Veldexal, 25 mg 10 pcs

Pharmacotherapeutic group: nonsteroidal anti-inflammatory drug (NSAID)

ATC code: M01AE17

Pharmacological properties

Pharmacodynamics

Dexketoprofen trometamol refers to non-steroidal anti-inflammatory drugs (NSAIDs) with analgesic, anti-inflammatory and antipyretic effects. The mechanism of action of dexketoprofen is based on inhibition of prostaglandin synthesis at the level of cyclooxygenases (COX-1 and COX-2).

The analgesic effect comes within 30 min after oral administration, the duration of therapeutic effect is 4-6 h.

Pharmacokinetics

Absorption. Time of reaching maximum concentration (ÒCmax) of dexketoprofen in blood plasma after a single oral single dose is on average 30 min (15-60 min). Simultaneous intake of food slows down absorption of dexketoprofen.

The areas under the curve “concentration-time” (AUC) after single and repeated doses are similar, indicating that there is no cumulation of the drug.

Distribution. Dexketoprofen is characterized by high degree of binding to blood plasma proteins (99 %). Mean volume of distribution (Vd) is less than 0.25 l/kg, the period of half-distribution is about 0.35 h.

Metabolism and excretion. The main way of dexketoprofen metabolism is its conjugation with glucuronic acid with subsequent excretion by the kidneys. The elimination half-life (T1/2) of dexketoprofen is 1.65 hours. In elderly patients the elimination half-life is prolonged up to 48 % and total clearance of the drug decreases.

Indications

Muscular-skeletal pain (mild to moderately expressed), algodysmenorrhea, toothache.

The drug is intended for symptomatic treatment, reduction of pain and inflammation at the time of use.

Active ingredient

How to take, the dosage

Dexetoprofen is taken orally with meals. Simultaneous intake of food slows down absorption of dexketoprofen, therefore in case of acute pain it is recommended to use the drug at least 30 min before meals.

In order to achieve the following dosing regimens, if 12.5 mg dosage is necessary, including patients in special groups, the preparation of dexketoprofen from other manufacturers should be used with the possibility of using the minimum dose (with a dash).

Depending on the intensity of the pain syndrome, the recommended dose for adults is 12.5 mg dexketoprofen (1/2 tablet) every 4-6 hours or 25 mg dexketoprofen (1 tablet) every 8 hours.

The maximum daily dose is 75 mg.

Dexketoprofen is not suitable for long-term therapy; the course of treatment with the drug should not exceed 3-5 days.

Patients 65 years and older

Elderly patients should take the drug starting with the lowest recommended dose.

The maximum daily dose is 50 mg.

The doses recommended for the general population may be used if well tolerated.

Patients with hepatic impairment

Patients with mild to moderate hepatic impairment should take the drug starting with the lowest recommended dose.

The maximum daily dose is 50 mg.

The use of dexectoprofen in patients with severe hepatic impairment is contraindicated.

Patients with renal impairment

Patients with mild renal impairment – chronic kidney disease, stage 2 (GFR 60-89 ml/min/1.73 m2) should take dexketoprofen starting with the lowest recommended dose.

The maximum daily dose is 50 mg.

The use of dexketoprofen in patients with chronic kidney disease stages 3a (FFR 45-59 mL/min/1.73 m

The use of dexketoprofen in patients with chronic kidney disease stages 3a (FFR 45-59 mL/min/1.73 msup>2), 3b (GFR 30-44 ml/min/1.73 m2), and 4 (GFR < 30 ml/min/1.73 m2) is contraindicated.

Interaction

The following interactions are typical for all NSAIDs. Undesirable combinations

With other NSAIDs, including salicylates in high doses (more than 3 g per day): simultaneous use of several NSAIDs due to the synergistic effect increases the risk of gastrointestinal bleeding and ulcers.

With anticoagulants: Dexketoprofen, as well as other NSAIDs, may increase the effect of anticoagulants such as warfarin due to the high degree of binding to plasma proteins, inhibition of platelet aggregation and gastrointestinal mucosal damage. If concomitant use is necessary, close monitoring of the patient’s condition and regular monitoring of laboratory parameters are required.

