Dexarom

INSTRUCTION for medical use of the medicinal product DEXAROM (DEXAROM)

Composition:

Active substance: 1 ml of solution for injection contains 36.9 mg of dexketoprofen trometamol, equivalent to 25 mg of dexketoprofen

(1 ampoule of 2 ml contains 73.8 mg of dexketoprofen trometamol, equivalent to 50 mg of dexketoprofen);

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

Pharmaceutical form.

Solution for injection.

Main physicochemical properties: clear, colorless solution.

Pharmacotherapeutic group.

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

ATC code M01A E17

Pharmacological Properties

Pharmacodynamics.

Dexketoprofen trometamol is the tromethamine salt of (S)-(+)-2-(3-benzoylphenyl) propionic acid, exerting 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 drug effect.

Pharmacodynamics

Inhibitory effects of dexketoprofen trometamol 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 trometamol exerts a pronounced analgesic effect. The analgesic effect of dexketoprofen trometamol administered intramuscularly or intravenously in patients with moderate to severe pain has been studied in various pain conditions associated with surgical procedures (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 of dexketoprofen trometamol 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. In patients receiving morphine via a patient-controlled analgesia device for postoperative pain, the addition of dexketoprofen trometamol resulted in a significantly lower morphine requirement (by 30–45%) compared to patients receiving placebo.

Pharmacokinetics.

Absorption

After intramuscular administration of dexketoprofen trometamol 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 is on average 0.25 L/kg. The distribution half-life is approximately 0.35 hours, and the elimination half-life is 1–2.7 hours.

Pharmacokinetic studies of repeated administration demonstrated that Cmax and AUC after the last intramuscular or intravenous dose did not differ from those after single administration, indicating the absence of drug accumulation.

Metabolism and excretion

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

Elderly patients

After administration of single and multiple doses, the extent of drug exposure in healthy elderly 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 in maximum concentration or time to reach maximum concentration were observed. The mean elimination half-life increased (by up to 48%), and the total clearance decreased.

Preclinical safety data

Standard preclinical studies—pharmacological safety, genotoxicity, and immunopharmacology—did not reveal any specific hazard for humans. Chronic toxicity studies in animals identified a no-observed-adverse-effect level (NOAEL) that was twice 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 pathologies such as erosions. These reactions 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 embryonic/fetal development or indirectly via maternal gastrointestinal toxicity.

Clinical characteristics.

Indications.

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

Contraindications.

• Hypersensitivity to dexketoprofen, to any other nonsteroidal anti-inflammatory drug (NSAID), or to excipients of the medicinal product;
• if substances with similar action, e.g. acetylsalicylic acid or other NSAIDs, provoke asthma attacks, bronchospasm, acute rhinitis, or cause 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 bleeding or increased bleeding tendency;
• Crohn’s disease or ulcerative colitis;
• severe heart failure;
• moderate to severe renal impairment (creatinine clearance ≤ 59 mL/min);
• severe hepatic impairment (10–15 points on the Child–Pugh scale);
• hemorrhagic diathesis and other coagulation disorders;
• pronounced dehydration (due to vomiting, diarrhea, or insufficient fluid intake);
• third trimester of pregnancy and breastfeeding period.

Due to ethanol content, the medicinal product Dexarom is contraindicated for neuroaxial (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 selective cyclooxygenase-2 inhibitors), including salicylates in high doses (≥ 3 g/day). Concomitant use of multiple NSAIDs increases the risk of gastrointestinal ulceration and gastrointestinal bleeding due to mutual enhancement of effects;
• anticoagulants: NSAIDs enhance the effect of anticoagulants, e.g. warfarin, due to high plasma protein binding of dexketoprofen and inhibition of platelet function, as well as damage to gastric and duodenal mucosa. If concomitant use is necessary, it should be performed under physician supervision with monitoring of appropriate laboratory parameters;
• heparin: increased risk of bleeding (due to inhibition of platelet function and damage to gastric and duodenal mucosa). If concomitant use is necessary, it should be performed under physician supervision with monitoring of appropriate laboratory parameters;
• corticosteroids: increased risk of gastrointestinal ulceration and gastrointestinal bleeding;
• lithium (reports with several NSAIDs): NSAIDs increase lithium blood levels, potentially leading to toxicity (reduced renal excretion of lithium). Therefore, lithium levels in blood should be monitored at the beginning of dexketoprofen therapy, during dose adjustments, or upon discontinuation of the drug;
• high-dose methotrexate (≥ 15 mg weekly): 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 agents.

