With the objective of comparing incidence of adverse events of the opioids codeine, hydrocodone, and tramadol in the relief of cancer pain, we conducted a randomized controlled trial in which patients with cancer were randomly assigned according to a computer-generated schedule to receive one of the three opioids. Of the 177 patients who participated, 62 patients received hydrocodone, 59 patients received codeine, and 56 patients received tramadol. The pain experienced by the participants originated most frequently from the stomach, breast, or prostate gland and was classified as either somatic (33%), visceral (52%), mixed (6%), or neuropathic (9%). At the first visit, 60% of the patients described their pain intensity as moderate (4-6/10), with the remaining 40% of the patients describing their pain as severe (7-10/10). The symptoms most associated with pain were weakness, insomnia, and anorexia. In 77% of the total number of cases, the patient was aware of his/her diagnosis prior to admittance to the palliative care unit. Of the total number of cases, 57% fell in the age range of 60-89 years old and 50% of the participants were female. No significant statistical difference in the analgesic efficacy of the three opioids was found (p: 0.69; χ²: 0.73). Use of tramadol produced higher rates of adverse events than codeine and hydrocodone: vomiting, dizziness, loss of appetite, and weakness (p < 0.05). (PsycInfo Database Record (c) 2021 APA, all rights reserved)
BACKGROUND: Analgesics are an essential component of the treatment of cancer-associated pain. Pharmacologic treatment is usually begun with nonopioid analgesics, most frequently acetaminophen. If pain relief is not achieved, the so-called "weak" opioids, such as codeine and hydrocodone, may be used in combination with acetaminophen. Adverse effects (AEs) of the opioids include constipation, somnolence, nausea, and vomiting. Based on the results of a literature search, data comparing the effects of the opioids are lacking. OBJECTIVE: The purpose of this study was to compare the analgesic efficacy and tolerability of codeine phosphate versus hydrocodone bitartrate in combination with acetaminophen in the relief of cancer-related pain. METHODS: This 23-day, prospective, double-blind, randomized, parallel-group study was conducted at 3 Colombian centers: University Libre, Social Security Institute, and General Hospital of Medellín, Cali, Colombia. Outpatients with cancer were eligible for the study if they were aged ≥18 years and had chronic (duration, ≥3 months) moderate to severe cancer-related pain (score on 10-cm visual analog scale [VAS], >3 cm [moderate]; score on a 4-point verbal pain-intensity scale, >1 [moderate]). Eligible patients were randomly assigned to receive 1 tablet of codeine/acetaminophen (C/A) 30/500 mg or hydrocodone/acetaminophen (H/A) 5/500 mg PO q4h (total daily doses, 150/2500 and 25/2500 mg, respectively) for 23 days. In both groups, if pain intensity was rated as >3 on the VAS at week 1 or 2, the dosage was doubled. The primary end point was the proportion of patients who achieved pain relief (defined as a score of >1 on a 5-point verbal rating scale [VRS] (0 = none; 1 = a little; 2 = some; 3 = a lot; and 4 = complete) on study days 1 and 2 and weeks 1, 2, and 3. The secondary end point was the proportion of patients in whom pain was decreased (VAS score, ≤3 cm). AEs were self-reported on a 4-point VRS (0 = absent; 1 = mild; 2 = moderate; and 3 = severe). RESULTS: Of the 121 patients who participated, 59 received C/A and 62 received H/A. Of the total number of cases, 59% were aged 60 to 89 years, and 55% were men. At baseline, 88% of the patients described their pain intensity as moderate; 12%, severe. Of the patients who received C/A, 58% responded to the initial dosage of 150/2500 mg/d, and 8% of the patients responded to the double dosage; 34% did not experience pain relief. In patients with H/A, pain was reported as absent or mild in 56% of patients at the starting dosage of 25/2500 mg/d; an additional 15% of the patients responded to the double dosage; the remaining 29% of patients did not experience any pain relief. None of the between-group differences in response rates were significant. The most common AEs in the C/A and H/A groups were constipation (36% and 29%, respectively), dizziness (24% and 19%), vomiting (24% and 16%), and dry mouth (15% and 18%), with no significant differences between groups. CONCLUSION: In this study, efficacy and tolerability were comparable between C/A and H/A over 23 days of treatment in these patients with moderate or severe, chronic, cancer-related pain. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
