Basic Information
ID DDInter1516 and DDInter429
Interaction 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. Coadministration with opioids may increase the oral bioavailability of gabapentin.
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.
References [1] Eipe N, Penning J "Postoperative respiratory depression associated with pregabalin: a case series and a preoperative decision algorithm." Pain Res Manag 16 (2011): 353-6 [2] Smith RV, Havens JR, Walsh SL "Gabapentin misuse, abuse and diversion: a systematic review." Addiction 111 (2016): 1160-74 [3] Government of Canada "Summary Safety Review - Gabapentin - Assessing the Potential Risk of Serious Breathing Problems. Available from: URL: https://www.canada.ca/en/health-canada/services/drugs-health-products/medeffect-canada/safety-reviews/summary-safety-review-gabapentin-as" ([2016, Sep 16]): [4] US Food and Drug Administration "FDA warns about serious breathing problems with seizure and nerve pain medicines gabapentin (Neurontin, Gralise, Horizant) and pregabalin (Lyrica, Lyrica CR) When used with CNS depressants or in patients with lung problems. Available from: URL: https://ww" ([2019, Dec 19]): [5] "Product Information. Neurontin (gabapentin)." Parke-Davis, Morris Plains, NJ. [6] Eckhardt K, Ammon S, Hofmann U, Riebe A, Gugeler N, Mikus G "Gabapentin enhances the analgesic effect of morphine in healthy volunteers." Anesth Analg 91 (2000): 185-91 [7] "Product Information. Lyrica (pregabalin)." Pfizer U.S. Pharmaceuticals Group, New York, NY. [8] Peckham AM, Evoy KE, Covvey JR, Ochs L, Fairman KA, Sclar DA "Predictors of gabapentin overuse with or without concomitant opioids in a commercially insured U.S. population." Pharmacotherapy 38 (2018): 436-43 [9] Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 31-7 [10] "Product Information. Fycompa (perampanel)." Eisai Inc, Teaneck, NJ. [11] Gilman AG, Rall TW, Nies AS, Taylor P, eds. "Goodman and Gilman's the Pharmacological Basis of Therapeutics. 8th ed." New York, NY: Pergamon Press Inc. (1990): [12] "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc, Rockville, MD.
Alternative for Pregabalin N03A
Lacosamide
Alternative for Codeine N02A
Naloxone

R05D
Benzonatate
Potential Metabolism Interactions
Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.