PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Antipropulsives

    DEA CLASS

    Rx, schedule V

    DESCRIPTION

    Oral antidiarrheal agent containing diphenoxylate (structurally related to meperidine) and atropine (added in subtherapeutic quantities to discourage abuse or overdosage); schedule C-V controlled substance.

    COMMON BRAND NAMES

    Lomotil, Lonox, Vi-Atro

    HOW SUPPLIED

    Diphenoxylate Hydrochloride, Atropine Sulfate/Diphenoxylate, Atropine/Lomotil Oral Sol: 5mL, 2.5-0.025mg
    Diphenoxylate Hydrochloride, Atropine Sulfate/Diphenoxylate, Atropine/Lomotil/Lonox/Vi-Atro Oral Tab: 2.5-0.025mg

    DOSAGE & INDICATIONS

    For adjunctive therapy in the management of diarrhea including AIDS-associated diarrhea† with no identifiable infectious agent.
    NOTE: Reduce dose or discontinue use as soon as symptoms are relieved; if chronic treatment is needed, the maintenance dose may be as low as 25% of the initial dose. Improvement is usually noted within 48 hours and should not be continued for more than 10 days.
    Oral dosage (tablets)
    Adults and Adolescents

    Initially, 5 mg (2 tablets) PO 3 to 4 times per day, reduce to 2.5 mg PO 2 to 3 times per day, if needed; discontinue as soon as possible. Do not exceed 20 mg/day PO.

    Oral dosage (oral solution)
    Adults and Adolescents

    Initially, 5 mg (10 mL) PO 3 to 4 times per day, reduce to 2.5 mg PO 2 to 3 times per day, if needed; discontinue as soon as possible. Do not exceed 20 mg/day PO.

    Children 9 to 12 years (23 to 55 kg)

    Initially, 0.3 to 0.4 mg/kg/day PO in divided doses, roughly 1.75 to 2.5 mg (3.5 to 5 mL) PO 4 times daily; reduce dose or discontinue use as soon as possible.

    Children 6 to 8 years (17 to 32 kg)

    Initially, 0.3 to 0.4 mg/kg/day PO in divided doses, roughly 1.25 to 2.5 mg (2.5 to 5 mL) PO 4 times daily; reduce dose or discontinue use as soon as possible.

    Children 5 years (16 to 23 kg)

    Initially, 0.3 to 0.4 mg/kg/day PO in divided doses, roughly 1.25 to 2.25 mg (2.5 to 4.5 mL) PO 4 times daily; reduce dose or discontinue use as soon as possible.

    Children 4 years (14 to 20 kg)

    Initially, 0.3 to 0.4 mg/kg/day PO in divided doses, roughly 1 to 2 mg (2 to 4 mL) PO 4 times daily; reduce dose or discontinue use as soon as possible.

    Children 3 years (12 to 16 kg)

    Initially, 0.3 to 0.4 mg/kg/day PO in divided doses, roughly 1 to 1.5 mg (2 to 3 mL) PO 4 times daily; reduce dose or discontinue use as soon as possible.

    Children 2 years (11 to 14 kg)

    Initially, 0.3 to 0.4 mg/kg/day PO in divided doses, roughly 0.75 to 1.5 mg (1.5 to 3 mL) PO 4 times daily; reduce dose or discontinue use as soon as possible.

    MAXIMUM DOSAGE

    Adults

    20 mg/day PO.

    Elderly

    20 mg/day PO.

    Adolescents

    20 mg/day PO.

    Children

    2—12 years: 0.4 mg/kg/day PO.
    < 2 years: Not recommended.

    Infants

    Do not use.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Dose with caution; hepatic coma may be precipitated. Contraindicated for use if obstructive jaundice is present.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    ADMINISTRATION

     
    NOTE: For acute symptoms, if clinical improvement is not apparent within 48 hours, atropine; diphenoxylate is not likely to be effective. For chronic symptoms, if clinical improvement is not apparent within 10 days at a maximum daily dose of 20 mg, atropine; diphenoxylate is not likely to be effective.

    Oral Administration

    Dosage is expressed in terms of diphenoxylate. One tablet or 5 ml of oral solution each contain 2.5 mg of diphenoxylate and 0.025 mg of atropine.

    STORAGE

    Lomotil:
    - Store below 77 degrees F
    Lonox :
    - Store below 77 degrees F
    Vi-Atro:
    - Store below 77 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Atropine; diphenoxylate is contraindicated in patients with known hypersensitivity to diphenoxylate or atropine; allergic-type reactions have been reported. Although diphenoxylate has a chemical structure similar to that of meperidine hydrochloride, cross-hypersensitivity between meperidine and diphenoxylate has not been reported in the literature, and recommendations for using diphenoxylate in patients with a history of meperidine hypersensitivity, and vice versa, are not available. It should be noted that true opiate agonist hypersensitivity is rare. Meperidine is a member of the phenylpiperidine subclass; other opiate agonists that are also included in the phenylpiperidine subclass are sufentanil and fentanyl.
     
    Subtherapeutic doses of atropine, found in atropine; diphenoxylate, are not likely to cause prominent anticholinergic adverse effects; however, atropine; diphenoxylate should be avoided in patients in whom anticholinergic medications are contraindicated. The warnings and precautions for use of anticholinergic agents should be observed.

    Dehydration, electrolyte imbalance

    Atropine; diphenoxylate should not be administered to patients experiencing dehydration or electrolyte imbalance. Diphenoxylate and atropine may lead to retention of fluid in the intestine, due to inhibition of peristalsis. This may further aggravate dehydration and electrolyte imbalance. Rehydration should be undertaken before therapy is initiated and appropriate administration of fluid and electrolytes should accompany the use of atropine; diphenoxylate.

    Pregnancy

    Atropine; diphenoxylate is classified as FDA pregnancy risk category C. Adequate studies in pregnant women have not been conducted; therefore, atropine; diphenoxylate should be used during pregnancy only when clearly needed.

    Breast-feeding

    According to the manufacturer, caution should be exercised when administering atropine; diphenoxylate to a nursing woman. The active metabolite of diphenoxylate, diphenoxylic acid, and atropine are excreted into breast milk. Incompatibilities with breast-feeding have not been reported. An alternate, such as loperamide, which is considered usually compatible with breast-feeding by the American Academy of Pediatrics, may be considered. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Substance abuse

    Although symptoms of dependence have not been reported in patients receiving therapeutic dosages of diphenoxylate, opiate withdrawal can follow the cessation of higher dosage regimens. Atropine; diphenoxylate should be prescribed cautiously to patients with a history of opiate substance abuse.

    Hepatic disease, jaundice

    Atropine; diphenoxylate is contraindicated for use by patients with obstructive jaundice and should be administered with extreme caution to patients with hepatic disease (e.g., cirrhosis), hepatorenal syndrome, or abnormal liver function tests because of the risk of developing hepatic coma. Reduced dosages of atropine; diphenoxylate have been recommended.

    Ulcerative colitis

    Atropine; diphenoxylate and other drugs that inhibit intestinal motility or prolong transit time can induce toxic megacolon in patients with acute ulcerative colitis. Patients with ulcerative colitis should be monitored closely and atropine; diphenoxylate therapy discontinued if signs of toxicity (e.g., abdominal distension) occur.

    Gastroenteritis, infection

    Atropine; diphenoxylate should not be used in cases of diarrhea caused by poisoning or infection with enterotoxin-producing bacteria (bacterial gastroenteritis) because expulsion of the toxic intestinal contents may be a necessary protective mechanism.

    Pseudomembranous colitis

    Atropine; diphenoxylate is contraindicated in cases of diarrhea caused by pseudomembranous colitis.

    Children, Down's syndrome, infants, neonates

    Atropine; diphenoxylate should not be administered to neonates, infants, or children under 2 years of age or to patients with Down's syndrome; there is an increased risk of toxicity in these populations. Signs of atropinism (e.g., dryness of the skin and mucous membranes, increased pupillary dilatation, and tachycardia) may become evident in children, even at recommended doses. Also, young children may be predisposed to delayed diphenoxylate toxicity and have greater response variability.

    MAOI therapy

    The concomitant administration of atropine; diphenoxylate and MAOI therapy may increase the risk of hypertensive crisis. Avoid concurrent use (see Drug Interactions).

    Geriatric

    Use atropine; diphenoxylate with caution in geriatric patients. Dependence, sedation, and cognitive impairment are potential concerns with chronic administration of diphenoxylate in the elderly. Geriatric patients may have an increased susceptibility to the respiratory depressant effects of diphenoxylate or the anticholinergic effects of atropine. According to the Beers Criteria, anti-spasmodics such as atropine are considered potentially inappropriate medications (PIMs) in geriatric patients and should be avoided due to high anticholinergic activity and uncertain effectiveness. The Beers expert panel also recommends avoiding drugs with strong anticholinergic properties in geriatric patients with the following disease states or symptoms due to the potential for exacerbation of the condition or increased risk of adverse effects: dementia/cognitive impairment (adverse CNS effects), delirium/high risk of delirium (possible new-onset or worsening delirium), or lower urinary tract symptoms/benign prostatic hyperplasia in men (possible urinary retention or hesitancy).