OBJECTIVES: To assess the clinical equivalence of tramadol and codeine (reference drugs at the second step of the WHO analgesic scale) in terms of effectiveness, safeness and patient preference. MATERIALS AND METHODS: Double-blind randomized cross-sectional study. Sixty patients with oncologic pain were included. Codeine (Co) and tramadol (Tra) were administered in equivalent doses (individually titrated). Analgesic effectiveness was measured using a VAS and safeness was assessed according to the incidence of nausea, vomiting, sleep disorders, constipation and mood changes. Finally, patient preference for one of the two drugs was determined. Wilcoxon and Chi-square tests were conducted for non-parametric data, as well as the t-test for parametric data. RESULTS: A total of 44 patients (23 sequence Tra-Co and 21 sequence Co-Tra) were analyzed. Baseline characteristics of both groups were similar. The initial severity of pain (VA S ) was 6.2 ± 2.6 in the Tra-Co group and 6.6 ± 2.5 in the Co - Tra group. The average maximum doses used were 68.25 ± 24.2 mg for tramadol and 48.8 ± 15.5 mg for codeine each 6 hours. Both drugs were equally effective for the management of pain in the two periods; first Tra 4.1 ± 2.5 and Co 3.4 ± 2.2; second Tra 2.3 ± 2.9 and Co 2.3 ± 1.8. Incidence of side effects and use of laxatives and antiemetics were not significantly different in both groups . Patient preference was equal for both drugs. CONCLUSIONS: Tramadol and codeine are equally effective for the management of oncologic pain, as well as similar in their side effects and patient preference. This findings support the clinical equivalence of both drugs at the second step of the WHO scale for the management of cancer pain
Evaluated the clinical efficacy and safety of controlled-release codeine (CRC) in the management of chronic cancer pain. 30 Ss (mean age 64.4 yrs) were administered CRC (100, 150, or 200 mg) or placebo every 12 hrs for 7 days preceding the study. Pain intensity was assessed by the Ss twice a day using a visual analog scale (VAS). Pain disability index measured the degree to which pain interfered with functioning across a range of activities. Efficacy of CRC over a 12 hr dosing interval was recorded by the consumption of "rescue" analgesic during consecutive 4 hr intervals. Results indicate that chronic mild to moderate pain can be well controlled with 12-hourly formulation of CRC. The VAS pain intensity scores and pain scores were lower with CRC than with placebo. The "rescue" analgesic consumption was significantly lower in the CRC group than with the placebo treatment. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Evaluates the acute analgesic potency and tolerance of a single oral dose of piroxicam, codeine, and a combination of both drugs in a sample of 88 patients (aged 18–80 yrs) with chronic pain due to cancer. Assessments of pain intensity and relief were made by a nurse in 6 hourly increments after dosing. After 6 hrs, patient and nurse both gave a global impression of therapy. Volunteered side effects and their severity were noted. No significant differences distinguished the 3 treatment groups for pain intensity, analgesic efficacy, speed of action, or side effects. Results suggest that piroxicam may be of use in treating certain types of cancer pain. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Seventy-five patients with moderate to severe cancer pain were randomly assigned in a double-blind fashion to receive first-dose ketorolac tromethamine 10 mg orally, acetaminophen 600 mg plus codeine 60 mg orally, or placebo, followed by subsequent doses of ketorolac or acetaminophen plus codeine four times daily for 7 days. Patient characteristics were similar among the treatment groups. The first-dose observation documented that both ketorolac and acetaminophen plus codeine produced an equivalent reduction in cancer pain and were superior to placebo as measured by pain intensity differences and pain relief. Multidose comparison documented a small but statistically significant advantage in mean daily pain relief favoring acetaminophen plus codeine, although there were no differences in mean daily ratings of overall effects for either study medication. Adverse symptoms were acceptable with both ketorolac and acetaminophen plus codeine. We conclude that ketorolac has significant analgesic activity in patients with cancer pain, although its precise role in the treatment regimen of these patients remains undefined.
