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Drug Interactions between Bellatal ER and Duradyne DHC

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

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Major

PHENobarbital HYDROcodone

Applies to: Bellatal ER (atropine / hyoscyamine / phenobarbital / scopolamine) and Duradyne DHC (acetaminophen / hydrocodone)

GENERALLY AVOID: Barbiturates may potentiate the central nervous system (CNS) depressant effects of opioids. Concomitant use may result in profound sedation, respiratory depression, coma, and death. On the other hand, some barbiturates can also induce the hepatic metabolism of opioids that are metabolized by CYP450 3A4 such as butorphanol, fentanyl, hydrocodone, methadone and oxycodone, resulting in enhanced clearance. Reduced analgesic efficacy or withdrawal symptoms may occur in patients maintained on their opioid regimen following the addition of a barbiturate. Conversely, discontinuation of the barbiturate may increase plasma concentrations of the opioid and potentiate the risk of overdose and fatal respiratory depression.

MANAGEMENT: The use of opioids in conjunction with other CNS depressants such as barbiturates should generally be avoided unless alternative treatment options are inadequate. If coadministration is necessary, the dosage and duration of each drug should be limited to the minimum required to achieve desired clinical effect, and patients should be closely monitored for signs and symptoms of CNS and respiratory depression. Particular caution is advisable when a barbiturate is added to or withdrawn from therapy in patients receiving opioids that are CYP450 3A4 substrates, as there may be an increased risk of withdrawal symptoms (e.g., restlessness, insomnia, sweating, lacrimation, or rhinorrhea) following initiation of the barbiturate and overdose following discontinuation. A dosage adjustment for one or both drugs may be required.

References

  1. Liu S-J, Wang RI "Case report of barbiturate-induced enhancement of methadone metabolism and withdrawal syndrome." Am J Psychiatry 141 (1984): 1287-8
  2. Bell J, Seres V, Bowron P, Lewis J, Batey R "The use of serum methadone levels in patients receiving methadone maintenance." Clin Pharmacol Ther 43 (1988): 623-9
  3. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  4. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company PROD (2001):
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  6. "Product Information. Ionsys (fentanyl)." Ortho McNeil Pharmaceutical (2006):
  7. Cerner Multum, Inc. "Australian Product Information." O 0
  8. "Product Information. Zohydro ER (hydrocodone)." Zogenix, Inc (2013):
  9. "Product Information. Butorphanol Tartrate (butorphanol)." Apotex Corporation (2017):
  10. "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc (2018):
View all 10 references

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Moderate

acetaminophen PHENobarbital

Applies to: Duradyne DHC (acetaminophen / hydrocodone) and Bellatal ER (atropine / hyoscyamine / phenobarbital / scopolamine)

MONITOR: Barbiturates may increase the hepatotoxic potential of acetaminophen and decrease its therapeutic effects. The mechanism may be related to accelerated CYP450 metabolism of acetaminophen with consequent increase in hepatotoxic metabolites. This interaction is of greatest concern in cases of acetaminophen overdose.

MANAGEMENT: Monitoring for altered efficacy and safety is recommended. Prolonged use or high doses of acetaminophen should be avoided by patients on barbiturate therapy.

References

  1. Pirotte JH "Apparent potentiation by phenobarbital of hepatotoxicity from small doses of acetaminophen." Ann Intern Med 101 (1984): 403
  2. Douidar SM, Ahmed AE "A novel mechanism for the enhancement of acetaminophen hepatotoxicity by phenobarbital." J Pharmacol Exp Ther 240 (1987): 578-83
  3. Wright N, Prescott LF "Potentiation by previous drug therapy of hepatotoxicity following paracetamol overdose." Scott Med J 18 (1973): 56-8
  4. Bock KW, Wiltfang J, Blume R, Ullrich D, Bircher J "Paracetamol as a test drug to determine glucuronide formation in man: effects of inducers and of smoking." Eur J Clin Pharmacol 31 (1987): 677-83
View all 4 references

