Dexketoprofen

Pharmacological properties

dexketoprofen trometamol - propionic acid tromethamine salt - has an analgesic, anti-inflammatory and antipyretic effect and refers to NSAIDs.

The mechanism of its action is based on a decrease in prostaglandin synthesis due to inhibition of COX. In particular, the conversion of arachidonic acid to cyclic PGG endoperoxides is inhibited₂ and PGH₂from which prostaglandins PGE are formed₁PGE₂PGF_2αPGD₂as well as prostacyclin PGI₂ and thromboxanes TxA₂ and TxB₂. In addition, inhibition of prostaglandin synthesis can affect other inflammatory mediators, such as kinins, which can also indirectly affect the main effect of the drug.

The inhibitory effect of dexketoprofen trometamol on the activity of COX-1 and COX-2 was established. Clinical trials for various types of pain have shown that dexketoprofen trometamol has a pronounced analgesic effect. The analgesic effect of dexketoprofen trometamol for i / m and iv administration to patients with moderate to severe pain was studied for various types of pain during surgical interventions (orthopedic and gynecological operations, operations on the abdominal cavity), as well as pain in the musculoskeletal system (acute lower back pain) and renal colic. In the course of the studies, the analgesic effect of the drug was manifested quickly and reached a maximum during the first 45 minutes. The duration of the analgesic effect after applying 50 mg of dexketoprofen trometamol, as a rule, is 8 hours. Studies have shown that the use of the drug Alfort Dex can significantly reduce the dose of opiates when used simultaneously to relieve postoperative pain. If patients who were prescribed morphine for the relief of postoperative pain with a patient-controlled pain relief device were prescribed dexketoprofen trometamol, they required much less morphine (30–45%) than patients who received placebo.

The analgesic effect of the tablets lasts 4-6 hours.

Pharmacokinetics After i / m administration of dexketoprofen trometamol to person C_max achieved after 20 minutes (10 to 45 minutes). It is proved that with a single i / m or iv 25-50 mg AUC (concentration / time) is proportional to the dose. Pharmacokinetic studies of repeated use of the drug proved that AUC and C_max (average maximum value) after the last i / m and iv administration does not differ from the indicators after a single application, which indicates the absence of cumulation of the drug. Similar to other drugs with a high degree of binding to blood plasma proteins (99%), the distribution volume of dexketoprofen is on average 0.25 L / kg. The half-life is approximately 0.35 hours, and T_½ - 1-2.7 hours. The metabolism of dexketoprofen mainly occurs by conjugation with glucuronic acid, followed by excretion by the kidneys. After the administration of dexketoprofen trometamol in the urine, only the optical isomer S - (+) is determined, which indicates the absence of transformation of the drug into the optical isomer R - (-). After the introduction of single and multiple doses, the degree of effect of the drug on healthy elderly volunteers (from 65 years old) participating in the study was significantly higher (up to 55%) than on young volunteers, however, there was no statistically significant difference in the maximum concentration and time to reach it observed. Average T_½ increased (up to 48%), and a certain total clearance decreased.

Following oral administration of dexketoprofen trometamol C_max in blood plasma is achieved on average after 30 minutes (15-60 minutes). The distribution time of dexketoprofen is 0.35 hours.Like other drugs that have a high degree of binding to plasma proteins (99%), the average distribution volume is less than 0.25 l / kg body weight. After the use of dexketoprofen trometamol in the urine, only the S - (+) - enantiomer is determined, which proves the absence of its inversion in the R - (+) - enantiomer in the human body. When studying the pharmacokinetics of multiple doses, it was found that after the last use of dexketoprofen trometamol, the AUC bioavailability was not higher than after its single use, which proves the absence of cumulation of the drug.

The elimination of dexketoprofen trometamol occurs mainly due to glucuronidation and further excretion by the kidneys. T_½ dexketoprofen is 1.65 hours.

Dexketoprofen when administered orally has a linear relationship with a dose-dependent effect in systemic use.

Indications

Rr for injections. symptomatic treatment for acute pain of medium and high intensity in the case when oral administration of the drug is impractical, for example, postoperative pain, renal colic and lower back pain (back pain).

Tablets. Symptomatic treatment of mild to moderate pain, for example, musculoskeletal pain, pain during menstruation (dysmenorrhea), toothache.

Application

Tablets. depending on the type and intensity of pain, the recommended dose is 12.5 mg (½ tablets) every 4-6 hours or 25 mg every 8 hours. The total daily dose should not exceed 75 mg.

Undesirable effects of the drug can be minimized by applying the minimum effective doses for the shortest possible time necessary to eliminate the symptoms. The drug is not intended for prolonged therapy; the duration of treatment should be limited by the time symptoms are present.

Like other NSAIDs, Alfort Dex should be taken primarily with food or after meals. However, intake along with food delays absorption; in case of acute pain, it is recommended to take the drug at least 30 minutes before meals.

Elderly patients. It is recommended to start treatment with low doses. The daily dose is 50 mg. With good tolerability of the drug, the dose can be increased to the usual. You should also regularly monitor for the presence of gastrointestinal bleeding.

Impaired liver function of mild to moderate severity. Treatment should be started with the minimum recommended dose and under strict medical supervision. The daily dose is 50 mg. Alfort Dex should not be used in patients with severe hepatic impairment.

Impaired renal function of mild severity. For patients with mild renal failure, the initial dose should be reduced to a daily dose of 50 mg. Alfort Dex should not be used in patients with moderate to severe renal failure.

Rr for injections. Adults The recommended dose is 50 mg with an interval of 8-12 hours. If necessary, a repeated dose is administered after 6 hours. The maximum daily dose should not exceed 150 mg. The drug is intended for short-term use, therefore, it should be used only during acute pain (no more than 2 days). Patients should be transferred to oral administration of analgesics, if possible. Adverse reactions can be reduced by using the smallest effective dose for the shortest possible time necessary to improve the condition. In case of postoperative pain of moderate or severe severity, the drug can be used according to indications in the same recommended doses in combination with opioid analgesics.

