diphenoxylate/atropine (Rx)

Brand and Other Names:Lomotil
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

diphenoxylate/atropine (Schedule V)

tablet

  • 2.5mg/0.025mg

solution

  • 2.5mg/0.025mg/5mL

Diarrhea

5 mg diphenoxylate/0.05 mg atropine (2 tablets) PO q6hr; not to exceed 20 mg diphenoxylate daily until initial control of diarrhea achieved (usually 48 hr)

Contact physician if diarrhea continues beyond 48 hr; discontinue use if clinical improvement not seen within 10 days of dosing with maximum dose

Maintenance: As low as 25% of initial daily dosage

Dosage Forms & Strengths

diphenoxylate/atropine (Schedule V)

tablet

  • 2.5mg/0.025mg

solution

  • 2.5mg/0.025mg/5mL

Diarrhea

<2 years

  • Safety and efficacy not established

2-13 years (liquid formulation only)

  • Initial: 0.3 to 0.4 mg diphenoxylate/kg/day in 4 divided doses
  • 2 years (11-14 kg): 1.5-3 mL PO q6hr
  • 3 years (12-16 kg): 2-3 mL PO q6hr
  • 4 years (14-20 kg ): 2-4 mL PO q6hr
  • 5 years (16-23 kg): 2.5-4.5 mL PO q6hr
  • 6-8 years (17-32 kg): 2.5-5 mL PO q6hr
  • 9-12 years (23 to 55 kg): 3.5-5 mL PO q6hr

≥13 years

  • 5 mg diphenoxylate/0.05 mg atropine PO q6hr; not to exceed 20 mg diphenoxylate daily until initial control of diarrhea achieved (ususally 48 hr)
  • Contact physician if diarrhea continues beyond 48 hr; discontinue use if clinical improvement not seen within 10 days of dosing with maximum dose
  • Maintenance: As low as 25% of initial dosage
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Interactions

Interaction Checker

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            Contraindicated (1)

            • alvimopan

              alvimopan, diphenoxylate hcl. receptor binding competition. Contraindicated. Contraindicated in opioid tolerant patients (ie, those who have taken therapeutic doses of opioids for >7 consecutive days immediately prior to taking alvimopan). Patients recently exposed to opioids are expected to be more sensitive to the effects of alvimopan and therefore may experience abdominal pain, nausea and vomiting, and diarrhea.

            Serious - Use Alternative (26)

            • buprenorphine

              buprenorphine, diphenoxylate hcl. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • buprenorphine buccal

              buprenorphine buccal, diphenoxylate hcl. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • butorphanol

              butorphanol, diphenoxylate hcl. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • calcium/magnesium/potassium/sodium oxybates

              diphenoxylate hcl, calcium/magnesium/potassium/sodium oxybates. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • cimetidine

              cimetidine increases effects of diphenoxylate hcl by decreasing metabolism. Avoid or Use Alternate Drug.

            • eluxadoline

              atropine, eluxadoline. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that cause constipation. Increases risk for constipation related serious adverse reactions. .

            • glucagon

              glucagon increases effects of atropine by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of anticholinergic drugs and glucagon increase the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. .

            • glucagon intranasal

              glucagon intranasal increases effects of atropine by Other (see comment). Avoid or Use Alternate Drug. Comment: Coadministration of anticholinergic drugs and glucagon increase the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. .

            • glycopyrronium tosylate topical

              glycopyrronium tosylate topical, atropine. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration of glycopyrronium tosylate topical with other anticholinergic medications may result in additive anticholinergic adverse effects.

            • isocarboxazid

              isocarboxazid increases toxicity of diphenoxylate hcl by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • linezolid

              linezolid increases toxicity of diphenoxylate hcl by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • macimorelin

              atropine, macimorelin. unspecified interaction mechanism. Avoid or Use Alternate Drug. Drugs that may blunt the growth hormone (GH) response to macrimorelin may impact the accuracy of the diagnostic test. Allow sufficient washout time of drugs affecting GH release before administering macimorelin.

            • metoclopramide intranasal

              diphenoxylate hcl, metoclopramide intranasal. Either increases effects of the other by Other (see comment). Avoid or Use Alternate Drug. Comment: Avoid use of metoclopramide intranasal or interacting drug, depending on importance of drug to patient.

            • nalbuphine

              nalbuphine, diphenoxylate hcl. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • pentazocine

              pentazocine, diphenoxylate hcl. Other (see comment). Avoid or Use Alternate Drug. Comment: Mixed opiate agonist/antagonists usually produce additive sedation with narcotics; however, in narcotic addicted pts., the antagonist activity may provoke withdrawal Sx.

            • phenelzine

              phenelzine increases toxicity of diphenoxylate hcl by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • pramlintide

              pramlintide, atropine. Either increases effects of the other by pharmacodynamic synergism. Contraindicated. Synergistic inhibition of GI motility.