    ADVERSE REACTIONS

    Severe

    ileus / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    toxic megacolon / Delayed / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known

    Moderate

    euphoria / Early / Incidence not known
    depression / Delayed / Incidence not known
    constipation / Delayed / Incidence not known
    respiratory depression / Rapid / Incidence not known

    Mild

    nausea / Early / 3.0-7.0
    vomiting / Early / 3.0-7.0
    dizziness / Early / 5.0-5.0
    drowsiness / Early / 4.0-4.0
    xerostomia / Early / 3.0-3.0
    headache / Early / 2.5-2.5
    restlessness / Early / Incidence not known
    malaise / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    abdominal pain / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known

    DRUG INTERACTIONS

    Abatacept: Because abatacept has been shown to potentiate the onset of respiratory infections, concomitant use of drugs that decrease mucociliary clearance should be used cautiously. Anticholinergics, such as atropine, have been shown to be capable of depressing the mucociliary transport system.
    Acetaminophen; Butalbital: Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Acetaminophen; Butalbital; Caffeine: Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Acetaminophen; Butalbital; Caffeine; Codeine: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Acetaminophen; Caffeine; Dihydrocodeine: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Codeine: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Acetaminophen; Dextromethorphan; Doxylamine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Acetaminophen; Dextromethorphan; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
    Acetaminophen; Diphenhydramine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Acetaminophen; Guaifenesin; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Acetaminophen; Hydrocodone: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Acetaminophen; Oxycodone: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Acetaminophen; Pentazocine: Pentazocine may partially block the analgesic, respiratory depressant and CNS depressant effects of pure opiate agonists. Due to their antagonistic properties, pentazocine may cause withdrawal symptoms in patients receiving chronic opiate agonists. Pentazocine may also be used concurrently with some opiate agonists and cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of pure opiate agonist used; antagonistic effects are more common at low to moderate doses of the pure opiate agonist. For example, some patients who received methadone for the daily treatment of narcotic dependence have experienced withdrawal symptoms after receiving pentazocine. Withdrawal symptoms may include anxiety, agitation, mood changes, hallucinations, dysphoria, weakness, and diarrhea. Use pentazocine with caution in any patient receiving anticholinergic agents. Coadministration of pentazocine with antimuscarinics may result in additive anticholinergic effects, such as urinary retention and constipation.
    Acetaminophen; Propoxyphene: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events.
    Acetaminophen; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
    Aclidinium: Although aclidinium is minimally absorbed into the systemic circulation after inhalation, there is the potential for aclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics.Per the manufaturer, avoid concomitant administration of aclidinium with other anticholinergic medications, when possible.
    Acrivastine; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Albuterol; Ipratropium: Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for tiotropium to have additive anticholinergic effects when administered with other antimuscarinics. Per the manufaturer, avoid concomitant administration of ipratropium with other anticholinergic medications, such as antimucarinics.
    Aldesleukin, IL-2: Concurrent administration of diphenoxylate/difenoxin with aldesleukin can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use with caution. Patients developing mood disturbances, moderate to severe lethargy/somnolence while on aldesleukin should seek evaluation from their health care provider.
    Alfentanil: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Alosetron: Patients taking medications that decrease GI motility may be at greater risk for serious complications from alosetron, like constipation, via a pharmacodynamic interaction. Constipation is the most frequently reported adverse effect with alosetron. Alosetron, if used with drugs such as antidiarrheals, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus. Alosetron, if combined with antimuscarinics, may seriously worsen constipation, leading to events such as GI obstruction, impaction or paralytic ileus. Although specific recommendations are not available from the manufacturer, it would be prudent to avoid antimuscarinics in patients taking alosetron.
    Aluminum Hydroxide: Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Aluminum Hydroxide; Magnesium Carbonate: Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Aluminum Hydroxide; Magnesium Hydroxide: Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction. Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction. Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Aluminum Hydroxide; Magnesium Trisilicate: Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Amantadine: Amantadine may exhibit anticholinergic activity. Antimuscarinics, such as atropine, may potentiate the anticholinergic effects of amantadine, and may increase the risk of antimuscarinic-related side effects. Concomitant administration of amantadine and diphenoxylate/difenoxin may cause an additive decrease in GI motility and should be used cautiously.
    Ambenonium Chloride: Routine administration of atropine with ambenonium chloride is contraindicated. Belladonna derivatives, such as atropine, may suppress the parasympathomimetic symptoms of excessive gastrointestinal stimulation. This leaves only the more serious symptoms (fasciculation and paralysis of voluntary muscles) as signs of overdosage.
    Amitriptyline: Concurrent administration of can potentiate the CNS and respiratory depressant effects of diphenoxylate/difenoxin and the CNS deoressant effects of the tricyclic antidepressant (TCA). Both TCAs and diphenoxylate/difenoxin may cause constipation. Use caution during coadministration. Cases of severe GI reactions including toxic megacolon and adynamic ileus have been rarely reported. In some cases, a dosage reduction of diphenoxylate or difenoxin might be needed to manage any noted side effects.
    Amitriptyline; Chlordiazepoxide: Concurrent administration of can potentiate the CNS and respiratory depressant effects of diphenoxylate/difenoxin and the CNS deoressant effects of the tricyclic antidepressant (TCA). Both TCAs and diphenoxylate/difenoxin may cause constipation. Use caution during coadministration. Cases of severe GI reactions including toxic megacolon and adynamic ileus have been rarely reported. In some cases, a dosage reduction of diphenoxylate or difenoxin might be needed to manage any noted side effects.
    Amobarbital: Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Amoxapine: Depending on the specific agent, additive anticholinergic effects may be seen when amoxapine is used concomitantly with other anticholinergic agents. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive CNS effects are also possible when these drugs are combined with amoxapine. Diphenoxylate/difenoxin decreases GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Amoxapine also decreases GI motility and may produce additive effects with diphenoxylate/difenoxin if used concomitantly.
    Antacids: Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Anxiolytics; Sedatives; and Hypnotics: Concurrent administration of diphenoxylate/difenoxin with anxiolytics, sedatives, and hypnotics can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Apraclonidine: Concurrent administration of diphenoxylate/difenoxin with apraclonidine can theoretically potentiate the CNS-depressant effects of diphenoxylate/difenoxin.
    Aripiprazole: Concurrent administration of diphenoxylate/difenoxin with aripiprazole can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Asenapine: Drugs that can cause CNS depression, if used concomitantly with asenapine, may increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness. Caution should be used when asenapine is given in combination with other centrally-acting medications including opiate agonists.
    Aspirin, ASA; Butalbital; Caffeine: Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Aspirin, ASA; Caffeine; Dihydrocodeine: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events.
    Aspirin, ASA; Carisoprodol: Concurrent administration of diphenoxylate/difenoxin with carisoprodol can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Aspirin, ASA; Carisoprodol; Codeine: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Concurrent administration of diphenoxylate/difenoxin with carisoprodol can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Aspirin, ASA; Oxycodone: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Atomoxetine: Atropine and atomoxetine should be combined cautiously in patients with known cardiac disease. Atropine or scopolamine may alter the heart rate; the predominant clinical effect is sinus tachycardia. An additive effect on heart rate may occur as atomoxetine may elevate heart rate as well as blood pressure.
    Atracurium: Concurrent administration of diphenoxylate/difenoxin with neuromuscular blockers can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Atropine: Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. Atropine is commonly added in small amounts to these formulas for diarrhea as a deterrant to diphenoxylate abuse. However, therapeutic doses of systemic atropine may cause additive side effects. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. Atropine is commonly added in small amounts to these formulas for diarrhea as a deterrant to diphenoxylate abuse. However, therapeutic doses of systemic atropine may cause additive side effects. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive. Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as hyoscyamine. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Atropine; Difenoxin: Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. Atropine is commonly added in small amounts to these formulas for diarrhea as a deterrant to diphenoxylate abuse. However, therapeutic doses of systemic atropine may cause additive side effects. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Atropine; Edrophonium: Coadministration of Atropine and Edrophonium Chloride can produce mutually antagonistic effects. Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. Atropine is commonly added in small amounts to these formulas for diarrhea as a deterrant to diphenoxylate abuse. However, therapeutic doses of systemic atropine may cause additive side effects. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. Atropine is commonly added in small amounts to these formulas for diarrhea as a deterrant to diphenoxylate abuse. However, therapeutic doses of systemic atropine may cause additive side effects. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive. Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as hyoscyamine. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Azelastine: An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including opiate agonists. A dose reduction of one or both drugs may be warranted.
    Azelastine; Fluticasone: An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including opiate agonists. A dose reduction of one or both drugs may be warranted.
    Baclofen: Concurrent administration of diphenoxylate/difenoxin with baclofen can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Barbiturates: Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as the belladonna alkaloids. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Belladonna; Opium: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as the belladonna alkaloids. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Benzodiazepines: Concomitant administration of benzodiazepines with CNS-depressant drugs, such as diphenoxylate/difenoxin, can potentiate the CNS effects of either agent.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as hyoscyamine. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Benzonatate: Concurrent administration of diphenoxylate/difenoxin with benzonatate can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Bethanechol: Pharmacodynamic interactions between antidiarrheals and drugs that enhance peristalsis are theoretically possible. It is wise to avoid use of antidiarrheals in patients who require bethanechol.
    Bisacodyl: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: Diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with bismuth may increase the risk of serious GI related adverse events.
    Bismuth Subsalicylate: Diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with bismuth may increase the risk of serious GI related adverse events.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: Diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with bismuth may increase the risk of serious GI related adverse events.
    Botulinum Toxins: The use of systemic antimuscarinic/anticholinergic agents following the administration of botulinum toxins may result in a potentiation of systemic anticholinergic effects (e.g., blurred vision, dry mouth, constipation, or urinary retention).
