Drug Interactions between Dicomal-DH and gepirone
This report displays the potential drug interactions for the following 2 drugs:
- Dicomal-DH (hydrocodone/phenylephrine/pyrilamine)
- gepirone
Interactions between your drugs
pyrilamine HYDROcodone
Applies to: Dicomal-DH (hydrocodone / phenylephrine / pyrilamine) and Dicomal-DH (hydrocodone / phenylephrine / pyrilamine)
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.
References
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- Sotaniemi EA, Anttila M, Rautio A, et al. (1981) "Propranolol and sotalol metabolism after a drinking party." Clin Pharmacol Ther, 29, p. 705-10
- Grabowski BS, Cady WJ, Young WW, Emery JF (1980) "Effects of acute alcohol administration on propranolol absorption." Int J Clin Pharmacol Ther Toxicol, 18, p. 317-9
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- Naylor GJ, McHarg A (1977) "Profound hypothermia on combined lithium carbonate and diazepam treatment." Br Med J, 2, p. 22
- Stovner J, Endresen R (1965) "Intravenous anaesthesia with diazepam." Acta Anaesthesiol Scand, 24, p. 223-7
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- Feldman SA, Crawley BE (1970) "Interaction of diazepam with the muscle-relaxant drugs." Br Med J, 1, p. 336-8
- Ochs HR, Greenblatt DJ, Verburg-Ochs B (1984) "Propranolol interactions with diazepam, lorazepam and alprazolam." Clin Pharmacol Ther, 36, p. 451-5
- Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF (1988) "Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic." Psychopharmacology (Berl), 96, p. 63-6
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- Markowitz JS, Wells BG, Carson WH (1995) "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother, 29, p. 603-9
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- Ferslew KE, Hagardorn AN, McCormick WF (1990) "A fatal interaction of methocarbamol and ethanol in an accidental poisoning." J Forensic Sci, 35, p. 477-82
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- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
HYDROcodone gepirone
Applies to: Dicomal-DH (hydrocodone / phenylephrine / pyrilamine) and gepirone
MONITOR: Opioids may potentiate the effects of serotonergic agents and increase the risk of serotonin syndrome. The interaction has primarily been reported with the phenylpiperidine opioids (e.g., meperidine, fentanyl) and tramadol, which are known to possess some serotonergic activity, although a few cases have involved other opioids such as oxycodone, methadone, morphine, hydromorphone, codeine, and buprenorphine. Serotonin syndrome is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucinations, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea. Since many serotonergic agents can also cause central nervous system depression, concomitant use with opioids may result in increased sedation and impairment of judgment, thinking, and psychomotor skills.
MANAGEMENT: Caution is advised when opioids are used concomitantly with serotonergic agents such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), other antidepressants/psychotropic agents (e.g., amoxapine, buspirone, lithium, maprotiline, mirtazepine, nefazodone, trazodone, vilazodone), 5-HT1 receptor agonists (triptans), 5-HT3 receptor antagonists, cyclobenzaprine, dextromethorphan, 5-hydroxytryptophan, and St. John's wort. Patients should be monitored for symptoms of the serotonin syndrome during treatment. Particular caution is advised when increasing the dosages of these agents. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures. Patients should also be advised of potentially additive central nervous system effects from these agents and to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them.
