INSTRUCTIONS FOR MEDICAL USE
ABENOL®
Trade name of the drug: Abenol®
Active substance (INN): Dexketoprofen trometamol
Pharmaceutical form: solution for injection 50 mg/2 ml
Contents:
1 ml of the drug contains:
Active ingredient: dexketoprofen trometamol – 36.9 mg (equivalent to 25.0 mg of dexketoprofen).
Excipients: 96% ethyl alcohol, sodium chloride, sodium hydroxide, water for injection.
Description: clear, colorless liquid with a characteristic odor of alcohol.
Pharmacotherapeutic group: Non-steroidal anti-inflammatory drugs.
ATX code: M01AE17.
Pharmacological properties
Dexetoprofen trometamol is an active substance of the drug – NSAID, which has analgesic, anti-inflammatory and antipyretic effect. The mechanism of action is associated with inhibition of GH synthesis at the level of COX-1 and COX-2.
Analgesic effect occurs 30 min after parenteral administration. Duration of analgesic effect after administration of 50 mg is 4-8 hours. In combined therapy with analgesics of opioid series dexketoprofen trometamol significantly (up to 30-45%) reduces the need for opioids.
Pharmacokinetics
Absorption. Cmax after i/m administration of dexketoprofen trometamol is reached on average in 20 min (10-45 min). AUC after a single administration at a dose of 25-50 mg is proportional to the dose, both when administered v/m and v/v. Corresponding pharmacokinetic parameters are similar after single and repeated IM or IV administration, indicating no drug cumulation.
Distribution. Dexketoprofen trometamol is characterized by high level of binding to plasma proteins (99%). The average value of Vd is less than 0.25 l/kg, the half-distribution time is about 0.35 h.
Excretion. The main way of dexketoprofen excretion is its conjugation with glucuronic acid with following excretion via the kidneys. T1/2 of dexketoprofen trometamol is about 1-2.7 hours. In elderly people prolongation of T1/2 (both after single and repeated IM or IV administration), up to 48% on average, and decrease of total clearance of the drug are observed.
Indications for use
- Control of pain syndrome of different genesis (including postoperative, post-traumatic pain, pain due to bone metastases, renal colic, algodysmenorrhea, sciatica, radiculitis, neuralgia, toothache);
- symptomatic treatment of acute and chronic inflammatory, inflammatory-degenerative and metabolic diseases of the musculoskeletal system (including rheumatoid arthritis, spondyloarthritis, arthrosis, osteochondrosis).
Dosage and administration
I / v and i / m.
Recommended dose for adults: 50 mg every 8-12 hours. If necessary, the drug can be administered repeatedly at 6-hour intervals. The daily dose is 150 mg.
The drug therapy should be started at lower doses in elderly patients and patients with hepatic and/or renal dysfunction; the daily dose is 50 mg. The drug is intended for short-term (not more than 2 days) use during acute pain syndrome. Later the patient may be transferred to oral analgesics.
Technique of I/m injection. The content of 1 amp (2 ml) is slowly injected deeply in v/m.
Technique of I/V injection. If necessary, the content of 1 amp. (2 ml) can be administered by slow intravenous injection of at least 15 s.
Technique for intravenous infusion. The content of 1 amp (2 ml) is diluted in 30-100 ml of physiological solution, glucose or Ringer’s solution (lactate). The solution should be prepared under aseptic conditions and always protected from exposure to daylight.
The diluted solution (should be clear) is administered by slow IV infusion for 10-30 min.
Side effects
Possible side effects when using dexketoprofen trometamol, as with other dexketoprofen preparations, are listed below in descending frequency of occurrence: frequently (1-10% of patients); infrequently (0.1-1% of patients); rarely (0.01-0.1% of patients); very rarely (less than 0.01% of patients), including individual reports.
Blood and lymphatic system: rare – anemia; very rare – neutropenia, thrombocytopenia.
CNS: infrequent – headache, dizziness, insomnia, somnolence; rarely – paresthesia.
Senses: infrequent – blurred vision; rarely – tinnitus.
Cardiovascular system: infrequent – arterial hypotension, fever, skin flushing; rarely – extrasystole, tachycardia, arterial hypertension, peripheral edema, superficial thrombophlebitis.
Respiratory system: rare – bradypnea; very rare – bronchospasm, dyspnea.