            • rasagiline

              rasagiline increases toxicity of diphenoxylate hcl by unknown mechanism. Avoid or Use Alternate Drug. Chemical structure of diphenoxylate is similar to meperidine, concurrent use may precipitate hypertensive crises.

            • revefenacin

              revefenacin and atropine both decrease cholinergic effects/transmission. Avoid or Use Alternate Drug. Coadministration may cause additive anticholinergic effects.

            • secretin

              atropine decreases effects of secretin by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Concomitant use of anticholinergic drugs may cause a hyporesponse to stimulation testing with secretin. Discontinue anticholinergic drugs at least 5 half-lives before administering secretin.

            • selegiline

              selegiline increases toxicity of diphenoxylate hcl by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

            • selegiline transdermal

              selegiline transdermal increases toxicity of diphenoxylate hcl by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death.

            • sodium oxybate

              diphenoxylate hcl, sodium oxybate. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Profound sedation, respiratory depression, coma, and death may result if coadministered. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.

            • tramadol

              tramadol, diphenoxylate hcl. Other (see comment). Avoid or Use Alternate Drug. Comment: Tramadol may reinitiate opiate dependence in pts. previously addicted to other opiates; it may also provoke withdrawal Sx. in pts. who are currently opiate dependent.

            • tranylcypromine

              tranylcypromine increases toxicity of diphenoxylate hcl by unknown mechanism. Avoid or Use Alternate Drug. Risk of hypotension, hyperpyrexia, somnolence, or death; separate by 14 d.

            • umeclidinium bromide/vilanterol inhaled

              atropine, umeclidinium bromide/vilanterol inhaled. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Concomitant use with other anticholinergic-containing drugs may lead to additive anticholinergic adverse effects.

            Monitor Closely (247)

            • abobotulinumtoxinA

              abobotulinumtoxinA increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects. .

            • aclidinium

              atropine and aclidinium both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • albuterol

              diphenoxylate hcl increases and albuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • alfentanil

              alfentanil and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • alprazolam

              alprazolam and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • amantadine

              atropine, amantadine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Potential for increased anticholinergic adverse effects.

            • amitriptyline

              atropine and amitriptyline both decrease cholinergic effects/transmission. Modify Therapy/Monitor Closely.

              diphenoxylate hcl and amitriptyline both increase sedation. Use Caution/Monitor.

            • amobarbital

              amobarbital and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • amoxapine

              atropine and amoxapine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • amoxapine

              diphenoxylate hcl and amoxapine both increase sedation. Use Caution/Monitor.

            • anticholinergic/sedative combos

              anticholinergic/sedative combos and atropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • apomorphine

              diphenoxylate hcl and apomorphine both increase sedation. Use Caution/Monitor.

            • arformoterol

              diphenoxylate hcl increases and arformoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • aripiprazole

              atropine decreases levels of aripiprazole by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              aripiprazole increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              atropine decreases levels of aripiprazole by pharmacodynamic antagonism. Use Caution/Monitor.

              diphenoxylate hcl and aripiprazole both increase sedation. Use Caution/Monitor.

            • armodafinil

              diphenoxylate hcl increases and armodafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • atracurium

              atracurium and atropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • azelastine

              azelastine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • baclofen

              baclofen and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • belladonna alkaloids

              atropine and belladonna alkaloids both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • belladonna and opium

              diphenoxylate hcl and belladonna and opium both increase sedation. Use Caution/Monitor.

              atropine and belladonna and opium both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • benperidol

              atropine decreases levels of benperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              benperidol increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              diphenoxylate hcl and benperidol both increase sedation. Use Caution/Monitor.

              atropine decreases levels of benperidol by pharmacodynamic antagonism. Use Caution/Monitor.

            • benzphetamine

              diphenoxylate hcl increases and benzphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • benztropine

              atropine and benztropine both decrease cholinergic effects/transmission. Use Caution/Monitor. Additive anticholinergic adverse effects may be seen with concurrent use.

            • bethanechol

              bethanechol increases and atropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • brexanolone

              brexanolone, diphenoxylate hcl. Either increases toxicity of the other by sedation. Use Caution/Monitor.

            • brompheniramine

              brompheniramine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • buprenorphine

              buprenorphine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • buprenorphine buccal

              buprenorphine buccal and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • buprenorphine, long-acting injection

              buprenorphine, long-acting injection increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Coadministration of buprenorphine with anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • butabarbital

              butabarbital and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • butalbital

              butalbital and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • butorphanol

              butorphanol and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • caffeine

              diphenoxylate hcl increases and caffeine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • carbachol

              carbachol increases and atropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • carbinoxamine

              carbinoxamine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • carisoprodol

              carisoprodol and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • cenobamate

              cenobamate, diphenoxylate hcl. Either increases effects of the other by sedation. Use Caution/Monitor.

