereditary problems of fructose intolerance should not take this medicinal product. May have a mild laxative effect. Caloric value 2.3 kcal/g of maltitol and isomalt.
The medicine also contains the dyes sunset yellow FCF (E 110) and cochineal red A (E 124), which may cause allergic reactions.
Celista® contains potassium compounds, which should be taken into account in patients with impaired or reduced kidney function or in patients on a potassium-controlled diet.
Use during pregnancy or breastfeeding.
Pregnancy.
Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryo/foetal development. Epidemiological data indicate an increased risk of miscarriage and congenital heart defects and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk of heart defects increased from less than 1% to approximately 1.5%. The risk is thought to increase with increasing dose and duration of treatment. In animals, use of a prostaglandin synthesis inhibitor during organogenesis has been shown to increase the incidence of various malformations, particularly of the cardiovascular system. Flurbiprofen should not be used during the first two trimesters of pregnancy unless clearly necessary. If flurbiprofen is used by a woman attempting to conceive, or during the first and second trimesters of pregnancy, the lowest possible dose should be used for the shortest possible period of time.
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, accompanied by oligohydramnios.
for the mother at the end of pregnancy and the newborn:
- increased bleeding time, antiplatelet effect, which can develop even at very low doses;
- suppression of uterine contractions, leading to a delay or increase in the duration of labor.
Therefore, flurbiprofen is contraindicated during the third trimester of pregnancy.
Breast-feeding.
In some studies, flurbiprofen has been found in breast milk at very low concentrations. It is unlikely that it would have any adverse effects on the breastfed infant. However, because of the possible adverse effects of NSAIDs on the breastfed infant, the drug is not recommended for use in breastfeeding women.
Fertility.
There is some evidence that drugs that inhibit prostaglandin/cyclooxygenase synthesis may impair female fertility due to effects on ovulation. This effect is reversible upon discontinuation of the drug.
The ability to influence the reaction speed when driving vehicles or other mechanisms.
Studies on the ability to influence the reaction rate when driving vehicles or other mechanisms have not been conducted.
Method of administration and doses
Suck the lollipops until completely dissolved.
Dosage.
Use the lowest effective dose for the shortest duration necessary to relieve symptoms. If symptoms persist, worsen, or last more than 3 days, consult a doctor.
It is not recommended to use the medicine for more than 3 days.
Adults and adolescents (aged 12 years and over).
Take 1 lozenge every 3–6 hours until pain is relieved. Maximum daily dose is 5 lozenges.
Elderly patients.
Due to limited clinical experience, no general dose recommendations can be given at this time. Elderly patients are at increased risk of severe adverse reactions (see section 4.4).
Liver failure.
No dose reduction is required in patients with mild to moderate hepatic impairment. Flurbiprofen is contraindicated in patients with severe hepatic impairment (see section 4.3).
Kidney failure.
No dose reduction is required in patients with mild to moderate renal impairment. Flurbiprofen is contraindicated in patients with severe renal impairment (see section 4.3).
Children.
Do not use in children under 12 years of age.
Overdose
Treatment. Treatment should be symptomatic and supportive, and include maintaining a patent airway and monitoring cardiac function and vital signs until the patient's condition is normal. Oral administration of activated charcoal within 1 hour of a potentially toxic dose or gastric lavage is recommended. Frequent or prolonged muscle spasms should be treated with intravenous diazepam or lorazepam. Bronchodilators should be used in the presence of bronchial asthma. There is no specific antidote to flurbiprofen.
Side effects
There have been reports of hypersensitivity reactions to NSAIDs, which may include:
- nonspecific allergic reactions and anaphylaxis;
- airway reactivity, for example: bronchial asthma, exacerbation of bronchial asthma, bronchospasm, shortness of breath;
- various skin reactions, for example: itching, urticaria, angioedema, less often - exfoliative and bullous dermatoses (including epidermal necrolysis and erythema multiforme).
Events such as oedema, hypertension and heart failure have been reported in association with NSAID treatment. Clinical trials and epidemiological data suggest that the use of some NSAIDs (particularly at high doses and in long-term treatment) may be associated with a slightly increased risk of arterial thrombotic events (e.g. myocardial infarction or stroke). There is insufficient evidence to exclude such a risk with flurbiprofen lozenges 8.75 mg.
The following adverse reactions have been observed with short-term use of flurbiprofen at non-prescription doses.
All adverse reactions are listed by system organ class and frequency: very common (≥ 1/10), common (≥ 1/100 - < 1/10), uncommon (≥ 1/1000 - < 1/100), rare (≥ 1/10000 - < 1/1000), rare (< 1/10000), frequency unknown (cannot be estimated from the available data).
On the part of the respiratory system, thoracic organs and mediastinum: often - throat irritation; infrequently - exacerbation of bronchial asthma and bronchospasm, shortness of breath, wheezing, blisters in the oropharynx, pharyngeal hypoesthesia.
Gastrointestinal: often - diarrhea, mouth ulcers, nausea, oral pain, oral paresthesia, oropharyngeal pain, oral discomfort (feeling of warmth, burning or tingling in the mouth); infrequently - bloating, abdominal pain, constipation, dry mouth, dyspepsia, flatulence, glossodynia, dysgeusia, oral dysesthesia, vomiting.
Hepatobiliary disorders: not known – hepatitis.
From the nervous system: often - dizziness, headache, paresthesia; infrequently - drowsiness.
On the part of the psyche: infrequently - insomnia.
Cardiovascular system: unknown - edema, hypertension and heart failure.
Blood and lymphatic system disorders: not known – anemia, thrombocytopenia.
On the part of the immune system: rarely - anaphylactic reactions.
Skin and subcutaneous tissue disorders: uncommon - various skin rashes, itching; unknown - severe forms of skin reactions, such as bullous-type reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis.
General disorders: uncommon - pyrexia, pain.
If adverse reactions occur, treatment should be discontinued and a doctor should be consulted.
Reporting of suspected adverse reactions.
Reporting suspected adverse reactions after the marketing authorisation of a medicinal product is an important procedure. It allows for continued monitoring of the benefit-risk balance of the medicinal product in question. Healthcare professionals should report any suspected adverse reactions via the national reporting system.
Expiration date
2 years.
The expiration date determines the use of the medicine until the last day of the specified month.
Storage conditions
Store in the original packaging at a temperature not exceeding 30 ° C. Keep out of the reach of children.
Packaging
12 lollipops in a blister; 1 blister in a pack.
Vacation category
Without a prescription.
Producer
LOZI'S PHARMACEUTICALS S.L.
Location of the manufacturer and address of its place of business.
Spain, 31795, Navarra, Lecaroz, Campus Empresarial.
Applicant
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the applicant.
Ukraine, 02093, Kyiv, Boryspilska St., 13.