    Brompheniramine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Brompheniramine; Carbetapentane; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. Concurrent administration of diphenoxylate/difenoxin with carbetapentane can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Brompheniramine; Dextromethorphan; Guaifenesin: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Brompheniramine; Guaifenesin; Hydrocodone: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Brompheniramine; Hydrocodone; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Brompheniramine; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Buprenorphine: Buprenorphine is an opioid analgesic. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Concurrent use of buprenorphine and antidiarrheals, such as atropine; diphenoxylate, can lead to severe constipation and possibly additive CNS depression. Buprenorphine is an opioid analgesic. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. In addition, concurrent use may also lead to additive CNS depression.
    Buprenorphine; Naloxone: Naloxone can antagonize the therapeutic efficacy of diphenoxylate in addition to precipitating withdrawal symptoms in patients who are physically dependent on opiate drugs including diphenoxylate. Buprenorphine is an opioid analgesic. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Concurrent use of buprenorphine and antidiarrheals, such as atropine; diphenoxylate, can lead to severe constipation and possibly additive CNS depression. Buprenorphine is an opioid analgesic. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. In addition, concurrent use may also lead to additive CNS depression.
    Bupropion: The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Bupropion; Naltrexone: When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur. The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including bupropion. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Buspirone: Concomitant use of CNS depressants, such as buspirone, can potentiate the effects of diphenoxylate/difenoxin, which may potentially lead to respiratory depression, CNS depression, sedation, or hypotensive responses. If concurrent use of codeine and buspirone is imperative, reduce the dose of one or both drugs.
    Butabarbital: Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Butorphanol: Butorphanol is a synthetic parenteral opiate agonist-antagonist. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Concurrent use of butorphanol and antidiarrheals, such as diphenoxylate, can lead to severe constipation and possibly additive CNS depression.
    Calcium Carbonate: Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Calcium Carbonate; Magnesium Hydroxide: Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction. Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction. Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Calcium Carbonate; Risedronate: Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Calcium Phosphate, Supersaturated: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Calcium; Vitamin D: Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Capsaicin; Metaxalone: Concurrent administration of diphenoxylate/difenoxin with metaxalone can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Carbetapentane; Chlorpheniramine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. Concurrent administration of diphenoxylate/difenoxin with carbetapentane can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbetapentane; Chlorpheniramine; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. Concurrent administration of diphenoxylate/difenoxin with carbetapentane can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbetapentane; Diphenhydramine; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. Concurrent administration of diphenoxylate/difenoxin with carbetapentane can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbetapentane; Guaifenesin: Concurrent administration of diphenoxylate/difenoxin with carbetapentane can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics.
    Carbetapentane; Guaifenesin; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. Concurrent administration of diphenoxylate/difenoxin with carbetapentane can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics.
    Carbetapentane; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. Concurrent administration of diphenoxylate/difenoxin with carbetapentane can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics.
    Carbetapentane; Phenylephrine; Pyrilamine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. Concurrent administration of diphenoxylate/difenoxin with carbetapentane can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbetapentane; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. Concurrent administration of diphenoxylate/difenoxin with carbetapentane can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics.
    Carbetapentane; Pyrilamine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. Concurrent administration of diphenoxylate/difenoxin with carbetapentane can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane is combined with other CNS depressants including anticholinergics. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbidopa; Levodopa: The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
    Carbidopa; Levodopa; Entacapone: Concurrent administration of diphenoxylate/difenoxin with COMT inhibitors can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
    Carbinoxamine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbinoxamine; Hydrocodone; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbinoxamine; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carbinoxamine; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Carisoprodol: Concurrent administration of diphenoxylate/difenoxin with carisoprodol can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Castor Oil: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Cetirizine: Concurrent administration of diphenoxylate/difenoxin with cetirizine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Dry mouth and drowsiness were more common in patients receiving cetirizine/levocetirizine vs. placebo, and caution may be necessary during concomitant use of cetirizine/levocetirizine with the antimuscarinics.
    Cetirizine; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. Concurrent administration of diphenoxylate/difenoxin with cetirizine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Dry mouth and drowsiness were more common in patients receiving cetirizine/levocetirizine vs. placebo, and caution may be necessary during concomitant use of cetirizine/levocetirizine with the antimuscarinics.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlophedianol; Guaifenesin; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Chloral Hydrate: Concurrent administration of diphenoxylate/difenoxin with anxiolytics, sedatives, and hypnotics can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Chlorcyclizine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlordiazepoxide; Clidinium: Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as clidinium. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Chlorpheniramine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Codeine: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Dextromethorphan: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Hydrocodone: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Hydrocodone; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpheniramine; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Chlorpromazine: Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including chlorpromazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
    Chlorthalidone; Clonidine: Concurrent administration of diphenoxylate/difenoxin with clonidine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Cholinergic agonists: The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
    Chondroitin; Glucosamine: Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Cisapride: The use of drugs that decrease GI motility, such as diphenoxylate/difenoxin, may pharmacodynamically oppose the effects of cisapride. In general, it would be illogical to use diphenoxylate/difenoxin in combination with prokinetic agents. Atropine is an anticholinergic drug and thus can antagonize the action of drugs that enhance gastrointestinal motility, such as cisapride. Use this combination with caution.
    Cisatracurium: Concurrent administration of diphenoxylate/difenoxin with neuromuscular blockers can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Citalopram: Concurrent administration of diphenoxylate/difenoxin with citalopram can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Citric Acid; Potassium Citrate: Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Citric Acid; Potassium Citrate; Sodium Citrate: Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Clemastine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Clobazam: Concurrent administration of diphenoxylate/difenoxin with clobazam can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Clomipramine: Concurrent administration of can potentiate the CNS and respiratory depressant effects of diphenoxylate/difenoxin and the CNS deoressant effects of the tricyclic antidepressant (TCA). Both TCAs and diphenoxylate/difenoxin may cause constipation. Use caution during coadministration. Cases of severe GI reactions including toxic megacolon and adynamic ileus have been rarely reported. In some cases, a dosage reduction of diphenoxylate or difenoxin might be needed to manage any noted side effects.
    Clonidine: Concurrent administration of diphenoxylate/difenoxin with clonidine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Clozapine: Diphenoxylate decreases GI motility. Other drugs that also decrease GI motility, such as clozapine, may produce additive effects with diphenoxylate if used concomitantly. The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including clozapine.
    Codeine: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Codeine; Guaifenesin: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Codeine; Phenylephrine; Promethazine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur. Concurrent administration of diphenoxylate/difenoxin with promethazine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with promethazine may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Codeine; Promethazine: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur. Concurrent administration of diphenoxylate/difenoxin with promethazine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with promethazine may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Colesevelam: Colesevelam may decrease the absorption of atropine if coadministered. To minimize potential for interactions, consider administering atropine at least 1 hour before or at least 4 hours after colesevelam; monitor drug response and/or serum drug concentrations.
    COMT inhibitors: Concurrent administration of diphenoxylate/difenoxin with COMT inhibitors can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Crofelemer: Pharmacodynamic interactions between crofelemer and antimuscarinics are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking medications that decrease GI motility, such as antimuscarinics, may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. Use caution and monitor GI symptoms during coadministration. Pharmacodynamic interactions between crofelemer and other antidiarrheals are theoretically possible. Crofelemer does not affect GI motility mechanisms, but does have antidiarrheal effects. Patients taking antidiarrheal medications that decrease GI motility may be at greater risk for serious complications from crofelemer, such as constipation with chronic use. During clinical trials with crofelemer, patients were excluded if they were actively using other antidiarrheal medications. Use caution and monitor GI symptoms during coadministration.
    Cyclizine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Cyclobenzaprine: Depending on the specific agent, additive anticholinergic effects may be seen when drugs with antimuscarinic properties like cyclobenzaprine are used concomitantly with other anticholinergics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur, depending on the interacting agent. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as cyclobenzaprine, may produce additive effects with diphenoxylate/difenoxin if used concomitantly.
    Cyproheptadine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Dantrolene: Concurrent administration of diphenoxylate/difenoxin with dantrolene can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Darifenacin: Antidiarrheals (e.g. atropine; diphenoxylate, atropine; difenoxin, or loperamide) decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been rarely reported to induce toxic megacolon. Constipation and dry mouth are reported side effects of darifenacin. Additive GI, CNS, or other anticholinergic effects may occur if used concomitantly.
    Desipramine: Concurrent administration of can potentiate the CNS and respiratory depressant effects of diphenoxylate/difenoxin and the CNS deoressant effects of the tricyclic antidepressant (TCA). Both TCAs and diphenoxylate/difenoxin may cause constipation. Use caution during coadministration. Cases of severe GI reactions including toxic megacolon and adynamic ileus have been rarely reported. In some cases, a dosage reduction of diphenoxylate or difenoxin might be needed to manage any noted side effects.
    Desloratadine: Concurrent administration of diphenoxylate/difenoxin with desloratadine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Desloratadine; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. Concurrent administration of diphenoxylate/difenoxin with desloratadine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Dexchlorpheniramine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Dexmedetomidine: Concurrent administration of diphenoxylate/difenoxin with dexmedetomidine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Dextromethorphan; Diphenhydramine; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Dextromethorphan; Guaifenesin; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
