Veldexal solution 25mg/ml 2ml ampoules, 5pcs

Composition

Per 1 ml:

Active ingredient: dexketoprofen trometamol-36.9 mg, in terms of dexketoprofen-25 mg.

Excipients: ethanol (95% ethyl alcohol), sodium chloride,1 M sodium hydroxide solution, water for injection.

Pharmacological action

Pharmacotherapy group:   nonsteroidal anti-inflammatory drug (NSAID).

ATX code: [M 01 AE 17]

Pharmacological properties

Pharmacodynamics

Dexketoprofen trometamol is a nonsteroidal anti-inflammatory drug (NSAID) derived from propionic acid. It has analgesic, anti-inflammatory and antipyretic effects. The mechanism of action is associated with inhibition of prostaglandin synthesis at the level of cyclooxygenase-1 and cyclooxygenase-2.

The analgesic effect occurs 30 minutes after parenteral use. The duration of the analgesic effect after use at a dose of 50 mg is 4-8 hours.

When combined with opioid analgesics, dexketoprofen significantly reduces the need for opioids (up to 30-45%).

Pharmacokinetics

Suction

After intramuscular (i/m) use of dexketoprofen, the maximum concentration (Cmax) in the blood serum is reached on average in 20 minutes (10-45 minutes). The area under the concentration-time curve (AUC) after a single dose of 25-50 mg is proportional to the dose, both with intramuscular and intravenous (IV) use. The corresponding pharmacokinetic parameters are similar after a single and repeated IV or IV use, which indicates that there is no accumulation of the drug.

Distribution

Dexketoprofen is characterized by a high level of binding to plasma proteins (99%). The average Vd is less than 0.25 l / kg, and the half – life is about 0.35 hours. Deduction

Dexketoprofen is primarily metabolized by conjugation with glucuronic acid, followed by renal elimination. The half-life (T 1/2) of dexketoprofen trometamol is about 1-2.7 hours

. Pharmacokinetics in the elderly

In the elderly, there is an increase in the duration of T 1/2 (both after a single and after repeated IV or iv use) by an average of 48% and a decrease in the total clearance of the drug.

Indications

– relief of the pain syndrome of different Genesis (including postoperative pain, pain in bone metastases, post-traumatic pain, pain in renal colic, algomenorrhea, sciatica, radiculitis, neuralgia, toothache);

– symptomatic treatment of acute and chronic inflammatory, inflammatory, degenerative and metabolic diseases of the musculoskeletal system (including rheumatoid arthritis, osteoarthritis, spondyloarthritis: ankylosing spondylitis, reactive arthritis, psoriatic arthritis).

The drug is intended for symptomatic therapy, reducing pain and inflammation at the time of use, and does not affect the progression of the disease.

Use during pregnancy and lactation

The use of the drug during pregnancy and lactation is contraindicated.

Contraindications

– hypersensitivity to dexketoprofen, as well as other NSAIDs or to any of the excipients included in the composition of the drug;

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

– erosive-ulcerative lesions of the gastrointestinal tract and duodenum ulcer;

gastro – intestinal bleeding, a history of other active bleeding (including suspected intracranial bleeding), anticoagulant therapy;

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

severe disturbances of liver function (10-15 points on a scale child-Pugh);

– progressing kidney disease, severe renal dysfunction (creatinine clearance less than 30 ml/min);

– confirmed hyperkalemia;

decompensated heart failure;

– after the coronary artery bypass grafting;

– hemophilia and other blood coagulation disorders;

pregnancy, lactation;

– age up to 18 years (efficacy and safety not established).

The drug is contraindicated for neuroaxial (epidural or subshell, intra-shell) use, due to the ethanol contained in the drug.

With caution

Peptic ulcer of the stomach and duodenum, ulcerative colitis, Crohn’s disease, a history of liver disease, hepatic porphyria, chronic renal failure (creatinine clearance 30-60 ml/min), chronic heart failure, arterial hypertension, a significant decrease in the volume of circulating blood (including after surgery), elderly patients (older than 65 years, including those receiving diuretics, weakened patients and low body weight), bronchial asthma asthma, concomitant use of glucocorticosteroids (including prednisone), anticoagulants (including warfarin), antiplatelet agents (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), coronary heart disease, cerebrovascular diseases, dielipidemia/hyperlipidemia, diabetes mellitus, peripheral arterial diseases, smoking, presence of Helicobacter pylori infection, systemic connective tissue diseases, long-term use of nonsteroidal anti-inflammatory drugs, tuberculosis, severe osteoporosis, alcoholism, severe somatic diseases.

Side effects

The frequency of adverse reactions that were observed during the above clinical trials is presented in accordance with the WHO classification: very common ≥ 10%; often ≥ 1% and < 10%; infrequently ≥ 0.1% and < 1%; rarely ≥ 0.01% and

< 0.1%; very rare

Local reactions

Often-pain at the injection site; infrequently-inflammatory reaction, hematoma, hemorrhages at the injection site, feeling hot, chills, fatigue; rarely-back pain, fainting, fever; very rarely-anaphylactic shock, facial edema.

