Sertophen

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SERTOFEN (SERTOFEN)

Composition:

Active substance: dexketoprofen;

One film-coated tablet contains dexketoprofen (as trometamol) 25 mg;

Excipients: microcrystalline cellulose (PH 101), microcrystalline cellulose (PH 102), corn starch, sodium starch glycolate (type A), glyceryl distearate; film coating: Opadry white II 85F18422 (polyvinyl alcohol, titanium dioxide (E 171), macrogol, talc).

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: white, round, biconvex film-coated tablets with a dividing line on both sides.

Pharmacotherapeutic group.

Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives.

ATC code M01A E17.

Pharmacological properties.

Pharmacodynamics.

Dexketoprofen trometamol is a propionic acid salt that exerts analgesic, anti-inflammatory, and antipyretic effects and belongs to the class of nonsteroidal anti-inflammatory drugs (NSAIDs).

Its mechanism of action is based on reducing the synthesis of prostaglandins by inhibiting cyclooxygenase. Specifically, the conversion of arachidonic acid into cyclic endoperoxides PGG2 and PGH2 is inhibited, from which prostaglandins PGE1, PGE2, PGF2α, PGD2, as well as prostacyclin PGI2 and thromboxanes TxА2 and TxВ2 are formed. In addition, the inhibition of prostaglandin synthesis may affect other mediators of inflammation such as kinins, which may also indirectly influence the primary action of dexketoprofen.

Inhibitory effects on COX-1 and COX-2 isoenzymes have been demonstrated in animals and humans.

Clinical studies have shown that dexketoprofen provides effective analgesia, which develops within 30 minutes after administration and lasts 4–6 hours.

Pharmacokinetics.

Absorption. After oral administration, the maximum plasma concentration (Cmax) of dexketoprofen is reached on average within 30 minutes (15–60 minutes). When administered with food, the area under the curve (AUC) remains unchanged, however, the Cmax value decreases and the absorption rate slows down (tmax increases).

Distribution. The distribution time and elimination half-life of dexketoprofen are 0.35 and 1.65 hours, respectively. Due to its high degree of plasma protein binding (99%), the mean volume of distribution is less than 0.25 L/kg. Multiple-dose pharmacokinetic studies have shown that after the last dose, the AUC values were not higher than those after a single dose, indicating absence of accumulation.

Metabolism and elimination. After administration of dexketoprofen, only the S-(+)-enantiomer is detected in urine, demonstrating the absence of inversion into the R-(+)-enantiomer in the human body. Elimination occurs mainly via glucuronidation followed by renal excretion.

Clinical characteristics.

Indications.

Symptomatic treatment of mild to moderate pain, for example: musculoskeletal pain, painful menstruation (dysmenorrhea), dental pain.

Contraindications.

• Hypersensitivity to dexketoprofen, other nonsteroidal anti-inflammatory drugs (NSAIDs), or to any component of the medicinal product.
• Asthmatic attacks, bronchospasm, acute rhinitis, or development of nasal polyps, urticaria, or angioedema following the use of drugs with a similar mechanism of action, such as acetylsalicylic acid and other NSAIDs.
• Known phototoxic or photoallergic reactions during treatment with ketoprofen or fibrates.
• Active phase of peptic ulcer disease / gastrointestinal bleeding, recurrent peptic ulcer disease / gastrointestinal bleeding in medical history.
• History of gastrointestinal bleeding or perforation associated with the use of NSAIDs.
• Other active bleeding or increased bleeding tendency.
• Hemorrhagic diathesis and other coagulation disorders.
• Chronic dyspepsia.
• Crohn’s disease or ulcerative colitis.
• Severe heart failure.
• Moderate to severe renal impairment (creatinine clearance < 59 ml/min).
• Severe hepatic impairment (Child–Pugh score 10–15 points).
• Severe dehydration (caused by vomiting, diarrhea, or insufficient fluid intake).
• Third trimester of pregnancy (see section "Use during pregnancy or breastfeeding").
• Breastfeeding period (see section "Use during pregnancy or breastfeeding").

Interaction with other medicinal products and other types of interactions.

