Dexketoprofen, 25 mg/ml 2 ml 10 pcs

Pharmacotherapeutic group

Non-steroidal anti-inflammatory drug (NSAID)

ATC code

M01AE

Pharmacodynamics:

Dexketoprofen trometamol refers to non-steroidal anti-inflammatory drugs (NSAIDs) propionic acid derivative. It has analgesic anti-inflammatory and antipyretic effects. The mechanism of action is related to inhibition of prostaglandin synthesis at the level of cyclooxygenase-1 and cyclooxygenase-2.

The analgesic effect comes 30 minutes after parenteral administration. Duration of analgesic effect after administration at a dose of 50 mg is 4-8 hours.

In combined therapy with opioid analgesics dexectoprofen significantly (up to 30-45%) reduces the need for opioids.

Pharmacokinetics:

Vis absorption

After intramuscular (i/m) administration of dexketoprofen, the maximum concentration (Cmax) in serum is reached on average in 20 min (10-45 min). The area under the curve “concentration-time” (AUC) after a single administration at a dose of 25-50 mg is proportional to the dose, both when administered v/m and intravenous (IV). The corresponding pharmacokinetic parameters are similar after a single and repeated intravenous or intravenous administration, indicating no cumulation of the drug.

Distribution

Dexketoprofen is characterized by high level of binding to plasma proteins (99%). Mean Vd value is less than 025 l/kg half-distribution time is about 035 h.

The metabolism of dexketoprofen mainly occurs by conjugation with glucuronic acid with subsequent excretion by the kidneys. The elimination half-life (T1/2) of dexketoprofen trometamol is about 1 -27 hours.

Pharmacokinetics in the elderly

In the elderly there is an increase in the T1/2 period (both after single and after repeated intravenous or intravenous administration) of up to 48% on average and a decrease in the total clearance of the drug.

Indications

– Control of pain syndrome of different genesis (including postoperative pain with bone metastases post-traumatic pain kidney colic pain algodysmenorrhea sciatica sciatica neuralgia toothache);

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

The drug is intended as symptomatic therapy to reduce pain and inflammation at the time of use has no effect on the progression of the disease.

Active ingredient

Composition

Composition per 1 ml:

Active ingredient: dexketoprofen trometamol – 36.88 mg, in terms of dexketoprofen – 25.00 mg.

Alcoholic substances: ethanol (in terms of 100 % of substance) – 100.00 mg, sodium chloride – 4.00 mg, sodium hydroxide – to pH 6.5-8.5, water for injection – up to 1.00 ml.

How to take, the 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, the drug may be administered repeatedly at 6-hour intervals. Maximum daily dose is 150 mg. Dexetoprofen is indicated for short-term use (not more than 2 days) during acute pain syndrome.

In patients with mild to moderate hepatic impairment (5-9 points by Child-Pugh score) the total daily dose should be reduced to 50 mg and frequent monitoring of liver function parameters should be carried out. Dexetoprofen should not be administered to patients with severe hepatic impairment.

For patients with mild renal dysfunction (creatinine clearance 30-60 ml/min) the daily dose should be reduced to 50 mg. Dexetoprofen should not be administered to patients with moderate to severe renal impairment (creatinine clearance less than 30 ml/min).

Patients in the elderly

Dose adjustment for elderly patients is usually not necessary; however, due to physiologic impairment of renal function, it is recommended to decrease the drug dose: total daily dose 50 mg for mild renal impairment in elderly patients.

Preparing solutions

For preparation of the drug solution for intravenous infusion the content of one ampoule (2 ml) is diluted in 30-100 ml of 09% sodium chloride glucose solution or Ringer’s solution. The solution should be prepared under aseptic conditions protecting it from exposure to daylight. The diluted solution should be clear and colorless administered by slow intravenous infusion lasting 10-30 minutes.

Interaction

Undesirable combinations

With other NSAIDs including salicylates in high doses (more than 3 g/day)

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

With oral anticoagulants heparin in doses greater than prophylactic and ticlopidine

The risk of bleeding increases due to inhibition of platelet aggregation and damage to the digestive tract mucosa.

