Basic Information
ID DDInter1997 and DDInter722
Interaction 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.
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.
References [1] Hamilton MJ, Bush M, Smith P, Peck AW "The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man." Br J Clin Pharmacol 14 (1982): 791-7 [2] Stambaugh JE, Lane C "Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination." Cancer Invest 1 (1983): 111-7 [3] Sotaniemi EA, Anttila M, Rautio A, et al. "Propranolol and sotalol metabolism after a drinking party." Clin Pharmacol Ther 29 (1981): 705-10 [4] Grabowski BS, Cady WJ, Young WW, Emery JF "Effects of acute alcohol administration on propranolol absorption." Int J Clin Pharmacol Ther Toxicol 18 (1980): 317-9 [5] Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF "The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam." Clin Pharmacol Ther 43 (1988): 412-9 [6] MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM "Diazepam actions and plasma concentrations following ethanol ingestion." Eur J Clin Pharmacol 11 (1977): 345-9 [7] Divoll M, Greenblatt DJ, Lacasse Y, Shader RI "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl) 73 (1981): 381-3 [8] Naylor GJ, McHarg A "Profound hypothermia on combined lithium carbonate and diazepam treatment." Br Med J 2 (1977): 22 [9] Stovner J, Endresen R "Intravenous anaesthesia with diazepam." Acta Anaesthesiol Scand 24 (1965): 223-7 [10] Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF "Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation." J Pharm Pharmacol 36 (1984): 244-7 [11] Feldman SA, Crawley BE "Interaction of diazepam with the muscle-relaxant drugs." Br Med J 1 (1970): 336-8 [12] Ochs HR, Greenblatt DJ, Verburg-Ochs B "Propranolol interactions with diazepam, lorazepam and alprazolam." Clin Pharmacol Ther 36 (1984): 451-5 [13] Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF "Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic." Psychopharmacology (Berl) 96 (1988): 63-6 [14] Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I "Midazolam-morphine sedative interaction in patients." Anesth Analg 68 (1989): 282-5 [15] "Product Information. Iopidine (apraclonidine ophthalmic)." Alcon Laboratories Inc [16] Greiff JMC, Rowbotham D "Pharmacokinetic drug interactions with gastrointestinal motility modifying agents." Clin Pharmacokinet 27 (1994): 447-61 [17] Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G "The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine." Acta Psychiatr Scand 80 Suppl (1989): 95-8 [18] Markowitz JS, Wells BG, Carson WH "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother 29 (1995): 603-9 [19] "Product Information. Ultram (tramadol)." McNeil Pharmaceutical (2001): [20] "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories (2001): [21] "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc) (2001): [22] "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals (2001): [23] "Product Information. Meridia (sibutramine)." Knoll Pharmaceutical Company (2001): [24] "Product Information. Tasmar (tolcapone)." Valeant Pharmaceuticals (2001): [25] Miller LG "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med 158 (1998): 2200-11 [26] "Product Information. Precedex (dexmedetomidine)." Abbott Pharmaceutical (2001): [27] "Product Information. Trileptal (oxcarbazepine)." Novartis Pharmaceuticals (2001): [28] Ferslew KE, Hagardorn AN, McCormick WF "A fatal interaction of methocarbamol and ethanol in an accidental poisoning." J Forensic Sci 35 (1990): 477-82 [29] Plushner SL "Valerian: valeriana officinalis." Am J Health Syst Pharm 57 (2000): 328-35 [30] "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc (2002): [31] "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals (2002): [32] Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0 [33] Cerner Multum, Inc. "Australian Product Information." O 0 [34] "Product Information. Fycompa (perampanel)." Eisai Inc (2012): [35] "Product Information. Belsomra (suvorexant)." Merck & Co., Inc (2014): [36] "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc (2015):
Alternative for Difelikefalin V03A
Calcium acetate Hydroxocobalamin Fomepizole Dexrazoxane Levoleucovorin Arginine
Physostigmine Oxygen Trilaciclib Palifermin Sugammadex
More
Alternative for Fentanyl N01A
Desflurane Sevoflurane Etomidate Enflurane Nitrous oxide Propofol
Halothane Isoflurane

N02A
Acetaminophen Acetylsalicylic acid Naloxone
More
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.