Elderly patients. Dose corrections are usually not required. However, due to the physiological decrease in renal function, a lower dose is recommended, namely, the maximum daily dose is 50 mg for mild renal impairment.

Violations of the liver.For patients with mild or moderate liver pathology (5–9 points on the Child-Pugh scale), the maximum daily dose should be reduced to 50 mg and liver function should be carefully monitored. In severe liver diseases, the drug is contraindicated (10-15 points on the Child-Pugh scale).

Violations of the kidneys. For patients with impaired renal function of mild degree (creatinine clearance - 50–80 ml / min), the maximum daily dose should be reduced to 50 mg. In case of impaired renal function of moderate or severe degree (creatinine clearance of 50 ml / min), the drug is contraindicated.

V / m introduction. Injection solution should be slowly injected deep into the muscle.

IV infusion. For intravenous infusion, dilute the contents of a 2 ml ampoule in 30–100 ml of 0.9% sodium chloride solution, glucose solution or ringer-lactate solution. A solution for infusion should be prepared under aseptic conditions, avoiding the influence of natural daylight. The prepared solution should be transparent. Infusion must be carried out within 10-30 minutes. Avoid the influence of natural daylight on the cooked solution.

Alfort Dex, diluted in 100 ml of 0.9% sodium chloride solution or in glucose solution, can be mixed with dopamine, heparin, hydroxyzine, lidocaine, morphine, pethidine and theophylline.

Alfort Dex cannot be mixed in solution for infusions with promethazine and pentazocine.

IV injection (bolus injection). If necessary, the contents of one ampoule (2 ml of solution for injection) should be administered for at least 15 s.

The drug can be mixed in small volumes (for example in a syringe) with solutions for injection of heparin, lidocaine, morphine and theophylline.

Alfort Dex cannot be mixed in small volumes (for example in a syringe) with solutions of dopamine, promethazine pentazocine, pethidine and hydrocortisone, since a white precipitate forms.

The drug can only be mixed with the above medicines.

With i / m or iv injection, the drug should be immediately administered after it has been recruited from an ampoule. Solution for infusion must be used immediately after its preparation.

When storing diluted solutions of the preparation in plastic bags or in products adapted for administration from ethyl vinyl acetate, cellulose propionate, low density polyethylene and polyvinyl chloride, no changes in the active substance were observed due to sorption.

The drug Alfort Dex is intended for single use, so the remains of the finished solution should be disposed of. Before drug administration it is necessary to be convinced that solution is transparent and colorless. A solution containing solid particles cannot be used.

Contraindications

• Hypersensitivity to dexketoprofen or excipients of the drug; asthma attacks, bronchospasm, acute rhinitis or the development of nasal polyps, urticaria or angioedema resulting from the use of drugs of a similar effect, for example acetylsalicylic acid or other NSAIDs; active phase of peptic ulcer or bleeding, suspected bleeding or with a recurring peptic ulcer or bleeding in history (at least two confirmed facts of ulcer or bleeding) or chronic dyspepsia; gastrointestinal bleeding, other bleeding in the active phase or increased bleeding; gastrointestinal bleeding or a history of perforation associated with prior NSAID therapy; Crohns disease or ulcerative colitis; history of ba; severe heart failure; impaired renal function of moderate or severe degree (creatinine clearance 50 ml / min); severe dysfunction of the liver (10-15 points on the child scale - I drink); hemorrhagic diathesis and other bleeding disorders; iii trimester of pregnancy and lactation.

Rr for injections. Use for the purpose of neuroaxial (intrathecal or epidural) administration (due to the content of ethanol).

Side effects

The following are adverse reactions, the connection of which with dexketoprofen trometamol, according to clinical data, is recognized as the lowest possible, as well as adverse reactions reported in the post-marketing period.

Most often, adverse reactions from the digestive tract are noted. So, it is possible to develop stomach ulcers and duodenal ulcers, perforation or bleeding in the digestive tract, sometimes fatal, especially in elderly patients. According to reports, nausea, vomiting, diarrhea, flatulence, constipation, dyspepsia, abdominal pain, melena, vomiting with an admixture of blood, ulcerative stomatitis, exacerbation of colitis, Crohns disease may appear during the use of the drug. Gastritis is less common. Also, with the use of NSAIDs, edema, hypertension, heart failure can occur.

As with other NSAIDs, it is possible to develop aseptic meningitis, which mainly develops in patients with systemic lupus erythematosus or with mixed collagenosis, and blood reactions (purpura, hypoplastic and hemolytic anemia, rarely agranulocytosis and bone marrow hypoplasia).

Bullous reactions are possible, including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare).

According to the results of clinical studies and epidemiological data, the use of certain NSAIDs, especially in high doses and for a long time, may be accompanied by some increase in the risk of developing pathology caused by arterial thrombosis, such as myocardial infarction or stroke.

special instructions

Use with caution in patients with a history of allergic conditions. avoid the use of Alfort Dex in combination with other NSAIDs, including selective cog-2 inhibitors.adverse reactions can be reduced by applying the smallest effective dose for the shortest possible time necessary to improve the condition.

Gastrointestinal bleeding, ulceration or perforation, in some cases with a fatal outcome, were observed for all NSAIDs at different stages of treatment, regardless of the presence of precursor symptoms or the presence of a serious digestive tract history. With the development of gastrointestinal bleeding, the drug should be discontinued. The risk of gastrointestinal bleeding, ulcer formation or perforation increases with an increase in the dose of NSAIDs in patients with a history of ulcer, especially