Diphenoxylate + Atropine


Concise Prescribing Info
Indications/Uses
Diarrhoea.
Dosage/Direction for Use
Adult : PO Each tab or 5 mL soln contains diphenoxylate HCl 2.5 mg and atropine sulphate 0.025 mg: Initial: 5 mg 4 times/day, may reduce to 5 mg/day once satisfactory control is achieved. Max: 20 mg/day.
Dosage Details
Oral
Diarrhoea
Adult: Each tab or 5 mL soln contains diphenoxylate HCl 2.5 mg and atropine sulphate 0.025 mg: Initially, 5 mg 4 times daily, may reduce dose to 5 mg daily once satisfactory control is achieved. Max: 20 mg daily.
Child: As oral soln: Recommended dose: 2 yr 1.5-3 mL. 3 yr 2-3 mL. 4 yr 2-4 mL. 5 yr 2.5-4.5 mL. 6-8 yr 2.5-5 mL. 9-12 yr 3.5-5 mL. Dose is given 4 times daily.
Administration
May be taken with or without food.
Contraindications
Jaundice, intestinal obstruction, acute ulcerative colitis, raised intracranial pressure, head injury, myasthenia gravis, pyloric stenosis, paralytic ileus, prostatic enlargement. Childn <2 yr.
Special Precautions
Patient w/ history of physical dependence, cirrhosis or advanced hepatorenal disease. Hepatic and renal impairment. Childn. Pregnancy and lactation. Not indicated as treatment for diarrhoea associated w/ pseudomembranous colitis or enterotoxin-producing bacteria.
Adverse Reactions
Significant: Intestinal fluid retention.
Nervous: Sedation, dizziness, drowsiness, lethargy, restlessness or insomnia, headache, numbness of extremities, euphoria, mental depression, weakness, general malaise, confusion.
CV: Tachycardia, flushing.
GI: Nausea, vomiting, abdominal discomfort or distention, dry mouth, swollen gums, anorexia, pancreatitis, paralytic ileus.
Hepatic: Toxic megacolon.
Genitourinary: Urinary retention.
Ophthalmologic: Blurred vision.
Dermatologic: Pruritus, angioedema, giant urticaria, dryness of skin and mucous membrane.
Potentially Fatal: Resp depression, coma.
Patient Counseling Information
This drug may cause CNS depression, drowsiness, or dizziness, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor for signs of atropism (e.g. dryness of skin and mucous membranes, tachycardia, thirst, flushing), number and consistency of stools. Assess signs of toxicity, fluid and electrolyte loss, hypotension, and resp depression.
Overdosage
Symptoms: Dryness of skin and mucous membrane, flushing, hypothermia, tachycardia, nystagmus, pinpoint pupils, hypotonic reflexes, lethargy, coma, and severe resp depression. Management: Establish patient airway and artificial ventilation may be needed. Employ gastric lavage and admin of slurry of an activated charcoal for conscious patients may be indicated. Administer naloxone to reverse resp depression.
Drug Interactions
Increased antimuscarinic side effects w/ amantadine, antihistamines, and TCAs. Antagonises the effect of domperidone, metoclopramide, bethanechol, carbachol, cisapride, galantamine, neostigomine, pyridostigmine, and pilocarpine. May potentiate CNS depressant effects of barbiturates and tranquilizers. May precipitate hypertensive crisis when concomitantly used w/ MAOIs. May reduce absorption of ketoconazole. May reduce plasma concentration of levodopa. Increased effect w/ memantine.
Food Interaction
May potentiate CNS depressant effect of alcohol.
Action
Description: Diphenoxylate, a synthetic opioid derivative, is an antidiarrhoeal agent acting on smooth muscle of the intestinal tract, inhibiting excessive GI motility and propulsion. Commercial preparations contain subtherapeutic amount of atropine, an antimuscarinic agent, to counteract its abuse.
Pharmacokinetics:
Absorption: Diphenoxylate: Well absorbed from the GI tract. Bioavailability: Approx 90%. Time to peak plasma concentration: Approx 2 hr. Atropine: Rapidly and well absorbed.
Distribution: Diphenoxylate: Enters breast milk. Atropine: Widely distributed throughout the body; crosses the blood brain barrier and enters breast milk. Plasma protein binding: 14-22%.
Metabolism: Diphenoxylate: Rapidly and extensively metabolised in the liver via ester hydrolysis to diphenoxylic acid, an active metabolite, and hydroxydiphenoxylic acid. Atropine: Metabolised in the liver via enzymatic hydrolysis.
Excretion: Diphenoxylate: Mainly via faeces (49% as unchanged drug and metabolites) and urine (approx 14% as unchanged drug). Elimination half-life: 2.5 hr. Atropine: Via urine (13-50% as unchanged drug and metabolites).
Chemical Structure

Chemical Structure Image

Source: National Center for Biotechnology Information. PubChem Database. Diphenoxylate, CID=13505, https://pubchem.ncbi.nlm.nih.gov/compound/Diphenoxylate (accessed on Jan. 21, 2020)


Chemical Structure Image
Atropine

Source: National Center for Biotechnology Information. PubChem Database. Atropine, CID=174174, https://pubchem.ncbi.nlm.nih.gov/compound/dl-Hyoscyamine (accessed on Jan. 21, 2020)

Storage
Store between 20-25°C. Tab: Protect from light.
MIMS Class
References
Anon. Atropine (Systemic). Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 22/06/2017.

Anon. Diphenoxylate and Atropine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/06/2017.

Buckingham R (ed). Diphenoxylate Hydrochloride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/06/2017.

Diphenoxylate Hydrochloride and Atropine Sulfate Solution (West-Ward Pharmaceuticals Corp.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 02/06/2017.

Diphenoxylate Hydrochloride and Atropine Sulfate Tablet (Greenstone LLC). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 02/06/2017.

Joint Formulary Committee. Co-phenotrope. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 22/06/2017.

McEvoy GK, Snow EK, Miller J et al (eds). Diphenoxylate Hydrochloride. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 02/06/2017.

Disclaimer: This information is independently developed by MIMS based on Diphenoxylate + Atropine from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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