    Dextromethorphan; Promethazine: Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur. Concurrent administration of diphenoxylate/difenoxin with promethazine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with promethazine may increase the risk of serious GI related adverse events.
    Dextromethorphan; Quinidine: The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Digoxin: Anticholinergics, because of their ability to cause tachycardia, can antagonize the beneficial actions of digoxin in atrial fibrillation/flutter. Routine therapeutic monitoring should be continued when an antimuscarinic agent is prescribed with digoxin until the effects of combined use are known.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events.
    Dimenhydrinate: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Diphenhydramine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Diphenhydramine; Hydrocodone; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Diphenhydramine; Ibuprofen: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Diphenhydramine; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Disopyramide: Coadministration of disopyramide and diphenoxylate/difenoxin may cause an additive decrease in GI motility and should be used cautiously. In addition to its electrophysiologic effects, disopyramide exhibits clinically significant anticholinergic properties. These can be additive with other anticholinergics. Clinicians should be aware that urinary retention, particularly in males, and aggravation of glaucoma are realistic possibilities of using disopyramide with other anticholinergic agents.
    Docusate Sodium; Senna: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Donepezil: The therapeutic benefits of donepezil, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Donepezil; Memantine: The adverse effects of anticholinergics, such as dry mouth, urinary hesitancy or blurred vision may be enhanced with use of memantine; dosage adjustments of the anticholinergic drug may be required when memantine is coadministered. In addition, preliminary evidence indicates that chronic anticholinergic use in patients with Alzheimer's Disease may possibly have an adverse effect on cognitive function. Therefore, the effectiveness of drugs used in the treatment of Alzheimer's such as memantine, may be adversely affected by chronic antimuscarinic therapy. The therapeutic benefits of donepezil, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Doxacurium: Concurrent administration of diphenoxylate/difenoxin with neuromuscular blockers can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Doxepin: Concurrent administration of can potentiate the CNS and respiratory depressant effects of diphenoxylate/difenoxin and the CNS deoressant effects of the tricyclic antidepressant (TCA). Both TCAs and diphenoxylate/difenoxin may cause constipation. Use caution during coadministration. Cases of severe GI reactions including toxic megacolon and adynamic ileus have been rarely reported. In some cases, a dosage reduction of diphenoxylate or difenoxin might be needed to manage any noted side effects.
    Doxylamine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Doxylamine; Pyridoxine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Dronabinol, THC: Concurrent administration of diphenoxylate/difenoxin with dronabinol can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Use caution if coadministration of dronabinol with anticholinergics is necessary. Concurrent use of dronabinol, THC with anticholinergics may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
    Edrophonium: Coadministration of Atropine and Edrophonium Chloride can produce mutually antagonistic effects.
    Eluxadoline: Avoid use of eluxadoline with medications that may cause constipation, such as anticholinergics. Discontinue use of eluxadoline in patients who develop severe constipation lasting more than 4 days.
    Entacapone: Concurrent administration of diphenoxylate/difenoxin with COMT inhibitors can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Ephedrine: Atropine can potentiate the pressor effects of ephedra alkaloids. Atropine is thought to block the compensatory reflex sinus bradycardia normally seen after the administration of ephedrine, the primary alkaloid found in ephedra, ma huang and consequently can increase pressor response.
    Erythromycin: Anticholinergics can antagonize the stimulatory effects of erythromycin on the GI tract (when erythromycin is used therapeutically for improving GI motility). Avoid chronic administration of antimuscarinics along with prokinetic agents under most circumstances. In addition, erythromycin is a CYP3A4 inhibitor and can reduce the metabolism of drugs metabolized by CYP3A4, including some anticholinergics. Diphenoxylate/difenoxin decreases GI motility. It may antagonize the muscarinic and/or prokinetic effects of erythromycin (when used for GI motility). Use these drugs in combination should be avoided.
    Erythromycin; Sulfisoxazole: Anticholinergics can antagonize the stimulatory effects of erythromycin on the GI tract (when erythromycin is used therapeutically for improving GI motility). Avoid chronic administration of antimuscarinics along with prokinetic agents under most circumstances. In addition, erythromycin is a CYP3A4 inhibitor and can reduce the metabolism of drugs metabolized by CYP3A4, including some anticholinergics. Diphenoxylate/difenoxin decreases GI motility. It may antagonize the muscarinic and/or prokinetic effects of erythromycin (when used for GI motility). Use these drugs in combination should be avoided.
    Escitalopram: Concurrent administration of diphenoxylate/difenoxin with escitalopram can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Eszopiclone: Concurrent administration of diphenoxylate/difenoxin with anxiolytics, sedatives, and hypnotics can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Ethanol: Alcohol is associated with CNS depression. The combined use of alcohol and CNS depressants can lead to additive CNS depression, which could be dangerous in tasks requiring mental alertness and fatal in overdose. Alcohol taken with other CNS depressants can lead to additive respiratory depression, hypotension, profound sedation, or coma. Consider the patient's use of alcohol or illicit drugs when prescribing CNS depressant medications. In many cases, the patient should receive a lower dose of the CNS depressant initially if the patient is not likely to be compliant with avoiding alcohol.
    Ethotoin: Concurrent administration of diphenoxylate/difenoxin with hydantoins can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Etomidate: Additive CNS depression may occur if diphenoxylate/difenoxin is used concomitantly with other CNS depressants, including etomidate.
    Ezogabine: Caution is advisable during concurrent use of ezogabine and medications that may affect voiding such as anticholinergic agents. Ezogabine has caused urinary retention requiring catheterization in some cases. The anticholinergic effects of antimuscariinic and anticholinergic medications on the urinary tract may be additive. Additive sedation or other CNS effects may also occur.
    Fentanyl: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Fesoterodine: Antidiarrheals (e.g. atropine; diphenoxylate, atropine; difenoxin, or loperamide) decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been rarely reported to induce toxic megacolon. Constipation and dry mouth are reported side effects of fesoterodine. Additive GI, CNS, or other anticholinergic effects may occur if used concomitantly.
    Fexofenadine; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
    Flavoxate: Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as flavoxate. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Fluoxetine: Concurrent administration of diphenoxylate/difenoxin with fluoxetine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Fluoxetine; Olanzapine: Concurrent administration of diphenoxylate/difenoxin with fluoxetine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Drugs that decrease GI motility, such as olanzapine, may produce additive effects with antidiarrheals, such as diphenoxylate/difenoxin, if used concomitantly. The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including olanzapine. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Fluphenazine: Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including fluphenazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
    Food: Avoid administering marijuana and atropine together as concurrent use may result in adverse cardiovascular effects, such as tachycardia and cardiac arrhythmias. Marijuana is known to produce significant increases in heart rate and cardiac output lasting for 2-3 hours. Further, rare case reports of myocardial infarction and cardiac arrhythmias have been associated with marijuana use. Atropine has also been reported to produce a wide range of cardiovascular effects including asystole, atrial fibrillation, premature ventricular contractions (PVCs), ventricular fibrillation, palpitations, and sinus tachycardia. Coadministration of marijuana with atropine may result in significant cardiovascular adverse events and thus, should be avoided.
    Fosphenytoin: Concurrent administration of diphenoxylate/difenoxin with hydantoins can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Galantamine: The therapeutic benefits of galantamine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Glucagon: The concomitant use of intravenous glucagon and anticholinergics increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility. Concomitant use is not recommended.
    Glucosamine: Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Glycopyrrolate: Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as glycopyrrolate. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Glycopyrrolate; Formoterol: Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as glycopyrrolate. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Guaifenesin; Hydrocodone: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Guaifenesin; Hydrocodone; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Guaifenesin; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Guaifenesin; Potassium Guaiacolsulfonate: Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Guaifenesin; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
    Guanabenz: Concurrent administration of diphenoxylate/difenoxin with guanabenz can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Guanfacine: Concurrent administration of diphenoxylate/difenoxin with guanfacine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Haloperidol: Haloperidol can potentiate the actions of other CNS depressants, such as opiate agonists, Caution should be exercised with simultaneous use of these agents due to potential excessive CNS effects.
    Hetastarch; Dextrose; Electrolytes: Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Homatropine; Hydrocodone: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as systemic homatropine. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Hydantoins: Concurrent administration of diphenoxylate/difenoxin with hydantoins can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Hydrochlorothiazide, HCTZ; Methyldopa: Concurrent administration of diphenoxylate/difenoxin with methyldopa can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Hydrocodone: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Hydrocodone; Ibuprofen: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Hydrocodone; Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Hydrocodone; Potassium Guaiacolsulfonate: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Hydrocodone; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Concurrent use of antidiarrheals and hydrocodone can lead to severe constipation and possibly additive CNS depression. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use.
    Hydrocortisone; Lidocaine: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Hydromorphone: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Hydroxyzine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Hyoscyamine: Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as hyoscyamine. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as hyoscyamine. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Ibritumomab Tiuxetan: Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Ibuprofen lysine: Use caution in combining ibuprofen lysine with renally eliminated medications like atropine, as ibuprofen may reduce renal blood flow.
    Ibuprofen; Oxycodone: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Ibuprofen; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
    Imipramine: Concurrent administration of can potentiate the CNS and respiratory depressant effects of diphenoxylate/difenoxin and the CNS deoressant effects of the tricyclic antidepressant (TCA). Both TCAs and diphenoxylate/difenoxin may cause constipation. Use caution during coadministration. Cases of severe GI reactions including toxic megacolon and adynamic ileus have been rarely reported. In some cases, a dosage reduction of diphenoxylate or difenoxin might be needed to manage any noted side effects.
    Indacaterol; Glycopyrrolate: Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as glycopyrrolate. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Iodine; Potassium Iodide, KI: Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Ipratropium: Although ipratropium is minimally absorbed into the systemic circulation after inhalation, there is the potential for tiotropium to have additive anticholinergic effects when administered with other antimuscarinics. Per the manufaturer, avoid concomitant administration of ipratropium with other anticholinergic medications, such as antimucarinics.
