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Drug Interactions between amitriptyline / chlordiazepoxide and amprenavir

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

amitriptyline chlordiazePOXIDE

Applies to: amitriptyline / chlordiazepoxide and amitriptyline / chlordiazepoxide

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 (36)
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  2. Stambaugh JE, Lane C (1983) "Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination." Cancer Invest, 1, p. 111-7
  3. Sotaniemi EA, Anttila M, Rautio A, et al. (1981) "Propranolol and sotalol metabolism after a drinking party." Clin Pharmacol Ther, 29, p. 705-10
  4. 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
  5. Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF (1988) "The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam." Clin Pharmacol Ther, 43, p. 412-9
  6. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM (1977) "Diazepam actions and plasma concentrations following ethanol ingestion." Eur J Clin Pharmacol, 11, p. 345-9
  7. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI (1981) "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl), 73, p. 381-3
  8. Naylor GJ, McHarg A (1977) "Profound hypothermia on combined lithium carbonate and diazepam treatment." Br Med J, 2, p. 22
  9. Stovner J, Endresen R (1965) "Intravenous anaesthesia with diazepam." Acta Anaesthesiol Scand, 24, p. 223-7
  10. Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF (1984) "Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation." J Pharm Pharmacol, 36, p. 244-7
  11. Feldman SA, Crawley BE (1970) "Interaction of diazepam with the muscle-relaxant drugs." Br Med J, 1, p. 336-8
  12. Ochs HR, Greenblatt DJ, Verburg-Ochs B (1984) "Propranolol interactions with diazepam, lorazepam and alprazolam." Clin Pharmacol Ther, 36, p. 451-5
  13. 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
  14. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I (1989) "Midazolam-morphine sedative interaction in patients." Anesth Analg, 68, p. 282-5
  15. "Product Information. Iopidine (apraclonidine ophthalmic)." Alcon Laboratories Inc
  16. Greiff JMC, Rowbotham D (1994) "Pharmacokinetic drug interactions with gastrointestinal motility modifying agents." Clin Pharmacokinet, 27, p. 447-61
  17. Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G (1989) "The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine." Acta Psychiatr Scand, 80 Suppl, p. 95-8
  18. Markowitz JS, Wells BG, Carson WH (1995) "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother, 29, p. 603-9
  19. (2001) "Product Information. Ultram (tramadol)." McNeil Pharmaceutical
  20. (2001) "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories
  21. (2001) "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc)
  22. (2001) "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals
  23. (2001) "Product Information. Meridia (sibutramine)." Knoll Pharmaceutical Company
  24. (2001) "Product Information. Tasmar (tolcapone)." Valeant Pharmaceuticals
  25. Miller LG (1998) "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med, 158, p. 2200-11
  26. (2001) "Product Information. Precedex (dexmedetomidine)." Abbott Pharmaceutical
  27. (2001) "Product Information. Trileptal (oxcarbazepine)." Novartis Pharmaceuticals
  28. 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
  29. Plushner SL (2000) "Valerian: valeriana officinalis." Am J Health Syst Pharm, 57, p. 328-35
  30. (2002) "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc
  31. (2002) "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals
  32. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  33. Cerner Multum, Inc. "Australian Product Information."
  34. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  35. (2014) "Product Information. Belsomra (suvorexant)." Merck & Co., Inc
  36. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
Moderate

amitriptyline amprenavir

Applies to: amitriptyline / chlordiazepoxide and amprenavir

MONITOR: Product labeling for certain protease inhibitors (PIs) such as amprenavir and atazanavir states that serious and/or life-threatening drug interactions may occur with tricyclic antidepressants (TCAs), presumably due to PI inhibition of TCA metabolism via CYP450 3A4. High plasma levels of TCAs could conceivably lead to serious adverse reactions including QT interval prolongation and ventricular arrhythmias such as ventricular tachycardia and torsade de pointes. However, the clinical significance of such an interaction is unknown, as it has not been studied and there are no case reports of it published in the medical literature. Moreover, many TCAs are thought to be substrates of multiple CYP450 isoenzymes, thus the effects of CYP450 3A4 inhibition alone are unknown. Some TCAs such as desipramine, doxepin, and nortriptyline are also thought to be primarily metabolized by CYP450 2D6, which is not known to be inhibited by most PIs (except ritonavir) to any significant extent.

