Drug Interaction Report - Drugs

3/25/2014 Drug Interaction Report - Drugs.com

http://www.drugs.com/interactions-check.php?drug_list=133-0,1654-0,1956-0,233-109,1606-976,2296-1524,1937-2171,72-8500,1979-1274,11-12,1752-1120&pr 1/14

Drug Interaction ReportDrug interactions for the following 11 drug(s):

Drug List: My Drug List

alprazolam

montelukast

propranolol

Abilify (aripiprazole)

Concerta (methylphenidate)

Effexor (venlafaxine)

Lyrica (pregabalin)

Percocet 5 / 325 (acetaminophen / oxycodone)

Seroquel (quetiapine)

Tylenol (acetaminophen)

Zofran (ondansetron)

Interactions between your selected drugs

aripiprazole pregabalinApplies to: Abilify (aripiprazole), Lyrica (pregabalin)

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.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive

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or prolonged CNS and respiratory depression. 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. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI "Benzodiazepine overdosage: plasma concentrations and clinical outcome."Psychopharmacology (Berl) 73 (1981): 381-3

2. Plushner SL "Valerian: valeriana off icinalis." Am J Health Syst Pharm 57 (2000): 328-35

3. Lemberger L, Row e H, Bosomw orth JC, Tenbarge JB, Bergstrom RF "The effect of f luoxetine on the pharmacokinetics and psychomotorresponses of diazepam." Clin Pharmacol Ther 43 (1988): 412-9

View all 33 references

alprazolam aripiprazoleApplies to: alprazolam, Abilify (aripiprazole)



patients.





activities.

References





oxycodone aripiprazoleApplies to: Percocet 5 / 325 (acetaminophen / oxycodone), Abilify (aripiprazole)



patients.





activities.



References





venlafaxine aripiprazoleApplies to: Effexor (venlafaxine), Abilify (aripiprazole)



patients.





activities.

References





quetiapine aripiprazoleApplies to: Seroquel (quetiapine), Abilify (aripiprazole)

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.

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. Kulik AV, Wilbur R "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry 6 (1982):75-82

2. Mann SC, Boger WP "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry 135 (1978):1097-100

3. 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


alprazolam pregabalinApplies to: alprazolam, Lyrica (pregabalin)



patients.





activities.

References





oxycodone pregabalinApplies to: Percocet 5 / 325 (acetaminophen / oxycodone), Lyrica (pregabalin)



patients.







activities.

References





venlafaxine pregabalinApplies to: Effexor (venlafaxine), Lyrica (pregabalin)



patients.





activities.

References





quetiapine pregabalinApplies to: Seroquel (quetiapine), Lyrica (pregabalin)



patients.





activities.

References







propranolol aripiprazoleApplies to: propranolol, Abilify (aripiprazole)

MONITOR: Phenothiazines and neuroleptic agents may potentiate the hypotensive effect of some medications

secondary to their peripheral alpha-1 adrenergic blocking activity. Orthostatic hypotension and syncope

associated with vasodilation may occur, particularly during initial dosing and/or parenteral administration of the

phenothiazine or neuroleptic.

MANAGEMENT: Close clinical monitoring for development of hypotension is recommended if phenothiazines

or neuroleptic agents are used in patients receiving antihypertensive medications or vasodilators. A lower

starting dosage and slower titration of the phenothiazine or neuroleptic may be appropriate, especially in the

elderly. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify

their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients

should also avoid driving or operating hazardous machinery until they know how the medications affect them.

References

1. "Product Information. Seroquel (quetiapine)." Zeneca Pharmaceuticals, Wilmington, DE.

2. "Product Information. Clozaril (clozapine)." Sandoz Pharmaceuticals Corporation, East Hanover, NJ.

3. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company, Indianapolis, IN.


venlafaxine quetiapineApplies to: Effexor (venlafaxine), Seroquel (quetiapine)



patients.





activities.

References







ondansetron quetiapineApplies to: Zofran (ondansetron), Seroquel (quetiapine)

GENERALLY AVOID: There is some concern that quetiapine may have additive cardiovascular effects in

combination with other drugs that are known to prolong the QT interval of the electrocardiogram. In clinical

trials, quetiapine was not associated with a persistent increase in QT intervals, and there was no statistically

significant difference between quetiapine and placebo in the proportions of patients experiencing potentially

important changes in ECG parameters including QT, QTc, and PR intervals. However, QT prolongation and

torsade de pointes have been reported during postmarketing use in cases of quetiapine overdose and in

patients with risk factors such as underlying illness or concomitant use of drugs known to cause electrolyte

imbalance or increase QT interval. In general, the risk of an individual agent or a combination of agents

causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be

increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and

electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT

prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Coadministration of quetiapine with other drugs that can prolong the QT interval should

generally be avoided. Caution and clinical monitoring are recommended if concomitant use is required.

Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate

the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart

rhythm, shortness of breath, or syncope.

References

1. Glassman AH, Bigger JT Jr "Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death." Am J Psychiatry 158(2001): 1774-82

2. View eg WV "New generation antipsychotic drugs and QTc interval prolongation." Prim Care Companion J Clin Psychiatry 5 (2003): 205-15

3. View eg WV, Schneider RK, Wood MA "Torsade de pointes in a patient w ith complex medical and psychiatric conditions receiving low -dosequetiapine." Acta Psychiatr Scand 112 (2005): 318-22


propranolol alprazolamApplies to: propranolol, alprazolam

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics,

antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially

during initiation of therapy and dose escalation. Coadministration with antihypertensive agents, in particular

vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution is advised during coadministration of these agents. Close monitoring for development

of hypotension is recommended. Patients should be advised to avoid rising abruptly from a sitting or

recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope,

orthostasis, or tachycardia.



References

1. Feder R "Bradycardia and syncope induced by f luoxetine." J Clin Psychiatry 52 (1991): 139

2. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1

3. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selectiveserotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40


propranolol oxycodoneApplies to: propranolol, Percocet 5 / 325 (acetaminophen / oxycodone)

MONITOR: Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics,

antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially

during initiation of therapy and dose escalation. Coadministration with antihypertensive agents, in particular

vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

MANAGEMENT: Caution is advised during coadministration of these agents. Close monitoring for development

of hypotension is recommended. Patients should be advised to avoid rising abruptly from a sitting or

recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope,

orthostasis, or tachycardia.

References

1. Feder R "Bradycardia and syncope induced by f luoxetine." J Clin Psychiatry 52 (1991): 139

2. Sternbach H "Fluoxetine-associated potentiation of calcium-channel blockers." J Clin Psychopharmacol 11 (1991): 390-1

3. Rodriguez de la Torre B, Dreher J, Malevany I, et al. "Serum levels and cardiovascular effects of tricyclic antidepressants and selectiveserotonin reuptake inhibitors in depressed patients." Ther Drug Monit 23 (2001): 435-40


alprazolam oxycodoneApplies to: alprazolam, Percocet 5 / 325 (acetaminophen / oxycodone)



patients.





activities.

References



3. Lemberger L, Row e H, Bosomw orth JC, Tenbarge JB, Bergstrom RF "The effect of f luoxetine on the pharmacokinetics and psychomotor



responses of diazepam." Clin Pharmacol Ther 43 (1988): 412-9


alprazolam venlafaxineApplies to: alprazolam, Effexor (venlafaxine)



patients.





activities.

References





oxycodone venlafaxineApplies to: Percocet 5 / 325 (acetaminophen / oxycodone), Effexor (venlafaxine)

MONITOR: Coadministration of oxycodone with serotonin reuptake inhibitors has been associated with

development of the serotonin syndrome. The mechanism of interaction is unknown. Unlike other analgesics

such as phenylpiperidine opioids (e.g., meperidine) and tramadol, oxycodone is not known to possess

serotonergic activity and has not previously been associated with the serotonin syndrome. The report

describes a bone marrow transplant patient who developed severe tremors and visual hallucinations after he

dramatically increased his dosage of oxycodone while on a stable dosage of sertraline and cyclosporine.

Discontinuation of cyclosporine did not completely resolve his hallucinations and had no effect on the tremors

after 72 hours, which led to consideration of a possible sertraline-oxycodone interaction. The patient's

symptoms resolved after sertraline was withheld and cyproheptadine (a central serotonin antagonist)

administered. Serotonin syndrome is a rare but serious and potentially fatal condition thought to result from

hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms of the serotonin syndrome may include

mental status changes such as irritability, altered consciousness, confusion, hallucinations, and coma;

autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and

mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and

gastrointestinal symptoms such as abdominal cramping , nausea, vomiting, and diarrhea.

MANAGEMENT: Until more data are available, caution is advised if oxycodone is prescribed in combination

with serotonin reuptake inhibitors, particularly in complicated patients such as transplant patients who are also


http://www.drugs.com/interactions-check.php?drug_list=133-0,1654-0,1956-0,233-109,1606-976,2296-1524,1937-2171,72-8500,1979-1274,11-12,1752-1120&p 10/14

receiving cyclosporine. Patients should be monitored for symptoms of the serotonin syndrome during

treatment. Particular caution is advised when increasing the dosages of these agents. If serotonin syndrome

develops or is suspected during the course of therapy, all serotonergic agents should be discontinued

immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the

administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be

managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis,

intubation, and mechanical ventilation in addition to the other measures. Patients should also be advised of

potentially additive central nervous system effects from these agents and to avoid hazardous activities

requiring complete mental alertness and motor coordination until they know how these agents affect them.

