Flamadex, 25 mg 10 pcs

Pharmacoherapeutic group: non-steroidal anti-inflammatory drug CodeATX: M01AE17 Pharmacological action Pharmacodynamics

Dexketoprofen trometamol, the active substance of Flamadex? refers to non-steroidal anti-inflammatory drugs (NSAIDs) with analgesic, anti-inflammatory and antipyretic effects. The mechanism of action of Dexectoprofen is based on inhibition of proglacidin synthesis at the level of cyclooxygenase (COX-1 and COX-2).

The analgesic effect comes within 30 minutes after oral administration of the drug, therapeutic effect lasts for 4-6 hours.

Pharmacokinetics

Intake

The time of reaching the maximum concentration (TStah) of dexketoprofen in blood plasma after a single oral single dose is on average 30 min (15-60 min). Simultaneous intake of food slows down absorption of dexketoprofen. Areas under the curve “concentration-time” (AUC) after a single and repeated intake are similar, which indicates the absence of cumulation of the drug.

Distribution

Dexketoprofen is characterized by high degree of binding to plasma proteins (99 %). Mean volume of distribution (Vd) is less than 0.25 l/kg, period of half-distribution is approximately 0.35 h.

Metabolism and excretion

The main way of dexketoprofen metabolism is its conjugation with glucuronic acid with subsequent excretion by the kidneys. The potency period (Tie) of dexketoprofen is 1.65 h. In elderly patients there is prolongation of Tie up to 48 % and decrease of total clearance of the drug.

Indications

Active ingredient

Composition

How to take, the dosage

The drug Flamadex/” is taken orally with food. Taking food at the same time slows down absorption of dexketoprofen, therefore in case of acute pain the drug should be taken at least 30 minutes before eating.
Depending on intensity of pain syndrome the recommended dose for adults is 12.5 mg (1/2 tablet of Flamadex?) every 4-6 hours or 25 mg (1 tablet of the drug Flamadex?) every 8 hours.
The maximum daily dose is 75 mg.
The drug Flamadex/” is not intended for long-term therapy, the treatment course should not exceed 3-5 days.
Patients 65 years and older
Patients of advanced age should take the drug Flamadex? starting with the minimum recommended dose. The maximum daily dose is 50 mg.
Doses recommended for the general population may be used if well tolerated.
Patients with hepatic impairment
Patients with mild to moderate hepatic impairment should take Flamadex? starting with the minimum recommended dose. The maximum daily dose is 50 mg. Flamadex? is contraindicated in patients with severe hepatic insufficiency. Patients with renal insufficiency
Patients with renal insufficiency of mild degree of severity-chronic kidney disease, stage 2 (GFR 60-89 ml/min/1.73 m2) should take Flamadex?, starting with the lowest recommended dose. The maximum daily dose is 50 mg.
The use of Flamadex? in patients with chronic kidney disease stages Za (FFR 45-59 mpm/1.73 m2), 36 (FFR 30-44 ml/min/1.73 m2) and 4 (FFR < 30 ml/min/1.73 m2) is contraindicated.

Interaction

The following interactions are typical for all NSAIDs.

Desirable combinations

With other NSAIDs, including salicylates in high doses (more than 3 g/day): simultaneous use of several NSAIDs due to synergistic effects increases the risk of gastrointestinal bleeding and ulcers.

With anticoagulants: Dexketoprofen, like other NSAIDs, may increase the effect of anticoagulants such as warfarin due to the high degree of binding to blood plasma proteins, inhibition of platelet aggregation and damage to the gastrointestinal mucosa. If concomitant use is necessary, close monitoring of the patient’s condition and regular monitoring of laboratory parameters are required.

With heparin: concomitant use increases the risk of bleeding (due to inhibition of platelet aggregation and damaging effect on the mucous membrane of the gastrointestinal tract). If concomitant use is necessary, close monitoring of the patient’s condition and regular monitoring of laboratory parameters are required.

With glucocorticosteroids: concomitant use increases the risk of gastrointestinal ulcers and bleeding.

Lithium preparations: NSAIDs increase concentration of lithium in plasma up to and including toxic concentration, therefore this parameter should be controlled when concomitant use with Dexectoprofen, when changing dosage, and also after discontinuation of NSAIDs.

With methotrexate at high doses (15 mg/week and more): hematologic toxicity of methotrexate may increase due to decreased renal clearance with concomitant use of NSAIDs.

With hydantoins and sulfonamides: possible increase in their toxic effects.

With diuretics, angiotensin-converting enzyme inhibitors (ACE), antibiotics from the group of aminoglycosides, angiotensin II receptor antagonists: simultaneous use with NSAIDs is associated with the risk of acute renal failure in dehydrated patients (reduced glomerular filtration due to reduced prostaglandin synthesis). Concomitant use of NSAIDs may reduce the antihypertensive effect of some drugs. In concurrent use of dexectoprofen and diuretics it is necessary to ascertain that the patient does not have signs of dehydration, and also in the beginning of concurrent use it is necessary to control renal function.

