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Drug Interactions between bismuth subsalicylate / metronidazole / tetracycline and D-Tal

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

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Interactions between your drugs

Moderate

metroNIDAZOLE PHENobarbital

Applies to: bismuth subsalicylate / metronidazole / tetracycline and D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine)

ADJUST DOSE: Coadministration with a barbiturate may significantly decrease the plasma concentrations and pharmacologic effects of nitroimidazoles. The proposed mechanism is barbiturate induction of nitroimidazole metabolism via hepatic microsomal enzymes. The interaction has been reported with metronidazole and has been attributed to treatment failure in patients with trichomoniasis, giardiasis, or amebiasis given the normally recommended dosages of metronidazole while being treated concomitantly with phenobarbital. Significantly increased clearance and shortened half-life of metronidazole were demonstrated. In many cases, metronidazole dosage had to be doubled or even tripled to achieve a cure. No data are available for tinidazole.

MANAGEMENT: Patients treated concomitantly with a barbiturate may require a higher dosage of metronidazole to achieve a cure. Two- to threefold dosage increases are not uncommon. Pharmacologic response to metronidazole should be monitored and the dosage adjusted as necessary. Given its structural similarities to metronidazole, the same precaution may be applicable during therapy with tinidazole, although clinical data are lacking.

References

  1. "Product Information. Flagyl (metronidazole)." Searle PROD (2001):
  2. Loft S, Sonne J, Poulsen HE, Peterson KT, Jorgensen BG, Dossing M "Inhibition and induction of metronidazole and antipyrine metabolism." Eur J Clin Pharmacol 32 (1987): 35-41
  3. Mead PB, Gibson M, Schentag JJ, Ziemniak JA "Possible alteration of metronidazole metabolism by phenobarbital." N Engl J Med 306 (1982): 1490
  4. Gupte S "Phenobarbital and metabolism of metronidazole." N Engl J Med 308 (1983): 529
  5. "Product Information. Tindamax (tinidazole)." Presutti Laboratories Inc (2004):
View all 5 references

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Moderate

atropine hyoscyamine

Applies to: D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine) and D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine)

MONITOR: Agents with anticholinergic properties (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; disopyramide) may have additive effects when used in combination. Excessive parasympatholytic effects may result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures. Central nervous system-depressant effects may also be additively or synergistically increased when these agents are combined, especially in elderly or debilitated patients. Use of neuroleptics in combination with other neuroleptics or anticholinergic agents may increase the risk of tardive dyskinesia. In addition, some neuroleptics and tricyclic antidepressants may cause prolongation of the QT interval and theoretically, concurrent use of two or more drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Caution is advised when agents with anticholinergic properties are combined, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A reduction in anticholinergic dosages may be necessary if excessive adverse effects develop.

References

  1. Stadnyk AN, Glezos JD "Drug-induced heat stroke." Can Med Assoc J 128 (1983): 957-9
  2. Zelman S, Guillan R "Heat stroke in phenothiazine-treated patients: a report of three fatalities." Am J Psychiatry 126 (1970): 1787-90
  3. Mann SC, Boger WP "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry 135 (1978): 1097-100
  4. Warnes H, Lehmann HE, Ban TA "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J 96 (1967): 1112-3
  5. Gershon S, Neubauer H, Sundland DM "Interaction between some anticholinergic agents and phenothiazines." Clin Pharmacol Ther 6 (1965): 749-56
  6. Sarnquist F, Larson CP Jr "Drug-induced heat stroke." Anesthesiology 39 (1973): 348-50
  7. Johnson AL, Hollister LE, Berger PA "The anticholinergic intoxication syndrome: diagnosis and treatment." J Clin Psychiatry 42 (1981): 313-7
  8. Lee BS "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry 47 (1986): 571
  9. Forester D "Fatal drug-induced heat stroke." JACEP 7 (1978): 243-4
  10. Moreau A, Jones BD, Banno V "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry 31 (1986): 339-41
  11. Hvizdos AJ, Bennett JA, Wells BG, Rappaport KB, Mendel SA "Anticholinergic psychosis in a patient receiving usual doses of haloperidol." Clin Pharm 2 (1983): 174-8
  12. Cohen MA, Alfonso CA, Mosquera M "Development of urinary retention during treatment with clozapine and meclizine [published erratum appears in Am J Psychiatry 1994 Jun;151(6):952]." Am J Psychiatry 151 (1994): 619-20
  13. "Product Information. Cogentin (benztropine)." Merck & Co., Inc PROD (2001):
  14. Kulik AV, Wilbur R "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry 6 (1982): 75-82
  15. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories PROD (2001):
View all 15 references