            • cevimeline

              cevimeline increases and atropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • chloral hydrate

              chloral hydrate and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • chlordiazepoxide

              chlordiazepoxide and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • chlorpheniramine

              chlorpheniramine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • chlorpromazine

              diphenoxylate hcl and chlorpromazine both increase sedation. Use Caution/Monitor.

              chlorpromazine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              atropine decreases levels of chlorpromazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              atropine decreases levels of chlorpromazine by pharmacodynamic antagonism. Use Caution/Monitor.

            • chlorzoxazone

              chlorzoxazone and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • cisatracurium

              atropine and cisatracurium both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • cinnarizine

              cinnarizine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • clemastine

              clemastine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • clomipramine

              diphenoxylate hcl and clomipramine both increase sedation. Use Caution/Monitor.

              atropine and clomipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • clonazepam

              clonazepam and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • clozapine

              atropine decreases levels of clozapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              atropine decreases levels of clozapine by pharmacodynamic antagonism. Use Caution/Monitor.

              clozapine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • clorazepate

              clorazepate and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • clozapine

              diphenoxylate hcl and clozapine both increase sedation. Use Caution/Monitor.

            • codeine

              codeine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • cyclizine

              cyclizine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

              atropine and cyclizine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • cyclobenzaprine

              cyclobenzaprine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

              atropine and cyclobenzaprine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • cyproheptadine

              cyproheptadine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • darifenacin

              atropine and darifenacin both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • dantrolene

              dantrolene and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • desipramine

              diphenoxylate hcl and desipramine both increase sedation. Use Caution/Monitor.

            • dexchlorpheniramine

              dexchlorpheniramine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • dexfenfluramine

              diphenoxylate hcl increases and dexfenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dexmedetomidine

              dexmedetomidine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • dexmethylphenidate

              diphenoxylate hcl increases and dexmethylphenidate decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dextroamphetamine

              diphenoxylate hcl increases and dextroamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dextromoramide

              dextromoramide and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • diamorphine

              diamorphine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • diazepam

              diazepam and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • dicyclomine

              atropine and dicyclomine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • diethylpropion

              diphenoxylate hcl increases and diethylpropion decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • difenoxin hcl

              difenoxin hcl and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • digoxin

              atropine increases levels of digoxin by unknown mechanism. Use Caution/Monitor.

              diphenoxylate hcl will increase the level or effect of digoxin by unspecified interaction mechanism. Use Caution/Monitor. Measure serum digoxin concentrations before initiating concomitant drugs; continue monitoring and reduce digoxin dose as necessary

            • dimenhydrinate

              dimenhydrinate and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • diphenhydramine

              atropine and diphenhydramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • diphenhydramine

              diphenhydramine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • dipipanone

              diphenoxylate hcl and dipipanone both increase sedation. Use Caution/Monitor.

            • dobutamine

              diphenoxylate hcl increases and dobutamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • donepezil

              donepezil increases and atropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dopamine

              diphenoxylate hcl increases and dopamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dopexamine

              diphenoxylate hcl increases and dopexamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • dosulepin

              diphenoxylate hcl and dosulepin both increase sedation. Use Caution/Monitor.

              atropine and dosulepin both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • doxepin

              diphenoxylate hcl and doxepin both increase sedation. Use Caution/Monitor.

              atropine and doxepin both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • doxylamine

              doxylamine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • droperidol

              atropine decreases levels of droperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              atropine decreases levels of droperidol by pharmacodynamic antagonism. Use Caution/Monitor.

              droperidol increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • droperidol

              diphenoxylate hcl and droperidol both increase sedation. Use Caution/Monitor.

            • echothiophate iodide

              echothiophate iodide increases and atropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ephedrine

              diphenoxylate hcl increases and ephedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epinephrine

              diphenoxylate hcl increases and epinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • epinephrine racemic

              diphenoxylate hcl increases and epinephrine racemic decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • esketamine intranasal

              esketamine intranasal, diphenoxylate hcl. Either increases toxicity of the other by sedation. Modify Therapy/Monitor Closely.

            • estazolam

              estazolam and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • ethanol

              diphenoxylate hcl and ethanol both increase sedation. Use Caution/Monitor.

            • etomidate

              etomidate and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • fenfluramine

              diphenoxylate hcl increases and fenfluramine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • fentanyl

              fentanyl, atropine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • fentanyl intranasal

              fentanyl intranasal, atropine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • fentanyl transdermal

              fentanyl transdermal, atropine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • fentanyl transmucosal

              fentanyl transmucosal, atropine. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration of fentanyl with anticholinergics may increase risk for urinary retention and/or severe constipation, which may lead to paralytic ileus.

            • fesoterodine

              atropine and fesoterodine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • flavoxate

              atropine and flavoxate both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • fluphenazine

              atropine decreases levels of fluphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

              fluphenazine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              atropine decreases levels of fluphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              diphenoxylate hcl and fluphenazine both increase sedation. Use Caution/Monitor.