With lithium preparations

Lithium NSAIDs increase plasma lithium concentration (decreased renal excretion of lithium) which may reach toxic levels; therefore, when dosage changes or dexectoprofen is discontinued, blood lithium level should be monitored.

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

Methotrexate toxicity is increased due to decreased renal clearance when using NSAIDs.

With glucocorticosteroids

The risk of ulcer and gastrointestinal bleeding increases.

Hydantoin derivatives and sulfonamides

The severity of their toxic effects may increase.

Combinations requiring caution

With diuretics ACE inhibitors antibacterial agents from the group of aminoglycosides and angiotensin II receptor antagonists/p>

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 (decreased glomerular filtration due to reduced prostaglandin synthesis). If dexectoprofen and diuretics are used in combination, ensure that the patient is adequately hydrated and monitor renal function before prescribing.

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

Hematological toxicity of methotrexate is increased due to decreased renal clearance when using NSAIDs. It is necessary to conduct weekly monitoring of blood picture during the first weeks of combined treatment. In patients with even mild renal dysfunction and in elderly patients close monitoring is necessary.

With pentoxifylline

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

With zidovudine

The toxic effects of zidovudine on reticulocytes may occur, which after the first week of NSAID use may lead to severe anemia. Blood cell and reticulocyte counts should be performed after 1-2 weeks from the start of combined treatment.

With oral hypoglycemic drugs

In view of a possible increase in hypoglycemic effect due to the ability of NSAIDs to displace them from their binding sites with plasma proteins.

With heparins (low molecular weight)

An increased risk of bleeding.

Combinations to be taken into consideration

With beta-blockers

Their antihypertensive effect may decrease due to inhibition of prostaglandin synthesis by NSAIDs.

With cyclosporine and tacrolimus

Their nephrotoxicity may be increased by the effect of NSAIDs on renal prostaglandins. Renal function should be monitored during combination therapy.

With thrombolytic drugs

The risk of bleeding increases;

With probenecid

. Increased plasma concentration of dexketoprofen may be due to an inhibitory effect on tubular secretion and/or conjugation with glucuronic acid and requires correction of dexketoprofen dose.

With cardiac glycosides

PTCP may lead to an increase in their plasma concentrations.

With mifepristone

Because of the theoretical risk of changes in the effectiveness of mifepristone by prostaglandin synthesis inhibitors, NSAIDs should be administered 8-12 days after mifepristone.

With quinolone antibiotics

High risk of seizures when using NSAIDs in combination with high doses of quinolones.

Pharmaceutical interactions

Dexketoprofen should not be mixed in the same syringe with dopamine promethazine pentazocine pethidine or hydroxyzine solution (precipitate will form).

Dexketoprofen can be mixed in the same syringe with heparin lidocaine morphine and theophylline solution.

Diluted IV solution must not be mixed with promethazine or pentazocine.

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

Special Instructions

Caution should be exercised when prescribing the drug in patients concomitantly taking agents which may increase the risk of ulceration or bleeding: corticosteroids anticoagulants (e.g., warfarin) selective serotonin reuptake inhibitors or antiaggregants (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 allergy. Dexketoprofen should be used with caution in patients with chronic heart failure NYHA functional class I-II.

Dexketoprofen may cause increase in creatinine and plasma nitrogen levels with adverse effects on the urinary system leading to development of glomerulonephritis interstitial nephritis papillary necrosis nephrotic syndrome and acute renal failure.

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

Dexketoprofen should be used with caution in patients with impaired hematopoiesis patients with systemic lupus erythematosus or other connective tissue diseases.

Like other NSAIDs, dexketoprofen may mask the symptoms of infectious diseases. Single cases of exacerbation of infections localized in the soft tissues have been reported when using NSAIDs. Therefore, medical monitoring of patients with signs of bacterial infection or worsening of the condition during dexectoprofen treatment is required.

