Drug Interaction Report

Drug interactions for the following 4 drug(s):

My Interactions List: (Unsaved)

diclofenac

bupropion

escitalopram

methylphenidate

Interactions between your drugs

Major
buPROPion  methylphenidate
Applies to: bupropion, methylphenidate
MONITOR CLOSELY: The use of bupropion is associated with a dose-related risk of seizures. The risk
may be further increased when coadministered with selective serotonin reuptake inhibitors (SSRI
antidepressants or anorectics), monoamine oxidase inhibitors, neuroleptic agents, central nervous
system stimulants, opioids, tricyclic antidepressants, other tricyclic compounds (e.g.,
cyclobenzaprine, phenothiazines), systemic steroids, or any substance that can reduce the seizure
threshold (e.g., carbapenems, cholinergic agents, fluoroquinolones, interferons, chloroquine,
mefloquine, lindane, theophylline). These agents are often individually epileptogenic and may have
additive effects when combined. The estimated incidence of seizures is approximately 0.4% for
immediate-release bupropion hydrochloride at dosages between 300 to 450 mg/day (equivalent to
348 to 522 mg/day of bupropion hydrobromide), but increases almost tenfold between 450 mg and
600 mg/day (equivalent to 522 and 696 mg/day of bupropion hydrobromide). Data for sustained-
release (SR) bupropion hydrochloride revealed a seizure incidence of approximately 0.1% at dosages
up to 300 mg/day and 0.4% at 400 mg/day. Likewise, in clinical trials, an overall seizure incidence of
approximately 0.1% has been reported with extended-release (XL) bupropion hydrochloride at
dosages up to 450 mg/day and approximately 0.39% at 450 mg/day. The 0.4% seizure incidence may
exceed that of other marketed antidepressants by as much as 4-fold.

MANAGEMENT: Extreme caution is advised if bupropion is administered with any substance that can
reduce the seizure threshold, particularly in the elderly and in patients with a history of seizures or
other risk factors for seizures (e.g., head trauma; brain tumor; severe hepatic cirrhosis; metabolic
disorders; CNS infections; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or
stimulants; diabetes treated with oral hypoglycemic agents or insulin). Bupropion as well as
concomitant medications should be initiated at the lower end of the dosage range and titrated
gradually as needed and as tolerated. The maximum recommended dosage for the specific
bupropion formulation should not be exceeded. Bupropion should be discontinued and not restarted
in patients who experience a seizure during treatment.
References
1. "Product Information. Wellbutrin XL (buPROPion)." GlaxoSmithKline, Philadelphia, PA.

2. Masco HL, Kiev A, Holloman LC, Batey SR, Johnston JA, Lineberry CG "Safety and efficacy of bupropion and nortriptyline in outpatients with
depression." Curr Ther Res Clin Exp 55 (1994): 851-63

3. Sheehan DV, Welch JB, Fishman SM "A case of bupropion-induced seizure." J Nerv Ment Dis 174 (1986): 496-8

View all 15 references

Major
buPROPion  escitalopram
Applies to: bupropion, escitalopram
MONITOR CLOSELY: The use of bupropion is associated with a dose-related risk of seizures. The risk
may be further increased when coadministered with other agents that can reduce the seizure
threshold, including selective serotonin reuptake inhibitors (SSRIs) such as citalopram and
escitalopram. The estimated incidence of seizures is approximately 0.4% for immediate-release
bupropion hydrochloride at dosages between 300 to 450 mg/day (equivalent to 348 to 522 mg/day of
bupropion hydrobromide), but increases almost tenfold between 450 mg and 600 mg/day (equivalent
to 522 and 696 mg/day of bupropion hydrobromide). Data for sustained-release (SR) bupropion
hydrochloride revealed a seizure incidence of approximately 0.1% at dosages up to 300 mg/day and
0.4% at 400 mg/day. Likewise, in clinical trials, an overall seizure incidence of approximately 0.1% has
been reported with extended-release (XL) bupropion hydrochloride at dosages up to 450 mg/day and
approximately 0.39% at 450 mg/day. The 0.4% seizure incidence may exceed that of other marketed
antidepressants by as much as 4-fold.

Pharmacokinetically, bupropion may increase the plasma concentrations of citalopram. The

mechanism of interaction has not been described. Unlike other SSRIs, citalopram is not known to be
significantly metabolized by CYP450 2D6, which is inhibited by bupropion and its metabolite,
hydroxybupropion. In one study, bupropion increased citalopram peak plasma concentration (Cmax)
and systemic exposure (AUC) by 30% and 40%, respectively. Citalopram did not affect the
pharmacokinetics of bupropion and its three active metabolites. The interaction has not been studied
with escitalopram.