Ciramadol is a new opioid agonist-antagonist analgesic with low potential for dependency. Forty-three patients with moderate to severe chronic pain from primary or metastatic malignancy of the bone or major organs were enrolled in a randomized double-blind study that compared orally administered ciramadol (30 mg or 90 mg) to codeine (60 mg) and placebo. A single-dose, four-way crossover design, with a randomized Latin-square treatment sequence, was used. Data for 40 patients who received the above four study medications were included in the final statistical analysis of efficacy. Analgesic efficacy was measured at 0, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, and 6.0 hours, using standard visual and verbal pain relief and pain intensity scales. All active therapies provided greater pain relief than placebo (P less than .05). Ciramadol 30 mg and codeine 60 mg demonstrated equal analgesic activity, whereas ciramadol 90 mg was superior to both therapies. The predominant adverse experiences associated with ciramadol were nausea and drowsiness, which were apparently not dose related. Ciramadol appears to be an effective analgesic at the doses tested, with tolerable gastrointestinal central nervous system side effects at both the 30-and 90-mg dose levels.
The relative analgesic potency of single graded intramuscular doses of oxycodone and morphine was evaluated in a double-blind study in patients with chronic pain due to cancer. When both intensity and duration of analgesia are considered (total analgesic effect), oxycodone was 2/3 to 3/4 as potent as morphine, while in terms of peak analgesia, it was 8/10 to equipotent. In doses producing equivalent peak effect, oxycodone had a shorter duration of action than morphine. Intramuscular oxycodone was also compared to intramuscular codeine in a similar patient group. In terms of total analgesic effect, oxycodone was 10 times as potent as codeine, while in terms of peak analgesia it was 12 times as potent. These relative potency relationships of oxycodone, taken in conjunction with the oral/parenteral potency ratios of codeine and oxycodone established in the previous paper and several previous relative potency assays involving morphine, oxymorphone and codeine, demonstrate a highly consistent pattern of analgesic structure-activity relationships encompassing morphine, oxymorphone, codeine and oxycodone. The results of these studies do not appear to support the hypothesis that, in man, the analgesic activity of codeine is due to its O-demethylation to morphine.
The purpose of this study was to compare the analgesic efficacy and tolerability of opioids hydrocodone and tramadol in the relief of cancer pain.
METHODS:
One hundred and eighteen patients with chronic cancer pain participated in a double-blind, randomized controlled trial. Sixty-two patients received hydrocodone and 56 patients received tramadol.
RESULTS:
Hydrocodone/acetaminophen was effective in relieving pain in 56.5% of the patients at the starting dose of 25 mg/2500 mg/d. An additional 14.5% of the patients responded to a double dose, and the remaining 29% of patients did not experience any pain relief from hydrocodone administration. One dose of tramadol at 200 mg/d produced pain relief in 62% of the patients and alleviated pain in another 11% of patients at a dose of 400 mg/d, and remaining 27% of patients did not experience pain relief from tramadol. No significant statistical difference in the analgesic efficacy of tramadol clorhydrate and hydrocodone/acetaminophen was found. The groups differed significantly in the incidence of side effects like nausea (P=0.03; relative risk (RR), 1.69; confidence interval (IC) 95%, 1.03-2.77), vomiting (P=0.02; RR, 2.21; IC 95%, 1.14-4.32), dizziness (P=0.03; RR, 2.12; IC 95%, 1.17-3.86), loss of appetite (P=0.02; RR, 3.27; IC 95%, 1.12-9.55) and weakness (P=0.019; RR, 7.75; IC 95%, 0.98-61.05).