From the central nervous system

Infrequently-headache, dizziness, insomnia, drowsiness; rarely-paresthesia.

From the side of the skin

Infrequently-dermatitis, rash, sweating; rarely-acne, urticaria; very rarely-severe skin reactions (Stevens-Johnson syndrome, Lyell’s syndrome), angioedema, allergic dermatitis, photosensitization.

From the urinary system

Rarely-polyuria, renal colic; very rarely-nephritis or nephrotic syndrome.

From the side of metabolism

Rare: hyperglycemia, hypoglycemia, hypertriglyceridemia.

From the musculoskeletal system

Rarely-muscle spasm, difficulty moving in the joints.

From the digestive system

Often – nausea, vomiting; rarely – abdominal pain, dyspepsia, diarrhea, constipation, hematemesis, dry mouth, rarely – erosive and ulcerative lesions of the gastrointestinal tract (GIT), including bleeding and perforation, anorexia, increase in liver enzymes, jaundice; rarely – a failure of the pancreas, liver damage.

From the side of hematopoietic organs

Rarely-anemia; very rarely-neutropenia, thrombocytopenia.

Respiratory system disorders

Rarely-bradypnea; very rarely-bronchospasm, dyspnea.

From the side of the senses

Infrequently-blurred vision; rarely-tinnitus.

From the cardiovascular system

Infrequently-hypotension, fever, hyperemia of the skin; rarely-extrasystole, tachycardia, hypertension, peripheral edema, superficial thrombophlebitis.

From the side of the reproductive system

Rarely-in women-a violation of the menstrual cycle, in men-a violation of the function of the prostate gland.

Laboratory parameters

Rarely – ketonuria, proteinuria.

Other services

Aseptic meningitis, which occurs mainly in patients with systemic lupus erythematosus or mixed connective tissue diseases, hematological disorders (purpura, aplastic and hemolytic anemia, rarely-agranulocytosis and bone marrow hypoplasia).

Interaction

Unwanted combinations

With other NSAIDs, including high-dose salicylates (more than 3 g / day)

Simultaneous use of several NSAIDs increases the risk of gastrointestinal bleeding and ulcers.

With oral anticoagulants, heparin in doses exceeding the preventive ones, and ticlopidine

There is an increased risk of bleeding due to inhibition of platelet aggregation and damage to the mucous membrane of the digestive tract.

With lithium preparations

, NSAIDs increase the concentration of lithium in the blood plasma (a decrease in renal excretion of lithium), which can reach toxic levels, so the level of lithium in the blood should be monitored when prescribing, changing the dose or discontinuing dexketoprofen.

With methotrexate in high doses (at least 15 mg / week)

The toxicity of methotrexate increases due to a decrease in its renal clearance when using NSAIDs.

With glucocorticosteroids

The risk of ulcers and gastrointestinal bleeding increases.

Hydantoin derivatives and sulfonamides

The severity of their toxic manifestations may increase.

Combinations that require caution

With diuretics, ACE inhibitors, antibacterial drugs from the group of aminoglycosides and angiotensin II receptor antagonists

Dexketoprofen weakens the effect of diuretics and other antihypertensive agents. Treatment with NSAIDs is associated with the risk of acute renal failure in patients with dehydration (reduced glomerular filtration rate due to reduced prostaglandin synthesis). When using dexketoprofen and diuretics in combination, make sure that the patient is adequately hydrated and monitor renal function before prescribing.

With methotrexate in low (less than 15 mg/week) doses

The hematological toxicity of methotrexate increases due to a decrease in its renal clearance when using NSAIDs. Weekly monitoring of the blood picture should be carried out in the first weeks of combined treatment. In the presence of even minor violations of renal function, as well as in the elderly, careful monitoring is necessary.

With pentoxifylline

The risk of bleeding increases. Active clinical monitoring and frequent monitoring of bleeding time or blood clotting time is required.

With zidovudine

Zidovudine may have a toxic effect on reticulocytes, which may lead to severe anemia after the first week of NSAID use. It is necessary to count blood cells and reticulocytes 1-2 weeks after the start of combined treatment.

With oral hypoglycemic medications

Due to the possible increase in hypoglycemic effect due to the ability of NSAIDs to displace them from the sites of binding to plasma proteins.

With heparins (low molecular weight)

Increased risk of bleeding.

Combinations to take into account

With beta blockers

It is possible to reduce their antihypertensive effect due to the inhibition of prostaglandin synthesis by NSAIDs.

With cyclosporine and tacrolimus

It is possible to increase their nephrotoxicity due to the effect of NSAIDs on renal prostaglandins. When conducting combination therapy, it is necessary to monitor renal function.

With thrombolytic drugs, the risk of bleeding increases. With probenecid

It is possible to increase the concentration of dexketoprofen in blood plasma, which may be due to an inhibitory effect on tubular secretion and/or conjugation with glucuronic acid and requires dose adjustment of dexketoprofen.

With cardiac glycosides

, NSAIDs can lead to an increase in their concentration in blood plasma.

With Mifepristone

Due to the theoretical risk of changing the effectiveness of mifepristone under the influence of prostaglandin synthesis inhibitors, NSAIDs should be prescribed 8-12 days after taking mifepristone.