Concomitant use of the following agents with NSAIDs requires caution:

• diuretics, angiotensin-converting enzyme (ACE) inhibitors, aminoglycoside antibiotics, and angiotensin II receptor antagonists. Dexketoprofen reduces the efficacy of diuretics and other antihypertensive agents. In some patients with impaired renal function (e.g. due to dehydration or in elderly patients), concomitant use of agents that inhibit cyclooxygenase 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 (< 15 mg weekly): 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. Even with mild renal impairment or in elderly patients, treatment should be conducted under strict physician supervision;
• 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 impact on reticulocytes, which after 1 week of NSAID use may lead to severe anemia. Blood tests and reticulocyte count should be performed within 1–2 weeks after initiation of NSAID therapy;
• sulfonylurea agents: NSAIDs may enhance the hypoglycemic effect of these agents by displacing sulfonylureas from plasma protein binding sites.

Potential interactions should be considered when using the following agents:

• beta-blockers: NSAIDs may reduce their antihypertensive effect by inhibiting 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 tubular secretion and glucuronidation 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 medicinal products for medical termination of pregnancy;
• quinolone antibiotics: animal studies have shown that high-dose quinolone derivatives in combination with NSAIDs increase the risk of seizures;
• tenofovir: when used concomitantly with NSAIDs, plasma urea nitrogen and creatinine concentrations may increase; therefore, renal function should be monitored to assess potential effects of combined use;
• deferasirox: concomitant use with NSAIDs increases the risk of gastrointestinal tract toxicity. Careful patient monitoring is required when using this medicinal product together with deferasirox;
• pemetrexed: concomitant use with NSAIDs may reduce pemetrexed elimination; therefore, particular caution is required when using high-dose NSAIDs. In patients with mild to moderate renal impairment (creatinine clearance 45–79 mL/min), NSAID use should be avoided for two days before and two days after pemetrexed administration.

Special precautions for use

Use with caution in patients with a history of allergic conditions. Avoid using the medicinal product Dexarom in combination with other NSAIDs, including selective COX-2 inhibitors. Adverse reactions can be minimized by using the lowest effective dose for the shortest duration necessary to control symptoms.

Gastrointestinal safety

Gastrointestinal bleeding, ulceration, or perforation, sometimes fatal, have been reported with the use of all NSAIDs at any stage of treatment, regardless of the presence of warning symptoms or a history of serious gastrointestinal disorders. If gastrointestinal bleeding or ulceration occurs, treatment with 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: Elderly patients have an increased frequency of adverse reactions to NSAIDs, particularly gastrointestinal bleeding and perforation, sometimes fatal. Treatment in these patients should be initiated at the lowest possible dose. NSAIDs should be prescribed with caution in patients with a history of gastrointestinal disorders (e.g., ulcerative colitis, Crohn’s disease), as these conditions may be exacerbated. When using any NSAID in patients with a history of esophagitis, gastritis, and/or peptic ulcer, ensure these conditions are in remission. Patients with existing gastrointestinal symptoms or a history of gastrointestinal disorders should be monitored during treatment for possible complications, particularly gastrointestinal bleeding. For such patients and those taking low-dose acetylsalicylic acid or other agents increasing gastrointestinal risk, consider concomitant use of protective agents such as misoprostol or proton pump inhibitors.

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.

Prescribe the drug with caution in patients concurrently using agents that increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents like acetylsalicylic acid.

