Flamadex - instructions for use, dose, side effects, contraindications

Excipients: Ethanol (ethyl alcohol 95% in terms of 100% substance) 200.0 mg, sodium chloride 8.0 mg, sodium disulfite 2.0 mg, sodium hydroxide to pH 6.5-8.5, water for injection up to 2 ml .

Description:Ptransparent colorless solution.

Pharmacotherapeutic group:NSAIDs

ATX: & nbsp

M.01.A.E Propionic acid derivatives

M.01.A.E.17 Dexketoprofen

Pharmacodynamics:

Non-steroidal anti-inflammatory drug (NSAID), a derivative of propionic acid. Has analgesic, anti-inflammatory and antipyretic effect. The mechanism of action is associated with inhibition of the synthesis of prostaglandins at the level of cyclooxygenase-1 and cyclooxygenase-2.

The analgesic effect occurs 30 minutes after parenteral administration.

The duration of analgesic effect after the administration of a dose of 50 mg is about 4-8 hours.

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

Pharmacokinetics:

Suction

After intramuscular (intramuscular) injection of dexketoprofen, the maximum concentration (C_mOh) in the blood serum is achieved on average after 20 min (10-45 min). The area under the concentration-time curve (AUC) after a single administration in a dose of 25-50 mg is proportional to the dose for both in / m and intravenous (IV) administration. The corresponding pharmacokinetic parameters are similar after a single and repeated IM or IV injection, which indicates the absence of cumulation of the drug.

Distribution

Dexketoprofen is characterized by a high level of binding to plasma proteins (99%). Average value Vd is less than 0.25 l / kg, half-distribution time is about 0.35 h.

Excretion

The metabolism of dexketoprofen mainly occurs by conjugation with glucuronic acid, followed by excretion by the kidneys.Half-life (T_1/2) of dexketoprofen trometamol is about 1-2 hours.

Pharmacokinetics in special clinical cases

In elderly people there is an increase in duration T_1/2 (both after a single dose, and after repeated IM or IV), an average of 48% and a decrease in the total clearance of the drug.

Indications:

- The relief of pain syndrome of various genesis (including postoperative pain, bone metastases, posttraumatic pain, pain in renal colic, algodismenorea, 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, the progression of the disease is not affected.

Contraindications:

- Hypersensitivity to dexketoprofen or other NSAIDs or to any of the excipients that make up the drug (incl.to sulfites);

- complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid or other NSAIDs (including in history);

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

- gastrointestinal hemorrhages in anamnesis, other active bleeding (including suspicion of intracranial bleeding), anticoagulant therapy;

- inflammatory bowel disease (ulcerative colitis, Crohn's disease) in the stage of exacerbation;

- severe violations of the liver (10-15 points on the scale Child-Pugh);

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

- confirmed hyperkalemia;

- Decompensated heart failure;

- period after aortocoronary shunting;

- hemophilia and other disorders of blood clotting;

- pregnancy, the period of breastfeeding;

- children and adolescence up to 18 years.

Flamadex® is contraindicated for neuroaxial (epidural or intrathecal) administration because of the ethanol in the formulation.

Carefully:

Stomach and duodenal ulcer, ulcerative colitis, Crohn's disease, 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 number after surgical intervention), elderly patients (including those receiving diuretics, weakened patients and low body weight), bronchial asthma, simultaneous reception of glucocorticosteroids (including prednisone it), anticoagulants (including warfarin), antiaggregants (including acetylsalicylic acid, clopidogrel), selective serotonin reuptake inhibitors (including citalopram, fluoxetine, paroxetine, sertraline), ischemic heart disease, cerebrovascular disease, dyslipidemia / hyperlipidemia, diabetes mellitus, peripheral arterial disease, smoking, infection Helicobacter pylori, systemic connective tissue diseases, long-term use of non-steroidal anti-inflammatory drugs, tuberculosis, severe osteoporosis, alcoholism, severe physical illnesses.

Pregnancy and lactation:

The use of Flamadex® during pregnancy and during lactation is contraindicated.

Dosing and Administration:

Intramuscularly (deep, slow), intravenously struino (slowly for at least 15 seconds) or drip (10-30 min).

Recommended Adult Dose: 50 mg every 8-12 hours. If necessary, repeated administration of the drug with a 6-hour interval is possible. The daily dose should not exceed 150 mg.

Flamadex® is indicated for short-term use, and treatment should be limited to a period of acute symptoms (no more than 2 days).

Impaired liver function

In patients with mild to moderate liver function impairment (5-9 points on the Child-Pugh scale), the total daily dose should be reduced to 50 mg and frequent monitoring of liver functional parameters. Flamadex® should not be administered to patients with severe liver dysfunction.

Impaired renal function

For patients with mild renal impairment (creatinine clearance 30-60 ml / min), the daily dose is reduced to 50 mg. Flamadex^® Do not administer to 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 in connection with the physiological decline in kidney 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.

