Back pain is a pressing and common problem in modern healthcare. Single episodes of pain in the lumbosacral region, according to various sources, are reported by 60-90% of people, while back pain is detected annually in 25-40% of the world's population. Most often, the pain episode is short-term in nature, but in approximately 4% of the working population, back pain causes long-term disability, and in another 1% - permanent disability [1]. Despite the improvement of pain pharmacotherapy, it is not always possible to achieve adequate and rapid relief of a painful episode, which is the main reason for subsequent chronic pain. According to research results [2, 3], 70% of patients with acute nonspecific lumbodynia/lumbar ischialgia continued to experience functional limitations due to pain after 1 week, 69% continued to take analgesics continuously due to severe pain. After 3 months, almost ½ of the patients reported limitation of daily activity due to back pain, 46% of respondents continued to periodically take analgesics.
There is an acute problem of adverse events, such as gastroenteropathy, kidney damage, increased blood pressure (BP), and an increased risk of ischemic damage to the heart and brain, when using nonsteroidal anti-inflammatory drugs (NSAIDs). This is especially true in the presence of comorbid diseases, in particular in middle-aged and elderly people. Solving this problem requires a balanced approach to the prescription of pain relievers, taking into account both their strengths and weaknesses.
The search for drugs that have, on the one hand, a pronounced analgesic effect and anti-inflammatory activity, and on the other, a favorable safety profile, remains an urgent task. In this context, it is necessary to note the unjustifiably rare use of naproxen in Russia, which has the lowest risk of cardiovascular complications and is widely used in clinical practice abroad.
The purpose of this study was to evaluate the effectiveness and safety of the drug Nalgesin Forte (naproxen 550) in patients with nonspecific pain syndrome in the lumbosacral spine.
Material and methods
The study included 90 patients, of whom 88 took at least one dose of the drug. Among the patients, 68% were female. The average age of the patients was 42.8±12.4 years.
The main inclusion criterion is acute pain in the lumbosacral region with an intensity according to VAS from 40 to 80 mm (with a 100 mm ruler). The study did not include patients with radiculopathy, as well as with possible specific causes of pain, which could be evidenced by an unexplained decrease in body weight, indications of a history of trauma, or an increase in body temperature. Additional exclusion criteria were the presence of diseases of the gastrointestinal tract (GIT), such as erosive and ulcerative changes in the stomach and duodenum, intestinal bleeding, as well as inflammatory bowel diseases in the acute stage. Due to the possible impact on the bioavailability of the drug, the following groups of patients were not included in the study population: with impaired liver and kidney function, with multicomponent therapy for concomitant diseases, with diabetes mellitus, with gastric surgery.
All patients were examined using the following clinical scales and questionnaires:
- visual analogue scale (VAS) with gradation from 0 to 100 mm - assessment of pain severity [4];
— Oswestry questionnaire — assessment of disability in low back pain [5];
— Schober test — assessment of range of motion [6];
— General Clinical Impression Scale—a physician’s assessment of the effectiveness of treatment [7].
In addition, the following safety and tolerability parameters of naproxen were assessed:
- laboratory parameters (complete blood count, complete urinalysis, biochemical blood test with determination of liver enzymes (aspartate aminotransferase, alanine aminotransferase, bilirubin, gamma-glutamyl transpeptidase), as well as glucose and creatinine levels;
- blood pressure level, heart rate (HR), measured at inclusion and at the control visit.
At the time of inclusion, the average value of back pain was 63.0±13.1 mm according to the VAS, 15.8±3.6 cm according to the Schober test, and 46.9±22.0% according to the Oswestry questionnaire. These data indicate a relatively high intensity of pain in the study population.
Patients who met the requirements of the protocol were prescribed Nalgesin Forte at a dose of 550 mg 2 times a day after the screening visit. When the pain syndrome was relieved (VAS score less than 10 mm) at the 2nd visit (7 days from the start of therapy), patients completed the study with evaluation of efficacy and safety parameters. If pain persisted, treatment with the study drug was extended for another 7 days, followed by assessment of the effectiveness and safety of therapy (3rd visit).
Statistical processing of the obtained data was carried out using the method of descriptive statistics using the Statistica 8 program. Intergroup differences were assessed using the Mann-Whitney test. The Wilcoxon test was used to compare dependent groups before and after treatment. Differences were considered statistically significant at p
<0,05.
