Diphenoxylate and Atropine
Diphenoxylate hydrochloride and atropine sulfate
Also known as: Lomotil · Logen · Lonox · Lomanate · co-phenotrope · R 1132 · NIH 7562 · difenoxilato
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
Audited v13 dosing evidence
Structured calculator evidenceAntitussive agent (extra-label)
Verified clinician required
- q8-12h
NA
Governing clinical context (2)
- ■ May be given with or without food. If your animal vomits or acts sick after receiving the drug on an empty stomach, try giving the next dose with food or a small treat. If vomiting continues, contact your veterinarian.
- Diphenoxylate/atropine tablets should be stored at room temperature of 20°C to 25°C (68°F-77°F). Diphenoxylate/atropine oral solution should be stored at room temperature of 20°C to 25°C (68°F-77°F); avoid freezing.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
Diphenoxylate is a synthetic phenylpiperidine-derivative opiate agonist, structurally related to meperidine. It is primarily used in veterinary medicine as an antidiarrheal and antitussive (cough suppressant) agent, most commonly in dogs.
Key pharmacological features include:
- Motility Modification: It slows gastrointestinal transit time, allowing for greater fluid absorption and reducing diarrhea.
- Abuse Deterrent: Commercial formulations include a sub-therapeutic dose of atropine sulfate. At normal doses, the atropine has no clinical effect, but if taken in excessive amounts, it produces unpleasant anticholinergic side effects (e.g., dry mouth, tachycardia), discouraging abuse.
- Controlled Substance: Due to its opiate nature, it is classified as a Class-V controlled substance.
Clinical Pearl: Use in cats is highly controversial due to the risk of paradoxical excitatory behavior. In dogs weighing less than 10 kg, liquid formulations are strongly preferred to allow for accurate dose titration and avoid accidental overdose from potent tablet forms.
Mechanism of action
Diphenoxylate exerts its effects primarily through interaction with opioid receptors in the gastrointestinal tract and central nervous system:
- GI Motility: Binds to μ-opioid receptors in the enteric nervous system (myenteric plexus) → decreases the release of acetylcholine and prostaglandins → inhibits excessive GI propulsion and increases segmental (non-propulsive) contractions → prolongs intestinal transit time.
- Secretion Reduction: Decreases intestinal secretion induced by cholera toxin, prostaglandin E2, and non-cAMP/cGMP mediated diarrheas. Enhances mucosal fluid and electrolyte absorption.
- Antitussive Effect: Acts directly on the medullary cough center in the brain → depresses the cough reflex.
- Atropine Component: Acts as a competitive antagonist at muscarinic acetylcholine receptors, though its dose in this combination is too low to exert significant systemic anticholinergic effects unless overdosed.
Safety & warnings
Contraindications
- Known hypersensitivity to narcotic analgesics
- Patients receiving monoamine oxidase inhibitors (MAOIs)
- Diarrhea caused by toxic ingestion (until the toxin is eliminated from the GI tract)
- Intestinal obstruction
- Bacterial-induced acute diarrhea (may enhance bacterial proliferation)
Adverse effects
- Constipation
- Bloat
- Sedation
- Paralytic ileus (potential)
- Toxic megacolon (potential)
- Pancreatitis (potential)
- CNS depression or excitation
- Excitatory behavior (especially in cats)
Precautions
Use with caution in patients with respiratory disease, hepatic encephalopathy (hepatic coma may result), hypothyroidism, severe renal insufficiency, adrenocortical insufficiency (Addison's disease), head injuries or increased intracranial pressure, acute abdominal conditions (may obscure diagnosis), and in geriatric or severely debilitated patients.
- Small Dogs: Extreme care is required when dosing dogs under 10 kg; liquid formulations are recommended for accurate titration.
- Cats: Use is controversial and generally not recommended due to potential excitatory behavior.
- Horses/Infectious Diarrhea: Opiates may have a detrimental effect in acute diarrhea by enhancing bacterial proliferation, delaying microbe clearance, and prolonging the febrile state.
- Nursing/Pregnancy: Category C. Excreted in maternal milk; use caution in nursing patients.
Drug interactions
May cause increased CNS or respiratory depression when used concurrently.
Contraindicated. Do not use opiate antidiarrheals for at least 14 days after receiving MAOIs due to risk of severe adverse reactions.
Monitoring
- Clinical efficacy (resolution of diarrhea or cough)
- Fluid and electrolyte status (especially in severe diarrhea)
- CNS effects (sedation or excitation), particularly if using high dosages
- Bowel movements (monitor for constipation)
- Plasma amylase and lipase (may be artificially increased for up to 24 hours post-administration)
Pharmacokinetics
Absorption
In humans, rapidly absorbed after oral administration. Bioavailability of tablets is ~90% of the solution. Onset of action is 45-60 minutes, sustained for 3-4 hours.
Distribution
Crosses the blood-brain barrier and is excreted in maternal milk.
Metabolism
Metabolized into diphenoxylic acid, which is an active metabolite.
Elimination
Primarily excreted via feces and urine.
Overdose
Acute overdosage can result in severe CNS, cardiovascular, gastrointestinal, or respiratory toxicity.
- Delayed Absorption: Because opiates significantly reduce GI motility, absorption of the drug from the GI tract may be delayed and prolonged, meaning toxicity can worsen over time.
- Opiate Toxicity: Signs include profound sedation, respiratory depression, and pinpoint pupils. Naloxone may be necessary to reverse the opiate effects.
- Atropine Toxicity: Massive overdoses may induce atropine toxicity (dry mouth, tachycardia, hyperthermia, dilated pupils, agitation).
Available products
Formulations
- Tablets
- Oral Liquid/Solution
Human-labeled
- Diphenoxylate HCl Tablets: 2.5 mg with 0.025 mg Atropine Sulfate (e.g., Lomotil, Logen, Lonox)
- Diphenoxylate HCl Liquid: 2.5 mg with 0.025 mg Atropine Sulfate per 5 mL (e.g., Lomotil, Lomanate)
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Tablets should be stored at room temperature in well-closed, light-resistant containers. Oral solution should be stored at room temperature in tight, light-resistant containers; avoid freezing.
Client information
Important Information for Pet Owners
- Purpose: This medication is used to treat diarrhea or to suppress a chronic, hacking cough in dogs.
- When to Call the Vet: Contact your veterinarian immediately if the diarrhea persists for more than 48 hours, if your pet becomes extremely lethargic/listless, develops a high fever, or shows signs of abdominal pain.
- Watch for Constipation: Because this drug slows down the gut, it can cause constipation, especially when used long-term for coughing. Let your vet know if your pet is straining to defecate; a stool softener may be needed.
- Dosing Accuracy: If you have a small dog and are using the liquid form, measure the dose very carefully. Overdosing can cause serious side effects, including severe drowsiness and breathing problems.
- Storage: Keep this medication strictly out of reach of children and other pets. It is a controlled substance.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.