Tramadol adverse effects

There is one published report of unintentional tramadol overdose causing acute fulminant hepatic necrosis and death. The exact amount taken was not known, but may have been more than twice the maximum daily dose of 100 mg four times a day for a period of days. Hepatitis and liver failure are listed as possible adverse effects in some US, but no UK product information [54]. 

ALFENTANIL, BUPRENORPHINE, FENTANYL, TRAMADOL PROTEASE INHIBITORS Possibly t adverse effects when buprenorphine is co administered with indinavir, ritonavir (with or without lopinavir) or saquinavir Inhibition of CYP3A4 (CYP2D6 in the case of tramadol) Halve the starting dose and titrate to effect. For single injection of fentanyl, monitor sedation and respiratoiy function closely. If continued use of fentanyl, i dose may be required. Concomitant use of ritonavir and transdermal fentanyl is not recommended... 

The analgesic effect of fentanyl 1.5 pg/kg has been compared with that of tramadol 1.5 mg/kg in 61 patients receiving standardized anesthetics for day-case arthroscopic knee surgery (3). Opioid adverse effects and analgesia were similar in the two groups. 

Nalbuphine has similar efficacy and incidence of adverse effects to tramadol and paracetamol (acetaminophen) (3). Dysrhythmias and coughing occurred more often with nalbuphine than fentanyl (4). 

Finally, 60 women undergoing cesarean section were randomly given epidural tramadol 100 mg, epidural tramadol 200 mg, or saline (94). Pain scores and adverse effects were evaluated for 24 hours after surgery. In all three groups there were no opioid-related adverse effects and epidural tramadol 100 mg provided adequate postoperative analgesia. 

Intramuscular tramadol (50 or 100 mg) during labor is associated with fewer adverse effects than pethidine 75 mg (SEDA-18, 83). Pethidine and the higher dose of tramadol had similar analgesic efficacy, but pethidine was associated with a significantly lower neonatal respiratory rate at birth. 

The reported adverse effects of tramadol are nausea, vomiting, sweating, dry mouth, dizziness, sedation, headache, and hypertension (SEDA-17, 84) (SEDA-20, 81). The atypical analgesic effects of tramadol and its associated adverse effects profile have been reviewed (1). 

The metabolism of tramadol by CYP2D6 is important for its analgesic effect tramadol may therefore be a poor analgesic in poor metabolizers by CYP2D6, while extensive metabolizers may have better analgesia and more adverse effects (SEDA-21, 90). 

In a review of the use of tramadol in musculoskeletal pain the authors concluded that tramadol can be used at Step 2 of the analgesic ladder, since its efficacy, alone or in conjunction with NSAIDs, in the management of chronic musculoskeletal pain without increasing the frequency of adverse effects has been confirmed (2,3). 

In a randomized, controlled study in 60 boys (aged 1-7 years) undergoing unilateral herniorrhaphy, caudal 0.25% bupivacaine 1 mg/kg plus tramadol 1.5 mg/kg resulted in superior analgesia (quality and duration) with no significant increase in opioid-related adverse effects compared with children who received 0.25% bupivacaine 1 mg/kg alone or caudal tramadol 1.5 mg/kg in 0.9% saline alone (4). 

Since the monoamine effects of tramadol resemble the effect of antidepressants, it has been compared with clomipramine + levomepromazine in patients with postherpetic neuralgia. The incidence of adverse effects was 77% with tramadol and 83% with clomipramine (SEDA-20, 81). 

Tramadol and non-steroidal anti-inflammatory drugs have been compared in two studies of patients with joint pain associated with osteoarthritis (8,9). In an open, randomized study 60 patients with osteoarthritis taking NSAIDs were given either modified-release tramadol 100 mg 8-hourly or modified-release dihydrocodeine 60 mg 8-hourly for 4 days the controls were 30 patients who took an NSAID alone (8). Both opioids provided adequate analgesic adjuncts to NSAIDs, but tramadol caused significantly more minor initial adverse effects. 

In a comparison of tramadol (1 or 2 mg/kg) and fentanyl (2 pg/kg) for postoperative analgesia after pediatric anesthesia, the two drugs had equal analgesic potency and produced similar hemodynamic stability and a similar incidence of adverse effects (12). 

