7 Interactions found for:

The following applies to the ingredients: Oxycodone and Pregabalin (found in Lyrica)

MONITOR CLOSELY: Concomitant use of opioids with gabapentinoids (e.g., gabapentin, pregabalin) may increase the risk of opioid overdose and serious adverse effects such as profound sedation, respiratory depression, syncope, and death due to potentially additive depressant effects on the central nervous system. Using administrative databases, investigators (Gomes T, et al.) conducted a matched case-control study among residents of Ontario, Canada, who received opioid analgesics for non-cancer pain (n=5875; 1256 cases who died of an opioid-related cause and 4619 matched controls) and found that concomitant gabapentin exposure was associated with a 49% higher risk of death from an opioid overdose after adjustment for potential confounders including opioid dose. Moreover, moderate-dose (900 to 1799 mg daily) and high-dose (>=1800 mg daily) gabapentin use was associated with a nearly 60% increase in the odds of opioid-related death compared to no concomitant gabapentin use, and very high-dose (>=2500 mg daily) gabapentin use was associated with a nearly 2-fold increase. By contrast, no significant association between concomitant exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and opioid-related death was observed in a prespecified sensitivity analysis. Concomitant use of opioids has also been reported to increase the risk of gabapentinoid misuse or abuse, particularly in patients with a history of addiction. One retrospective cohort analysis of claims data for a commercially insured U.S. population found that among patients with prolonged gabapentin use (>=120 days over a one year period), concomitant prolonged treatment with opioids increased the risk of misuse of one or both drugs by more than 6-fold. Data from several small studies suggest that in the United States and Europe, approximately 15% to 26% and 7% to 21% of patients with opioid use disorder also misused or abused gabapentin and pregabalin, respectively. Concurrent overuse of both opioids and gabapentin has been reported to quadruple the odds of an emergency department visit or hospital stay for respiratory depression.

Coadministration with opioids may increase the oral bioavailability of gabapentin. The precise mechanism has not been established, but may involve increased gabapentin absorption due to delayed gastrointestinal transit induced by opioids. In 12 healthy male volunteers, single-dose administration of gabapentin 600 mg two hours following controlled-release morphine sulfate 60 mg increased gabapentin systemic exposure (AUC) by 44% and decreased apparent oral clearance and apparent renal clearance by 23% and 16%, respectively, compared to administration with placebo. The pharmacokinetics of morphine and its glucuronides were not altered. Gabapentin has also been reported to reduce the plasma concentrations of hydrocodone in a dose-dependent manner. The mechanism of this interaction is unknown. When immediate-release gabapentin 125 mg or 500 mg was coadministered with hydrocodone 10 mg, hydrocodone Cmax decreased by 3% and 21%, respectively, while AUC decreased by 4% and 22%, respectively. Gabapentin AUC was increased 14% by hydrocodone.

MANAGEMENT: Caution is advised when opioids and gabapentinoids are coadministered, particularly in patients with additional risk factors for respiratory depression such as advanced age, renal insufficiency, or chronic lung disease. The dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect, with cautious titration and dosage adjustments when needed. Use of additional central nervous system depressants should be avoided if possible. Patients should be monitored closely for signs and symptoms of respiratory depression and sedation, and advised to avoid driving or operating hazardous machinery until they know how these medications affect them. For patients who have been receiving extended therapy with both an opioid and a gabapentinoid (either for analgesia or seizure control) and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms and increased seizure risk.

The following applies to the ingredients: Oxycodone

GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including oxycodone. Concomitant use may result in additive CNS depression and impairment of judgment, thinking, and psychomotor skills. In more severe cases, hypotension, respiratory depression, profound sedation, coma, or even death may occur.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of oxycodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of oxycodone by certain compounds present in grapefruit, resulting in decreased formation of metabolites noroxycodone and noroxymorphone and increased formation of oxymorphone due to a presumed shifting of oxycodone metabolism towards the CYP450 2D6-mediated route. In 12 healthy, nonsmoking volunteers, administration of a single 10 mg oral dose of oxycodone hydrochloride on day 4 of a grapefruit juice treatment phase (200 mL three times a day for 5 days) increased mean oxycodone peak plasma concentration (Cmax), systemic exposure (AUC) and half-life by 48%, 67% and 17% (from 3.5 to 4.1 hours), respectively, compared to administration during an equivalent water treatment phase. Grapefruit juice also decreased the metabolite-to-parent AUC ratio of noroxycodone by 44% and that of noroxymorphone by 45%. In addition, oxymorphone Cmax and AUC increased by 32% and 56%, but the metabolite-to-parent AUC ratio remained unchanged. Pharmacodynamic changes were modest and only self-reported performance was significantly impaired after grapefruit juice. Analgesic effects were not affected.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with oxycodone. Any history of alcohol or illicit drug use should be considered when prescribing oxycodone, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Due to a high degree of interpatient variability with respect to grapefruit juice interactions, patients treated with oxycodone may also want to avoid or limit the consumption of grapefruit and grapefruit juice.

The following applies to the ingredients: Pregabalin (found in Lyrica)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.