Renal safety

The medicinal product 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 prevent dehydration, which may exacerbate renal toxicity. Like other NSAIDs, the drug may increase plasma concentrations of blood urea nitrogen and creatinine. Similar to other inhibitors of prostaglandin synthesis, its use may be associated with renal adverse reactions, including glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome, and acute renal failure. Renal function disturbances are most common in elderly patients.

Hepatic safety

The medicinal product should be used with caution in patients with impaired liver function. As with other NSAIDs, the drug may cause transient and mild elevations in certain liver function parameters, as well as marked increases in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity. If such increases occur, treatment should be discontinued.

Hepatic function disturbances are most common in elderly patients.

Cardiovascular and cerebrovascular safety

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

Non-selective NSAIDs can reduce platelet aggregation and prolong bleeding time by inhibiting prostaglandin synthesis. The concomitant use of dexketoprofen trometamol and low-molecular-weight heparin at prophylactic doses in the postoperative period has been studied in clinical trials, with no effect on coagulation parameters observed. However, patients receiving dexketoprofen trometamol together with agents affecting hemostasis (e.g., warfarin, other coumarins, or heparins) require close medical supervision. Cardiovascular adverse events are most common 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 is likely 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 symptoms of hypersensitivity occur, the medicinal product Dexarom should be discontinued.

Other information

Particular caution is required when prescribing the medicinal product 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 considered necessary by the physician, regular monitoring of liver and kidney function is recommended.

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

Patients with asthma associated 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. This drug may trigger asthma attacks or bronchospasm, especially in patients allergic to acetylsalicylic acid or NSAIDs.

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

Dexarom should be administered with caution in patients with coagulation disorders, systemic lupus erythematosus, or mixed connective tissue diseases.

Masking symptoms of underlying infections: Dexketoprofen may mask symptoms of infection, potentially delaying appropriate treatment and worsening infection outcomes. Such masking has been observed in bacterial community-acquired pneumonia and bacterial complications of varicella. When this medicinal product is used to relieve pain associated with infection, infection should be monitored. In outpatient settings, patients should consult a physician if symptoms persist or worsen.

Dexarom contains 12.4% v/v ethanol (alcohol), i.e., up to 200 mg per dose, equivalent to 5 mL of beer or 2.08 mL of wine per dose.

The medicinal product may adversely affect individuals with alcoholism. The ethanol content should be considered when using in pregnant women, breastfeeding women, children, and patients at risk (e.g., those with liver disease or epilepsy).

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

Use during pregnancy or breastfeeding

Use of the medicinal product Dexarom is contraindicated during the third trimester of pregnancy and during breastfeeding.

Pregnancy

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

From the 20th week of pregnancy, use of dexketoprofen trometamol may cause oligohydramnios (low amniotic fluid) due to impaired fetal kidney function. This may occur soon after starting treatment and is usually reversible upon discontinuation. Additionally, there have been reports of arterial duct constriction after second-trimester treatment, most of which resolved after stopping treatment. Therefore, dexketoprofen trometamol should not be prescribed during the first and second trimesters unless clearly necessary. If dexketoprofen trometamol is used by women attempting to conceive or during the first and second trimesters of pregnancy, the dose should be as low as possible and treatment duration as short as possible. Antenatal monitoring for oligohydramnios and arterial duct constriction should be considered after exposure to dexketoprofen trometamol for several days starting from the 20th week of pregnancy. Dexketoprofen trometamol should be discontinued if oligohydramnios or arterial duct constriction is detected.

During the third trimester, all prostaglandin synthesis inhibitors cause:

Risks to the fetus:

• cardiopulmonary toxicity (premature closure/obstruction of the arterial duct and pulmonary hypertension);
• impaired renal function, potentially progressing to renal failure with oligohydramnios;

Risks at the end of pregnancy for mother and child:

• prolonged bleeding time (due to inhibition of platelet aggregation), which may occur even with low doses;
• delayed uterine contractions, leading to delayed labor and prolonged delivery.