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Moderate

atropine hyoscyamine

Applies to: Bellatal ER (atropine / hyoscyamine / phenobarbital / scopolamine) and Bellatal ER (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: Bellatal ER (atropine / hyoscyamine / phenobarbital / scopolamine) and Bellatal ER (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: Bellatal ER (atropine / hyoscyamine / phenobarbital / scopolamine) and Bellatal ER (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: Bellatal ER (atropine / hyoscyamine / phenobarbital / scopolamine) and Bellatal ER (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 HYDROcodone

Applies to: Bellatal ER (atropine / hyoscyamine / phenobarbital / scopolamine) and Duradyne DHC (acetaminophen / hydrocodone)

MONITOR: Coadministration of opioids with anticholinergic agents may result in additive central nervous system (CNS), gastrointestinal, and genitourinary effects. The risk and/or severity of adverse effects such as sedation, dizziness, confusion, cognitive and psychomotor impairment, dry mouth, constipation, and urinary retention may increase. Severe constipation may lead to paralytic ileus in some cases.

MANAGEMENT: Caution and close monitoring of central nervous system, gastrointestinal, and genitourinary adverse effects are recommended when opioids are used with anticholinergic agents. 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. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals PROD (2002):
  2. "Product Information. Dolophine (methadone)." Lilly, Eli and Company PROD (2002):
  3. "Product Information. Tylenol with Codeine (acetaminophen-codeine)." Janssen Pharmaceuticals PROD (2001):
  4. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  5. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical PROD (2001):
  6. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company PROD (2001):
  7. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  8. "Product Information. DepoDur (morphine liposomal)." Endo Laboratories LLC (2004):
  9. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  10. "Product Information. Opana (oxymorphone)." Endo Laboratories LLC (2006):
  11. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):
  12. "Product Information. Exalgo (hydromorphone)." Covidien (2010):
  13. "Product Information. Belbuca (buprenorphine)." Endo Pharmaceuticals Solutions Inc (2016):
  14. "Product Information. Alfentanil Hydrochloride (alfentanil)." Akorn Inc (2017):
  15. "Product Information. SUFentanil Citrate (sufentanil)." Akorn Inc (2017):
  16. "Product Information. Lortab (acetaminophen-hydrocodone)." Akorn Inc (2017):
  17. "Product Information. Levorphanol Tartrate (levorphanol)." Sentynl Therapeutics (2017):
  18. "Product Information. Naloxone HCl-Pentazocine HCl (naloxone-pentazocine)." Actavis U.S. (Amide Pharmaceutical Inc) (2018):
  19. "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc (2018):
View all 19 references

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Moderate

hyoscyamine HYDROcodone

Applies to: Bellatal ER (atropine / hyoscyamine / phenobarbital / scopolamine) and Duradyne DHC (acetaminophen / hydrocodone)

MONITOR: Coadministration of opioids with anticholinergic agents may result in additive central nervous system (CNS), gastrointestinal, and genitourinary effects. The risk and/or severity of adverse effects such as sedation, dizziness, confusion, cognitive and psychomotor impairment, dry mouth, constipation, and urinary retention may increase. Severe constipation may lead to paralytic ileus in some cases.