Gastrointestinal system: frequently – nausea, vomiting, infrequently – abdominal pain, dyspepsia, diarrhea, constipation, hematemesis, dry mouth, rarely – erosive-ulcerative lesions of the gastrointestinal tract, including bleeding and perforations, anorexia, very rarely – damage to the pancreas.
Liver and gallbladder: rare – increased liver enzymes activity, jaundice; very rare – liver damage.
The urinary system: rare – polyuria, renal colic, very rare – nephritis or nephrotic syndrome.
The reproductive system: rare – menstrual disorders (women), prostate disorders (men).
Musculoskeletal system: rare – muscle spasm, difficulty in moving the joints.
Skin: infrequent – dermatitis, rash, sweating, rarely – urticaria, acne, very rare – severe skin reactions (Stevens-Johnson syndrome, Lyell syndrome), angioedema, allergic dermatitis, photosensitization.
Metabolism: rarely – hyperglycemia, hypoglycemia, hypertriglyceridemia.
Laboratory parameters: rarely – ketonuria, proteinuria.
Local and general reactions: frequent – pain at the injection site; infrequent – inflammatory reaction, hematoma, hemorrhages at the injection site, fever, fatigue; rare – back pain, fainting, fever; very rare – anaphylactic shock, facial edema.
Other disorders: aseptic meningitis, occurring mainly in patients with systemic lupus erythematosus or mixed connective tissue diseases, hematologic disorders (purpura, aplastic and hemolytic anemia); rarely – agranulocytosis and bone marrow hypoplasia
Contraindications
- Hypersensitivity to dexectoprofen or other NSAIDs, or any of the excipients included in the preparation;
- gastric and duodenal ulcer;
- gastrointestinal bleeding in the history, other active bleeding (including suspected intracranial bleeding), anticoagulant therapy;
- gastrointestinal diseases (Crohn’s disease, nonspecific ulcerative colitis);
- severe liver dysfunction (10-15 points on the Child-Pugh scale);
- severe renal impairment (creatinine Cl<50 ml/min);
- bronchial asthma (including anamnesis);
- severe heart failure;
- treatment of pain syndrome in case of aortocoronary bypass surgery;
- hemorrhagic diathesis or other coagulation disorders;
- childhood.
Contraindicated for neuraxial (epidural or subbolon, intrathecal) administration due to the ethanol contained in the drug.
Caution: history of allergic conditions; hematopoietic disorders; systemic lupus erythematosus or mixed connective tissue diseases; simultaneous therapy with other drugs (see “Interaction”); predisposition to hypovolemia; coronary heart disease; advanced age (over 65 years).
Drug interactions
Undesirable combinations
Concomitant administration of several NSAIDs, including salicylates in high doses (more than 3 g/day) increases the risk of gastrointestinal bleeding and ulcers due to synergistic action.
Concomitant use with oral anticoagulants, heparin in doses higher than prophylactic, and ticlopidine increases the risk of bleeding due to inhibition of platelet aggregation and damage to the gastrointestinal mucosa. NSAIDs increase the concentration of lithium in blood plasma, up to toxic, in connection with which this indicator should be monitored when prescribing, changing the dose and after withdrawal of NSAIDs.
When used with methotrexate at high doses (15 mg/week or more), hematological toxicity of methotrexate increases due to its decreased renal clearance during NSAID therapy.
When concomitant use with hydantoins and sulfonamides there is a risk of increased toxicity of these drugs.
Combinations requiring caution
If concomitant use with diuretics, ACE inhibitors is necessary, it should be taken into account that NSAID therapy is associated with the risk of acute renal failure in patients with dehydration (decreased glomerular filtration due to inhibition of prostaglandin synthesis). NSAIDs may reduce the hypotensive effect of some drugs. When concomitant use with diuretics, it is necessary to make sure that the patient’s water balance is adequate, and to monitor renal function before prescribing NSAIDs.
When concomitant use with methotrexate at low doses (less than 15 mg/week), hematological toxicity of methotrexate may increase due to its decreased renal clearance during NSAID therapy. It is necessary to monitor the blood cell count weekly during the first weeks of concomitant therapy. In the presence of even mild renal dysfunction, as well as in the elderly, close medical supervision is required.
Simultaneous use with pentoxifylline increases the risk of bleeding. Intensive clinical monitoring and frequent monitoring of bleeding time (clotting time) is necessary.
