Tramadol is opioid analgesic
Tramadol is a weak central-acting opioid analgesic. The analgesic effect is due to non-selective agonistic interaction with the opioid mu-, delta- and kappa-receptors (with greater affinity for mu-receptors). It also affects the monoaminergic system involved in the regulation of painful stimuli. In therapeutic dosages, tramadol has almost no effect on hemodynamic parameters, does not inhibit respiratory function, and has little effect on gastrointestinal motility. With proper prescription and controlled use, addiction and drug dependence are extremely rare (about 2.5 cases per 1 million people taking the drug).
In diseases of the musculoskeletal system, weak opioids (mainly tramadol hydrochloride) are rarely used in our country: with irreversible changes in osteoarthrosis, ischemic injuries accompanied by tissue necrosis (vasculitis), with severe complications (herpes zoster, osteoporotic fractures). In UK, severe Opioids for the treatment of non-oncological pain are practically not used.
Zaldiar – 37.5 mg of tramadol and 325 mg of paracetamol
Recently, the combined drug Zaldiar was introduced into practice, including fixed doses of tramadol hydrochloride and paracetamol. One tablet contains 37.5 mg of tramadol and 325 mg of paracetamol. The drug is recommended for the treatment of moderate and severe pain of various origins and can be defined as a second-stage remedy for patients who require greater efficacy than that which paracetamol or NSAIDs can provide. The absorption of tramadol is slower than paracetamol. The average half-life of tramadol is 4.7–5.1 h, paracetamol — 2-3 h. Synergism of the analgesic action of two active substances in small doses reduces the risk of side effects. In UK, Zaldiar is subject to quantitative accounting and is discharged by a doctor on a prescription form 148-1 / y.
The indications for Zaldiar are quite wide – injuries, pain in cancer patients, musculoskeletal pain, the postoperative period, anesthesia during painful diagnostic and therapeutic manipulations, etc. Zaldiar is prescribed in cases where a combination of rapid onset and long duration analgesic action is desired. Such situations can occur in acute pain or in patients with chronic diseases that are characterized by variability in the intensity of pain.
The introduction of the combined analgesic Zaldiar into a wide clinical practice was facilitated by a good evidence base. A number of serious clinical trials were conducted in patients with musculoskeletal pain. Tramadol / paracetamol was compared with placebo, tramadol monotherapy and codeine / paracetamol combination. For back pain, osteoarthritis and fibromyalgia, the average daily dose of tramadol / paracetamol was 3-4 tablets per day. These tests have shown the efficacy and safety of the combination of tramadol / paracetamol for short term use (7-14 days). In a number of trials, tramadol / paracetamol (compared with placebo) was used as an adjunctive analgesic in patients receiving a stable dose of NSAIDs. The efficacy of the combination was also proven in these studies compared to placebo. The efficacy of long-term use was also assessed in longer trials . A double-blind, randomized multicenter trial of tramadol / paracetamol (309 patients) and the well-known combination codeine / paracetamol (153 patients) were also conducted in parallel groups for 4 weeks with chronic lower back pain and pain in osteoarthrosis. A similar efficacy and a similar side effect profile were shown (with tramadol / paracetamol being significantly less likely to cause constipation and drowsiness). Average daily doses for tramadol / paracetamol were 131 mg / 1133 mg (3.5 tablets) and codeine / paracetamol 105 mg / 1054 (3.5 tablets).
After the end of this study, 311 patients continued to receive tramadol / paracetamol in an open 23-month trial, which showed the possibility of maintaining long-term adequate analgesia. At the same time, there was no decrease in efficacy or increase in daily doses of the drug (ie, there was no development of tolerance), tolerance remained good even after two years of treatment, there was not a single case of developing addiction or withdrawal syndrome. In long-term studies of the effectiveness of tramadol / paracetamol, adverse effects were often noted, the most frequent were vomiting, nausea, dizziness, headache, and drowsiness, which were moderate and mild in intensity. In one case, the development of withdrawal syndrome was reported.
In London, the successful use of a short (7-day) course of Zaldiar for the treatment of joint pain. The experience of a more prolonged use of weak opioids for the treatment of patients with osteoarthrosis is absent in Russia. In the context of increasing interest in the use of weak opioids for the treatment of chronic musculoskeletal pain, we found it interesting to get our own experience of long-term use of Zaldiar. To this end, a study was undertaken to investigate the efficacy and safety of monotherapy with the analgesic drug Zaldiar in chronic pain syndrome of medium and strong intensity in patients with primary osteoarthritis of the knee and / or hip joints with long-term (45 days) intake in the outpatient setting.
An open, single-phase prospective study included 30 patients who signed informed consent. The average age of patients ranged from 45 to 80 years, with an average of 62 ± 10 years, 29 women, and 1 man. Most patients had a third (66%) or fourth (13%) x-ray stage of arthrosis (according to Kellgren). The increase in body mass index was observed in the majority of patients; the average value of body mass index was 31.3 ± 6.9 kg. 75% of patients had comorbidities, from 1 to 5 (most often arterial hypertension).
The criteria for inclusion in the study were: a reliable diagnosis of osteoarthritis of the knee (allowed to combine with hip arthrosis), moderate and severe pain (at least 50 mm on a visual analogue scale – VAS), which was not stopped by conventional NSAID therapy and / or paracetamol during the previous 4 weeks The entire test period (45 days) patients kept a “Diary”, in which the intensity of the pain syndrome, Zaldiar dose and the effect of treatment were recorded daily. Patients determined the dose of the drug independently, taking into account the recommendations: a single dose of 1-2 tablets, the interval between doses – at least 6 hours, the maximum daily dose – no more than 8 tablets. During the study, no other interventions for osteoarthrosis were allowed. It was specifically stipulated that if the maximum dose (8 tablets) of Zaldiar will not cause the desired analgesia, additional paracetamol intake is allowed (up to 1.5 g per day). Patients with traditional contraindications for taking analgesics that are part of Zaldiar were not included in the test.
In the process of the study, the following were carried out: assessment of the intensity of pain on YOUR before taking the drug, after 2 weeks of taking and after 45 days of taking; consideration of the minimum, average and maximum daily doses; assessment of the subjective impression of patients about the effect of pain relief, as well as the assessment of the effect of therapy by a doctor The effect was evaluated as “very good”, “good”, “satisfactory”, “insignificant”, “no effect”. Achieving a good and satisfactory effect was regarded as adequate pain relief.
The main endpoint of effectiveness with respect to the dynamics of symptoms was the change in the WOMAC index. (WOMAC Osteoarthritis Index, proposed by Western Ontario and McMaster Universities; version of the pain index for YOUR). Symptoms were assessed by the WOMAC pain and functional scale at baseline, after 3 weeks and 6 weeks. Laboratory tests (each visit) were obligatory: hemoglobin (Hb), ESR, bilirubin, transaminases – alanine (ALT) and aspartic (AST), creatinine, alkaline phosphatase (ALP).
The registration of adverse symptoms associated with the intake of the investigational drug, and the assessment of the degree of their severity in points on a scale:
- 0 – no undesirable reactions
- 1 – weak,
- 2 – moderately
- 3 – strongly pronounced; and an estimate of the frequency of adverse reactions in percent.
A few weeks after the end of treatment, patients were specifically interviewed for signs of withdrawal.