MANAGEMENT: Extreme caution is advised if bupropion is administered with any substance that can
reduce the seizure threshold, particularly in the elderly and in patients with a history of seizures or
other risk factors for seizures (e.g., head trauma; brain tumor; severe hepatic cirrhosis; metabolic
disorders; CNS infections; excessive use of alcohol or sedatives; addiction to opiates, cocaine, or
stimulants; diabetes treated with oral hypoglycemic agents or insulin). Bupropion as well as
concomitant medications should be initiated at the lower end of the dosage range and titrated
gradually as needed and as tolerated. The maximum recommended dosage for the specific
bupropion formulation should not be exceeded. Clinical and laboratory monitoring may be
appropriate for citalopram or escitalopram whenever bupropion is added to or withdrawn from
therapy. Bupropion should be discontinued and not restarted in patients who experience a seizure
during treatment.

References
1. "Product Information. Zyban (bupropion)." Glaxo Wellcome, Research Triangle Park, NC.

2. Dufresne RL, Weber SS, Becker RE "Bupropion hydrochloride." Drug Intell Clin Pharm 18 (1984): 957-64

3. Storrow AB "Bupropion overdose and seizure." Am J Emerg Med 12 (1994): 183-4

View all 15 references

 Moderate
diclofenac  escitalopram
Applies to: diclofenac, escitalopram
MONITOR: Serotonin reuptake inhibitors (SRIs) may potentiate the risk of bleeding in patients treated
with ulcerogenic agents and agents that affect hemostasis such as anticoagulants, platelet
inhibitors, thrombin inhibitors, thrombolytic agents, or agents that commonly cause
thrombocytopenia. The tricyclic antidepressant, clomipramine, is also a strong SRI and may interact
similarly. Serotonin release by platelets plays an important role in hemostasis, thus SRIs may alter
platelet function and induce bleeding. Published case reports have documented the occurrence of
bleeding episodes in patients treated with psychotropic agents that interfere with serotonin reuptake.
Bleeding events related to SRIs have ranged from ecchymosis, hematoma, epistaxis, and petechiae to
life-threatening hemorrhages. Additional epidemiological studies have confirmed the association
between use of these agents and the occurrence of upper gastrointestinal bleeding, and concurrent
use of NSAIDs or aspirin was found to potentiate the risk. Preliminary data also suggest that there
may be a pharmacodynamic interaction between SSRIs and oral anticoagulants that can cause an
increased bleeding diathesis. Concomitant administration of paroxetine and warfarin, specifically, has
been associated with an increased frequency of bleeding without apparent changes in the disposition
of either drug or changes in the prothrombin time. Bleeding has also been reported with fluoxetine
and warfarin, while citalopram and sertraline have been reported to prolong the prothrombin time of
patients taking warfarin by about 5% to 8%. In the RE-LY study (Randomized Evaluation of Long-term
anticoagulant therapy), SRIs were associated with an increased risk of bleeding in all treatment
groups.

MANAGEMENT: Caution is advised if SRIs or clomipramine are used in combination with other drugs
that affect hemostasis. Close clinical and laboratory observation for hematologic complications is
recommended. Patients should be advised to promptly report any signs of bleeding to their physician,
including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased
menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or
bruising, red or brown urine, or red or black stools.

References
1. Krivy J, Wiener J "Sertraline and platelet counts in idiopathic thrombocytopenia purpura." Lancet 345 (1995): 132

2. "Product Information. Savella (milnacipran)." Forest Pharmaceuticals, St. Louis, MO.

3. Bannister SJ, Houser VP, Hulse JD, Kisicki JC, Rasmussen JG "Evaluation of the potential for interactions of paroxetine with diazepam, cimetidine,
warfarin, and digoxin." Acta Psychiatr Scand Suppl 350 (1989): 102-6

View all 39 references

Moderate
methylphenidate  escitalopram
Applies to: methylphenidate, escitalopram
MONITOR: Coadministration with methylphenidate may increase the plasma concentrations and
effects of selective serotonin reuptake inhibitors (SSRIs). Human pharmacologic studies have shown
that methylphenidate may inhibit the metabolism of some antidepressants including SSRIs. There
have been isolated reports of adverse reactions such as hallucinations, confusion, seizures, and
serotonin syndrome during concomitant use of methylphenidate with an SSRI, which resolved
following discontinuation of one or both drugs. Nevertheless, the combination has been used
therapeutically to improve clinical response in the treatment of attention-deficit hyperactivity disorder
and to augment the effects of SSRIs in the treatment of depression.