The drug interactions listed below are generally characteristic of the NSAID class.

Combinations with dexketoprofen not recommended for use.

• Other NSAIDs (including selective cyclooxygenase-2 inhibitors and high-dose salicylates ≥ 3 g/day): increased risk of peptic ulcers and gastrointestinal bleeding due to synergistic effects.
• Anticoagulants (e.g., warfarin): enhanced anticoagulant effect (see section "Special precautions for use") due to high plasma protein binding of dexketoprofen, as well as due to inhibition of platelet function and damage to the gastric and duodenal mucosa. If concomitant use is necessary, it should be performed under medical supervision with careful monitoring of relevant laboratory parameters.
• Heparin: increased risk of bleeding (due to inhibition of platelet function and damage to the gastric and duoden游戏副本

Special precautions for use.

The medicinal product should be used with caution in patients with a history of allergic diseases.

Adverse reactions to the medicinal product can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms (see section "Dosage and administration").

Concomitant use of the medicinal product with other NSAIDs, including selective cyclooxygenase-2 inhibitors, should be avoided.

Gastrointestinal effects.

When using NSAID-class medicinal products, peptic ulcers, with or without perforation, and gastrointestinal bleeding (including fatal outcomes) may develop in the gastrointestinal tract. These adverse events may occur at any time during treatment, with or without preceding symptoms, and are independent of the presence of severe gastrointestinal disorders in the patient's history. If gastrointestinal bleeding or peptic ulcer develops during treatment with the medicinal product, therapy should be discontinued immediately.

The risk of developing the aforementioned adverse events increases proportionally with higher NSAID doses and in patients with a history of gastric or duodenal ulcer, especially complicated by bleeding or perforation (see section "Contraindications"), as well as in elderly patients. During treatment with the medicinal product, physicians should closely monitor patients due to the possibility of gastrointestinal bleeding.

In elderly individuals, the frequency of adverse reactions to NSAIDs is increased, particularly gastrointestinal bleeding and perforations, which may be fatal (see section "Dosage and administration"). These patients should initiate treatment with the lowest effective dose.

Before starting treatment with dexketoprofen trometamol in patients with a history of esophagitis, gastritis, and/or peptic ulcer disease, as with other NSAIDs, it should be ensured that these conditions are in remission.

Patients with existing gastrointestinal symptoms or gastrointestinal disorders in their history should be monitored for the development of gastrointestinal complications, particularly gastrointestinal bleeding.

The medicinal product should be used with caution in patients with a history of gastrointestinal disorders (ulcerative colitis, Crohn's disease), as there is a risk of exacerbation (see section "Adverse reactions").

To reduce the risk of gastrointestinal adverse reactions, physicians may prescribe protective agents for the gastrointestinal mucosa (misoprostol, proton pump inhibitors). This also applies to patients requiring concomitant low-dose acetylsalicylic acid or other agents that increase the risk of gastrointestinal complications (see section "Interaction with other medicinal products and other forms of interaction").

Patients should be informed that they must report any abdominal discomfort (particularly gastrointestinal bleeding), especially at the beginning of treatment, to their physician.

Caution is required in patients receiving concomitant medications that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents (acetylsalicylic acid) (see section "Interaction with other medicinal products and other forms of interaction").

Renal function effects.

The medicinal product should be used with caution in patients with impaired renal function, as NSAID use may lead to worsening renal function, fluid retention, and edema.

Caution should be exercised when administering the medicinal product to patients taking diuretics or prone to hypovolemia, as there is an increased risk of nephrotoxic effects of dexketoprofen.

During treatment, adequate fluid intake should be ensured to prevent dehydration and possibly associated increased nephrotoxicity.

Dexketoprofen may increase plasma levels of blood urea nitrogen and creatinine. Similar to other prostaglandin inhibitors, dexketoprofen use may be associated with renal adverse reactions, which can lead to glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome, and acute renal failure. Elderly patients are more susceptible to renal disorders (see section "Dosage and administration").

Hepatic function effects.

The medicinal product should be used with caution in patients with impaired liver function (see section "Dosage and administration").

