Drug Interactions between Alkabel-SR and Fentanyl Transdermal System
This report displays the potential drug interactions for the following 2 drugs:
- Alkabel-SR (atropine/hyoscyamine/phenobarbital/scopolamine)
- Fentanyl Transdermal System (fentanyl)
Interactions between your drugs
fentaNYL PHENobarbital
Applies to: Fentanyl Transdermal System (fentanyl) and Alkabel-SR (atropine / hyoscyamine / phenobarbital / scopolamine)
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 Particular caution is advisable when a barbiturate is added to or withdrawn from therapy in patients receiving opioids that are CYP450 3A4 substrates, as there may be an increased risk of withdrawal symptoms (e.g., restlessness,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
- Liu S-J, Wang RI (1984) "Case report of barbiturate-induced enhancement of methadone metabolism and withdrawal syndrome." Am J Psychiatry, 141, p. 1287-8
- Bell J, Seres V, Bowron P, Lewis J, Batey R (1988) "The use of serum methadone levels in patients receiving methadone maintenance." Clin Pharmacol Ther, 43, p. 623-9
- "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
- (2001) "Product Information. OxyContin (oxycodone)." Purdue Frederick Company
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2006) "Product Information. Ionsys (fentanyl)." Ortho McNeil Pharmaceutical
- Cerner Multum, Inc. "Australian Product Information."
- (2013) "Product Information. Zohydro ER (hydrocodone)." Zogenix, Inc
- (2017) "Product Information. Butorphanol Tartrate (butorphanol)." Apotex Corporation
- (2018) "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc
atropine fentaNYL
Applies to: Alkabel-SR (atropine / hyoscyamine / phenobarbital / scopolamine) and Fentanyl Transdermal System (fentanyl)
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
- (2002) "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals
- (2002) "Product Information. Dolophine (methadone)." Lilly, Eli and Company
- (2001) "Product Information. Tylenol with Codeine (acetaminophen-codeine)." Janssen Pharmaceuticals
- "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
- (2001) "Product Information. Ultram (tramadol)." McNeil Pharmaceutical
- (2001) "Product Information. OxyContin (oxycodone)." Purdue Frederick Company
- (2001) "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals
- (2004) "Product Information. DepoDur (morphine liposomal)." Endo Laboratories LLC
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2006) "Product Information. Opana (oxymorphone)." Endo Laboratories LLC
- (2009) "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals
- (2010) "Product Information. Exalgo (hydromorphone)." Covidien
- (2016) "Product Information. Belbuca (buprenorphine)." Endo Pharmaceuticals Solutions Inc
- (2017) "Product Information. Alfentanil Hydrochloride (alfentanil)." Akorn Inc
- (2017) "Product Information. SUFentanil Citrate (sufentanil)." Akorn Inc
- (2017) "Product Information. Lortab (acetaminophen-hydrocodone)." Akorn Inc
- (2017) "Product Information. Levorphanol Tartrate (levorphanol)." Sentynl Therapeutics
- (2018) "Product Information. Naloxone HCl-Pentazocine HCl (naloxone-pentazocine)." Actavis U.S. (Amide Pharmaceutical Inc)
- (2018) "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc
atropine hyoscyamine
Applies to: Alkabel-SR (atropine / hyoscyamine / phenobarbital / scopolamine) and Alkabel-SR (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
- Stadnyk AN, Glezos JD (1983) "Drug-induced heat stroke." Can Med Assoc J, 128, p. 957-9
- Zelman S, Guillan R (1970) "Heat stroke in phenothiazine-treated patients: a report of three fatalities." Am J Psychiatry, 126, p. 1787-90
- Mann SC, Boger WP (1978) "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry, 135, p. 1097-100
- Warnes H, Lehmann HE, Ban TA (1967) "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J, 96, p. 1112-3
- Gershon S, Neubauer H, Sundland DM (1965) "Interaction between some anticholinergic agents and phenothiazines." Clin Pharmacol Ther, 6, p. 749-56
- Sarnquist F, Larson CP Jr (1973) "Drug-induced heat stroke." Anesthesiology, 39, p. 348-50
- Johnson AL, Hollister LE, Berger PA (1981) "The anticholinergic intoxication syndrome: diagnosis and treatment." J Clin Psychiatry, 42, p. 313-7
- Lee BS (1986) "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry, 47, p. 571
