Diarrhea, adjunct therapy: Note: Only the liquid product is recommended for use in children under 13 years of age; do not exceed recommended doses; reduce dose as soon as symptoms are initially controlled; maintenance doses may be as low as 25% of initial dose; if no improvement within 48 hours of therapy, diphenoxylate is not likely to be effective
Weight-directed dosing: Children 2 to 12 years: Oral: Liquid (2.5 mg diphenoxylate and 0.025 mg atropine per 5 mL): Initial: Diphenoxylate: 0.3 to 0.4 mg/kg/day in 4 divided doses, reduce dose as soon as symptoms controlled; maximum daily dose: 10 mg/day diphenoxylate
Age-directed fixed dosing:
Children ≥2 years: Oral: Liquid (2.5 mg diphenoxylate and 0.025 mg atropine per 5 mL):
2 years (11 to 14 kg): 1.5 to 3 mL 4 times daily
3 years (12 to 16 kg): 2 to 3 mL 4 times daily
4 years (14 to 20 kg): 2 to 4 mL 4 times daily
5 years (16 to 23 kg): 2.5 to 4.5 mL 4 times daily
6 to 8 years (17 to 32 kg): 2.5 to 5 mL 4 times daily
9 to <13 years (23 to 55 kg): 3.5 to 5 mL 4 times daily
Adolescents: Oral (liquid [2.5 mg diphenoxylate and 0.025 mg atropine per 5 mL] or tablets [2.5 mg diphenoxylate and 0.025 mg atropine per tablet]): Initial: Diphenoxylate: 5 mg 4 times daily until control achieved; maximum daily dose: 20 mg/day. Once control achieved, reduce dose as needed; maintenance doses may be as low as 25% of initial daily dose required for control.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling. Use with extreme caution in patients with advanced hepatorenal disease.
There are no dosage adjustments provided in the manufacturer's labeling. Use with extreme caution in patients with abnormal hepatic function and in advanced hepatorenal disease.
(For additional information see "Diphenoxylate and atropine: Drug information")
Diarrhea, adjunct therapy:
Oral: Initial: Diphenoxylate 5 mg/atropine sulfate 0.05 mg (2 tablets or 10 mL) 4 times daily until control achieved, usually within 48 hours; maximum daily dose: diphenoxylate 20 mg/atropine 0.2 mg per day (8 tablets or 40 mL per day). Reduce dose as needed once control is achieved; maintenance doses may be as low as 25% of initial daily dose required for control. Discontinue use if clinical improvement is not seen within 10 days of dosing with the maximum dose.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: The amount of atropine in commercial preparations is subtherapeutic and unlikely to accumulate when used in recommended doses.
Altered kidney function: No dosage adjustment necessary for any degree of kidney impairment (limited excretion of diphenoxylate in the urine) (Ref).
Hemodialysis, intermittent (thrice weekly): Diphenoxylate is unlikely to be dialyzed (large volume of distribution): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Diphenoxylate is unlikely to be dialyzed (large volume of distribution): No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).
There are no specific dosage adjustments provided in the manufacturer's labeling. Use with extreme caution in patients with abnormal hepatic function and in advanced hepatorenal disease as use may precipitate hepatic encephalopathy resulting in coma.
The following adverse drug reactions are derived from product labeling unless otherwise specified.
Postmarketing:
Dermatologic: Pruritus, urticaria
Gastrointestinal: Abdominal distress, anorexia, gingival swelling, nausea, non-Hirschsprung megacolon, pancreatitis, paralytic ileus, toxic megacolon, vomiting
Hypersensitivity: Anaphylaxis, angioedema
Nervous system: Confusion, depression, dizziness, drowsiness, euphoria, hallucination, headache, lethargy, malaise, numbness of extremities, restlessness, sedated state
Hypersensitivity to diphenoxylate, atropine, or any component of the formulation; obstructive jaundice; diarrhea associated with pseudomembranous enterocolitis (Clostridioides difficile) or other enterotoxin-producing bacteria; pediatric patients <6 years of age (tablets only).
Canadian labeling: Additional contraindications (not in US labeling): Jaundice
Concerns related to adverse effects:
• Atropinism: Use may cause atropinism (hyperthermia, tachycardia, urinary retention, flushing, dryness of the skin and mucous membranes), particularly in pediatric patients with Down syndrome. Monitor patients for signs of atropinism.
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).
• GI effects: Use may slow GI motility and may enhance bacterial overgrowth and the release of bacterial exotoxins; has been reported to result in serious GI complications in patients with infectious diarrhea, including sepsis, prolonged and/or worsened diarrhea. Use is contraindicated in patients with diarrhea associated with organisms that penetrate the GI mucosa (toxigenic E. coli, Salmonella, Shigella), and pseudomembranous enterocolitis (Clostridioides difficile) associated with broad-spectrum antibiotics.
• Dehydration/electrolyte imbalance: In case of severe dehydration or electrolyte imbalance, withhold diphenoxylate/atropine treatment until corrective therapy has been initiated. Use in conjunction with fluid and electrolyte therapy when appropriate. Inhibiting peristalsis may lead to fluid retention in the intestine aggravating dehydration and electrolyte imbalance.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment or advanced hepatorenal disease (hepatic coma may be precipitated).
• Renal impairment: Use with caution in patients with renal impairment or advanced hepatorenal disease.
• Ulcerative colitis: Use with caution in patients with acute ulcerative colitis; use may induce toxic megacolon. Monitor patients with acute ulcerative colitis carefully and discontinue promptly if abdominal distention occurs or if other untoward symptoms develop.