Dexketoprofen may cause transient increases in certain liver function parameters, as well as significant increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. If significant elevations in liver enzymes occur, the use of the medicinal product should be discontinued.

Elderly patients are more susceptible to liver disorders (see section "Dosage and administration").

Cardiovascular system effects.

Patients with arterial hypertension and/or mild to moderate heart failure require monitoring and medical advice. The medicinal product should be used with particular caution in patients with a history of heart disease, particularly previous episodes of heart failure, as the risk of developing heart failure increases during dexketoprofen treatment: fluid retention and edema have been observed during NSAID therapy.

Clinical studies and epidemiological data suggest a slightly increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke) during treatment with certain NSAIDs (especially at high doses and over prolonged periods). Data to exclude such risk with dexketoprofen use are insufficient.

Therefore, in cases of uncontrolled arterial hypertension, congestive heart failure, ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease, dexketoprofen should be prescribed only after careful patient assessment. Similarly careful evaluation is required before initiating long-term treatment in patients with risk factors for cardiovascular disease (such as arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

All non-selective NSAIDs can reduce platelet aggregation and prolong bleeding time due to inhibition of prostaglandin synthesis. The medicinal product is not recommended for patients taking agents affecting hemostasis, such as warfarin, other coumarin derivatives, or heparins (see section "Interaction with other medicinal products and other forms of interaction").

Most cardiovascular function disturbances occur in elderly patients (see section "Dosage and administration").

Skin effects.

Very rarely, severe skin reactions (some fatal), including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported during NSAID use. Adverse reactions most commonly develop early in treatment; in most cases, within the first month of therapy. At the first signs of skin rash, mucosal lesions, or other signs of hypersensitivity, the use of the medicinal product should be discontinued.

Masking symptoms of underlying infections.

Dexketoprofen may mask symptoms of infectious diseases, potentially delaying appropriate treatment and thereby complicating disease progression. This has been observed in bacterial community-acquired pneumonia and bacterial complications of varicella. When using the medicinal product to relieve pain associated with infection, monitoring of the infectious disease is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Other information.

The medicinal product should be used with particular caution in patients with congenital porphyrin metabolism disorders (e.g., acute intermittent porphyria), dehydrated patients, and immediately after major surgery.

If prolonged use of the medicinal product is necessary, regular monitoring of kidney and liver function and blood tests should be performed.

Very rarely, severe hypersensitivity reactions (e.g., anaphylactic shock) may occur during dexketoprofen use. If such reactions occur, the use of the medicinal product should be discontinued immediately. Depending on symptoms, appropriate treatment should be initiated.

Patients with asthma and chronic rhinitis/sinusitis and/or nasal polyps have an increased risk of allergic reactions to acetylsalicylic acid and other NSAIDs. Dexketoprofen use may cause bronchospasm, particularly in patients allergic to acetylsalicylic acid and other NSAIDs (see section "Contraindications").

In special cases, severe infectious complications of the skin and soft tissues may develop during varicella. Currently, the role of NSAIDs in worsening varicella-related infections cannot be excluded. Therefore, the use of the medicinal product should be avoided in varicella.

Dexketoprofen should be used with caution in patients with hematological disorders, systemic lupus erythematosus, and mixed connective tissue disease.

The medicinal product contains less than 1 mmol of sodium (23 mg) per tablet, i.e., practically sodium-free.

Pediatric patients.

Safety of use in children and adolescents has not been established.

Use during pregnancy or breastfeeding.

The medicinal product is contraindicated during the third trimester of pregnancy and during breastfeeding (see section "Contraindications").

Pregnancy. Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or embryonic and fetal development. According to epidemiological studies, the use of agents that inhibit prostaglandin synthesis in early pregnancy increases the risk of miscarriage, cardiac malformations, and gastroschisis. The absolute risk of cardiovascular malformations was increased by at least 1%, sometimes up to 1.5%. The risk is considered to increase with higher doses and longer duration of therapy. In animal studies, administration of prostaglandin synthesis inhibitors resulted in increased miscarriage rates before and after implantation and increased embryonic and fetal mortality. Furthermore, in animals treated with prostaglandin synthesis inhibitors during organogenesis, the frequency of fetal developmental abnormalities, including cardiovascular anomalies, increased. However, animal studies with dexketoprofen did not reveal toxic effects on reproductive organs.

