diphenoxylate hydrochloride and atropine sulfate
Lofene, Logen, Lomanate, Lomotil, Lonox

Available forms
Available by prescription only
Liquid: 2.5 mg diphenoxylate hydrochloride and 0.025 mg atropine sulfate/5 ml
Tablets: 2.5 mg diphenoxylate hydrochloride and 0.025 mg atropine sulfate per tablet

Indications and dosages
 Acute, nonspecific diarrhea. Adults: 5 mg diphenoxylate component P.O. q.i.d.; then adjust, p.r.n.
Children age 2 and older: 0.3 to 0.4 mg/kg diphenoxylate component P.O. daily in four divided doses using the liquid form; or administer according to diphenoxylate component, as follows:
Children ages 8 to 12: 2 mg P.O. five times daily.
Children ages 5 to 8: 2 mg P.O. q.i.d.
Children ages 2 to 5: 2 mg P.O. t.i.d.

Pharmacodynamics
Antidiarrheal action: Diphenoxylate is a meperidine analogue that inhibits GI motility locally and centrally. In high doses, it may produce an opiate effect. Atropine is added in subtherapeutic doses to prevent abuse by deliberate overdose.

Pharmacokinetics
Absorption: About 90% of an oral dose is absorbed.
Distribution: Distributed in breast milk.
Metabolism: Metabolized extensively by the liver.
Excretion: Metabolites are excreted mainly in feces via the biliary tract, with lesser amounts excreted in urine.

Contraindications and precautions
Contraindicated in patients hypersensitive to diphenoxylate or atropine and in patients with acute diarrhea caused by poison (until toxic material is eliminated from GI tract), acute diarrhea caused by organisms that penetrate intestinal mucosa, or diarrhea resulting from antibiotic-induced pseudomembranous enterocolitis or enterotoxin-producing bacteria. Also contraindicated in patients with obstructive jaundice and in children younger than age 2.
  Use cautiously in children age 2 and older; in patients with hepatic disease, narcotic dependence, or acute ulcerative colitis; and in pregnant women. Stop therapy immediately if abdominal distention or other signs of toxic megacolon develop.

Interactions
Drug-drug. CNS depressants such as barbiturates, narcotic agents, tranquilizers: Increases depressant effect. Avoid use together.
MAO inhibitors: Increases risk of hypertensive crisis. Avoid use together.
Drug-lifestyle. Alcohol use: May enhance CNS depression. Discourage alcohol use.

Adverse reactions
CNS: sedation, dizziness, headache, drowsiness, lethargy, restlessness, depression, euphoria, malaise, confusion, hyperthermia, numbness in limbs.
CV: tachycardia.
EENT: mydriasis.
GI: dry mouth, nausea, vomiting, abdominal discomfort or distention, paralytic ileus, anorexia, fluid retention in bowel or megacolon, increased serum amylase, pancreatitis, swollen gums, possible physical dependence with long-term use.
GU: urine retention.
Respiratory: respiratory depression.
Skin: pruritus, rash, dry skin, flushing, urticaria.
Other: angioedema, anaphylaxis.

Effects on lab test results
None reported.

Overdose and treatment
Effects of overdose include drowsiness, low blood pressure, marked seizures, apnea, blurred vision, miosis, flushing, dry mouth and mucous membranes, and psychotic episodes.
 Treatment is supportive; maintain airway and support vital functions. A narcotic antagonist such as naloxone may be given. Emesis, gastric lavage, and administration of activated charcoal may be performed. Mechanical respiration may be needed. Monitor patient for 48 to 72 hours.

Special considerations
• Fluid retention in the bowel or megacolon may mask depletion of extracellular fluid and electrolytes, especially in young children treated for acute gastroenteritis.
• Drug is usually ineffective in treating antibiotic-induced diarrhea.
• Reduce dosage as soon as symptoms are controlled.
Breast-feeding patients
• Drug appears in breast milk; drug effects have been reported in breast-fed infants of women taking drug.
Pediatric patients
• Drug is contraindicated in children younger than age 2; some children may experience respiratory depression.
• Children, especially those with Down syndrome, appear to be particularly sensitive to atropine content of drug.
Geriatric patients
• Elderly patients may be more susceptible to respiratory depression and to exacerbation of glaucoma.

Patient education
• Warn patient to take drug exactly as prescribed and not to exceed recommended dose.
• Advise patient to maintain adequate fluid intake during course of diarrhea and teach him about diet and fluid replacement.
• Caution patient to avoid driving during therapy because drowsiness and dizziness may occur.
• Advise patient to call if drug isn’t effective within 48 hours.
• Warn patient that prolonged use may result in tolerance and that use of larger-than-recommended doses may result in drug dependence.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use