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Moderate

atropine scopolamine

Applies to: D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine) and D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine)

MONITOR: Agents with anticholinergic properties (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; disopyramide) may have additive effects when used in combination. Excessive parasympatholytic effects may result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures. Central nervous system-depressant effects may also be additively or synergistically increased when these agents are combined, especially in elderly or debilitated patients. Use of neuroleptics in combination with other neuroleptics or anticholinergic agents may increase the risk of tardive dyskinesia. In addition, some neuroleptics and tricyclic antidepressants may cause prolongation of the QT interval and theoretically, concurrent use of two or more drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Caution is advised when agents with anticholinergic properties are combined, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A reduction in anticholinergic dosages may be necessary if excessive adverse effects develop.

References

  1. Stadnyk AN, Glezos JD "Drug-induced heat stroke." Can Med Assoc J 128 (1983): 957-9
  2. Zelman S, Guillan R "Heat stroke in phenothiazine-treated patients: a report of three fatalities." Am J Psychiatry 126 (1970): 1787-90
  3. Mann SC, Boger WP "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry 135 (1978): 1097-100
  4. Warnes H, Lehmann HE, Ban TA "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J 96 (1967): 1112-3
  5. Gershon S, Neubauer H, Sundland DM "Interaction between some anticholinergic agents and phenothiazines." Clin Pharmacol Ther 6 (1965): 749-56
  6. Sarnquist F, Larson CP Jr "Drug-induced heat stroke." Anesthesiology 39 (1973): 348-50
  7. Johnson AL, Hollister LE, Berger PA "The anticholinergic intoxication syndrome: diagnosis and treatment." J Clin Psychiatry 42 (1981): 313-7
  8. Lee BS "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry 47 (1986): 571
  9. Forester D "Fatal drug-induced heat stroke." JACEP 7 (1978): 243-4
  10. Moreau A, Jones BD, Banno V "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry 31 (1986): 339-41
  11. Hvizdos AJ, Bennett JA, Wells BG, Rappaport KB, Mendel SA "Anticholinergic psychosis in a patient receiving usual doses of haloperidol." Clin Pharm 2 (1983): 174-8
  12. Cohen MA, Alfonso CA, Mosquera M "Development of urinary retention during treatment with clozapine and meclizine [published erratum appears in Am J Psychiatry 1994 Jun;151(6):952]." Am J Psychiatry 151 (1994): 619-20
  13. "Product Information. Cogentin (benztropine)." Merck & Co., Inc PROD (2001):
  14. Kulik AV, Wilbur R "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry 6 (1982): 75-82
  15. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories PROD (2001):
View all 15 references

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Moderate

PHENobarbital scopolamine

Applies to: D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine) and D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine)

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

  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 PROD
  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 PROD (2001):
  20. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories PROD (2001):
  21. "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc) PROD (2001):
  22. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  23. "Product Information. Meridia (sibutramine)." Knoll Pharmaceutical Company PROD (2001):
  24. "Product Information. Tasmar (tolcapone)." Valeant Pharmaceuticals PROD (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 PROD (2001):
  27. "Product Information. Trileptal (oxcarbazepine)." Novartis Pharmaceuticals PROD (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):
View all 36 references

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Moderate

hyoscyamine scopolamine

Applies to: D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine) and D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine)

MONITOR: Agents with anticholinergic properties (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; disopyramide) may have additive effects when used in combination. Excessive parasympatholytic effects may result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures. Central nervous system-depressant effects may also be additively or synergistically increased when these agents are combined, especially in elderly or debilitated patients. Use of neuroleptics in combination with other neuroleptics or anticholinergic agents may increase the risk of tardive dyskinesia. In addition, some neuroleptics and tricyclic antidepressants may cause prolongation of the QT interval and theoretically, concurrent use of two or more drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Caution is advised when agents with anticholinergic properties are combined, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A reduction in anticholinergic dosages may be necessary if excessive adverse effects develop.