Use of dexketoprofen from the 20th week of pregnancy may cause oligohydramnios due to fetal renal dysfunction. This disorder may occur soon after starting treatment and is usually reversible upon discontinuation of the medicinal product. Additionally, reports of arterial duct constriction after treatment in the second trimester have been documented, which resolved in most cases after treatment cessation. The medicinal product may be used during the first and second trimesters of pregnancy only if absolutely necessary. When prescribing dexketoprofen during the first and second trimesters of pregnancy, the lowest possible effective dose should be used for the shortest possible duration.

Prenatal monitoring for oligohydramnios and arterial duct constriction may be advisable if exposure to dexketoprofen occurs for several days starting from the 20th gestational week. The use of the medicinal product should be discontinued if oligohydramnios is detected.

During the third trimester of pregnancy, use of prostaglandin synthesis inhibitors may lead to the following fetal abnormalities:

• Cardiovascular toxicity, e.g., premature closure of the arterial duct and pulmonary hypertension;
• Renal dysfunction, which may progress and lead to renal failure with development of oligohydramnios (see above).

In women near term and in neonates, the following effects may occur:

• Prolonged bleeding time due to inhibition of platelet aggregation, even at low doses;
• Inhibition of uterine contractility, leading to delayed labor and prolonged delivery.

The medicinal product is contraindicated during the third trimester of pregnancy.

Breastfeeding period. There are no data on the passage of dexketoprofen into breast milk. The medicinal product is contraindicated during breastfeeding (see section "Contraindications").

Fertility. Like other NSAIDs, dexketoprofen may affect female fertility and therefore is not recommended for women planning pregnancy. Consideration should be given to discontinuing the medicinal product in women unable to conceive and in women undergoing infertility evaluation. When prescribing dexketoprofen to women planning pregnancy, the lowest possible effective dose should be used for the shortest possible duration.

Ability to influence reaction speed when driving or operating machinery.

During dexketoprofen use, dizziness, visual disturbances, or somnolence may occur, which may affect the ability to drive or operate machinery.

Method of Administration and Dosage

The medicinal product is intended for oral administration. Tablets should be swallowed with an adequate amount of liquid (e.g., a glass of water). Concomitant food intake reduces the rate of absorption of the active substance; therefore, in case of acute pain, the medicinal product is recommended to be taken at least 30 minutes before a meal.

Adverse reactions to the medicinal product can be minimized by using the lowest effective doses for the shortest duration necessary to relieve symptoms (see section "Special Instructions").

The medicinal product is not intended for long-term therapy; treatment continues only as long as symptoms are present.

Adults.

Depending on the type and intensity of pain, the recommended dose of the medicinal product is 12.5 mg (½ film-coated tablet) every 4–6 hours or 25 mg (1 film-coated tablet) every 8 hours. The daily dose should not exceed 75 mg.

Elderly Patients.

For these patients, treatment should be initiated with the lowest doses (daily dose of 50 mg). If the medicinal product is well tolerated, the dose may be increased to the usual level.

Patients with Hepatic Impairment.

For patients with mild to moderate hepatic impairment, treatment should be initiated with the lowest doses (daily dose of 50 mg) under strict medical supervision. The medicinal product is contraindicated in patients with severe hepatic insufficiency (see section "Contraindications").

Patients with Renal Impairment.

For patients with mild renal impairment (creatinine clearance 60–89 mL/min) (see section "Special Instructions"), treatment should be initiated with the lowest doses (daily dose of 50 mg). The medicinal product is contraindicated in patients with moderate or severe renal impairment (creatinine clearance < 59 mL/min) (see section "Contraindications").

Children.

The safety and efficacy of dexketoprofen in children (under 18 years of age) have not been established. The medicinal product should not be used in this patient population.

Overdose.

Symptoms.

The clinical picture of overdose is unknown. Analogous medicinal products may cause gastrointestinal disturbances (vomiting, anorexia, abdominal pain) and nervous system effects (drowsiness, vertigo, disorientation, headache).