- Forester D (1978) "Fatal drug-induced heat stroke." JACEP, 7, p. 243-4
- Moreau A, Jones BD, Banno V (1986) "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry, 31, p. 339-41
- Hvizdos AJ, Bennett JA, Wells BG, Rappaport KB, Mendel SA (1983) "Anticholinergic psychosis in a patient receiving usual doses of haloperidol." Clin Pharm, 2, p. 174-8
- Cohen MA, Alfonso CA, Mosquera M (1994) "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, p. 619-20
- (2001) "Product Information. Cogentin (benztropine)." Merck & Co., Inc
- Kulik AV, Wilbur R (1982) "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry, 6, p. 75-82
- (2001) "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories
fentaNYL hyoscyamine
Applies to: Fentanyl Transdermal System (fentanyl) and Alkabel-SR (atropine / hyoscyamine / phenobarbital / scopolamine)
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
- (2002) "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals
- (2002) "Product Information. Dolophine (methadone)." Lilly, Eli and Company
- (2001) "Product Information. Tylenol with Codeine (acetaminophen-codeine)." Janssen Pharmaceuticals
- "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
- (2001) "Product Information. Ultram (tramadol)." McNeil Pharmaceutical
- (2001) "Product Information. OxyContin (oxycodone)." Purdue Frederick Company
- (2001) "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals
- (2004) "Product Information. DepoDur (morphine liposomal)." Endo Laboratories LLC
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2006) "Product Information. Opana (oxymorphone)." Endo Laboratories LLC
- (2009) "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals
- (2010) "Product Information. Exalgo (hydromorphone)." Covidien
- (2016) "Product Information. Belbuca (buprenorphine)." Endo Pharmaceuticals Solutions Inc
- (2017) "Product Information. Alfentanil Hydrochloride (alfentanil)." Akorn Inc
- (2017) "Product Information. SUFentanil Citrate (sufentanil)." Akorn Inc
- (2017) "Product Information. Lortab (acetaminophen-hydrocodone)." Akorn Inc
- (2017) "Product Information. Levorphanol Tartrate (levorphanol)." Sentynl Therapeutics
- (2018) "Product Information. Naloxone HCl-Pentazocine HCl (naloxone-pentazocine)." Actavis U.S. (Amide Pharmaceutical Inc)
- (2018) "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc
atropine scopolamine
Applies to: Alkabel-SR (atropine / hyoscyamine / phenobarbital / scopolamine) and Alkabel-SR (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
- Stadnyk AN, Glezos JD (1983) "Drug-induced heat stroke." Can Med Assoc J, 128, p. 957-9
- Zelman S, Guillan R (1970) "Heat stroke in phenothiazine-treated patients: a report of three fatalities." Am J Psychiatry, 126, p. 1787-90
- Mann SC, Boger WP (1978) "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry, 135, p. 1097-100
- Warnes H, Lehmann HE, Ban TA (1967) "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J, 96, p. 1112-3
- Gershon S, Neubauer H, Sundland DM (1965) "Interaction between some anticholinergic agents and phenothiazines." Clin Pharmacol Ther, 6, p. 749-56
- Sarnquist F, Larson CP Jr (1973) "Drug-induced heat stroke." Anesthesiology, 39, p. 348-50
- Johnson AL, Hollister LE, Berger PA (1981) "The anticholinergic intoxication syndrome: diagnosis and treatment." J Clin Psychiatry, 42, p. 313-7
- Lee BS (1986) "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry, 47, p. 571
- Forester D (1978) "Fatal drug-induced heat stroke." JACEP, 7, p. 243-4
- Moreau A, Jones BD, Banno V (1986) "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry, 31, p. 339-41
- Hvizdos AJ, Bennett JA, Wells BG, Rappaport KB, Mendel SA (1983) "Anticholinergic psychosis in a patient receiving usual doses of haloperidol." Clin Pharm, 2, p. 174-8
- Cohen MA, Alfonso CA, Mosquera M (1994) "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, p. 619-20
- (2001) "Product Information. Cogentin (benztropine)." Merck & Co., Inc
- Kulik AV, Wilbur R (1982) "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry, 6, p. 75-82
- (2001) "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories
fentaNYL scopolamine
Applies to: Fentanyl Transdermal System (fentanyl) and Alkabel-SR (atropine / hyoscyamine / phenobarbital / scopolamine)
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