            • flurazepam

              flurazepam and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • galantamine

              galantamine increases and atropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • formoterol

              diphenoxylate hcl increases and formoterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • glycopyrrolate

              atropine and glycopyrrolate both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • glycopyrrolate inhaled

              atropine and glycopyrrolate inhaled both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • haloperidol

              atropine decreases levels of haloperidol by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              haloperidol increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              atropine decreases levels of haloperidol by pharmacodynamic antagonism. Use Caution/Monitor.

              diphenoxylate hcl and haloperidol both increase sedation. Use Caution/Monitor.

            • henbane

              atropine and henbane both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • hydromorphone

              diphenoxylate hcl and hydromorphone both increase sedation. Use Caution/Monitor.

            • homatropine

              atropine and homatropine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • huperzine A

              huperzine A increases and atropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • hydroxyzine

              hydroxyzine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • hyoscyamine

              atropine and hyoscyamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • hyoscyamine spray

              atropine and hyoscyamine spray both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • iloperidone

              atropine decreases levels of iloperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              iloperidone increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              diphenoxylate hcl and iloperidone both increase sedation. Use Caution/Monitor.

              atropine decreases levels of iloperidone by pharmacodynamic antagonism. Use Caution/Monitor.

            • imipramine

              atropine and imipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              diphenoxylate hcl and imipramine both increase sedation. Use Caution/Monitor.

            • incobotulinumtoxinA

              atropine, incobotulinumtoxinA. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.

            • isocarboxazid

              diphenoxylate hcl, isocarboxazid. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of serotonin syndrome.

            • ipratropium

              atropine and ipratropium both decrease cholinergic effects/transmission. Use Caution/Monitor. Due to the poor systemic absorption of ipratropium, interaction unlikely at regularly recommended dosages.

            • isoproterenol

              diphenoxylate hcl increases and isoproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ketamine

              ketamine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • ketotifen, ophthalmic

              diphenoxylate hcl and ketotifen, ophthalmic both increase sedation. Use Caution/Monitor.

            • lasmiditan

              lasmiditan, diphenoxylate hcl. Either increases effects of the other by sedation. Use Caution/Monitor. Coadministration of lasmiditan and other CNS depressant drugs, including alcohol have not been evaluated in clinical studies. Lasmiditan may cause sedation, as well as other cognitive and/or neuropsychiatric adverse reactions.

            • lemborexant

              lemborexant, diphenoxylate hcl. Either increases effects of the other by sedation. Modify Therapy/Monitor Closely. Dosage adjustment may be necessary if lemborexant is coadministered with other CNS depressants because of potentially additive effects.

            • levalbuterol

              diphenoxylate hcl increases and levalbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • levorphanol

              diphenoxylate hcl and levorphanol both increase sedation. Use Caution/Monitor.

            • linezolid

              diphenoxylate hcl, linezolid. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of serotonin syndrome.

            • lisdexamfetamine

              diphenoxylate hcl increases and lisdexamfetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • lofepramine

              atropine and lofepramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              diphenoxylate hcl and lofepramine both increase sedation. Use Caution/Monitor.

            • lofexidine

              diphenoxylate hcl and lofexidine both increase sedation. Use Caution/Monitor.

            • loxapine

              atropine decreases levels of loxapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              atropine decreases levels of loxapine by pharmacodynamic antagonism. Use Caution/Monitor.

              loxapine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • loprazolam

              loprazolam and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • lorazepam

              lorazepam and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • lormetazepam

              lormetazepam and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • loxapine

              diphenoxylate hcl and loxapine both increase sedation. Use Caution/Monitor.

            • loxapine inhaled

              loxapine inhaled increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              diphenoxylate hcl and loxapine inhaled both increase sedation. Use Caution/Monitor.

              atropine decreases levels of loxapine inhaled by pharmacodynamic antagonism. Use Caution/Monitor.

            • lurasidone

              lurasidone, diphenoxylate hcl. Either increases toxicity of the other by Other (see comment). Use Caution/Monitor. Comment: Potential for increased CNS depressant effects when used concurrently; monitor for increased adverse effects and toxicity.

            • maprotiline

              atropine and maprotiline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • maprotiline

              diphenoxylate hcl and maprotiline both increase sedation. Use Caution/Monitor.

            • marijuana

              diphenoxylate hcl and marijuana both increase sedation. Use Caution/Monitor.

            • meclizine

              atropine and meclizine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • melatonin

              diphenoxylate hcl and melatonin both increase sedation. Use Caution/Monitor.

            • meperidine

              diphenoxylate hcl and meperidine both increase sedation. Use Caution/Monitor.

            • meprobamate

              diphenoxylate hcl and meprobamate both increase sedation. Use Caution/Monitor.

            • metaproterenol

              diphenoxylate hcl increases and metaproterenol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • metaxalone

              metaxalone and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • methadone

              diphenoxylate hcl and methadone both increase sedation. Use Caution/Monitor.

