Quick answers
- What is Difenoxin and atropine sulfate used for?
- The FDA-approved label (Motofen, Legacy Pharma USA Inc., March 23, 2026) says: “MOTOFEN ® is indicated as adjunctive therapy in the management of acute nonspecific diarrhea and acute exacerbations of chronic functional diarrhea.” This page is not medical advice. Talk to your doctor or pharmacist before you start, stop or change any medicine.
- What are the side effects of Difenoxin and atropine sulfate?
- The “Adverse Reactions” section of the FDA label (Motofen, Legacy Pharma USA Inc., March 23, 2026) begins: “In view of the small amount of atropine present (0.025 mg/tablet), such effects such as dryness of the skin and mucous membranes, flushing, hyperthermia, tachycardia and urinary retention are very unlikely to occur, except perhaps in children. Many of the adverse effects reported during clinical investigation of MOTOFEN ® are difficult to distinguish from symptoms associated with the diarrheal syndrome.” … This page is not medical advice. Talk to your doctor or pharmacist before you start, stop or change any medicine.
- What are the drug interactions of Difenoxin and atropine sulfate?
- The “Drug Interactions” section of the FDA label (Motofen, Legacy Pharma USA Inc., March 23, 2026) begins: “Since the chemical structure of difenoxin hydrochloride is similar to meperidine hydrochloride, the concurrent use of MOTOFEN ® with monoamine oxidase inhibitors may, in theory, precipitate a hypertensive crisis. MOTOFEN ® may potentiate the action of barbiturates, tranquilizers, narcotics, and alcohol. When these medications are used concomitantly with MOTOFEN ®, the patient should be closely monitored.” … This page is not medical advice. Talk to your doctor or pharmacist before you start, stop or change any medicine.
- Does Difenoxin and atropine sulfate have a boxed warning?
- No. None of the 2 FDA labels we found for this medicine has a boxed warning.
- Is there a shortage of Difenoxin and atropine sulfate?
- No current shortage is listed by the FDA for the products of this medicine (FDA data from October 30, 2026).
- Has Difenoxin and atropine sulfate been recalled?
- No recall linked to the products of this medicine appears in the FDA enforcement reports we use.
- Who makes Difenoxin and atropine sulfate?
- 2 companies list prescription products of Difenoxin and atropine sulfate in the FDA NDC Directory, including Sebela Pharmaceuticals Inc. and Legacy Pharma USA Inc.
What Difenoxin and atropine sulfate is used for
Quoted from the “Indications and Usage” section of the FDA-approved label.
MOTOFEN ® is indicated as adjunctive therapy in the management of acute nonspecific diarrhea and acute exacerbations of chronic functional diarrhea.
— FDA label: Motofen, Legacy Pharma USA Inc., effective March 23, 2026. Read the full label on DailyMed →
Label quoted: the one for the most common form (tablet, oral), Motofen, Legacy Pharma USA Inc.; it covers 1 product in the FDA NDC Directory. The side effects, interactions, dosage and pregnancy quotes below come from this same label.
The FDA has 2 labels for products of this medicine (different makers and forms); uses can differ between them. Check the label that comes with your own medicine.
This page is not medical advice. Talk to your doctor or pharmacist before you start, stop or change any medicine.
Boxed warning
A boxed warning (“black box”) is the FDA’s strongest warning on a drug label, for serious or life-threatening risks.
The label quoted above has no boxed warning.
0 of 2 FDA labels for this medicine have a boxed warning.
Difenoxin and atropine sulfate side effects
Quoted from the “Adverse Reactions” section of the FDA-approved label. Tell your doctor about any side effect that worries you.
In view of the small amount of atropine present (0.025 mg/tablet), such effects such as dryness of the skin and mucous membranes, flushing, hyperthermia, tachycardia and urinary retention are very unlikely to occur, except perhaps in children. Many of the adverse effects reported during clinical investigation of MOTOFEN ® are difficult to distinguish from symptoms associated with the diarrheal syndrome.
Read more of this section
However, the following events were reported at the stated frequencies: Gastrointestinal: Nausea, 1 in 15 patients; vomiting, 1 in 30 patients; dry mouth, 1 in 30 patients; epigastric distress, 1 in 100 patients; and constipation, 1 in 300 patients. Central Nervous System: Dizziness and light-headedness, 1 in 20 patients; drowsiness, 1 in 25 patients; and headache, 1 in 40 patients; tiredness, nervousness, insomnia and confusion ranged from 1 in 200 to 1 in 600 patients. Other less frequent reactions: Burning eyes and blurred vision occurred in a few cases. The following adverse reactions have been reported in patients receiving chemically-related drugs: numbness of extremities, euphoria, depression, sedation, anaphylaxis, angioneurotic edema, urticaria, swelling of the gums, pruritus, toxic megacolon, paralytic ileus, pancreatitis, and anorexia. THIS MEDICATION SHOULD BE KEPT IN A CHILD-RESISTANT CONTAINER AND OUT OF THE REACH OF CHILDREN SINCE AN OVERDOSAGE MAY RESULT IN SEVERE RESPIRATORY DEPRESSION AND COMA, POSSIBLY LEADING TO PERMANENT BRAIN DAMAGE OR DEATH.
