Flamadex, 25 mg/ml 2 ml 5 pcs

Pharmaceutical effects:

A nonsteroidal anti-inflammatory drug (NSAID), 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 about 4-8 hours.

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

Pharmacokinetics:

Absorption After intramuscular (i/m) administration of dexketoprofen the maximum concentration (Cmax) in blood 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 single and repeated v/m or v/v administration, indicating that there is no cumulation of the drug.

Distribution Dexketoprofen 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.

Elimation 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 1-2.7 hours. Pharmacokinetics in special clinical cases In elderly people, an increase in T1/2 duration (both after a single injection and after repeated intravenous or intravenous administration) of up to 48% on average and a decrease in total clearance of the drug are observed.

Indications

– pain relief of different genesis (incl.ч. Post-operative pain, pain from bone metastases, post-traumatic pain, pain from the kidney 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, sciatica, radiculitis, neuralgia, toothache).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, it has no effect on the progression of the disease.

Active ingredient

Composition

1 ampoule (2 ml):

– dexketoprofen trometamol (in terms of dexketoprofen) 50 mg

Auxiliary substances:

ethanol (95% ethyl alcohol in terms of 100% substance) 200 mg,

sodium chloride 8 mg,

p> sodium disulfite 2 mg,

sodium hydroxide to pH 6.5-8.5,

water for injection to 2 ml

Description:

Pure colorless solution.

How to take, the dosage

Intramuscularly (deeply, slowly), intravenously by jetting (slowly for at least 15 seconds) or drip (10-30 minutes).
Recommended dose for adults: 50 mg every 8-12 hours. If necessary, the drug may be administered repeatedly at 6-hour intervals. The daily dose should not exceed 150 mg. Flamadex® is indicated for short-term use, and treatment with it should be limited to the period of acute symptoms (not more than 2 days).

Hepatic impairment.

In patients with mild to moderate hepatic impairment (Child-Pugh scores 5-9), the total daily dose should be reduced to 50 mg and frequent monitoring of liver function parameters should be performed. Flamadex® should not be prescribed in patients with severe hepatic impairment.

Induced renal function.

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

Patients of advanced age.

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

The rules for preparation of solutions.

In order to prepare Flamadex® solution 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 exposure to daylight. The prepared solution should be clear and colorless.

Interaction

Common types of interaction are typical for all NSAIDs, including dexectoprofen.
Undesirable combinations:
– with other NSAIDs, including salicylates in high doses (≥ 3 g / day): concomitant use of several NSAIDs increases the risk of gastrointestinal bleeding and ulcers;
– with oral anticoagulants, heparin in doses higher than prophylactic;
– with ticlopidine (increased risk of bleeding due to inhibition of platelet aggregation and lesions of the digestive tract mucosa);
– with lithium preparations – NSAIDs increase the concentration of lithium in blood plasma (decreased renal excretion of lithium), which may reach toxic levels, therefore blood lithium levels should be monitored when prescribing, changing the dose or cancelling dexectoprofen;
– with methotrexate at high (at least 15 mg/week) doses – methotrexate toxicity increases due to decreased renal clearance when using NSAIDs;
– with glucocorticosteroids: risk of ulcer 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 agents from the group of aminoglycosides and angiotensin II receptor antagonists. Dexetoprofen 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 prescription;
– with methotrexate at low (less than 15 mg/week) doses – hematological toxicity of methotrexate increases due to its decreased renal clearance when using NSAIDs. Weekly monitoring of blood picture should be carried out during the first weeks of combined treatment. In the presence of even minor renal dysfunction, as well as in elderly people, 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 – toxic effect of zidovudine on reticulocytes may occur, which after the first week of NSAID use may lead to severe anemia. It is necessary to count blood cells and reticulocytes in 1-2 weeks from the beginning of combined treatment;
– with oral hypoglycemic drugs – due to possible increased hypoglycemic effect due to the ability of NSAIDs to displace them from their binding sites with blood plasma proteins;
Combinations to be considered:
– with beta-blockers – possible decrease of their antihypertensive effect due to inhibition of prostaglandin synthesis by NSAIDs;
– with cyclosporine and tacrolimus: possible increase of their nephrotoxicity, due to NSAID effect on renal prostaglandins. When combined therapy it is necessary to monitor renal function;
– with thrombolytic drugs – increased risk of bleeding;
– with probenecid: dexketoprofen concentration in plasma may increase, which may be due to inhibitory effect on tubular secretion and/or conjugation with glucuronic acid and requires correction of dexketoprofen dose;
– with cardiac glycosides – NSAIDs may lead to increased plasma concentrations;
– with mifepristone – due to theoretical risk of inhibitors of prostaglandin synthesis altering mifepristone efficacy, 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 interaction.
Flamadex® must not be mixed in the same syringe with a solution of dopamine, promethazine, pentazocine, pethidine or hydroxyzine (precipitate is formed).
Flamadex® can be mixed in the same syringe with a solution of heparin, lidocaine, morphine and theophylline.
Flamadex® I.V. solution must not be mixed with promethazine or pentazocine.
Flamadex® solution is compatible with the following injection solutions: dopamine, heparin, hydroxyzine, lidocaine, morphine, pethidine and theophylline.