            • methamphetamine

              diphenoxylate hcl increases and methamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • methocarbamol

              methocarbamol and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • methscopolamine

              atropine and methscopolamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • methylenedioxymethamphetamine

              diphenoxylate hcl increases and methylenedioxymethamphetamine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • metoclopramide intranasal

              atropine will decrease the level or effect of metoclopramide intranasal by Other (see comment). Use Caution/Monitor. Coadministration of metoclopramide intranasal with drugs that impair GI motility may decrease systemic absorption of metoclopramide. Monitor for reduced therapeutic effect.

            • midazolam

              midazolam and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • midazolam intranasal

              midazolam intranasal, diphenoxylate hcl. Either increases toxicity of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Concomitant use of barbiturates, alcohol, or other CNS depressants may increase risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect.

            • midodrine

              diphenoxylate hcl increases and midodrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • mirtazapine

              diphenoxylate hcl and mirtazapine both increase sedation. Use Caution/Monitor.

            • modafinil

              diphenoxylate hcl increases and modafinil decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • morphine

              diphenoxylate hcl and morphine both increase sedation. Use Caution/Monitor.

            • motherwort

              diphenoxylate hcl and motherwort both increase sedation. Use Caution/Monitor.

            • moxonidine

              diphenoxylate hcl and moxonidine both increase sedation. Use Caution/Monitor.

            • nabilone

              diphenoxylate hcl and nabilone both increase sedation. Use Caution/Monitor.

            • nalbuphine

              diphenoxylate hcl and nalbuphine both increase sedation. Use Caution/Monitor.

            • neostigmine

              neostigmine increases and atropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • norepinephrine

              diphenoxylate hcl increases and norepinephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • nortriptyline

              diphenoxylate hcl and nortriptyline both increase sedation. Use Caution/Monitor.

              atropine and nortriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • olanzapine

              diphenoxylate hcl and olanzapine both increase sedation. Use Caution/Monitor.

              atropine decreases levels of olanzapine by pharmacodynamic antagonism. Use Caution/Monitor.

              atropine decreases levels of olanzapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              olanzapine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • oliceridine

              atropine increases toxicity of oliceridine by Other (see comment). Use Caution/Monitor. Comment: Anticholinergic drugs may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus. Monitor for signs of urinary retention or reduced gastric motility if oliceridine is coadministered with anticholinergics.

            • opium tincture

              diphenoxylate hcl and opium tincture both increase sedation. Use Caution/Monitor.

            • onabotulinumtoxinA

              atropine and onabotulinumtoxinA both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • orphenadrine

              atropine and orphenadrine both decrease cholinergic effects/transmission. Use Caution/Monitor.

              orphenadrine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • oxazepam

              oxazepam and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • oxybutynin

              atropine and oxybutynin both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • oxybutynin topical

              atropine and oxybutynin topical both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • oxybutynin transdermal

              atropine and oxybutynin transdermal both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • oxycodone

              diphenoxylate hcl and oxycodone both increase sedation. Use Caution/Monitor.

            • oxymorphone

              diphenoxylate hcl and oxymorphone both increase sedation. Use Caution/Monitor.

            • paliperidone

              atropine decreases levels of paliperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              atropine decreases levels of paliperidone by pharmacodynamic antagonism. Use Caution/Monitor.

              diphenoxylate hcl and paliperidone both increase sedation. Use Caution/Monitor.

              paliperidone increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • pancuronium

              atropine and pancuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • papaveretum

              diphenoxylate hcl and papaveretum both increase sedation. Use Caution/Monitor.

            • papaverine

              diphenoxylate hcl and papaverine both increase sedation. Use Caution/Monitor.

            • pegvisomant

              diphenoxylate hcl decreases effects of pegvisomant by unknown mechanism. Use Caution/Monitor.

            • pentazocine

              diphenoxylate hcl and pentazocine both increase sedation. Use Caution/Monitor.

            • pentobarbital

              pentobarbital and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • perphenazine

              atropine decreases levels of perphenazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              perphenazine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              atropine decreases levels of perphenazine by pharmacodynamic antagonism. Use Caution/Monitor.

              diphenoxylate hcl and perphenazine both increase sedation. Use Caution/Monitor.

            • phendimetrazine

              diphenoxylate hcl increases and phendimetrazine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • physostigmine

              physostigmine increases and atropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenelzine

              diphenoxylate hcl, phenelzine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of serotonin syndrome.

            • phenobarbital

              phenobarbital and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • phentermine

              diphenoxylate hcl increases and phentermine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenylephrine

              diphenoxylate hcl increases and phenylephrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • phenylephrine PO

              diphenoxylate hcl increases and phenylephrine PO decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor. .

            • pholcodine

              diphenoxylate hcl and pholcodine both increase sedation. Use Caution/Monitor.

            • pilocarpine

              pilocarpine increases and atropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pilocarpine ophthalmic

              pilocarpine ophthalmic increases and atropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • pimozide

              atropine decreases levels of pimozide by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              pimozide increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              diphenoxylate hcl and pimozide both increase sedation. Use Caution/Monitor.

              atropine decreases levels of pimozide by pharmacodynamic antagonism. Use Caution/Monitor.