— FDA label: Motofen, Legacy Pharma USA Inc., effective March 23, 2026. Read the full label on DailyMed →
Difenoxin and atropine sulfate drug interactions
Quoted from the “Drug Interactions” section of the FDA-approved label. Tell your pharmacist about every medicine, vitamin and herbal product you take.
Since the chemical structure of difenoxin hydrochloride is similar to meperidine hydrochloride, the concurrent use of MOTOFEN ® with monoamine oxidase inhibitors may, in theory, precipitate a hypertensive crisis. MOTOFEN ® may potentiate the action of barbiturates, tranquilizers, narcotics, and alcohol. When these medications are used concomitantly with MOTOFEN ®, the patient should be closely monitored.
Read more of this section
Diphenoxylate hydrochloride, from which the principal active metabolite difenoxin is derived, was found to inhibit the hepatic microsomal enzyme system at a dose of 2 mg/kg/day in studies conducted with male rats. Therefore, difenoxin has the potential to prolong the biological half-lives of drugs for which the rate of elimination is dependent on the microsomal drug metabolizing enzyme system.
— FDA label: Motofen, Legacy Pharma USA Inc., effective March 23, 2026. Read the full label on DailyMed →
Difenoxin and atropine sulfate dosage
Quoted from the “Dosage and Administration” section of the FDA-approved label. Your own dose is the one your doctor prescribes: do not change it on your own.
The recommended starting dose of MOTOFEN ® tablets in adults is 2 tablets then 1 tablet after each loose stool or 1 tablet every 3 to 4 hours as needed, but the total dosage during any 24-hour treatment period should not exceed 8 tablets. In the treatment of diarrhea, if clinical improvement is not observed in 48 hours, continued administration of this type of medication is not recommended.
Read more of this section
For acute diarrheas and acute exacerbations of functional diarrhea, treatment beyond 48 hours is usually not necessary. Studies in children below the age of 12 have been inadequate to evaluate the safety and effectiveness of MOTOFEN ® in this age group. MOTOFEN ® is contraindicated in children under 2 years of age.
— FDA label: Motofen, Legacy Pharma USA Inc., effective March 23, 2026. Read the full label on DailyMed →
Difenoxin and atropine sulfate in pregnancy
Quoted from the pregnancy part of the FDA-approved label. Ask your doctor before you take any medicine while pregnant or planning a pregnancy.
/Teratogenic Effects Pregnancy Category C. Reproduction studies in rats and rabbits with doses at 31 and 61 times the human therapeutic dose respectively, on a mg/kg basis, demonstrated no evidence of teratogenesis due to MOTOFEN ®. Pregnant rats receiving oral doses of difenoxin hydrochloride/atropine 20 times the maximum human dose had an increase in delivery time as well as a significant increase in the percent of stillbirths.
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Neonatal survival in rats was also reduced with most deaths occurring within four days of delivery. There are no well controlled studies in pregnant women. MOTOFEN ® should be used during pregnancy only if the potential benefit justifies the potential risk of the fetus.
— FDA label: Motofen, Legacy Pharma USA Inc., effective March 23, 2026. Read the full label on DailyMed →
Difenoxin and atropine sulfate and breastfeeding
Quoted from the nursing mothers / lactation part of the FDA-approved label.
Because of the potential for serious adverse reactions in nursing infants from MOTOFEN ®, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
— FDA label: Motofen, Legacy Pharma USA Inc., effective March 23, 2026. Read the full label on DailyMed →
When Difenoxin and atropine sulfate should not be used
Quoted from the “Contraindications” section of the FDA-approved label.
MOTOFEN ® is contraindicated in patients with diarrhea associated with organisms that penetrate the intestinal mucosa (toxigenic E. coli, Salmonella species, Shigella) and pseudomembranous colitis associated with broad spectrum antibiotics. Antiperistaltic agents should not be used in the conditions because they may prolong and/or worsen diarrhea.
Read more of this section
MOTOFEN ® is contraindicated in children under 2 years of age because of the decreased margin of safety of drugs in this class in younger age groups. MOTOFEN ® is contraindicated in patients with a known hypersensitivity to difenoxin, atropine, or any of the inactive ingredients, and in patients who are jaundiced.
— FDA label: Motofen, Legacy Pharma USA Inc., effective March 23, 2026. Read the full label on DailyMed →
Difenoxin and atropine sulfate overdose
Quoted from the “Overdosage” section of the FDA-approved label. If someone may have taken too much, call Poison Help at 1-800-222-1222 (or 911 in an emergency).
Diagnosis and Treatment In the event of overdosage (initial signs may include dryness of the skin and mucous membranes, flushing, hyperthermia and tachycardia followed by lethargy or coma, hypotonic reflexes, nystagmus, pinpoint pupils and respiratory depression) gastric lavage, establishment of a patent airway and possibly mechanically assisted respiration are advised.