With heparin: concomitant use increases the risk of bleeding (due to inhibition of platelet aggregation and damaging effect on the gastrointestinal mucosa). If concomitant use is necessary, close monitoring of the patient’s condition and regular monitoring of laboratory parameters are required.

With glucocorticosteroids: Simultaneous use increases the risk of gastrointestinal ulcers and bleeding.

With lithium preparations: NSAIDs increase concentration of lithium in plasma up to and including toxic concentration, therefore this parameter should be controlled when using with Dexectoprofen, when changing dosage, and also after discontinuation of NSAIDs.

With methotrexate at high doses (15 mg/week or more): there may be increased hematologic toxicity of methotrexate due to decreased renal clearance when used concomitantly with NSAIDs.

With hydantoins and sulfonamides: possible increase in their toxic effects.

Combinations requiring caution

With diuretics, angiotensin-converting enzyme (ACE) inhibitors, antibiotics from the group of aminoglycosides, angiotensin-II receptor antagonists: concomitant use with NSAIDs is associated with the risk of acute renal failure in dehydrated patients (decreased glomerular filtration due to reduced prostaglandin synthesis). Concomitant use of NSAIDs may reduce the antihypertensive effect of some drugs. In concomitant use of dexectoprofen and diuretics it is necessary to make sure that the patient does not have signs of dehydration, and also at the beginning of concomitant use monitor renal function.

With methotrexate at low doses (less than 15 mg weekly): hematologic toxicity of methotrexate may increase due to decreased renal clearance with NSAID therapy. Blood cell counts should be performed at the beginning of concomitant use. In the presence of renal dysfunction, even of mild degree, as well as in elderly persons, close medical supervision is necessary.

With pentoxifylline: there may be an increased risk of bleeding. Close clinical monitoring and regular monitoring of bleeding time (clotting time) is necessary.

With zidovudine: there is a risk of increased erythrocyte toxicity due to effects on reticulocytes, with development of severe anemia one week after initiation of NSAID use. It is necessary to perform a general blood test with reticulocyte count 1-2 weeks after the start of NSAID therapy.

With oral hypoglycemic agents: NSAIDs may increase the hypoglycemic effect of sulfonylurea due to its displacement from plasma protein binding sites.

Combinations to be taken into consideration

With beta-adrenoblockers: Concomitant use with NSAIDs may decrease the antihypertensive effect of beta-adrenoblockers due to inhibition of prostaglandin synthesis.

With cyclosporine and tacrolimus: NSAIDs may increase nephrotoxicity, which is mediated by the action of renal prostaglandins. Renal function should be monitored during concomitant therapy.

With thrombolytics: increased risk of bleeding.

The risk of bleeding from the gastrointestinal tract is increased when concomitant use with serotonin reuptake inhibitors (citalopram, fluoxetine, sertraline) and anticoagulants.

With probenecid: increased plasma concentrations of NSAIDs may occur, which may be due to the inhibitory effect of probenecid on renal tubular secretion and/or conjugation with glucuronic acid, which requires adjustment of the NSAID dose.

With cardiac glycosides: concomitant use with NSAIDs may lead to increased plasma concentrations of cardiac glycosides.

With mifepristone: Due to the theoretical risk of prostaglandin inhibitors changing the effectiveness of mifepristone, NSAIDs should not be used earlier than 8-12 days after mifepristone withdrawal.

With quinolones: Evidence from animal experiments indicates a high risk of seizures when high-dose quinolones are used concomitantly with NSAIDs.

If it is necessary to concomitantly use dexketoprofen with the above medicinal products, a physician should be consulted.

Special Instructions

Unwanted side effects can be minimized by using the drug at the lowest effective dose with the shortest duration of use necessary to control pain syndrome.

The risk of GI complications is increased in patients with a history of GI ulcers, in elderly patients, with increasing doses of NSAIDs; therefore, Dexectoprofen should be started at the lowest recommended dose in these patients.