            • pirbuterol

              diphenoxylate hcl increases and pirbuterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • prabotulinumtoxinA

              atropine, prabotulinumtoxinA. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Use of anticholinergic drugs after administration of botulinum toxin-containing products may potentiate systemic anticholinergic effects.

            • pralidoxime

              atropine and pralidoxime both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • primidone

              primidone and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • prochlorperazine

              diphenoxylate hcl and prochlorperazine both increase sedation. Use Caution/Monitor.

              atropine decreases levels of prochlorperazine by pharmacodynamic antagonism. Use Caution/Monitor.

              prochlorperazine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              atropine decreases levels of prochlorperazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • promethazine

              atropine decreases levels of promethazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              promethazine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              promethazine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

              atropine decreases levels of promethazine by pharmacodynamic antagonism. Use Caution/Monitor.

            • propantheline

              atropine and propantheline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • propofol

              propofol and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • propylhexedrine

              diphenoxylate hcl increases and propylhexedrine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • protriptyline

              diphenoxylate hcl and protriptyline both increase sedation. Use Caution/Monitor.

              atropine and protriptyline both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • pyridostigmine

              pyridostigmine increases and atropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • quazepam

              quazepam and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • quetiapine

              diphenoxylate hcl and quetiapine both increase sedation. Use Caution/Monitor.

              atropine decreases levels of quetiapine by pharmacodynamic antagonism. Use Caution/Monitor.

              atropine decreases levels of quetiapine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              quetiapine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • ramelteon

              diphenoxylate hcl and ramelteon both increase sedation. Use Caution/Monitor.

            • rapacuronium

              atropine and rapacuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • rimabotulinumtoxinB

              atropine, rimabotulinumtoxinB. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Anticholinergics may enhance botulinum toxin effects. Closely monitor for increased neuromuscular blockade.

            • risperidone

              diphenoxylate hcl and risperidone both increase sedation. Use Caution/Monitor.

              atropine decreases levels of risperidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              atropine decreases levels of risperidone by pharmacodynamic antagonism. Use Caution/Monitor.

              risperidone increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • rocuronium

              atropine and rocuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • salmeterol

              diphenoxylate hcl increases and salmeterol decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • scopolamine

              atropine and scopolamine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • scullcap

              diphenoxylate hcl and scullcap both increase sedation. Use Caution/Monitor.

            • secobarbital

              secobarbital and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • sevoflurane

              sevoflurane and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • shepherd's purse

              diphenoxylate hcl and shepherd's purse both increase sedation. Use Caution/Monitor.

            • solifenacin

              atropine and solifenacin both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • stiripentol

              stiripentol, diphenoxylate hcl. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence.

            • succinylcholine

              succinylcholine increases and atropine decreases cholinergic effects/transmission. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • sufentanil

              diphenoxylate hcl and sufentanil both increase sedation. Use Caution/Monitor.

            • tapentadol

              diphenoxylate hcl and tapentadol both increase sedation. Use Caution/Monitor.

            • temazepam

              temazepam and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • terbutaline

              diphenoxylate hcl increases and terbutaline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • thioridazine

              thioridazine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              diphenoxylate hcl and thioridazine both increase sedation. Use Caution/Monitor.

              atropine decreases levels of thioridazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              atropine decreases levels of thioridazine by pharmacodynamic antagonism. Use Caution/Monitor.

            • thiothixene

              diphenoxylate hcl and thiothixene both increase sedation. Use Caution/Monitor.

              atropine decreases levels of thiothixene by pharmacodynamic antagonism. Use Caution/Monitor.

              thiothixene increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              atropine decreases levels of thiothixene by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            • tiotropium

              atropine and tiotropium both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • topiramate

              diphenoxylate hcl and topiramate both increase sedation. Modify Therapy/Monitor Closely.

            • tolterodine

              atropine and tolterodine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • tramadol

              diphenoxylate hcl and tramadol both increase sedation. Use Caution/Monitor.

            • tranylcypromine

              diphenoxylate hcl, tranylcypromine. Mechanism: pharmacodynamic synergism. Use Caution/Monitor. Risk of serotonin syndrome.

            • trazodone

              diphenoxylate hcl and trazodone both increase sedation. Use Caution/Monitor.

            • triazolam

              triazolam and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • triclofos

              triclofos and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • trifluoperazine

              diphenoxylate hcl and trifluoperazine both increase sedation. Use Caution/Monitor.

              atropine decreases levels of trifluoperazine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              trifluoperazine increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

              atropine decreases levels of trifluoperazine by pharmacodynamic antagonism. Use Caution/Monitor.

            • trihexyphenidyl

              atropine and trihexyphenidyl both decrease cholinergic effects/transmission. Use Caution/Monitor. Potential for additive anticholinergic effects.

            • trimipramine

              diphenoxylate hcl and trimipramine both increase sedation. Use Caution/Monitor.

            • trimipramine

              atropine and trimipramine both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • triprolidine

              triprolidine and diphenoxylate hcl both increase sedation. Use Caution/Monitor.