- (2002) "Product Information. Demerol (meperidine)." Sanofi Winthrop Pharmaceuticals
- (2002) "Product Information. Dolophine (methadone)." Lilly, Eli and Company
- (2001) "Product Information. Tylenol with Codeine (acetaminophen-codeine)." Janssen Pharmaceuticals
- "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
- (2001) "Product Information. Ultram (tramadol)." McNeil Pharmaceutical
- (2001) "Product Information. OxyContin (oxycodone)." Purdue Frederick Company
- (2001) "Product Information. Kadian (morphine)." Astra-Zeneca Pharmaceuticals
- (2004) "Product Information. DepoDur (morphine liposomal)." Endo Laboratories LLC
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2006) "Product Information. Opana (oxymorphone)." Endo Laboratories LLC
- (2009) "Product Information. Nucynta (tapentadol)." PriCara Pharmaceuticals
- (2010) "Product Information. Exalgo (hydromorphone)." Covidien
- (2016) "Product Information. Belbuca (buprenorphine)." Endo Pharmaceuticals Solutions Inc
- (2017) "Product Information. Alfentanil Hydrochloride (alfentanil)." Akorn Inc
- (2017) "Product Information. SUFentanil Citrate (sufentanil)." Akorn Inc
- (2017) "Product Information. Lortab (acetaminophen-hydrocodone)." Akorn Inc
- (2017) "Product Information. Levorphanol Tartrate (levorphanol)." Sentynl Therapeutics
- (2018) "Product Information. Naloxone HCl-Pentazocine HCl (naloxone-pentazocine)." Actavis U.S. (Amide Pharmaceutical Inc)
- (2018) "Product Information. Apadaz (acetaminophen-benzhydrocodone)." KemPharm, Inc
PHENobarbital scopolamine
Applies to: Alkabel-SR (atropine / hyoscyamine / phenobarbital / scopolamine) and Alkabel-SR (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
- Hamilton MJ, Bush M, Smith P, Peck AW (1982) "The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man." Br J Clin Pharmacol, 14, p. 791-7
- Stambaugh JE, Lane C (1983) "Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination." Cancer Invest, 1, p. 111-7
- Sotaniemi EA, Anttila M, Rautio A, et al. (1981) "Propranolol and sotalol metabolism after a drinking party." Clin Pharmacol Ther, 29, p. 705-10
- Grabowski BS, Cady WJ, Young WW, Emery JF (1980) "Effects of acute alcohol administration on propranolol absorption." Int J Clin Pharmacol Ther Toxicol, 18, p. 317-9
- Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF (1988) "The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam." Clin Pharmacol Ther, 43, p. 412-9
- MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM (1977) "Diazepam actions and plasma concentrations following ethanol ingestion." Eur J Clin Pharmacol, 11, p. 345-9
- Divoll M, Greenblatt DJ, Lacasse Y, Shader RI (1981) "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl), 73, p. 381-3
- Naylor GJ, McHarg A (1977) "Profound hypothermia on combined lithium carbonate and diazepam treatment." Br Med J, 2, p. 22
- Stovner J, Endresen R (1965) "Intravenous anaesthesia with diazepam." Acta Anaesthesiol Scand, 24, p. 223-7
- Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF (1984) "Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation." J Pharm Pharmacol, 36, p. 244-7
- Feldman SA, Crawley BE (1970) "Interaction of diazepam with the muscle-relaxant drugs." Br Med J, 1, p. 336-8
- Ochs HR, Greenblatt DJ, Verburg-Ochs B (1984) "Propranolol interactions with diazepam, lorazepam and alprazolam." Clin Pharmacol Ther, 36, p. 451-5
- Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF (1988) "Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic." Psychopharmacology (Berl), 96, p. 63-6
- Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I (1989) "Midazolam-morphine sedative interaction in patients." Anesth Analg, 68, p. 282-5
- "Product Information. Iopidine (apraclonidine ophthalmic)." Alcon Laboratories Inc
- Greiff JMC, Rowbotham D (1994) "Pharmacokinetic drug interactions with gastrointestinal motility modifying agents." Clin Pharmacokinet, 27, p. 447-61
- Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G (1989) "The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine." Acta Psychiatr Scand, 80 Suppl, p. 95-8
- Markowitz JS, Wells BG, Carson WH (1995) "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother, 29, p. 603-9
- (2001) "Product Information. Ultram (tramadol)." McNeil Pharmaceutical
- (2001) "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories
- (2001) "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc)
- (2001) "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals
- (2001) "Product Information. Meridia (sibutramine)." Knoll Pharmaceutical Company
- (2001) "Product Information. Tasmar (tolcapone)." Valeant Pharmaceuticals
- Miller LG (1998) "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med, 158, p. 2200-11
- (2001) "Product Information. Precedex (dexmedetomidine)." Abbott Pharmaceutical
- (2001) "Product Information. Trileptal (oxcarbazepine)." Novartis Pharmaceuticals
- Ferslew KE, Hagardorn AN, McCormick WF (1990) "A fatal interaction of methocarbamol and ethanol in an accidental poisoning." J Forensic Sci, 35, p. 477-82
- Plushner SL (2000) "Valerian: valeriana officinalis." Am J Health Syst Pharm, 57, p. 328-35
- (2002) "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc
- (2002) "Product Information. Lexapro (escitalopram)." Forest Pharmaceuticals
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Cerner Multum, Inc. "Australian Product Information."
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2014) "Product Information. Belsomra (suvorexant)." Merck & Co., Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
hyoscyamine scopolamine
Applies to: Alkabel-SR (atropine / hyoscyamine / phenobarbital / scopolamine) and Alkabel-SR (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
- Stadnyk AN, Glezos JD (1983) "Drug-induced heat stroke." Can Med Assoc J, 128, p. 957-9
- Zelman S, Guillan R (1970) "Heat stroke in phenothiazine-treated patients: a report of three fatalities." Am J Psychiatry, 126, p. 1787-90
- Mann SC, Boger WP (1978) "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry, 135, p. 1097-100
- Warnes H, Lehmann HE, Ban TA (1967) "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J, 96, p. 1112-3
- Gershon S, Neubauer H, Sundland DM (1965) "Interaction between some anticholinergic agents and phenothiazines." Clin Pharmacol Ther, 6, p. 749-56
- Sarnquist F, Larson CP Jr (1973) "Drug-induced heat stroke." Anesthesiology, 39, p. 348-50
- Johnson AL, Hollister LE, Berger PA (1981) "The anticholinergic intoxication syndrome: diagnosis and treatment." J Clin Psychiatry, 42, p. 313-7
- Lee BS (1986) "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry, 47, p. 571
- Forester D (1978) "Fatal drug-induced heat stroke." JACEP, 7, p. 243-4
- Moreau A, Jones BD, Banno V (1986) "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry, 31, p. 339-41
- Hvizdos AJ, Bennett JA, Wells BG, Rappaport KB, Mendel SA (1983) "Anticholinergic psychosis in a patient receiving usual doses of haloperidol." Clin Pharm, 2, p. 174-8
- Cohen MA, Alfonso CA, Mosquera M (1994) "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, p. 619-20
- (2001) "Product Information. Cogentin (benztropine)." Merck & Co., Inc
- Kulik AV, Wilbur R (1982) "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry, 6, p. 75-82
- (2001) "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories
Drug and food interactions
fentaNYL food
Applies to: Fentanyl Transdermal System (fentanyl)
GENERALLY AVOID: Alcohol may potentiate the central nervous system (CNS) depressant effects of opioid analgesics including fentanyl. 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 grapefruit juice during treatment with oral transmucosal formulations of fentanyl may result in increased plasma concentrations of fentanyl, which is primarily metabolized by CYP450 3A4 isoenzyme in the liver and intestine. Certain compounds present in grapefruit are known to inhibit CYP450 3A4 and may increase the bioavailability of swallowed fentanyl (reportedly up to 75% of a dose) and/or decrease its systemic clearance. The clinical significance is unknown. In 12 healthy volunteers, consumption of 250 mL regular-strength grapefruit juice the night before and 100 mL double-strength grapefruit juice one hour before administration of oral transmucosal fentanyl citrate (600 or 800 mcg lozenge) did not significantly affect fentanyl pharmacokinetics, overall extent of fentanyl-induced miosis (miosis AUC), or subjective self-assessment of various clinical effects compared to control. However, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability. The possibility of significant interaction in some patients should be considered.
MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol during treatment with fentanyl. Any history of alcohol or illicit drug use should be considered when prescribing fentanyl, and therapy initiated at a lower dosage if necessary. Patients should be closely monitored for signs and symptoms of sedation, respiratory depression, and hypotension. Due to a high degree of interpatient variability with respect to grapefruit juice interactions, patients treated with fentanyl should preferably avoid the consumption of grapefruit and grapefruit juice. In addition, patients receiving transdermal formulations of fentanyl should be cautioned that drug interactions and drug effects may be observed for a prolonged period beyond removal of the patch, as significant amounts of fentanyl are absorbed from the skin for 17 hours or more after the patch is removed.
References
- "Product Information. Duragesic Transdermal System (fentanyl)." Janssen Pharmaceutica, Titusville, NJ.
- (2001) "Product Information. Actiq (fentanyl)." Abbott Pharmaceutical
- Kharasch ED, Whittington D, Hoffer C (2004) "Influence of Hepatic and Intestinal Cytochrome P4503A Activity on the Acute Disposition and Effects of Oral Transmucosal Fentanyl Citrate." Anesthesiology, 101, p. 729-737
- Tateishi T, Krivoruk Y, Ueng YF, Wood AJ, Guengerich FP, Wood M (1996) "Identification of human cytochrome P-450 3A4 as the enzyme responsible for fentanyl and sufentanil N-dealkylation." Anesth Analg, 82, p. 167-72
- Labroo RB, Paine MF, Thummel KE, Kharasch ED (1997) "Fentanyl metabolism by human hepatic and intestinal cytochrome P450 3A4: implicaitons for interindividual variability in disposition, efficacy, and drug interactions." Drug Metab Dispos, 25, p. 1072-80
PHENobarbital food
Applies to: Alkabel-SR (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
- Gupta RC, Kofoed J (1966) "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J, 94, p. 863-5
- Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS (1971) "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med, 51, p. 346-51
- Saario I, Linnoila M (1976) "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh), 38, p. 382-92
- Stead AH, Moffat AC (1983) "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol, 2, p. 5-14
- Seixas FA (1979) "Drug/alcohol interactions: avert potential dangers." Geriatrics, 34, p. 89-102
atropine food
Applies to: Alkabel-SR (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
- Linnoila M (1973) "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol, 6, p. 107-12
hyoscyamine food
Applies to: Alkabel-SR (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
- Linnoila M (1973) "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol, 6, p. 107-12
scopolamine food
Applies to: Alkabel-SR (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
- Linnoila M (1973) "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol, 6, p. 107-12
scopolamine food
Applies to: Alkabel-SR (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
- Ebert U, Oertel R, Kirch W (2000) "Influence of grapefruit juice on scopolamine pharmacokinetics and pharmacodynamics in healthy male and female subjects." Int J Clin Pharm Therapeutics, 38, p. 523-31
Therapeutic duplication warnings
No warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
No interaction information available. |
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