diphenoxylate/atropine

Contraindicated in:

Hypersensitivity;
Severe liver disease;
Infectious diarrhea (due to Escherichia coli, Salmonella, or Shigella);
Diarrhea associated with Clostridioides difficile-associated diarrhea;
Dehydration;
Angle-closure glaucoma;
Pedi: Children <2 yr (for diphenoxylate/atropine).

Use Cautiously in:

Physical dependence on opioids;
Inflammatory bowel disease;
Prostatic hyperplasia;
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Children <12 yr (safety and effectiveness of difenoxin/atropine not established);
Geri: Older adults more sensitive to effects.

Adv. Reactions/Side Effects ⬆ ⬇

CV: tachycardia

Derm: flushing

EENT: blurred vision, dry eyes

GI: constipation, dry mouth, epigastric distress, ileus, nausea, vomiting

GU: urinary retention

Neuro: dizziness, confusion, drowsiness, headache, insomnia, nervousness

Interactions ⬆ ⬇

Drug-drug:

Additive CNS depression with other CNS depressants, including alcohol, antihistamines, opioid analgesics, and sedative/hypnotics.
Additive anticholinergic properties with other drugs having anticholinergic properties, including tricyclic antidepressants and disopyramide.
Use with MAO inhibitors may result in hypertensive crisis.

Drug-Natural Products:

↑anticholinergic effects with angel’s trumpet, jimson weed, and scopolia.

Availability ⬆ ⬇

Difenoxin/Atropine

Tablets: 1 mg difenoxin/0.025 mg atropine

Diphenoxylate/Atropine

(Generic available)

Tablets: 2.5 mg diphenoxylate/0.025 mg atropine

Route/Dosage ⬆ ⬇

Difenoxin/Atropine

Doses given are in terms of difenoxin; each tablet contains 1 mg difenoxin with 0.025 mg of atropine
PO (Adults ): 2 tablets initially; then 1 tablet after each loose stool or every 3–4 hr as needed (not to exceed 8 tablets/day).

Diphenoxylate/Atropine

PO (Adults ): 5 mg of diphenoxylate 3–4 times daily initially; then 5 mg of diphenoxylate once daily as needed (not to exceed 20 mg/day).

US Brand Names ⬆ ⬇

diphenoxylate/atropine: Lomotil,

difenoxin/atropine : Motofen

Action ⬆ ⬇

Inhibits excess GI motility.
Structurally related to opioid analgesics but has no analgesic properties.
Atropine added to discourage abuse.

Therapeutic effects:

Decreased GI motility with subsequent decrease in diarrhea.

Classifications ⬆ ⬇

Therapeutic Classification: antidiarrheals

Pharmacologic Classification: anticholinergics

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed from the GI tract.

Distribution: Enters breast milk.

Metabolism/Excretion: Diphenoxylate: Mostly metabolized by the liver with some conversion to an active antidiarrheal compound (difenoxin). Difenoxin: Metabolized by the liver. Minimal excretion in urine.

Half-Life: Diphenoxylate: 2.5 hr; difenoxin: 4.5 hr.

Contr. Subst. Schedule ⬆ ⬇

Schedule V (C-V)diphenoxylate/atropine
Schedule IV (C-IV)difenoxin/atropine

Time/Action Profile ⬆ ⬇

(antidiarrheal action)

ROUTE	ONSET	PEAK	DURATION
Difenoxin-PO	45–60 min	2 hr	3–4 hr
Diphenoxylate-PO	45–60 min	2 hr	3–4 hr

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Instruct patient to take as directed. Do not take more than the prescribed amount because of the habit-forming potential and risk of overdose in children. If on a scheduled dosing regimen, missed doses should be taken as soon as possible unless almost time for next dose. Do not double doses. Advise patient that treatment of acute diarrhea should be continued for 24–36 hr before it is considered ineffective.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Medication may cause drowsiness. Advise patient to avoid driving or other activities requiring alertness until response to drug is known.
Advise patient that frequent mouth rinses, good oral hygiene, and sugarless gum or candy may relieve dry mouth.
Caution patient to avoid alcohol and other CNS depressants concurrently with this medication.
Advise patient to inform health care professional of medication regimen prior to treatment or surgery.
Instruct patient to notify health care professional if diarrhea persists or if fever, abdominal pain, or palpitations occur.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Indications ⬇

Contraind./Precautions ⬆ ⬇