Special Instructions

Flamadex® should be prescribed with caution in patients with a history of allergies. In patients with symptoms of gastrointestinal disorders or with a history of gastrointestinal disease, medical supervision is required, especially in cases of gastrointestinal bleeding. In cases of gastrointestinal bleeding in patients taking dexketoprofen, the drug should be stopped immediately.

Patients taking concomitant medications which may increase the risk of ulceration or bleeding: corticosteroids, anticoagulants (e.g., warfarin), selective serotonin reuptake inhibitors or antiaggregants (including acetylsalicylic acid) should be treated with caution.

Dexketoprofen may cause reversible inhibition of platelet aggregation and increase bleeding time.
Flamadex® should be used with caution in patients with chronic heart failure NYHA functional class I-II.

Like other NSAIDs, Flamadex® may cause elevated plasma creatinine and nitrogen levels and have adverse effects on the urinary system, leading to 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 AST and ALT activity is possible. In this case, control of liver and kidney functions is necessary in elderly patients. In case of significant increase of relevant indicators Flamadex® should be discontinued.
Flamadex® should be used with caution in patients with hematopoiesis disorders, patients with systemic lupus erythematosus or other connective tissue diseases.

Like other NSAIDs, Flamadex® may mask symptoms of infectious diseases. Single cases of exacerbation of infections localized in the soft tissues have been reported when using NSAIDs. Therefore, medical supervision of patients with signs of bacterial infection or deterioration of the condition during dexectoprofen treatment is required.
Caution should be exercised when prescribing the drug to patients with impaired hepatic, renal or cardiac function or with conditions that may cause fluid retention in the body. In these patients, the use of NSAIDs may lead to a worsening of the condition and fluid retention in the body. Caution should also be exercised when prescribing dexketoprofen to patients who use diuretics or are prone to hypovolemia, because they have an increased risk of nephrotoxicity.

Perhaps caution is necessary when prescribing in the elderly as they are more likely to have renal, hepatic or cardiovascular dysfunction and to have adverse reactions such as gastrointestinal bleeding or perforated bowel.

Each vial of Flamadex® contains 200 mg of ethanol.

Impact on ability to drive and operate vehicles and other mechanisms requiring increased concentration

In connection with possible dizziness and somnolence during treatment with Flamadex® , the ability to concentrate and the speed of psychomotor reactions may be reduced.

Formulation.

The solution for intravenous and intramuscular administration is 25 mg/ml.

2 ml in ampoules of translucent glass with a colored break ring or with a colored dot and a notch. One, two or three color rings and/or two-dimensional barcode, and/or alphanumeric coding or without additional color rings, two-dimensional barcode, alphanumeric coding are additionally printed on the ampoules.

Five ampoules each in a contour cell pack of polyvinyl chloride film and aluminum foil or plastic foil, or without foil and film.

1 or 2 contour cell packs together with the instruction for use in a carton pack.
Conditions for storage.