    Itraconazole: Antimuscarinics can raise intragastric pH. This effect may decrease the oral bioavailability of itraconazole; antimuscarinics should be used cautiously in patients receiving itraconazole.
    Ketamine: Concurrent administration of diphenoxylate/difenoxin with ketamine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Lactulose: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Lanthanum Carbonate: Oral compounds known to interact with antacids, like anticholinergics, should not be taken within 2 hours of dosing with lanthanum carbonate. If these agents are used concomitantly, space the dosing intervals appropriately. Monitor serum concentrations and clinical condition.
    Laxatives: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Levocetirizine: Concurrent administration of diphenoxylate/difenoxin with cetirizine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Dry mouth and drowsiness were more common in patients receiving cetirizine/levocetirizine vs. placebo, and caution may be necessary during concomitant use of cetirizine/levocetirizine with the antimuscarinics.
    Levodopa: The doses of antimuscarinics and levodopa may need to be adjusted when the drugs are given simultaneously. Through central antimuscarinic actions, anticholinergics can potentiate the dopaminergic effects of levodopa. While some patients may benefit from this interaction, clinicians should be ready to decrease doses of levodopa if an antimuscarinic is added.
    Levorphanol: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events.
    Linaclotide: Several agents (e.g., antimuscarinics) have an antagonistic effect at muscarinic cholinergic receptors (an anticholinergic effect). Thus antimuscarinic drugs can promote constipation and pharmacodynamically oppose the action of drugs used for the treatment of constipation, such as linaclotide. The clinical significance of these potential interactions is uncertain.
    Linezolid: The concomitant administration of diphenoxylate or difenoxin and monoamine oxidase inhibitors (MAOIs) may cause hypertensive crisis. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor; therefore, linezolid has the potential for interaction with difenoxin or diphenoxylate. The chemical structure of diphenoxylate hydrochloride is similar to that of meperidine hydrochloride. Meperidine is contraindicated in patients who are receiving traditional MAOIs or those who have recently received such agents. Therapeutic doses of meperidine have occasionally precipitated unpredictable, severe, and occasionally fatal reactions in patients who have received a MAOI within 14 days. Avoid concurrent use.
    Loperamide: Diphenoxylate and difenoxin decrease GI motility. Coadministration with loperamide may result in an additive decrease in GI motility, severe constipation, obstruction/impaction, or paralytic ileus and possibly additive CNS depression. Loperamide decreases GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Systemic atropine, an anticholinergic, may produce additive GI and CNS effects with loperamide if used concomitantly. Atropine is commonly added in small amounts to atropine; diphenoxylate formulas for diarrhea as a deterrant to diphenoxylate abuse. However, therapeutic doses of systemic atropine may cause additive side effects. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Loperamide; Simethicone: Diphenoxylate and difenoxin decrease GI motility. Coadministration with loperamide may result in an additive decrease in GI motility, severe constipation, obstruction/impaction, or paralytic ileus and possibly additive CNS depression. Loperamide decreases GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Systemic atropine, an anticholinergic, may produce additive GI and CNS effects with loperamide if used concomitantly. Atropine is commonly added in small amounts to atropine; diphenoxylate formulas for diarrhea as a deterrant to diphenoxylate abuse. However, therapeutic doses of systemic atropine may cause additive side effects. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Loratadine: Concurrent administration of diphenoxylate/difenoxin with loratadine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Loratadine; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine. Concurrent administration of diphenoxylate/difenoxin with loratadine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Loxapine: Concurrent administration of diphenoxylate/difenoxin with loxapine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Lubiprostone: Antimuscarinic drugs can promote constipation and pharmacodynamically oppose the action of drugs used for the treatment of constipation, such as lubiprostone. The clinical significance of these potential interactions is uncertain.
    Lurasidone: Antipsychotic agents may disrupt core temperature regulation; therefore, caution is recommended during concurrent use of lurasidone and medications with anticholinergic activity such as antimuscarinics. Concurrent use of lurasidone and medications with anticholinergic activity may contribute to heat-related disorders. Monitor patients for heat intolerance, decreased sweating, or increased body temperature if lurasidone is used with antimuscarinics. Concurrent administration of diphenoxylate/difenoxin with lurasidone can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Magnesium Citrate: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Magnesium Hydroxide: Antacids may inhibit the oral absorption of anticholinergics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction. Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Magnesium Sulfate; Potassium Sulfate; Sodium Sulfate: Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Maprotiline: Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as maprotiline, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of atropine may be enhanced when combined with other commonly used drugs with moderate to significant anticholinergic effects including maprotiline.
    Meclizine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Memantine: The adverse effects of anticholinergics, such as dry mouth, urinary hesitancy or blurred vision may be enhanced with use of memantine; dosage adjustments of the anticholinergic drug may be required when memantine is coadministered. In addition, preliminary evidence indicates that chronic anticholinergic use in patients with Alzheimer's Disease may possibly have an adverse effect on cognitive function. Therefore, the effectiveness of drugs used in the treatment of Alzheimer's such as memantine, may be adversely affected by chronic antimuscarinic therapy.
    Meperidine: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Meperidine; Promethazine: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur. Concurrent administration of diphenoxylate/difenoxin with promethazine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with promethazine may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Mephobarbital: Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Meprobamate: Concurrent administration of diphenoxylate/difenoxin with anxiolytics, sedatives, and hypnotics can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Metaxalone: Concurrent administration of diphenoxylate/difenoxin with metaxalone can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Methadone: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as hyoscyamine. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Methocarbamol: Concurrent administration of diphenoxylate/difenoxin with methocarbamol can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Methohexital: Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Methscopolamine: Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as methscopolamine. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Methylcellulose: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Methyldopa: Concurrent administration of diphenoxylate/difenoxin with methyldopa can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Metoclopramide: Diphenoxylate/difenoxin decreases GI motility. Diphenoxylate/difenoxin may antagonize the muscarinic and/or prokinetic effects of other drugs, including metoclopramide. Drugs with significant antimuscarinic activity, such as anticholinergics and antimuscarinics, may slow GI motility and thus may reduce the prokinetic actions of metoclopramide. Monitor patients for an increase in gastrointestinal complaints, such as reflux or constipation. Additive drowsiness may occur as well. The clinical significance is uncertain.
    Metyrapone: Concurrent administration of diphenoxylate/difenoxin with metyrapone can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Metyrosine: Concurrent administration of diphenoxylate/difenoxin with metyrosine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Mineral Oil: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Minocycline: Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants like diphenoxylate. Caution should be exercised when using these agents concurrently.
    Mirtazapine: Consistent with the pharmacology of mirtazapine and the drug's side effect profile, additive effects may occur with other CNS-active agents, including diphenoxylate/difenoxin. Mirtazapine exhibits weak anticholinergic activity that is not expected to be clinically significant. However, the anticholinergic effects may be additive to the antimuscarinics. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation.
    Mitotane: Concurrent administration of diphenoxylate/difenoxin with mitotane can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Mivacurium: Concurrent administration of diphenoxylate/difenoxin with neuromuscular blockers can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Molindone: Antipsychotics are associated with anticholinergic effects; therefore, additive effects may be seen during concurrent use of molindone and other drugs having anticholinergic activity such as antimuscarinics. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other CNS effects may also occur. Concurrent administration of diphenoxylate/difenoxin with molindone can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Monoamine oxidase inhibitors: The concomitant administration of diphenoxylate or difenoxin and monoamine oxidase inhibitors can cause hypertensive crisis. Avoid concurrent use.
    Morphine: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Morphine; Naltrexone: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Nabilone: Concurrent administration of diphenoxylate/difenoxin with nabilone can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. Concurrent use of nabilone with anticholinergics may result in pronounced tachycardia and drowsiness.
    Nalbuphine: Concurrent administration of diphenoxylate/difenoxin with nalbuphine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Naloxone: Naloxone can antagonize the therapeutic efficacy of diphenoxylate in addition to precipitating withdrawal symptoms in patients who are physically dependent on opiate drugs including diphenoxylate.
    Naltrexone: When naltrexone is used as adjuvant treatment of opiate or alcohol dependence, use is contraindicated in patients currently receiving opiate agonists. Naltrexone will antagonize the therapeutic benefits of opiate agonists and will induce a withdrawal reaction in patients with physical dependence to opioids. Also, patients should be opiate-free for at least 7-10 days prior to initiating naltrexone therapy. If there is any question of opioid use in the past 7-10 days and the patient is not experiencing opioid withdrawal symptoms and/or the urine is negative for opioids, a naloxone challenge test needs to be performed. If a patient receives naltrexone, and an opiate agonist is needed for an emergency situation, large doses of opiate agonists may ultimately overwhelm naltrexone antagonism of opiate receptors. Immediately following administration of exogenous opiate agonists, the opiate plasma concentration may be sufficient to overcome naltrexone competitive blockade, but the patient may experience deeper and more prolonged respiratory depression and thus, may be in danger of respiratory arrest and circulatory collapse. Non-receptor mediated actions like facial swelling, itching, generalized erythema, or bronchoconstriction may occur presumably due to histamine release. A rapidly acting opiate agonist is preferred as the duration of respiratory depression will be shorter. Patients receiving naltrexone may also experience opiate side effects with low doses of opiate agonists. If the opiate agonist is taken in such a way that high concentrations remain in the body beyond the time naltrexone exerts its therapeutic effects, serious side effects may occur.
    Naproxen; Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
    Neostigmine: Coadministration of atropine and neostigmine may produce a mutually antagonistic effect.
    Neuromuscular blockers: Concurrent administration of diphenoxylate/difenoxin with neuromuscular blockers can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Nitrofurantoin: Antimuscarinics can delay gastric emptying, possibly increasing the bioavailability of nitrofurantoin.
    Norepinephrine: Pharmacologically, sufficient doses of atropine block various types of vagal reflex bradycardia. Because norepinephrine causes vagal reflex bradycardia, the concomitant use of atropine and norepinephrine may increase the pressor effect of norepinephrine.