MANAGEMENT: Until further information is available, caution is advised if protease inhibitors must be used with certain TCAs. Pharmacologic response and plasma TCA levels should be monitored more closely whenever a PI is added to or withdrawn from therapy, and the TCA dosage adjusted as necessary.

References (17)
  1. von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, Duan SX, Harmatz JS, Shader RI (1994) "Inhibition of desipramine hydroxylation in vitro by serotonin-reuptake-inhibitor antidepressants, and by quinidine and ketoconazole: a model system to predict drug interactions in vivo." J Pharmacol Exp Ther, 268, p. 1278-83
  2. Vonmoltke LL, Greenblatt DJ, Court MH, Duan SX, Harmatz JS, Shader RI (1995) "Inhibition of alprazolam and desipramine hydroxylation in vitro by paroxetine and fluvoxamine: comparison with other selective serotonin reuptake inhibitor antidepressants." J Clin Psychopharmacol, 15, p. 125-31
  3. Nielsen KK, Flinois JP, Beaune P, Brosen K (1996) "The biotransformation of clomipramine in vitro, identification of the cytochrome p450s responsible for the separate metabolic pathways." J Pharmacol Exp Ther, 277, p. 1659-64
  4. Ghahramani P, Ellis SW, Lennard MS, Ramsay LE, Tucker GT (1997) "Cytochromes p450 mediating the n-demethylation of amitriptyline." Br J Clin Pharmacol, 43, p. 137-44
  5. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  6. Venkatakrishnan K, Schmider J, Harmatz JS, et al. (2001) "Relative contribution of CYP3A to amitriptyline clearance in humans: in vitro and in vivo studies." J Clin Pharmacol, 41, p. 1043-54
  7. Shimoda K, Someya T, Yokono A, et al. (2002) "The Impact of CYP2C19 and CYP2D6 Genotypes on Metabolism of Amitriptyline in Japanese Psychiatric Patients." J Clin Psychopharmacol, 22, p. 371-378
  8. Yang TJ, Krausz KW, Sai Y, Gonzalez FJ, Gelbon HV (1999) "Eight inhibitory monoclonal antibodies define the role of individual P-450S in human liver microsomal diazepam, 7-ethoxycoumarin, and imipramine metabolism." Drug Metab Dispos, 27, p. 102-9
  9. Tacke U, Leinonen E, Lillsunde P, et al. (1992) "Debrisoquine hydroxylation phenotypes of patients with high versus low to normal serum antidepressant concentrations." J Clin Psychopharmacol, 12, p. 262-7
  10. Eap CB, Bender S, Gastpar M, et al. (2000) "Steady state plasma levels of the enantiomers of trimipramine and its metabolites in CYP2D6-, CYP2C19- and CYP3A4/5-phenotyped patients." Ther Drug Monit, 22, p. 209-14
  11. (2003) "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb
  12. Kirchheiner J, Muller G, Meineke I, Wernecke KD, Roots I, Brockmoller J (2003) "Effects of polymorphisms in CYP2D6, CYP2C9, and CYP2C19 on trimipramine pharmacokinetics." J Clin Psychopharmacol, 23, p. 459-66
  13. (2003) "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline
  14. Hartter S, Tybring G, Friedberg T, Weigmann H, Hiemke C (2002) "The N-demethylation of the doxepin isomers is mainly catalyzed by the polymorphic CYP2C19." Pharm Res, 19, p. 1034-7
  15. Kirchheiner J, Meineke I, Muller G, Roots I, Brockmoller J (2002) "Contributions of CYP2D6, CYP2C9 and CYP2C19 to the biotransformation of E- and Z-doxepin in healthy volunteers." Pharmacogenetics, 12, p. 571-80
  16. Haritos VS, Ghabrial H, Ahokas JT, Ching MS (2000) "Role of cytochrome P450 2D6 (CYP2D6) in the stereospecific metabolism of E- and Z-doxepin." Pharmacogenetics, 10, p. 591-603
  17. Venkatakrishnan K, Greenblatt DJ, von Moltke LL, Schmider J, Harmatz JS, Shader RI (1998) "Five distinct human cytochromes mediate amitriptyline N-demethylation in vitro: dominance of CYP 2C19 and 3A4." J Clin Pharmacol, 38, p. 112-21
Moderate

chlordiazePOXIDE amprenavir

Applies to: amitriptyline / chlordiazepoxide and amprenavir

MONITOR: Coadministration with amprenavir or its prodrug, fosamprenavir, may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by amprenavir.