With methotrexate in low doses (less than 15 mg/week): hematological toxicity of methotrexate may increase due to the decrease of its renal clearance in combination with NSAIDs. Blood cell count at the beginning of concomitant use is necessary. In the presence of renal dysfunction, even to a mild degree, as well as in the elderly, close medical monitoring is necessary.

With pvntoxifylline: there may be an increased risk of bleeding. Close clinical monitoring and regular monitoring of bleeding time (clotting time) is necessary.

With zidovudine: there is a risk of increased erythrocyte toxicity due to the effect on reticulocytes, with development of severe anemia after a week of NSAID use. It is necessary to perform a complete blood count with reticulocyte count 1-2 weeks after the start of NSAID therapy.

With oral hypoglycemic agents: NSAIDs may increase hypoglycemic effect of sulfonylurea due to displacement of sulfonylurea from plasma proteins binding sites.

Combinations to be considered with p-adrenoblockers: concomitant use with NSAIDs may decrease the antihypertensive effect of B-adrenoblockers due to inhibition of prostaglandin synthesis.

With cyclosporine and tacrolimus: NSAIDs may increase nephrotoxicity, which is mediated by the action of renal prostaglandins. Concomitant use should monitor renal function.

With thrombolytics: the risk of bleeding increases.

The risk of bleeding from the gastrointestinal tract increases with concomitant use with serotonin reuptake inhibitors (citalopram, fluoxetine, sertraline) and anticoagulants.

With probenecid: there may be an increase in plasma concentrations of NSAIDs, which may be due to the inhibitory effect of probenecid on renal tubular secretion and/or conjugation with glucuronic acid; the dose of NSAIDs may need to be adjusted.

With cardiac glycosides: concomitant use with NSAIDs may lead to increased plasma concentrations of cardiac glycosides.

With mifepristone: Due to the theoretical risk of the effectiveness of mifepristone being affected by inhibitors of prostaglandin synthesis, NSAIDs should not be used earlier than 8-12 days after mifepristone withdrawal.

With quinolones: Evidence from animal studies suggests a high risk of seizures with high-dose quinolones.

If Flamadex? should be used with any of the above medications, a physician should be consulted.

Special Instructions

Unwanted side effects can be minimized when the drug is used in the lowest effective dose with the shortest duration of use necessary to control pain syndrome.

The risk of GI complications is increased in patients with a history of GI ulcers, in elderly patients, and with increasing doses of NSAIDs; therefore, Flamadex should be started at the lowest recommended dose in these patients.

Patients in the above categories, as well as patients who require concomitant use of low-dose acetylsalicylic acid or other agents that increase the risk of GI complications, additional concomitant use of gastroprotectors (misoprostol or proton pump blockers) is recommended.

In patients concomitantly taking anticoagulants or anticoagulants, glucocorticosteroids, the risk of gastrointestinal bleeding also increases.

Patients with a history of gastrointestinal tract disorders or gastrointestinal diseases should be under close medical supervision. If gastrointestinal bleeding or ulceration occurs, the use of Flamadex? should be discontinued.

The drug Flamadex? should be used with caution in patients with a history of gastrointestinal diseases (ulcerative colitis, Crohn’s disease), because of the possible exacerbation of these diseases.

All NSAIDs may inhibit platelet aggregation and prolong bleeding time by inhibiting prostaglandin synthesis. In this regard, the use of the drug Flamadex? in patients simultaneously taking drugs that affect the hemostatic system, such as warfarin, coumarin derivatives and heparin, is not recommended. Like other NSAIDs, Flamadex? may increase plasma creatinine and nitrogen concentrations. Like other inhibitors of prostaglandin synthesis, Flamadex? may have adverse effects on the urinary system, which may lead to glomerulonephritis, interstitial nephritis, papillary necrosis, nephrotic syndrome and acute renal failure. Caution should be exercised when using the drug in patients concomitantly using diuretics and patients with possible development of hypovolemia due to increased risk of nephrotoxicity.

As with other NSAIDs, during the therapy with Flamadex? a slight transient increase in liver enzymes activity may be observed. In elderly patients, hepatic and renal function should be monitored. In case of significant increase of the corresponding indicators, Flamadex* should be discontinued.

Like other NSAIDs, dexketoprofen may mask the symptoms of infectious diseases. If signs of infection or if the patient has worsened while using Flamadex*, the patient should immediately see a physician.

The drug may cause fluid retention, therefore Flamadex* should be used with caution in patients with arterial hypertension, renal and/or cardiac insufficiency. In case of worsening of the condition the drug Flamadex? should be discontinued.

In patients with uncontrolled arterial hypertension, coronary heart disease, congestive heart failure, peripheral arterial disease and/or cerebrovascular disease the drug should be used with caution. The same approach is applied to patients with risk factors of cardiovascular diseases (arterial hypertension, hyperlipidemia, diabetes mellitus, smoking).

Patients with a history of cardiovascular diseases, especially those with heart failure, should be treated with caution due to a possible risk of progression when prescribing Flamadex? Clinical studies and epidemiological data suggest that NSAIDs, especially in high doses and with long-term use, may lead to a negligible risk of acute myocardial infarction or stroke. There is insufficient data to exclude the risk of these events with dexectoprofen.

