Dexatiphen-n

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DEXATIFEN-N (DEXATIFEN-N)

Composition:

Active substance: dexketoprofen;

1 ml of solution contains 25 mg of dexketoprofen (as dexketoprofen trometamol);

Excipients: ethanol 96%, sodium chloride, sodium hydroxide, water for injections.

Pharmaceutical form. Solution for injection.

Main physicochemical properties: clear, colorless liquid.

Pharmacotherapeutic group. Non-steroidal anti-inflammatory and antirheumatic agents. Propionic acid derivatives. Dexketoprofen. ATC code M01A E17.

Pharmacological Properties

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

Mechanism of Action

The mechanism of action of NSAIDs is based on reducing the synthesis of prostaglandins by inhibiting cyclooxygenase activity. 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, inhibition of prostaglandin synthesis may affect other mediators of inflammation such as kinins, which may also indirectly influence the primary action of the drug.

Pharmacodynamics

Inhibitory effects of dexketoprofen on the activity of cyclooxygenase-1 and cyclooxygenase-2 have been demonstrated in laboratory animals and in humans.

Clinical Efficacy and Safety

Clinical studies in various types of pain have demonstrated that dexketoprofen exerts pronounced analgesic effects. The analgesic effect of dexketoprofen administered intramuscularly or intravenously to patients with moderate to severe pain intensity has been studied in various pain conditions associated with surgical interventions (orthopedic and gynecological surgeries, abdominal surgeries), as well as musculoskeletal pain (acute low back pain) and renal colic. In these studies, the analgesic effect of the drug began rapidly and reached its maximum within the first 45 minutes. The duration of analgesic action after administration of 50 mg dexketoprofen is typically 8 hours. Clinical studies have shown that the use of dexketoprofen allows a significant reduction in opioid dosage when used concomitantly to manage postoperative pain.

When patients receiving morphine via a patient-controlled analgesia device for postoperative pain management were also administered dexketoprofen, they required significantly less morphine (by 30–45%) compared to patients receiving placebo.

Pharmacokinetics

Absorption

After intramuscular administration of dexketoprofen in humans, maximum concentration is reached approximately within 20 minutes (10–45 minutes). It has been demonstrated that after single intramuscular or intravenous administration of 25–50 mg of the drug, the area under the concentration-time curve (AUC) is proportional to the dose.

Distribution

Similar to other drugs with a high degree of plasma protein binding (99%), the volume of distribution of dexketoprofen averages 0.25 L/kg. The distribution half-life is approximately 0.35 hours, and the elimination half-life is 1–2.7 hours.

Multiple-dose pharmacokinetic studies have shown that Cmax and AUC after the last intramuscular or intravenous administration do not differ from those after single administration, indicating absence of drug accumulation.

Biotransformation and Elimination

Metabolism of dexketoprofen occurs mainly via conjugation with glucuronic acid followed by renal excretion. After administration, only the S-(+) optical isomer is detected in urine, indicating absence of in vivo conversion of the drug to the R-(-) optical isomer in humans.

Elderly Patients

After administration of single and multiple doses, the extent of drug exposure in elderly healthy volunteers (aged 65 years and older) participating in the study was significantly higher (up to 55%) compared to younger volunteers; however, no statistically significant differences were observed in maximum concentration or time to reach it. The mean elimination half-life was prolonged (by up to 48%), and total clearance was reduced.

Preclinical Safety Data

Standard preclinical studies—evaluating pharmacological safety, genotoxicity, and immunopharmacology—did not reveal any special hazard for humans. Chronic toxicity studies in animals identified the no-observed-adverse-effect level (NOAEL), which was 2 times higher than the recommended human dose. When higher doses were administered to monkeys, the main adverse reactions were fecal blood, reduced body weight gain, and, at the highest dose, gastrointestinal lesions such as erosions. These effects occurred at doses where drug exposure was 14–18 times higher than at the maximum recommended human dose. Carcinogenicity studies in animals have not been conducted.

Like all NSAIDs, dexketoprofen may lead to embryonic or fetal death in animals due to a direct effect on development or indirectly via maternal gastrointestinal tract injury.

Clinical characteristics.

Indications.

Symptomatic treatment of moderate to severe acute pain when oral administration of the drug is inappropriate, e.g., in postoperative pain, renal colic, and lower back pain.

