63 Hydrocodone/acetaminophen decreased pain in 57% of participants at a starting dose of 25 mg/2500 mg/day (5 doses per day). A total of 62 study patients received hydrocodone/acetaminophen and 56 received tramadol.
#Acetaminophen cod 3 vs hydrocodone trial
evaluated 118 study patients with cancer pain and compared hydrocodone/acetaminophen with tramadol in a double-blind, randomized-controlled trial (RCT). 61 Reddy and coworkers found hydrocodone to be more potent than morphine. 61 Hydrocodone has equivalent potency as morphine on a milligram-for-milligram basis. 60 Polymorphisms of CYP2D6 potentially affect hydrocodone metabolism and therapeutic efficacy. CYP3A4 and CYP2D6 generate hydrocodone metabolites: norhydrocodone and hydromorphone, respectively. Hydrocodone is metabolized by both cytochrome P450-dependent oxidative metabolism and glucuronides. Hydrocodone is structurally similar to morphine, differing by having a single bond at carbons 7 and 8 and a keto (=O) group at 6-carbon. Mehta MD, in Pain Care Essentials and Innovations, 2021 Hydrocodone These combinations provide a synergistic effect and the side effects are reduced.Įric Prommer MD, FAAHPM, HMDC. Hydrocodone is available only for oral use in combination with acetaminophen or acetylsalicylic acid. Drug dependence and addiction are seen with long-term use. Like other opioids, hydrocodone can cause respiratory depression, sedation, and impairment of mental and physical performance, constipation and urinary retention.
Hydrocodone is considered a weak analgesic. Some of the hydrocodone metabolites (dihydromorphine, dihydrocodeine, and hydromorphone) are pharmacologically active and may produce adverse effects if their excretion is impaired. The O-demethylation to dihydromorphine is mediated by polymorphically expressed cytochrome P 450 CYP2D6 enzyme. Hydrocodone undergoes O-demethylation, N-dealkylation, and 6-ketoreduction to the corresponding 6-α and 6-ß hydroxymetabolites. It has a bioavailibity of 50% and is available as oral formulations in combination with non-opioid analgesics. Hydrocodone is a semisynthetic opioid with multiple actions qualitatively similar to codeine. 16,17 As pharmacogenetic testing becomes more widely available, pharmacists with access to this patient data will be able to anticipate significant pharmacogenetic–drug interactions and help clinicians manage them.ĭhanalakshmi Koyyalagunta, in Pain Management, 2007 Hydrocodone Postmortem analysis showed the patient had a CYP2D6 ∗ 2A/∗41 genotype, which is associated with poor metabolizer status. Postmortem hydrocodone blood concentration was 0.14 μg/mL, a concentration associated with fatality while the hydromorphone concentration was below the limit of detection 0.008 μg/mL (a finding expected in a poor metabolizer at CYP2D6). The patient used approximately 30 mg of hydrocodone over 24 hours along with clarithromycin, a potent CYP3A4 inhibitor. In this case, a young girl was given hydrocodone 3 times per day for cold symptoms, and clarithromycin for an ear infection. A case report describing a fatal hydrocodone overdose provides evidence for the seriousness of drug interactions in patients that are poor metabolizers at CYP2D6. Patients who are poor metabolizers at CYP2D6 are at risk for the accumulation of hydrocodone when given a potent CYP 3A4 inhibitor. Clinicians need to be aware that hydrocodone is converted by P450 hepatic enzymes CYP2D6 to hydromorphone and CYP3A4 to norhydrocodone. Hydrocodone is slightly less potent than oxycodone and is found in the following combination products: Norco, Hycet oral solution (hydrocodone and acetaminophen), and Vicoprofen (hydrocodone and ibuprofen). Hydrocodone, an opium derivative, found in both combination products and single entity extended-release (ER) formulations was rescheduled from Schedule III to Schedule II on Octoby the Drug Enforcement Administration.
Mark Holtsman PharmD, Charity Hale PharmD, in Essentials of Pain Medicine (Fourth Edition), 2018 Hydrocodone
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