    Nortriptyline: Concurrent administration of can potentiate the CNS and respiratory depressant effects of diphenoxylate/difenoxin and the CNS deoressant effects of the tricyclic antidepressant (TCA). Both TCAs and diphenoxylate/difenoxin may cause constipation. Use caution during coadministration. Cases of severe GI reactions including toxic megacolon and adynamic ileus have been rarely reported. In some cases, a dosage reduction of diphenoxylate or difenoxin might be needed to manage any noted side effects.
    Octreotide: Diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with octreotide may increase the risk of serious GI related adverse events.
    Olanzapine: Drugs that decrease GI motility, such as olanzapine, may produce additive effects with antidiarrheals, such as diphenoxylate/difenoxin, if used concomitantly. The anticholinergic effects of atropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including olanzapine. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
    Omeprazole; Sodium Bicarbonate: Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Opiate Agonists: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events.
    Orphenadrine: Concurrent administration of diphenoxylate/difenoxin with orphenadrine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. The anticholinergic effects of atropine may be enhanced when combined with other commonly used drugs with moderate to significant anticholinergic effects including orphenadrine. Clinicians should note that anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
    Oxycodone: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Oxymorphone: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Pancuronium: Concurrent administration of diphenoxylate/difenoxin with neuromuscular blockers can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Papaverine: Concurrent administration of diphenoxylate/difenoxin with papaverine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Pegvisomant: Diphenoxylate/difenoxin is a synthetic opiate agonist with a chemical structure similar to that of meperidine. In clinical trials, patients taking opiate agonists often required higher serum pegvisomant concentrations to achieve appropriate IGF-I suppression compared with patients not receiving opiate agonists. The mechanism of this interaction is unknown.
    Pentazocine: Pentazocine may partially block the analgesic, respiratory depressant and CNS depressant effects of pure opiate agonists. Due to their antagonistic properties, pentazocine may cause withdrawal symptoms in patients receiving chronic opiate agonists. Pentazocine may also be used concurrently with some opiate agonists and cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of pure opiate agonist used; antagonistic effects are more common at low to moderate doses of the pure opiate agonist. For example, some patients who received methadone for the daily treatment of narcotic dependence have experienced withdrawal symptoms after receiving pentazocine. Withdrawal symptoms may include anxiety, agitation, mood changes, hallucinations, dysphoria, weakness, and diarrhea. Use pentazocine with caution in any patient receiving anticholinergic agents. Coadministration of pentazocine with antimuscarinics may result in additive anticholinergic effects, such as urinary retention and constipation.
    Pentazocine; Naloxone: Naloxone can antagonize the therapeutic efficacy of diphenoxylate in addition to precipitating withdrawal symptoms in patients who are physically dependent on opiate drugs including diphenoxylate. Pentazocine may partially block the analgesic, respiratory depressant and CNS depressant effects of pure opiate agonists. Due to their antagonistic properties, pentazocine may cause withdrawal symptoms in patients receiving chronic opiate agonists. Pentazocine may also be used concurrently with some opiate agonists and cause additive CNS, respiratory, and hypotensive effects. The additive or antagonistic effects are dependent upon the dose of pure opiate agonist used; antagonistic effects are more common at low to moderate doses of the pure opiate agonist. For example, some patients who received methadone for the daily treatment of narcotic dependence have experienced withdrawal symptoms after receiving pentazocine. Withdrawal symptoms may include anxiety, agitation, mood changes, hallucinations, dysphoria, weakness, and diarrhea. Use pentazocine with caution in any patient receiving anticholinergic agents. Coadministration of pentazocine with antimuscarinics may result in additive anticholinergic effects, such as urinary retention and constipation.
    Pentobarbital: Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Perampanel: Concurrent administration of diphenoxylate/difenoxin with perampanel can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Perphenazine: Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including perphenazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
    Perphenazine; Amitriptyline: Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including perphenazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur. Concurrent administration of can potentiate the CNS and respiratory depressant effects of diphenoxylate/difenoxin and the CNS deoressant effects of the tricyclic antidepressant (TCA). Both TCAs and diphenoxylate/difenoxin may cause constipation. Use caution during coadministration. Cases of severe GI reactions including toxic megacolon and adynamic ileus have been rarely reported. In some cases, a dosage reduction of diphenoxylate or difenoxin might be needed to manage any noted side effects.
    Phenobarbital: Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Phenothiazines: Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to other agents with CNS and anticholinergic effects, such as the phenothiazines. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Phentermine; Topiramate: Use caution if carbonic anhydrase inhibitors are administered with anticholinergics and monitor for excessive anticholinergic adverse effects. The use of topiramate with agents that may increase the risk for heat-related disorders, such as anticholinergics, may lead to oligohidrosis, hyperthermia and/or heat stroke.
    Phenylephrine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect.
    Phenylephrine; Promethazine: Atropine blocks the vagal reflex bradycardia caused by sympathomimetic agents, such as phenylephrine, and increases its pressor effect. Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur. Concurrent administration of diphenoxylate/difenoxin with promethazine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with promethazine may increase the risk of serious GI related adverse events.
    Phenytoin: Concurrent administration of diphenoxylate/difenoxin with hydantoins can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Physostigmine: Coadministration of atropine and physostigmine may produce a mutually antagonistic effect.
    Pimozide: Due to the effects of pimozide on cognition, it should be used cautiously with other CNS depressants including diphenoxylate/difenoxin.
    Polyethylene Glycol: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Polyethylene Glycol; Electrolytes: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Polyethylene Glycol; Electrolytes; Bisacodyl: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Potassium Citrate: Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Potassium Iodide, KI: Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Potassium Phosphate; Sodium Phosphate: Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Potassium Salts: Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Potassium: Drugs that decrease GI motility may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. The use of solid oral dosage forms of potassium chloride is contraindicated in patients taking glycopyrrolate oral solution. In one study, healthy subjects were examined for GI irritation following the administration of oral potassium for at least 7 days. Glycopyrrolate was coadministered to some subjects in order to study the additional effects of delayed gastric emptying. Results indicated that subjects administered wax-matrix tablets had the highest incidence of erosions (43%) and ulcers (11%). Evidence of GI irritation was less frequent among subjects receiving liquid (0%) and microencapsulated (10.5% erosions, 1.2% ulcers) formulations. Therefore, if oral potassium supplementation is necessary in a patient taking antimuscarinics, a liquid formulation should be considered. If a solid formulation is being prescribed, the patient should be counseled on strategies that can be used to avoid GI irritation such as taking potassium products only while seated or standing, remaining upright for 10 minutes after each dose, and ingesting each dose with plenty of fluids. Drugs that decrease GI motility, like diphenoxylate/difenoxin, may increase the risk of GI irritation from sustained-release solid oral dosage forms of potassium salts. Immediate release potassium formulations may be preferred in patients requiring diphenoxylate/difenoxin therapy.
    Pramipexole: The use of opiate agonists in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
    Pramlintide: Pramlintide slows gastric emptying and the rate of nutrient delivery to the small intestine. Medications that have depressive effects on GI motility or slow nutritive absorption could potentiate the actions of pramlintide leading to further reductions in blood glucose concentrations and possibly hypoglycemia. Patients with gastrointestinal disease or taking drugs that affect gastrointestinal motility were excluded from clinical trials. Per the manufacturer, pramlintide therapy should not be considered in patients taking medications that significantly alter gastric motility such as diphenoxylate/difenoxin, Clinicians should advise their patients to monitor blood glucose concentrations closely when initiating or discontinuing one of these drugs. Pramlintide therapy should not be considered in patients taking medications that alter gastric motility, such as anticholinergics. Pramlintide slows gastric emptying and the rate of nutrient delivery to the small intestine. Medications that have depressive effects on GI could potentiate the actions of pramlintide.
    Pregabalin: Concurrent administration of diphenoxylate/difenoxin with pregabalin can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Primidone: Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Procainamide: The anticholinergic effects of procainamide may be significant and may be enhanced when combined with anticholinergics. Anticholinergic agents administered concurrently with procainamide may produce additive antivagal effects on AV nodal conduction, although this is not as well documented for procainamide as for quinidine.
    Procarbazine: Opiate agonists may cause additive sedation or other CNS effects when given in combination with procarbazine.
    Prochlorperazine: Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including prochlorperazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
    Promethazine: Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including promethazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur. Concurrent administration of diphenoxylate/difenoxin with promethazine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with promethazine may increase the risk of serious GI related adverse events.
    Propoxyphene: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events.
    Proton pump inhibitors: The American College of Gastroenterology states that the effectiveness of proton pump inhibitors (PPIs) may be theoretically decreased if given with other antisecretory agents (e.g., anticholinergics). Proton pump inhibitors (PPIs) inhibit only actively secreting H+-pumps.
    Protriptyline: Concurrent administration of can potentiate the CNS and respiratory depressant effects of diphenoxylate/difenoxin and the CNS deoressant effects of the tricyclic antidepressant (TCA). Both TCAs and diphenoxylate/difenoxin may cause constipation. Use caution during coadministration. Cases of severe GI reactions including toxic megacolon and adynamic ileus have been rarely reported. In some cases, a dosage reduction of diphenoxylate or difenoxin might be needed to manage any noted side effects.
    Pseudoephedrine: Atropine blocks the vagal reflex bradycardia caused by pseudoephedrine, and increases its pressor effect. Patients need to be asked whether they have taken pseudoephedrine before receiving atropine.
    Psyllium: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Pyridostigmine: Coadministration of atropine and pyridostigmine bromide may produce a mutually antagonistic effect.
    Quinidine: The anticholinergic effects of quinidine may be significant and may be enhanced when combined with antimuscarinics.
    Rapacuronium: Concurrent administration of diphenoxylate/difenoxin with neuromuscular blockers can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Rasagiline: The concomitant administration of diphenoxylate/difenoxin and monoamine oxidase inhibitors (MAOIs) can cause hypertensive crisis. Although rasagiline differs from most other MAOIs because it is MAO-B selective at recommended doses, it may be advisable to avoid co-administration with diphenoxylate/difenoxin until specific information becomes available about the safety of this combination. MAOIs exhibit secondary anticholinergic actions. Additive anticholinergic effects may be seen when MAOIs are used concomitantly with antimuscarinics. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive CNS effects are also possible when many of these drugs are combined with MAOIs.
    Remifentanil: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Risperidone: Concurrent administration of diphenoxylate/difenoxin with risperidone can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Ritodrine: Ritodrine induced systemic hypertension may be exagerrated in the presence of parasympatholytic agents like atropine.