Patients in the above categories, as well as patients who require concomitant use of low doses of acetylsalicylic acid or other agents that increase the risk of gastrointestinal complications, additional concomitant use of gastroprotectors (misoprostol or proton pump blockers) is recommended.

In patients concomitantly taking anticoagulants or anticoagulants, glucocorticosteroids, the risk of gastrointestinal bleeding also increases.

Patients with a history of gastrointestinal disorders or gastrointestinal disease should be under close medical supervision. If gastrointestinal bleeding or ulcerative lesions occur, dexketoprofen therapy should be discontinued.

Dexketoprofen should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn’s disease) because exacerbation of these diseases is possible.

All NSAIDs may inhibit platelet aggregation and increase bleeding time due to inhibition of prostaglandin synthesis. Therefore, the use of dexectoprofen in patients concomitantly receiving drugs that affect the hemostatic system, such as warfarin, coumarin derivatives and heparin, is not recommended.

Like other NSAIDs, dexketoprofen may increase plasma creatinine and nitrogen concentrations. Like other inhibitors of prostaglandin synthesis, dexketoprofen may have adverse effects on the urinary system, which may lead to the development of glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome and acute renal failure. Caution should be exercised when using the drug in patients concomitantly using diuretics and in patients who may develop hypovolemia due to increased risk of nephrotoxicity.

As with other NSAIDs, during dexectoprofen therapy a slight transient increase in liver enzymes activity may be observed. In elderly patients it is necessary to monitor the liver and renal function. In case of significant increase of the corresponding indicators dexketoprofen should be canceled.

Like other NSAIDs, dexketoprofen may mask the symptoms of infectious diseases. If signs of infection or deterioration of well-being are found during dexketoprofen therapy, the patient should immediately consult a physician.

The drug may cause fluid retention in the body, therefore in patients with arterial hypertension, with renal and/or heart failure dexketoprofen should be used with extreme caution. In case of worsening of the condition the drug should be discontinued.

In patients with uncontrolled arterial hypertension, coronary heart disease, congestive heart failure, peripheral artery disease and/or cerebrovascular disease the drug should be used with caution. The same approach is applied to patients with risk factors of cardiovascular diseases (arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

Patients with a history of cardiovascular disease, especially those with heart failure, should be cautioned when prescribing dexketoprofen due to the possible risk of progression.

Clinical studies and epidemiologic data suggest that NSAIDs, especially in high doses and with long-term use, may lead to a small risk of acute myocardial infarction or stroke. There are insufficient data to exclude the risk of these events with dexectoprofen.

Elderly patients are particularly susceptible to adverse reactions when using NSAIDs, including the risk of life-threatening gastrointestinal bleeding and perforations, decreased renal, hepatic and cardiac function. Appropriate clinical monitoring is required when dexectoprofen is used in this patient population.

There are data on the occurrence of rare cases of skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) when using NSAIDs. At the first manifestations of skin rash, lesions of the mucous membranes or other signs of allergic reactions the use of dexketoprofen should be stopped immediately and a physician should be consulted.

Impact on the ability to drive and operate vehicles

Contraindications

– hypersensitivity to dexectoprofen, other components of the drug and other NSAIDs;

– complete or incomplete combination of bronchial asthma, recurrent polyposis of the nose and sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including history);

– gastrointestinal erosive-ulcerative lesions in the acute stage;

– gastrointestinal bleeding or perforations in the history, including those associated with previous use of NSAIDs;

– gastrointestinal bleeding; other active bleeding (including suspected intracranial hemorrhage);

– inflammatory bowel disease (Crohn’s disease, ulcerative colitis) in the acute stage;

– severe hepatic insufficiency (10-15 points on the Child-Pugh scale);

– progressive renal disease, confirmed hyperkalemia;

– chronic kidney disease: Stage 3a (glomerular filtration rate (GFR) 45-59 ml/min/1.73 m2), 3b (GFR 30-44 ml/min/1.73 m2) and 4 (FFR < 30 ml/min/1.73 m2);

The period after aortocoronary bypass surgery;

– Severe heart failure (NYHA class III-IV);

– hemorrhagic diathesis and other blood clotting disorders;

– Age less than 18 years old (due to lack of efficacy and safety data);

– Pregnancy and breast-feeding.