Read more of this section
The narcotic antagonist naloxone may be used in the treatment of respiratory depression caused by narcotic analgesics of pharmacologically related compounds such as MOTOFEN ® tablets. When naloxone is administered intravenously, the onset of action is generally apparent within two minutes. Naloxone may be administered subcutaneously or intramuscularly providing a slightly less rapid onset of action but a more prolonged effect. To counteract respiratory depression caused by MOTOFEN ® overdosage, the following dosage schedule for naloxone should be followed: Adult Dosage: The usual initial adult dose of naloxone is 0.4 mg (one mL) administered intravenously. If respiratory function does not adequately improve after the initial dose, the same IV dose may be repeated at two-to-three minute intervals. Children: The usual adult dose of naloxone for children is 0.01 mg/kg of body weight administered intravenously and repeated at two-to-three minute intervals if necessary. Since the duration of action of difenoxin hydrochloride is longer than that of naloxone, improvement of respiration following administration may be followed by recurrent respiratory depression. Consequently, continuous observation is necessary until the effect of difenoxin hydrochloride on respiration (which effect may persist for many hours) has passed. Supplemental intramuscular doses of naloxone may be utilized to produce a longer lasting effect. TREAT ALL POSSIBLE MOTOFEN ® OVERDOSAGES AS SERIOUS AND MAINTAIN MEDICAL OBSERVATION FOR AT LEAST 48 HOURS, PREFERABLY UNDER CONTINUOUS HOSPITAL CARE. Although signs of overdosage and respiratory depression may not be evident soon after ingestion of difenoxin hydrochloride, respiratory depression may occur from 12 to 30 hours later.
— FDA label: Motofen, Legacy Pharma USA Inc., effective March 23, 2026. Read the full label on DailyMed →
Forms and how it is given
| Dosage forms | Tablet |
|---|---|
| Route | Oral |
| Prescription products | 2 in the FDA NDC Directory |
| Brand names | Motofen |
What pharmacies pay (NADAC)
The National Average Drug Acquisition Cost (NADAC) is the average price U.S. retail pharmacies paid to buy one unit of a medicine (one tablet, one mL or one gram), from a monthly survey of pharmacy invoices by the Centers for Medicare & Medicaid Services (CMS). State Medicaid programs use it to pay pharmacies.
This is not the price you pay. What you pay depends on your insurance (copay or coinsurance), your pharmacy and any discounts, and pharmacies also charge for filling a prescription. Ask your pharmacist or your health plan what your price will be.
| Strength and form | Generic or brand | Pharmacies pay |
|---|---|---|
| atropine sulfate 0.025 mg · difenoxin hydrochloride 1 mg tablet | Brand: Motofen | $6.91 per tablet |
NADAC list of November 4, 2026; these prices took effect on August 19, 2026. Shown only where a package’s NDC code matches the NADAC list exactly, and only for that exact strength and form: nothing is averaged across strengths. Strengths and forms not listed here have no NADAC price.
Source: NADAC (National Average Drug Acquisition Cost) 2026, data.medicaid.gov (CMS) →
Companies that list this medicine
Labelers in the FDA NDC Directory: the company named on the package (maker or distributor), with the number of prescription products.
- Sebela Pharmaceuticals Inc.1 product
- Legacy Pharma USA Inc.1 product
FDA approval history
- NDA: New Drug Application: how a new (usually brand-name) medicine is approved.
| Application | Sponsor | Approved | Later changes approved |
|---|---|---|---|
| NDA017744 MOTOFEN, MOTOFEN HALF-STRENGTH | Legacy | July 14, 1978 | 21, latest March 28, 2017 2017: Labeling · 2001: Manufacturing (CMC) · 2001: Manufacturing (CMC) |
Shortage status
The FDA drug shortage list does not show these products.
Recalls
No recall linked to these products (by their NDC code) appears in the FDA enforcement reports.
Official identifiers
| RxCUI (RxNorm) | 1190738, 1190740 |
|---|---|
| SPL set ID of the quoted label | 1fa11c67-5492-469c-9475-6bfa0e5e9ff8 |
| FDA labels (SPL) | 2 |
| FDA applications | NDA017744 |
| Active ingredients (FDA) | ATROPINE / DIFENOXIN |
Next steps
- Find a pharmacy near youAsk which price applies to you and whether your product is affected by a recall
- Latest FDA drug recallsAll medicines, newest first
- Sebela Pharmaceuticals Inc.Maker or distributor
- Legacy Pharma USA Inc.Maker or distributor
- All prescription drugs A to ZSearch by generic, brand or Spanish name
Sources
- FDA-approved label on DailyMed (National Library of Medicine) — Motofen, Legacy Pharma USA Inc., effective March 23, 2026; via openFDA, FDA data exported October 30, 2026, retrieved October 31, 2026
- NDC Directory (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 30, 2026, retrieved October 31, 2026
- Drugs@FDA (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 30, 2026, retrieved October 31, 2026
- Drug recall enforcement reports (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 27, 2026, retrieved October 31, 2026
- Drug shortages (openFDA) — U.S. Food and Drug Administration (FDA), FDA data exported October 30, 2026, retrieved October 31, 2026
openFDA data is provided by the FDA as is; it may be incomplete. Always rely on the label that comes with your medicine. FDA Enforcement Report search →