In a dark place at a temperature not more than 25 °С. Keep out of reach of children.

Period of validity.

2 years. Do not use after the expiration date printed on the package.

Contraindications

– hypersensitivity to dexketoprofen or other NSAIDs or to any of the excipients included in the preparation (including sulfites). sulfites);
– full or partial combination of bronchial asthma, recurrent polyposis of the nose and sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including in anamnesis);
– erosive-ulcerative lesions of the gastrointestinal tract and duodenum;
– gastrointestinal bleeding in the anamnesis, other active bleeding (including in the anamnesis.ч. Suspected intracranial bleeding), anticoagulant therapy;
– inflammatory bowel diseases (ulcerative colitis, Crohn’s disease) in the acute stage;
– severe liver function abnormalities (10-15 points by Child-Pugh score);
– progressive renal disease, severe renal impairment (creatinine clearance less than 30 ml/min);
– confirmed hyperkalemia;
– decompensated heart failure;
– period after coronary artery bypass grafting;
– haemophilia and other blood clotting disorders;
– pregnancy, lactation;
– children and adolescents under 18 years old.
Flamadex® is contraindicated for neuroaxial (epidural or intrathecal) administration due to ethanol contained in the drug.
With caution:
Gastric and duodenal ulcer, ulcerative colitis, Crohn’s disease, liver diseases in anamnesis, hepatic porphyria, chronic renal insufficiency (creatinine clearance 30-60 ml/min), chronic heart failure, arterial hypertension, significant reduction of circulating blood volume (including after surgical operation), elderly patients (including those treated with diuretics), elderly patients (including those treated with ureters).including those receiving diuretics, frail patients and those with low body weight), bronchial asthma, concomitant use of glucocorticosteroids (including prednisolone). Anticoagulants (including prednisolone), anticoagulants (including warfarin), antiplatelet agents (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 connective tissue disease, long-term use of non-steroidal anti-inflammatory drugs, tuberculosis, significant osteoporosis, alcoholism, severe medical conditions.

Side effects

Frequency of side effects: frequently (1-10%), infrequently (0.1-1%), rarely (0.01-0.1%), very rarely (less than 0.01%, including some reports).

Hematopoietic system: rare – anemia; very rare – neutropenia, thrombocytopenia.

CNS disorders: infrequent – headache, dizziness, insomnia, somnolence; rarely – paresthesia.

Sensory system disorders: infrequent blurred vision; rarely – tinnitus.

Cardiovascular system: infrequent arterial hypotension, fever, skin hyperemia; rarely – extrasystole, tachycardia, arterial hypertension, peripheral edema, superficial thrombophlebitis.

Respiratory system: rarely – bradypnoea; very rarely – bronchospasm, dyspnoea.

Digestive system disorders: frequent – nausea, vomiting; infrequent – abdominal pain, dyspepsia, diarrhea, constipation, hematemesis, dry mouth; rare – erosive and ulcerative lesions of the gastrointestinal tract (GIT), including bleeding and perforations, anorexia, increased liver enzyme activity, jaundice; very rare – pancreatic lesions, liver damage.

As to the urinary system: rarely – polyuria, renal colic; very rarely – nephritis or nephrotic syndrome.

Reproductive system disorders: rare – in women – menstrual disorders, in men – disorders of prostate function.

Muscular system: rare – muscle spasm, difficulty with movement in the joints.

Dermatological reactions: sometimes – dermatitis, rash, sweating, rarely – acne, very rare – photosensitization.
Allergic reactions: rare – urticaria, very rare – severe skin reactions (Stevens-Johnson syndrome, Lyell syndrome), angioedema, allergic dermatitis.

Metabolism disorders: rarely – hyperglycemia, hypoglycemia, hypertriglyceridemia.

Laboratory disorders: rarely – ketonuria, proteinuria.

Local and general reactions: often – pain at the injection site; infrequent – inflammatory reaction, hematoma, hemorrhages at the injection site, fever, fatigue; rarely – back pain, fainting, fever; very rare – anaphylactic shock, facial edema

Other: Aseptic meningitis, occurring 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).

Similarities