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Drug Interactions between Donnapine and Kato

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

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Interactions between your drugs

Major

atropine potassium chloride

Applies to: Donnapine (atropine / hyoscyamine / phenobarbital / scopolamine) and Kato (potassium chloride)

CONTRAINDICATED: The following interaction does not apply to all products containing potassium chloride, including split dose products used for colon preparation prior to colonoscopy. It is applicable to certain oral solid formulations of potassium chloride used primarily for potassium supplementation, and the prescriber should consult the individual product labeling for more specific information and guidance.

Concomitant use of agents with anticholinergic properties (e.g., antihistamines, antispasmodics, neuroleptics, phenothiazines, skeletal muscle relaxants, tricyclic antidepressants, the class IA antiarrhythmic disopyramide) may potentiate the risk of upper gastrointestinal injury associated with oral solid formulations of potassium chloride. The proposed mechanism involves increased gastrointestinal transit time due to reduction of stomach and intestinal motility by anticholinergic agents, thereby creating a high localized concentration of potassium ions in the region of a dissolving tablet or capsule and increasing the contact time with GI mucosa. Solid formulations of potassium chloride have been associated with upper GI bleeding and small bowel ulceration, stenosis, perforation, and obstruction. Deaths have been reported rarely. In clinical studies, short-term coadministration of wax-matrix or microencapsulated formulations of potassium chloride at high dosages in combination with an anticholinergic agent such as glycopyrrolate resulted in more frequent and more serious endoscopic lesions than potassium therapy alone. However, the lesions were not accompanied by bleeding or epigastric symptoms. Some investigators have suggested a higher risk of upper GI lesions with wax-matrix than microencapsulated formulations, although existing data are limited and conflicting.

MANAGEMENT: The use of certain oral solid formulations of potassium chloride is considered contraindicated in patients receiving agents with anticholinergic properties at sufficient doses to exert anticholinergic effects. A liquid formulation of potassium chloride should be considered. Patients prescribed a solid oral formulation should be advised to discontinue potassium therapy and contact their physician if they experience potential symptoms of upper GI injury such as severe vomiting, abdominal pain, distention, and gastrointestinal bleeding.

References

  1. Lambert JR, Newman A "Ulceration and stricture of the esophagus due to oral potassium chloride (slow release tablet) therapy." Am J Gastroenterol 73 (1980): 508-11
  2. Farquharson-Roberts MA, Giddings AE, Nunn AJ "Perforation of small bowel due to slow release potassium chloride (slow-K)." Br Med J 3 (1975): 206
  3. Wynn V "Potassium chloride and bowel ulceration." Br Med J 5477 (1965): 1546
  4. McMahon FG, Ryan JR, Akdamar K, Ertan A "Effect of potassium chloride supplements on upper gastrointestinal mucosa." Clin Pharmacol Ther 35 (1984): 852-5
  5. McMahon FG, Ryan JR, Akdamar K, Ertan A "Upper gastrointestinal lesions after potassium chloride supplements: a controlled clinical trial." Lancet 2 (1982): 1059-61
  6. Leijonmarck CE, Raf L "Gastrointestinal lesions and potassium chloride supplements." Lancet 1 (1985): 56-7
  7. Lofgren RP, Rothe PR, Carlson GJ "Jejunal perforation associated with slow-release potassium chloride therapy." South Med J 75 (1982): 1154-5
  8. Leijonmarck CE, Raf L "Ulceration of the small intestine due to slow-release potassium chloride tablets." Acta Chir Scand 151 (1985): 273-8
  9. Weiss SM, Rutenberg HL, Paskin DL, Zaren HA "Gut lesions due to slow-release KCI tablets." N Engl J Med 296 (1977): 111-2
  10. "Product Information. K-Dur (potassium chloride)." Schering Corporation PROD (2001):
  11. Heffernan SJ, Murphy JJ "Ulceration of small intestine and slow-release potassium tablets." Br Med J 2 (1975): 746
View all 11 references

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Major

potassium chloride hyoscyamine

Applies to: Kato (potassium chloride) and Donnapine (atropine / hyoscyamine / phenobarbital / scopolamine)

CONTRAINDICATED: The following interaction does not apply to all products containing potassium chloride, including split dose products used for colon preparation prior to colonoscopy. It is applicable to certain oral solid formulations of potassium chloride used primarily for potassium supplementation, and the prescriber should consult the individual product labeling for more specific information and guidance.

