Usage
Atropine + Diphenoxylate is prescribed for the treatment of acute and chronic diarrhea. It belongs to the antidiarrheal pharmacological classification. The medication works by slowing intestinal motility and reducing fecal volume.
Alternate Names
This combination drug is also known as co-phenotrope. Brand names include Lomotil, Atridol, Atrolate, Atrotil, Co-Phenotrope, Dhamotil, Dimotil, Intard, Logen, Lomanate, Lonox, and Reasec.
How It Works
Pharmacodynamics: Diphenoxylate acts on opioid receptors in the gut, reducing peristalsis (intestinal contractions). Atropine, an anticholinergic, counteracts potential opioid side effects and further decreases motility by reducing gastrointestinal secretions.
Pharmacokinetics:
- Absorption: Diphenoxylate is well-absorbed from the gastrointestinal tract. Atropine is rapidly absorbed.
- Metabolism: Diphenoxylate is primarily metabolized in the liver to diphenoxylic acid, an active metabolite. Atropine is also metabolized in the liver.
- Elimination: Metabolites are primarily excreted in the feces and a small amount in urine.
Mode of Action: Diphenoxylate acts on mu opioid receptors in the gut to inhibit peristalsis and reduce intestinal motility. Atropine exerts its anticholinergic effects by competitively inhibiting the actions of acetylcholine at muscarinic receptors, further decreasing gastrointestinal motility and secretions.
Elimination pathways: Primarily hepatic metabolism followed by fecal excretion. A small amount of the drug is excreted unchanged in urine.
Dosage
Standard Dosage
Adults:
Initial dose: 5 mg (two tablets or 10 mL) four times daily.
Maintenance dose: After initial control, the dose can be reduced to as little as 5 mg once daily.
Maximum dose: 20 mg of diphenoxylate per day.
Children:
- Children younger than 6 years: Not recommended due to the risk of serious side effects.
- Children 6 to 12 years: Use liquid formulation only. Initial: 0.3 to 0.4 mg diphenoxylate/kg/day in four divided doses. Adjust dosage based on weight and response. See detailed pediatric dosing guidelines in sources for mL-based doses for different age groups.
- Children 13 years and older: Same as adult dose.
Special Cases:
- Elderly Patients: Start with a lower dose and monitor closely for adverse effects.
- Patients with Renal Impairment: Use with caution. Monitor renal function. Dosage adjustments may be necessary.
- Patients with Hepatic Dysfunction: Use with caution. Monitor liver function. Dosage adjustments may be necessary.
- Patients with Comorbid Conditions: Use with caution in patients with glaucoma, acute ulcerative colitis, or obstructive jaundice.
Clinical Use Cases
Atropine + Diphenoxylate is generally not indicated for use in specific clinical settings like intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations. Its use is limited to the management of diarrhea.
Dosage Adjustments
Adjustments should be based on the patient’s response to treatment and the presence of any comorbid conditions. Close monitoring is crucial, especially in elderly patients and those with renal or hepatic impairment.
Side Effects
Common Side Effects:
Drowsiness, dizziness, headache, nausea, vomiting, dry mouth, constipation, abdominal discomfort.
Rare but Serious Side Effects:
Respiratory depression, paralytic ileus, toxic megacolon (especially in patients with ulcerative colitis), anticholinergic toxicity (tachycardia, hyperthermia, urinary retention, confusion).
Long-Term Effects:
Potential for dependence with prolonged use at high doses.
Adverse Drug Reactions (ADR):
Anaphylaxis, angioedema, severe anticholinergic effects.
Contraindications
- Hypersensitivity to diphenoxylate or atropine
- Children under 6 years of age (tablet form)
- Obstructive jaundice
- Diarrhea associated with pseudomembranous colitis or enterotoxin-producing bacteria
Drug Interactions
- CNS depressants: Increased risk of respiratory depression and sedation.
- MAO inhibitors: Potential for hypertensive crisis.
- Anticholinergics: Enhanced anticholinergic effects.
- Opioid analgesics: Increased risk of CNS and respiratory depression.
Pregnancy and Breastfeeding
Pregnancy Safety Category: C. Use with caution during pregnancy only if clearly needed. Both diphenoxylate and atropine can be excreted in breast milk, potentially causing adverse effects in the infant.
Drug Profile Summary
- Mechanism of Action: Slows intestinal motility via opioid receptor agonism (diphenoxylate) and anticholinergic effects (atropine).
- Side Effects: Drowsiness, dizziness, dry mouth, constipation, abdominal discomfort; rarely, respiratory depression, paralytic ileus, toxic megacolon, anticholinergic toxicity.
- Contraindications: Hypersensitivity, children <6 years (tablets), obstructive jaundice, diarrhea associated with specific infections.
- Drug Interactions: CNS depressants, MAO inhibitors, anticholinergics, opioids.
- Pregnancy & Breastfeeding: Use with caution; excreted in breast milk.
- Dosage: Adults: Initially 5 mg four times daily, then reduce as needed. Children 6-12 years: Liquid formulation only, dose based on weight. Not recommended for children <6 years.
- Monitoring Parameters: Stool frequency and consistency, signs of dehydration, respiratory status, and anticholinergic effects.
Popular Combinations
Not typically used in combination with other drugs for diarrhea management.
Precautions
- Use with caution in patients with hepatic or renal impairment, glaucoma, or a history of drug dependence.
- Avoid alcohol.
- May cause drowsiness; avoid driving or operating machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Atropine + Diphenoxylate?
A: Adults: 5 mg four times a day initially, then reduce as needed. Children 6-12 years: Use liquid formulation, dose based on weight. Not for children under 6 years old.
Q2: What are the common side effects?
A: Drowsiness, dizziness, dry mouth, constipation, and abdominal discomfort.
Q3: Is Atropine + Diphenoxylate safe during pregnancy?
A: Pregnancy Category C. Use with caution only if clearly needed. Discuss risks and benefits with the patient.
Q4: Can Atropine + Diphenoxylate be used in children?
A: Not recommended for children under 6 years. Use liquid formulation only for children aged 6-12. Adjust dose based on weight. Adult dosing for children 13 and older.
Q5: What are the contraindications for this medication?
A: Hypersensitivity to the drug, children under 6 years (tablet form), obstructive jaundice, and diarrhea caused by certain infections (e.g., C. difficile, E. coli, Salmonella, Shigella).
Q6: How does Atropine + Diphenoxylate work?
A: Diphenoxylate decreases intestinal motility by acting on opioid receptors in the gut. Atropine, an anticholinergic, helps to reduce secretions and further slows bowel movements.
Q7: What should I monitor in a patient taking this medication?
A: Monitor stool frequency and consistency, fluid and electrolyte balance, signs of dehydration, respiratory status, and any potential anticholinergic effects.
Q8: What are the signs of an overdose?
A: Dry mouth, blurred vision, flushing, rapid heart rate, urinary retention, confusion, and respiratory depression.
Q9: Are there any significant drug interactions?
A: Yes. It interacts with CNS depressants (e.g., alcohol, benzodiazepines), MAO inhibitors, other anticholinergic medications, and opioid analgesics. Concurrent use should be avoided or carefully monitored.