With caution

Gastric and duodenal ulcer, ulcerative colitis, Crohn’s disease, liver disease in anamnesis, hepatic porphyria, chronic kidney disease, stage

1 (GFR 60-89 mL/min/1.73 m2), chronic heart failure, arterial hypertension, significant decrease in circulating blood volume (including after surgery), elderly patients over age 65 (including those receiving diuretics, weakened patients and patients with low body weight), bronchial asthma, concomitant use of glucocorticosteroids (including prednisolone), anticoagulants (including warfarin), antiaggregants (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), coronary heart disease, cerebrovascular disease, dyslipidemia/hyperlipidemia, diabetes, peripheral artery disease smoking, Helicobacter pylori infection, systemic lupus erythematosus (SLE) and other systemic connective tissue diseases, long-term use of NSAIDs, tuberculosis, severe osteoporosis, alcoholism, severe medical conditions.

Side effects

Possible side effects are listed according to the World Health Organization classification below in descending order of frequency of occurrence: very frequently (≥1/10), frequently (≥1/100 and < 1/10), infrequently (≥1/1000 and < 1/100), rarely (≥1/10000 and < 1/1000), very rarely (< 1/10000), including individual reports.

Blood and lymphatic system disorders: very rare – neutropenia, thrombocytopenia.

Disorders of the immune system: rarely – laryngeal edema; very rare – anaphylactic reactions, including anaphylactic shock.

Metabolism and nutrition disorders: rare – anorexia.

Mental disorders: infrequent – insomnia, feeling of anxiety.

Nervous system disorders: infrequent headache, dizziness, somnolence; rare – paraesthesia, syncope (transient syncope).

Visual disorders: very rare – blurred vision.

Hearing and labyrinth disorders: infrequent – vertigo; very rare – tinnitus.

Chronic disorders: infrequent – feeling of palpitations, fever, skin hyperemia; rare – increase in blood pressure; very rare – tachycardia, decreased blood pressure.

Disorders of the respiratory system, thorax and mediastinum:

Rarely – bradypnea; very rarely – bronchospasm, dyspnea.

Gastrointestinal disorders: frequently – nausea, vomiting, abdominal pain, dyspepsia, diarrhea; infrequently – gastritis, constipation, dry mouth, flatulence; rarely – erosive-ulcerative lesions of the gastrointestinal tract (GIT), bleeding from ulcer or its perforation; very rarely – damage of pancreas.

Hepatic and biliary tract disorders: rarely – hepatitis, increased activity of “liver” enzymes, including aspartate aminotransferase and alanine aminotransferase (ACT and ALT); very rarely – liver damage.

Skin and subcutaneous tissue disorders: infrequent – skin rash; rare – urticaria, acne, sweating; very rare – severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell syndrome)), angioedema, facial edema, allergic dermatitis, photosensitization, itching.

Muscular and connective tissue disorders: rarely – back pain.

Repnal and urinary tract disorders: rare – polyuria, acute renal failure; very rare – nephritis or nephrotic syndrome.

Gender and mammary gland disorders: rare – in women – menstrual cycle disorders, in men – transient prostate dysfunction with prolonged use.

General disorders and disorders at the site of administration: infrequent – increased fatigue, asthenia, chills, general malaise; very rare – peripheral edema.

As with other NSAIDs, the following side effects may occur: aseptic meningitis, occurring mainly in patients with systemic lupus erythematosus or other systemic connective tissue diseases, hematologic disorders (thrombocytopenic purpura, aplastic and hemolytic anemia), rarely – agranulocytosis and bone marrow hypoplasia.

Overdose

Symptoms: nausea, anorexia, abdominal pain, headache, dizziness, disorientation, insomnia.

Treatment: symptomatic therapy, if necessary – gastric lavage, activated charcoal; hemodialysis is ineffective.

Pregnancy use

The use of dexectoprofen in pregnancy and during breastfeeding is contraindicated.

Similarities