Treatment.

In case of overdose, symptomatic therapy should be initiated immediately according to the patient's clinical condition. If an adult or child has ingested a dose exceeding 5 mg/kg body weight, an adsorbent should be administered within 1 hour. Hemodialysis may be used to eliminate dexketoprofen.

Adverse Reactions

The adverse reactions listed below were observed during clinical trials and post-marketing use of dexketoprofen. Adverse reactions at least possibly related to dexketoprofen are categorized by organ systems and frequency of occurrence: common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare, including isolated cases (< 1/10000).

Blood and lymphatic system disorders:

very rare — neutropenia, thrombocytopenia.

Immune system disorders:

rare — laryngeal edema; very rare — anaphylactic reactions, including anaphylactic shock.

Metabolism and nutrition disorders:

rare — loss of appetite.

Psychiatric disorders:

uncommon — insomnia, restlessness.

Nervous system disorders:

uncommon — headache, dizziness, somnolence; rare — paresthesia, syncope.

Eye disorders:

very rare — blurred vision.

Ear and labyrinth disorders:

uncommon — vertigo; very rare — tinnitus.

Cardiac disorders:

uncommon — palpitations; very rare — tachycardia.

Vascular disorders:

uncommon — flushing; rare — arterial hypertension; very rare — arterial hypotension.

Respiratory, thoracic and mediastinal disorders:

rare — bradypnea; very rare — bronchospasm, dyspnea.

Gastrointestinal disorders:

common — nausea and/or vomiting, abdominal pain, diarrhea, dyspepsia; uncommon — gastritis, constipation, dry mouth, flatulence; rare — peptic ulcer, ulcer bleeding or perforation (see section "Special precautions"); very rare — pancreatitis.

Hepatobiliary disorders:

rare — hepatocellular disorders.

Skin and subcutaneous tissue disorders:

uncommon — rash; rare — urticaria, acne, increased sweating; very rare — Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome), facial angioedema, photosensitivity, pruritus.

Musculoskeletal and connective tissue disorders:

rare — back pain.

Renal and urinary disorders:

rare — acute renal failure, polyuria; very rare — nephritis or nephrotic syndrome.

Reproductive system and breast disorders:

rare — menstrual cycle disturbances, prostate gland function disorders.

General disorders:

uncommon — fatigue, pain, asthenia, muscle stiffness, malaise; rare — peripheral edema.

Laboratory findings:

rare — liver function test abnormalities.

The most commonly observed adverse reactions are gastrointestinal. Peptic ulceration, perforation, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients (see section "Special precautions"). According to available data, during dexketoprofen use, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, hematemesis, ulcerative stomatitis, exacerbation of colitis, Crohn's disease (see section "Special precautions") may occur. Gastritis is less frequently observed.

Edema, arterial hypertension, and heart failure have been reported during use of NSAIDs.

As with other NSAIDs, aseptic meningitis (occurring mainly in patients with systemic lupus erythematosus or mixed connective tissue disease) and blood disorders (purpura, hypoplastic and hemolytic anemia, rarely agranulocytosis and bone marrow hypoplasia) are possible.

Bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), are possible.

According to clinical studies and epidemiological data, use of certain NSAIDs, particularly at high doses and for prolonged periods, may be associated with a small increased risk of arterial thrombotic events (e.g., myocardial infarction or stroke) (see section "Special precautions").

Reporting suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is important. It allows ongoing monitoring of the benefit-risk balance of the medicine. Healthcare professionals, pharmacists, patients, or their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life.

5 years.

Storage conditions.

Store at temperatures not exceeding 25 °C in the original packaging and keep out of reach of children.

Packaging.

10 tablets in a blister; 1 or 2 blisters in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

UORLD MEDICIN ILAC SAN. VE TIC. A.S., Turkey /
WORLD MEDICINE ILAC SAN. VE TIC. A.S., Turkey.

Manufacturer's address.

15 Temmuz Mahallesi Cami Yolu Caddesi No:50 Gunesli Bagcilar/Istanbul, Turkey.

Marketing Authorization Holder.

WORLD MEDICINE, LLC, Ukraine.