References

1. Rosebraugh CJ, f loxkhart DA, Yasuda SU, Woosley RL "Visual hallucination and tremor induced by sertraline and oxycodone in a bonemarrow transplant patient." J Clin Pharmacol 41 (2001): 224-7

propranolol quetiapineApplies to: propranolol, Seroquel (quetiapine)

MONITOR: Phenothiazines and neuroleptic agents may potentiate the hypotensive effect of some medications

secondary to their peripheral alpha-1 adrenergic blocking activity. Orthostatic hypotension and syncope

associated with vasodilation may occur, particularly during initial dosing and/or parenteral administration of the

phenothiazine or neuroleptic.

MANAGEMENT: Close clinical monitoring for development of hypotension is recommended if phenothiazines

or neuroleptic agents are used in patients receiving antihypertensive medications or vasodilators. A lower

starting dosage and slower titration of the phenothiazine or neuroleptic may be appropriate, especially in the

elderly. Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify

their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia. Patients

should also avoid driving or operating hazardous machinery until they know how the medications affect them.

References

1. "Product Information. Seroquel (quetiapine)." Zeneca Pharmaceuticals, Wilmington, DE.

2. "Product Information. Clozaril (clozapine)." Sandoz Pharmaceuticals Corporation, East Hanover, NJ.

3. "Product Information. Zyprexa (olanzapine)." Lilly, Eli and Company, Indianapolis, IN.


alprazolam quetiapineApplies to: alprazolam, Seroquel (quetiapine)



patients.







activities.

References





oxycodone quetiapineApplies to: Percocet 5 / 325 (acetaminophen / oxycodone), Seroquel (quetiapine)



patients.





activities.

References





propranolol acetaminophenApplies to: propranolol, Tylenol (acetaminophen), Percocet 5 / 325 (acetaminophen / oxycodone)

Two studies have suggested that propranolol may increase the pharmacologic effects of acetaminophen. The

mechanism may be related to inhibition of acetaminophen metabolism. The clinical significance of this

interaction is unknown.

References

1. Baraka OZ, Truman CA, Ford JM, Roberts JC "The effect of propranolol on paracetamol metabolism in man." Br J Clin Pharmacol 29 (1990):261-4

2. Baraka OZ, Ford JM, Truman CA, Roberts CJ "Effect of propranolol on the metabolic pathw ays for paracetamol in man." Br J Clin Pharmacol28 (1989): p230-1

No other interactions were found between your selected drugs.



Note: this does not necessarily mean no interactions exist. ALWAYS consult with your doctor or pharmacist.

Other drugs that your selected drugs interact with

alprazolam interacts with more than 400 other drugs.

montelukast interacts with more than 50 other drugs.

propranolol interacts with more than 400 other drugs.

Abilify (aripiprazole) interacts with more than 400 other drugs.

Concerta (methylphenidate) interacts with more than 100 other drugs.

Effexor (venlafaxine) interacts with more than 400 other drugs.

Lyrica (pregabalin) interacts with more than 200 other drugs.

Percocet 5 / 325 (acetaminophen / oxycodone) interacts with more than 400 other drugs.

Seroquel (quetiapine) interacts with more than 500 other drugs.

Tylenol (acetaminophen) interacts with more than 80 other drugs.

Zofran (ondansetron) interacts with more than 100 other drugs.

Interactions between your selected drugs and food

propranolol foodApplies to: propranolol

ADJUST DOSING INTERVAL: The bioavailability of propranolol may be enhanced by food.

MANAGEMENT: Patients may be instructed to take propranolol at the same time each day, preferably with or

immediately following meals.

References

1. Olanoff LS, Walle T, Cow art TD, et al "Food effects on propranolol systemic and oral clearance: support for a blood f low hypothesis." ClinPharmacol Ther 40 (1986): 408-14

2. Byrne AJ, McNeil JJ, Harrison PM, Louis W, Tonkin AM, McLean AJ "Stable oral availability of sustained release propranolol w hen co-administered w ith hydralazine or food: evidence implicating substrate delivery rate as a determinant of presystemic drug interactions." Br JClin Pharmacol 17 (1984): s45-50

alprazolam foodApplies to: alprazolam

GENERALLY AVOID: The pharmacologic activity of oral midazolam, triazolam, and alprazolam may be

increased if taken after drinking grapefruit juice. The proposed mechanism is CYP450 3A4 enzyme inhibition.

MANAGEMENT: The manufacturer recommends that grapefruit juice should not be taken with oral midazolam.

Patients taking triazolam or alprazolam should be monitored for excessive sedation. Alternatively, the patient

could consume orange juice which does not interact with these drugs.