Contraindications.

• Hypersensitivity to dexketoprofen, to any other nonsteroidal anti-inflammatory drug (NSAID), or to excipients of the drug;
• patients in whom administration of substances with similar action, e.g., acetylsalicylic acid or other NSAIDs, triggers attacks of bronchial asthma, bronchospasm, acute rhinitis, nasal polyps, urticaria, or angioneurotic edema;
• if photoallergic or phototoxic reactions occurred during treatment with ketoprofen or fibrates;
• gastrointestinal bleeding or perforation in medical history associated with NSAID therapy;
• active peptic ulcer/gastrointestinal bleeding or history of gastrointestinal bleeding, ulcers, or perforations;
• chronic dyspepsia;
• active gastrointestinal bleeding or increased bleeding tendency;
• Crohn’s disease or ulcerative colitis;
• severe heart failure;
• moderate or severe renal impairment (creatinine clearance ≤59 ml/min);
• severe hepatic impairment (Child-Pugh score 10–15 points);
• hemorrhagic diathesis and other coagulation disorders;
• in cases of severe dehydration (due to vomiting, diarrhea, or insufficient fluid intake);
• third trimester of pregnancy and breastfeeding period.

Due to the presence of ethanol in the medicinal product, dexketoprofen is contraindicated for neuraxial (intrathecal or epidural) administration.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of the following agents with NSAIDs is not recommended:

• other NSAIDs, including salicylates in high doses (≥ 3 g/day). Concurrent use of multiple NSAIDs increases the risk of gastrointestinal ulceration and gastrointestinal bleeding due to their mutually enhancing effects;
• anticoagulants: NSAIDs enhance the effect of anticoagulants, e.g., warfarin, due to the high degree of plasma protein binding of dexketoprofen, as well as inhibition of platelet function and damage to the gastric and duodenal mucosa. If concomitant use is necessary, it should be performed under strict medical supervision with monitoring of appropriate laboratory parameters;
• heparins: increased risk of bleeding (due to inhibition of platelet function and damage to the gastric and duodenal mucosa). If concomitant use is necessary, it should be performed under strict medical supervision with monitoring of appropriate laboratory parameters;
• corticosteroids: increased risk of gastrointestinal ulceration and gastrointestinal bleeding;
• lithium (reports exist for several NSAIDs): NSAIDs increase lithium blood levels, potentially leading to toxicity (reduced renal excretion of lithium); therefore, lithium blood levels must be monitored at the start of dexketoprofen therapy, during dose adjustments, or upon discontinuation;
• high-dose methotrexate (at least 15 mg per week): due to reduced renal clearance of methotrexate under NSAID therapy, its overall negative effect on the blood system is enhanced;
• hydantoin derivatives and sulfonamides: possible increase in toxicity of these substances.

Concomitant use of the following agents with NSAIDs requires caution:

• diuretics, angiotensin-converting enzyme (ACE) inhibitors, aminoglycoside antibiotics, and angiotensin II receptor antagonists: dexketoprofen may reduce the efficacy of diuretics and other antihypertensive agents. In some patients with impaired renal function (e.g., dehydration or elderly patients), concomitant use of cyclooxygenase inhibitors with ACE inhibitors, angiotensin II receptor antagonists, or aminoglycoside antibiotics may worsen renal function, which is usually reversible. When using dexketoprofen with any diuretic, ensure the patient is not dehydrated and monitor renal function at the beginning of treatment;
• low-dose methotrexate (less than 15 mg per week): due to reduced renal clearance of methotrexate under NSAID therapy, its overall negative effect on the blood system is enhanced. During the first weeks of concomitant use, weekly blood tests are required. Treatment should be closely monitored in patients with even mild renal impairment and in elderly patients;
• pentoxifylline: risk of bleeding. Monitoring should be intensified, and bleeding time should be checked more frequently;
• zidovudine: risk of increased toxic effect on erythrocytes due to effects on reticulocytes, leading to severe anemia after 1 week of NSAID use. Blood tests and reticulocyte counts should be performed 1–2 weeks after starting NSAID therapy;
• sulfonylurea preparations: NSAIDs can enhance the hypoglycemic effect of these agents by displacing them from plasma protein binding sites.

