Drug Interaction Report
15 potential interactions and/or warnings found for the following 2 drugs:
- Parcopa (carbidopa / levodopa)
- Phenohytro (atropine / hyoscyamine / phenobarbital / scopolamine)
Interactions between your drugs
atropine levodopa
Applies to: Phenohytro (atropine / hyoscyamine / phenobarbital / scopolamine), Parcopa (carbidopa / levodopa)
MONITOR: Anticholinergic agents may decrease the absorption and oral bioavailability of levodopa. The proposed mechanism involves increased gastrointestinal transit time due to reduction of stomach and intestinal motility by anticholinergic agents, thereby increasing the gastric degradation of levodopa and reducing the amount available for absorption in the small intestine. In one study, pretreatment with trihexyphenidyl decreased the peak plasma concentration (Cmax) and delayed the time to peak concentration (Tmax) of levodopa in 3 of 6 healthy volunteers and 4 of 6 Parkinson patients. In another study, 42% of patients receiving levodopa with anticholinergic therapy developed abnormal involuntary movements compared to 19% of those treated with levodopa alone. Discontinuation or dosage reduction of anticholinergic therapy resulted in disappearance or amelioration of the symptoms in 9 of 10 cases, although subsequent aggravation of Parkinsonism necessitated resumption of anticholinergic therapy in 5 cases. There is also a case report describing a patient who required large doses of levodopa during concomitant therapy with homatropine. Following discontinuation of homatropine, the patient exhibited symptoms of levodopa toxicity and required a significant decrease in the levodopa dosage. Other studies have reported no effect of anticholinergic agents on levodopa blood levels or pharmacologic effects.
MANAGEMENT: Although certain anticholinergic agents may be used as adjunctive therapy in Parkinson's disease, clinicians should recognize their potential to reduce the oral bioavailability of levodopa in some patients. Pharmacologic response to levodopa should be monitored more closely whenever anticholinergic agents are added to or withdrawn from therapy, and the dosages of the drugs adjusted as necessary.
References
- Bergmann S, Curzon G, Friedel J, et al. (1974) "The absorption and metabolism of a standard oral dose of levodopa in patients with parkinsonism." Br J Clin Pharmacol, 1, p. 417-24
- Birket-Smith E (1974) "Abnormal involuntary movements induced by anticholinergic therapy." Acta Neurol Scand, 50, p. 801-11
- Rivera-Calimlim L, Dujovne CA, Morgan JP, Lasagna L, Bianchine JR (1971) "Absorption and metabolism of L-dopa by the human stomach." Eur J Clin Invest, 1, p. 313-20
- Algeri S, Cerletti C, Curcio M, et al. (1976) "Effect of anticholinergic drugs on gastro-intestinal absorption of L-dopa in rats and man." Eur J Pharmacol, 35, p. 293-9
- Fermaglich J, O'Dougherty DS (1972) "Effect of gastric motility on levodopa." Dis Nerv Syst, 33, p. 624-5
- Hughes R, Polgar JG, Weightman D, Walton JN (1971) "Levodopa in Parkinsonism: the effects of withdrawal of anticholinergic drugs." Br Med J, 2, p. 487-91
atropine hyoscyamine
Applies to: Phenohytro (atropine / hyoscyamine / phenobarbital / scopolamine), Phenohytro (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
atropine scopolamine
Applies to: Phenohytro (atropine / hyoscyamine / phenobarbital / scopolamine), Phenohytro (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
levodopa PHENobarbital
Applies to: Parcopa (carbidopa / levodopa), Phenohytro (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
levodopa hyoscyamine
Applies to: Parcopa (carbidopa / levodopa), Phenohytro (atropine / hyoscyamine / phenobarbital / scopolamine)
MONITOR: Anticholinergic agents may decrease the absorption and oral bioavailability of levodopa. The proposed mechanism involves increased gastrointestinal transit time due to reduction of stomach and intestinal motility by anticholinergic agents, thereby increasing the gastric degradation of levodopa and reducing the amount available for absorption in the small intestine. In one study, pretreatment with trihexyphenidyl decreased the peak plasma concentration (Cmax) and delayed the time to peak concentration (Tmax) of levodopa in 3 of 6 healthy volunteers and 4 of 6 Parkinson patients. In another study, 42% of patients receiving levodopa with anticholinergic therapy developed abnormal involuntary movements compared to 19% of those treated with levodopa alone. Discontinuation or dosage reduction of anticholinergic therapy resulted in disappearance or amelioration of the symptoms in 9 of 10 cases, although subsequent aggravation of Parkinsonism necessitated resumption of anticholinergic therapy in 5 cases. There is also a case report describing a patient who required large doses of levodopa during concomitant therapy with homatropine. Following discontinuation of homatropine, the patient exhibited symptoms of levodopa toxicity and required a significant decrease in the levodopa dosage. Other studies have reported no effect of anticholinergic agents on levodopa blood levels or pharmacologic effects.