Buy Naproxen tablets 250 mg No. 30 in pharmacies
Instructions for use Naproxen-Acri tab. 250mg No. 30
Dosage forms tablets 250 mg Synonyms Nalgesin Nalgesin forte Sanaprox Group Anti-inflammatory drugs - propionic acid derivatives International nonproprietary name Naproxen Composition Active ingredient - naproxen. Manufacturers Akrikhin KhFK (Russia) Pharmacological action The drug has an anti-inflammatory, analgesic, antipyretic effect. The mechanism of action is associated with non-selective suppression of the activity of cyclooxygenase types 1 and 2, as a result of which the synthesis of prostaglandins, modulators of pain, fever and inflammation, is inhibited. It has a more prolonged effect compared to other non-steroidal anti-inflammatory drugs. When taken orally, the drug is quickly absorbed from the gastrointestinal tract, bioavailability is about 90%. Binding to plasma proteins is almost complete (up to 98%). The maximum concentration in the blood is reached after 2-3 hours. The half-life is approximately 12 hours. The drug is metabolized in the liver and excreted from the body mainly by the kidneys (up to 98%) in the form of conjugates or unchanged (10%). 0.5-2.5% of the drug is excreted in bile. If renal function is impaired due to chronic pyelonephritis, accumulation of metabolites is possible. Side effects Possible headache, tinnitus, dizziness, slow reaction rate, drowsiness, weakness, heartburn, nausea, vomiting, epigastric discomfort, sweating, allergic skin reactions (skin rashes, urticaria, itching), Quincke's edema. In rare cases, visual disturbances and hearing loss, NSAID gastropathy (damage to the antrum of the stomach in the form of mucosal erythema, hemorrhages, erosions and ulcers), erosive and ulcerative lesions of other parts of the gastrointestinal tract, bleeding and perforation of the gastrointestinal tract; eosinophilic pneumonia; liver and/or kidney dysfunction; leukopenia, thrombocytopenia, granulocytopenia, aplastic and/or hemolytic anemia. Indications for use Rheumatism, rheumatoid arthritis, reactive synovitis with deforming osteoarthritis, ankylosing spondylitis, articular syndrome with exacerbation of gout, neuralgia, myalgia, migraine, toothache, adnexitis, primary dysmenorrhea, tumor, traumatic, postoperative pain, diseases of the ENT organs, febrile condition. Contraindications Hypersensitivity, “aspirin” triad (asthma, rhinitis, recurrent nasal polyposis), other manifestations of intolerance to NSAIDs, peptic ulcer of the stomach and duodenum in the acute phase. Restrictions on use: Severe cardiac, hepatic and renal failure, hematopoietic disorders, adolescence (up to 16 years), pregnancy, breastfeeding (breastfeeding should be avoided). Directions for use and dosage : Orally, during meals. Adults: at the beginning of treatment and in acute conditions - 500-1000 mg/day in 2 doses (morning and evening); maintenance dose - 500 mg/day in 1 or 2 doses. Acute attack of gout - 750 mg in 1 dose, then 250-500 mg every 8 hours for 2-3 days. Children: 10 mg/kg/day in 2 doses every 12 hours. Overdose Symptoms: drowsiness, heartburn, dyspepsia, nausea, vomiting. Treatment: gastric lavage, administration of activated carbon - 0.5 g/kg; dialysis is not effective. Interaction Increases the toxicity of hydantoin, indirect anticoagulants, sulfonamides, methotrexate (blocks tubular secretion). Reduces the natriuretic and diuretic effect of furosemide, hypotension caused by beta blockers. Reduces the excretion of lithium salts and increases its concentration in plasma. Antacids containing magnesium and aluminum reduce absorption. Special instructions With long-term use, it is necessary to monitor the functions of the liver and kidneys, the composition of peripheral blood. If it is necessary to determine 17-ketosteroids or 5-hydroxyindoleacetic acid, treatment should be discontinued 48 hours before the test. Storage conditions List B. In a dry place, protected from light.
results
The main endpoint (control) point for assessing the effectiveness of the study drug was a reduction in pain by more than 30% from the initial level. By the end of the 1st week of therapy, a clinically significant reduction in pain was noted by 88.5% of patients, and by the end of the 2nd week of therapy - by 93.1%. Thus, in general, 95% of patients achieved results by the 1st week of therapy.
An important point in the effectiveness study was the assessment of complete pain relief (VAS less than 10 mm). Thus, 44.8% of patients after 7 days of taking naproxen considered that the drug completely relieved pain. By the 3rd visit, which took place 14 days from the start of therapy, 67.8% of patients (based on their VAS assessment) were completely free of pain. The average value on the VAS scale before treatment was 63.0 mm, and after the course of therapy - 10.1 mm. Reduction in the severity of pain on the VAS scale by 52.9 mm (6.2 times from the initial level) during therapy with naproxen ( p
<0.0001) allows us to conclude that the study drug is highly effective in the treatment of nonspecific pain in the lower back.
Positive dynamics during therapy with Nalgesin Forte (naproxen) were also noted in the increase in patient activity, assessed using the Oswestry questionnaire (Fig. 1).
Rice. 1. Dynamics of daily activity of patients during naproxen therapy. The control visit was the 2nd visit for patients who completed the study after 7 days, and the 3rd visit for patients who completed the study after 14 days.