    Rivastigmine: The therapeutic benefits of rivastigmine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Rocuronium: Concurrent administration of diphenoxylate/difenoxin with neuromuscular blockers can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Secobarbital: Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Secretin: Discontinue anticholinergic medications at least 5 half-lives before administering secretin. Patients who are receiving anticholinergics at the time of stimulation testing may be hyporesponsive to secretin stimulation and produce a false result. Consider additional testing and clinical assessments for aid in diagnosis.
    Sedating H1-blockers: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Senna: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Sildenafil: Diphenoxylate/difenoxin is a synthetic opiate agonist with a chemical structure similar to that of meperidine. Prolonged erections have been reported in two patients taking sildenafil with dihydrocodeine. In both cases, patients reported erections subsided immediately after orgasm when taking sildenafil alone. Although more data are needed, use caution when prescribing opiate agonists and sildenafil concomitantly.
    Sincalide: Sincalide-induced gallbladder ejection fraction may be affected by anticholinergics. False study results are possible in patients with drug-induced hyper- or hypo-responsiveness; thorough patient history is important in the interpretation of procedure results.
    Sodium Bicarbonate: Antacids may inhibit the oral absorption of antimuscarinics. Simultaneous oral administration should be avoided when feasible; separate dosing by at least 2 hours to limit an interaction.
    Sodium Oxybate: Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Specifically, sodium oxybate use is contraindicated in patients being treated with sedative hypnotic drugs. Sodium oxybate (GHB) has the potential to impair cognitive and motor skills. Concurrent administration of diphenoxylate/difenoxin with sodium oxybate can potentiate the CNS-depressant effects of diphenoxylate/difenoxin.
    Sodium Phosphate Monobasic Monohydrate; Sodium Phosphate Dibasic Anhydrous: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Solifenacin: Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like solifenacin are used concomitantly with other antimuscarinics. Blurred vision and dry mouth would be common effects. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur. Antidiarrheals (e.g. atropine; diphenoxylate, atropine; difenoxin, or loperamide) decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been rarely reported to induce toxic megacolon. Constipation and dry mouth are reported side effects of solifenacin. Additive GI, CNS, or other anticholinergic effects may occur if used concomitantly.
    Sorbitol: Diphenoxylate can decrease GI motility. Drugs used to treat constipation, such as laxatives, would counteract the effect of antidiarrheals. In general, it would be illogical to concurrently administer these drugs at the same time. If an antidiarrheal medication is needed, it would be wise to temporarily discontinue use of agents with laxative effects.
    Succinylcholine: Concurrent administration of diphenoxylate/difenoxin with neuromuscular blockers can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Sufentanil: Concurrent administration of diphenoxylate/difenoxin with other opiate agonists can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with opiate agonists may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Tacrine: The therapeutic benefits of tacrine, a cholinesterase inhibitor, may be diminished during chronic co-administration with antimuscarinics or medications with potent anticholinergic activity. When concurrent use is not avoidable, the patient should be monitored for cognitive decline and anticholinergic side effects. Clinicians should generally avoid multiple medications with anticholinergic activity in the patient with dementia. Some of the common selective antimuscarinic drugs for bladder problems, (such as oxybutynin, darifenacin, trospium, fesoterodine, tolerodine, or solifenacin), do not routinely cause problems with medications used for dementia, but may cause anticholinergic side effects in some patients. Atropine may be used to offset bradycardia in cholinesterase inhibitor overdose.
    Tapentadol: Concurrent administration of diphenoxylate/difenoxin with tapentadol can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. In addition, diphenoxylate/difenoxin use may cause constipation; cases of severe GI reactions including toxic megacolon and adynamic ileus have been reported. Reduced GI motility when combined with tapentadol may increase the risk of serious GI related adverse events. Opiate agonists should be used cautiously with antimuscarinics since additive depressive effects on GI motility or bladder function may been seen. Opioids increase the tone and decrease the propulsive contractions of the smooth muscle of the gastrointestinal tract. Prolongation of the gastrointestinal transit time may be the mechanism of the constipating effect. Opiate analgesics combined with antimuscarinics can cause severe constipation or paralytic ileus, especially with chronic use. Pharmacology texts report that meperidine exerts less pronounced effects on GI smooth muscle than other opiate agonists.
    Tegaserod: Drugs that exert significant anticholinergic properties such as antimuscarinics may pharmacodynamically oppose the effects of prokinetic agents such as tegaserod. Avoid administering antimuscarinics along with tegaserod under most circumstances. Inhaled respiratory antimuscarinics, such as ipratropium, are unlikely to interact with tegaserod. Ophthalmic anticholinergics may interact if sufficient systemic absorption of the eye medication occurs.
    Tetrabenazine: Concurrent administration of diphenoxylate/difenoxin with tetrabenazine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Thiazide diuretics: Coadministration of thiazides and antimuscarinics (e.g., atropine and biperiden) may result in increased bioavailability of the thiazide. This is apparently a result of a decrease in gastrointestinal motility and rate of stomach emptying by the antimuscarinic agent. In addition, diuretics can increase urinary frequency, which may aggravate bladder symptoms.
    Thiopental: Concurrent administration of diphenoxylate/difenoxin with barbiturates can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Thiothixene: Depending on the specific agent, additive anticholinergic effects may be seen when phenothiazines are used concomitantly with other drugs with antimuscarinic activity.
    Tiotropium: Although tiotropium is minimally absorbed into the systemic circulation after inhalation, tiotropium may have additive anticholinergic effects when administered with other antimuscarinics. Per the manufaturer, avoid concomitant administration of tiotropium with other anticholinergic medications when possible.
    Tiotropium; Olodaterol: Although tiotropium is minimally absorbed into the systemic circulation after inhalation, tiotropium may have additive anticholinergic effects when administered with other antimuscarinics. Per the manufaturer, avoid concomitant administration of tiotropium with other anticholinergic medications when possible.
    Tolcapone: Concurrent administration of diphenoxylate/difenoxin with COMT inhibitors can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Tolterodine: Additive anticholinergic effects may be seen when tolterodine is used concomitantly with other antimuscarinics. When possible, avoid concurrent use, especially in the elderly, who are more susceptible to the anticholinergic effects. Consider alternatives to these other medications, if available. Clinicians should note that antimuscarinic effects might be seen not only on bladder smooth muscle, but also on GI function, the eye, and temperature regulation. Blurred vision, constipation, and dry mouth may be more prominent additive effects. With many of the listed agents, additive drowsiness may also occur when combined. Antidiarrheals (e.g., atropine; diphenoxylate, atropine; difenoxin, and loperamide) decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been rarely reported to induce toxic megacolon. Tolterodine has been reported to cause dry mouth and constipation as potential side effects. Other anticholinergic and CNS effects may also be additive.
    Topiramate: Use caution if carbonic anhydrase inhibitors are administered with anticholinergics and monitor for excessive anticholinergic adverse effects. The use of topiramate with agents that may increase the risk for heat-related disorders, such as anticholinergics, may lead to oligohidrosis, hyperthermia and/or heat stroke.
    Trazodone: Concurrent administration of diphenoxylate/difenoxin with trazodone can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Tricyclic antidepressants: Concurrent administration of can potentiate the CNS and respiratory depressant effects of diphenoxylate/difenoxin and the CNS deoressant effects of the tricyclic antidepressant (TCA). Both TCAs and diphenoxylate/difenoxin may cause constipation. Use caution during coadministration. Cases of severe GI reactions including toxic megacolon and adynamic ileus have been rarely reported. In some cases, a dosage reduction of diphenoxylate or difenoxin might be needed to manage any noted side effects. Depending on the specific agent, additive anticholinergic effects may be seen when tricyclic antidepressants (TCAs) are used concomitantly with other anticholinergics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive CNS effects are also possible when many of these drugs are combined with tricyclic antidepressants.
    Trifluoperazine: Additive anticholinergic effects may be seen when anticholinergics are used concomitantly with phenothiazines, including trifluoperazine. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness or other additive CNS effects may also occur.
    Trihexyphenidyl: Diphenoxylate is a synthetic opiate derivative that appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. The effects can be additive to antimuscarinic agents, such as trihexyphenidyl. In some cases, constipation might occur, and effects on the CNS or bladder function may also be additive.
    Trimethobenzamide: Trimethobenzamide has CNS depressant effects and may cause drowsiness. The concurrent use of trimethobenzamide with other medications that cause CNS depression, like the anticholinergics, may potentiate the effects of either trimethobenzamide or the anticholinergic.
    Trimipramine: Concurrent administration of can potentiate the CNS and respiratory depressant effects of diphenoxylate/difenoxin and the CNS deoressant effects of the tricyclic antidepressant (TCA). Both TCAs and diphenoxylate/difenoxin may cause constipation. Use caution during coadministration. Cases of severe GI reactions including toxic megacolon and adynamic ileus have been rarely reported. In some cases, a dosage reduction of diphenoxylate or difenoxin might be needed to manage any noted side effects.
    Triprolidine: An enhanced CNS depressant effect may occur when diphenoxylate/difenoxin is combined with other CNS depressants. Diphenoxylate/difenoxin decreases GI motility. Other drugs that also decrease GI motility, such as sedating H1 blockers, may produce additive effects with diphenoxylate/difenoxin if used concomitantly. The anticholinergic effects of sedating H1-blockers may be enhanced when combined with other antimuscarinics. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur when antimuscarinics are combined with sedating antihistamines.
    Trospium: Additive anticholinergic effects may be seen when trospium is used concomitantly with other antimuscarinics. When possible, avoid concurrent use, especially in the elderly, who are more susceptible to the anticholinergic effects. Consider alternatives to these other medications, if available. Clinicians should note that antimuscarinic effects might be seen not only on bladder smooth muscle, but also on GI function, the eye, and temperature regulation. Blurred vision, constipation, and dry mouth may be more prominent additive effects. With many of the listed agents, additive drowsiness may also occur when combined with trospium.
    Tubocurarine: Concurrent administration of diphenoxylate/difenoxin with neuromuscular blockers can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Umeclidinium: There is the potential for umeclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufaturer, avoid concomitant administration of umeclidinium with other anticholinergic medications when possible.
    Umeclidinium; Vilanterol: There is the potential for umeclidinium to have additive anticholinergic effects when administered with other anticholinergics or antimuscarinics. Per the manufaturer, avoid concomitant administration of umeclidinium with other anticholinergic medications when possible.
    Vecuronium: Concurrent administration of diphenoxylate/difenoxin with neuromuscular blockers can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Zaleplon: Concurrent administration of diphenoxylate/difenoxin with anxiolytics, sedatives, and hypnotics can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Ziprasidone: Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including diphenoxylate/difenoxin.
    Zolpidem: Concurrent administration of diphenoxylate/difenoxin with anxiolytics, sedatives, and hypnotics can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration.
    Zonisamide: Zonisamide use is associated with case reports of decreased sweating, hyperthermia, heat intolerance, or heat stroke and should be used with caution in combination with other drugs that may also predispose patients to heat-related disorders like anticholinergics.