MANAGEMENT: Caution and close monitoring of central nervous system, gastrointestinal, and genitourinary adverse effects are recommended when opioids are used with anticholinergic agents. 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. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals PROD (2002):
  2. "Product Information. Dolophine (methadone)." Lilly, Eli and Company PROD (2002):
  3. "Product Information. Tylenol with Codeine (acetaminophen-codeine)." Janssen Pharmaceuticals PROD (2001):
  4. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  5. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical PROD (2001):
  6. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company PROD (2001):
  7. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  8. "Product Information. DepoDur (morphine liposomal)." Endo Laboratories LLC (2004):
  9. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  10. "Product Information. Opana (oxymorphone)." Endo Laboratories LLC (2006):
  11. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):
  12. "Product Information. Exalgo (hydromorphone)." Covidien (2010):
  13. "Product Information. Belbuca (buprenorphine)." Endo Pharmaceuticals Solutions Inc (2016):
  14. "Product Information. Alfentanil Hydrochloride (alfentanil)." Akorn Inc (2017):
  15. "Product Information. SUFentanil Citrate (sufentanil)." Akorn Inc (2017):
  16. "Product Information. Lortab (acetaminophen-hydrocodone)." Akorn Inc (2017):
  17. "Product Information. Levorphanol Tartrate (levorphanol)." Sentynl Therapeutics (2017):
  18. "Product Information. Naloxone HCl-Pentazocine HCl (naloxone-pentazocine)." Actavis U.S. (Amide Pharmaceutical Inc) (2018):
  19. "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc (2018):
View all 19 references

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Moderate

scopolamine HYDROcodone

Applies to: Bellatal ER (atropine / hyoscyamine / phenobarbital / scopolamine) and Duradyne DHC (acetaminophen / hydrocodone)

MONITOR: Coadministration of opioids with anticholinergic agents may result in additive central nervous system (CNS), gastrointestinal, and genitourinary effects. The risk and/or severity of adverse effects such as sedation, dizziness, confusion, cognitive and psychomotor impairment, dry mouth, constipation, and urinary retention may increase. Severe constipation may lead to paralytic ileus in some cases.

MANAGEMENT: Caution and close monitoring of central nervous system, gastrointestinal, and genitourinary adverse effects are recommended when opioids are used with anticholinergic agents. 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. "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals PROD (2002):
  2. "Product Information. Dolophine (methadone)." Lilly, Eli and Company PROD (2002):
  3. "Product Information. Tylenol with Codeine (acetaminophen-codeine)." Janssen Pharmaceuticals PROD (2001):
  4. "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
  5. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical PROD (2001):
  6. "Product Information. OxyContin (oxycodone)." Purdue Frederick Company PROD (2001):
  7. "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  8. "Product Information. DepoDur (morphine liposomal)." Endo Laboratories LLC (2004):
  9. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  10. "Product Information. Opana (oxymorphone)." Endo Laboratories LLC (2006):
  11. "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals (2009):
  12. "Product Information. Exalgo (hydromorphone)." Covidien (2010):
  13. "Product Information. Belbuca (buprenorphine)." Endo Pharmaceuticals Solutions Inc (2016):
  14. "Product Information. Alfentanil Hydrochloride (alfentanil)." Akorn Inc (2017):
  15. "Product Information. SUFentanil Citrate (sufentanil)." Akorn Inc (2017):
  16. "Product Information. Lortab (acetaminophen-hydrocodone)." Akorn Inc (2017):
  17. "Product Information. Levorphanol Tartrate (levorphanol)." Sentynl Therapeutics (2017):
  18. "Product Information. Naloxone HCl-Pentazocine HCl (naloxone-pentazocine)." Actavis U.S. (Amide Pharmaceutical Inc) (2018):
  19. "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc (2018):
View all 19 references

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Minor

acetaminophen atropine

Applies to: Duradyne DHC (acetaminophen / hydrocodone) and Bellatal ER (atropine / hyoscyamine / phenobarbital / scopolamine)

Anticholinergic agents may delay and/or decrease the gastrointestinal absorption of acetaminophen by reducing gastric motility and delaying gastric emptying. However, the clinical relevance is probably minimal.

References

  1. Nimmo J, Heading RC, Tothill P, Prescott LF "Pharmacological modification of gastric emptying: effects of propantheline and metoclopramide on paracetamol absorption." Br Med J 1 (1973): 587-9
  2. Clark JM, Seager SJ "Gastric emptying following premedication with glycopyrrolate or atropine." Br J Anaesth 55 (1983): 1195-9
  3. "Product Information. Transderm-Scop (scopolamine)." Ciba Self-Medication Inc PROD

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Minor

acetaminophen hyoscyamine

Applies to: Duradyne DHC (acetaminophen / hydrocodone) and Bellatal ER (atropine / hyoscyamine / phenobarbital / scopolamine)

Anticholinergic agents may delay and/or decrease the gastrointestinal absorption of acetaminophen by reducing gastric motility and delaying gastric emptying. However, the clinical relevance is probably minimal.