In a comparison of the analgesic effects of intermittent boluses of tramadol or morphine after abdominal surgery in 523 patients, tramadol caused more adverse effects (43 versus 34%), although the difference was not statistically significant. The commonest adverse effects were nausea (32 and 22%), vomiting (4.9 and 3.8%), urinary retention (3.0 and 2.7%), and sweating (3.8 and 0.4%) (SEDA-20, 81). 

In a randomized, double-blind study in 20 patients with severe postoperative pain given either intravenous tramadol 1 mg/kg or morphine 0.1 mg/kg, both drugs were effective analgesics but higher dosages than those usually administered were necessary (15). Tramadol did not cause any severe adverse effects, but with morphine there was one case each of severe sedation and respiratory depression. 

In a double-blind study 150 patients with post-traumatic musculoskeletal pain were allocated to either tramadol 100 mg, with possible increases to a total of 200 mg, or morphine 5 mg or 10 mg with a total increase to 20 mg (17). Analgesic efficacy and adverse effect profiles were similar in the two groups. 

In two randomized, double-blind studies tramadol provided effective and safe long-term relief of pain in diabetic neuropathy (20) and fibromyalgia (21). The adverse effects (constipation, nausea, and headache) were well tolerated. 

In 129 patients with severe joint pain associated with osteoarthritis, tramadol was significantly more effective than placebo, but 26 patients taking tramadol and 43 taking placebo withdrew because of ineffectiveness or adverse effects the main adverse effects of tramadol were nausea and constipation (9). 

Tramadol has been combined with various drugs in order to enhance efficacy or reduce adverse effects. 

The analgesic efficacy of tramadol can be further enhanced by adding injectable lysine acetyl salicylate (aspirin) after orthopedic surgery with no significant increase in adverse effects (26). 

In a double-blind, randomized, controlled study, the addition of a tramadol infusion to morphine for PCA in 69 patients undergoing elective abdominal surgery resulted in improved analgesic efficacy and reduced morphine requirements, with a relative lack of adverse effects (32). 

The role of tramadol in the treatment of rheumatologi-cal pain has been reviewed (33). Tramadol causes fewer opioid adverse effects for a given level of analgesia compared with traditional opioids. Common adverse effects, such as nausea and dizziness, usually occur only at the beginning of therapy, abate with time, and are further minimized by up-titrating the dosage over several days (34). 

When tramadol 1 mg/kg was given intravenously to 110 adults for postoperative shivering, few adverse effects were reported two had transient hypotension and two complained of nausea without vomiting. Similarly, mild adverse effects were reported in 20% of patients in a trial of tramadol in cancer pain (SEDA-16, 86), and when it was used to relieve severe pain in sports injuries (SEDA-16, 86). 

The results of postmarketing surveillance of modified-released tramadol in Germany have been published (52). Modified-release tramadol (mean daily dose 236 mg usually divided into two doses) was used in 3153 patients, of whom most had severe or very severe pain. During the 6-week trial, 316 adverse effects were reported by a total of 206 patients (6.5%). Adverse effects were, in... 

The use of modified-release tramadol in chronic malignant pain has been examined in an open, prospective study in 146 patients with moderate to severe cancer pain 90 patients completed the 6-week trial (53). Dropouts were due to opioid adverse effects (20%), inadequate pain relief (9%), or both (2.5%). There was at least one adverse effect in 86%. Overall, 433 adverse effect events were reported but some reduced in frequency over the 6 weeks. Modified-release tramadol (400 mg/day) provided fast and efficient pain relief in almost 60% of patients both during initial dosing and long-term treatment. 

NSAIDs are often administered with opioids because they usually reduce the opioid requirements and some of the opioid-induced Averse effects. Enhanced pain relief has been reported with various combinations including dextromethorphan with ketorolac or tenoxicam, oxycodone with ibuprofen, and tramadol with ketorolac without increased adverse effects. See also coxibs , (p.l79). However, cases of respiratory depression have been reported, see Morphine below. Myoclonus has been reported with high does of morphine administered with NSAIDs, see C3pioids Morphine + Miscellaneous , p.l90. 

Parecoxib had no effect on the pharmacokinetics of alfentanil or fentanyl, and celecoxib and rofecoxib appeared not to affect the pharmacokinetics of tramadol Coxibs can reduce the perioperative opioid requirement, but adverse effects are not necessarily reduced. 

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