Upon inclusion in the study, many patients reported a significant impact of pain on daily activities. At the inclusion visit, the extreme degree of influence was noted by 1/3 of the patients, of which 23 (26.1%) patients as critical and 6 (6.87%) patients as emergency. At the follow-up visit, none of the patients reported the limitation of daily activities as extreme or critical. The majority of patients - 71 (81.6%) - experienced minimal restrictions in activities during therapy, which did not have a significant impact on daily activities. The average Oswestry questionnaire scores decreased by more than 4.78 times (from 46.9 points at the inclusion visit to 9.8 points at the control visit).
Mobility in the lumbosacral region was assessed using the Schober test, which assesses movement in the sagittal plane. The amplitude of movements in the Schober test increased by 27% (from 15.7 cm at the 1st visit to 20.0 cm at the control visit), with p
<0,0001.
The results of assessing the effectiveness of treatment using the General Clinical Impression scale are presented in Fig. 2.
Rice. 2. Assessing the effectiveness of treatment using the General Clinical Impression scale.
95.4% showed an improvement in their condition, with 81.6% significant and very significant.
Assessment of safety and adverse events during therapy
During the study, 94.3% of patients noted the absence of adverse reactions. Adverse reactions were reported in 5 patients (5.7%). 80% of them had a mild severity, mainly characterized by gastrointestinal disorders (nausea, epigastric discomfort), which did not contribute to either dose reduction or drug discontinuation. In only 1 case, an adverse event (not related to the use of the drug), manifested by increased back pain, was regarded as severe and required a change in the treatment regimen. At the inclusion visit and control visit, both somatic (BP, heart rate) and laboratory (blood, urine) parameters were monitored in all patients. No significant deviations were observed with the use of naproxen. It should be noted that in general, patients showed high adherence to therapy. Compliance of more than 80% was noted in 98% of patients at the 2nd visit and 100% at the 3rd visit.
Cardiovascular safety of celecoxib, naproxen, and ibuprofen in patients with arthritis
Nonsteroidal anti-inflammatory drugs (NSAIDs) first began to be used in clinical practice in the 1960s, and are currently one of the most commonly prescribed drugs (more than 100,000 prescriptions annually in the United States alone). The mechanism of action of NSAIDs is the inhibition of cyclooxygenase (COX), which is accompanied by a decrease in inflammation and pain by reducing the synthesis of prostaglandins. However, it must be remembered that the flip side of decreased prostaglandin synthesis in the stomach is an increased risk of erosive and ulcerative lesions. This problem can be solved by the use of selective COX-2 inhibitors.
But not everything is so simple with these drugs. In 2004, rofecoxib was banned due to its high cardiovascular risk. Another study showed an increased cardiovascular risk with doses higher than the approved dose of celecoxib. In this regard, the results of the Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen (PRECISION) study, which compared the outcomes of therapy with celecoxib (including cardiovascular), naproxen and ibuprofen, are interesting.
Methods
The analysis included patients with rheumatic diseases (osteoarthritis, rheumatoid arthritis) who were randomized to receive ibuprofen, naproxen, or celecoxib.
The purpose of the study
Celecoxib was shown to meet the noninferiority threshold for composite cardiovascular death (including death due to bleeding), myocardial infarction, and nonfatal stroke.
The noninferiority criterion was defined as a hazard ratio (HR) of 1.12 or lower with an upper limit of 97.5% confidence interval (CI) of 1.33 or lower in the intention-to-treat analysis or 1.40 or lower in the on-treatment analysis. .
results
The study randomized 24,081 patients, with a mean daily dose of celecoxib 209 mg, naproxen 852 mg, ibuprofen 2045 mg. The average duration of treatment was 20.3±16.0 months, the average follow-up period was 34.1±13.4 months.
It was noted that 68.8% of patients discontinued study drug therapy and 27.4% of patients were excluded from the analysis.
In the intention-to-treat analysis, 188 patients in the celecoxib group (2.3%), 201 patients in the naproxen group (2.5%), and 218 patients on ibuprofen therapy (2.7%) met the composite endpoint. HR for celecoxib vs. naproxen was 0.93; 95% CI, 0.76-1.13; HR for celecoxib vs. ibuprofen was 0.85; 95% CI, 0.70-1.04; P<0.001 for noninferiority for both comparisons).
In the on-treatment analysis, 134 patients in the celecoxib group (1.7%), 144 in the naproxen group (1.8%), and 155 patients in the ibuprofen group (1.9%) met the composite endpoint. HR for celecoxib vs. naproxen is 0.90; 95% CI, 0.71-1.15; HR for celecoxib vs. ibuprofen was 0.81; 95% CI, 0.65-1.02; P<0.001 for noninferiority for both comparisons).
Conclusion
The use of celecoxib in medium doses is not inferior in cardiovascular safety to the drugs naproxen and ibuprofen.
Source:
Steven E. Nissen, et al. Cardiovascular Safety of Celecoxib, Naproxen, or Ibuprofen for Arthritis. NEJM November 2016