(dye fen OKS i late & A troe peen)
Diarrhea: Adjunctive management of diarrhea
Hypersensitivity to diphenoxylate, atropine, or any component of the formulation; obstructive jaundice; diarrhea associated with pseudomembranous enterocolitis or enterotoxin-producing bacteria
Canadian labeling: Additional contraindications (not in US labeling): Jaundice
Diarrhea: Oral: Note: If no improvement within 48 hours (acute symptoms) or 10 days at maximum dose (chronic symptoms) therapy is likely to be ineffective.
Initial: Diphenoxylate 5 mg (2 tablets) 3 or 4 times daily until control achieved (maximum: 20 mg/day), then reduce dose as needed; maintenance doses may be as low as 25% of initial daily dose required for control.
Refer to adult dosing.
Diarrhea: Note: If no improvement within 48 hours (acute symptoms) therapy is likely to be ineffective.
US labeling: Children ≥2 years to <13 years (liquid only): Oral:
Initial: Diphenoxylate 0.3 to 0.4 mg/kg/day in 4 divided doses or alternatively:
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 12 years (23 to 55 kg): 3.5 to 5 mL 4 times daily
Maintenance: Doses may be as low as 25% of initial daily dose; reduce dose as soon as possible after symptoms have been controlled
Canadian labeling: ≥4 years and Adolescents: Oral: Initial: Diphenoxylate 0.3 to 0.4 mg/kg/day in divided doses or alternatively:
4 to 8 years (20 to 27 kg): 2.5 mg 3 times daily
9 to 12 years (27 to 36 kg): 2.5 mg 4 times daily
≥13 years: 5 mg 4 times daily
There are no specific dosage adjustments provided in the manufacturer 's labeling. Use with extreme caution in patients with advanced hepatorenal disease.
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.
Use of the liquid preparation is recommended in children <13 years of age; use only plastic dropper provided when measuring liquid. 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 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F); protect from light.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Oral: Diphenoxylate hydrochloride 2.5 mg and atropine sulfate 0.025 mg per 5 mL (5 mL, 10 mL, 60 mL)
Lomotil: Diphenoxylate hydrochloride 2.5 mg and atropine sulfate 0.025 mg per 5 mL (60 mL) [contains alcohol 15%; cherry flavor] [DSC]
Tablet, Oral: Diphenoxylate hydrochloride 2.5 mg and atropine sulfate 0.025 mg
Lomotil: Diphenoxylate hydrochloride 2.5 mg and atropine sulfate 0.025 mg
AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy
Analgesics (Opioid): Anticholinergic Agents may enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy
Dimethindene: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination
EPHEDrine (Systemic): Atropine (Systemic) may enhance the therapeutic effect of EPHEDrine (Systemic). Monitor therapy
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy
Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy
Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification
Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. 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. Avoid combination
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy
RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to secretin. Consider therapy modification
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. 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. Consider therapy modification
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
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. Consider therapy modification
Watch 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
Frequency not defined.
Cardiovascular: Flushing, tachycardia
Central nervous system: Confusion, depression, dizziness, drowsiness, euphoria, headache, hyperthermia, lethargy, malaise, numbness, restlessness, sedation
Dermatologic: Pruritus, urticaria, xeroderma
Gastrointestinal: Abdominal distress, anorexia, gingival swelling, nausea, pancreatitis, paralytic ileus, toxic megacolon, vomiting, xerostomia
Genitourinary: Urinary retention
Hypersensitivity: Anaphylaxis, angioedema
Concerns related to adverse effects:
- 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).
- 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.
- Renal impairment: Use with caution in patients with renal impairment.
- Ulcerative colitis: Use with caution in patients with acute ulcerative colitis.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
Special populations:
- Pediatric: Use with caution in children; not recommended for use in children <2 years of age (US labeling) or <4 years (Canadian labeling). Younger children may be predisposed to delayed toxicity; signs of atropinism may occur even at recommended doses, especially in patients with Down syndrome.
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 there is no response within 48 hours in children, diphenoxylate/atropine is unlikely to be effective and should be discontinued. If chronic diarrhea is not improved symptomatically within 10 days at maximum dosage, control is unlikely with further use. Reduction of intestinal motility may be deleterious in diarrhea resulting from Shigella, Salmonella, toxigenic strains of E. coli, and pseudomembranous enterocolitis associated with broad-spectrum antibiotics; use is not recommended.
- Dependence: Physical and psychological dependence have been reported with higher than recommended dosing.
C
Animal reproduction studies have not been conducted with this combination. Refer to individual agents.
Diphenoxylate inhibits excessive GI motility and GI propulsion; commercial preparations contain a subtherapeutic amount of atropine to discourage abuse
Diphenoxylate: Well absorbed
Diphenoxylate: Extensively hepatic via ester hydrolysis to diphenoxylic acid (active)
Diphenoxylate: Primarily feces (49% as unchanged drug and metabolites); urine (~14%, [<1%] and metabolites)
Within 45 to 60 minutes
Diphenoxylate: Serum: ~2 hours
Diphenoxylate: 2.5 hours; Diphenoxylic acid: 12 to 14 hours
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience dry mouth, fatigue, dizziness, or headache. Have patient report immediately to prescriber signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), signs of fluid and electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, very bad dizziness or passing out, fast heartbeat, more thirst, seizures, feeling very tired or weak, not hungry, unable to pass urine or change in the amount of urine produced, dry mouth, dry eyes, or nausea or vomiting), difficulty breathing, slow breathing, shallow breathing, burning or numbness feeling, tachycardia, difficult urination, mood changes, vision changes, confusion, severe constipation, severe abdominal pain, or abdominal edema (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.