Rules for the preparation of solutions

To prepare a solution of Flamadex ® for intravenous infusion, the contents of one ampoule (2 ml) are diluted in 30-100 ml of 0.9% solution of sodium chloride, glucose solution or Ringer's solution. The solution should be prepared in aseptic conditions, protecting from exposure to daylight. The prepared solution must be clear and colorless.

Side effects:

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

On the part of the hematopoiesis system: rarely anemia; very rarely - neutropenia, thrombocytopenia.

From the side of the central nervous system: infrequently - headache, dizziness, insomnia, drowsiness; rarely - paresthesia.

From the sense organs: infrequently - blurred vision; rarely - noise in the ears.

From the cardiovascular system: infrequently - arterial hypotension, a feeling of heat, hyperemia of the skin; rarely - extrasystole, tachycardia, arterial hypertension, peripheral edema, superficial thrombophlebitis.

From the respiratory system: rarely - bradypnoe; very rarely - bronchospasm, dyspnoea.

From the digestive system: often - nausea, vomiting; infrequently - abdominal pain, dyspepsia, diarrhea, constipation, hematemesis, dry mouth; rarely - erosive and ulcerative lesions of the gastrointestinal tract (GIT), including bleeding and perforation, anorexia, increased activity of hepatic enzymes, jaundice; very rarely - the defeat of the pancreas, liver damage.

From the urinary system: rarely - polyuria, renal colic; very rarely - nephritis or nephrotic syndrome.

On the part of the reproductive system: rarely - in women - a menstrual cycle, in men - a violation of the function of the prostate gland.

From the musculoskeletal system: rarely - muscle spasm, difficulty in movement in the joints.

Dermatological reactions: sometimes - dermatitis, rash, sweating; rarely - acne; very rarely photosensitization.

Allergic reactions: rarely - hives; very rarely - severe skin reactions (Stevens-Johnson syndrome, Lyell's syndrome), angioedema, allergic dermatitis.

From the side of metabolism: rarely - hyperglycemia, hypoglycemia, hypertriglyceridemia.

From the laboratory indicators: rarely - ketonuria, proteinuria.

Local and general reactions: often - pain at the injection site; infrequently - inflammatory reaction, hematoma, hemorrhages at the injection site, a feeling of heat, chills, fatigue; rarely - back pain, fainting, fever; very rarely - anaphylactic shock, swelling of the face.

Other: aseptic meningitis, which occurs 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).

Overdose:

Cases of overdose are not described. There may be vomiting, anorexia, abdominal pain, dizziness, disorientation, headache, drowsiness.

Treatment: symptomatic therapy; if necessary, hemodialysis.

Interaction:

Common types of interaction characteristic of all NSAIDs, including dexketoprofen

Unwanted combinations:

- with other NSAIDs, including salicylates in high doses (≥ 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;

- with ticlopidine (increased risk of bleeding due to inhibition of platelet aggregation and lesions of the mucous membrane of the digestive tract);

- with lithium preparations - NSAIDs increase the concentration of lithium in blood plasma (decrease in renal lithium excretion), which can reach toxic levels, so the level of lithium in the blood should be monitored when prescribing, changing the dose or removing dexketoprofen;

- with methotrexate in high (at least 15 mg / week) doses - the toxicity of methotrexate is increased due to a decrease in its renal clearance when using NSAIDs;

- with glucocorticosteroids: increased risk of ulcers and gastrointestinal bleeding;

- derivatives of hydantoin 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 weaken the action of diuretics and other antihypertensive agents. Treatment of NSAIDs is associated with a risk of developing acute renal failure in patients with dehydration (decreased glomerular filtration due to reduced synthesis of prostaglandins). With the combined use of dexketoprofen and diuretics, you should ensure adequate hydration of the patient and control the function of the kidneys before the appointment;

- with methotrexate in low (less than 15 mg / week) doses - the hematological toxicity of methotrexate is increased due to a decrease in its renal clearance with NSAIDs. Weekly monitoring of the blood picture in the first weeks of combined treatment should be performed. In the presence of even minor violations of kidney function, as well as in the elderly, careful monitoring is necessary;

- with pentoxifylline - the risk of bleeding increases. It requires active clinical monitoring and frequent monitoring of bleeding time or clotting time;

- with zidovudine - there may be a toxic effect of zidovudine on reticulocytes, which after the first week of NSAID use may lead to the development of severe anemia. It is necessary to count blood cells and reticulocytes 1-2 weeks after the beginning of the combined treatment;

- with oral hypoglycemic drugs - in view of the possible increase in hypoglycemic effects in connection with the ability of NSAIDs to displace them from the binding sites with plasma proteins.