With quinolone antibiotics

There is a high risk of seizures when NSAIDs are used in combination with high doses of quinolones.

Pharmaceutical interaction

Dexketoprofen should not be mixed in the same syringe with a solution of dopamine, promethazine, pentazocine, pethidine or hydroxyzine (a precipitate forms).

Dexketoprofen can be mixed in one syringe with a solution of heparin, lidocaine, morphine and theophylline.

The diluted solution of the drug for intravenous drip use should not be mixed with promethazine or pentazocine.

The diluted solution of the drug is compatible with the following solutions for injection: dopamine, heparin, hydroxyzine, lidocaine, morphine, pethidine and theophylline.

How to take, course of use and dosage

Intravenously (slowly for at least 15 seconds) and intramuscularly (injected deeply, slowly). Recommended dose for adults: 50 mg every 8-12 hours. If necessary, repeated use of the drug with a 6-hour interval is possible. The maximum daily dose is 150 mg.

Dexketoprofen is indicated for short-term use (no more than 2 days) during acute pain syndrome.

Impaired liver function

In patients with mild to moderate hepatic impairment (5-9 points on the Child-Pugh scale), the total daily dose should be reduced to 50 mg and frequent monitoring of liver function should be carried out. Dexketoprofen should not be used in patients with severe hepatic impairment.

Impaired renal function

For patients with mild renal impairment (creatinine clearance 30-60 ml / min), the daily dose is reduced to 50 mg. Dexketoprofen should not be used in patients with moderate or severe renal insufficiency (creatinine clearance less than 30 ml / min).

Elderly patients

Dose adjustment for elderly patients is usually not required, but due to a physiological decrease in renal function, it is recommended to reduce the dose of the drug: a total daily dose of 50 mg for mild renal impairment in elderly patients.

Preparation of solutions

To prepare a solution of the drug for intravenous infusion, the contents of one ampoule (2 ml) are diluted in 30-100 ml of 0.9% sodium chloride solution, glucose solution or Ringer’s solution. The solution should be prepared under aseptic conditions, protected from daylight. The diluted solution should be clear and colorless, administered by slow intravenous infusion lasting 10-30 minutes.

Overdose

Cases of overdose are not described.

Symptoms: vomiting, nausea, anorexia, abdominal pain, dizziness, disorientation, headache, drowsiness may occur.

Treatment: symptomatic therapy; if necessary, hemodialysis.

Special instructions

Patients with symptoms of gastrointestinal disorders or a history of gastrointestinal diseases should be monitored by a doctor, especially for gastrointestinal bleeding. In cases of gastrointestinal bleeding in patients taking dexketoprofen, the drug is immediately discontinued.

Caution should be exercised in patients taking concomitant medications that may increase the risk of ulceration or bleeding: corticosteroids, anticoagulants (such as warfarin), selective serotonin reuptake inhibitors, or antiplatelet agents (including acetylsalicylic acid).

Dexketoprofen may cause reversible inhibition of platelet aggregation and increase bleeding time.

Dexketoprofen should be used with caution in patients with a history of allergies. Dexketoprofen should be used with caution in patients with chronic heart failure of NYHA functional class I-II.

Dexketoprofen can cause an increase in the level of creatinine and nitrogen in blood plasma, have a negative effect on the urinary system, leading to the development of glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome and acute renal failure.

As with other NSAIDs, there may be a slight transient increase in the values of some liver tests, a significant increase in the activity of ACT and ALT in the blood serum. At the same time, monitoring of liver and kidney functions is necessary in elderly patients. In case of a significant increase in the corresponding indicators, Dexketoprofen should be discontinued.

Dexketoprofen should be used with caution in patients with hematopoietic disorders, patients with systemic lupus erythematosus or other connective tissue diseases.

Like other NSAIDs, dexketoprofen may mask the symptoms of infectious diseases. Isolated cases of exacerbation of infectious processes localized in soft tissues have been reported with the use of NSAIDs. Therefore, medical supervision of patients with signs of bacterial infection or worsening of the condition during treatment with dexketoprofen is required.

Caution should be exercised when prescribing the drug to patients with impaired liver, kidney, heart function or conditions that may cause fluid retention in the body. In these patients, the use of NSAIDs can lead to deterioration of the condition and fluid retention in the body. Caution should also be exercised when prescribing dexketoprofen to patients using diuretics or predisposed to hypovolemia, as they have an increased risk of developing nephrotoxicity.

Caution is necessary when prescribing the drug to the elderly, since they are more likely to have impaired renal, liver or cardiovascular function, as well as the occurrence of adverse reactions, such as gastrointestinal bleeding or intestinal perforation.

Each ampoule of the drug contains 200 mg of ethanol.

Influence on the ability to drive vehicles and mechanisms

Due to possible dizziness and drowsiness during the period of taking the drug, the ability to concentrate and the speed of psychomotor reactions may decrease.

Storage conditions

In a place protected from light at a temperature not exceeding 25 ° C. Keep out of reach of children.

Shelf

life is 2 years.

Do not use after the expiration date.

Active ingredient

Dexketoprofen

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection and infusion