            • trospium chloride

              atropine and trospium chloride both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • umeclidinium bromide

              umeclidinium bromide and atropine both decrease cholinergic effects/transmission. Use Caution/Monitor. If possible, avoid coadministration of additional anticholinergic agents

            • vecuronium

              atropine and vecuronium both decrease cholinergic effects/transmission. Use Caution/Monitor.

            • xylometazoline

              diphenoxylate hcl increases and xylometazoline decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • yohimbine

              diphenoxylate hcl increases and yohimbine decreases sedation. Effect of interaction is not clear, use caution. Use Caution/Monitor.

            • ziconotide

              diphenoxylate hcl and ziconotide both increase sedation. Use Caution/Monitor.

            • ziprasidone

              diphenoxylate hcl and ziprasidone both increase sedation. Use Caution/Monitor.

              atropine decreases levels of ziprasidone by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

              atropine decreases levels of ziprasidone by pharmacodynamic antagonism. Use Caution/Monitor.

              ziprasidone increases effects of atropine by pharmacodynamic synergism. Use Caution/Monitor. Additive anticholinergic effects, possible hypoglycemia.

            • zotepine

              atropine decreases levels of zotepine by pharmacodynamic antagonism. Use Caution/Monitor.

              diphenoxylate hcl and zotepine both increase sedation. Use Caution/Monitor.

              atropine decreases levels of zotepine by inhibition of GI absorption. Applies only to oral form of both agents. Use Caution/Monitor.

            Minor (31)

            • amitriptyline

              amitriptyline increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

            • amoxapine

              amoxapine increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

            • atenolol

              atropine increases levels of atenolol by unknown mechanism. Minor/Significance Unknown.

            • brimonidine

              brimonidine increases effects of diphenoxylate hcl by pharmacodynamic synergism. Minor/Significance Unknown. Increased CNS depression.

            • chlorpromazine

              chlorpromazine increases toxicity of atropine by unknown mechanism. Minor/Significance Unknown.

            • clomipramine

              clomipramine increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

            • desipramine

              atropine and desipramine both decrease cholinergic effects/transmission. Minor/Significance Unknown.

              desipramine increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

            • dextroamphetamine

              dextroamphetamine increases effects of diphenoxylate hcl by unspecified interaction mechanism. Minor/Significance Unknown.

            • dimenhydrinate

              dimenhydrinate increases toxicity of atropine by pharmacodynamic synergism. Minor/Significance Unknown. Additive anticholinergic effects.

            • donepezil

              donepezil decreases effects of atropine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • doxepin

              doxepin increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

            • eucalyptus

              diphenoxylate hcl and eucalyptus both increase sedation. Minor/Significance Unknown.

            • fluphenazine

              fluphenazine increases toxicity of atropine by unknown mechanism. Minor/Significance Unknown.

            • galantamine

              galantamine decreases effects of atropine by pharmacodynamic antagonism. Minor/Significance Unknown.

            • imipramine

              imipramine increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

            • levodopa

              atropine, levodopa. Other (see comment). Minor/Significance Unknown. Comment: Anticholinergic agents may enhance the therapeutic effects of levodopa; however, anticholinergic agents can exacerbate tardive dyskinesia. In high dosage, anticholinergics may decrease the effects of levodopa by delaying its GI absorption. .

            • lidocaine

              lidocaine increases toxicity of diphenoxylate hcl by pharmacodynamic synergism. Minor/Significance Unknown. Risk of increased CNS depression.

            • lofepramine

              lofepramine increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

            • maprotiline

              maprotiline increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

            • nortriptyline

              nortriptyline increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

            • perphenazine

              perphenazine increases toxicity of atropine by unknown mechanism. Minor/Significance Unknown.

            • prochlorperazine

              prochlorperazine increases toxicity of atropine by unknown mechanism. Minor/Significance Unknown.

            • promazine

              promazine increases toxicity of atropine by unknown mechanism. Minor/Significance Unknown.

            • promethazine

              promethazine increases toxicity of atropine by unknown mechanism. Minor/Significance Unknown.

            • protriptyline

              protriptyline increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

            • sage

              diphenoxylate hcl and sage both increase sedation. Minor/Significance Unknown.

            • thioridazine

              thioridazine increases toxicity of atropine by unknown mechanism. Minor/Significance Unknown.

            • trazodone

              atropine and trazodone both decrease cholinergic effects/transmission. Minor/Significance Unknown.

              trazodone increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

            • trifluoperazine

              trifluoperazine increases toxicity of atropine by unknown mechanism. Minor/Significance Unknown.

            • trimipramine

              trimipramine increases levels of atropine by unknown mechanism. Minor/Significance Unknown.

            • ziconotide

              ziconotide, diphenoxylate hcl. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Additive decreased GI motility. Additive analgesia. Ziconotide does NOT potentiate opioid induced respiratory depression.