MANAGEMENT: Although certain anticholinergic agents may be used as adjunctive therapy in Parkinson's disease, clinicians should recognize their potential to reduce the oral bioavailability of levodopa in some patients. Pharmacologic response to levodopa should be monitored more closely whenever anticholinergic agents are added to or withdrawn from therapy, and the dosages of the drugs adjusted as necessary.
References
- Bergmann S, Curzon G, Friedel J, et al. (1974) "The absorption and metabolism of a standard oral dose of levodopa in patients with parkinsonism." Br J Clin Pharmacol, 1, p. 417-24
- Birket-Smith E (1974) "Abnormal involuntary movements induced by anticholinergic therapy." Acta Neurol Scand, 50, p. 801-11
- Rivera-Calimlim L, Dujovne CA, Morgan JP, Lasagna L, Bianchine JR (1971) "Absorption and metabolism of L-dopa by the human stomach." Eur J Clin Invest, 1, p. 313-20
- Algeri S, Cerletti C, Curcio M, et al. (1976) "Effect of anticholinergic drugs on gastro-intestinal absorption of L-dopa in rats and man." Eur J Pharmacol, 35, p. 293-9
- Fermaglich J, O'Dougherty DS (1972) "Effect of gastric motility on levodopa." Dis Nerv Syst, 33, p. 624-5
- Hughes R, Polgar JG, Weightman D, Walton JN (1971) "Levodopa in Parkinsonism: the effects of withdrawal of anticholinergic drugs." Br Med J, 2, p. 487-91
levodopa scopolamine
Applies to: Parcopa (carbidopa / levodopa), Phenohytro (atropine / hyoscyamine / phenobarbital / scopolamine)
MONITOR: Anticholinergic agents may decrease the absorption and oral bioavailability of levodopa. The proposed mechanism involves increased gastrointestinal transit time due to reduction of stomach and intestinal motility by anticholinergic agents, thereby increasing the gastric degradation of levodopa and reducing the amount available for absorption in the small intestine. In one study, pretreatment with trihexyphenidyl decreased the peak plasma concentration (Cmax) and delayed the time to peak concentration (Tmax) of levodopa in 3 of 6 healthy volunteers and 4 of 6 Parkinson patients. In another study, 42% of patients receiving levodopa with anticholinergic therapy developed abnormal involuntary movements compared to 19% of those treated with levodopa alone. Discontinuation or dosage reduction of anticholinergic therapy resulted in disappearance or amelioration of the symptoms in 9 of 10 cases, although subsequent aggravation of Parkinsonism necessitated resumption of anticholinergic therapy in 5 cases. There is also a case report describing a patient who required large doses of levodopa during concomitant therapy with homatropine. Following discontinuation of homatropine, the patient exhibited symptoms of levodopa toxicity and required a significant decrease in the levodopa dosage. Other studies have reported no effect of anticholinergic agents on levodopa blood levels or pharmacologic effects.
MANAGEMENT: Although certain anticholinergic agents may be used as adjunctive therapy in Parkinson's disease, clinicians should recognize their potential to reduce the oral bioavailability of levodopa in some patients. Pharmacologic response to levodopa should be monitored more closely whenever anticholinergic agents are added to or withdrawn from therapy, and the dosages of the drugs adjusted as necessary.
References
- Bergmann S, Curzon G, Friedel J, et al. (1974) "The absorption and metabolism of a standard oral dose of levodopa in patients with parkinsonism." Br J Clin Pharmacol, 1, p. 417-24
- Birket-Smith E (1974) "Abnormal involuntary movements induced by anticholinergic therapy." Acta Neurol Scand, 50, p. 801-11
- Rivera-Calimlim L, Dujovne CA, Morgan JP, Lasagna L, Bianchine JR (1971) "Absorption and metabolism of L-dopa by the human stomach." Eur J Clin Invest, 1, p. 313-20
- Algeri S, Cerletti C, Curcio M, et al. (1976) "Effect of anticholinergic drugs on gastro-intestinal absorption of L-dopa in rats and man." Eur J Pharmacol, 35, p. 293-9
- Fermaglich J, O'Dougherty DS (1972) "Effect of gastric motility on levodopa." Dis Nerv Syst, 33, p. 624-5
- Hughes R, Polgar JG, Weightman D, Walton JN (1971) "Levodopa in Parkinsonism: the effects of withdrawal of anticholinergic drugs." Br Med J, 2, p. 487-91
PHENobarbital scopolamine
Applies to: Phenohytro (atropine / hyoscyamine / phenobarbital / scopolamine), Phenohytro (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: Phenohytro (atropine / hyoscyamine / phenobarbital / scopolamine), Phenohytro (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
PHENobarbital food
Applies to: Phenohytro (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
levodopa food
Applies to: Parcopa (carbidopa / levodopa)
GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of levodopa. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.