References
- Meyer D, Halfin V (1981) "Toxicity secondary to meperidine in patients on monoamine oxidase inhibitors: a case report and critical review." J Clin Psychopharmacol, 1, p. 319-21
- Zornberg GL, Bodkin JA, Cohen BM (1991) "Severe adverse interaction between pethidine and selegiline." Lancet, 337, p. 246
- Hansen TE, Dieter K, Keepers GA (1990) "Interaction of fluoxetine and pentazocine." Am J Psychiatry, 147, p. 949-50
- Sternbach H (1991) "The serotonin syndrome." Am J Psychiatry, 148, p. 705-13
- Noble WH, Baker A (1992) "MAO inhibitors and coronary artery surgery: a patient death." Can J Anaesth, 39, p. 1061-6
- Insler SR, Kraenzler EJ, Licina MG, Savage RM, Starr NJ (1994) "Cardiac surgery in a patient taking monoamine oxidase inhibitors - an adverse fentanyl reaction." Anesth Analg, 78, p. 593-7
- Mason BJ, Blackburn KH (1997) "Possible serotonin syndrome associated with tramadol and sertraline coadministration." Ann Pharmacother, 31, p. 175-7
- Mills KC (1997) "Serotonin syndrome: A clinical update." Crit Care Clin, 13, p. 763
- Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG (1998) "Serotonin syndrome resulting from drug interactions." Med J Aust, 169, p. 523-5
- Egberts AC, ter Borg J, Brodie-Meijer CC (1997) "Serotonin syndrome attributed to tramadol addition to paroxetine therapy." Int Clin Psychopharmacol, 12, p. 181-2
- Rosebraugh CJ, floxkhart DA, Yasuda SU, Woosley RL (2001) "Visual hallucination and tremor induced by sertraline and oxycodone in a bone marrow transplant patient." J Clin Pharmacol, 41, p. 224-7
- Lange-Asschenfeldt C, Weigmann H, Hiemke C, Mann K (2002) "Serotonin syndrome as a result of fluoxetine in a patient with tramadol abuse: plasma level-correlated symptomatology." J Clin Psychopharmacol, 22, p. 440-1
- Kesavan S, Sobala GM (1999) "Serotonin syndrome with fluoxetine plus tramadol." J R Soc Med, 92, p. 474-5
- Gonzalez-Pinto A, Imaz H, De Heredia JL, Gutierrez M, Mico JA (2001) "Mania and tramadol-fluoxetine combination." Am J Psychiatry, 158, p. 964-5
- Dougherty JA, Young H, Shafi T (2002) "Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine." Ann Pharmacother, 36, p. 1647-1648
- Martin TG (1996) "Serotonin syndrome." Ann Emerg Med, 28, p. 520-6
- Tissot TA (2003) "Probable meperidine-induced serotonin syndrome in a patient with a history of fluoxetine use." Anesthesiology, 98, p. 1511-1512
- Roy S, Fortier LP (2003) "Fentanyl-induced rigidity during emergence from general anesthesia potentiated by venlafexine." Can J Anaesth, 50, p. 32-5
- Gillman PK (1995) "Possible serotonin syndrome with moclobemide and pethidine." Med J Aust, 162, p. 554
- Houlihan DJ (2004) "Serotonin syndrome resulting from coadministration of tramadol, venlafaxine, and mirtazapine." Ann Pharmacother, 38, p. 411-3
- (2004) "Venlafaxine + tramadol: serotonin syndrome." Prescrire Int, 13, p. 57
- Mahlberg R, Kunz D, Sasse J, Kirchheiner J (2004) "Serotonin syndrome with tramadol and citalopram." Am J Psychiatry, 161, p. 1129
- Mittino D, Mula M, Monaco F (2004) "Serotonin syndrome associated with tramadol-sertraline coadministration." Clin Neuropharmacol, 27, p. 150-1
- Lantz MS, Buchalter EN, Giambanco V (1998) "Serotonin syndrome following the administration of tramadol with paroxetine." Int J Geriatr Psychiatry, 13, p. 343-5
- Gillman PK (2005) "Monoamine oxidase inhibitors, opioid analgesics and serotonin toxicity." Br J Anaesth
- Kitson R, Carr B (2005) "Tramadol and severe serotonin syndrome." Anaesthesia, 60, p. 934-5
- Gnanadesigan N, Espinoza RT, Smith R, Israel M, Reuben DB (2005) "Interaction of serotonergic antidepressants and opioid analgesics: Is serotonin syndrome going undetected?" J Am Med Dir Assoc, 6, p. 265-9
- Hunter B, Kleinert MM, Osatnik J, Soria E (2006) "Serotonergic syndrome and abnormal ocular movements: worsening of rigidity by remifentanil?" Anesth Analg, 102, p. 1589