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            Adverse Effects

            1-10%

            Anticholinergic effects

            Blurred vision

            Sedation

            Nausea

            Vomiting

            Abdominal discomfort

            Dryness of skin or mouth

            Frequency Not Defined

            Pancreatitis

            Toxic megacolon

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            Warnings

            Contraindications

            Hypersensitivity to diphenoxylate or atropine

            Children aged <6 years owing to risks of respiratory and CNS depression (tablets only)

            Obstructive jaundice

            Diarrhea associated with pseudomembranous enterocolitis or infectious enterotoxin-producing bacteria

            Cautions

            Cases of severe respiratory depression and coma, leading to permanent brain damage or death reported in children aged <6 years administered tablets (see Contraindications)

            May cause CNS depression; may impair physical or mental abilities; patients should use caution when performing tasks requiring mental alertness, including operating heavy machinery or driving

            Use should be accompanied by appropriate fluid and electrolyte therapy, when indicated; if severe dehydration or electrolyte imbalance present, drug should be withheld until appropriate corrective therapy initiated; drug-induced inhibition of peristalsis may result in fluid retention in intestine, which may further aggravate dehydration and electrolyte imbalance

            Use with extreme caution in patients with advanced hepatorenal disease and in all patients with abnormal liver function; hepatic coma may be precipitated

            Therapy may slow GI motility and may enhance bacterial overgrowth and the release of bacterial endotoxins, which have been reported to result in serious GI complications, including sepsis and prolonged and/or worsening diarrhea

            In patients with acute ulcerative colitis, agents that inhibit intestinal motility or prolong intestinal transit time reported to induce toxic megacolon; patients with acute ulcerative colitis should be carefully observed and therapy discontinued promptly if abdominal distention occurs or if other untoward symptoms develop

            Improvement of symptoms expected within 48 hours; if no improvement within this time, drug is unlikely to be effective

            Do not exceed recommended dosage; reduce initial dosage for maintenance

            Give consideration to development of adverse reactions associated with use of atropine; therapy has caused atropinism (hyperthermia, tachycardia, urinary retention, flushing, dryness of the skin and mucous membranes) particularly in pediatric patients with Down’s syndrome; therapy is not indicated for use in pediatric patients; monitor patients for signs of atropinism

            Diphenoxylate hydrochloride may potentiate action of other drugs that cause dizziness or drowsiness, including barbiturates, benzodiazepines and other sedatives/hypnotics, anxiolytics, and tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, and alcohol; patient should be closely observed when any of these are used concomitantly

            Renal impairment

            Hepatic impairment

            Coadministration with opioids increases risk of anticholinergic and opioid toxicities; initial presenting symptoms may be delayed by up to 30 hr due to prolonged gastric emptying time induced by diphenoxylate

            Therapy contraindicated in patients with diarrhea associated with organisms that penetrate the GI mucosa; antiperistaltic agents, slow gastrointestinal motility and may enhance bacterial overgrowth and release of bacterial exotoxins; drug has been reported to result in serious GI complications in patients with infectious diarrhea, including sepsis, prolonged and/or worsened diarrhea; prolonged fever and the delay in resolution of stool pathogens reported in study of Shigellosis in adults

            Since chemical structure of diphenoxylate hydrochloride is similar to that of meperidine hydrochloride, concurrent use with monoamine oxidase (MAO) inhibitors may, in theory, precipitate hypertensive crisis

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            Pregnancy & Lactation

            Pregnancy

            There are no adequate and well-controlled studies in pregnant women; drug should be used during pregnancy only if anticipated benefit justifies potential risk to fetus; diphenoxylate hydrochloride shown to have effect on fertility in rats when given in doses 50 times human dose; a decrease in maternal weight gain of 30% at 20 mg/kg/day and of 10% at 4 mg/kg/day; at 10 times human dose (4 mg/kg/day), average litter size was slightly reduced

            Lactation

            Exercise caution when drug is administered to nursing woman, since physicochemical characteristics of major metabolite, diphenoxylic acid, are such that it may be excreted in breast milk and since it is known that atropine is excreted in breast milk

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Diphenoxylate: Acts on smooth muscle of intestinal tract, inhibiting GI motility and excessive GI propulsion (like morphine)

            Atropine: Subtherapeutic quantity of atropine is added to discourage deliberate overdose of diphenoxylate

            Absorption

            Onset: 45 min-1 hr

            Duration: 3-4 hr

            Peak plasma time: 2 hr

            Bioavailability: 90%

            Distribution

            Vd: 324.2 L

            Metabolism

            Extensively metabolized in liver to active metabolite, diphenoxylic acid (difenoxin), which is 5 times more potent than diphenoxylate

            Metabolites: Diphenoxylic acid (active), hydroxydiphenoxylic acid (inactive)

            Elimination

            Half-life: 2.5 hr (diphenoxylate); 3-14 hr (diphenoxylic acid)

            Renal clearance: 1483 mL/min

            Excretion: Feces via bile (49%), urine (14%)

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            Images

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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.