References

  1. Stadnyk AN, Glezos JD "Drug-induced heat stroke." Can Med Assoc J 128 (1983): 957-9
  2. Zelman S, Guillan R "Heat stroke in phenothiazine-treated patients: a report of three fatalities." Am J Psychiatry 126 (1970): 1787-90
  3. Mann SC, Boger WP "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry 135 (1978): 1097-100
  4. Warnes H, Lehmann HE, Ban TA "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J 96 (1967): 1112-3
  5. Gershon S, Neubauer H, Sundland DM "Interaction between some anticholinergic agents and phenothiazines." Clin Pharmacol Ther 6 (1965): 749-56
  6. Sarnquist F, Larson CP Jr "Drug-induced heat stroke." Anesthesiology 39 (1973): 348-50
  7. Johnson AL, Hollister LE, Berger PA "The anticholinergic intoxication syndrome: diagnosis and treatment." J Clin Psychiatry 42 (1981): 313-7
  8. Lee BS "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry 47 (1986): 571
  9. Forester D "Fatal drug-induced heat stroke." JACEP 7 (1978): 243-4
  10. Moreau A, Jones BD, Banno V "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry 31 (1986): 339-41
  11. Hvizdos AJ, Bennett JA, Wells BG, Rappaport KB, Mendel SA "Anticholinergic psychosis in a patient receiving usual doses of haloperidol." Clin Pharm 2 (1983): 174-8
  12. Cohen MA, Alfonso CA, Mosquera M "Development of urinary retention during treatment with clozapine and meclizine [published erratum appears in Am J Psychiatry 1994 Jun;151(6):952]." Am J Psychiatry 151 (1994): 619-20
  13. "Product Information. Cogentin (benztropine)." Merck & Co., Inc PROD (2001):
  14. Kulik AV, Wilbur R "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry 6 (1982): 75-82
  15. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories PROD (2001):
View all 15 references

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Moderate

tetracycline bismuth subsalicylate

Applies to: bismuth subsalicylate / metronidazole / tetracycline and bismuth subsalicylate / metronidazole / tetracycline

ADJUST DOSING INTERVAL: Administration of a bismuth-containing preparation within two to three hours of a tetracycline may significantly decrease serum tetracycline concentrations. Data are available for tetracycline and doxycycline. The proposed mechanism is chelation of tetracycline by bismuth.

MANAGEMENT: Administration of a tetracycline and bismuth-containing preparation should be separated by two to three hours. Patients should be monitored for diminished tetracycline efficacy.

References

  1. Ericsson CD, Feldman S, Pickering LK, Cleary TG "Influence of subsalicylate bismuth on absorption of doxycycline." JAMA 247 (1982): 2266-7
  2. Albert KS, Welch RD, DeSante KA, DiSanto AR "Decreased tetracycline bioavailability caused by a bismuth subsalicylate antidiarrheal mixture." J Pharm Sci 68 (1979): 586-8
  3. "Product Information. Seysara (sarecycline)." Allergan Inc (2018):
  4. "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc. (2018):
View all 4 references

