Motofen is the brand name for an antiperistaltic anti-diarrheal medication, containing 1.0 mg difenoxin HCl and 0.025 mg atropine (U.S. Food and Drug Administration: Schedule IV Combination). Atropine is purposely added at 25 micrograms per tablet, or ¹/₂₄ to ¹/₄₀ of the usual therapeutic dose for atropine to minimize the potential of misuse by swallowing large numbers of tablets or preparing them for injection since difenoxin is chemically related to the pethidine-piritramide subgroup of the opioid family, and could theoretically be misused. Although unlikely, physical and mental withdrawal symptoms (from both anticholinergic rebound caused by atropine, and opiate withdrawal caused by the difenoxin) is possible if taken for long periods of time. However, both of these compounds are responsible for the medicinal effects of the medicine (both atropine and difenoxin slow gut movement).

This combination medication should not be confused with Lomotil (2.5 mg diphenoxylate and 0.025 mg atropine – a Schedule V Combination), because the active ingredients in the two medications are different compounds, except for the inclusion of atropine. Motofen is approximately 2 to 4 times more effective in treating symptoms than Lomotil.