Potential interactions should be considered when using the following agents:

• beta-blockers: NSAIDs may reduce their antihypertensive effect due to inhibition of prostaglandin synthesis;
• cyclosporine and tacrolimus: possible increase in nephrotoxicity due to NSAID effects on renal prostaglandins; renal function should be monitored during combination therapy;
• thrombolytic agents: increased risk of bleeding;
• antiplatelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding;
• probenecid: possible increase in dexketoprofen plasma concentration, likely due to inhibition of renal tubular secretion and glucuronic acid conjugation of the drug, requiring dose adjustment of dexketoprofen;
• cardiac glycosides: NSAIDs may increase glycoside plasma concentrations;
• mifepristone: theoretically, there is a risk of altered mifepristone efficacy under the influence of prostaglandin synthetase inhibitors. Limited data suggest that concomitant administration of NSAIDs on the same day as prostaglandin does not adversely affect mifepristone or prostaglandin efficacy regarding cervical ripening or contractility, nor does it reduce the clinical efficacy of drugs for medical termination of pregnancy;
• quinolone antibiotics: animal studies indicate that high-dose quinolone derivatives in combination with NSAIDs increase the risk of seizures;
• tenofovir: concomitant use with NSAIDs may increase blood urea nitrogen and creatinine levels; therefore, renal function should be monitored to assess potential effects of combined use;
• deferasirox: concomitant use with NSAIDs may increase the risk of gastrointestinal toxicity; careful patient monitoring is required when using this medicinal product with deferasirox;
• pemetrexed: concomitant use with NSAIDs may reduce pemetrexed elimination; therefore, particular caution is required when using NSAIDs at high doses. Patients with mild to moderate renal impairment (creatinine clearance 45–79 ml/min) should avoid NSAID use for two days before and two days after pemetrexed administration.

Special precautions for use.

Dexketoprofen should be used with caution in patients with a history of allergic conditions. Avoid using dexketoprofen in combination with other NSAIDs, including selective cyclooxygenase-2 inhibitors. Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to relieve symptoms.

Gastrointestinal safety

Gastrointestinal bleeding, ulceration, or perforation, in some cases fatal, have been observed with all NSAIDs at various stages of treatment, regardless of the presence of prodromal symptoms or a history of serious gastrointestinal disorders. If gastrointestinal bleeding develops, the drug should be discontinued. The risk of gastrointestinal bleeding, ulceration, or perforation increases with higher NSAID doses, in patients with a history of peptic ulcer, particularly if complicated by bleeding or perforation, and in elderly patients.

Elderly patients have an increased frequency of adverse reactions to NSAIDs, especially gastrointestinal bleeding and perforation, sometimes fatal. Treatment in such patients should be initiated with the lowest possible dose. As with all NSAIDs, patients with a history of esophagitis, gastritis, and/or peptic ulcer should be treated only if these conditions are in remission. Patients with existing gastrointestinal symptoms or a history of gastrointestinal disorders should be monitored for possible gastrointestinal complications during treatment, particularly gastrointestinal bleeding. NSAIDs should be used cautiously in patients with a history of inflammatory bowel disease (ulcerative colitis, Crohn's disease), as there is a risk of exacerbation.

For such patients and those taking low-dose acetylsalicylic acid or other agents that increase the risk of gastrointestinal adverse reactions, concomitant therapy with protective agents (e.g., misoprostol or proton pump inhibitors) should be considered.

Patients, especially elderly ones, with a history of gastrointestinal adverse reactions should inform their physician about any unusual gastrointestinal symptoms, including gastrointestinal bleeding, particularly during the initial stages of treatment.

The drug should be prescribed with caution to patients who are concurrently using agents that may increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents such as acetylsalicylic acid.

Renal safety

The drug should be used with caution in patients with impaired renal function, as NSAIDs may worsen renal function, cause fluid retention, and edema. Due to the increased risk of nephrotoxicity, the drug should be used cautiously in patients receiving diuretics or those at risk of hypovolemia. During treatment, adequate fluid intake should be maintained to avoid dehydration, which may exacerbate renal toxicity. As with other NSAIDs, the drug may increase plasma urea nitrogen and creatinine levels. Similar to other prostaglandin synthesis inhibitors, its use may be associated with renal adverse reactions, including glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome, and acute renal failure.

Renal function disturbances occur most frequently in elderly patients.

