diphenoxylate/atropine

diphenoxylate/atropine: dye-fen-OX-i-late/A-troe-peen

difenoxin/atropine : dye-fen-OX-in/A-troe-peen

Classifications ⬆ ⬇

Therapeutic Classification: antidiarrheals

Pharmacologic Classification: anticholinergics

Indications ⬆ ⬇

REMS

Adjunctive therapy in the treatment of diarrhea.

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.

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.

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

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Severe liver disease;
Infectious diarrhea (due to
Escherichia coli
,
Salmonella
, or
Shigella
);
Diarrhea associated with
Clostridioides difficile
-associated diarrhea (CDAD);
Dehydrated patients;
Angle-closure glaucoma;
Known alcohol intolerance (some liquid diphenoxylate/atropine products only).
Pedi: Children 2 yr (for diphenoxylate/atropine);

Use Cautiously in:

Patients physically dependent on opioids;
Inflammatory bowel disease;
Prostatic hyperplasia;
OB: Safety not established in pregnancy or lactation;
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.

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

Adult doses given are in terms of diphenoxylate—each tablet contains 2.5 mg diphenoxylate with 0.025 mg of atropine; pediatric doses are given in mg of diphenoxylate and in mL of diphenoxylate/atropine liquid; each 5 mL of liquid contains 2.5 mg diphenoxylate with 0.025 mg of atropine
PO (Adults ): 5 mg 3–4 times daily initially, then 5 mg once daily as needed (not to exceed 20 mg/day).
PO (Children ): use liquid only: 0.3–0.4 mg/kg/day in 4 divided doses.

Availability ⬆ ⬇

Difenoxin/Atropine

Tablets: 1 mg difenoxin/0.025 mg atropine

Diphenoxylate/Atropine

(Generic available)

Tablets: 2.5 mg diphenoxylate/0.025 mg atropine
Liquidcherry flavor: 2.5 mg diphenoxylate/0.025 mg atropine per 5 mL

Assessment ⬆ ⬇

Assess the frequency and consistency of stools and bowel sounds prior to and throughout therapy.
Assess patient's fluid and electrolyte balance and skin turgor for dehydration.

Lab Test Considerations:

Evaluate liver function tests periodically during prolonged therapy.
- Diphenoxylate/atropine may cause increased serum amylase concentrations.

Implementation ⬆ ⬇

Risk of dependence increases with high-dose, long-term use. Atropine has been added to discourage abuse.
PO: Diphenoxylate/atropine tablets may be administered with food if GI irritation occurs. Tablets may be crushed and administered with patient’s fluid of choice. Use calibrated measuring device for liquid preparations.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication 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.
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.
Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

section name header

Pronunciation ⬇