- Ailawadhi S, Sung KW, Carlson LA, Baer MR (2007) "Serotonin syndrome caused by interaction between citalopram and fentanyl." J Clin Pharm Ther, 32, p. 199-202
- Vizcaychipi MP, Walker S, Palazzo M (2007) "Serotonin syndrome triggered by tramadol." Br J Anaesth, 99, p. 919
- Das PK, Warkentin DI, Hewko R, Forrest DL (2008) "Serotonin syndrome after concomitant treatment with linezolid and meperidine." Clin Infect Dis, 46, p. 264-5
- Rang ST, Field J, Irving C (2008) "Serotonin toxicity caused by an interaction between fentanyl and paroxetine." Can J Anaesth, 55, p. 521-5
- Guo SL, Wu TJ, Liu CC, Ng CC, Chien CC, Sun HL (2009) "Meperidine-induced serotonin syndrome in a susceptible patient." Br J Anaesth
- Davis JJ, Buck NS, Swenson JD, Johnson KB, Greis PE (2013) "Serotonin syndrome manifesting as patient movement during total intravenous anesthesia with propofol and remifentanil." J Clin Anesth, 25, p. 52-4
- Hillman AD, Witenko CJ, Sultan SM, Gala G (2015) "Serotonin syndrome caused by fentanyl and methadone in a burn injury." Pharmacotherapy, 35, p. 112-7
- Mateo-Carrasco H, Munoz-Aguilera EM, Garcia-Torrecillas JM, Abu Al-Robb H (2015) "Serotonin syndrome probably triggered by a morphine-phenelzine interaction." Pharmacotherapy, 35, e102-5
- Abadie D, Rousseau V, Logerot S, Cottin J, Montastruc JL, Montastruc F (2015) "Serotonin Syndrome: Analysis of Cases Registered in the French Pharmacovigilance Database." J Clin Psychopharmacol
- Shakoor M, Ayub S, Ahad A, Ayub Z (2014) "Transient serotonin syndrome caused by concurrent use of tramadol and selective serotonin reuptake inhibitor." Am J Case Rep, 15, p. 562-4
- Larson KJ, Wittwer ED, Nicholson WT, Weingarten TN, Price DL, Sprung J (2015) "Myoclonus in patient on fluoxetine after receiving fentanyl and low-dose methylene blue during sentinel lymph node biopsy." J Clin Anesth, 27, p. 247-51
- US Food and Drug Administration (FDA) (2018) FDA Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines; requires label changes. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM491302.pdf
Drug and food interactions
HYDROcodone food
Applies to: Dicomal-DH (hydrocodone / phenylephrine / pyrilamine)
GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including hydrocodone. 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: Consumption of alcohol while taking some sustained-release formulations of hydrocodone may cause rapid release of the drug, resulting in high systemic levels of hydrocodone that may be potentially lethal. Alcohol apparently can disrupt the release mechanism of some sustained-release formulations. In study subjects, the rate of absorption of hydrocodone from an extended-release formulation was found to be affected by coadministration with 40% alcohol in the fasted state, as demonstrated by an average 2.4-fold (up to 3.9-fold in one subject) increase in hydrocodone peak plasma concentration and a decrease in the time to peak concentration. Alcohol also increased the extent of absorption by an average of 1.2-fold (up to 1.7-fold in one subject).
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of hydrocodone. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of hydrocodone by certain compounds present in grapefruit. Increased hydrocodone concentrations could conceivably increase or prolong adverse drug effects and may cause potentially fatal respiratory depression.
MANAGEMENT: Patients taking sustained-release formulations of hydrocodone should not consume alcohol or use medications that contain alcohol. In general, potent narcotics such as hydrocodone should not be combined with alcohol. Patients should also avoid consumption of grapefruit or grapefruit juice during treatment with hydrocodone.
References
- (2013) "Product Information. Zohydro ER (hydrocodone)." Zogenix, Inc
pyrilamine food
Applies to: Dicomal-DH (hydrocodone / phenylephrine / pyrilamine)
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.