Hepatic safety

The drug should be used with caution in patients with impaired liver function. As with other NSAIDs, the drug may cause transient and minor elevations in certain liver parameters, as well as marked increases in AST and ALT activity. If such elevations occur, therapy should be discontinued.

Hepatic function disturbances occur most frequently in elderly patients.

Cardiovascular and cerebrovascular safety

Patients with hypertension and/or mild to moderate heart failure require monitoring and medical advice. Particular caution is required when treating patients with a history of heart disease, especially previous episodes of heart failure (the risk of developing heart failure increases during treatment), as fluid retention and edema may occur with NSAID therapy. Clinical studies and epidemiological data suggest that some NSAIDs (especially at high doses and with prolonged use) may slightly increase the risk of arterial thrombotic events (e.g., myocardial infarction or stroke). Data to exclude such risks with dexketoprofen use are insufficient. Therefore, dexketoprofen should be prescribed only after careful assessment of the patient's condition in cases of uncontrolled hypertension, congestive heart failure, ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. Similarly careful assessment is required before initiating long-term treatment in patients with cardiovascular risk factors (e.g., hypertension, hyperlipidemia, diabetes, smoking).

Non-selective NSAIDs can reduce platelet aggregation and prolong bleeding time by inhibiting prostaglandin synthesis. The concomitant use of dexketoprofen and low-molecular-weight heparin at prophylactic doses in the postoperative period has been studied in clinical trials, and no effect on coagulation parameters was observed. However, patients receiving dexketoprofen concurrently with agents affecting hemostasis, such as warfarin, other coumarin derivatives, or heparins, require close medical supervision. Cardiovascular adverse events occur most frequently in elderly patients.

Skin reactions

There have been reports of very rare cases of serious skin reactions (some fatal) associated with NSAID use, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The risk appears highest during the initial stages of treatment, with most cases occurring within the first month of therapy. If skin rashes, signs of mucosal involvement, or other hypersensitivity symptoms occur, treatment should be discontinued.

Masking symptoms of underlying infections

Dexketoprofen may mask symptoms of infection, potentially delaying diagnosis and timely treatment, thereby worsening infection outcomes. Such cases have been observed in bacterial pneumonia and bacterial complications of varicella. If Dexamethasone-N must be administered to relieve pain associated with an infectious process, monitoring of the infection is recommended. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Other information

Particular caution should be exercised when prescribing the drug to patients:

• with inherited porphyrin metabolism disorders (e.g., acute intermittent porphyria);
• with dehydration;
• immediately after major surgical procedures.

If prolonged use of dexketoprofen is deemed necessary by the physician, regular monitoring of liver and kidney function is recommended.

Very rarely, severe acute hypersensitivity reactions (e.g., anaphylactic shock) have been observed. If early signs of severe hypersensitivity reactions occur after taking dexketoprofen, treatment should be discontinued. Any necessary treatment in such cases should be administered under medical supervision, depending on the symptoms.

Patients with asthma combined with chronic rhinitis, chronic sinusitis, and/or nasal polyps are at higher risk of allergy to acetylsalicylic acid and/or NSAIDs compared to other patients. Administration of this drug may trigger asthma attacks or bronchospasm, particularly in patients allergic to acetylsalicylic acid or NSAIDs.

Severe infectious complications involving the skin and soft tissues may occur during varicella. Data to exclude the role of NSAIDs in exacerbating this infectious process are lacking. Therefore, dexketoprofen is not recommended in varicella.

The drug should be administered with caution to patients with coagulation disorders, systemic lupus erythematosus, and mixed connective tissue diseases.

As with other NSAIDs, dexketoprofen may mask symptoms of infectious diseases during its use. In isolated cases, activation of soft tissue infections has been reported during NSAID use. Therefore, if symptoms of bacterial infection appear or worsen during treatment, patients are advised to seek immediate medical attention.

One ampoule of Dexamethasone-N contains 200 mg of ethanol, equivalent to 5 mL of beer or 2.08 mL of wine per dose. The drug may adversely affect individuals with alcoholism. The ethanol content should be considered when using the drug during the first and second trimesters of pregnancy, in children, and in high-risk patients (e.g., those with liver disease or epilepsy). The drug contains less than 1 mmol of sodium (23 mg) per dose, i.e., practically sodium-free.

Use during pregnancy or breastfeeding.

The use of Dexamethasone-N is contraindicated during the third trimester of pregnancy and during breastfeeding.