MANAGEMENT: Pharmacologic response to SSRIs should be monitored more closely whenever

methylphenidate (racemic) or dexmethylphenidate (the more pharmacologically active d-enantiomer)
is added to or withdrawn from therapy, and the dosage of one or both drugs adjusted as necessary.

References
1. Stoll AL, Pillay SS, Diamond L, Workum SB, Cole JO "Methylphenidate augmentation of serotonin selective reuptake inhibitors: a case series." J Clin
Psychiatry 57 (1996): 72-6

2. Findling RL "Open-label treatment of comorbid depression and attentional disorders with co-administration of serotonin reuptake inhibitors and
psychostimulants in children, adolescents, and adults: a case series." J Child Adolesc Psychopharmacol 6 (1996): 165-75

3. Gammon GD, Brown TE "Fluoxetine and methylphenidate in combination for treatment of attention deficit disorder and comorbid depressive
disorder." J Child Adolesc Psychopharmacol 3 (1993): 1-10

View all 8 references

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 drug and disease interactions

diclofenac interacts with more than 300 other drugs and more than 10 diseases.
bupropion interacts with more than 400 other drugs and 8 diseases.
escitalopram interacts with more than 600 other drugs.
methylphenidate interacts with more than 100 other drugs and more than 10 diseases.

Drug and food interactions

Moderate
buPROPion  food
Applies to: bupropion
GENERALLY AVOID: Excessive use or abrupt discontinuation of alcohol after chronic ingestion may
precipitate seizures in patients receiving bupropion. Additionally, there have been rare postmarketing
reports of adverse neuropsychiatric events or reduced alcohol tolerance in patients who drank
alcohol during treatment with bupropion. According to one forensic report, a patient died after taking
large doses of both bupropion and alcohol. It is uncertain whether a drug interaction was involved.
Single-dose studies in healthy volunteers given bupropion and alcohol failed to demonstrate either a
significant pharmacokinetic or pharmacodynamic interaction.

MANAGEMENT: The manufacturer recommends that alcohol consumption be minimized or avoided

during bupropion treatment. The use of bupropion is contraindicated in patients undergoing abrupt
discontinuation of alcohol.

References
1. "Product Information. Wellbutrin (bupropion)." Glaxo Wellcome, Research Triangle Park, NC.

2. Posner J, Bye A, Jeal S, Peck AW, Whiteman P "Alcohol and bupropion pharmacokinetics in healthy male volunteers." Eur J Clin Pharmacol 26
(1984): 627-30

3. Hamilton MJ, Bush MS, Peck AW "The effect of bupropion, a new antidepressant drug, and alcohol and their interaction in man." Eur J Clin
Pharmacol 27 (1984): 75-80

View all 4 references

 Moderate
methylphenidate  food
Applies to: 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. Ritalin LA (methylphenidate)." Quality Care Products/Lake Erie Medical , Temperance, MI.

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

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

Moderate
escitalopram  food
Applies to: escitalopram
GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents.
Use in combination may result in additive central nervous system depression and/or impairment of
judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and
advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid
hazardous activities requiring complete 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. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15
(1986): 31-7

2. "Product Information. Fycompa (perampanel)." Eisai Inc, Teaneck, NJ.

3. "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc, Rockville, MD.

View all 4 references

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or
therapeutic class to treat the same condition. This can be intentional in cases where drugs
with similar actions are used together for demonstrated therapeutic benefit. It can also be
 unintentional in cases where a patient has been treated by more than one doctor, or had
prescriptions filled at more than one pharmacy, and can have potentially adverse
consequences.

Duplication
Antidepressants
Therapeutic duplication
The recommended maximum number of medicines in the 'antidepressants' category to be taken
concurrently is usually one. Your list includes two medicines belonging to the 'antidepressants'
category:

bupropion
escitalopram

Note: The benefits of taking this combination of medicines may outweigh any risks associated with
therapeutic duplication. This information does not take the place of talking to your doctor. Always
check with your healthcare provider to determine if any adjustments to your medications are needed.

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.

Unknown No information available.

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

Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to
your personal circumstances.