References

  1. Nimmo J, Heading RC, Tothill P, Prescott LF "Pharmacological modification of gastric emptying: effects of propantheline and metoclopramide on paracetamol absorption." Br Med J 1 (1973): 587-9
  2. Clark JM, Seager SJ "Gastric emptying following premedication with glycopyrrolate or atropine." Br J Anaesth 55 (1983): 1195-9
  3. "Product Information. Transderm-Scop (scopolamine)." Ciba Self-Medication Inc PROD

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Minor

acetaminophen scopolamine

Applies to: Duradyne DHC (acetaminophen / hydrocodone) and Bellatal ER (atropine / hyoscyamine / phenobarbital / scopolamine)

Anticholinergic agents may delay and/or decrease the gastrointestinal absorption of acetaminophen by reducing gastric motility and delaying gastric emptying. However, the clinical relevance is probably minimal.

References

  1. Nimmo J, Heading RC, Tothill P, Prescott LF "Pharmacological modification of gastric emptying: effects of propantheline and metoclopramide on paracetamol absorption." Br Med J 1 (1973): 587-9
  2. Clark JM, Seager SJ "Gastric emptying following premedication with glycopyrrolate or atropine." Br J Anaesth 55 (1983): 1195-9
  3. "Product Information. Transderm-Scop (scopolamine)." Ciba Self-Medication Inc PROD

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Drug and food interactions

Major

HYDROcodone food

Applies to: Duradyne DHC (acetaminophen / hydrocodone)

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

  1. "Product Information. Zohydro ER (hydrocodone)." Zogenix, Inc (2013):

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Major

acetaminophen food

Applies to: Duradyne DHC (acetaminophen / hydrocodone)

GENERALLY AVOID: Chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, which has included rare cases of fatal hepatitis and frank hepatic failure requiring liver transplantation. The proposed mechanism is induction of hepatic microsomal enzymes during chronic alcohol use, which may result in accelerated metabolism of acetaminophen and increased production of potentially hepatotoxic metabolites.

MANAGEMENT: In general, chronic alcoholics should avoid regular or excessive use of acetaminophen. Alternative analgesic/antipyretic therapy may be appropriate in patients who consume three or more alcoholic drinks per day. However, if acetaminophen is used, these patients should be cautioned not to exceed the recommended dosage (maximum 4 g/day in adults and children 12 years of age or older).

References

  1. Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med 145 (1985): 2019-23
  2. O'Dell JR, Zetterman RK, Burnett DA "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA 255 (1986): 2636-7
  3. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med 104 (1986): 399-404
  4. Thummel KE, Slattery JT, Nelson SD "Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen." J Pharmacol Exp Ther 245 (1988): 129-36
  5. McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA 244 (1980): 251-3
  6. Kartsonis A, Reddy KR, Schiff ER "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med 105 (1986): 138-9
  7. Prescott LF, Critchley JA "Drug interactions affecting analgesic toxicity." Am J Med 75 (1983): 113-6
  8. "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical PROD (2002):
  9. Whitcomb DC, Block GD "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA 272 (1994): 1845-50
  10. Bonkovsky HL "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  11. Nelson EB, Temple AR "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  12. Zimmerman HJ, Maddrey WC "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology 22 (1995): 767-73
View all 12 references

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Major

PHENobarbital food

Applies to: Bellatal ER (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

atropine food

Applies to: Bellatal ER (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: Bellatal ER (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: Bellatal ER (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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Minor

scopolamine food

Applies to: Bellatal ER (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.