To assess methadone analgesia, adverse effects, and calculation method of equianalgesic doses with oral morphine.
Methadone was administered to 21 opioid-tolerant cancer patients because of pain (numerical rating scale [NRS] > 5) on morphine (ten patients), transdermal fentanyl (TF; four patients), morphine, ketamine, and TF (one patient), tramadol (one patient), pethidine (one patient), pain with drowsiness on morphine with ketamine (three patients), and pain with nausea on morphine (one patient). Dose ratios of equivalent daily dose of oral morphine (ddom) to daily dose of oral methadone (ddomet) were 4:1 (ddom to 100 mg), 6:1 (101-300 mg), 12:1 (301-1,000 mg), and 20:1 (over 1,000 mg). Previous opioid treatment was stopped completely (stop-start approach) in 19 patients; two received methadone and other opioids. The mean ddom before switch was 812 +/- 486 mg. Methadone was administered regularly three times daily; 20 patients received oral methadone, one patient received rectal suppositories. Breakthrough pain was treated with methadone (half of regular dose), morphine, fentanyl, metamizol, ketoprofen, or ketamine.
Mean time of methadone treatment was 38.3 +/- 27.1 days (range 3-95 days), mean daily doses: start 48.1 +/- 19.7 mg, maximal 148.5 +/- 104.1 mg, treatment completion 131.1 +/- 104.3 mg. Good analgesia (NRS < 4) was observed in 11 patients, partial (NRS 4-5) in nine patients, and unsatisfactory (NRS > 5) in one patient. Adverse effects such as drowsiness (six patients), constipation (six patients), nausea and vomiting (two patients), sweating (two patients), and respiratory depression (one patient) the last one resolved by methadone cessation and naloxone.
Results confirmed high analgesic efficacy, acceptable methadone adverse event profile, safety, and effectiveness of ddom to ddomet dose calculation method.
[Show abstract][Hide abstract] ABSTRACT: In most cancer patients, pain is successfully treated with pharmacological measures such as opioid analgesics alone or opioid analgesics combined with adjuvant analgesics (co-analgesics). Opioids for mild-to-moderate pain (formerly called weak opioids) are usually recommended in the treatment of cancer pain of moderate intensity. There is a debate whether the second step of the WHO analgesic ladder, which, in Poland, is composed of opioids such as tramadol, codeine, dihydrocodeine (DHC), is still needed for cancer pain treatment. One of the most interesting and useful drugs in this group is tramadol. Its unique mechanism of action, analgesic efficacy and profile of adverse effects are responsible for its successful use in patients with different types of acute and chronic pain, including neuropathic pain. The aim of this article is to summarize the data regarding pharmacodynamics, pharmacokinetics, possible drug interactions, adverse effects, dosing guidelines, equipotency with other opioid analgesics and clinical studies comparing efficacy, adverse reactions and safety of tramadol to other opioids in cancer pain treatment.
[Show abstract][Hide abstract] ABSTRACT: Methadone is an opioid analgesic of step 3 of the World Health Organization (WHO) analgesic ladder.
To outline pharmacodynamics, pharmacokinetics, drug interactions, equianalgesic dose ratio with other opioids, dosing rules, adverse effects and methadone clinical studies in patients with cancer pain. A review of relevant literature on methadone use in cancer pain was conducted.
Methadone is used in opioid rotation and administered to patients with cancer pain not responsive to morphine or other strong opioids when intractable opioid adverse effects appear. Methadone is considered as the first strong opioid analgesic and in patients with renal impairment. Methadone possesses different pharmacodynamics and pharmacokinetics in comparison to other opioids. The advantages of methadone include multimode analgesic activity, high oral and rectal bioavailability, long lasting analgesia, lack of active metabolites, excretion mainly with faeces, low cost and a weak immunosuppressive effect. The disadvantages include long and changeable plasma half-life, high bound to serum proteins, metabolism through P450 system, numerous drug interactions, lack of clear equianalgesic dose ratio to other opioids, QT interval prolongation, local reactions when administered subcutaneously.
Methadone is an important opioid analgesic at step 3 of the WHO analgesic ladder. Future controlled studies may focus on establishment of methadone equianalgesic dose ratio with other opioids and its role as the first strong opioid in comparative studies with analgesia, adverse effects and quality of life taken into consideration.
International Journal of Clinical Practice 08/2009; 63(7):1095-109. DOI:10.1111/j.1742-1241.2008.01990.x · 2.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic pain affects up to 50 million Americans every day. Traditional treatment has included acetaminophen, nonsteroidal antiinflammatory drugs (NSAIDs), or opioids. The combination of NSAIDs and opioids can provide effective treatment for up to 90% of patients with chronic pain, but the NSAIDs have the potential for significant, even life-threatening side effects. Additionally, the nonselective cyclooxygenase inhibitors with 16,000 deaths per year in the United States might not be any safer. The opioids are great for short-term pain, but may need to be adjusted or changed frequently due to the development of tolerance. Understanding of the mechanism of opioids and NSAIDs has improved greatly over the past decade, but is still incomplete.
Seminars in Interventional Radiology 12/2010; 27(4):400-11. DOI:10.1055/s-0030-1267855
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