    PREGNANCY AND LACTATION

    Pregnancy

    Atropine; diphenoxylate is classified as FDA pregnancy risk category C. Adequate studies in pregnant women have not been conducted; therefore, atropine; diphenoxylate should be used during pregnancy only when clearly needed.

    According to the manufacturer, caution should be exercised when administering atropine; diphenoxylate to a nursing woman. The active metabolite of diphenoxylate, diphenoxylic acid, and atropine are excreted into breast milk. Incompatibilities with breast-feeding have not been reported. An alternate, such as loperamide, which is considered usually compatible with breast-feeding by the American Academy of Pediatrics, may be considered. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Diphenoxylate: Diphenoxylate appears to exert its effect locally and centrally on the smooth mucle cells of the GI tract to inhibit GI motility and slow excess GI propulsion. Unlike morphine, this agent does not possess analgesic activity or opiate-like effects at recommended dosages. In higher doses, diphenoxylate can cause euphoria and physical dependence, and the administration of opiate antagonists can cause withdrawal symptoms in patients who have been receiving high doses of diphenoxylate.
    Atropine: The anticholinergic effects of atropine are generally insignificant when Lomotil(R) is used in normal doses. However, signs of atropinism (e.g., dryness of the skin and mucous membranes, and tachycardia) may become evident in children at recommended doses.

    PHARMACOKINETICS

    Atropine; diphenoxylate is administered orally. Diphenoxylate is extensively metabolized by the liver to an active metabolite diphenoxylic acid, which has a half-life of 3—14 hours, and to inactive metabolites. These metabolites are excreted primarily in the feces via the bile. A small amount of a dose is excreted in the urine. Therapeutic concentrations of atropine are not expected.

    Oral Route

    Following oral administration of atropine; diphenoxylate, diphenoxylate is almost completely absorbed (90%) following oral administration, and the onset of action usually occurs within 45 minutes to 1 hour. The drug has a duration of effect of 3—4 hours.