Inhibition of prostaglandin synthesis may adversely affect pregnancy and/or fetal development. According to epidemiological studies, the use of drugs that inhibit prostaglandin synthesis during early pregnancy increases the risk of miscarriage, congenital heart defects, and abdominal wall defects. The absolute risk of cardiovascular abnormalities increases from <1% to approximately 1.5%. The risk is considered to increase with higher drug doses and longer treatment duration. In animal studies, prostaglandin synthesis inhibitors increased pre- and post-implantation losses and embryofetal mortality. Furthermore, in animals treated with prostaglandin synthesis inhibitors during organogenesis, an increased incidence of fetal malformations, including cardiovascular abnormalities, was observed. However, animal studies with dexketoprofen did not reveal reproductive organ toxicity.

From the 20th week of pregnancy, dexketoprofen use may cause oligohydramnios due to fetal renal dysfunction. This may occur shortly after starting treatment and is usually reversible upon discontinuation.

Additionally, there are reports of arterial duct constriction after second-trimester treatment, most of which resolved after stopping treatment. Therefore, dexketoprofen should not be prescribed during the first and second trimesters of pregnancy except in cases of extreme necessity. When prescribing dexketoprofen to women planning pregnancy or during the first and second trimesters, the lowest effective dose for the shortest possible duration should be used.

Fetal monitoring for oligohydramnios and arterial duct constriction should be considered after several days of drug exposure, starting from the 20th gestational week. The drug should be discontinued if oligohydramnios or arterial duct constriction is detected.

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

• cardiopulmonary toxicity (premature constriction/closure of the arterial duct and pulmonary hypertension);
• renal dysfunction (see above);

and risks to the mother near term and to the newborn:

• possible prolongation of bleeding time, antiaggregatory effect, which may occur even at very low doses;
• inhibition of uterine contractions, leading to delayed or prolonged labor.

Therefore, dexketoprofen is contraindicated during the third trimester of pregnancy (see section "Contraindications").

Breastfeeding period.

There are no data on the passage of dexketoprofen into breast milk. The drug is contraindicated during breastfeeding.

Fertility.

Like all other NSAIDs, dexketoprofen may reduce female fertility and therefore is not recommended for women planning pregnancy. For women experiencing fertility problems or undergoing infertility evaluation, discontinuation of the drug should be considered.

Ability to affect reaction speed when driving or operating machinery.

Dizziness, visual disturbances, or somnolence may occur during treatment with the drug. In such cases, the ability to react quickly, orient in traffic situations, and drive or operate machinery may be impaired.

Method of Administration and Dosage

To minimize adverse reactions, the lowest effective dose for the shortest duration should be used (see section "Special Warnings and Precautions for Use").

Adults

The recommended dose is 50 mg every 8–12 hours. If necessary, the next dose may be administered after 6 hours. The maximum daily dose should not exceed 150 mg. Dexatifen-N is intended for short-term use and should only be administered during episodes of acute pain (no longer than 2 days). Patients should be switched to oral analgesics as soon as possible. For moderate to severe postoperative pain, the drug may be used as indicated at the same recommended doses in combination with opioid analgesics.

Elderly Patients

Dose adjustment is generally not required. However, due to physiological decline in renal function, a lower dose is recommended: the maximum daily dose should not exceed 50 mg in patients with mild renal impairment.

Hepatic Impairment

For patients with mild to moderate hepatic impairment (5–9 points on the Child–Pugh scale), the maximum daily dose should be reduced to 50 mg, and liver function should be closely monitored. The drug is contraindicated in patients with severe hepatic impairment (10–15 points on the Child–Pugh scale).

Renal Impairment

For patients with mild renal impairment (creatinine clearance 60–89 mL/min), the maximum daily dose should be reduced to 50 mg. The drug is contraindicated in patients with moderate to severe renal impairment (creatinine clearance < 59 mL/min).

Children and Adolescents

The drug should not be used in children and adolescents due to lack of data on efficacy and safety.

Method of Administration

Intramuscular Injection

The contents of one ampoule (2 mL) should be administered slowly by deep intramuscular injection.