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Drug and food interactions

Major

metroNIDAZOLE food

Applies to: bismuth subsalicylate / metronidazole / tetracycline

CONTRAINDICATED: Use of alcohol or products containing alcohol during nitroimidazole therapy may result in a disulfiram-like reaction in some patients. There have been a few case reports involving metronidazole, although data overall are not convincing. The presumed mechanism is inhibition of aldehyde dehydrogenase (ALDH) by metronidazole in a manner similar to disulfiram. Following ingestion of alcohol, inhibition of ALDH results in increased concentrations of acetaldehyde, the accumulation of which can produce an unpleasant physiologic response referred to as the 'disulfiram reaction'. Symptoms include flushing, throbbing in head and neck, throbbing headache, respiratory difficulty, nausea, vomiting, sweating, thirst, chest pain, palpitation, dyspnea, hyperventilation, tachycardia, hypotension, syncope, weakness, vertigo, blurred vision, and confusion. Severe reactions may result in respiratory depression, cardiovascular collapse, arrhythmia, myocardial infarction, acute congestive heart failure, unconsciousness, convulsions, and death. However, some investigators have questioned the disulfiram-like properties of metronidazole. One study found neither elevations in blood acetaldehyde nor objective or subjective signs of a disulfiram-like reaction to ethanol in six subjects treated with metronidazole (200 mg three times a day for 5 days) compared to six subjects who received placebo.

MANAGEMENT: Because clear evidence is lacking concerning the safety of ethanol use during nitroimidazole therapy, patients should be apprised of the potential for interaction. Consumption of alcoholic beverages and products containing propylene glycol is specifically contraindicated during and for at least 3 days after completion of metronidazole and benznidazole therapy according to their product labeling.

References

  1. Giannini AJ, DeFrance DT "Metronidazole and alcohol: potential for combinative abuse." J Toxicol Clin Toxicol 20 (1983): 509-15
  2. Alexander I "Alcohol-antabuse syndrome in patients receiving metronidazole during gynaecological treatment." Br J Clin Pract 39 (1985): 292-3
  3. Harries DP, Teale KF, Sunderland G "Metronidazole and alcohol: potential problems." Scott Med J 35 (1990): 179-80
  4. "Product Information. Flagyl (metronidazole)." Searle PROD (2001):
  5. Edwards DL, Fink PC, Van Dyke PO "Disulfiram-like reaction associated with intravenous trimethoprim-sulfamethoxazole and metronidazole." Clin Pharm 5 (1986): 999-1000
  6. Williams CS, Woodcock KR "Do ethanol and metronidazole interact to produce a disulfiram-like reaction?." Ann Pharmacother 34 (2000): 255-7
  7. Visapaa JP, Tillonen JS, Kaihovaara PS, Salaspuro MP "Lack of disulfiram-like reaction with metronidazole and ethanol." Ann Pharmacother 36 (2002): 971-4
  8. Krulewitch CJ "An unexpected adverse drug effect." J Midwifery Womens Health 48 (2003): 67-8
  9. "Product Information. Benznidazole (benznidazole)." Everett Laboratories Inc (2017):
View all 9 references

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Major

PHENobarbital food

Applies to: D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine)

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

References

  1. Gupta RC, Kofoed J "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J 94 (1966): 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med 51 (1971): 346-51
  3. Saario I, Linnoila M "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh) 38 (1976): 382-92
  4. Stead AH, Moffat AC "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol 2 (1983): 5-14
  5. Seixas FA "Drug/alcohol interactions: avert potential dangers." Geriatrics 34 (1979): 89-102
View all 5 references

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Moderate

tetracycline food

Applies to: bismuth subsalicylate / metronidazole / tetracycline

ADJUST DOSING INTERVAL: Administration with food, particularly dairy products, significantly reduces tetracycline absorption. The calcium content of these foods forms nonabsorbable chelates with tetracycline.

MANAGEMENT: Tetracycline should be administered one hour before or two hours after meals.