Combinations that need to be considered:

- with beta-blockers - it is possible to reduce their antihypertensive effect in connection with the inhibition of NSAIDs in the synthesis of prostaglandins;

- with cyclosporine and tacrolimus: it is possible to enhance their nephrotoxicity, due to the effect of NSAIDs on renal prostaglandins. When performing combined therapy, it is necessary to monitor kidney function;

- with thrombolytic drugs - increases the risk of bleeding;

- with probenecid: it is possible to increase the concentration of dexketoprofen in the blood plasma, which may be due to the inhibitory effect on tubular secretion and / or conjugation with glucuronic acid and requires dose adjustmentdexketoprofen;

- with cardiac glycosides - NSAIDs can lead to an increase in their concentration in the blood plasma;

- with mifepristone - in connection with the theoretical risk of changing the effectiveness of mifepristone under the influence of inhibitors of the synthesis of prostaglandins, NSAIDs should be administered 8-12 days after taking mifepristone;

- antibiotics of the quinolone series: a high risk of seizures when using NSAIDs in combination with high doses of quinolones.

Pharmaceutical interaction

Flamadex® can not mix in one syringe with a solution of dopamine, promethazine, pentazocine, pethidine or hydroxysin (a precipitate is formed).

Flamadex® can mix in one syringe with a solution of heparin, lidocaine, morphine and theophylline.

A prepared solution of the preparation Flamadex® for IV infusion can not mix with promethazine or pentazocine.

A prepared solution of Flamadex® compatible with the following solutions for injection: dopamine, heparin, hydroxyzine, lidocaine, morphine, pethidine and theophylline.

Special instructions:

Flamadex® should be used with caution in patients with an allergy in history.

In persons with symptoms of gastrointestinal disorders or with gastrointestinal diseases in the anamnesis, a doctor's supervision is required, especially with gastrointestinal bleeding. In cases of development of gastrointestinal bleeding in patients taking dexketoprofen, the drug is immediately canceled.

Caution is advised to prescribe the drug to patients taking drugs at the same time that may increase the risk of ulcers or bleeding: corticosteroids, anticoagulants (eg, warfarin), selective serotonin reuptake inhibitors or antiplatelet agents (including, acetylsalicylic acid).

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

Flamadex® should be used with caution in patients with chronic heart failure I-II functional class for NYHA.

Similarly to other NSAIDs, Flamadex® can cause an increase in the level of creatinine and nitrogen in the 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 performance of some liver samples, a significant increase in activity ACT and ALT in serum. At the same time, control of liver and kidney functions is necessary in elderly patients. In the case of a significant increase in the relevant indicators, Flamadex® should be discontinued.

Flamadex® should be used with caution in patients with hemopoiesis, patients with systemic lupus erythematosus or other connective tissue diseases.

Like other NSAIDs, Flamadex® can mask the symptoms of infectious diseases. Single cases of exacerbation of infectious processes localized in soft tissues during the application of NSAIDs have been reported. Therefore, medical supervision of patients with signs of bacterial infection or deterioration during treatment with dexketoprofen is required.

Care should be taken when prescribing the drug to patients with impaired liver, kidney, heart, or with conditions that can cause fluid retention in the body. In these patients, the use of NSAIDs may lead to impairment and fluid retention in the body.Care should also be taken when prescribing dexketoprofen to patients who use diuretics or are prone to hypovolemia, because they have a greater risk of developing nephrotoxicity.

Caution is necessary when prescribing the drug to elderly people, because they are more likely to detect violations of the kidneys, liver or cardiovascular system, as well as the occurrence of unwanted reactions, such as gastrointestinal bleeding or intestinal perforation.

Each ampoule of Flamadex® contains 200 mg of ethanol.

Effect on the ability to drive transp. cf. and fur:

In connection with the possible dizziness and drowsiness against the background of treatment with Flamadex®, a decrease in the ability to concentrate attention and speed of psychomotor reactions is possible.

Form release / dosage:

Solution for intravenous and intramuscular administration, 25 mg / ml.

Packaging:

2 ml per ampoule of light-protective glass with a color fracture ring or with a colored dot and a notch. One, two or three color rings and / or a two-dimensional bar code and / or alphanumeric coding or without additional color rings, a two-dimensional bar code, and alphanumeric coding are additionally applied to the ampoules.

By 5 ampoules in a contour cell box made of a polyvinylchloride film and aluminum foil or a polymer film, or without a foil and film.

1 or 2 contour mesh packages together with instructions for use in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 of the year.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-002805

Date of registration:12.01.2015

Date of cancellation:2020-01-12

The owner of the registration certificate:FarmSirma Soteks, ZAO FarmSirma Soteks, ZAO Russia

Manufacturer: & nbsp

Labororios Lesvy S.L. Spain

Representation: & nbspPharm Company Sotex CJSC Pharm Company Sotex CJSC Russia

Information update date: & nbsp07.01.2016

Illustrated instructions

Instructions

Flamadex® (FLAMADEX®)