When concomitant use with zidovudine, there is a risk of increased toxic effects on red blood cells due to the effect on reticulocytes, with the development of severe anemia a week after administration of NSAIDs. All blood cells and reticulocytes should be monitored 1-2 weeks after initiation of NSAID therapy.
Hypoglycemic effect of sulfonylurea derivatives may be increased due to its displacement from binding sites with plasma proteins under the influence of NSAIDs.
When concomitant use with preparations of low molecular weight heparin, the risk of bleeding increases.
Combinations that should be taken into account
NSAIDs may decrease the hypotensive effect of beta-adrenoblockers, which is caused by inhibition of prostaglandin synthesis.
When concomitant use with cyclosporine and tacrolimus, NSAIDs may increase nephrotoxicity, which is mediated by the action of renal prostaglandins. Renal function should be monitored during combination therapy.
When concomitant use with thrombolytics, the risk of bleeding increases.
When concomitant use with probenecid, plasma concentrations of NSAIDs may increase, which may be due to inhibition of renal secretion and/or conjugation with glucuronic acid. This requires adjustment of the NSAID dose.
NSAIDs may cause increased plasma concentrations of cardiac glycosides.
Because of the theoretical risk of prostaglandin inhibitors altering mifepristone’s effectiveness, NSAIDs should not be prescribed any earlier than 8-12 days after mifepristone withdrawal.
Experimental animal data indicate a high risk of convulsions when NSAIDs are administered with high-dose ciprofloxacin.
Pharmaceutical interaction
The drug should not be mixed in the same syringe with dopamine, promethazine, pentazocine, pethidine or hydroxyzine solution (precipitate is formed).
The drug can be mixed in the same syringe with a solution of heparin, lidocaine, morphine and theophylline.
Diluted solution for infusion should not be mixed with promethazine or pentazocine.
Diluted solution of the drug for infusion is compatible with the following solutions for injection: dopamine, heparin, hydroxyzine, lidocaine, morphine, pethidine and theophylline.
When diluted solutions of the drug for infusion are stored in plastic containers or when using infusion systems made of ethyl vinyl acetate, propionate cellulose, low-density polyethylene or polyvinyl chloride, absorption of the active substance by the listed materials does not occur.
Special Indications
In patients with digestive system disorders or gastrointestinal diseases in the anamnesis, constant monitoring is necessary. In case of gastrointestinal bleeding or ulcerous lesions, the drug therapy should be discontinued.
Since all NSAIDs can inhibit platelet aggregation and increase bleeding time due to inhibition of prostaglandin synthesis, simultaneous administration of dexketoprofenatrometamol and low molecular weight heparin drugs in prophylactic doses in the postoperative period has been studied in controlled clinical trials. No effect on coagulation parameters was observed. Nevertheless, when concomitant administration of the drug with other drugs affecting blood clotting, careful medical monitoring is required.
As other NSAIDs, it may increase plasma creatinine and nitrogen levels. Like other inhibitors of prostaglandin synthesis, it may have adverse effects on the urinary system, which may lead to glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome and acute renal failure.
During therapy with the drug, as well as other NSAIDs, there may be a slight transient increase in some liver parameters, as well as a significant increase in serum levels of AST and ALT. In this case, monitoring of liver and kidney functions is necessary in elderly patients. In case of significant increase in the corresponding indicators, the drug should be discontinued.
Like other NSAIDs, dexketoprofenatrometamol may mask the symptoms of infectious diseases. In the case of symptoms of bacterial infection or deterioration of well-being during therapy with the drug, the patient should inform the doctor.
Each vial contains 200 mg of ethanol
Influence on the ability to drive motor transport and operate machinery
Due to possible dizziness and somnolence during the drug therapy, concentration ability and speed of psychomotor reactions may decrease.
Overdose
Symptoms: nausea, anorexia, abdominal pain, headache, dizziness, disorientation, insomnia.
Treatment: symptomatic therapy; if necessary – gastric lavage, dialysis.
Form of production
Solution for injection 50 mg/2 ml #3 or #5 in a contour cell pack.
Storage conditions
Store in a dark place at temperatures under 25°C.
After dilution the solution is stored for 24 hours at 2 to 8°C in a dark place. Keep out of the reach of children!
Shelf life
2 years. Do not use after expiration date.
Conditions for dispensing from pharmacies
Released by a doctor’s prescription.