References
- Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
- Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
gepirone food
Applies to: gepirone
GENERALLY AVOID: Grapefruit and/or grapefruit juice may increase the plasma concentrations and effects of gepirone. The proposed mechanism is inhibition of CYP450 3A4 mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. For example, when subjects who were at steady state on the strong CYP450 3A4 inhibitor ketoconazole (200 mg twice daily) received a single dose of gepirone (36.3 mg), the maximum plasma concentration (Cmax) and systemic exposure (AUC) of gepirone increased by approximately 5-fold. Similarly, when subjects who were at steady state on the moderate CYP450 3A4 inhibitor verapamil (80 mg three times daily) received a single dose of gepirone (18.2 mg), the maximum plasma concentration (Cmax) and systemic exposure (AUC) of gepirone increased by approximately 2.6-fold. In general, the effects of grapefruit products are concentration-, dose-, and preparation-dependent and can vary widely among both brands and individual patients. Some preparations have demonstrated strong CYP450 3A4 inhibition, while others have demonstrated moderate inhibition.
ADJUST DOSING INTERVAL: Food enhances the bioavailability of gepirone and its major active metabolites (3'-OH-gepirone and 1-PP). The magnitude of the effect is dependent on the fat content of the meal, but the systemic exposure of gepirone and its major metabolites was consistently higher under fed conditions as compared to the fasted state. The peak plasma concentration (Cmax) of gepirone after intake of a low-fat (about 200 calorie) breakfast was 27% higher, after a medium-fat (about 500 calorie) breakfast was 55% higher, and after a high-fat (about 850 calorie) breakfast was 62% higher than the Cmax achieved in the fasted state. Likewise, the systemic exposure (AUC) of gepirone was about 14% higher after a low-fat breakfast, 22% higher after a medium-fat breakfast, and 32% to 37% higher after a high-fat breakfast when compared to the AUC achieved in the fasted state. The effect of varying amounts of fat on the AUC and Cmax of 3'-OH-gepirone and 1-PP were similar to that of gepirone.
MANAGEMENT: Coadministration of gepirone with grapefruit products should be avoided. If grapefruit juice is consumed, monitoring for adverse effects (e.g., QT prolongation, serotonin syndrome, dizziness, nausea, insomnia, abdominal pain, and/or dyspepsia) should be considered. Gepirone should be taken orally with food at the approximately the same time each day. Tablets should be swallowed whole.
References
- (2023) "Product Information. Exxua (gepirone)." Mission Pharmacal Company, 1
- FDA. U.S. Food and Drug Administration (2024) Grapefruit juice and some drugs don't mix. https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix
- Chen M, Zhou S, Fabriaga E, Zhang P, Zhou Q (2024) Food-drug interactions precipitated by fruit juices other than grapefruit juice: an update review. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326888/
- Kiani J, Imam SZ (2024) Medicinal importance of grapefruit juice and its interaction with various drugs. https://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-6-33
phenylephrine food
Applies to: Dicomal-DH (hydrocodone / phenylephrine / pyrilamine)
MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.
MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.
References
- Rosenblatt JE, Lake CR, van Kammen DP, Ziegler MG, Bunney WE Jr (1979) "Interactions of amphetamine, pimozide, and lithium on plasma norepineophrine and dopamine-beta-hydroxylase in schizophrenic patients." Psychiatry Res, 1, p. 45-52
- Cavanaugh JH, Griffith JD, Oates JA (1970) "Effect of amphetamine on the pressor response to tyramine: formation of p-hydroxynorephedrine from amphetamine in man." Clin Pharmacol Ther, 11, p. 656
- (2001) "Product Information. Adderall (amphetamine-dextroamphetamine)." Shire Richwood Pharmaceutical Company Inc
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- (2001) "Product Information. Sanorex (mazindol)." Novartis Pharmaceuticals
- (2001) "Product Information. Focalin (dexmethylphenidate)." Mikart Inc
- (2002) "Product Information. Strattera (atomoxetine)." Lilly, Eli and Company
Therapeutic duplication warnings
No warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
No interaction information available. |
Further information
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