Concomitant use of agents with anticholinergic properties (e.g., antihistamines, antispasmodics, neuroleptics, phenothiazines, skeletal muscle relaxants, tricyclic antidepressants, the class IA antiarrhythmic disopyramide) may potentiate the risk of upper gastrointestinal injury associated with oral solid formulations of potassium chloride. The proposed mechanism involves increased gastrointestinal transit time due to reduction of stomach and intestinal motility by anticholinergic agents, thereby creating a high localized concentration of potassium ions in the region of a dissolving tablet or capsule and increasing the contact time with GI mucosa. Solid formulations of potassium chloride have been associated with upper GI bleeding and small bowel ulceration, stenosis, perforation, and obstruction. Deaths have been reported rarely. In clinical studies, short-term coadministration of wax-matrix or microencapsulated formulations of potassium chloride at high dosages in combination with an anticholinergic agent such as glycopyrrolate resulted in more frequent and more serious endoscopic lesions than potassium therapy alone. However, the lesions were not accompanied by bleeding or epigastric symptoms. Some investigators have suggested a higher risk of upper GI lesions with wax-matrix than microencapsulated formulations, although existing data are limited and conflicting.

MANAGEMENT: The use of certain oral solid formulations of potassium chloride is considered contraindicated in patients receiving agents with anticholinergic properties at sufficient doses to exert anticholinergic effects. A liquid formulation of potassium chloride should be considered. Patients prescribed a solid oral formulation should be advised to discontinue potassium therapy and contact their physician if they experience potential symptoms of upper GI injury such as severe vomiting, abdominal pain, distention, and gastrointestinal bleeding.

References

  1. Lambert JR, Newman A "Ulceration and stricture of the esophagus due to oral potassium chloride (slow release tablet) therapy." Am J Gastroenterol 73 (1980): 508-11
  2. Farquharson-Roberts MA, Giddings AE, Nunn AJ "Perforation of small bowel due to slow release potassium chloride (slow-K)." Br Med J 3 (1975): 206
  3. Wynn V "Potassium chloride and bowel ulceration." Br Med J 5477 (1965): 1546
  4. McMahon FG, Ryan JR, Akdamar K, Ertan A "Effect of potassium chloride supplements on upper gastrointestinal mucosa." Clin Pharmacol Ther 35 (1984): 852-5
  5. McMahon FG, Ryan JR, Akdamar K, Ertan A "Upper gastrointestinal lesions after potassium chloride supplements: a controlled clinical trial." Lancet 2 (1982): 1059-61
  6. Leijonmarck CE, Raf L "Gastrointestinal lesions and potassium chloride supplements." Lancet 1 (1985): 56-7
  7. Lofgren RP, Rothe PR, Carlson GJ "Jejunal perforation associated with slow-release potassium chloride therapy." South Med J 75 (1982): 1154-5
  8. Leijonmarck CE, Raf L "Ulceration of the small intestine due to slow-release potassium chloride tablets." Acta Chir Scand 151 (1985): 273-8
  9. Weiss SM, Rutenberg HL, Paskin DL, Zaren HA "Gut lesions due to slow-release KCI tablets." N Engl J Med 296 (1977): 111-2
  10. "Product Information. K-Dur (potassium chloride)." Schering Corporation PROD (2001):
  11. Heffernan SJ, Murphy JJ "Ulceration of small intestine and slow-release potassium tablets." Br Med J 2 (1975): 746
View all 11 references

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Major

potassium chloride scopolamine

Applies to: Kato (potassium chloride) and Donnapine (atropine / hyoscyamine / phenobarbital / scopolamine)

CONTRAINDICATED: The following interaction does not apply to all products containing potassium chloride, including split dose products used for colon preparation prior to colonoscopy. It is applicable to certain oral solid formulations of potassium chloride used primarily for potassium supplementation, and the prescriber should consult the individual product labeling for more specific information and guidance.