Special populations:
• Pediatric: Cases of severe respiratory depression and coma, leading to permanent brain damage or death have been reported in patients <6 years of age. Use is contraindicated in children <6 years of age (tablets only).
Other warnings/precautions:
• Appropriate use: Do not exceed recommended dosage; overdose may result in severe respiratory depression, coma, and possible permanent brain damage or death. Clinical improvement of acute diarrhea is usually observed within 48 hours. If clinical improvement is not seen within 10 days of dosing with the maximum dose, discontinue use.
• Dependence: Physical and psychological dependence have been reported with higher than recommended dosing.
Large doses of anticholinergics may cause a paradoxical reaction in children characterized by hyperexcitability. Oral solution contains 15% alcohol.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Liquid, Oral:
Generic: Diphenoxylate hydrochloride 2.5 mg and atropine sulfate 0.025 mg per 5 mL (60 mL)
Tablet, Oral:
Lomotil: Diphenoxylate hydrochloride 2.5 mg and atropine sulfate 0.025 mg
Generic: Diphenoxylate hydrochloride 2.5 mg and atropine sulfate 0.025 mg
Yes
Liquid (Diphenoxylate-Atropine Oral)
2.5-0.025 mg/5 mL (per mL): $1.40
Tablets (Diphenoxylate-Atropine Oral)
2.5-0.025 mg (per each): $0.17 - $0.88
Tablets (Lomotil Oral)
2.5-0.025 mg (per each): $3.62
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Lomotil: Diphenoxylate hydrochloride 2.5 mg and atropine sulfate 0.025 mg
C-V
Oral: May be administered with food to decrease GI upset; use calibrated measuring device for administration; household teaspoons should be avoided. Dropper has a 2 mL (1 mg) capacity and is calibrated in increments of 1/2 mL (0.25 mg).
Oral solution: Store at 20°C to 25°C (68°F to 77°F). Discard opened bottle after 90 days.
Tablet: Store at <25°C (<77°F).
Adjunct therapy for the management of diarrhea (FDA approved in ages ≥2 years and adults)
Lomotil may be confused with LaMICtal, LamISIL, lamoTRIgine, Lanoxin, Lasix, loperamide
Beers Criteria: Atropine is identified in the Beers Criteria as a potentially inappropriate medications to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its highly anticholinergic properties and uncertain effectiveness as an antispasmodic (Beers Criteria [AGS 2023]).
KIDs List: Diphenoxylate/atropine, when used in pediatric patients <6 years of age, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be avoided due to risk of respiratory depression and death (strong recommendation; moderate quality of evidence) (PPA [Meyers 2020]).
Lomotil [US, Canada, and multiple international markets] may be confused with Ludiomil brand name for maprotiline [multiple international markets]
Lomotil: Brand name for diphenoxylate [US, Canada, and multiple international markets], but also the brand name for loperamide [Mexico, Philippines]
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Alpha1-Agonists: Atropine (Systemic) may enhance the hypertensive effect of Alpha1-Agonists. Risk C: Monitor therapy
Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Amezinium: Atropine (Systemic) may enhance the stimulatory effect of Amezinium. Risk C: Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Chlorprothixene: Anticholinergic Agents may enhance the anticholinergic effect of Chlorprothixene. Risk C: Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination
CloZAPine: Anticholinergic Agents may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Disulfiram: May enhance the adverse/toxic effect of Products Containing Ethanol. Management: Do not use disulfiram with dosage forms that contain ethanol. Risk X: Avoid combination
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
EPHEDrine (Systemic): Atropine (Systemic) may enhance the therapeutic effect of EPHEDrine (Systemic). Risk C: Monitor therapy
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Macimorelin: Atropine (Systemic) may diminish the diagnostic effect of Macimorelin. Risk X: Avoid combination
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Methotrimeprazine: Products Containing Ethanol may enhance the adverse/toxic effect of Methotrimeprazine. Specifically, a disulfiram-like reaction may occur and CNS depressant effects may be increased. Management: Avoid products containing alcohol in patients treated with methotrimeprazine. Risk X: Avoid combination
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: Diphenoxylate may enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Ornidazole: May enhance the adverse/toxic effect of Products Containing Ethanol. Specifically, a disulfiram-like reaction may occur. Risk X: Avoid combination
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination
Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid combination
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination
Ritodrine: Atropine (Systemic) may enhance the adverse/toxic effect of Ritodrine. Risk C: Monitor therapy
Rivastigmine: Anticholinergic Agents may diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Anticholinergic Agents. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Secnidazole: Products Containing Ethanol may enhance the adverse/toxic effect of Secnidazole. Risk X: Avoid combination
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
Animal reproduction studies have not been conducted with this combination. Refer to individual agents.
Monitor for signs of atropinism (dryness of skin and mucous membranes, tachycardia, thirst, flushing); monitor number and consistency of stools; observe for signs of toxicity, fluid and electrolyte loss, hypotension, and respiratory depression.
Diphenoxylate inhibits excessive GI motility and GI propulsion; commercial preparations contain a subtherapeutic amount of atropine to discourage abuse
Atropine: See Atropine monograph.
Diphenoxylate:
Onset of action: Within 45 to 60 minutes.
Absorption: Well absorbed.
Distribution: Vd: Diphenoxylate: 4.6 L/kg (Baer 2005).
Metabolism: Extensively hepatic via ester hydrolysis to diphenoxylic acid (active).
Bioavailability: ~90%.
Half-life elimination: Diphenoxylate: 2.5 hours; Diphenoxylic acid: 4.4 hours (Baer 2005).
Time to peak, serum: ~2 hours.
Excretion: Primarily feces (49% as unchanged drug and metabolites); urine (~14%, as unchanged drug [<1%] and metabolites).
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