MANAGEMENT: Caution is advised if amprenavir must be used concurrently with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever amprenavir is added to or withdrawn from therapy.

References (3)
  1. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  2. (2003) "Product Information. Lexiva (fosamprenavir)." GlaxoSmithKline
  3. (2021) "Product Information. Qelbree (viloxazine)." Supernus Pharmaceuticals Inc

Drug and food interactions

Moderate

chlordiazePOXIDE food

Applies to: amitriptyline / chlordiazepoxide

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 (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. 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.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
Moderate

amprenavir food

Applies to: amprenavir

GENERALLY AVOID: Administration with a high-fat meal may decrease the oral bioavailability of amprenavir. The mechanism is unknown. In healthy volunteers, consumption of a standardized high-fat meal decreased the peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of amprenavir (1200 mg single oral dose) by 36% and 21%, respectively, compared to administration in the fasted state. The time to reach Cmax (Tmax) was increased 44% following a high-fat meal.

Grapefruit juice does not appear to significantly affect the pharmacokinetics of amprenavir. In 12 healthy volunteers, administration with grapefruit juice (200 mL) decreased the mean peak plasma concentration (Cmax) of amprenavir (1200 mg single oral dose) by 22% compared to water. The median time to reach Cmax (Tmax) was prolonged from 0.75 to 1.13 hours. These pharmacokinetic changes are not thought to be clinically significant, since antiretroviral response is more closely associated with systemic exposure (AUC) and trough plasma concentration (Cmin), which were not affected in the study.

MANAGEMENT: Amprenavir may be taken with or without food, but should not be taken with a high-fat meal.

References (2)
  1. (2001) "Product Information. Agenerase (amprenavir)." Glaxo Wellcome
  2. Demarles D, Gillotin C, Bonaventure-Paci S, Vincent I, Fosse S, Taburet AM (2002) "Single-dose pharmacokinetics of amprenavir coadministered with grapefruit juice." Antimicrob Agents Chemother, 46, p. 1589-1590
Moderate

amitriptyline food

Applies to: amitriptyline / chlordiazepoxide

GENERALLY AVOID: Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

MANAGEMENT: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.

References (7)
  1. Dorian P, Sellers EM, Reed KL, et al. (1983) "Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction." Eur J Clin Pharmacol, 25, p. 325-31
  2. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  3. Sandoz M, Vandel S, Vandel B, Bonin B, Allers G, Volmat R (1983) "Biotransformation of amitriptyline in alcoholic depressive patients." Eur J Clin Pharmacol, 24, p. 615-21
  4. Ciraulo DA, Barnhill JG, Jaffe JH (1988) "Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers." Clin Pharmacol Ther, 43, p. 509-18
  5. Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M (1975) "Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving." Clin Pharmacol Ther, 17, p. 515-22
  6. Ciraulo DA, Barnhill JG, Jaffe JH, Ciraulo AM, Tarmey MF (1990) "Intravenous pharmacokinetics of 2-hydroxyimipramine in alcoholics and normal controls." J Stud Alcohol, 51, p. 366-72
  7. Ciraulo DA, Alderson LM, Chapron DJ, Jaffe JH, Subbarao B, Kramer PA (1982) "Imipramine disposition in alcoholics." J Clin Psychopharmacol, 2, p. 2-7
Moderate

amitriptyline food

Applies to: amitriptyline / chlordiazepoxide

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.

References (4)
  1. (2024) "Product Information. Cytisine (cytisinicline)." Consilient Health Ltd
  2. jeong sh, Newcombe D, sheridan j, Tingle M (2015) "Pharmacokinetics of cytisine, an a4 b2 nicotinic receptor partial agonist, in healthy smokers following a single dose." Drug Test Anal, 7, p. 475-82
  3. Vaughan DP, Beckett AH, Robbie DS (1976) "The influence of smoking on the intersubject variation in pentazocine elimination." Br J Clin Pharmacol, 3, p. 279-83
  4. Zevin S, Benowitz NL (1999) "Drug interactions with tobacco smoking: an update" Clin Pharmacokinet, 36, p. 425-38

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.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor 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.
Unknown No interaction information available.

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