Caution should be exercised when prescribing the drug to patients with impaired liver function of the heart or with conditions that may cause fluid retention in the body. In these patients, use of NSAIDs may lead to a worsening of the condition and fluid retention in the body.

Patients who use diuretics or who are prone to hypovolemia should also be cautioned when prescribing Dexketoprofen as they are at increased risk of nephrotoxicity. Caution should be exercised when prescribing in the elderly as they are more frequently diagnosed with renal, hepatic or cardiovascular disorders as well as the occurrence of adverse reactions such as gastrointestinal bleeding or perforated bowel.

Each vial contains 200 mg of ethanol.

Attention and reaction time may decrease due to possible dizziness and somnolence when taking this drug.

Contraindications

– Hypersensitivity to dexketoprofen or other NSAIDs or any of the excipients included in the preparation;

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

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

– gastrointestinal bleeding in the history of other active bleeding (including in the anamnesis.ч. suspected intracranial bleeding) anticoagulant therapy;

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

p> – severe liver function disorders (10-15 points in Child-Pugh score);

– progressive renal disease severe renal function disorders (creatinine clearance less than 30 ml/min);

– confirmed hyperkalemia;

– decompensated heart failure;

– period after coronary artery bypass grafting;

– Hemophilia and other blood clotting disorders;

– pregnancy period breastfeeding;

– under 18 years of age (efficacy and safety not established).

The drug is contraindicated for neuroaxial (epidural or supradural intracavitary) administration because of the ethanol in the drug.

Side effects

The incidence of adverse reactions that were observed during the above clinical trials is presented according to the WHO classification: very common ≥10%; common ≥1% and < 10%; infrequent ≥01% and < 1%; rare ≥001% and < 01%; very rare < 001%; frequency unknown – the incidence of adverse reactions cannot be determined from available data.

Local reactions

Often – pain at the injection site; infrequent – inflammatory reaction hematoma hemorrhage at the injection site fever chills fatigue; rare – back pain fainting fever; very rare – anaphylactic shock facial edema.

The central nervous system

Infrequent – headache dizziness insomnia somnolence; rarely – paresthesia.

Skin disorders

Infrequent – dermatitis rash sweating; rare – acne urticaria; very rare – severe skin reactions (Stevens-Johnson syndrome Lyell syndrome) angioedema allergic dermatitis photosensitization.

Arenal system disorders

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

Metabolic disorders

Rarely: hyperglycemia hypoglycemia hypertriglyceridemia.

Musculoskeletal disorders

Rarely: muscle spasm difficulty of movement in the joints.

Digestive system disorders

Often – nausea vomiting; infrequent – abdominal pain dyspepsia diarrhea constipation haematemesis dry mouth; infrequent – erosive-ulcerative lesions of the gastrointestinal tract (GIT) including bleeding and perforations anorexia increased liver enzyme activity jaundice; very rare – pancreatic lesions liver damage.

Hematopoietic organs

Seldom anemia; very rarely – neutropenia thrombocytopenia.

Respiratory system disorders

Rarely – bradypnoea; very rare – bronchospasm dyspnoea.

Sensory system disorders

Infrequent – blurred vision; rarely – tinnitus.

Cardiovascular system disorders

Infrequent – arterial hypotension, fever, flushing of the skin; rare – extrasystole, tachycardia, arterial hypertension. peripheral edema superficial thrombophlebitis.

Rarely – in women – menstrual cycle disorders in men – disruption of prostate function.

Laboratory findings

Rarely – ketonuria proteinuria.

Other

Aseptic meningitis occurring primarily in patients with systemic lupus erythematosus or mixed connective tissue diseases hematological disorders (aplastic purpura and hemolytic anemia rarely – agranulocytosis and bone marrow hypoplasia).

Overdose

No cases of overdose have been described.

Symptoms: possible vomiting nausea anorexia abdominal pain dizziness disorientation headache drowsiness.

Treatment: symptomatic therapy; hemodialysis if necessary.

Pregnancy use

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