Drug Interactions between Fioricet with Codeine and Lyrica

GENERALLY AVOID: Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants (e.g., nonbenzodiazepine sedatives/hypnotics, anxiolytics, muscle relaxants, general anesthetics, antipsychotics, other opioids, alcohol) may result in profound sedation, respiratory depression, coma, and death. The risk of hypotension may also be increased with some CNS depressants (e.g., alcohol, benzodiazepines, phenothiazines).

MANAGEMENT: The use of opioids in conjunction with benzodiazepines or other CNS depressants should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, 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. 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. Cough medications containing opioids (e.g., codeine, hydrocodone) should not be prescribed to patients using benzodiazepines or other CNS depressants including alcohol. For patients who have been receiving extended therapy with both an opioid and a benzodiazepine and require discontinuation of either medication, a gradual tapering of dose is advised, since abrupt withdrawal may lead to withdrawal symptoms. Severe cases of benzodiazepine withdrawal, primarily in patients who have received excessive doses over a prolonged period, may result in numbness and tingling of extremities, hypersensitivity to light and noise, hallucinations, and epileptic seizures.

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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.

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MONITOR: Barbiturates may increase the hepatotoxic potential of acetaminophen and decrease its therapeutic effects. The mechanism may be related to accelerated CYP450 metabolism of acetaminophen with consequent increase in hepatotoxic metabolites. This interaction is of greatest concern in cases of acetaminophen overdose.

MANAGEMENT: Monitoring for altered efficacy and safety is recommended. Prolonged use or high doses of acetaminophen should be avoided by patients on barbiturate therapy.

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MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring 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.

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