Intravenous Infusion

For intravenous infusion, the contents of one 2 mL ampoule should be diluted in 30–100 mL of 0.9% sodium chloride solution, glucose solution, or Ringer’s lactate solution. The infusion solution must be prepared under aseptic conditions and protected from exposure to natural daylight. The prepared solution should be clear and transparent. The infusion should be administered intravenously over 10–30 minutes at a slow rate.

Dexatifen-N diluted in 100 mL of 0.9% sodium chloride solution or glucose solution may be mixed with dopamine, heparin, hydroxyzine, lidocaine, morphine, pethidine, and theophylline.

Intravenous Bolus Injection
If necessary, the contents of one ampoule (2 mL of injection solution) may be administered intravenously slowly over at least 15 seconds. The drug may be mixed in small volumes (e.g., in a syringe) with injection solutions of heparin, lidocaine, morphine, and theophylline.

Dexatifen-N must not be mixed in small volumes (e.g., in a syringe) with dopamine, promethazine, pentazocine, pethidine, or hydroxyzine solutions, as precipitation may occur.

Diluted infusion solutions must not be mixed with promethazine or pentazocine.

The drug may only be mixed with medicinal products specified above.

After drawing the solution from the ampoule, it should be administered immediately when given by intramuscular or intravenous bolus injection.

No change in active ingredient concentration due to adsorption has been observed during storage of diluted solutions in polyethylene bags or administration devices made of ethylene-vinyl acetate, cellulose propionate, low-density polyethylene, or polyvinyl chloride.

Dexatifen-N is intended for single use only; any unused portion of the prepared solution should be discarded.

The ampoule should be removed from the aluminum foil pouch immediately before use.

The solution should be visually inspected before administration to ensure it is clear and colorless. Solutions containing particulate matter must not be used.

Children

The drug should not be used in children and adolescents due to lack of data on efficacy and safety.

Overdose

Symptoms of overdose are unknown. Similar medicinal products may cause gastrointestinal disturbances (vomiting, anorexia, abdominal pain) and nervous system effects (drowsiness, dizziness, disorientation, headache). In case of accidental overdose, symptomatic treatment appropriate to the patient’s condition should be initiated immediately. Dexketoprofen is removed from the body by dialysis.

Adverse reactions.

The table below lists adverse reactions by organ systems and frequency of occurrence, which, according to clinical trial data, are considered at least possible to be related to dexketoprofen, as well as adverse reactions reported after marketing of the drug.

Gastrointestinal disorders were observed most frequently.

Peptic ulceration, perforation, or gastrointestinal bleeding, sometimes fatal, may occur, particularly in elderly patients. According to available data, nausea, vomiting, diarrhea, flatulence, constipation, dyspeptic symptoms, abdominal pain, melena, vomiting with blood, ulcerative stomatitis, exacerbation of colitis, and Crohn's disease may develop during treatment with the medicinal product. Gastritis has been observed less frequently.

Edema, arterial hypertension, and heart failure, which may be associated with the use of NSAIDs, have also been reported.

As with other NSAIDs, the following adverse reactions are possible: aseptic meningitis, occurring predominantly in patients with systemic lupus erythematosus or mixed connective tissue diseases, and blood disorders (purpura, aplastic and hemolytic anemia; agranulocytosis and bone marrow hypoplasia are rare).

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

According to results of clinical trials and epidemiological data, the use of certain NSAIDs, particularly at high doses and over prolonged periods, may be associated with a slight increase in the risk of thrombotic events such as myocardial infarction and stroke.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after medicinal product registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

Shelf life of the medicinal product in original packaging

2 years.

Shelf life after reconstitution

After dilution, the solution should be stored for up to 24 hours at a temperature of 2 to 8 °C.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C. To protect from light, keep ampoules in the secondary packaging. Store out of reach of children.

Incompatibility.

Dexatifen-N must not be mixed in small volumes (e.g., in a syringe) with solutions of dopamine, promethazine, pentazocine, meperidine, or hydrocortisone, as a white precipitate may form.

Diluted infusion solutions prepared as described in the section "Administration and dosage" must not be mixed with promethazine or pentazocine.

Packaging. 2 ml in a polyethylene ampoule; 1 ampoule in an aluminum foil pouch; 5 pouches in a cardboard box.

Prescription status. Prescription only.

Manufacturer. LLC "FARMASEL".

Manufacturer's address and site of operations.

3, Prorizna Street, Kvitneve, Brovary District, Kyiv Oblast, 07408, Ukraine.