Breastfeeding

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

Fertility

Like all other NSAIDs, dexketoprofen trometamol may reduce female fertility and therefore is not recommended for women attempting to conceive. If a woman experiences fertility problems or is undergoing infertility evaluation, discontinuation of the drug should be considered.

Ability to affect reaction speed when driving or operating machinery

Dizziness, visual disturbances, or drowsiness may occur during treatment with Dexarom. 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

Adults. The recommended dose is 50 mg every 8–12 hours. If necessary, the dose may be repeated after 6 hours. The maximum daily dose should not exceed 150 mg. The medicinal product is intended for short-term use; therefore, it should be used only during episodes of acute pain (no longer than 2 days). Patients should be switched to oral analgesics as soon as possible. The lowest effective dose should be used for the shortest duration necessary to relieve symptoms. 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: maximum daily dose of 50 mg in patients with mild renal impairment.

Liver disease. In 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 dysfunction. In 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 medicinal product should not be used in children and adolescents due to lack of data on efficacy and safety.

Method of Administration

Intramuscular injection. The injection solution should be administered slowly and deeply into the muscle.

Intravenous infusion. For intravenous infusion, the contents of a 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, avoiding exposure to natural daylight. The prepared solution must be clear. The infusion should be administered over 10–30 minutes. Exposure of the prepared solution to natural daylight must be avoided.

Dexarom 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.

Dexarom must not be mixed in the infusion solution with promethazine or pentazocine.

Intravenous injection (bolus administration).

If necessary, the contents of one ampoule (2 mL of injection solution) may be administered intravenously 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.

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

The drug should only be mixed with medicinal products listed above.

When administered intramuscularly or intravenously by injection, the drug should be administered immediately after being drawn from the ampoule. The solution for intravenous infusion should be used immediately after preparation. Subsequently, responsibility for storage conditions and duration lies with the healthcare professional. The prepared solution retains its properties for 24 hours at 25°C, provided it is protected from daylight.

When diluted solutions of the drug are stored in polyethylene bags or in administration devices made of ethylene vinyl acetate, cellulose propionate, low-density polyethylene, or polyvinyl chloride, no changes in active ingredient content due to adsorption have been observed.

The medicinal product Dexarom is intended for single use only; therefore, any unused portion of the prepared solution must be discarded. Before administration, ensure that the solution 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 trometamol is eliminated from the body by dialysis.

Adverse reactions.

The adverse reactions listed in the table below are considered to have, based on clinical data, a minimally possible association with dexketoprofen trometamol, as well as adverse reactions reported during the post-marketing period.

Gastrointestinal disorders were observed most frequently.

The development of peptic ulcer disease, perforation, or gastrointestinal bleeding, sometimes fatal, is possible, 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 occur during treatment with the drug. Gastritis is observed less frequently. Edema, arterial hypertension, and heart failure, which may be caused by the use of NSAIDs, have also been reported. As with other NSAIDs, the following adverse reactions are possible: aseptic meningitis, which generally occurs in patients with systemic lupus erythematosus or mixed connective tissue diseases, and blood disorders (purpura, aplastic and hemolytic anemia, rarely agranulocytosis and bone marrow hypoplasia). Bullous reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare), may also occur.

According to results of clinical studies and epidemiological data, the use of certain NSAIDs, especially at high doses and over prolonged periods, may be associated with a small increased risk of arterial thrombotic events, such as myocardial infarction and stroke.

Reporting of suspected adverse reactions

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

Shelf life.

4 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging, out of the reach of children. No special storage conditions required.

Incompatibilities.

Dexarom must not be mixed in small volumes (e.g., in a syringe) with solutions of dopamine, promethazine, pentazocine, meperidine, or hydroxyzine, as precipitation may occur.

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

Packaging.

2 ml in a vial made of brown glass; 5 vials in a blister pack.

1 or 2 blister packs in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

K.T. ROMPHARM COMPANY S.R.L.

(S.C. ROMPHARM COMPANY S.R.L.)

Manufacturer's location and address of the place of business.

Eroilor str., No 1A, Otopeni city, 075100, county Ilfov, Romania