Elderly patients are particularly susceptible to adverse reactions when using NSAIDs, including the risk of gastrointestinal bleeding and life-threatening perforations, decreased renal, liver and heart function. Appropriate clinical monitoring is necessary when using Flamadex? in this category of patients.

There are data on the occurrence of rare cases of skin reactions (such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) when using NSAIDs. At the first manifestations of skin rash, lesions of mucous membranes or other signs of allergic reactions the drug Flamadex? should be immediately stopped and a doctor should be consulted.

Impact on ability to drive, mechanisms Due to possible dizziness and drowsiness during dexectoprofen administration, concentration ability and responsiveness of patients may decrease, especially during the first hour after administration. Therefore, during the use of Flamadex? caution should be exercised when driving vehicles and engaging in potentially dangerous activities that require increased concentration and quick psychomotor reactions.

Synopsis

Contraindications

Gastrointestinal bleeding or perforations in history, including those associated with previous use of NSAIDs;

Hepatic failure of severe severity (10-15 points on the Child-Pugh scale);

Heavy heart failure (NYHA class III-IV);

With caution

Gastric and duodenal ulcer, ulcerative colitis, Crohn’s disease, liver disease in anamnesis, hepatic porphyria, chronic kidney disease, stage 2 (GFR 60-89 ml/min/1.73 m2), chronic heart failure, arterial hypertension, significant decrease in circulating blood volume (incl.After surgery, elderly patients over 65 years of age (including those on diuretics, patients with debility and low body weight), bronchial asthma, concomitant use of glucocorticosteroids (including prednisalone), anticoagulants (including anticoagulants (incl. warfarin), antiplatelet agents (incl. acetylsalicylic acid, copidotrel), selective serotonin reuptake inhibitors (incl. citalopram, fluoxetine, paroxetine, sertraline), coronary heart disease, cerebrovascular disease, dyslipidemia/hyperlipidemia, diabetes, peripheral arterial disease, smoking, Helicobacter pylori infection, systemic lupus erythematosus (SLE) and other systemic connective tissue diseases, long-term use of nonheroin anti-inflammatory drugs, tuberculosis, severe osteoporosis, alcoholism, severe somatic diseases.

Side effects

Possible side effects are listed according to the World Health Organization classification in descending order of frequency of occurrence: very common (21/10), common (a 1/100, < 1/10), infrequent (a 1/1000, < 1/100), rare (a 1/10000, < 1/1000), very rare (< 1/10000), including individual reports.

Blood and lymphatic system disorders: very rare – neutropenia, thrombocytopenia.

Disorders of the immune system: rarely – laryngeal edema; very rare – anaphylactic reactions, including anaphylactic shock.

Nervous system disorders: infrequent – headache, dizziness, somnolence; rare-paresthesias, syncolalia (transient syncope).

Psychiatric disorders: infrequent-insomnia, feeling of anxiety. Auditory organ and labyrinth disorders: infrequent- vertigo; very rare- tinnitus.

VIight organ disorders: very rare- blurred vision.

Cardiovascular system disorders: infrequent – palpitations, fever, skin flushing; rare – increase of blood pressure; very rare – tachycardia, decreased blood pressure. Respiratory system disorders: rare – bradypnoea; very rare – bronchospasm, shortness of breath.

Gastrointestinal tract disorders: frequent-nausea, vomiting, abdominal pain, dyspepsia, diarrhea; infrequent-gastritis, constipation, dry mouth, flatulence; rare- erosive- ulcerative lesions of the gastrointestinal tract (GIT), bleeding from ulcer or its perforation; very rare- pancreatic lesions Liver and biliary tract disorders: Rarely – hepatitis, increased activity of “liver” enzymes, including. including aspartate aminotransferase and alanine transferase (ACT and AST); very rare – liver damage.

Repnal and urinary tract disorders: rare – polyuria, acute renal failure, very rare – nephritis or nephrotic syndrome. Reproductive system disorders: rare – in women – menstrual cycle disorders, in men – transient prostate disorders with prolonged use. Skin and subcutaneous tissue disorders: infrequent – skin rash; rare – urticaria, acne, increased sweating; very rare – severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome)), angioedema of the face, allergic dermatitis, photosensitization, itching.

Metabolic disorders: rarely-anorexia.

General disorders: infrequently- increased fatigue, asthenia, chills, general malaise; very rarely-peripheral edema.

As with other NSAIDs, the following side effects may occur: aseptic meningitis, developing mainly in patients with systemic lupus erythematosus or other systemic connective tissue diseases, hematologic disorders (thrombocytopenic purpura, aplastic and hemolytic anemia, in rare cases – granulocytosis and bone marrow plaques). Overdose

Symptoms: nausea, anorexia, abdominal pain, headache, dizziness, disorientation, insomnia.

Treatment: symptomatic therapy, if necessary – gastric lavage, activated charcoal administration, hemodialysis is ineffective.

The treatment is symptomatic.

Pregnancy use

Similarities