References

1. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruitjuice." Clin Pharmacol Ther 58 (1995): 127-31

2. Kupferschmidt HHT, Ha HR, Ziegler WH, Meier PJ, Krahenbuhl S "Interaction betw een grapefruit juice and midazolam in humans." ClinPharmacol Ther 58 (1995): 20-8

3. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit andprobable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77


oxycodone foodApplies to: Percocet 5 / 325 (acetaminophen / oxycodone)

GENERALLY AVOID: The central nervous system-depressant effects of oxycodone and alcohol may be

additive. Combining these agents may result in additive CNS-depression and impairment of judgment,

thinking, and psychomotor skills. In more severe cases, respiratory depression, hypotension, profound

sedation, and coma can occur.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of oxycodone. The proposed

mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism of oxycodone by certain compounds

present in grapefruit, resulting in decreased formation of metabolites noroxycodone and noroxymorphone and

increased formation of oxymorphone due to a presumed shifting of oxycodone metabolism towards the

CYP450 2D6-mediated route. In 12 healthy, nonsmoking volunteers, administration of a single 10 mg oral

dose of oxycodone hydrochloride on day 4 of a grapefruit juice treatment phase (200 mL three times a day for

5 days) increased mean oxycodone peak plasma concentration (Cmax), systemic exposure (AUC) and half-life

by 48%, 67% and 17% (from 3.5 to 4.1 hours), respectively, compared to administration during an equivalent

water treatment phase. Grapefruit juice also decreased the metabolite-to-parent AUC ratio of noroxycodone

by 44% and that of noroxymorphone by 45%. In addition, oxymorphone Cmax and AUC increased by 32% and

56%, but the metabolite-to-parent AUC ratio remained unchanged. Pharmacodynamic changes were modest

and only self-reported performance was significantly impaired after grapefruit juice. Analgesic effects were not

affected.

MANAGEMENT: Patients should not consume alcoholic beverages or use drug products that contain alcohol

during treatment with oxycodone. Any history of alcohol or illicit drug use should be considered when

prescribing oxycodone, and therapy initiated at a lower dosage if necessary. Patients should be closely

monitored for signs of sedation, respiratory depression, and hypotension. Due to a high degree of interpatient

variability with respect to grapefruit juice interactions, patients treated with oxycodone may also want to avoid

or limit the consumption of grapefruit and grapefruit juice.

References

1. Nieminen TH, Hagelberg NM, Saari TI, et al "Grapefruit juice enhances the exposure to oral oxycodone." Basic Clin Pharmacol Toxicol 107(2010): 782-8

methylphenidate foodApplies to: Concerta (methylphenidate)

GENERALLY AVOID: Alcohol may exacerbate the adverse central nervous system effects of psychoactive



drugs, including methylphenidate.

GENERALLY AVOID: Consumption of alcohol while taking certain sustained-release formulations of

methylphenidate may cause rapid release of the drug, resulting in increased systemic levels of

methylphenidate. In vitro studies have been conducted using Metadate CD 60 mg and Ritalin LA 40 mg

capsules, as well as Concerta 18 mg tablet. At an alcohol concentration of 40%, an increase in the release

rate of methylphenidate was observed in the first hour for Metadate CD and Ritalin LA, resulting in 84% and

98% of the methylphenidate being released, respectively. In contrast, there was no increased release of

methylphenidate in the first hour for Concerta. These results are considered to be representative of the other

available strengths of the corresponding product.

MANAGEMENT: Patients treated with methylphenidate should be advised to avoid alcohol or medications that

contain alcohol.

References

1. "Product Information. Concerta (methylphenidate)." Alza, Palo Alto, CA.

2. "Product Information. Metadate CD Capsules (methylphenidate)" Celltech Pharmaceuticals, Inc, Applegate, WI.

Drug Interaction Classification

The classifications below are a guideline only. The relevance of a particular drug interaction to a specific patient is difficult to

determine using this tool alone given the large number of variables that may apply.

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.

Do not stop taking any medications without consulting your healthcare provider.

Disclaimer: Every effort has been made to ensure that the information provided by Multum is accurate, up-to-date and complete, but no

guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a

reference resource beyond the date hereof. This material does not endorse drugs, diagnose patients, or recommend therapy. Multum's

information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill, know ledge, and judgement of

healthcare practitioners in patient care. The absence of a w arning for a given drug or combination thereof in no w ay should be construed to

indicate that the drug or combination is safe, effective, or appropriate for any given patient. Multum Information Services, Inc. does not assume

any responsibility for any aspect of healthcare administered w ith the aid of information Multum provides. Copyright 2000-2014 Multum

Information Services, Inc. The information contained herein is not intended to cover all possible uses, directions, precautions, w arnings, drug

interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check w ith your doctor, nurse, or

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Drug Interaction Report - Drugs