Concomitant use of agents with anticholinergic properties (e.g., antihistamines, antispasmodics, neuroleptics, phenothiazines, skeletal muscle relaxants, tricyclic antidepressants, the class IA antiarrhythmic disopyramide) may potentiate the risk of upper gastrointestinal injury associated with oral solid formulations of potassium chloride. The proposed mechanism involves increased gastrointestinal transit time due to reduction of stomach and intestinal motility by anticholinergic agents, thereby creating a high localized concentration of potassium ions in the region of a dissolving tablet or capsule and increasing the contact time with GI mucosa. Solid formulations of potassium chloride have been associated with upper GI bleeding and small bowel ulceration, stenosis, perforation, and obstruction. Deaths have been reported rarely. In clinical studies, short-term coadministration of wax-matrix or microencapsulated formulations of potassium chloride at high dosages in combination with an anticholinergic agent such as glycopyrrolate resulted in more frequent and more serious endoscopic lesions than potassium therapy alone. However, the lesions were not accompanied by bleeding or epigastric symptoms. Some investigators have suggested a higher risk of upper GI lesions with wax-matrix than microencapsulated formulations, although existing data are limited and conflicting.

MANAGEMENT: The use of certain oral solid formulations of potassium chloride is considered contraindicated in patients receiving agents with anticholinergic properties at sufficient doses to exert anticholinergic effects. A liquid formulation of potassium chloride should be considered. Patients prescribed a solid oral formulation should be advised to discontinue potassium therapy and contact their physician if they experience potential symptoms of upper GI injury such as severe vomiting, abdominal pain, distention, and gastrointestinal bleeding.

References

  1. Lambert JR, Newman A "Ulceration and stricture of the esophagus due to oral potassium chloride (slow release tablet) therapy." Am J Gastroenterol 73 (1980): 508-11
  2. Farquharson-Roberts MA, Giddings AE, Nunn AJ "Perforation of small bowel due to slow release potassium chloride (slow-K)." Br Med J 3 (1975): 206
  3. Wynn V "Potassium chloride and bowel ulceration." Br Med J 5477 (1965): 1546
  4. McMahon FG, Ryan JR, Akdamar K, Ertan A "Effect of potassium chloride supplements on upper gastrointestinal mucosa." Clin Pharmacol Ther 35 (1984): 852-5
  5. McMahon FG, Ryan JR, Akdamar K, Ertan A "Upper gastrointestinal lesions after potassium chloride supplements: a controlled clinical trial." Lancet 2 (1982): 1059-61
  6. Leijonmarck CE, Raf L "Gastrointestinal lesions and potassium chloride supplements." Lancet 1 (1985): 56-7
  7. Lofgren RP, Rothe PR, Carlson GJ "Jejunal perforation associated with slow-release potassium chloride therapy." South Med J 75 (1982): 1154-5
  8. Leijonmarck CE, Raf L "Ulceration of the small intestine due to slow-release potassium chloride tablets." Acta Chir Scand 151 (1985): 273-8
  9. Weiss SM, Rutenberg HL, Paskin DL, Zaren HA "Gut lesions due to slow-release KCI tablets." N Engl J Med 296 (1977): 111-2
  10. "Product Information. K-Dur (potassium chloride)." Schering Corporation PROD (2001):
  11. Heffernan SJ, Murphy JJ "Ulceration of small intestine and slow-release potassium tablets." Br Med J 2 (1975): 746
View all 11 references

Switch to consumer interaction data

Moderate

atropine hyoscyamine

Applies to: Donnapine (atropine / hyoscyamine / phenobarbital / scopolamine) and Donnapine (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: Donnapine (atropine / hyoscyamine / phenobarbital / scopolamine) and Donnapine (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: Donnapine (atropine / hyoscyamine / phenobarbital / scopolamine) and Donnapine (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: Donnapine (atropine / hyoscyamine / phenobarbital / scopolamine) and Donnapine (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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Drug and food interactions

Major

PHENobarbital food

Applies to: Donnapine (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: Donnapine (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: Donnapine (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: Donnapine (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: Donnapine (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.