References

  1. "Product Information. Achromycin (tetracycline)." Lederle Laboratories PROD (2001):
  2. "Product Information. Declomycin (demeclocycline)." Lederle Laboratories PROD (2001):

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Moderate

atropine food

Applies to: D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine)

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Linnoila M "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol 6 (1973): 107-12

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Moderate

hyoscyamine food

Applies to: D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine)

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Linnoila M "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol 6 (1973): 107-12

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Moderate

scopolamine food

Applies to: D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine)

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Linnoila M "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol 6 (1973): 107-12

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Moderate

tetracycline food

Applies to: bismuth subsalicylate / metronidazole / tetracycline

GENERALLY AVOID: The bioavailability of oral tetracyclines and iron salts may be significantly decreased during concurrent administration. Therapeutic failure may result. The proposed mechanism is chelation of tetracyclines by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In ten healthy volunteers, simultaneous oral administration of ferrous sulfate 200 mg and single doses of various tetracyclines (200 mg to 500 mg) resulted in reductions in the serum levels of methacycline and doxycycline by 80% to 90%, oxytetracycline by 50% to 60%, and tetracycline by 40% to 50%. In another study, 300 mg of ferrous sulfate reduced the absorption of tetracycline by 81% and that of minocycline by 77%. Conversely, the absorption of iron has been shown to be decreased by up to 78% in healthy subjects and up to 65% in patients with iron depletion when ferrous sulfate 250 mg was administered with tetracycline 500 mg. Available data suggest that administration of iron 3 hours before or 2 hours after a tetracycline largely prevents the interaction with most tetracyclines except doxycycline. Due to extensive enterohepatic cycling, iron binding may occur with doxycycline even when it is given parenterally. It has also been shown that when iron is administered up to 11 hours after doxycycline, serum concentrations of doxycycline may still be reduced by 20% to 45%.

MANAGEMENT: Coadministration of a tetracycline with any iron-containing product should be avoided if possible. Otherwise, patients should be advised to stagger the times of administration by at least three to four hours, although separating the doses may not prevent the interaction with doxycycline.

References

  1. Neuvonen PJ "Interactions with the absorption of tetracyclines." Drugs 11 (1976): 45-54
  2. Gothoni G, Neuvonen PJ, Mattila M, Hackman R "Iron-tetracycline interaction: effect of time interval between the drugs." Acta Med Scand 191 (1972): 409-11
  3. Venho VM, Salonen RO, Mattila MJ "Modification of the pharmacokinetics of doxycycline in man by ferrous sulphate or charcoal." Eur J Clin Pharmacol 14 (1978): 277-80
  4. "Product Information. Minocin (minocycline)." Lederle Laboratories PROD (2002):
  5. Campbell NR, Hasinoff BB "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol 31 (1991): 251-5
  6. Bateman FJ "Effects of tetracyclines." Br Med J 4 (1970): 802
  7. Neuvonen PJ, Gothoni G, Hackman R, Bjorksten K "Interference of iron with the absorption of tetracyclines in man." Br Med J 4 (1970): 532-4
  8. Greenberger NJ "Absorption of tetracyclines: interference by iron." Ann Intern Med 74 (1971): 792-3
  9. Neuvonen PJ, Penttila O "Effect of oral ferrous sulphate on the half-life of doxycycline in man." Eur J Clin Pharmacol 7 (1974): 361-3
  10. "Product Information. Seysara (sarecycline)." Allergan Inc (2018):
  11. "Product Information. Nuzyra (omadacycline)." Paratek Pharmaceuticals, Inc. (2018):
View all 11 references

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Minor

scopolamine food

Applies to: D-Tal (atropine / hyoscyamine / phenobarbital / scopolamine)

The coadministration with grapefruit juice may delay the absorption and increase the bioavailability of oral scopolamine. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In an open-label, crossover study consisting of 14 subjects, the consumption of grapefruit juice (compared to water) was associated with a 30% increase in mean systemic bioavailability and a 153% increase in time to reach peak serum concentration (Tmax) of scopolamine. However, the perceived pharmacodynamic effect of the drug, as measured by % change in subjective alertness compared to baseline, was similar after coadministration with water and grapefruit juice. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of of scopolamine but may delay its onset of action following oral administration. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability.

References

  1. Ebert U, Oertel R, Kirch W "Influence of grapefruit juice on scopolamine pharmacokinetics and pharmacodynamics in healthy male and female subjects." Int J Clin Pharm Therapeutics 38 (2000): 523-31

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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.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.