MONITOR: Limited clinical data suggest that high protein content in the diet may reduce or cause fluctuations in the clinical response to oral and enteral formulations of levodopa in patients with Parkinson's disease. Proposed mechanisms include delayed gastric emptying, decreased levodopa absorption when taken with a protein rich diet, and competition with certain amino acids for transport across the gut wall and/or the blood brain barrier. Data have been conflicting. Clinical studies have variously reported no effect, reduced levodopa absorption with low-protein meals, reduced effects of oral and enteral formulations of levodopa with high daily protein intake, and no differences compared to fasting with high-protein meals. Neuroleptic malignant-like symptoms were reported in a patient with Parkinson's disease who was receiving pramipexole, entacapone, and immediate-release levodopa/carbidopa, after the protein content of his enteral feedings via nasogastric tube was increased from 0.88 g/kg/day to 1.8 g/kg/day; symptoms improved after the protein was reduced to 1 g/kg/day and bromocriptine was administered. Another patient receiving immediate-release carbidopa/levodopa, pramipexole, and entacapone experienced severe rigidity after initiation of continuous enteral nutrition via oral gastric tube containing 1.4 g/kg/day of protein; his Parkinsonian symptoms improved after the protein content was reduced to 0.9 g/kg/day, the feeding was changed to bolus feedings, and the levodopa was administered between boluses.
MANAGEMENT: In general, alcohol consumption should be avoided or limited during treatment with CNS-depressant agents. Until more data are available, it is advisable to avoid large fluctuations in daily protein intake and to monitor patients for altered effects of oral and enteral levodopa formulations if the protein content of the diet is increased.
References
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT (2009) "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm, 66, p. 1438-67
- (2022) "Product Information. Duopa (carbidopa-levodopa)." AbbVie US LLC
- (2021) "Product Information. Duodopa (carbidopa-levodopa)." AbbVie Pty Ltd, 18
- (2023) "Product Information. Vyalev (foscarbidopa-foslevodopa)." AbbVie Corporation
- (2022) "Product Information. Dhivy (carbidopa-levodopa)." Avion Pharmaceuticals
atropine food
Applies to: Phenohytro (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: Phenohytro (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: Phenohytro (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
levodopa food
Applies to: Parcopa (carbidopa / levodopa)
ADJUST DOSING INTERVAL: The oral bioavailability and pharmacologic effects of levodopa and carbidopa may be decreased during concurrent administration with iron-containing products. The proposed mechanism is chelation of levodopa and carbidopa by the iron cation, forming an insoluble complex that is poorly absorbed from the gastrointestinal tract. In nine patients with Parkinson's disease, administration of levodopa-carbidopa 100 mg-25 mg with ferrous sulfate 325 mg decreased levodopa peak plasma concentration (Cmax) and systemic exposure (AUC) by 47% and 30%, respectively, and carbidopa Cmax and AUC by 77% and 82%, respectively, compared to administration with placebo. There was also evidence of reduced efficacy of levodopa in some patients. In another study consisting of eight healthy subjects, coadministration of levodopa 250 mg with ferrous sulfate 325 mg resulted in greater than 50% reductions in the Cmax and AUC of levodopa compared to administration of levodopa alone. The magnitude of the interaction was the greatest in patients whose plasma levels of levodopa were the highest following administration of levodopa alone.
MANAGEMENT: Until more information is available, patients receiving levodopa and/or carbidopa in combination with iron-containing products should be advised to separate the times of administration by as much as possible. Patients should be monitored for reduced efficacy of levodopa, and the dosage adjusted as necessary.
References
- Campbell NR, Hasinoff B (1989) "Ferrous sulfate reduces levodopa bioavailability: chelation as a possible mechanism." Clin Pharmacol Ther, 45, p. 220-5
- Campbell NR, Hasinoff BB (1991) "Iron supplements: a common cause of drug interactions." Br J Clin Pharmacol, 31, p. 251-5
- Campbell NR, Rankine D, Goodridge AE, Hasinoff BB, Kara M (1990) "Sinemet-ferrous sulphate interaction in patients with Parkinson's disease." Br J Clin Pharmacol, 30, p. 599-605
- Greene RJ, Hall AD, Hider RC (1990) "The interaction of orally administered iron with levodopa and methyldopa therapy." J Pharm Pharmacol, 42, p. 502-4
scopolamine food
Applies to: Phenohytro (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 duplication 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.
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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